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Sample records for early goal-directed therapy

  1. EARLY GOAL DIRECTED THERAPY AT SEPTIC SYOK

    Directory of Open Access Journals (Sweden)

    Ayu Widyanti

    2013-04-01

    Full Text Available Sepsis is the most commom cause of death in children with critically ill. Using WHO criteria (severe sepsis defined as sepsis with acidosis, hypotension or both, it was determined that in 1995 there were more than 42.000 cases of severe sepsis in children in the United States with mortality rate was 10.3%. To answer that finding, evicende based protocol was made, it called early goal directed therapy (EGDT. EGDT is a comprehensive strategy to evaluate patient with septic shock include, challenge of fluid, antibiotic, vasopressor, measurement of central vein oxygen saturation, PRC transfusion, administering inotropic dan mechanic ventilation. All of these must be done in the first 6 hours since sepsis or septic shock was found, because if there is a delay of resuscitation, anything we do to increase oxygenation level of the cell will be useless.

  2. Early management of sepsis with emphasis on early goal directed therapy: AME evidence series 002

    OpenAIRE

    Zhang, Zhongheng; Hong, Yucai; Smischney, Nathan J.; Kuo, Han-Pin; Tsirigotis, Panagiotis; Rello, Jordi; Kuan, Win Sen; Jung, Christian; Robba, Chiara; Taccone, Fabio Silvio; Leone, Marc; Spapen, Herbert; Grimaldi, David; Van Poucke, Sven; Simpson, Steven Q.

    2017-01-01

    Severe sepsis and septic shock are major causes of morbidity and mortality in patients entering the emergency department (ED) or intensive care unit (ICU). Despite substantial efforts to improve patient outcome, treatment of sepsis remains challenging to clinicians. In this context, early goal directed therapy (EGDT) represents an important concept emphasizing both early recognition of sepsis and prompt initiation of a structured treatment algorithm. As part of the AME evidence series on seps...

  3. Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.

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    Rowan, Kathryn M; Angus, Derek C; Bailey, Michael; Barnato, Amber E; Bellomo, Rinaldo; Canter, Ruth R; Coats, Timothy J; Delaney, Anthony; Gimbel, Elizabeth; Grieve, Richard D; Harrison, David A; Higgins, Alisa M; Howe, Belinda; Huang, David T; Kellum, John A; Mouncey, Paul R; Music, Edvin; Peake, Sandra L; Pike, Francis; Reade, Michael C; Sadique, M Zia; Singer, Mervyn; Yealy, Donald M

    2017-06-08

    After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and

  4. Predictors of Unattempted Central Venous Catheterization in Septic Patients Eligible for Early Goal-directed Therapy

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    David R. Vinson

    2014-02-01

    Full Text Available Introduction: Central venous catheterization (CVC can be an important component of the management of patients with severe sepsis and septic shock. CVC, however, is a time- and resource-intensive procedure associated with serious complications. The effects of the absence of shock or the presence of relative contraindications on undertaking central line placement in septic emergency department (ED patients eligible for early goal-directed therapy (EGDT have not been well described. We sought to determine the association of relative normotension (sustained systolic blood pressure >90 mmHg independent of or in response to an initial crystalloid resuscitation of 20 mL/kg, obesity (body mass index [BMI] ≥30, moderate thrombocytopenia (platelet count <50,000 per μL, and coagulopathy (international normalized ratio ≥2.0 with unattempted CVC in EGDT-eligible patients. Methods: This was a retrospective cohort study of 421 adults who met EGDT criteria in 5 community EDs over a period of 13 months. We compared patients with attempted thoracic (internal jugular or subclavian CVC with those who did not undergo an attempted thoracic line. We also compared patients with any attempted CVC (either thoracic or femoral with those who did not undergo any attempted central line. We used multivariate logistic regression analysis to calculate adjusted odd ratios (AORs. Results: In our study, 364 (86.5% patients underwent attempted thoracic CVC and 57 (13.5% did not. Relative normotension was significantly associated with unattempted thoracic CVC (AOR 2.6 95% confidence interval [CI], 1.6-4.3, as were moderate thrombocytopenia (AOR 3.9; 95% CI, 1.5-10.1 and coagulopathy (AOR 2.7; 95% CI, 1.3-5.6. When assessing for attempted catheterization of any central venous site (thoracic or femoral, 382 (90.7% patients underwent attempted catheterization and 39 (9.3% patients did not. Relative normotension (AOR 2.3; 95% CI, 1.2-4.5 and moderate thrombocytopenia (AOR 3.9; 95

  5. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators.

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    Angus, D C; Barnato, A E; Bell, D; Bellomo, R; Chong, C-R; Coats, T J; Davies, A; Delaney, A; Harrison, D A; Holdgate, A; Howe, B; Huang, D T; Iwashyna, T; Kellum, J A; Peake, S L; Pike, F; Reade, M C; Rowan, K M; Singer, M; Webb, S A R; Weissfeld, L A; Yealy, D M; Young, J D

    2015-09-01

    To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control: 22.4% [582/2601]; pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity [I(2) = 57%; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0%; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and ICU admission [OR 2.19 (95% CI 1.82-2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I(2) = 71%; P < 0.001) but did not change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07); P = 0.33]. EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

  6. Monitoring of peri-operative fluid administration by individualized goal-directed therapy

    DEFF Research Database (Denmark)

    Bundgaard-Nielsen, M; Holte, Kathrine; Secher, N H

    2007-01-01

    (n = 725) found a reduced hospital stay. Post-operative nausea and vomiting (PONV) and ileus were reduced in three studies and complications were reduced in four studies. Of the monitors that may be applied for goal-directed therapy, only oesophageal Doppler has been tested adequately; however......, several other options exist. CONCLUSION: Goal-directed therapy with the maximization of flow-related haemodynamic variables reduces hospital stay, PONV and complications, and facilitates faster gastrointestinal functional recovery. So far, oesophageal Doppler is recommended, but other monitors...

  7. Monitoring of peri-operative fluid administration by individualized goal-directed therapy

    DEFF Research Database (Denmark)

    Bundgaard-Nielsen, M; Holte, Kathrine; Secher, N H

    2007-01-01

    BACKGROUND: In order to avoid peri-operative hypovolaemia or fluid overload, goal-directed therapy with individual maximization of flow-related haemodynamic parameters has been introduced. The objectives of this review are to update research in the area, evaluate the effects on outcome and assess...

  8. Goal-directed fluid therapy: stroke volume optimisation and cardiac dimensions in supine healthy humans

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    Jans, O.; Tollund, C.; Bundgaard-Nielsen, M.

    2008-01-01

    BACKGROUND: Based on maximisation of cardiac stroke volume (SV), peri-operative individualised goal-directed fluid therapy improves patient outcome. It remains, however, unknown how fluid therapy by this strategy relates to filling of the heart during supine rest as reference for the anaesthetised...... by thoracic electrical admittance, central venous oxygenation and pressure, and arterial plasma atrial natriuretic peptide. Also, muscle and brain oxygenation were assessed by near infrared spectroscopy (n=7). RESULTS: The HUT reduced the mentioned indices of CBV, the end-diastolic dimensions of the heart...... therapy is that when a maximal SV is established for patients, cardiac pre-load is comparable to that of supine healthy subjects Udgivelsesdato: 2008/4...

  9. Early goal-directed nutrition versus standard of care in adult intensive care patients

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    Allingstrup, Matilde Jo; Kondrup, Jens; Wiis, Jørgen

    2017-01-01

    Purpose: We assessed the effects of early goal-directed nutrition (EGDN) vs. standard nutritional care in adult intensive care unit (ICU) patients. Methods: We randomised acutely admitted, mechanically ventilated ICU patients expected to stay longer than 3 days in the ICU. In the EGDN group we...... estimated nutritional requirements by indirect calorimetry and 24-h urinary urea aiming at covering 100% of requirements from the first full trial day using enteral and parenteral nutrition. In the standard of care group we aimed at providing 25 kcal/kg/day by enteral nutrition. If this was not met by day 7......, patients were supplemented with parenteral nutrition. The primary outcome was physical component summary (PCS) score of SF-36 at 6 months. We performed multiple imputation for data of the non-responders. Results: We randomised 203 patients and included 199 in the intention-to-treat analyses; baseline...

  10. Early goal-directed nutrition in icU patients (EAT-ICU)

    DEFF Research Database (Denmark)

    Allingstrup, Matilde Jo; Kondrup, Jens; Wiis, Jørgen

    2016-01-01

    -energy nutrition based on measured requirements on short-term clinical outcomes and long-term physical quality of life in ICU patients. METHODS: The EAT-ICU trial is a single-centre, randomised, parallel-group trial with concealed allocation and blinded outcome assessment. A total of 200 consecutive, acutely...... admitted, mechanically ventilated intensive care patients will be randomised 1:1 to early goal-directed nutrition versus standard of care to show a potential 15% relative risk reduction in the primary outcome measure (physical function) at six months (two-sided significance level α = 0.05; power β = 80......%). Secondary outcomes include energy- and protein balances, metabolic control, new organ failure, use of life support, nosocomial infections, ICU- and hospital length of stay, mortality and cost analyses. CONCLUSION: The optimal nutrition strategy for ICU patients remains unsettled. The EAT-ICU trial...

  11. Outcomes of implementation of enhanced goal directed therapy in high-risk patients undergoing abdominal surgery

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    Lakshmi Kumar

    2015-01-01

    Full Text Available Background and Aims: Advanced monitoring targeting haemodynamic and oxygenation variables can improve outcomes of surgery in high-risk patients. We aimed to assess the impact of goal directed therapy (GDT targeting cardiac index (CI and oxygen extraction ratio (O 2 ER on outcomes of high-risk patients undergoing abdominal surgery. Methods: In a prospective randomised trial, forty patients (American Society of Anaesthesiologists II and III undergoing major abdominal surgeries were randomised into two groups. In-Group A mean arterial pressure ≥ 65 mmHg, central venous pressure ≥ 8-10 mmHg, urine output ≥ 0.5 mL/kg/h and central venous oxygen saturation ≥ 70% were targeted intra-operatively and 12 h postoperatively. In-Group-B (enhanced GDT, in addition to the monitoring in-Group-A, CI ≥ 2.5 L/min/m 2 and O 2 ER ≤ 27% were targeted. The end-points were lactate levels and base deficit during and after surgery. The secondary end points were length of Intensive Care Unit (ICU and hospital stay and postoperative complications. Wilcoxon Mann Whitney and Chi-square tests were used for statistical assessment. Results: Lactate levels postoperatively at 4 and 8 h were lower in-Group-B (P < 0.05. The mean base deficit at 3, 4, 5 and 6 h intra-operatively and postoperatively after 4, 8 and 12 h were lower in-Group-B (P < 0.05. There were no significant differences in ICU stay (2.10 ± 1.52 vs. 2.90 ± 2.51 days or hospital stay (10.85 + 4.39 vs. 13.35 + 6.77 days between Group A and B. Conclusions: Implementation of enhanced GDT targeting CI and OER was associated with improved tissue oxygenation.

  12. Impairments in goal-directed actions predict treatment response to cognitive-behavioral therapy in social anxiety disorder.

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    Gail A Alvares

    Full Text Available Social anxiety disorder is characterized by excessive fear and habitual avoidance of social situations. Decision-making models suggest that patients with anxiety disorders may fail to exhibit goal-directed control over actions. We therefore investigated whether such biases may also be associated with social anxiety and to examine the relationship between such behavior with outcomes from cognitive-behavioral therapy. Patients diagnosed with social anxiety and controls completed an instrumental learning task in which two actions were performed to earn food outcomes. After outcome devaluation, where one outcome was consumed to satiety, participants were re-tested in extinction. Results indicated that, as expected, controls were goal-directed, selectively reducing responding on the action that previously delivered the devalued outcome. Patients with social anxiety, however, exhibited no difference in responding on either action. This loss of a devaluation effect was associated with greater symptom severity and poorer response to therapy. These findings indicate that variations in goal-directed control in social anxiety may represent both a behavioral endophenotype and may be used to predict individuals who will respond to learning-based therapies.

  13. Neutrophil gelatinase-associated lipocalin and albuminuria as predictors of acute kidney injury in patients treated with goal-directed haemodynamic therapy after major abdominal surgery.

    LENUS (Irish Health Repository)

    Cullen, Mr

    2013-10-11

    Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a new biomarker for the early identification of acute kidney injury (AKI). There is also increasing evidence of an association between urinary albumin\\/creatinine ratio (ACR) and AKI. The primary aim of this study was to evaluate the clinical utility of these biomarkers to predict AKI in a population of perioperative patients treated with goal-directed haemodynamic therapy (GDHT). Secondary aims were to examine NGAL and ACR as sensitive biomarkers to detect the effects of GDHT and to investigate the association of these biomarkers with secondary outcomes.

  14. Combination of brain-computer interface training and goal-directed physical therapy in chronic stroke: a case report.

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    Broetz, Doris; Braun, Christoph; Weber, Cornelia; Soekadar, Surjo R; Caria, Andrea; Birbaumer, Niels

    2010-09-01

    There is no accepted and efficient rehabilitation strategy to reduce focal impairments for patients with chronic stroke who lack residual movements. A 67-year-old hemiplegic patient with no active finger extension was trained with a brain-computer interface (BCI) combined with a specific daily life-oriented physiotherapy. The BCI used electrical brain activity (EEG) and magnetic brain activity (MEG) to drive an orthosis and a robot affixed to the patient's affected upper extremity, which enabled him to move the paralyzed arm and hand driven by voluntary modulation of micro-rhythm activity. In addition, the patient practiced goal-directed physiotherapy training. Over 1 year, he completed 3 training blocks. Arm motor function, gait capacities (using Fugl-Meyer Assessment, Wolf Motor Function Test, Modified Ashworth Scale, 10-m walk speed, and goal attainment score), and brain reorganization (functional MRI, MEG) were repeatedly assessed. The ability of hand and arm movements as well as speed and safety of gait improved significantly (mean 46.6%). Improvement of motor function was associated with increased micro-oscillations in the ipsilesional motor cortex. This proof-of-principle study suggests that the combination of BCI training with goal-directed, active physical therapy may improve the motor abilities of chronic stroke patients despite apparent initial paralysis.

  15. Evaluation of financial burden following complications after major surgery in France: Potential return after perioperative goal-directed therapy.

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    Landais, Alain; Morel, Morgane; Goldstein, Jacques; Loriau, Jerôme; Fresnel, Annie; Chevalier, Corinne; Rejasse, Gilles; Alfonsi, Pascal; Ecoffey, Claude

    2017-06-01

    Perioperative goal-directed therapy (PGDT) has been demonstrated to improve postoperative outcomes and reduce the length of hospital stays. The objective of our analysis was to evaluate the cost of complications, derived from French hospital payments, and calculate the potential cost savings and length of hospital stay reductions. The billing of 2388 patients who underwent scheduled high-risk surgery (i.e. major abdominal, gynaecologic, urological, vascular, and orthopaedic interventions) over three years was retrospectively collected from three French hospitals (one public-teaching, one public, and one private hospital). A relationship between mortality, length of hospital stays, cost/patient, and severity scores, based mainly on postoperative complications but also on preoperative clinical status, were analysed. Statistical analysis was performed using Student's t-tests or Wilcoxon tests. Our analyses determined that a severity score of 3 or 4 was associated with complications in 90% of cases and this represented 36% of patients who, compared with those with a score of 1 or 2, were associated with significantly increased costs (€ 8205±3335 to € 22,081±16,090; Prisk surgeries per year), the potential financial savings ranged from € 40M to € 68M, not including the costs of PGDT and its implementation. Our analysis demonstrates that patients with complications are significantly more expensive to care for than those without complications. In our model, it was projected that implementing PGDT during high-risk surgery may significantly reduce healthcare costs and the length of hospital stays in France while probably improving patient access to care and reducing waiting times for procedures. Copyright © 2017. Published by Elsevier Masson SAS.

  16. The influence of goal-directed fluid therapy on the prognosis of elderly patients with hypertension and gastric cancer surgery

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    Zeng K

    2014-10-01

    Full Text Available Kai Zeng,* Yanzhen Li,* Min Liang, Youguang Gao, Hongda Cai, Caizhu LinDepartment of Anesthesia, the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China*These authors contributed equally to this workPurpose: We aimed to investigate the influence of perioperative goal-directed fluid therapy (GDFT on the prognosis of elderly patients with gastric cancer and hypertension. Methods: Sixty elderly patients (>60 years old with primary hypertension who received gastric cancer radical surgery and who were American Society of Anesthesiologists (ASA class II or III were enrolled in the current study. Selected patients were divided randomly into two arms, comprising a conventional intraoperative fluid management arm (arm C, n=30 and a GDFT arm (arm G, n=30. Patients in arm C were infused with crystalloids or colloids according to the methods of Miller’s Anesthesia (6th edition, while those in arm G were infused with 200 mL hydroxyethyl starch over 15 minutes under the FloTrac/Vigileo monitoring system, with stroke volume variation between 8% and 13%. Hemodynamics and tissue perfusion laboratory indicators in patients were recorded continuously from 30 minutes before the operation to 24 hours after the operation. Results: Compared with arm C, the average intraoperative intravenous infusion quantity in arm G was significantly reduced (2,732±488 mL versus 3,135±346 mL, P<0.05, whereas average colloid fluid volume was significantly increased (1,235±360 mL versus 760±280 mL, P<0.05. In addition, there were more patients exhibiting intraoperatively and postoperatively stable hemodynamics and less patients with low blood pressure in arm G. Postoperative complications were less frequent, and the time of postoperative hospital stay shorter, in arm G. No significant differences were observed in mortality between the two arms.Conclusion: Our research showed that GDFT stabilized perioperative hemodynamics and reduced the

  17. Dynamic muscle O2 saturation response is impaired during major non-cardiac surgery despite goal-directed haemodynamic therapy.

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    Feldheiser, A; Hunsicker, O; Kaufner, L; Köhler, J; Sieglitz, H; Casans Francés, R; Wernecke, K-D; Sehouli, J; Spies, C

    2016-03-01

    Near-infrared spectroscopy combined with a vascular occlusion test (VOT) could indicate an impairment of microvascular reactivity (MVR) in septic patients by detecting changes in dynamic variables of muscle O2 saturation (StO2). However, in the perioperative context the consequences of surgical trauma on dynamic variables of muscle StO2 as indicators of MVR are still unknown. This study is a sub-analysis of a randomised controlled trial in patients with metastatic primary ovarian cancer undergoing debulking surgery, during which a goal-directed haemodynamic algorithm was applied using oesophageal Doppler. During a 3 min VOT, near-infrared spectroscopy was used to assess dynamic variables arising from changes in muscle StO2. At the beginning of surgery, values of desaturation and recovery slope were comparable to values obtained in healthy volunteers. During the course of surgery, both desaturation and recovery slope showed a gradual decrease. Concomitantly, the study population underwent a transition to a surgically induced systemic inflammatory response state shown by a gradual increase in norepinephrine administration, heart rate, and Interleukin-6, with a peak immediately after the end of surgery. Higher rates of norepinephrine and a higher heart rate were related to a faster decline in StO2 during vascular occlusion. Using near-infrared spectroscopy combined with a VOT during surgery showed a gradual deterioration of MVR in patients treated with optimal haemodynamic care. The deterioration of MVR was accompanied by the transition to a surgically induced systemic inflammatory response state. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. The hemodynamic "target": a visual tool of goal-directed therapy for septic patients Alvo hemodinâmico: uma ferramenta visual de terapia "goal-directed" para pacientes sépticos

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    Fabrice Vallée

    2007-01-01

    Full Text Available OBJECTIVE: To improve understanding of the hemodynamic status of patients with sepsis by nursing teams through the attainment of hemodynamic parameters using a pentaxial "target" diagram as a clinical tool. Parameters include cardiac index (CI, arterial oxygen saturation (SaO2, mean arterial pressure (MAP, arterial blood lactate, and central venous oxygen saturation (ScvO2. METHODS: Design: Prospective descriptive study. Setting: The intensive care unit of a university hospital. Patients: During a 6-month period, 38 intubated septic shock patients were included in the study. Survivors and nonsurvivors were compared. Interventions: MAP, CI, SaO2, ScvO2 and lactate were measured at 0, 6, 12, 24, 36, and 48 h. Measurements were recorded on the target diagram along with the norepinephrine infusion rate and the hemoglobin (Hb level. The number of lactate and ScvO2 measurements achieved during the target period were compared to a 6-month retrospective control period just before starting the protocol. We assessed the nurse knowledge status prior to the introduction of target diagram. We then performed a post-test after implementing the new recording technique. MEASUREMENTS AND RESULTS: The nursing team expressed a positive attitude toward the target concept. The mean number of lactate and ScvO2 measurements performed for each patient during the control period was significantly lower than during the target period, and those values were rarely used as goal values before the introduction of the target diagram. At 24 hours, 46% of the survivors had achieved all the goal parameter values of the target diagram, compared to only 10% of nonsurvivors (P = .01. CONCLUSION: The target diagram is a visual multiparametric tool involving all the medical and nursing team that helps achieve goal-directed therapy for septic patients. The number of goal values reached at each time point during the first 48 hours was closely linked to mortality.OBJETIVO: Melhorar a

  19. Perioperative utility of goal-directed therapy in high-risk cardiac patients undergoing coronary artery bypass grafting: “A clinical outcome and biomarker-based study”

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    Poonam Malhotra Kapoor

    2016-01-01

    Full Text Available Goal-directed therapy (GDT encompasses guidance of intravenous (IV fluid and vasopressor/inotropic therapy by cardiac output or similar parameters to help in early recognition and management of high-risk cardiac surgical patients. With the aim of establishing the utility of perioperative GDT using robust clinical and biochemical outcomes, we conducted the present study. This multicenter randomized controlled study included 130 patients of either sex, with European system for cardiac operative risk evaluation ≥3 undergoing coronary artery bypass grafting on cardiopulmonary bypass. The patients were randomly divided into the control and GDT group. All the participants received standardized care; arterial pressure monitored through radial artery, central venous pressure (CVP through a triple lumen in the right internal jugular vein, electrocardiogram, oxygen saturation, temperature, urine output per hour, and frequent arterial blood gas (ABG analysis. In addition, cardiac index (CI monitoring using FloTrac™ and continuous central venous oxygen saturation (ScVO2 using PreSep™ were used in patients in the GDT group. Our aim was to maintain the CI at 2.5–4.2 L/min/m2, stroke volume index 30–65 ml/beat/m2, systemic vascular resistance index 1500–2500 dynes/s/cm5/m2, oxygen delivery index 450–600 ml/min/m2, continuous ScVO2 >70%, and stroke volume variation 30%, and urine output >1 ml/kg/h. The aims were achieved by altering the administration of IV fluids and doses of inotropes or vasodilators. The data of sixty patients in each group were analyzed in view of ten exclusions. The average duration of ventilation (19.89 ± 3.96 vs. 18.05 ± 4.53 h, P = 0.025, hospital stay (7.94 ± 1.64 vs. 7.17 ± 1.93 days, P = 0.025, and Intensive Care Unit (ICU stay (3.74 ± 0.59 vs. 3.41 ± 0.75 days, P = 0.012 was significantly less in the GDT group, compared to the control group. The extra volume added and the number of inotropic dose adjustments were

  20. Goal-Directed Fluid Therapy Based on Stroke Volume Variation in Patients Undergoing Major Spine Surgery in the Prone Position: A Cohort Study.

    Science.gov (United States)

    Bacchin, Maria Renata; Ceria, Chiara Marta; Giannone, Sandra; Ghisi, Daniela; Stagni, Gaetano; Greggi, Tiziana; Bonarelli, Stefano

    2016-09-15

    A retrospective observational study. The aim of this study was to test whether a goal-directed fluid therapy (GDFT) protocol, based on stroke volume variation (SVV), applied in major spine surgery performed in the prone position, would be effective in reducing peri-operative red blood cells transfusions. Recent literature shows that optimizing perioperative fluid therapy is associated with lower complication rates and faster recovery. Data from 23 patients who underwent posterior spine arthrodesis surgery and whose intraoperative fluid administration were managed with the GDFT protocol were retrospectively collected and compared with data from 23 matched controls who underwent the same surgical procedure in the same timeframe, and who received a liberal intraoperative fluid therapy. Patients in the GDFT group received less units of transfused red blood cells (primary endpoint) in the intra (0 vs. 2.0, P = 0.0 4) and postoperative period (2.0 vs. 4.0, P = 0.003). They also received a lower amount of intraoperative crystalloids, had fewer blood losses, and lower intraoperative peak lactate. In the postoperative period, patients in the GDFT group had fewer pulmonary complications and blood losses from surgical drains, needed less blood product transfusions, had a shorter intensive care unit stay, and a faster return of bowel function. We found no difference in the total length of stay among the two groups. Our study shows that application of a GDFT based on SVV in major spine surgery is feasible and can lead to reduced blood losses and transfusions, better postoperative respiratory performance, shorter ICU stay, and faster return of bowel function. 3.

  1. Goal directed fluid therapy decreases postoperative morbidity but not mortality in major non-cardiac surgery: a meta-analysis and trial sequential analysis of randomized controlled trials.

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    Som, Anirban; Maitra, Souvik; Bhattacharjee, Sulagna; Baidya, Dalim K

    2017-02-01

    Optimum perioperative fluid administration may improve postoperative outcome after major surgery. This meta-analysis and systematic review has been aimed to determine the effect of dynamic goal directed fluid therapy (GDFT) on postoperative morbidity and mortality in non-cardiac surgical patients. Meta-analysis of published prospective randomized controlled trials where GDFT based on non-invasive flow based hemodynamic measurement has been compared with a standard care. Data from 41 prospective randomized trials have been included in this study. Use of GDFT in major surgical patients does not decrease postoperative hospital/30-day mortality (OR 0.70, 95 % CI 0.46-1.08, p = 0.11) length of post-operative hospital stay (SMD -0.14; 95 % CI -0.28, 0.00; p = 0.05) and length of ICU stay (SMD -0.12; 95 % CI -0.28, 0.04; p = 0.14). However, number of patients having at least one postoperative complication is significantly lower with use of GDFT (OR 0.57; 95 % CI 0.43, 0.75; p infection (p = 0.002) and postoperative hypotension (p = 0.04) are also decreased with used of GDFT as opposed to a standard care. Though patients who received GDFT were infused more colloid (p infection, abdominal complications and postoperative hypotension is reduced.

  2. Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock.

    Science.gov (United States)

    Mouncey, Paul R; Osborn, Tiffany M; Power, G Sarah; Harrison, David A; Sadique, M Zia; Grieve, Richard D; Jahan, Rahi; Tan, Jermaine C K; Harvey, Sheila E; Bell, Derek; Bion, Julian F; Coats, Timothy J; Singer, Mervyn; Young, J Duncan; Rowan, Kathryn M

    2015-11-01

    Early goal-directed therapy (EGDT) is recommended in international guidance for the resuscitation of patients presenting with early septic shock. However, adoption has been limited and uncertainty remains over its clinical effectiveness and cost-effectiveness. The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following randomisation and on incremental cost-effectiveness at 1 year. The secondary objectives were to compare EGDT with usual resuscitation for requirement for, and duration of, critical care unit organ support; length of stay in the emergency department (ED), critical care unit and acute hospital; health-related quality of life, resource use and costs at 90 days and at 1 year; all-cause mortality at 28 days, at acute hospital discharge and at 1 year; and estimated lifetime incremental cost-effectiveness. A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. Fifty-six NHS hospitals in England. A total of 1260 patients who presented at EDs with septic shock. EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1. All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year. Following withdrawals, data on 1243 (EGDT, n = 623; usual resuscitation, n = 620) patients were included in the analysis. By 90 days, 184 (29.5%) in the EGDT and 181 (29.2%) patients in the usual-resuscitation group had died [p = 0.90; absolute risk reduction -0.3%, 95% confidence interval (CI) -5.4 to 4.7; relative risk 1.01, 95% CI 0.85 to 1.20]. Treatment intensity was greater for the EGDT group, indicated by the increased use of intravenous fluids, vasoactive drugs and red blood cell transfusions. Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced

  3. Comparison of cardiac output optimization with an automated closed-loop goal-directed fluid therapy versus non standardized manual fluid administration during elective abdominal surgery: first prospective randomized controlled trial.

    Science.gov (United States)

    Lilot, Marc; Bellon, Amandine; Gueugnon, Marine; Laplace, Marie-Christine; Baffeleuf, Bruno; Hacquard, Pauline; Barthomeuf, Felicie; Parent, Camille; Tran, Thomas; Soubirou, Jean-Luc; Robinson, Philip; Bouvet, Lionel; Vassal, Olivia; Lehot, Jean-Jacques; Piriou, Vincent

    2018-01-27

    An intraoperative automated closed-loop system for goal-directed fluid therapy has been successfully tested in silico, in vivo and in a clinical case-control matching. This trial compared intraoperative cardiac output (CO) in patients managed with this closed-loop system versus usual practice in an academic medical center. The closed-loop system was connected to a CO monitoring system and delivered automated colloid fluid boluses. Moderate to high-risk abdominal surgical patients were randomized either to the closed-loop or the manual group. Intraoperative final CO was the primary endpoint. Secondary endpoints were intraoperative overall mean cardiac index (CI), increase from initial to final CI, intraoperative fluid volume and postoperative outcomes. From January 2014 to November 2015, 46 patients were randomized. There was a lower initial CI (2.06 vs. 2.51 l min -1 m -2 , p = 0.042) in the closed-loop compared to the control group. No difference in final CO and in overall mean intraoperative CI was observed between groups. A significant relative increase from initial to final CI values was observed in the closed-loop but not the control group (+ 28.6%, p = 0.006 vs. + 1.2%, p = 0.843). No difference was found for intraoperative fluid management and postoperative outcomes between groups. There was no significant impact on the primary study endpoint, but this was found in a context of unexpected lower initial CI in the closed-loop group.Trial registry number ID-RCB/EudraCT: 2013-A00770-45. ClinicalTrials.gov Identifier NCT01950845, date of registration: 17 September 2013.

  4. Infants Show Stability of Goal-Directed Imitation

    Science.gov (United States)

    Sakkalou, Elena; Ellis-Davies, Kate; Fowler, Nia C.; Hilbrink, Elma E.; Gattis, Merideth

    2013-01-01

    Previous studies have reported that infants selectively reproduce observed actions and have argued that this selectivity reflects understanding of intentions and goals, or goal-directed imitation. We reasoned that if selective imitation of goal-directed actions reflects understanding of intentions, infants should demonstrate stability across…

  5. Habitual versus goal-directed action control in Parkinson disease.

    Science.gov (United States)

    de Wit, Sanne; Barker, Roger A; Dickinson, Anthony D; Cools, Roshan

    2011-05-01

    This study presents the first direct investigation of the hypothesis that dopamine depletion of the dorsal striatum in mild Parkinson disease leads to impaired stimulus-response habit formation, thereby rendering behavior slow and effortful. However, using an instrumental conflict task, we show that patients are able to rely on direct stimulus-response associations when a goal-directed strategy causes response conflict, suggesting that habit formation is not impaired. If anything our results suggest a disease severity-dependent deficit in goal-directed behavior. These results are discussed in the context of Parkinson disease and the neurobiology of habitual and goal-directed behavior.

  6. Object-based processes in the planning of goal-directed hand movements

    NARCIS (Netherlands)

    Bekkering, H.; Pratt, J.

    2004-01-01

    Theories in motor control suggest that the parameters specified during the planning of goal-directed hand movements to a visual target are defined in spatial parameters like direction and amplitude. Recent findings in the visual attention literature, however, argue widely for early object-based

  7. Goal Direction and Effectiveness, Emotional Maturity, and Nuclear Family Functioning

    Science.gov (United States)

    Klever, Phillip

    2009-01-01

    Differentiation of self, a cornerstone concept in Bowen theory, has a profound influence over time on the functioning of the individual and his or her family unit. This 5-year longitudinal study tested this hypothesis with 50 developing nuclear families. The dimensions of differentiation of self that were examined were goal direction and…

  8. Impaired acquisition of goal-directed action in healthy aging

    NARCIS (Netherlands)

    de Wit, S.; van de Vijver, I.; Ridderinkhof, K.R.

    2014-01-01

    According to dual-system theories, instrumental learning is supported by dissociable goal-directed and habitual systems. Previous investigations of the dual-system balance in healthy aging have yielded mixed results. To further investigate this issue, we compared performance of young (17-24 years)

  9. A Unifying Approach to Goal-Directed Evaluation

    DEFF Research Database (Denmark)

    Danvy, Olivier; Rhiger, Morten; Grobauer, Bernd

    2001-01-01

    Goal-directed evaluation, as embodied in Icon and Snobol, is built on the notions of backtracking and of generating successive results, and therefore it has always been something of a challenge to specify and implement. In this article, we address this challenge using computational monads and par...

  10. Goal-Directed Decision Making with Spiking Neurons.

    Science.gov (United States)

    Friedrich, Johannes; Lengyel, Máté

    2016-02-03

    Behavioral and neuroscientific data on reward-based decision making point to a fundamental distinction between habitual and goal-directed action selection. The formation of habits, which requires simple updating of cached values, has been studied in great detail, and the reward prediction error theory of dopamine function has enjoyed prominent success in accounting for its neural bases. In contrast, the neural circuit mechanisms of goal-directed decision making, requiring extended iterative computations to estimate values online, are still unknown. Here we present a spiking neural network that provably solves the difficult online value estimation problem underlying goal-directed decision making in a near-optimal way and reproduces behavioral as well as neurophysiological experimental data on tasks ranging from simple binary choice to sequential decision making. Our model uses local plasticity rules to learn the synaptic weights of a simple neural network to achieve optimal performance and solves one-step decision-making tasks, commonly considered in neuroeconomics, as well as more challenging sequential decision-making tasks within 1 s. These decision times, and their parametric dependence on task parameters, as well as the final choice probabilities match behavioral data, whereas the evolution of neural activities in the network closely mimics neural responses recorded in frontal cortices during the execution of such tasks. Our theory provides a principled framework to understand the neural underpinning of goal-directed decision making and makes novel predictions for sequential decision-making tasks with multiple rewards. Goal-directed actions requiring prospective planning pervade decision making, but their circuit-level mechanisms remain elusive. We show how a model circuit of biologically realistic spiking neurons can solve this computationally challenging problem in a novel way. The synaptic weights of our network can be learned using local plasticity rules

  11. Goal-directed learning and obsessive–compulsive disorder

    Science.gov (United States)

    Gillan, Claire M.; Robbins, Trevor W.

    2014-01-01

    Obsessive–compulsive disorder (OCD) has become a paradigmatic case of goal-directed dysfunction in psychiatry. In this article, we review the neurobiological evidence, historical and recent, that originally led to this supposition and continues to support a habit hypothesis of OCD. We will then discuss a number of recent studies that have directly tested this hypothesis, using behavioural experiments in patient populations. Based on this research evidence, which suggests that rather than goal-directed avoidance behaviours, compulsions in OCD may derive from manifestations of excessive habit formation, we present the details of a novel account of the functional relationship between these habits and the full symptom profile of the disorder. Borrowing from a cognitive dissonance framework, we propose that the irrational threat beliefs (obsessions) characteristic of OCD may be a consequence, rather than an instigator, of compulsive behaviour in these patients. This lays the foundation for a potential shift in both clinical and neuropsychological conceptualization of OCD and related disorders. This model may also prove relevant to other putative disorders of compulsivity, such as substance dependence, where the experience of ‘wanting’ drugs may be better understood as post hoc rationalizations of otherwise goal-insensitive, stimulus-driven behaviour. PMID:25267818

  12. A Unifying Approach to Goal-Directed Evaluation

    DEFF Research Database (Denmark)

    Danvy, Olivier; Grobauer, Bernd; Rhiger, Morten

    2001-01-01

    semantics coincides with Gudeman’s continuation semantics of Icon. We then compile Icon programs by specializing their interpreter (i.e., by using the first Futamura projection), using type-directed partial evaluation. Through various back ends, including a run-time code generator, we generate ML code, C......Goal-directed evaluation, as embodied in Icon and Snobol, is built on the notions of backtracking and of generating successive results, and therefore it has always been something of a challenge to specify and implement. In this article, we address this challenge using computational monads...... code, and OCaml byte code. Binding-time analysis and partial evaluation of the continuation-based interpreter automatically give rise to C programs that coincide with the result of Proebsting’s optimized compiler....

  13. Impaired cognitive plasticity and goal-directed control in adolescent obsessive-compulsive disorder.

    Science.gov (United States)

    Gottwald, Julia; de Wit, Sanne; Apergis-Schoute, Annemieke M; Morein-Zamir, Sharon; Kaser, Muzaffer; Cormack, Francesca; Sule, Akeem; Limmer, Winifred; Morris, Anna Conway; Robbins, Trevor W; Sahakian, Barbara J

    2018-01-22

    Youths with obsessive-compulsive disorder (OCD) experience severe distress and impaired functioning at school and at home. Critical cognitive domains for daily functioning and academic success are learning, memory, cognitive flexibility and goal-directed behavioural control. Performance in these important domains among teenagers with OCD was therefore investigated in this study. A total of 36 youths with OCD and 36 healthy comparison subjects completed two memory tasks: Pattern Recognition Memory (PRM) and Paired Associates Learning (PAL); as well as the Intra-Extra Dimensional Set Shift (IED) task to quantitatively gauge learning as well as cognitive flexibility. A subset of 30 participants of each group also completed a Differential-Outcome Effect (DOE) task followed by a Slips-of-Action Task, designed to assess the balance of goal-directed and habitual behavioural control. Adolescent OCD patients showed a significant learning and memory impairment. Compared with healthy comparison subjects, they made more errors on PRM and PAL and in the first stages of IED involving discrimination and reversal learning. Patients were also slower to learn about contingencies in the DOE task and were less sensitive to outcome devaluation, suggesting an impairment in goal-directed control. This study advances the characterization of juvenile OCD. Patients demonstrated impairments in all learning and memory tasks. We also provide the first experimental evidence of impaired goal-directed control and lack of cognitive plasticity early in the development of OCD. The extent to which the impairments in these cognitive domains impact academic performance and symptom development warrants further investigation.

  14. Goal-directed, habitual and Pavlovian prosocial behavior

    Directory of Open Access Journals (Sweden)

    Filip eGęsiarz

    2015-05-01

    Full Text Available Although prosocial behaviors have been widely studied across disciplines, the mechanisms underlying them are not fully understood. Evidence from psychology, biology and economics suggests that prosocial behaviors can be driven by a variety of seemingly opposing factors: altruism or egoism, intuition or deliberation, inborn instincts or learned dispositions, and utility derived from actions or their outcomes. Here we propose a framework inspired by research on reinforcement learning and decision making that links these processes and explains characteristics of prosocial behaviors in different contexts. More specifically, we suggest that prosocial behaviors inherit features of up to three decision-making systems employed to choose between self- and other- regarding acts: a goal-directed system that selects actions based on their predicted consequences, a habitual system that selects actions based on their reinforcement history, and a Pavlovian system that emits reflexive responses based on evolutionarily prescribed priors. This framework, initially described in the field of cognitive neuroscience and machine learning, provides insight into the potential neural circuits and computations shaping prosocial behaviors. Furthermore, it identifies specific conditions in which each of these three systems should dominate and promote other- or self- regarding behavior.

  15. Mediodorsal thalamus hypofunction impairs flexible goal-directed behavior.

    Science.gov (United States)

    Parnaudeau, Sébastien; Taylor, Kathleen; Bolkan, Scott S; Ward, Ryan D; Balsam, Peter D; Kellendonk, Christoph

    2015-03-01

    Cognitive inflexibility is a core symptom of several mental disorders including schizophrenia. Brain imaging studies in schizophrenia patients performing cognitive tasks have reported decreased activation of the mediodorsal thalamus (MD). Using a pharmacogenetic approach to model MD hypofunction, we recently showed that decreasing MD activity impairs reversal learning in mice. While this demonstrates causality between MD hypofunction and cognitive inflexibility, questions remain about the elementary cognitive processes that account for the deficit. Using the Designer Receptors Exclusively Activated by Designer Drugs system, we reversibly decreased MD activity during behavioral tasks assessing elementary cognitive processes inherent to flexible goal-directed behaviors, including extinction, contingency degradation, outcome devaluation, and Pavlovian-to-instrumental transfer (n = 134 mice). While MD hypofunction impaired reversal learning, it did not affect the ability to learn about nonrewarded cues or the ability to modulate action selection based on the outcome value. In contrast, decreasing MD activity delayed the ability to adapt to changes in the contingency between actions and their outcomes. In addition, while Pavlovian learning was not affected by MD hypofunction, decreasing MD activity during Pavlovian learning impaired the ability of conditioned stimuli to modulate instrumental behavior. Mediodorsal thalamus hypofunction causes cognitive inflexibility reflected by an impaired ability to adapt actions when their consequences change. Furthermore, it alters the encoding of environmental stimuli so that they cannot be properly utilized to guide behavior. Modulating MD activity could be a potential therapeutic strategy for promoting adaptive behavior in human subjects with cognitive inflexibility. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Speed/accuracy trade-off between the habitual and the goal-directed processes.

    Directory of Open Access Journals (Sweden)

    Mehdi Keramati

    2011-05-01

    Full Text Available Instrumental responses are hypothesized to be of two kinds: habitual and goal-directed, mediated by the sensorimotor and the associative cortico-basal ganglia circuits, respectively. The existence of the two heterogeneous associative learning mechanisms can be hypothesized to arise from the comparative advantages that they have at different stages of learning. In this paper, we assume that the goal-directed system is behaviourally flexible, but slow in choice selection. The habitual system, in contrast, is fast in responding, but inflexible in adapting its behavioural strategy to new conditions. Based on these assumptions and using the computational theory of reinforcement learning, we propose a normative model for arbitration between the two processes that makes an approximately optimal balance between search-time and accuracy in decision making. Behaviourally, the model can explain experimental evidence on behavioural sensitivity to outcome at the early stages of learning, but insensitivity at the later stages. It also explains that when two choices with equal incentive values are available concurrently, the behaviour remains outcome-sensitive, even after extensive training. Moreover, the model can explain choice reaction time variations during the course of learning, as well as the experimental observation that as the number of choices increases, the reaction time also increases. Neurobiologically, by assuming that phasic and tonic activities of midbrain dopamine neurons carry the reward prediction error and the average reward signals used by the model, respectively, the model predicts that whereas phasic dopamine indirectly affects behaviour through reinforcing stimulus-response associations, tonic dopamine can directly affect behaviour through manipulating the competition between the habitual and the goal-directed systems and thus, affect reaction time.

  17. Music as therapy in early history.

    Science.gov (United States)

    Thaut, Michael H

    2015-01-01

    The notion of music as therapy is based on ancient cross-cultural beliefs that music can have a "healing" effect on mind and body. Explanations for the therapeutic mechanisms in music have almost always included cultural and social science-based causalities about the uses and functions of music in society. However, it is also important to note that the view of music as "therapy" was also always strongly influenced by the view and understanding of the concepts and causes of disease. Magical/mystical concepts of illness and "rational" medicine probably lived side by side for thousands of years. Not until the late-nineteenth and early-twentieth centuries were the scientific foundations of medicine established, which allowed the foundations of music in therapy to progress from no science to soft science and most recently to actual brain science. Evidence for "early music therapy" will be discussed in four broad historical-cultural divisions: preliterate cultures; early civilizations in Mesopotamia, Egypt, Israel; Greek Antiquity; Middle Ages, Renaissance, and Baroque. In reviewing "early music therapy" practice, from mostly unknown periods of early history (using preliterate cultures as a window) to increasingly better documented times, including preserved notation samples of actual "healing" music, five theories and applications of early music therapy can be differentiated. © 2015 Elsevier B.V. All rights reserved.

  18. Early haemorrhage control and management of trauma-induced coagulopathy

    DEFF Research Database (Denmark)

    Stensballe, Jakob; Henriksen, Hanne H; Johansson, Pär I

    2017-01-01

    of trauma resuscitation using a ratio-driven strategy aiming at 1:1:1 of red blood cells, plasma and platelets while applying goal-directed therapy early and repeatedly to control trauma-induced coagulopathy. SUMMARY: Trauma resuscitation should focus on early goal-directed therapy with use of viscoelastic...... haemostatic assays while initially applying a ratio 1:1:1 driven transfusion therapy (with red blood cells, plasma and platelets) in order to sustain normal haemostasis and control further bleeding....

  19. Reliance on habits at the expense of goal-directed control following dopamine precursor depletion

    OpenAIRE

    de Wit, Sanne; Standing, Holly R.; DeVito, Elise E.; Robinson, Oliver J.; Ridderinkhof, K. Richard; Robbins, Trevor W.; Sahakian, Barbara J.

    2011-01-01

    Rationale Dopamine is well known to play an important role in learning and motivation. Recent animal studies have implicated dopamine in the reinforcement of stimulus?response habits, as well as in flexible, goal-directed action. However, the role of dopamine in human action control is still not well understood. Objectives We present the first investigation of the effect of reducing dopamine function in healthy volunteers on the balance between habitual and goal-directed action control. Metho...

  20. Sleep Deprivation Promotes Habitual Control over Goal-Directed Control: Behavioral and Neuroimaging Evidence.

    Science.gov (United States)

    Chen, Jie; Liang, Jie; Lin, Xiao; Zhang, Yang; Zhang, Yan; Lu, Lin; Shi, Jie

    2017-12-06

    Sleep is one of the most fundamental processes of life, playing an important role in the regulation of brain function. The long-term lack of sleep can cause memory impairments, declines in learning ability, and executive dysfunction. In the present study, we evaluated the effects of sleep deprivation on instrumental learning behavior, particularly goal-directed and habitual actions in humans, and investigated the underlying neural mechanisms. Healthy college students of either gender were enrolled and randomly divided into sleep deprivation group and sleep control group. fMRI data were collected. We found that one night of sleep deprivation led to greater responsiveness to stimuli that were associated with devalued outcomes in the slips-of-action test, indicating a deficit in the formation of goal-directed control and an overreliance on habits. Furthermore, sleep deprivation had no effect on the expression of acquired goal-directed action. The level of goal-directed action after sleep deprivation was positively correlated with baseline working memory capacity. The neuroimaging data indicated that goal-directed learning mainly recruited the ventromedial PFC (vmPFC), the activation of which was less pronounced during goal-directed learning after sleep deprivation. Activation of the vmPFC during goal-directed learning during training was positively correlated with the level of goal-directed action performance. The present study suggests that people rely predominantly on habits at the expense of goal-directed control after sleep deprivation, and this process involves the vmPFC. These results contribute to a better understanding of the effects of sleep loss on decision-making. SIGNIFICANCE STATEMENT Understanding the cognitive consequences of sleep deprivation has become extremely important over the past half century, given the continued decline in sleep duration in industrialized societies. Our results provide novel evidence that goal-directed action may be

  1. The Effects of Methylphenidate on Goal-Directed Behavior in a Rat Model of ADHD

    Directory of Open Access Journals (Sweden)

    Joman Y. Natsheh

    2015-11-01

    Full Text Available Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75-P105] Spontaneously Hypertensive Rats (SHR (ADHD rat model and Wistar-Kyoto rats (WKY, the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action-outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate, a commonly used ADHD medication, on goal-directed behavior, we injected rats with either Methylphenidate or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, methylphenidate administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how methylphenidate acts differently on SHR and WKY animals to restore or impair this behavior, respectively.

  2. Advanced Parkinson’s disease effect on goal-directed and habitual processes involved in visuomotor associative learning

    Directory of Open Access Journals (Sweden)

    Fadila eHadj-Bouziane

    2013-01-01

    Full Text Available The present behavioral study readdresses the question of habit learning in Parkinson's disease. Patients were early onset, non-demented, dopa-responsive, candidates for surgical treatment, similar to those we found earlier as suffering greater dopamine depletion in the putamen than in the caudate nucleus. The task was the same conditional associative learning task as that used previously in monkeys and healthy humans to unveil the striatum involvement in habit learning. Sixteen patients and 20 age- and education-matched healthy control subjects learned sets of 3 visuo-motor associations between complex patterns and joystick displacements during two testing sessions separated by a few hours. We distinguished errors preceding versus following the first correct response to compare patients' performance during the earliest phase of learning dominated by goal-directed actions with that observed later on, when responses start to become habitual. The disease significantly retarded both learning phases, especially in patients under sixty years of age. However, only the late phase deficit was disease severity-dependent and persisted on the second testing session. These findings provide the first corroboration in Parkinson patients of two ideas well-established in the animal literature. The first is the idea that associating visual stimuli to motor acts is a form of habit learning that engages the striatum. It is confirmed here by the global impairment in visuo-motor learning induced by Parkinson's disease. The second idea is that goal-directed behaviors are predominantly caudate-dependent whereas habitual responses are primarily putamen-dependent. At the advanced Parkinson's disease stages tested here, dopamine depletion is greater in the putamen than in the caudate nucleus. Accordingly, the late phase of learning corresponding to the emergence of habitual responses was more vulnerable to the disease than the early phase dominated by goal-directed

  3. Mirroring "meaningful" actions: sensorimotor learning modulates imitation of goal-directed actions.

    Science.gov (United States)

    Catmur, Caroline; Heyes, Cecilia

    2017-06-19

    Imitation is important in the development of social and technological skills throughout the lifespan. Experiments investigating the acquisition and modulation of imitation (and of its proposed neural substrate, the mirror neuron system) have produced evidence that the capacity for imitation depends on associative learning in which connections are formed between sensory and motor representations of actions. However, evidence that the development of imitation depends on associative learning has been found only for non-goal-directed actions. One reason for the lack of research on goal-directed actions is that imitation of such actions is commonly confounded with the tendency to respond in a spatially compatible manner. However, since the most prominent account of mirror neuron function, and hence of imitation, suggests that these cells encode goal-directed actions, it is important to establish whether sensorimotor learning can also modulate imitation of goal-directed actions. Experiment 1 demonstrated that imitation of goal-directed grasping can be measured while controlling for spatial compatibility, and Experiment 2 showed that this imitation effect can be modulated by sensorimotor training. Together these data support the hypothesis that the capacity for behavioural imitation, and the properties of the mirror neuron system, are constructed in the course of development through associative learning.

  4. Resolution of conflict between goal-directed actions: outcome encoding and neural control processes.

    Science.gov (United States)

    de Wit, Sanne; Ostlund, Sean B; Balleine, Bernard W; Dickinson, Anthony

    2009-07-01

    According to O-R theory of instrumental learning, incongruent biconditional discriminations should be impossible to solve in a goal-directed manner because the event acting as the outcome of one response also acts as a discriminative stimulus for an opposite response. Each event should therefore be associated with two competing responses. However, Dickinson and de Wit (2003) have presented evidence that rats can learn incongruent discriminations. The present study investigated whether rats were able to engage additional processes to solve incongruent discriminations in a goal-directed manner. Experiment 1 provides evidence that rats resolve the response conflict that arises in the incongruent discrimination by differentially encoding events in their roles as discriminative stimulus and as outcome. Furthermore, Experiment 2 shows that once goal-directed control has been established the dorsomedial prefrontal cortex is not directly involved in its maintenance but rather plays a central role in conflict resolution processes.

  5. Emotion, Intent and Voluntary Movement in Children with Autism. an Example: The Goal Directed Locomotion

    Science.gov (United States)

    Longuet, Sophie; Ferrel-Chapus, Carole; Oreve, Marie-Joelle; Chamot, Jean-Marc; Vernazza-Martin, Sylvie

    2012-01-01

    This article focuses on the impact of intentionality on goal directed locomotion in healthy and autistic children. Closely linked with emotions and motivation, it is directly connected with movement planning. Is planning only preserved when the goal of the action appears motivating for healthy and autistic children? Is movement programming similar…

  6. Music and Video Gaming during Breaks: Influence on Habitual versus Goal-Directed Decision Making.

    Directory of Open Access Journals (Sweden)

    Shuyan Liu

    Full Text Available Different systems for habitual versus goal-directed control are thought to underlie human decision-making. Working memory is known to shape these decision-making systems and their interplay, and is known to support goal-directed decision making even under stress. Here, we investigated if and how decision systems are differentially influenced by breaks filled with diverse everyday life activities known to modulate working memory performance. We used a within-subject design where young adults listened to music and played a video game during breaks interleaved with trials of a sequential two-step Markov decision task, designed to assess habitual as well as goal-directed decision making. Based on a neurocomputational model of task performance, we observed that for individuals with a rather limited working memory capacity video gaming as compared to music reduced reliance on the goal-directed decision-making system, while a rather large working memory capacity prevented such a decline. Our findings suggest differential effects of everyday activities on key decision-making processes.

  7. Goal-Directed and Goal-Less Imitation in Autism Spectrum Disorder

    Science.gov (United States)

    Wild, Kelly S.; Poliakoff, Ellen; Jerrison, Andrew; Gowen, Emma

    2012-01-01

    To investigate how people with Autism are affected by the presence of goals during imitation, we conducted a study to measure movement kinematics and eye movements during the imitation of goal-directed and goal-less hand movements. Our results showed that a control group imitated changes in movement kinematics and increased the level that they…

  8. Corticostriatal connectivity underlies individual differences in the balance between habitual and goal-directed action control

    NARCIS (Netherlands)

    Wit, S. de; Watson, A.J.P.; Harsay, H.A.; Cohen, M.X.; Vijver, I. van de; Ridderinkhof, K.R.

    2012-01-01

    Why are some individuals more susceptible to the formation of inflexible habits than others? In the present study, we used diffusion tensor imaging to demonstrate that brain connectivity predicts individual differences in relative goal-directed and habitual behavioral control in humans.

  9. Associative theories of goal-directed behaviour: a case for animal-human translational models

    NARCIS (Netherlands)

    de Wit, S.; Dickinson, A.

    2009-01-01

    Associative accounts of goal-directed action, developed in the fields of human ideomotor action and that of animal learning, can capture cognitive belief-desire psychology of human decision-making. Whereas outcome-response accounts can account for the fact that the thought of a goal can call to mind

  10. Product behavior and appearance effects on experienced engagement during experimental and goal-directed tasks

    NARCIS (Netherlands)

    Rozendaal, M.C.; Keyson, D.V.; Ridder, de H.

    2007-01-01

    This study examines how digital products can be designed towards increased levels of experienced engagement. An experiment was conducted in which 24 participants were asked to interact with a videogame that varied in behavior and appearance aspects during experiential and goal-directed tasks.

  11. Goal-Directed Action Control in Children with Autism Spectrum Disorders

    Science.gov (United States)

    Geurts, Hilde M; de Wit, Sanne

    2014-01-01

    Repetitive behavior is a key characteristic of autism spectrum disorders. Our aim was to investigate the hypothesis that this abnormal behavioral repetition results from a tendency to over-rely on habits at the expense of flexible, goal-directed action. Twenty-four children with autism spectrum disorders and 24 age- and gender-matched controls…

  12. Four Weeks of Goal-Directed Learning in Primary Physical Education Classes

    NARCIS (Netherlands)

    Platvoet, Sebastiaan W. J.; Elferink-Gemser, Marije T.; Kannekens, Rianne; de Niet, Mark; Visscher, Chris

    Relatively little is known about how practice relates to children's improvement in gross motor skill performance. The aim of this study is to determine to what extent 6- and 7-year-old children improve their gross motor skill performance in a four-week period, in which goal-directed learning is

  13. Goal-directed action control in children with autism spectrum disorders

    NARCIS (Netherlands)

    Geurts, H.M.; de Wit, S.

    2014-01-01

    Repetitive behavior is a key characteristic of autism spectrum disorders. Our aim was to investigate the hypothesis that this abnormal behavioral repetition results from a tendency to over-rely on habits at the expense of flexible, goal-directed action. Twenty-four children with autism spectrum

  14. Reliance on habits at the expense of goal-directed control following dopamine precursor depletion

    NARCIS (Netherlands)

    de Wit, S.; Standing, H.R.; DeVito, E.E.; Robinson, O.J.; Ridderinkhof, K.R.; Robbins, T.W.; Sahakian, B.J.

    2012-01-01

    Rationale Dopamine is well known to play an important role in learning and motivation. Recent animal studies have implicated dopamine in the reinforcement of stimulus-response habits, as well as in flexible, goal-directed action. However, the role of dopamine in human action control is still not

  15. Music and Video Gaming during Breaks: Influence on Habitual versus Goal-Directed Decision Making.

    Science.gov (United States)

    Liu, Shuyan; Schad, Daniel J; Kuschpel, Maxim S; Rapp, Michael A; Heinz, Andreas

    2016-01-01

    Different systems for habitual versus goal-directed control are thought to underlie human decision-making. Working memory is known to shape these decision-making systems and their interplay, and is known to support goal-directed decision making even under stress. Here, we investigated if and how decision systems are differentially influenced by breaks filled with diverse everyday life activities known to modulate working memory performance. We used a within-subject design where young adults listened to music and played a video game during breaks interleaved with trials of a sequential two-step Markov decision task, designed to assess habitual as well as goal-directed decision making. Based on a neurocomputational model of task performance, we observed that for individuals with a rather limited working memory capacity video gaming as compared to music reduced reliance on the goal-directed decision-making system, while a rather large working memory capacity prevented such a decline. Our findings suggest differential effects of everyday activities on key decision-making processes.

  16. Radiation therapy of early glottic cancer

    International Nuclear Information System (INIS)

    Neri, S.

    1987-01-01

    The control of early glottic cancer is equally satisfactory with either surgical resection or radiation therapy; this last method gives the patient good functional results. During the period from 1/1978 to 12/1985, 73 patients with early glottic carcinoma (T1 N0 M0) were treated in the Institute of Radiotherapy L. Galvani, University of Bologna; 45 were stage T1a (tumor limited to one vocal cord) and 28 were stage T1b (tumor of both vocal cords or involving anterior commissure); radiation treatment utilized a 60 Co machine and 5x5 cm fields; the median dose was 67.2 Gy (range 50-76) with conventional fractionation. Ten patients had local recurrence; the median time of recurrence was 13.4 months; 9/10 were treated by surgery and 2/10 died, so the overall control by radiotherapy with surgery in reserve was 100% in T1a tumers and 90.6% in T1b ones. The 5-years disease free survival rate was 93.1% in T1a tumors and 69% in T1b; lesions involving anterior commissure had the worst prognosis, independent of the dose and time-dose factor (3/10 recurrences in the group treated with TDF less than 110 and 4/18 recurrences in the group with TDF more than 110)

  17. Antiretroviral therapy in a community clinic - early lessons from a ...

    African Journals Online (AJOL)

    Antiretroviral therapy in a community clinic - early lessons from a pilot project. ... The HIV Research Unit, University of Cape Town, supplied training and ... Attention must be given to the diagnosis of tuberculosis during screening and early ART ...

  18. Goal-directed fluid optimization based on stroke volume variation and cardiac index during one-lung ventilation in patients undergoing thoracoscopy lobectomy operations: a pilot study

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    2013-07-01

    Full Text Available OBJECTIVES: This pilot study was designed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies. METHODS: Eighty patients undergoing thoracoscopic lobectomy were randomized into either a goal-directed therapy group or a control group. In the goal-directed therapy group, the stroke volume variation was controlled at 10%±1%, and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2. In the control group, the MAP was maintained at between 65 mm Hg and 90 mm Hg, heart rate was maintained at between 60 BPM and 100 BPM, and urinary output was greater than 0.5 mL/kg-1/h-1. The hemodynamic variables, arterial blood gas analyses, total administered fluid volume and side effects were recorded. RESULTS: The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal-directed therapy group was significantly higher than that of the control group, but there were no differences between the goal-directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia. The extubation time was significantly earlier in the goal-directed therapy group, but there was no difference in the length of hospital stay. Patients in the control group had greater urine volumes, and they were given greater colloid and overall fluid volumes. Nausea and vomiting were significantly reduced in the goal-directed therapy group. CONCLUSION: The results of this study demonstrated that an optimization protocol, based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device, increased the PaO2/FiO2-ratio and reduced the overall fluid volume, intubation time and postoperative complications (nausea and vomiting in thoracic surgery patients requiring one-lung ventilation.

  19. How to Build an Intentional Android: Infants' Imitation of a Robot's Goal-Directed Actions

    Science.gov (United States)

    Itakura, Shoji; Ishida, Hiraku; Kanda, Takayuki; Shimada, Yohko; Ishiguro, Hiroshi; Lee, Kang

    2008-01-01

    This study examined whether young children are able to imitate a robot's goal-directed actions. Children (24-35 months old) viewed videos showing a robot attempting to manipulate an object (e.g., putting beads inside a cup) but failing to achieve its goal (e.g., beads fell outside the cup). In 1 video, the robot made eye contact with a human…

  20. Reliance on habits at the expense of goal-directed control following dopamine precursor depletion.

    Science.gov (United States)

    de Wit, Sanne; Standing, Holly R; Devito, Elise E; Robinson, Oliver J; Ridderinkhof, K Richard; Robbins, Trevor W; Sahakian, Barbara J

    2012-01-01

    Dopamine is well known to play an important role in learning and motivation. Recent animal studies have implicated dopamine in the reinforcement of stimulus-response habits, as well as in flexible, goal-directed action. However, the role of dopamine in human action control is still not well understood. We present the first investigation of the effect of reducing dopamine function in healthy volunteers on the balance between habitual and goal-directed action control. The dietary intervention of acute dietary phenylalanine and tyrosine depletion (APTD) was adopted to study the effects of reduced global dopamine function on action control. Participants were randomly assigned to either the APTD or placebo group (ns = 14) to allow for a between-subjects comparison of performance on a novel three-stage experimental paradigm. In the initial learning phase, participants learned to respond to different stimuli in order to gain rewarding outcomes. Subsequently, an outcome-devaluation test and a slips-of-action test were conducted to assess whether participants were able to flexibly adjust their behaviour to changes in the desirability of the outcomes. APTD did not prevent stimulus-response learning, nor did we find evidence for impaired response-outcome learning in the subsequent outcome-devaluation test. However, when goal-directed and habitual systems competed for control in the slips-of-action test, APTD tipped the balance towards habitual control. These findings were restricted to female volunteers. We provide direct evidence that the balance between goal-directed and habitual control in humans is dopamine dependent. The results are discussed in light of gender differences in dopamine function and psychopathologies.

  1. Interaction of Instrumental and Goal-Directed Learning Modulates Prediction Error Representations in the Ventral Striatum.

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    Guo, Rong; Böhmer, Wendelin; Hebart, Martin; Chien, Samson; Sommer, Tobias; Obermayer, Klaus; Gläscher, Jan

    2016-12-14

    Goal-directed and instrumental learning are both important controllers of human behavior. Learning about which stimulus event occurs in the environment and the reward associated with them allows humans to seek out the most valuable stimulus and move through the environment in a goal-directed manner. Stimulus-response associations are characteristic of instrumental learning, whereas response-outcome associations are the hallmark of goal-directed learning. Here we provide behavioral, computational, and neuroimaging results from a novel task in which stimulus-response and response-outcome associations are learned simultaneously but dominate behavior at different stages of the experiment. We found that prediction error representations in the ventral striatum depend on which type of learning dominates. Furthermore, the amygdala tracks the time-dependent weighting of stimulus-response versus response-outcome learning. Our findings suggest that the goal-directed and instrumental controllers dynamically engage the ventral striatum in representing prediction errors whenever one of them is dominating choice behavior. Converging evidence in human neuroimaging studies has shown that the reward prediction errors are correlated with activity in the ventral striatum. Our results demonstrate that this region is simultaneously correlated with a stimulus prediction error. Furthermore, the learning system that is currently dominating behavioral choice dynamically engages the ventral striatum for computing its prediction errors. This demonstrates that the prediction error representations are highly dynamic and influenced by various experimental context. This finding points to a general role of the ventral striatum in detecting expectancy violations and encoding error signals regardless of the specific nature of the reinforcer itself. Copyright © 2016 the authors 0270-6474/16/3612650-11$15.00/0.

  2. Executive control of stimulus-driven and goal-directed attention in visual working memory.

    Science.gov (United States)

    Hu, Yanmei; Allen, Richard J; Baddeley, Alan D; Hitch, Graham J

    2016-10-01

    We examined the role of executive control in stimulus-driven and goal-directed attention in visual working memory using probed recall of a series of objects, a task that allows study of the dynamics of storage through analysis of serial position data. Experiment 1 examined whether executive control underlies goal-directed prioritization of certain items within the sequence. Instructing participants to prioritize either the first or final item resulted in improved recall for these items, and an increase in concurrent task difficulty reduced or abolished these gains, consistent with their dependence on executive control. Experiment 2 examined whether executive control is also involved in the disruption caused by a post-series visual distractor (suffix). A demanding concurrent task disrupted memory for all items except the most recent, whereas a suffix disrupted only the most recent items. There was no interaction when concurrent load and suffix were combined, suggesting that deploying selective attention to ignore the distractor did not draw upon executive resources. A final experiment replicated the independent interfering effects of suffix and concurrent load while ruling out possible artifacts. We discuss the results in terms of a domain-general episodic buffer in which information is retained in a transient, limited capacity privileged state, influenced by both stimulus-driven and goal-directed processes. The privileged state contains the most recent environmental input together with goal-relevant representations being actively maintained using executive resources.

  3. The Neural Representation of Goal-Directed Actions and Outcomes in the Ventral Striatum's Olfactory Tubercle

    Science.gov (United States)

    Gadziola, Marie A.

    2016-01-01

    The ventral striatum is critical for evaluating reward information and the initiation of goal-directed behaviors. The many cellular, afferent, and efferent similarities between the ventral striatum's nucleus accumbens and olfactory tubercle (OT) suggests the distributed involvement of neurons within the ventral striatopallidal complex in motivated behaviors. Although the nucleus accumbens has an established role in representing goal-directed actions and their outcomes, it is not known whether this function is localized within the nucleus accumbens or distributed also within the OT. Answering such a fundamental question will expand our understanding of the neural mechanisms underlying motivated behaviors. Here we address whether the OT encodes natural reinforcers and serves as a substrate for motivational information processing. In recordings from mice engaged in a novel water-motivated instrumental task, we report that OT neurons modulate their firing rate during initiation and progression of the instrumental licking behavior, with some activity being internally generated and preceding the first lick. We further found that as motivational drive decreases throughout a session, the activity of OT neurons is enhanced earlier relative to the behavioral action. Additionally, OT neurons discriminate the types and magnitudes of fluid reinforcers. Together, these data suggest that the processing of reward information and the orchestration of goal-directed behaviors is a global principle of the ventral striatum and have important implications for understanding the neural systems subserving addiction and mood disorders. SIGNIFICANCE STATEMENT Goal-directed behaviors are widespread among animals and underlie complex behaviors ranging from food intake, social behavior, and even pathological conditions, such as gambling and drug addiction. The ventral striatum is a neural system critical for evaluating reward information and the initiation of goal-directed behaviors. Here we

  4. Goal-Directed Fluid Resuscitation Protocol Based on Arterial Waveform Analysis of Major Burn Patients in a Mass Burn Casualty.

    Science.gov (United States)

    Chiao, Hao-Yu; Chou, Chang-Yi; Tzeng, Yuan-Sheng; Wang, Chih-Hsin; Chen, Shyi-Gen; Dai, Niann-Tzyy

    2018-02-01

    Adequate fluid titration during the initial resuscitation period of major burn patients is crucial. This study aimed to evaluate the feasibility and efficacy of a goal-directed fluid resuscitation protocol that used hourly urine output plus the arterial waveform analysis FloTrac (Edwards LifeSciences, Irvine, Calif) system for major burns to avoid fluid overload. We conducted a retrospective cohort study of 43 major burn patients at the Tri-Service General Hospital after the Formosa Fun Coast Dust Explosion on June 27, 2015. Because of the limited capacity of intensive care units (ICUs), 23 intubated patients were transferred from the burn wards or emergency department to the ICU within 24 hours. Fluid administration was adjusted to achieve a urine output of 30 to 50 mL/h, cardiac index greater than 2.5 L/min/m, and stroke volume variation (SVV) less than 12%. The hourly crystalloid fluid infusion rate was titrated based on SVV and hourly urine output. Of the 23 critically burned patients admitted to the ICU, 13 patients who followed the goal-directed fluid resuscitation protocol within 12 hours postburn were included in the analysis. The mean age (years) was 21.8, and the mean total body surface area (TBSA) burned (%) was 68.0. The mean Revised Baux score was 106.8. All patients sustained inhalation injury. The fluid volumes administered to patients in the first 24 hours and the second 24 hours (mL/kg/% total body surface area) were 3.62 ± 1.23 and 2.89 ± 0.79, respectively. The urine outputs in the first 24 hours and the second 24 hours (mL/kg/h) were 1.13 ± 0.66 and 1.53 ± 0.87, respectively. All patients achieved the established goals within 32 hours postburn. In-hospital mortality rate was 0%. The SVV-based goal-directed fluid resuscitation protocol leads to less unnecessary fluid administration during the early resuscitation phase. Clinicians can efficaciously manage the dynamic body fluid changes in major burn patients under the guidance of the protocol.

  5. Dynamical Intention: Integrated Intelligence Modeling for Goal-directed Embodied Agents

    Directory of Open Access Journals (Sweden)

    Eric Aaron

    2016-11-01

    Full Text Available Intelligent embodied robots are integrated systems: As they move continuously through their environments, executing behaviors and carrying out tasks, components for low-level and high-level intelligence are integrated in the robot's cognitive system, and cognitive and physical processes combine to create their behavior. For a modeling framework to enable the design and analysis of such integrated intelligence, the underlying representations in the design of the robot should be dynamically sensitive, capable of reflecting both continuous motion and micro-cognitive influences, while also directly representing the necessary beliefs and intentions for goal-directed behavior. In this paper, a dynamical intention-based modeling framework is presented that satisfies these criteria, along with a hybrid dynamical cognitive agent (HDCA framework for employing dynamical intentions in embodied agents. This dynamical intention-HDCA (DI-HDCA modeling framework is a fusion of concepts from spreading activation networks, hybrid dynamical system models, and the BDI (belief-desire-intention theory of goal-directed reasoning, adapted and employed unconventionally to meet entailments of environment and embodiment. The paper presents two kinds of autonomous agent learning results that demonstrate dynamical intentions and the multi-faceted integration they enable in embodied robots: with a simulated service robot in a grid-world office environment, reactive-level learning minimizes reliance on deliberative-level intelligence, enabling task sequencing and action selection to be distributed over both deliberative and reactive levels; and with a simulated game of Tag, the cognitive-physical integration of an autonomous agent enables the straightforward learning of a user-specified strategy during gameplay, without interruption to the game. In addition, the paper argues that dynamical intentions are consistent with cognitive theory underlying goal-directed behavior, and

  6. SHOULD I STAY OR SHOULD I GO? CONCEPTUAL UNDERPINNINGS OF GOAL-DIRECTED ACTIONS

    Directory of Open Access Journals (Sweden)

    GIOVANNI eMIRABELLA

    2014-11-01

    Full Text Available All actions, even the simplest like moving an arm to grasp a pen, are associated with energy costs. Thus all mobile organisms possess the ability to evaluate resources and select those behaviours that are most likely to lead to the greatest accrual of valuable items (rewards in the near or, especially in the case of humans, distant future. The evaluation process is performed at all possible stages of the series of decisions that lead to the building of a goal-directed action or to its suppression. This is because all animals have a limited amount of energy and resources; to survive and be able to reproduce they have to minimize the costs and maximize the outcomes of their actions. These computations are at the root of behavioral flexibility. Two executive functions play a major role in generating flexible behaviors: i the ability to predict future outcomes of goal-directed actions; and ii the ability to cancel them when they are unlikely to accomplish valuable results. These two processes operate continuously during the entire course of a movement: during its genesis, its planning and even its execution, so that the motor output can be modulated or suppressed at any time before its execution.In this review, functional interactions of the extended neural network subserving generation and inhibition of goal-directed movements will be outlined, leading to the intriguing hypothesis that the performance of actions and their suppression are not specified by independent sets of brain regions. Rather, it will be proposed that acting and stopping are functions emerging from specific interactions between largely overlapping brain regions, whose activity is intimately linked (directly or indirectly to the evaluations of pros and cons of an action. Such mechanism would allow the brain to perform as a highly efficient and flexible system, as different functions could be computed exploiting the same components operating in different configurations.

  7. Tryptophan Depletion Promotes Habitual over Goal-Directed Control of Appetitive Responding in Humans.

    Science.gov (United States)

    Worbe, Yulia; Savulich, George; de Wit, Sanne; Fernandez-Egea, Emilio; Robbins, Trevor W

    2015-02-05

    Optimal behavioral performance results from a balance between goal-directed and habitual systems of behavioral control, which are modulated by ascending monoaminergic projections. While the role of the dopaminergic system in behavioral control has been recently addressed, the extent to which changes in global serotonin neurotransmission could influence these 2 systems is still poorly understood. We employed the dietary acute tryptophan depletion procedure to reduce serotonin neurotransmission in 18 healthy volunteers and 18 matched controls. We used a 3-stage instrumental learning paradigm that includes an initial instrumental learning stage, a subsequent outcome-devaluation test, and a slip-of-action stage, which directly tests the balance between hypothetical goal-directed and habitual systems. We also employed a separate response inhibition control test to assess the behavioral specificity of the results. Acute tryptophan depletion produced a shift of behavioral performance towards habitual responding as indexed by performance on the slip-of-action test. Moreover, greater habitual responding in the acute tryptophan depletion group was predicted by a steeper decline in plasma tryptophan levels. In contrast, acute tryptophan depletion left intact the ability to use discriminative stimuli to guide instrumental choice as indexed by the instrumental learning stage and did not impair inhibitory response control. The major implication of this study is that serotonin modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. Our findings thus imply that diminished serotonin neurotransmission shifts behavioral control towards habitual responding. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  8. Real-time decreased sensitivity to an audio-visual illusion during goal-directed reaching.

    Directory of Open Access Journals (Sweden)

    Luc Tremblay

    Full Text Available In humans, sensory afferences are combined and integrated by the central nervous system (Ernst MO, Bülthoff HH (2004 Trends Cogn. Sci. 8: 162-169 and appear to provide a holistic representation of the environment. Empirical studies have repeatedly shown that vision dominates the other senses, especially for tasks with spatial demands. In contrast, it has also been observed that sound can strongly alter the perception of visual events. For example, when presented with 2 flashes and 1 beep in a very brief period of time, humans often report seeing 1 flash (i.e. fusion illusion, Andersen TS, Tiippana K, Sams M (2004 Brain Res. Cogn. Brain Res. 21: 301-308. However, it is not known how an unfolding movement modulates the contribution of vision to perception. Here, we used the audio-visual illusion to demonstrate that goal-directed movements can alter visual information processing in real-time. Specifically, the fusion illusion was linearly reduced as a function of limb velocity. These results suggest that cue combination and integration can be modulated in real-time by goal-directed behaviors; perhaps through sensory gating (Chapman CE, Beauchamp E (2006 J. Neurophysiol. 96: 1664-1675 and/or altered sensory noise (Ernst MO, Bülthoff HH (2004 Trends Cogn. Sci. 8: 162-169 during limb movements.

  9. When Preferences Are in the Way: Children's Predictions of Goal-Directed Behaviors.

    Science.gov (United States)

    Yang, Fan; Frye, Douglas

    2017-12-18

    Across three studies, we examined 4- to 7-year-olds' predictions of goal-directed behaviors when goals conflict with preferences. In Study 1, when presented with stories in which a character had to act against basic preferences to achieve an interpersonal goal (e.g., playing with a partner), 6- and 7-year-olds were more likely than 4- and 5-year-olds to predict the actor would act in accordance with the goal to play with the partner, instead of fulfilling the basic preference of playing a favored activity. Similar results were obtained in Study 2 with scenarios that each involved a single individual pursuing intrapersonal goals that conflicted with his or her basic preferences. In Study 3, younger children's predictions of goal-directed behaviors did not increase for novel goals and preferences, when the influences of their own preferences, future thinking, or a lack of impulse control were minimized. The results suggest that between ages 4 and 7, children increasingly integrate and give more weight to other sources of motivational information (e.g., goals) in addition to preferences when predicting people's behaviors. This increasing awareness may have implications for children's self-regulatory and goal pursuit behaviors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. Is goal-directed attentional guidance just intertrial priming? A review.

    Science.gov (United States)

    Lamy, Dominique F; Kristjánsson, Arni

    2013-07-01

    According to most models of selective visual attention, our goals at any given moment and saliency in the visual field determine attentional priority. But selection is not carried out in isolation--we typically track objects through space and time. This is not well captured within the distinction between goal-directed and saliency-based attentional guidance. Recent studies have shown that selection is strongly facilitated when the characteristics of the objects to be attended and of those to be ignored remain constant between consecutive selections. These studies have generated the proposal that goal-directed or top-down effects are best understood as intertrial priming effects. Here, we provide a detailed overview and critical appraisal of the arguments, experimental strategies, and findings that have been used to promote this idea, along with a review of studies providing potential counterarguments. We divide this review according to different types of attentional control settings that observers are thought to adopt during visual search: feature-based settings, dimension-based settings, and singleton detection mode. We conclude that priming accounts for considerable portions of effects attributed to top-down guidance, but that top-down guidance can be independent of intertrial priming.

  11. INSTALLING AN ERP SYSTEM WITH A METHODOLOGY BASED ON THE PRINCIPLES OF GOAL DIRECTED PROJECT MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Ioannis Zafeiropoulos

    2010-01-01

    Full Text Available This paper describes a generic methodology to support the process of modelling, adaptation and implementation (MAI of Enterprise Resource Planning Systems (ERPS based on the principles of goal directed project management (GDPM. The proposed methodology guides the project manager through specific stages in order to successfully complete the ERPS implementation. The development of the proper MAI methodology is deemed necessary because it will simplify the installation process of ERPS. The goal directed project management method was chosen since it provides a way of focusing all changes towards a predetermined goal. The main stages of the methodology are the promotion and preparation steps, the proposal, the contract, the implementation and the completion. The methodology was applied as a pilot application by a major ERPS development company. Important benefits were the easy and effective guidance for all installation and analysis stages, the faster installation for the ERPS and the control and cost reduction for the installation, in terms of time, manpower, technological equipment and other resources.

  12. Differentiating neural systems mediating the acquisition versus expression of goal-directed and habitual behavioral control

    Science.gov (United States)

    Liljeholm, Mimi; Dunne, Simon; O'Doherty, John P.

    2015-01-01

    Considerable behavioral data indicates that operant actions can become habitual, as evidenced by insensitivity to changes in the action-outcome contingency and in subjective outcome values. Notably, although several studies have investigated the neural substrates of habits, none has clearly differentiated the areas of the human brain that support habit formation from those that implement habitual control. We scanned participants with fMRI as they learned and performed an operant task in which the conditional structure of the environment encouraged either goal-directed encoding of the consequences of actions, or a habit-like mapping of actions to antecedent cues. Participants were also scanned during a subsequent assessment of insensitivity to outcome devaluation. We identified dissociable roles of the cerebellum and ventral striatum, across learning and test performance, in behavioral insensitivity to outcome devaluation. We also show that the inferior parietal lobule – an area previously implicated in several aspects of goal-directed action selection, including the attribution of intent and awareness of agency – predicts sensitivity to outcome devaluation. Finally, we reveal a potential functional homology between the human subgenual cortex and rodent infralimbic cortex in the implementation of habitual control. In summary, our findings suggest a broad systems division, at the cortical and subcortical levels, between brain areas mediating the encoding and expression of action-outcome and stimulus-response associations. PMID:25892332

  13. Habit strength is predicted by activity dynamics in goal-directed brain systems during training.

    Science.gov (United States)

    Zwosta, Katharina; Ruge, Hannes; Goschke, Thomas; Wolfensteller, Uta

    2018-01-15

    Previous neuroscientific research revealed insights into the brain networks supporting goal-directed and habitual behavior, respectively. However, it remains unclear how these contribute to inter-individual differences in habit strength which is relevant for understanding not only normal behavior but also more severe dysregulations between these types of action control, such as in addiction. In the present fMRI study, we trained subjects on approach and avoidance behavior for an extended period of time before testing the habit strength of the acquired stimulus-response associations. We found that stronger habits were associated with a stronger decrease in inferior parietal lobule activity for approach and avoidance behavior and weaker vmPFC activity at the end of training for avoidance behavior, areas associated with the anticipation of outcome identity and value. VmPFC in particular showed markedly different activity dynamics during the training of approach and avoidance behavior. Furthermore, while ongoing training was accompanied by increasing functional connectivity between posterior putamen and premotor cortex, consistent with previous assumptions about the neural basis of increasing habitualization, this was not predictive of later habit strength. Together, our findings suggest that inter-individual differences in habitual behavior are driven by differences in the persistent involvement of brain areas supporting goal-directed behavior during training. Copyright © 2017. Published by Elsevier Inc.

  14. Neural systems analysis of decision making during goal-directed navigation.

    Science.gov (United States)

    Penner, Marsha R; Mizumori, Sheri J Y

    2012-01-01

    The ability to make adaptive decisions during goal-directed navigation is a fundamental and highly evolved behavior that requires continual coordination of perceptions, learning and memory processes, and the planning of behaviors. Here, a neurobiological account for such coordination is provided by integrating current literatures on spatial context analysis and decision-making. This integration includes discussions of our current understanding of the role of the hippocampal system in experience-dependent navigation, how hippocampal information comes to impact midbrain and striatal decision making systems, and finally the role of the striatum in the implementation of behaviors based on recent decisions. These discussions extend across cellular to neural systems levels of analysis. Not only are key findings described, but also fundamental organizing principles within and across neural systems, as well as between neural systems functions and behavior, are emphasized. It is suggested that studying decision making during goal-directed navigation is a powerful model for studying interactive brain systems and their mediation of complex behaviors. Copyright © 2011. Published by Elsevier Ltd.

  15. Mapping the timecourse of goal-directed attention to location and colour in human vision.

    Science.gov (United States)

    Adams, Rachel C; Chambers, Christopher D

    2012-03-01

    Goal-directed attention prioritises perception of task-relevant stimuli according to location, features, or onset time. In this study we compared the behavioural timecourse of goal-directed selection to locations and colours by varying the stimulus-onset asynchrony (SOA) between cue and target in a strategic cueing paradigm. Participants reported the presence or absence of a target following prior information regarding its location or colour. Results revealed that preparatory selection by colour is more effective at enhancing perceptual sensitivity than selection by location, even though both types of cue provided equivalent overall information. More detailed analysis revealed that this advantage arose due a limitation of spatial attention in maintaining a sufficiently broad focus (>2°) for target detection across multiple stimuli. In contrast, when target stimuli fell within 2° of the spatial attention spotlight, the strategic advantages and speed of spatial and colour attention were equated. Our findings are consistent with the conclusion that, under spatially optimal conditions, prior spatial and colour information are equally proficient at guiding top-down selection. When spatial locations are ambiguous, however, colour-based selection is the more efficient mechanism. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Decreasing Striatopallidal Pathway Function Enhances Motivation by Energizing the Initiation of Goal-Directed Action

    Science.gov (United States)

    Carvalho Poyraz, Fernanda; Holzner, Eva; Bailey, Matthew R.; Meszaros, Jozsef; Kenney, Lindsay; Kheirbek, Mazen A.

    2016-01-01

    Altered dopamine D2 receptor (D2R) binding in the striatum has been associated with abnormal motivation in neuropsychiatric disorders, including schizophrenia. Here, we tested whether motivational deficits observed in mice with upregulated D2Rs (D2R-OEdev mice) are reversed by decreasing function of the striatopallidal “no-go” pathway. To this end, we expressed the Gαi-coupled designer receptor hM4D in adult striatopallidal neurons and activated the receptor with clozapine-N-oxide (CNO). Using a head-mounted miniature microscope we confirmed with calcium imaging in awake mice that hM4D activation by CNO inhibits striatopallidal function measured as disinhibited downstream activity in the globus pallidus. Mice were then tested in three operant tasks that address motivated behavior, the progressive ratio task, the progressive hold-down task, and outcome devaluation. Decreasing striatopallidal function in the dorsomedial striatum or nucleus accumbens core enhanced motivation in D2R-OEdev mice and control littermates. This effect was due to increased response initiation but came at the cost of goal-directed efficiency. Moreover, response vigor and the sensitivity to changes in reward value were not altered. Chronic activation of hM4D by administering CNO for 2 weeks in drinking water did not affect motivation due to a tolerance effect. However, the acute effect of CNO on motivation was reinstated after discontinuing chronic treatment for 48 h. Used as a therapeutic approach, striatopallidal inhibition should consider the risk of impairing goal-directed efficiency and behavioral desensitization. SIGNIFICANCE STATEMENT Motivation involves a directional component that allows subjects to efficiently select the behavior that will lead to an optimal outcome and an activational component that initiates and maintains the vigor and persistence of actions. Striatal output pathways modulate motivated behavior, but it remains unknown how these pathways regulate specific

  17. Decreasing Striatopallidal Pathway Function Enhances Motivation by Energizing the Initiation of Goal-Directed Action.

    Science.gov (United States)

    Carvalho Poyraz, Fernanda; Holzner, Eva; Bailey, Matthew R; Meszaros, Jozsef; Kenney, Lindsay; Kheirbek, Mazen A; Balsam, Peter D; Kellendonk, Christoph

    2016-06-01

    Altered dopamine D2 receptor (D2R) binding in the striatum has been associated with abnormal motivation in neuropsychiatric disorders, including schizophrenia. Here, we tested whether motivational deficits observed in mice with upregulated D2Rs (D2R-OEdev mice) are reversed by decreasing function of the striatopallidal "no-go" pathway. To this end, we expressed the Gαi-coupled designer receptor hM4D in adult striatopallidal neurons and activated the receptor with clozapine-N-oxide (CNO). Using a head-mounted miniature microscope we confirmed with calcium imaging in awake mice that hM4D activation by CNO inhibits striatopallidal function measured as disinhibited downstream activity in the globus pallidus. Mice were then tested in three operant tasks that address motivated behavior, the progressive ratio task, the progressive hold-down task, and outcome devaluation. Decreasing striatopallidal function in the dorsomedial striatum or nucleus accumbens core enhanced motivation in D2R-OEdev mice and control littermates. This effect was due to increased response initiation but came at the cost of goal-directed efficiency. Moreover, response vigor and the sensitivity to changes in reward value were not altered. Chronic activation of hM4D by administering CNO for 2 weeks in drinking water did not affect motivation due to a tolerance effect. However, the acute effect of CNO on motivation was reinstated after discontinuing chronic treatment for 48 h. Used as a therapeutic approach, striatopallidal inhibition should consider the risk of impairing goal-directed efficiency and behavioral desensitization. Motivation involves a directional component that allows subjects to efficiently select the behavior that will lead to an optimal outcome and an activational component that initiates and maintains the vigor and persistence of actions. Striatal output pathways modulate motivated behavior, but it remains unknown how these pathways regulate specific components of motivation. Here

  18. Autism: cause factors, early diagnosis and therapies.

    Science.gov (United States)

    Bhat, Shreya; Acharya, U Rajendra; Adeli, Hojjat; Bairy, G Muralidhar; Adeli, Amir

    2014-01-01

    Autism spectrum disorder (ASD) is a complex neurobiological disorder characterized by neuropsychological and behavioral deficits. Cognitive impairment, lack of social skills, and stereotyped behavior are the major autistic symptoms, visible after a certain age. It is one of the fastest growing disabilities. Its current prevalence rate in the U.S. estimated by the Centers for Disease Control and Prevention is 1 in 68 births. The genetic and physiological structure of the brain is studied to determine the pathology of autism, but diagnosis of autism at an early age is challenging due to the existing phenotypic and etiological heterogeneity among ASD individuals. Volumetric and neuroimaging techniques are explored to elucidate the neuroanatomy of the ASD brain. Nuroanatomical, neurochemical, and neuroimaging biomarkers can help in the early diagnosis and treatment of ASD. This paper presents a review of the types of autism, etiologies, early detection, and treatment of ASD.

  19. Dopaminergic modulation of positive expectations for goal-directed action: evidence from Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Noham eWolpe

    2015-10-01

    Full Text Available Parkinson’s disease (PD impairs the control of movement and cognition, including the planning of action and its consequences. This provides the opportunity to study the dopaminergic influences on the perception and awareness of action. Here we examined the perception of the outcome of a goal-directed action made by medicated patients with PD. A visuomotor task probed the integration of sensorimotor signals with the positive expectations of outcomes (Self priors, which in healthy adults bias perception towards success in proportion to trait optimism. We tested the hypotheses that (i the priors on the perception of the consequences of one’s own actions differ between patients and age- and sex-matched controls, and (ii that these priors are modulated by the levodopa dose equivalent in patients. There was no overall difference between patients and controls in the perceptual priors used. However, the precision of patient priors was inversely related to their levodopa dose equivalent. Patients with high levodopa dose equivalent showed more accurate priors, representing predictions that were closer to the true distribution of performance. Such accuracy has previously been demonstrated when observing the actions of others, suggesting abnormal awareness of action in these patients. These results confirm a link between dopamine and the positive expectation of the outcome of one’s own actions, and may have implications for the management of PD.

  20. The perceptual control of goal-directed locomotion: a common control architecture for interception and navigation?

    Science.gov (United States)

    Chardenon, A; Montagne, G; Laurent, M; Bootsma, R J

    2004-09-01

    Intercepting a moving object while locomoting is a highly complex and demanding ability. Notwithstanding the identification of several informational candidates, the role of perceptual variables in the control process underlying such skills remains an open question. In this study we used a virtual reality set-up for studying locomotor interception of a moving ball. The subject had to walk along a straight path and could freely modify forward velocity, if necessary, in order to intercept-with the head-a ball moving along a straight path that led it to cross the agent's displacement axis. In a series of experiments we manipulated a local (ball size) and a global (focus of expansion) component of the visual flow but also the egocentric orientation of the ball. The experimental observations are well captured by a dynamic model linking the locomotor acceleration to properties of both global flow and egocentric direction. More precisely the changes in locomotor velocity depend on a linear combination of the change in bearing angle and the change in egocentric orientation, allowing the emergence of adaptive behavior under a variety of circumstances. We conclude that the mechanisms underlying the control of different goal-directed locomotion tasks (i.e. steering and interceptive tasks) could share a common architecture.

  1. Monetary reward magnitude effects on behavior and brain function during goal-directed behavior.

    Science.gov (United States)

    Rosell-Negre, P; Bustamante, J C; Fuentes-Claramonte, P; Costumero, V; Benabarre, S; Barrós-Loscertales, A

    2017-08-01

    Reward may modulate the cognitive processes required for goal achievement, while individual differences in personality may affect reward modulation. Our aim was to test how different monetary reward magnitudes modulate brain activation and performance during goal-directed behavior, and whether individual differences in reward sensitivity affect this modulation. For this purpose, we scanned 37 subjects with a parametric design in which we varied the magnitude of monetary rewards (€0, €0.01, €0.5, €1 or €1.5) in a blocked fashion while participants performed an interference counting-Stroop condition. The results showed that the brain activity of left dorsolateral prefrontal cortex (DLPFC) and the striatum were modulated by increasing and decreasing reward magnitudes, respectively. Behavioral performance improved as the magnitude of monetary reward increased while comparing the non reward (€0) condition to any other reward condition, or the lower €0.01 to any other reward condition, and this improvement was related with individual differences in reward sensitivity. In conclusion, the locus of influence of monetary incentives overlaps the activity of the regions commonly involved in cognitive control.

  2. Dissociating Goal-Directed and Stimulus-Driven Determinants in Attentional Capture

    Directory of Open Access Journals (Sweden)

    Louis K. H. Chan

    2011-05-01

    Full Text Available Although attentional capture is now a commonplace finding, the exact roles played by goal-directed and stimulus-driven determents remain elusive. An unsettled issue is on the relative contribution of attentional set and visual saliency. In the present study, we investigated this issue by mixing color and orientation search trials, so that distractors of either feature dimension fell into the current attentional set. In our test, color features were more salient. As a result, in orientation search, whereas a color distractor produced huge capture (109 ms, an orientation distractor produced moderate capture (50 ms. With color targets, distractors were not interfering. On one hand, these results reflect that relative salience of the target and the distractor is critical for producing capture; on the other hand, a huge capture size associated with a nontarget dimension feature is novel. Similar previous measurements, but without matching the attentional set, consistently report attentional capture of only 20-30 ms. This comparison shows the role played by attentional set. Taken together, we suggest that visual saliency determines search order, and sets the platform for capture. However, attentional dwell time on the distractor is determined by how much it matches the current attentional set, and in turn explains the capture size.

  3. Purposeful Goal-Directed Movements Give Rise to Higher Tactile Discrimination Performance

    Directory of Open Access Journals (Sweden)

    Georgiana Juravle

    2011-10-01

    Full Text Available Tactile perception is inhibited during goal-directed reaching movements (sensory suppression. Here, participants performed simple reaching or exploratory movements (where contact with the table surface was maintained. We measured tactile discrimination thresholds for vibratory stimuli delivered to participants' wrists while executing the movement, and while at rest. Moreover, we measured discrimination performance (in a same vs. different task for the materials covering the table surface, during the execution of the different movements. The threshold and discrimination tasks could be performed either singly or together, both under active movement and passive conditions (ie, no movement required, but with tactile stimulation. Thresholds measured at rest were significantly lower than thresholds measured during both active movements and passive touches. This provides a clear indication of sensory suppression during movement execution. Moreover, the discrimination data revealed main effects of task (single vs. dual, movement execution type (passive vs. active, and movement type (reach vs. exploration: Discrimination performance was significantly higher under conditions of single-tasking, active movements, as well as exploratory movements. Therefore, active movement of the hand with the purpose of gaining tactual information about the surface of the table gives rise to enhanced performance, thus suggesting that we feel more when we need to; It would appear that tactual information is prioritized when relevant for the movement being executed.

  4. Emotion and goal-directed behavior: ERP evidence on cognitive and emotional conflict

    Science.gov (United States)

    Kanske, Philipp; Obermeier, Christian; Schröger, Erich; Kotz, Sonja A.

    2015-01-01

    Cognitive control supports goal-directed behavior by resolving conflict among opposing action tendencies. Emotion can trigger cognitive control processes, thus speeding up conflict processing when the target dimension of stimuli is emotional. However, it is unclear what role emotionality of the target dimension plays in the processing of emotional conflict (e.g. in irony). In two EEG experiments, we compared the influence of emotional valence of the target (emotional, neutral) in cognitive and emotional conflict processing. To maximally approximate real-life communication, we used audiovisual stimuli. Participants either categorized spoken vowels (cognitive conflict) or their emotional valence (emotional conflict), while visual information was congruent or incongruent. Emotional target dimension facilitated both cognitive and emotional conflict processing, as shown in a reduced reaction time conflict effect. In contrast, the N100 in the event-related potentials showed a conflict-specific reversal: the conflict effect was larger for emotional compared with neutral trials in cognitive conflict and smaller in emotional conflict. Additionally, domain-general conflict effects were observed in the P200 and N200 responses. The current findings confirm that emotions have a strong influence on cognitive and emotional conflict processing. They also highlight the complexity and heterogeneity of the interaction of emotion with different types of conflict. PMID:25925271

  5. Flexibility to contingency changes distinguishes habitual and goal-directed strategies in humans.

    Science.gov (United States)

    Lee, Julie J; Keramati, Mehdi

    2017-09-01

    Decision-making in the real world presents the challenge of requiring flexible yet prompt behavior, a balance that has been characterized in terms of a trade-off between a slower, prospective goal-directed model-based (MB) strategy and a fast, retrospective habitual model-free (MF) strategy. Theory predicts that flexibility to changes in both reward values and transition contingencies can determine the relative influence of the two systems in reinforcement learning, but few studies have manipulated the latter. Therefore, we developed a novel two-level contingency change task in which transition contingencies between states change every few trials; MB and MF control predict different responses following these contingency changes, allowing their relative influence to be inferred. Additionally, we manipulated the rate of contingency changes in order to determine whether contingency change volatility would play a role in shifting subjects between a MB and MF strategy. We found that human subjects employed a hybrid MB/MF strategy on the task, corroborating the parallel contribution of MB and MF systems in reinforcement learning. Further, subjects did not remain at one level of MB/MF behaviour but rather displayed a shift towards more MB behavior over the first two blocks that was not attributable to the rate of contingency changes but rather to the extent of training. We demonstrate that flexibility to contingency changes can distinguish MB and MF strategies, with human subjects utilizing a hybrid strategy that shifts towards more MB behavior over blocks, consequently corresponding to a higher payoff.

  6. Distinct roles of theta and alpha oscillations in the involuntary capture of goal-directed attention.

    Science.gov (United States)

    Harris, Anthony M; Dux, Paul E; Jones, Caelyn N; Mattingley, Jason B

    2017-05-15

    Mechanisms of attention assign priority to sensory inputs on the basis of current task goals. Previous studies have shown that lateralized neural oscillations within the alpha (8-14Hz) range are associated with the voluntary allocation of attention to the contralateral visual field. It is currently unknown, however, whether similar oscillatory signatures instantiate the involuntary capture of spatial attention by goal-relevant stimulus properties. Here we investigated the roles of theta (4-8Hz), alpha, and beta (14-30Hz) oscillations in human goal-directed visual attention. Across two experiments, we had participants respond to a brief target of a particular color among heterogeneously colored distractors. Prior to target onset, we cued one location with a lateralized, non-predictive cue that was either target- or non-target-colored. During the behavioral task, we recorded brain activity using electroencephalography (EEG), with the aim of analyzing cue-elicited oscillatory activity. We found that theta oscillations lateralized in response to all cues, and this lateralization was stronger if the cue matched the target color. Alpha oscillations lateralized relatively later, and only in response to target-colored cues, consistent with the capture of spatial attention. Our findings suggest that stimulus induced changes in theta and alpha amplitude reflect task-based modulation of signals by feature-based and spatial attention, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Feature Interactions Enable Decoding of Sensorimotor Transformations for Goal-Directed Movement

    Science.gov (United States)

    Barany, Deborah A.; Della-Maggiore, Valeria; Viswanathan, Shivakumar; Cieslak, Matthew

    2014-01-01

    Neurophysiology and neuroimaging evidence shows that the brain represents multiple environmental and body-related features to compute transformations from sensory input to motor output. However, it is unclear how these features interact during goal-directed movement. To investigate this issue, we examined the representations of sensory and motor features of human hand movements within the left-hemisphere motor network. In a rapid event-related fMRI design, we measured cortical activity as participants performed right-handed movements at the wrist, with either of two postures and two amplitudes, to move a cursor to targets at different locations. Using a multivoxel analysis technique with rigorous generalization tests, we reliably distinguished representations of task-related features (primarily target location, movement direction, and posture) in multiple regions. In particular, we identified an interaction between target location and movement direction in the superior parietal lobule, which may underlie a transformation from the location of the target in space to a movement vector. In addition, we found an influence of posture on primary motor, premotor, and parietal regions. Together, these results reveal the complex interactions between different sensory and motor features that drive the computation of sensorimotor transformations. PMID:24828640

  8. Emotion and goal-directed behavior: ERP evidence on cognitive and emotional conflict.

    Science.gov (United States)

    Zinchenko, Artyom; Kanske, Philipp; Obermeier, Christian; Schröger, Erich; Kotz, Sonja A

    2015-11-01

    Cognitive control supports goal-directed behavior by resolving conflict among opposing action tendencies. Emotion can trigger cognitive control processes, thus speeding up conflict processing when the target dimension of stimuli is emotional. However, it is unclear what role emotionality of the target dimension plays in the processing of emotional conflict (e.g. in irony). In two EEG experiments, we compared the influence of emotional valence of the target (emotional, neutral) in cognitive and emotional conflict processing. To maximally approximate real-life communication, we used audiovisual stimuli. Participants either categorized spoken vowels (cognitive conflict) or their emotional valence (emotional conflict), while visual information was congruent or incongruent. Emotional target dimension facilitated both cognitive and emotional conflict processing, as shown in a reduced reaction time conflict effect. In contrast, the N100 in the event-related potentials showed a conflict-specific reversal: the conflict effect was larger for emotional compared with neutral trials in cognitive conflict and smaller in emotional conflict. Additionally, domain-general conflict effects were observed in the P200 and N200 responses. The current findings confirm that emotions have a strong influence on cognitive and emotional conflict processing. They also highlight the complexity and heterogeneity of the interaction of emotion with different types of conflict. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Bidirectional modulation of goal-directed actions by prefrontal cortical dopamine.

    Science.gov (United States)

    Hitchcott, Paul K; Quinn, Jennifer J; Taylor, Jane R

    2007-12-01

    Instrumental actions are a vital cognitive asset that endows an organism with sensitivity to the consequences of its behavior. Response-outcome feedback allows responding to be shaped in order to maximize beneficial, and minimize detrimental, outcomes. Lesions of the medial prefrontal cortex (mPFC) result in behavior that is insensitive to changes in outcome value in animals and compulsive behavior in several human psychopathologies. Such insensitivity to changes in outcome value is a defining characteristic of instrumental habits: responses that are controlled by antecedent stimuli rather than goal expectancy. Little is known regarding the neurochemical substrates mediating this sensitivity. The present experiments used sensitivity to posttraining outcome devaluation to index the action-habit status of instrumental responding. Infusions of dopamine into the ventral mPFC (vmPFC), but not dorsal mPFC, restored outcome sensitivity bidirectionally-decreasing responding following outcome devaluation and increasing responding when the outcome was not devalued. This bidirectionality makes the possibility that these infusions nonspecifically dysregulated vmPFC dopamine transmission unlikely. VmPFC dopamine promoted instrumental responding appropriate to outcome value. Reinforcer consumption data indicated that this was not a consequence of altered sensitivity to the reinforcer itself. We suggest that vmPFC dopamine reengages attentional processes underlying goal-directed behavior.

  10. Non-goal-directed recall of specific events in apes after long delays.

    Science.gov (United States)

    Lewis, Amy; Call, Josep; Berntsen, Dorthe

    2017-07-12

    We examined if apes spontaneously remember one-time, distinctive events across long delays when probed by discriminant cues. Apes witnessed an experimenter hide a cache of food, which they could then retrieve. They retrieved one of two food types; one more distinctive than the other. Two, 10 or 50 weeks later, the apes returned to the same enclosure and found a piece of the previously hidden food on the ground. An experimenter who had not hidden the food was also present. Apes immediately searched the location where the food was previously hidden (no food was here), showing recall of the event. One week later, apes returned to the same enclosure, with the same food on the ground, but now the experimenter that had hidden the food was present. Again, apes immediately searched the hiding location. Apes that had not witnessed the hiding event did not search. There was no significant effect of food type, and retention declined from exposure to the two-week delay, then levelled, consistent with the forgetting curve in humans (Ebbinghaus, H. 1964 Memory: a contribution to experimental psychology (transl. H.A. Ruger & C.E. Bussenvis). New York, NY: Dover. (Original work published 1885.)). This is the first study to show apes can recall a one-time, non-goal-directed event longer than two weeks ago and that apes' recall declines in accordance with a standard retention function. © 2017 The Author(s).

  11. Goal-directed behaviour and instrumental devaluation: a neural system-level computational model

    Directory of Open Access Journals (Sweden)

    Francesco Mannella

    2016-10-01

    Full Text Available Devaluation is the key experimental paradigm used to demonstrate the presence of instrumental behaviours guided by goals in mammals. We propose a neural system-level computational model to address the question of which brain mechanisms allow the current value of rewards to control instrumental actions. The model pivots on and shows the computational soundness of the hypothesis for which the internal representation of instrumental manipulanda (e.g., levers activate the representation of rewards (or `action-outcomes', e.g. foods while attributing to them a value which depends on the current internal state of the animal (e.g., satiation for some but not all foods. The model also proposes an initial hypothesis of the integrated system of key brain components supporting this process and allowing the recalled outcomes to bias action selection: (a the sub-system formed by the basolateral amygdala and insular cortex acquiring the manipulanda-outcomes associations and attributing the current value to the outcomes; (b the three basal ganglia-cortical loops selecting respectively goals, associative sensory representations, and actions; (c the cortico-cortical and striato-nigro-striatal neural pathways supporting the selection, and selection learning, of actions based on habits and goals. The model reproduces and integrates the results of different devaluation experiments carried out with control rats and rats with pre- and post-training lesions of the basolateral amygdala, the nucleus accumbens core, the prelimbic cortex, and the dorso-medial striatum. The results support the soundness of the hypotheses of the model and show its capacity to integrate, at the system-level, the operations of the key brain structures underlying devaluation. Based on its hypotheses and predictions, the model also represents an operational framework to support the design and analysis of new experiments on the motivational aspects of goal-directed behaviour.

  12. Goal-directed mechanisms that constrain retrieval predict subsequent memory for new "foil" information.

    Science.gov (United States)

    Vogelsang, David A; Bonnici, Heidi M; Bergström, Zara M; Ranganath, Charan; Simons, Jon S

    2016-08-01

    To remember a previous event, it is often helpful to use goal-directed control processes to constrain what comes to mind during retrieval. Behavioral studies have demonstrated that incidental learning of new "foil" words in a recognition test is superior if the participant is trying to remember studied items that were semantically encoded compared to items that were non-semantically encoded. Here, we applied subsequent memory analysis to fMRI data to understand the neural mechanisms underlying the "foil effect". Participants encoded information during deep semantic and shallow non-semantic tasks and were tested in a subsequent blocked memory task to examine how orienting retrieval towards different types of information influences the incidental encoding of new words presented as foils during the memory test phase. To assess memory for foils, participants performed a further surprise old/new recognition test involving foil words that were encountered during the previous memory test blocks as well as completely new words. Subsequent memory effects, distinguishing successful versus unsuccessful incidental encoding of foils, were observed in regions that included the left inferior frontal gyrus and posterior parietal cortex. The left inferior frontal gyrus exhibited disproportionately larger subsequent memory effects for semantic than non-semantic foils, and significant overlap in activity during semantic, but not non-semantic, initial encoding and foil encoding. The results suggest that orienting retrieval towards different types of foils involves re-implementing the neurocognitive processes that were involved during initial encoding. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. A Neurocomputational Model of Goal-Directed Navigation in Insect-Inspired Artificial Agents.

    Science.gov (United States)

    Goldschmidt, Dennis; Manoonpong, Poramate; Dasgupta, Sakyasingha

    2017-01-01

    Despite their small size, insect brains are able to produce robust and efficient navigation in complex environments. Specifically in social insects, such as ants and bees, these navigational capabilities are guided by orientation directing vectors generated by a process called path integration. During this process, they integrate compass and odometric cues to estimate their current location as a vector, called the home vector for guiding them back home on a straight path. They further acquire and retrieve path integration-based vector memories globally to the nest or based on visual landmarks. Although existing computational models reproduced similar behaviors, a neurocomputational model of vector navigation including the acquisition of vector representations has not been described before. Here we present a model of neural mechanisms in a modular closed-loop control-enabling vector navigation in artificial agents. The model consists of a path integration mechanism, reward-modulated global learning, random search, and action selection. The path integration mechanism integrates compass and odometric cues to compute a vectorial representation of the agent's current location as neural activity patterns in circular arrays. A reward-modulated learning rule enables the acquisition of vector memories by associating the local food reward with the path integration state. A motor output is computed based on the combination of vector memories and random exploration. In simulation, we show that the neural mechanisms enable robust homing and localization, even in the presence of external sensory noise. The proposed learning rules lead to goal-directed navigation and route formation performed under realistic conditions. Consequently, we provide a novel approach for vector learning and navigation in a simulated, situated agent linking behavioral observations to their possible underlying neural substrates.

  14. Obesity-related differences between women and men in brain structure and goal-directed behavior

    Directory of Open Access Journals (Sweden)

    Annette eHorstmann

    2011-06-01

    Full Text Available Gender differences in the regulation of body weight are well documented. Here, we assessed obesity-related influences of gender on brain structure as well as performance in the Iowa Gambling Task. This task requires evaluation of both immediate rewards and long-term outcomes and thus mirrors the trade-off between immediate reward from eating and the long-term effect of overeating on body weight. In women, but not in men, we show that the preference for salient immediate rewards in the face of negative long-term consequences is higher in obese than in lean subjects. In addition, we report structural differences in the left dorsal striatum (i.e. putamen and right dorsolateral prefrontal cortex for women only. Functionally, both regions are known to play complimentary roles in habitual and goal-directed control of behavior in motivational contexts. For women as well as men, gray matter volume correlates positively with measures of obesity in regions coding the value and saliency of food (i.e. nucleus accumbens, orbitofrontal cortex as well as in the hypothalamus (i.e. the brain's central homeostatic centre. These differences between lean and obese subjects in hedonic and homeostatic control systems may reflect a bias in eating behavior towards energy intake exceeding the actual homeostatic demand. Although we cannot infer from our results the etiology of the observed structural differences, our results resemble neural and behavioral differences well known from other forms of addiction, however, with marked differences between women and men. These findings are important for designing gender-appropriate treatments of obesity and possibly its recognition as a form of addiction.

  15. Flexibility to contingency changes distinguishes habitual and goal-directed strategies in humans.

    Directory of Open Access Journals (Sweden)

    Julie J Lee

    2017-09-01

    Full Text Available Decision-making in the real world presents the challenge of requiring flexible yet prompt behavior, a balance that has been characterized in terms of a trade-off between a slower, prospective goal-directed model-based (MB strategy and a fast, retrospective habitual model-free (MF strategy. Theory predicts that flexibility to changes in both reward values and transition contingencies can determine the relative influence of the two systems in reinforcement learning, but few studies have manipulated the latter. Therefore, we developed a novel two-level contingency change task in which transition contingencies between states change every few trials; MB and MF control predict different responses following these contingency changes, allowing their relative influence to be inferred. Additionally, we manipulated the rate of contingency changes in order to determine whether contingency change volatility would play a role in shifting subjects between a MB and MF strategy. We found that human subjects employed a hybrid MB/MF strategy on the task, corroborating the parallel contribution of MB and MF systems in reinforcement learning. Further, subjects did not remain at one level of MB/MF behaviour but rather displayed a shift towards more MB behavior over the first two blocks that was not attributable to the rate of contingency changes but rather to the extent of training. We demonstrate that flexibility to contingency changes can distinguish MB and MF strategies, with human subjects utilizing a hybrid strategy that shifts towards more MB behavior over blocks, consequently corresponding to a higher payoff.

  16. Fronto-parietal coding of goal-directed actions performed by artificial agents.

    Science.gov (United States)

    Kupferberg, Aleksandra; Iacoboni, Marco; Flanagin, Virginia; Huber, Markus; Kasparbauer, Anna; Baumgartner, Thomas; Hasler, Gregor; Schmidt, Florian; Borst, Christoph; Glasauer, Stefan

    2018-03-01

    With advances in technology, artificial agents such as humanoid robots will soon become a part of our daily lives. For safe and intuitive collaboration, it is important to understand the goals behind their motor actions. In humans, this process is mediated by changes in activity in fronto-parietal brain areas. The extent to which these areas are activated when observing artificial agents indicates the naturalness and easiness of interaction. Previous studies indicated that fronto-parietal activity does not depend on whether the agent is human or artificial. However, it is unknown whether this activity is modulated by observing grasping (self-related action) and pointing actions (other-related action) performed by an artificial agent depending on the action goal. Therefore, we designed an experiment in which subjects observed human and artificial agents perform pointing and grasping actions aimed at two different object categories suggesting different goals. We found a signal increase in the bilateral inferior parietal lobule and the premotor cortex when tool versus food items were pointed to or grasped by both agents, probably reflecting the association of hand actions with the functional use of tools. Our results show that goal attribution engages the fronto-parietal network not only for observing a human but also a robotic agent for both self-related and social actions. The debriefing after the experiment has shown that actions of human-like artificial agents can be perceived as being goal-directed. Therefore, humans will be able to interact with service robots intuitively in various domains such as education, healthcare, public service, and entertainment. © 2017 Wiley Periodicals, Inc.

  17. Ethanol seeking by Long Evans rats is not always a goal-directed behavior.

    Directory of Open Access Journals (Sweden)

    Regina A Mangieri

    Full Text Available Two parallel and interacting processes are said to underlie animal behavior, whereby learning and performance of a behavior is at first via conscious and deliberate (goal-directed processes, but after initial acquisition, the behavior can become automatic and stimulus-elicited (habitual. With respect to instrumental behaviors, animal learning studies suggest that the duration of training and the action-outcome contingency are two factors involved in the emergence of habitual seeking of "natural" reinforcers (e.g., sweet solutions, food or sucrose pellets. To rigorously test whether behaviors reinforced by abused substances such as ethanol, in particular, similarly become habitual was the primary aim of this study.Male Long Evans rats underwent extended or limited operant lever press training with 10% sucrose/10% ethanol (10S10E reinforcement (variable interval (VI or (VR ratio schedule of reinforcement, or with 10% sucrose (10S reinforcement (VI schedule only. Once training and pretesting were complete, the impact of outcome devaluation on operant behavior was evaluated after lithium chloride injections were paired with the reinforcer, or unpaired 24 hours later. After limited, but not extended instrumental training, lever pressing by groups trained under VR with 10S10E and under VI with 10S was sensitive to outcome devaluation. In contrast, responding by both the extended and limited training 10S10E VI groups was not sensitive to ethanol devaluation during the test for habitual behavior.Operant behavior by rats trained to self-administer an ethanol-sucrose solution showed variable sensitivity to a change in the value of ethanol, with relative insensitivity developing sooner in animals that received time-variable ethanol reinforcement during training sessions. One important implication, with respect to substance abuse in humans, is that initial learning about the relationship between instrumental actions and the opportunity to consume ethanol

  18. Drunk decisions: Alcohol shifts choice from habitual towards goal-directed control in adolescent intermediate-risk drinkers.

    Science.gov (United States)

    Obst, Elisabeth; Schad, Daniel J; Huys, Quentin Jm; Sebold, Miriam; Nebe, Stephan; Sommer, Christian; Smolka, Michael N; Zimmermann, Ulrich S

    2018-05-01

    Studies in humans and animals suggest a shift from goal-directed to habitual decision-making in addiction. We therefore tested whether acute alcohol administration reduces goal-directed and promotes habitual decision-making, and whether these effects are moderated by self-reported drinking problems. Fifty-three socially drinking males completed the two-step task in a randomised crossover design while receiving an intravenous infusion of ethanol (blood alcohol level=80 mg%), or placebo. To minimise potential bias by long-standing heavy drinking and subsequent neuropsychological impairment, we tested 18- to 19-year-old adolescents. Alcohol administration consistently reduced habitual, model-free decisions, while its effects on goal-directed, model-based behaviour varied as a function of drinking problems measured with the Alcohol Use Disorders Identification Test. While adolescents with low risk for drinking problems (scoring towards goal-directed decision-making, such that alcohol possibly even improved their performance. We assume that alcohol disrupted basic cognitive functions underlying habitual and goal-directed decisions in low-risk drinkers, thereby enhancing hasty choices. Further, we speculate that intermediate-risk drinkers benefited from alcohol as a negative reinforcer that reduced unpleasant emotional states, possibly displaying a novel risk factor for drinking in adolescence.

  19. Neuronal activity in primate prefrontal cortex related to goal-directed behavior during auditory working memory tasks.

    Science.gov (United States)

    Huang, Ying; Brosch, Michael

    2016-06-01

    Prefrontal cortex (PFC) has been documented to play critical roles in goal-directed behaviors, like representing goal-relevant events and working memory (WM). However, neurophysiological evidence for such roles of PFC has been obtained mainly with visual tasks but rarely with auditory tasks. In the present study, we tested roles of PFC in auditory goal-directed behaviors by recording local field potentials in the auditory region of left ventrolateral PFC while a monkey performed auditory WM tasks. The tasks consisted of multiple events and required the monkey to change its mental states to achieve the reward. The events were auditory and visual stimuli, as well as specific actions. Mental states were engaging in the tasks and holding task-relevant information in auditory WM. We found that, although based on recordings from one hemisphere in one monkey only, PFC represented multiple events that were important for achieving reward, including auditory and visual stimuli like turning on and off an LED, as well as bar touch. The responses to auditory events depended on the tasks and on the context of the tasks. This provides support for the idea that neuronal representations in PFC are flexible and can be related to the behavioral meaning of stimuli. We also found that engaging in the tasks and holding information in auditory WM were associated with persistent changes of slow potentials, both of which are essential for auditory goal-directed behaviors. Our study, on a single hemisphere in a single monkey, reveals roles of PFC in auditory goal-directed behaviors similar to those in visual goal-directed behaviors, suggesting that functions of PFC in goal-directed behaviors are probably common across the auditory and visual modality. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Radiation therapy planning for early-stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Maraldo, Maja V; Dabaja, Bouthaina S; Filippi, Andrea R

    2015-01-01

    PURPOSE: Early-stage Hodgkin lymphoma (HL) is a rare disease, and the location of lymphoma varies considerably between patients. Here, we evaluate the variability of radiation therapy (RT) plans among 5 International Lymphoma Radiation Oncology Group (ILROG) centers with regard to beam arrangements...... axillary disease, and 1 had disease in the neck only. The median age at diagnosis was 34 years (range, 21-74 years), and 5 patients were male. Of the resulting 50 treatment plans, 15 were planned with volumetric modulated arc therapy (1-4 arcs), 16 with intensity modulated RT (3-9 fields), and 19 with 3...

  1. Verification of extended model of goal directed behavior applied on aggression

    Directory of Open Access Journals (Sweden)

    Katarína Vasková

    2016-01-01

    Full Text Available The study was aimed to verify Model of Goal Directed Behavior (EMGB by Perugini and Bagozzi (2001 applied on aggression by Richetin, Richardson and Boykin (2011. Two different studies were performed. Firstly original form of model was verified. In the second study, modification of EMGB through new conceptualization of scale of perceived behavioral control was executed. The research sample consisted together from 385 students of University of P.J. Šafárik and High school in Košice (182 respondents (78 men, 104 women with average age 20,84 years and standard deviation 1,94, who were involved in first study and 203 students (49 men and 154 women, with average age 19,71 and standard deviation 1,99 participated in second study who were administrated questionnaire by Richetin et al. (2011 and Richardson Conflict Response Questionnaire (Richardson & Green, 2006. Expectancy of comparable relationships between particular factors of EMGB in comparison to its published original version was verified. Data were analyzed by structural equation modeling. In first study was shown insufficient fit of EMGB model. There were hypothesized two main sources of problems. At first, weak relationship between attitudes and behavioral desire was shown. Following statistical procedures confirmed its direct impact on intention, what is in correspondence with another studies (see Leone, Perugini & Ercolani, 2004, Perugini & Bagozzi, 2001, Richetin et al., 2011. Second source of problems was identified in factor named perceived behavioral control. Difficulties from our point of view lied in conceptualization of the term and its subsequent measurement. In the second study was involved new conceptualization of control. It corresponded with Baumeister´s understanding of selfcontrol as asserting control over one´s emotions, thoughts and behavior. After this modification sufficient fit of EMGB was shown. Besides this, factor of self-control was the strongest predictor of

  2. Early diagnosis and empiric therapy for cirrhosis associated with infection

    Directory of Open Access Journals (Sweden)

    NAN Yuemin

    2015-03-01

    Full Text Available Infection is a frequent complication of cirrhosis, which often occurs in the lungs, chest, abdomen, biliary tract, urinary tract, soft tissue, and skin, and occasionally causes spontaneous bacteremia in patients. This paper reviews the risk factors and common types of infection in cirrhosis associated with infection, and the early diagnosis and symptomatic treatment of different types of infection. Moreover, this paper points out that cirrhosis associated with infection is a key factor for disease progression and the early diagnosis and treatment are essential for successful treatment. The third-generation cephalosporins are the first-line antibiotic agents. Drug-resistant bacteria should be treated with antibiotic compound containing β-lactamase inhibitors or carbapenems. Methicillin-resistant Staphylococcus aureus should be treated with glycopeptide antibiotics or combination therapies. Pulmonary mycoses are mainly treated with caspofungin or voriconazole. Antibiotics combined with supportive therapies including the administration of albumin can improve the treatment outcome and prognosis.

  3. Goal-directed hemostatic resuscitation for massively bleeding patients: the Copenhagen concept

    DEFF Research Database (Denmark)

    Johansson, Pär I

    2010-01-01

    Continued hemorrhage remains a major cause of mortality in massively transfused patients, many of whom develop coagulopathy. A review of transfusion practice for these patients at our hospital revealed that a significant proportion received suboptimal transfusion therapy. Survivors had higher pla...

  4. Hope and self-regulatory goals applied to an advertising context : promoting prevention stimulates goal-directed behavior.

    NARCIS (Netherlands)

    Poels, K.; Dewitte, S.

    2008-01-01

    This article proposes the existence of two types of hope which differ in terms of self-regulatory goals: prevention hope and promotion hope. Consistent with the functional emotion approach and regulatory focus theory, we show that prevention hope generates more goal-directed behavior compared to

  5. Hope and self regulatory goals applied to an advertising context : promoting prevention stimulates goal-directed behavior

    NARCIS (Netherlands)

    Poels, K.; Dewitte, S.; Astregaard, S.; Dwight, M.

    2007-01-01

    This article proposes the existence of two types of hope which differ in terms of self-regulatory goals: prevention hope and promotion hope. Consistent with the functional emotion approach and regulatory focus theory, we show that prevention hope generates more goal-directed behavior compared to

  6. Movement Structure in Young and Elderly Adults during Goal-Directed Movements of the Left and Right Arm

    Science.gov (United States)

    Poston, Brach; Van Gemmert, Arend W. A.; Barduson, Beth; Stelmach, George E.

    2009-01-01

    Elderly adults often exhibit performance deficits during goal-directed movements of the dominant arm compared with young adults. Recent studies involving hemispheric lateralization have provided evidence that the dominant and non-dominant hemisphere-arm systems are specialized for controlling different movement parameters and that hemispheric…

  7. Reinforcement Learning Approach to Generate Goal-directed Locomotion of a Snake-Like Robot with Screw-Drive Units

    DEFF Research Database (Denmark)

    Chatterjee, Sromona; Nachstedt, Timo; Tamosiunaite, Minija

    2014-01-01

    Abstract—In this paper we apply a policy improvement algorithm called Policy Improvement using Path Integrals (PI2) to generate goal-directed locomotion of a complex snake-like robot with screw-drive units. PI2 is numerically simple and has an ability to deal with high dimensional systems. Here...

  8. Effects of psychosocial stress on the goal-directed and habit memory systems during learning and later execution.

    Science.gov (United States)

    Fournier, Marion; d'Arripe-Longueville, Fabienne; Radel, Rémi

    2017-03-01

    Instrumental learning occurs through both goal-directed and habit memory systems, which are supported by anatomically distinct brain systems. Interestingly, stress may promote habits at the expense of goal-directed performance, since stress before training in an instrumental task was found to cause individuals to carry on with the learned association in spite of a devalued outcome. These findings nevertheless left pending questions, and it has been difficult to determine which system is primarily affected by stress (an improved habit system, an impaired goal-directed system, or both) and at what point the stress acts (at the moment of learning by making more resistant habits, or after devaluation by making individuals less sensitive to change in the outcome value). The present study (N=72 participants, 63 males and 9 females) aimed to answer these questions with (i) an instrumental task that dissociates the two memory systems and (ii) three conditions of psychosocial stress exposure (Trier Social Stress Test): stress induced before learning, before devaluation, and not induced for the control group. The study confirms that exposure to psychosocial stress leads to habitual performance. Moreover, it provides new insight into this effect by locating its origin as an impairment in the capacity of the goal-directed system rather than a reinforcement in habit learning. These results are discussed in light of recent neurobiological models of stress and memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Outcome producing potential influences twelve-month-olds' interpretation of a novel action as goal-directed.

    Science.gov (United States)

    Biro, Szilvia; Verschoor, Stephan; Coalter, Esther; Leslie, Alan M

    2014-11-01

    Learning about a novel, goal-directed action is a complex process. It requires identifying the outcome of the action and linking the action to its outcome for later use in new situations to predict the action or to anticipate its outcome. We investigated the hypothesis that linking a novel action to a salient change in the environment is critical for infants to assign a goal to the novel action. We report a study in which we show that 12-month-old infants, who were provided with prior experience with a novel action accompanied with a salient visible outcome in one context, can interpret the same action as goal-directed even in the absence of the outcome in another context. Our control condition shows that prior experience with the action, but without the salient effect, does not lead to goal-directed interpretation of the novel action. We also found that, for the case of 9-month-olds infants, prior experience with the outcome producing potential of the novel action does not facilitate a goal-directed interpretation of the action. However, this failure was possibly due to difficulties with generalizing the learnt association to another context rather than with linking the action to its outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Functional Magnetic Resonance Imaging of Goal-Directed Reaching in Children with Autism Spectrum Disorders: A Feasibility Study

    Directory of Open Access Journals (Sweden)

    Nicole M. G. Salowitz

    2014-04-01

    Full Text Available An unanswered question concerning the neural basis of autism spectrum disorders (ASD is how sensorimotor deficits in individuals with ASD are related to abnormalities of brain function. We previously described a robotic joystick and video game system that allows us to record functional magnetic resonance images (FMRI while adult humans make goal-directed wrist motions. We anticipated several challenges in extending this approach to studying goal-directed behaviors in children with ASD and in typically developing (TYP children. In particular we were concerned that children with autism may express increased levels of anxiety as compared to typically developing children due to the loud sounds and small enclosed space of the MRI scanner. We also were concerned that both groups of children might become restless during testing, leading to an unacceptable amount of head movement. Here we performed a pilot study evaluating the extent to which autistic and typically developing children exhibit anxiety during our experimental protocol as well as their ability to comply with task instructions. Our experimental controls were successful in minimizing group differences in drop-out due to anxiety. Kinematic performance and head motion also were similar across groups. Both groups of children engaged cortical regions (frontal, parietal, temporal, occipital while making goal-directed movements. In addition, the ASD group exhibited task-related correlations in subcortical regions (cerebellum, thalamus, whereas correlations in the TYP group did not reach statistical significance in subcortical regions. Four distinct regions in frontal cortex showed a significant group difference such that TYP children exhibited positive correlations between the hemodynamic response and movement, whereas children with ASD exhibited negative correlations. These findings demonstrate feasibility of simultaneous application of robotic manipulation and functional imaging to study goal-directed

  11. External radiation therapy in early stage prostate cancer

    International Nuclear Information System (INIS)

    Sandler, Howard M.

    1996-01-01

    Optimal therapy for adenocarcinoma of the prostate is controversial. Numerous options are available, however, comparison of results is difficult in view of the insufficiency of phase III randomized trials comparing alternative treatment strategies. These options include such strategies as no curative therapy (so-called watchful waiting), radiotherapy (external and/or internal), cryotherapy, or radical prostatectomy. Clearly, a broad spectrum of clinical approaches. When reported experiences involving radiation therapy and radical prostatectomy are compared, surgical patients tend to be younger, of earlier stage, of higher performance status, and have lower pre-therapy PSA. These prognostic factors influence the probability of disease control, and since patient selection can have a profound impact on results reporting, these issues need to be carefully controlled. A review of patients who are potentially candidates for surgery at the University of Michigan treated with conformal therapy external beam treatment, indicates that these relatively early patients are doing well. These issues will be elaborated upon further during the presentation

  12. A Comparison of Aphasia Therapy Outcomes before and after a Very Early Rehabilitation Programme Following Stroke

    Science.gov (United States)

    Godecke, Erin; Ciccone, Natalie A.; Granger, Andrew S.; Rai, Tapan; West, Deborah; Cream, Angela; Cartwright, Jade; Hankey, Graeme J.

    2014-01-01

    Background: Very early aphasia rehabilitation studies have shown mixed results. Differences in therapy intensity and therapy type contribute significantly to the equivocal results. Aims: To compare a standardized, prescribed very early aphasia therapy regimen with a historical usual care control group at therapy completion (4-5 weeks post-stroke)…

  13. Early Intervention for Borderline Personality Disorder: Psychodynamic Therapy in Adolescents.

    Science.gov (United States)

    Salzer, Simone; Cropp, Carola; Streeck-Fischer, Annette

    2014-01-01

    Borderline personality disorder (BPD) should be understood as a disorder of development (Streeck-Fischer 2008, 2013) that has its first manifestation in late childhood and adolescence. There are only few treatment studies of adolescents meeting the diagnostic criteria of borderline personality disorder, although early interventions for these patients are urgently needed (see Chanen & McCutcheon 2013). We examined the effectiveness of an inpatient psychodynamic therapy (PDT). Twenty-eight adolescents fulfilling the DSM-IV diagnostic criteria of borderline personality disorder were treated with psychodynamic therapy. The mean duration of treatment was 29.87 weeks (SD = 15.88). Outcomes were remission rates, GAF, GSI, SDQ, IIP and BPI scores. Assessments were made at admission and after treatment. Pre-post comparisons and comparisons with normative data were conducted. At the end of treatment 39.29% of the patients were remitted. We found significant improvements for the GAF, GSI, SDQ, IIP (all p0.001) and the BPI (p = 0.006). These clinically relevant improvements demonstrate the effectiveness of psychodynamic therapy in adolescents with borderline personality disorder and stress the usefulness of an early intervention for these patients.

  14. Endoscopic therapy in early adenocarcinomas (Barrett's cancer) of the esophagus.

    Science.gov (United States)

    Knabe, Mate; May, Andrea; Ell, Christian

    2015-07-01

    The incidence of early esophageal adenocarcinoma has been increasing significantly in recent decades. Prognosis depends greatly on the choice of treatment. Early cancers can be treated by endoscopic resection, whereas advanced carcinomas have to be sent for surgery. Esophageal resection is associated with high perioperative mortality (1-5%) even in specialized centers. Early diagnosis enables curative endoscopic treatment option. Patients with gastrointestinal symptoms and a familial risk for esophageal cancer should undergo upper gastrointestinal endoscopy. High-definition endoscopes have been developed with technical add-on that helps endoscopists to find fine irregularities in the esophageal mucosa, but interpreting the findings remains challenging. In this review we discussed novel and old diagnostic procedures and their values, as well as our own recommendations and those of the authors discussed for the diagnosis and treatment of early Barrett's carcinoma. Endoscopic resection is the therapy of choice in early esophageal adenocarcinoma. It is mandatory to perform a subsequent ablation of all residual Barrett's mucosa to avoid metachronous lesions. © 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  15. Motivation and value influences in the relative balance of goal-directed and habitual behaviours in obsessive-compulsive disorder.

    Science.gov (United States)

    Voon, V; Baek, K; Enander, J; Worbe, Y; Morris, L S; Harrison, N A; Robbins, T W; Rück, C; Daw, N

    2015-11-03

    Our decisions are based on parallel and competing systems of goal-directed and habitual learning, systems which can be impaired in pathological behaviours. Here we focus on the influence of motivation and compare reward and loss outcomes in subjects with obsessive-compulsive disorder (OCD) on model-based goal-directed and model-free habitual behaviours using the two-step task. We further investigate the relationship with acquisition learning using a one-step probabilistic learning task. Forty-eight OCD subjects and 96 healthy volunteers were tested on a reward and 30 OCD subjects and 53 healthy volunteers on the loss version of the two-step task. Thirty-six OCD subjects and 72 healthy volunteers were also tested on a one-step reversal task. OCD subjects compared with healthy volunteers were less goal oriented (model-based) and more habitual (model-free) to reward outcomes with a shift towards greater model-based and lower habitual choices to loss outcomes. OCD subjects also had enhanced acquisition learning to loss outcomes on the one-step task, which correlated with goal-directed learning in the two-step task. OCD subjects had greater stay behaviours or perseveration in the one-step task irrespective of outcome. Compulsion severity was correlated with habitual learning in the reward condition. Obsession severity was correlated with greater switching after loss outcomes. In healthy volunteers, we further show that greater reward magnitudes are associated with a shift towards greater goal-directed learning further emphasizing the role of outcome salience. Our results highlight an important influence of motivation on learning processes in OCD and suggest that distinct clinical strategies based on valence may be warranted.

  16. Is gaze following purely reflexive or goal-directed instead? Revisiting the automaticity of orienting attention by gaze cues.

    Science.gov (United States)

    Ricciardelli, Paola; Carcagno, Samuele; Vallar, Giuseppe; Bricolo, Emanuela

    2013-01-01

    Distracting gaze has been shown to elicit automatic gaze following. However, it is still debated whether the effects of perceived gaze are a simple automatic spatial orienting response or are instead sensitive to the context (i.e. goals and task demands). In three experiments, we investigated the conditions under which gaze following occurs. Participants were instructed to saccade towards one of two lateral targets. A face distracter, always present in the background, could gaze towards: (a) a task-relevant target--("matching" goal-directed gaze shift)--congruent or incongruent with the instructed direction, (b) a task-irrelevant target, orthogonal to the one instructed ("non-matching" goal-directed gaze shift), or (c) an empty spatial location (no-goal-directed gaze shift). Eye movement recordings showed faster saccadic latencies in correct trials in congruent conditions especially when the distracting gaze shift occurred before the instruction to make a saccade. Interestingly, while participants made a higher proportion of gaze-following errors (i.e. errors in the direction of the distracting gaze) in the incongruent conditions when the distracter's gaze shift preceded the instruction onset indicating an automatic gaze following, they never followed the distracting gaze when it was directed towards an empty location or a stimulus that was never the target. Taken together, these findings suggest that gaze following is likely to be a product of both automatic and goal-driven orienting mechanisms.

  17. Alcohol-paired contextual cues produce an immediate and selective loss of goal-directed action in rats

    Directory of Open Access Journals (Sweden)

    Sean B Ostlund

    2010-07-01

    Full Text Available We assessed whether the presence of contextual cues paired with alcohol would disrupt rats’ capacity to express appropriate goal-directed action control. Rats were first given differential context conditioning such that one set of contextual cues was paired with the injection of ethanol and a second, distinctive set of cues was paired with the injection of saline. All rats were then trained in a third, neutral context to press one lever for grain pellets and another lever for sucrose pellets. They were then given two extinction tests to evaluate their ability to choose between the two actions in response to the devaluation of one of the two food outcomes with one test conducted in the alcohol-paired context and the other conducted in the control (saline-paired context. In the control context, rats exhibited goal-directed action control; i.e., they were able selectively to withhold the action that previously earned the now devalued outcome. However, these same rats were impaired when tested in the alcohol-paired context, performing both actions at the same rate regardless of the current value of their respective outcomes. Subsequent testing revealed that the rats were capable of overcoming this impairment if they were giving response-contingent feedback about the current value of the food outcomes. These results provide a clear demonstration of the disruptive influence that alcohol-paired cues can exert on decision-making in general and goal-directed action selection and choice in particular.

  18. Tissue oxygenation as a target for goal-directed therapy in high-risk surgery : a pilot study

    NARCIS (Netherlands)

    van Beest, Paul A.; Vos, Jaap Jan; Poterman, Marieke; Kalmar, Alain F.; Scheeren, Thomas W. L.

    2014-01-01

    Background:  Tissue hypoperfusion occurs frequently during surgery and may contribute to postoperative organ dysfunction. There is a need for perioperative treatment protocols aiming at improving tissue oxygenation (StO(2)). We hypothesised that intra-operative optimisation of StO(2) improves tissue

  19. Functional integration processes underlying the instruction-based learning of novel goal-directed behaviors.

    Science.gov (United States)

    Ruge, Hannes; Wolfensteller, Uta

    2013-03-01

    How does the human brain translate symbolic instructions into overt behavior? Previous studies suggested that this process relies on a rapid control transition from the lateral prefrontal cortex (LPFC) to the anterior striatum (aSTR) and premotor cortex (PMC). The present fMRI study investigated whether the transfer from symbolic to pragmatic stimulus-response (S-R) rules relies on changes in the functional coupling among these and other areas and to which extent action goal representations might get integrated within this symbolic-pragmatic transfer. Goal integration processes were examined by manipulating the contingency between actions and differential outcomes (i.e. action goals). We observed a rapid strengthening of the functional coupling between the LPFC and the basal ganglia (aSTR and putamen) and orbitofrontal cortex (OFC) as well as between the LPFC and the anterior dorsal PMC (pre-PMd), the anterior inferior parietal lobule (aIPL), and the posterior superior parietal lobule (pSPL). Importantly, only some of these functional integration processes were sensitive to the outcome contingency manipulation, including LPFC couplings with aSTR, OFC, aIPL, and pre-PMd. This suggests that the symbolic-pragmatic rule transfer is governed by principles of both, instrumental learning (increasingly tighter coupling between LPFC and aSTR/OFC) and ideomotor learning (increasingly tighter coupling between LPFC and aIPL/pre-PMd). By contrast, increased functional coupling between LPFC and putamen was insensitive to outcome contingency possibly indicating an early stage of habit formation under instructed learning conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Parkinson's disease therapy: treatment of early and late disease

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Purpose To summarize the current strategies for the treatment of early and late Parkinson's disease (PD). Data sources The presented guidelines are based on the review of the literature as well as the author's extensive experience with the treatment of 7000 patients with PD over the past 25 years. Results An analysis of reported data as well as personal experience suggest that while young patients seem to have a slower progression of the disease, they are at a higher risk for developing levodopa induced complications, such as motor fluctuations and dyskinesias. It is, therefore, prudent practice to delay levodopa therapy, particularly in younger patients, until the PD symptoms become troublesome and interfere with social or occupational functioning. Other strategies, such as the use of deprenyl, amantadine, trihexyphenidyl and dopamine agonists, should be employed before instituting levodopa therapy. Entacopone and dopamine agonists are useful in smoothing out levodopa related motor fluctuations. Surgical interventions, such as pallidotomy and pallidal or subthalamic deep brain stimulation, are effective therapeutic strategies, but should be reserved only for patients in whom optimal medical therapy fails to provide satisfactory control of symptoms. Conclusion The medical and surgical treatment of patients with PD must be individualized and tailored to the needs of the individual patient.

  1. Goal directed worry rules are associated with distinct patterns of amygdala functional connectivity and vagal modulation during perseverative cognition

    OpenAIRE

    Meeten, Frances; Davey, Graham C L; Makovac, Elena; Watson, David R.; Garfinkel, Sarah N.; Critchley, Hugo D.; Ottaviani, Cristina

    2016-01-01

    Excessive and uncontrollable worry is a defining feature of Generalized Anxiety Disorder (GAD). An important endeavor in the treatment of pathological worry is to understand why some people are unable to stop worrying once they have started. Worry perseveration is associated with a tendency to deploy goal-directed worry rules (known as “as many as can” worry rules; AMA). These require attention to the goal of the worry task and continuation of worry until the aims of the “worry bout” are achi...

  2. Distributed coordination of heterogeneous agents using a semantic overlay network and a goal-directed graphplan planner.

    Directory of Open Access Journals (Sweden)

    António Luís Lopes

    Full Text Available In this paper, we describe a distributed coordination system that allows agents to seamlessly cooperate in problem solving by partially contributing to a problem solution and delegating the subproblems for which they do not have the required skills or knowledge to appropriate agents. The coordination mechanism relies on a dynamically built semantic overlay network that allows the agents to efficiently locate, even in very large unstructured networks, the necessary skills for a specific problem. Each agent performs partial contributions to the problem solution using a new distributed goal-directed version of the Graphplan algorithm. This new goal-directed version of the original Graphplan algorithm provides an efficient solution to the problem of "distraction", which most forward-chaining algorithms suffer from. We also discuss a set of heuristics to be used in the backward-search process of the planning algorithm in order to distribute this process amongst idle agents in an attempt to find a solution in less time. The evaluation results show that our approach is effective in building a scalable and efficient agent society capable of solving complex distributable problems.

  3. From Creatures of Habit to Goal-Directed Learners: Tracking the Developmental Emergence of Model-Based Reinforcement Learning.

    Science.gov (United States)

    Decker, Johannes H; Otto, A Ross; Daw, Nathaniel D; Hartley, Catherine A

    2016-06-01

    Theoretical models distinguish two decision-making strategies that have been formalized in reinforcement-learning theory. A model-based strategy leverages a cognitive model of potential actions and their consequences to make goal-directed choices, whereas a model-free strategy evaluates actions based solely on their reward history. Research in adults has begun to elucidate the psychological mechanisms and neural substrates underlying these learning processes and factors that influence their relative recruitment. However, the developmental trajectory of these evaluative strategies has not been well characterized. In this study, children, adolescents, and adults performed a sequential reinforcement-learning task that enabled estimation of model-based and model-free contributions to choice. Whereas a model-free strategy was apparent in choice behavior across all age groups, a model-based strategy was absent in children, became evident in adolescents, and strengthened in adults. These results suggest that recruitment of model-based valuation systems represents a critical cognitive component underlying the gradual maturation of goal-directed behavior. © The Author(s) 2016.

  4. How Does Awareness Modulate Goal-Directed and Stimulus-Driven Shifts of Attention Triggered by Value Learning?

    Directory of Open Access Journals (Sweden)

    Alexia Bourgeois

    Full Text Available In order to behave adaptively, attention can be directed in space either voluntarily (i.e., endogenously according to strategic goals, or involuntarily (i.e., exogenously through reflexive capture by salient or novel events. The emotional or motivational value of stimuli can also strongly influence attentional orienting. However, little is known about how reward-related effects compete or interact with endogenous and exogenous attention mechanisms, particularly outside of awareness. Here we developed a visual search paradigm to study subliminal value-based attentional orienting. We systematically manipulated goal-directed or stimulus-driven attentional orienting and examined whether an irrelevant, but previously rewarded stimulus could compete with both types of spatial attention during search. Critically, reward was learned without conscious awareness in a preceding phase where one among several visual symbols was consistently paired with a subliminal monetary reinforcement cue. Our results demonstrated that symbols previously associated with a monetary reward received higher attentional priority in the subsequent visual search task, even though these stimuli and reward were no longer task-relevant, and despite reward being unconsciously acquired. Thus, motivational processes operating independent of conscious awareness may provide powerful influences on mechanisms of attentional selection, which could mitigate both stimulus-driven and goal-directed shifts of attention.

  5. How Does Awareness Modulate Goal-Directed and Stimulus-Driven Shifts of Attention Triggered by Value Learning?

    Science.gov (United States)

    Bourgeois, Alexia; Neveu, Rémi; Vuilleumier, Patrik

    2016-01-01

    In order to behave adaptively, attention can be directed in space either voluntarily (i.e., endogenously) according to strategic goals, or involuntarily (i.e., exogenously) through reflexive capture by salient or novel events. The emotional or motivational value of stimuli can also strongly influence attentional orienting. However, little is known about how reward-related effects compete or interact with endogenous and exogenous attention mechanisms, particularly outside of awareness. Here we developed a visual search paradigm to study subliminal value-based attentional orienting. We systematically manipulated goal-directed or stimulus-driven attentional orienting and examined whether an irrelevant, but previously rewarded stimulus could compete with both types of spatial attention during search. Critically, reward was learned without conscious awareness in a preceding phase where one among several visual symbols was consistently paired with a subliminal monetary reinforcement cue. Our results demonstrated that symbols previously associated with a monetary reward received higher attentional priority in the subsequent visual search task, even though these stimuli and reward were no longer task-relevant, and despite reward being unconsciously acquired. Thus, motivational processes operating independent of conscious awareness may provide powerful influences on mechanisms of attentional selection, which could mitigate both stimulus-driven and goal-directed shifts of attention.

  6. Loss of lateral prefrontal cortex control in food-directed attention and goal-directed food choice in obesity.

    Science.gov (United States)

    Janssen, Lieneke K; Duif, Iris; van Loon, Ilke; Wegman, Joost; de Vries, Jeanne H M; Cools, Roshan; Aarts, Esther

    2017-02-01

    Loss of lateral prefrontal cortex (lPFC)-mediated attentional control may explain the automatic tendency to eat in the face of food. Here, we investigate the neurocognitive mechanism underlying attentional bias to food words and its association with obesity using a food Stroop task. We tested 76 healthy human subjects with a wide body mass index (BMI) range (19-35kg/m 2 ) using fMRI. As a measure of obesity we calculated individual obesity scores based on BMI, waist circumference and waist-to-hip ratio using principal component analyses. To investigate the automatic tendency to overeat directly, the same subjects performed a separate behavioral outcome devaluation task measuring the degree of goal-directed versus automatic food choices. We observed that increased obesity scores were associated with diminished lPFC responses during food attentional bias. This was accompanied by decreased goal-directed control of food choices following outcome devaluation. Together these findings suggest that deficient control of both food-directed attention and choice may contribute to obesity, particularly given our obesogenic environment with food cues everywhere, and the choice to ignore or indulge despite satiety. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Computational Properties of the Hippocampus Increase the Efficiency of Goal-Directed Foraging through Hierarchical Reinforcement Learning

    Directory of Open Access Journals (Sweden)

    Eric Chalmers

    2016-12-01

    Full Text Available The mammalian brain is thought to use a version of Model-based Reinforcement Learning (MBRL to guide goal-directed behavior, wherein animals consider goals and make plans to acquire desired outcomes. However, conventional MBRL algorithms do not fully explain animals’ ability to rapidly adapt to environmental changes, or learn multiple complex tasks. They also require extensive computation, suggesting that goal-directed behavior is cognitively expensive. We propose here that key features of processing in the hippocampus support a flexible MBRL mechanism for spatial navigation that is computationally efficient and can adapt quickly to change. We investigate this idea by implementing a computational MBRL framework that incorporates features inspired by computational properties of the hippocampus: a hierarchical representation of space, forward sweeps through future spatial trajectories, and context-driven remapping of place cells. We find that a hierarchical abstraction of space greatly reduces the computational load (mental effort required for adaptation to changing environmental conditions, and allows efficient scaling to large problems. It also allows abstract knowledge gained at high levels to guide adaptation to new obstacles. Moreover, a context-driven remapping mechanism allows learning and memory of multiple tasks. Simulating dorsal or ventral hippocampal lesions in our computational framework qualitatively reproduces behavioral deficits observed in rodents with analogous lesions. The framework may thus embody key features of how the brain organizes model-based RL to efficiently solve navigation and other difficult tasks.

  8. Early response to therapy and survival in multiple myeloma.

    Science.gov (United States)

    Schaar, C G; Kluin-Nelemans, J C; le Cessie, S; Franck, P F H; te Marvelde, M C; Wijermans, P W

    2004-04-01

    Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

  9. Early and Late Onset Side Effects of Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Francesco Borgia

    2018-01-01

    Full Text Available Photodynamic Therapy (PDT is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations.

  10. Photodynamic therapy in early esophageal squamous cell carcinoma

    Science.gov (United States)

    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea; Massetti, Renato; Meroni, Emmanuele

    1995-03-01

    From 1/1985 to 7/1993, 18 patients underwent endoscopic photodynamic therapy (PDT) for early stage esophageal squamous cell carcinoma -- as two patients had two synchronous esophageal cancers, 20 lesions were treated. Tumors were staged as Tis in 7 cases and T1 in 13. The average light energy delivered was 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. To obtain a more uniform distribution of laser light in 12 cases the irradiation was performed through the wall of a transparent tube previously placed over the endoscope and advanced into the stomach. The overall results show a complete response in 14/20 (70%) tumors. Three patients developed a local recurrence, 6, 12, and 14 months after therapy. After a follow-up of 5 to 75 months, there was no evidence of disease in 10/18 patients (56%). The actuarial survival rate was 95%, 79%, and 26% at 1, 3, and 5 years, respectively. Complications were skin reaction in one patient and esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage, in 2 patients. Endoscopic PDT proved to be safe and effective in the treatment of superficial carcinoma of the esophagus.

  11. Metacognitive reflective and insight therapy for people in early phase of a schizophrenia spectrum disorder.

    Science.gov (United States)

    Hillis, Jaclyn D; Leonhardt, Bethany L; Vohs, Jenifer L; Buck, Kelly D; Salvatore, Giampaolo; Popolo, Raffaele; Dimaggio, Giancarlo; Lysaker, Paul H

    2015-02-01

    Schizophrenia often involves a loss of metacognitive capacity, the ability to form complex and integrated representations of self and others. Independent of symptoms and neurocognition, deficits in synthetic metacognition are related to difficulties of engaging in goal-directed activities in social and vocational settings. Within this backdrop, we provide a case report of the effects of Metacognitive Reflective Insight Therapy (MERIT) that assisted a patient suffering from first episode schizophrenia during 2 years of individual psychotherapy. A total of 8 elements of MERIT that stimulate and promote metacognitive capacity are presented. As illustrated in this report, these procedures helped the patient move from a state in which he had virtually no complex ideas about himself or others to one in which he had developed integrated and realistic ideas about his own identity and the identity of others. He then could use these representations to understand and effectively respond to life challenges. © 2014 Wiley Periodicals, Inc.

  12. Contexts Paired with Junk Food Impair Goal-Directed Behavior in Rats: Implications for Decision Making in Obesogenic Environments.

    Science.gov (United States)

    Kendig, Michael D; Cheung, Ambrose M K; Raymond, Joel S; Corbit, Laura H

    2016-01-01

    The high prevalence of obesity and related metabolic diseases calls for greater understanding of the factors that drive excess energy intake. Calorie-dense palatable foods are readily available and often are paired with highly salient environmental cues. These cues can trigger food-seeking and consumption in the absence of hunger. Here we examined the effects of palatable food-paired environmental cues on control of instrumental food-seeking behavior. In Experiment 1, adult male rats received exposures to one context containing three "junk" foods (JFs context) and another containing chow (Chow context). Next, rats were food-deprived and trained to perform instrumental responses (lever-press) for two novel food rewards in a third, distinct context. Contextual influences on flexible control of food-seeking behavior were then assessed by outcome devaluation tests held in the JF, chow and training contexts. Devaluation was achieved using specific satiety and test order was counterbalanced. Rats exhibited goal-directed control over behavior when tested in the training and chow-paired contexts. Notably, performance was habitual (insensitive to devaluation) when tested in the JF context. In Experiment 2 we tested whether the impairment found in the JF context could be ameliorated by the presentation of a discrete auditory cue paired with the chow context, relative to a second cue paired with the JF context. Consistent with the results of Experiment 1, the devaluation effect was not significant when rats were tested in the JF context with the JF cue. However, presenting the chow cue increased the impact of the devaluation treatment leading to a robust devaluation effect. Further tests confirmed that performance in the chow context was goal-directed and that sensory-specific satiety in the JF context was intact. These results show that environments paired with palatable foods can impair goal-directed control over food-seeking behavior, but that this deficit was improved by

  13. Contexts paired with junk food impair goal-directed behaviour in rats: implications for decision making in obesogenic environments

    Directory of Open Access Journals (Sweden)

    Michael D. Kendig

    2016-11-01

    Full Text Available The high prevalence of obesity and related metabolic diseases calls for greater understanding of the factors that drive excess energy intake. Calorie-dense palatable foods are readily available and often are paired with highly salient environmental cues. These cues can trigger food-seeking and consumption in the absence of hunger. Here we examined the effects of palatable food-paired environmental cues on control of instrumental food-seeking behaviour. In Experiment 1, adult male rats received exposures to one context containing three ‘junk’ foods (JF context and another containing chow (Chow context. Next, rats were food-deprived and trained to perform instrumental responses (lever-press for two novel food rewards in a third, distinct context. Contextual influences on flexible control of food-seeking behaviour were then assessed by outcome devaluation tests held in the JF, chow, and training contexts. Devaluation was achieved using specific satiety and test order was counterbalanced. Rats exhibited goal-directed control over behaviour when tested in the training and chow-paired contexts. Notably, performance was habitual (insensitive to devaluation when tested in the JF context. In Experiment 2 we tested whether the impairment found in the JF context could be ameliorated by the presentation of a discrete auditory cue paired with the chow context, relative to a second cue paired with the JF context. Consistent with the results of Experiment 1, the devaluation effect was not significant when rats were tested in the JF context with the JF cue. However, presenting the chow cue increased the impact of the devaluation treatment leading to a robust devaluation effect. Further tests confirmed that performance in the chow context was goal-directed and that sensory-specific satiety in the JF context was intact. These results show that environments paired with palatable foods can impair goal-directed control over food-seeking behaviour, but that this

  14. Training of goal directed arm movements with motion interactive video games in children with cerebral palsy - a kinematic evaluation.

    Science.gov (United States)

    Sandlund, Marlene; Domellöf, Erik; Grip, Helena; Rönnqvist, Louise; Häger, Charlotte K

    2014-10-01

    The main aim of this study was to evaluate the quality of goal-directed arm movements in 15 children with cerebral palsy (CP) following four weeks of home-based training with motion interactive video games. A further aim was to investigate the applicability and characteristics of kinematic parameters in a virtual context in comparison to a physical context. Kinematics and kinetics were captured while the children performed arm movements directed towards both virtual and physical targets. The children's movement precision improved, their centre of pressure paths decreased, as did the variability in maximal shoulder angles when reaching for virtual objects. Transfer to a situation with physical targets was mainly indicated by increased movement smoothness. Training with motion interactive games seems to improve arm motor control in children with CP. The results highlight the importance of considering both the context and the task itself when investigating kinematic parameters.

  15. Goal-directed diuresis: A case - control study of continuous furosemide infusion in critically ill trauma patients

    Directory of Open Access Journals (Sweden)

    Daniel Dante Yeh

    2015-01-01

    Full Text Available Background: Excessive crystalloid administration is common and associated with negative outcomes in critically ill trauma patients. Continuous furosemide infusion (CFI to remove excessive fluid has not been previously described in this population. We hypothesized that a goal-directed CFI is more effective for fluid removal than intermittent bolus injection (IBI diuresis without excess incidence of hypokalemia or renal failure. Materials and Methods: CFI cases were prospectively enrolled between November 2011 and August 2012, and matched to historic IBI controls by age, gender, Injury Severity Score (ISS, and net fluid balance (NFB at diuresis initiation. Paired and unpaired analyses were performed to compare groups. The primary endpoints were net fluid balance, potassium and creatinine levels. Secondary endpoints included intensive care unit (ICU and hospital length of stay (LOS, ventilator-free days (VFD, and mortality. Results: 55 patients were included, with 19 cases and 36 matched controls. Mean age was 54 years, mean ISS was 32.7, and mean initial NFB was +7.7 L. After one day of diuresis with CFI vs. IBI, net 24 h fluid balance was negative (−0.55 L vs. +0.43 L, P = 0.026 only for the CFI group, and there was no difference in potassium and creatinine levels. Cumulative furosemide dose (59.4mg vs. 25.4mg, P < 0.001 and urine output (4.2 L vs. 2.8 L, P < 0.001 were also significantly increased with CFI vs. IBI. There were no statistically significant differences in ICU LOS, hospital LOS, VFD, or mortality. Conclusions: Compared to IBI, goal-directed diuresis by CFI is more successful in achieving net negative fluid balance in patients with fluid overload with no detrimental side effects on renal function or patient outcome.

  16. The attribution of navigational- and goal-directed agency in dogs (Canis familiaris) and human toddlers (Homo sapiens).

    Science.gov (United States)

    Tauzin, Tibor; Csík, Andor; Lovas, Kata; Gergely, György; Topál, József

    2017-02-01

    Both human infants and nonhuman primates can recognize unfamiliar entities as instrumental agents ascribing to them goals and efficiency of goal-pursuit. This competence relies on movement cues indicating distal sensitivity to the environment and choice of efficient goal-approach. Although dogs' evolved sensitivity to social cues allow them to recognize humans as communicative agents, it remains unclear whether they have also evolved a basic concept of instrumental agency. We used a preferential object-choice procedure to test whether adult pet dogs and human toddlers can identify unfamiliar entities as agents based on different types of movement cues that specify different levels of agency. In the navigational agency condition, dogs preferentially chose an object that modified its pathway to avoid collision with obstacles over another object showing no evidence of distal sensitivity (regularly bumping into obstacles). However, in the goal-efficiency condition where neither object collided with obstacles as it navigated toward a distal target, but only 1 of them exhibited efficient goal-approach as well, toddlers, but not dogs, showed a preference toward the efficient goal-directed agent. These findings indicate that dogs possess a limited concept of environmentally sensitive navigational agency that they attribute to self-propelled entities capable of modifying their movement to avoid colliding with obstacles. Toddlers, in contrast, demonstrated clear sensitivity to cues of efficient variability of goal-approach as the basis for differentiating, attributing, and showing preference for goal-directed instrumental agency. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. Using a virtual reality game to assess goal-directed hand movements in children: A pilot feasibility study.

    Science.gov (United States)

    Gabyzon, M Elboim; Engel-Yeger, B; Tresser, S; Springer, S

    2016-01-01

    Virtual reality gaming environments may be used as a supplement to the motor performance assessment tool box by providing clinicians with quantitative information regarding motor performance in terms of movement accuracy and speed, as well as sensory motor integration under different levels of dual tasking. To examine the feasibility of using the virtual reality game `Timocco' as an assessment tool for evaluating goal-directed hand movements among typically developing children. In this pilot study, 47 typically-developing children were divided into two age groups, 4-6 years old and 6-8 years old. Performance was measured using two different virtual environment games (Bubble Bath and Falling Fruit), each with two levels of difficulty. Discriminative validity (age effect) was examined by comparing the performance of the two groups, and by comparing the performance between levels of the games for each group (level effect). Test-retest reliability was examined by reassessing the older children 3-7 days after the first session. The older children performed significantly better in terms of response time, action time, game duration, and efficiency in both games compared to the younger children. Both age groups demonstrated poorer performance at the higher game level in the Bubble Bath game compared to the lower level. A similar level effect was found in the Falling Fruit game for both age groups in response time and efficiency, but not in action time. The performance of the older children was not significantly different between the two sessions at both game levels. The discriminative validity and test-retest reliability indicate the feasibility of using the Timocco virtual reality game as a tool for assessing goal-directed hand movements in children. Further studies should examine its feasibility for use in children with disabilities.

  18. Towards a three-dimensional framework of centrally regulated and goal-directed exercise behaviour: a narrative review.

    Science.gov (United States)

    Venhorst, Andreas; Micklewright, Dominic; Noakes, Timothy D

    2017-08-23

    The Central Governor Model (CGM) ignited a paradigm shift from concepts of catastrophic failure towards central regulation of exercise performance. However, the CGM has focused on the central integration of afferent feedback in homeostatic control. Accordingly, it neglected the important role of volitional self-regulatory control and the integration of affective components inherently attached to all physiological cues. Another limitation is the large reliance on the Gestalt phenomenon of perceived exertion. Thus, progress towards a comprehensive multidimensional model of perceived fatigability and exercise regulation is needed. Drawing on Gate Control Theory of pain, we propose a three-dimensional framework of centrally regulated and goal-directed exercise behaviour, which differentiates between sensory, affective and cognitive processes shaping the perceptual milieu during exercise. We propose that: (A) perceived mental strain and perceived physical strain are primary determinants of pacing behaviour reflecting sensory-discriminatory processes necessary to align planned behaviour with current physiological state, (B) core affect plays a primary and mediatory role in exercise and performance regulation, and its underlying two dimensions hedonicity and arousal reflect affective-motivational processes triggering approach and avoidance behaviour, and (C) the mindset-shift associated with an action crisis plays a primary role in volitional self-regulatory control reflecting cognitive-evaluative processes between further goal-pursuit and goal-disengagement. The proposed framework has the potential to enrich theory development in centrally regulated and goal-directed exercise behaviour by emphasising the multidimensional dynamic processes underpinning perceived fatigability and provides a practical outline for investigating the complex interplay between the psychophysiological determinants of pacing and performance during prolonged endurance exercise. © Article author

  19. Developing Mobile Clinical Decision Support for Nursing Home Staff Assessment of Urinary Tract Infection using Goal-Directed Design.

    Science.gov (United States)

    Jones, Wallace; Drake, Cynthia; Mack, David; Reeder, Blaine; Trautner, Barbara; Wald, Heidi

    2017-06-20

    Unique characteristics of nursing homes (NHs) contribute to high rates of inappropriate antibiotic use for asymptomatic bacteriuria (ASB), a benign condition. A mobile clinical decision support system (CDSS) may support NH staff in differentiating urinary tract infections (UTI) from ASB and reducing antibiotic days. We used Goal-Directed Design to: 1) Characterize information needs for UTI identification and management in NHs; 2) Develop UTI Decide, a mobile CDSS prototype informed by personas and scenarios of use constructed from Aim 1 findings; 3) Evaluate the UTI Decide prototype with NH staff. Focus groups were conducted with providers and nurses in NHs in Denver, Colorado (n= 24). Qualitative descriptive analysis was applied to focus group transcripts to identify information needs and themes related to mobile clinical decision support for UTI identification and management. Personas representing typical end users were developed; typical clinical context scenarios were constructed using information needs as goals. Usability testing was performed using cognitive walk-throughs and a think-aloud protocol. Four information needs were identified including guidance regarding resident assessment; communication with providers; care planning; and urine culture interpretation. Design of a web-based application incorporating a published decision support algorithm for evidence-based UTI diagnoses proceeded with a focus on nursing information needs during resident assessment and communication with providers. Certified nursing assistant (CNA) and registered nurse (RN) personas were constructed in 4 context scenarios with associated key path scenarios. After field testing, a high fidelity prototype of UTI Decide was completed and evaluated by potential end users. Design recommendations and content recommendations were elicited. Goal-Directed Design informed the development of a mobile CDSS supporting participant-identified information needs for UTI assessment and communication

  20. Couple Therapy with Veterans: Early Improvements and Predictors of Early Dropout.

    Science.gov (United States)

    Fischer, Melanie S; Bhatia, Vickie; Baddeley, Jenna L; Al-Jabari, Rawya; Libet, Julian

    2017-07-28

    Family services within Veterans Affairs Medical Centers fulfill an important role in addressing relationship distress among Veterans, which is highly prevalent and comorbid with psychopathology. However, even for evidence-based couple therapies, effectiveness is weaker compared to controlled studies, maybe because many Veteran couples drop out early and do not reach the "active" treatment stage after the 3-4 session assessment. In order to improve outcomes, it is critical to identify couples at high risk for early dropout, and understand whether couples may benefit from the assessment as an intervention. The current study examined (a) demographics, treatment delivery mode, relationship satisfaction, and psychological symptoms as predictors of dropout during and immediately following the assessment phase, and (b) changes in relationship satisfaction during assessment. 174 couples completed questionnaires during routine intake procedures. The main analyses focused on 140 male Veterans and their female civilian partners; 36.43% dropped out during the assessment phase and 24.74% of the remaining couples immediately following the first treatment session. More severe depressive symptoms in non-Veteran partners were associated with dropout during assessment. Relationship satisfaction improved significantly during the assessment phase for couples who did not drop out, with larger gains for non-Veteran partners. No demographics or treatment delivery mode were associated with dropout. Although more research is needed on engaging couples at risk for early dropout and maximizing early benefits, the findings suggest that clinicians should attend to the civilian partner's and Veteran's depressive symptoms at intake and consider the assessment part of active treatment. © 2017 Family Process Institute.

  1. Early Therapeutic Alliance and Treatment Outcome in Individual and Family Therapy for Adolescent Behavior Problems

    Science.gov (United States)

    Hogue, Aaron; Dauber, Sarah; Stambaugh, Leyla Faw; Cecero, John J.; Liddle, Howard A.

    2006-01-01

    The impact of early therapeutic alliance was examined in 100 clients receiving either individual cognitive-behavioral therapy (CBT) or family therapy for adolescent substance abuse. Observational ratings of adolescent alliance in CBT and adolescent and parent alliance in family therapy were used to predict treatment retention (in CBT only) and…

  2. Radiation therapy for early stages of Morbus Ledderhose

    Energy Technology Data Exchange (ETDEWEB)

    Heyd, Reinhard [Dept. of Radiotherapy, Klinikum Offenbach (Germany); Dorn, Anne Pia; Mueller-Schimpfle, Marcus [Central Inst. of Radiology, Municipal Hospitals, Frankfurt/Main-Hoechst (Germany); Herkstroeter, Markus [Radiotherapeutic Practice at the Municipal Hospitals, Frankfurt/Main-Hoechst (Germany); Roedel, Claus; Fraunholz, Ingeborg [Dept. of Radiotherapy and Oncology, Univ. Hospital Frankfurt/Main (Germany)

    2010-01-15

    Purpose: To evaluate the efficacy of radiation therapy (RT) in the treatment of early stages of benign plantar fibromatosis (Morbus Ledderhose [ML]). Patients and Methods: From 2003 to 2008, 24 patients (33 sites) with a mean age of 52 years received RT for symptomatic ML. Prior to RT, 19 patients complained of pain and 15 had walking difficulties. 21 patients (28 sites) were irradiated with orthovolt-age X-rays and three (five sites) received electron-beam irradiation. The RT protocol consisted of five weekly fractions of 3.0 Gy (15 Gy), repeated after 6 weeks to a total dose of 30 Gy in 20 patients (28 sites). In four patients (five sites), two single fractions of 4.0 Gy were applied, repeated at intervals of 4 weeks to total doses of 24-32 Gy. Primary study endpoints were the prevention of disease progression and the avoidance of a surgical intervention. Secondary endpoints were pain relief, improvement of gait, and patients' subjective satisfaction measured with a linear analog scale (LAS). Results: After a median follow-up of 22.5 months, none of the patients experienced a progression of number and size of the lesions or the clinical symptoms. In eleven sites (33.3%) complete remission of cords or nodules occurred, in 18 (54.5%) a reduced number or size was noted, and four sites (12.1%) were unchanged. Pain relief was achieved in 13/19 patients (68.4%), and an improvement of gait abnormalities was noted in 11/15 patients (73.3%). The patients' subjective satisfaction measured by means of the LAS revealed a median improvement of 3.5 points in 22/24 patients (91.6%). Skin or soft tissues toxicities RTOG grade > 2 were not noted. Conclusion: RT is effective for treatment of the early stages of ML and may obviate the need for a surgical intervention. Long-term follow-up studies including a larger number of patients are required to define the role of RT in the management of this disorder. (orig.)

  3. Radiation therapy for early stages of Morbus Ledderhose

    International Nuclear Information System (INIS)

    Heyd, Reinhard; Dorn, Anne Pia; Mueller-Schimpfle, Marcus; Herkstroeter, Markus; Roedel, Claus; Fraunholz, Ingeborg

    2010-01-01

    Purpose: To evaluate the efficacy of radiation therapy (RT) in the treatment of early stages of benign plantar fibromatosis (Morbus Ledderhose [ML]). Patients and Methods: From 2003 to 2008, 24 patients (33 sites) with a mean age of 52 years received RT for symptomatic ML. Prior to RT, 19 patients complained of pain and 15 had walking difficulties. 21 patients (28 sites) were irradiated with orthovolt-age X-rays and three (five sites) received electron-beam irradiation. The RT protocol consisted of five weekly fractions of 3.0 Gy (15 Gy), repeated after 6 weeks to a total dose of 30 Gy in 20 patients (28 sites). In four patients (five sites), two single fractions of 4.0 Gy were applied, repeated at intervals of 4 weeks to total doses of 24-32 Gy. Primary study endpoints were the prevention of disease progression and the avoidance of a surgical intervention. Secondary endpoints were pain relief, improvement of gait, and patients' subjective satisfaction measured with a linear analog scale (LAS). Results: After a median follow-up of 22.5 months, none of the patients experienced a progression of number and size of the lesions or the clinical symptoms. In eleven sites (33.3%) complete remission of cords or nodules occurred, in 18 (54.5%) a reduced number or size was noted, and four sites (12.1%) were unchanged. Pain relief was achieved in 13/19 patients (68.4%), and an improvement of gait abnormalities was noted in 11/15 patients (73.3%). The patients' subjective satisfaction measured by means of the LAS revealed a median improvement of 3.5 points in 22/24 patients (91.6%). Skin or soft tissues toxicities RTOG grade > 2 were not noted. Conclusion: RT is effective for treatment of the early stages of ML and may obviate the need for a surgical intervention. Long-term follow-up studies including a larger number of patients are required to define the role of RT in the management of this disorder. (orig.)

  4. Metformin therapy prevents early pregnancy loss in polycystic ovarian syndrome

    International Nuclear Information System (INIS)

    Hassan, J.A.; Anbareen, T.

    2011-01-01

    Background: The study was done to compare the early pregnancy loss rate in women with polycystic ovarian syndrome who received or did not receive metformin in pregnancy. Study type, settings and duration: A case control interventional study carried out at Civil Hospital Karachi, Hamdard University Hospital and Private Gynaecology clinics from January 2005 to July 2008. Subjects and Methods Eighty two non diabetic patients with polycystic ovarian syndrome who became pregnant were included in the study. A questionnaire was filled for all patients that included information on basic demography and mean age, parity, weight. Fasting blood sugar and serum insulin levels were done for all these women. Only patients with raised insulin levels (more than 10 mu/l) were included in the study and all were offered to use oral metformin throughout pregnancy as 500 mg three times a day with folic acid supplements 5 mg once daily. Those who agreed to take the drug throughout pregnancy and to comply with the therapy were taken as cases, while those who did not agree to take the medicine acted as controls. Patients with other causes of recurrent pregnancy loss were excluded from the study. All pregnancies were followed using serial ultrasound examination to see any pregnancy loss in the two groups. Eighty two cases of polycystic ovaries with pregnancy were seen during the study period. All cases had raised serum insulin levels. Fifty patients agreed to take metformin through out pregnancy while, 32 cases did not agree to take metformin during pregnancy and thus acted as controls. The two groups did not differ in mean age, parity, weight and mean fasting blood sugar levels. Fasting insulin levels were high in metformin group (18.40 mu/l ) than in controls (12.53 mu/l). Missed abortion rate was significantly lower (12%) in metformin group than in controls (28%) (p<0.028). No congenital anomalies were found in both the groups on ultrasound at 16-19 weeks. Metformin treatment during

  5. Metformin therapy prevents early pregnancy loss in polycystic ovarian syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, J A; Anbareen, T [Dow University of Health Sciences, Karachi (Pakistan). Dept. of Gynae; Anbareen, T [Hamdard University Hospital, Karachi (Pakistan)

    2011-01-15

    Background: The study was done to compare the early pregnancy loss rate in women with polycystic ovarian syndrome who received or did not receive metformin in pregnancy. Study type, settings and duration: A case control interventional study carried out at Civil Hospital Karachi, Hamdard University Hospital and Private Gynaecology clinics from January 2005 to July 2008. Subjects and Methods Eighty two non diabetic patients with polycystic ovarian syndrome who became pregnant were included in the study. A questionnaire was filled for all patients that included information on basic demography and mean age, parity, weight. Fasting blood sugar and serum insulin levels were done for all these women. Only patients with raised insulin levels (more than 10 mu/l) were included in the study and all were offered to use oral metformin throughout pregnancy as 500 mg three times a day with folic acid supplements 5 mg once daily. Those who agreed to take the drug throughout pregnancy and to comply with the therapy were taken as cases, while those who did not agree to take the medicine acted as controls. Patients with other causes of recurrent pregnancy loss were excluded from the study. All pregnancies were followed using serial ultrasound examination to see any pregnancy loss in the two groups. Eighty two cases of polycystic ovaries with pregnancy were seen during the study period. All cases had raised serum insulin levels. Fifty patients agreed to take metformin through out pregnancy while, 32 cases did not agree to take metformin during pregnancy and thus acted as controls. The two groups did not differ in mean age, parity, weight and mean fasting blood sugar levels. Fasting insulin levels were high in metformin group (18.40 mu/l ) than in controls (12.53 mu/l). Missed abortion rate was significantly lower (12%) in metformin group than in controls (28%) (p<0.028). No congenital anomalies were found in both the groups on ultrasound at 16-19 weeks. Metformin treatment during

  6. Acceptability of Early Antiretroviral Therapy Among South African Women.

    Science.gov (United States)

    Garrett, Nigel; Norman, Emily; Leask, Kerry; Naicker, Nivashnee; Asari, Villeshni; Majola, Nelisile; Karim, Quarraisha Abdool; Karim, Salim S Abdool

    2018-03-01

    WHO guidelines recommend immediate initiation of antiretroviral therapy (ART) for all individuals at HIV diagnosis regardless of CD4 count, but concerns remain about potential low uptake or poor adherence among healthy patients with high CD4 counts, especially in resource-limited settings. This study assessed the acceptability of earlier treatment among HIV-positive South African women, median age at enrollment 25 (IQR 22-30), in a 10 year prospective cohort study by (i) describing temporal CD4 count trends at initiation in relation to WHO guidance, (ii) virological suppression rates post-ART initiation at different CD4 count thresholds, and (iii) administration of a standardized questionnaire. 158/232 (68.1%) participants initiated ART between 2006 and 2015. Mean CD4 count at initiation was 217 cells/µl (range 135-372) before 2010, and increased to 531 cells/µl (range 272-1095) by 2015 (p suppression rates at 3, 6, 12 and 18 months were consistently above 85% with no statistically significant differences for participants starting ART at different CD4 count thresholds. A questionnaire assessing uptake of early ART amongst ART-naïve women, median age 28 (IQR 24-33), revealed that 40/51 (78.4%) were willing to start ART at CD4 ≥500. Of those unwilling, 6/11 (54.5%) started ART within 6 months of questionnaire administration. Temporal increases in CD4 counts, comparable virological suppression rates, and positive patient perceptions confirm high acceptability of earlier ART initiation for the majority of patients.

  7. Photodynamic therapy in patients with early central lung cancer

    Directory of Open Access Journals (Sweden)

    V. V. Sokolov

    2013-01-01

    Full Text Available The results of photodynamic therapy (PDT for early central lung cancer are represented in the article. The study included 37 patients (52 tumor lesions. For 52 lesions pre-invasive cancer (carcinoma in situ was determined in 6 cases, squamous cell cancer with invasion within mucosal and submucosal layers of bronchial wall – in 46 cases. 51 tumors were primary lesion, 1 – residual after radiotherapy. 17 of 37 patients underwent previous surgical or combined modality treatment for cancer in other anatomical sites. For PDT we used photosensitizers photogem, photosens and radachlorine. The treatment response was assessed 1 months later by data of endoscopy and morphological study, CT, US and endosonography. Complete regression was achieved in 86,5% of cases, partial regression – in 13,5%. The efficacy of PDT was depended on tumor size. For lesion up to 1 cm in size complete regression was in 100% of cases, from 1.5 cm to 2.0 cm – in 28.6%, for tumors more than 2 cm the complete regression was not achieved. The recurrence of tumor was diagnosed in 2 patients in the period from 1 to 5 years with following successful repeated courses of PDT. Adverse effects included inflammation changes in mucosa at the PDT region with transient (up to 6-7 days local fibrinous endobronchitis with obturation of segmental bronchial lumen by fibrin membranes (7 patients, scar stenosis of segmental bronchus (2 patients. All patients had increased sensitivity to sun exposure, mild skin burns at exposed areas of body were in 2 patients. The results showed that method was highly efficient and applicable for pre-invasive central lung cancer and in patients with multiple primary bronchial lesions and high risk of surgical complications. 

  8. The allocation of attention to learning of goal-directed actions: A cognitive neuroscience framework focusing on the basal ganglia

    Directory of Open Access Journals (Sweden)

    Liz eFranz

    2012-12-01

    Full Text Available The present paper builds on the idea that attention is largely in service of our actions. A framework and model which captures the allocation of attention for learning of goal-directed actions is proposed and developed. This framework highlights an evolutionary model based on the notion that rudimentary brain functions have become embedded into increasingly higher levels of networks which all contribute to adaptive learning. Background literature is presented alongside key evidence based on experimental studies in the so-called ‘split-brain’ (surgically divided cerebral hemispheres with a key focus on bimanual actions. The proposed multilevel cognitive-neural system of attention is built upon key processes of a highly-adaptive basal-ganglia-thalamic-cortical system. Although overlap with other existing findings and models is acknowledged where appropriate, the proposed framework is an original synthesis of cognitive experimental findings with supporting evidence of a neural system and a carefully formulated model of attention. It is the hope that this new synthesis will be informative in fields of cognition and other fields of brain sciences and will lead to new avenues for experimentation across domains.

  9. Response of the Pre-oriented Goal-directed Attention to Usual and Unusual Distractors: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Golnaz Baghdadi

    2017-03-01

    Full Text Available Introduction: In this study, we investigated the distraction power of the unusual and usual images on the attention of 20 healthy primary school children. Methods: Our study was different from previous ones in that the participants were asked to fix the initial position of their attention on a pre-defined location after being presented with unusual images as distractors. The goals were presented in locations, which were far from the attraction basin of distractors. Our expectation was that the pre-orienting of the attention to the position of targets can reduce the attractive effect of unusual images compared to the usual ones. The percentage of correct responses and the reaction time have been measured as behavioral indicators of attention performance. Results: Results showed that using the goal-directed attention, subjects ignored both kinds of distractors nearly the same way. Conclusion: With regard to previous reports about the more attraction towards the unusual images, it is suggested that the dynamics of the visual attention system be sensitive to the initial condition. That is, changing the initial position of the attention can lead to the decrement of the unusual images’ effects. However, several other possibilities such as a probable delay in processing unusual features could explain this observation, too. 

  10. On the relationship between feelings and action tendencies in the emotional regulation of goal-directed behaviour

    Directory of Open Access Journals (Sweden)

    Robert eLowe

    2011-12-01

    Full Text Available In this article, we review the nature of the functional and causal relationship between neurophysiologically/psychologically generated states of emotional feeling and action tendencies and extrapolate a novel perspective. Emotion research, over the past century and beyond, has tended to view feeling and action tendency as independent phenomena: Attempts to outline the functional and causal relationship that exists between them have been framed therein. Classically, such relationships have been viewed as unidirectional, but an argument for bidirectionality rooted in a dynamic systems perspective has gained strength in recent years whereby the feeling-action tendency relationship is viewed as a composite whole. On the basis of our review of somatic-visceral theories of feelings, we argue that feelings are grounded upon neural-dynamic representations (elevated and stable activation patterns of action tendency. Such representations amount to predictions, updated by cognitive and bodily feedback. Specifically, we view emotional feelings as minimalist predictions of the action tendency (what the agent is likely to do in a given situation. The essence of this point is captured by our exposition of action tendency prediction-feedback loops (ATPFL which we consider, above all, in the context of emotion regulation, and in particular, of emotion regulation of goal-directed behaviour. The perspective outlined may be of use to emotion theorists, computational modellers and roboticists.

  11. Simulating real world functioning in schizophrenia using a naturalistic city environment and single-trial, goal-directed navigation

    Directory of Open Access Journals (Sweden)

    John A Zawadzki

    2013-11-01

    Full Text Available Objective: To develop a virtual reality platform that would serve as a functionally meaningful measure of cognition in schizophrenia that would complement standard batteries of cognitive tests during clinical trials for cognitive treatments in schizophrenia, be amenable to human neuroimaging research, yet lend itself to neurobiological comparison with rodent analogues.Method: Thirty-three patients with schizophrenia and 33 healthy controls matched for age, sex, video gaming experience and education completed eight rapid, single-trial virtual navigation tasks within a naturalistic virtual city. Four trials tested their ability to find different targets seen during the passive viewing of a closed path that led them around different city blocks. Four subsequent trials tested their ability to return to four different starting points after viewing a path that took them several blocks away from the starting position. Results: Individuals with schizophrenia had difficulties in way-finding, measured as distance travelled to find targets previously encountered within the virtual city. They were also more likely not to notice the target during passive viewing, less likely to find novel shortcuts to targets and more likely to become lost and fail completely in finding the target. Total travel distances across all eight trials strongly correlated (negatively with neurocognitive measures and, for 49 participants who completed the Quality of Life Scale, psychosocial functioning. Conclusion: Single-trial, goal-directed navigation in a naturalistic virtual environment is a functionally meaningful measure of cognitive functioning in schizophrenia.

  12. Effects of Botulinum Toxin-A and Goal-Directed Physiotherapy in Children with Cerebral Palsy GMFCS Levels I & II.

    Science.gov (United States)

    Löwing, Kristina; Thews, Karin; Haglund-Åkerlind, Yvonne; Gutierrez-Farewik, Elena M

    2017-08-01

    To evaluate short and long-term effects of botulinum toxin-A combined with goal-directed physiotherapy in children with cerebral palsy (CP). A consecutive selection of 40 children, ages 4-12 years, diagnosed with unilateral or bilateral CP, and classified in GMFCS levels I-II. During the 24 months, 9 children received one BoNT-A injection, 10 children two injections, 11 children three injections, and 10 children received four injections. 3D gait analysis, goal-attainment scaling, and body function assessments were performed before and at 3, 12, and 24 months after initial injections. A significant but clinically small long-term improvement in gait was observed. Plantarflexor spasticity was reduced after three months and remained stable, while passive ankle dorsiflexion increased after 3 months but decreased slightly after 12 months. Goal-attainment gradually increased, reached the highest levels at 12 months, and levels were maintained at 24 months. The treatments' positive effect on spasticity reduction was identified, but did not relate to improvement in gait or goal-attainment. No long-term positive change in passive ankle dorsiflexion was observed. Goal attainment was achieved in all except four children. The clinical significance of the improved gait is unclear. Further studies are recommended to identify predictors for positive treatment outcome.

  13. Association of Gait Characteristics and Depression in Patients with Parkinson’s Disease Assessed in Goal-Directed Locomotion Task

    Directory of Open Access Journals (Sweden)

    Péter Kincses

    2017-01-01

    Full Text Available Introduction. In the genesis of Parkinson’s disease (PD clinical phenomenology the exact nature of the association between bradykinesia and affective variables is unclear. In the present study, we analyzed the gait characteristics and level of depression in PD and healthy volunteers. Methods. Patients with PD (n=48 and healthy controls (n=52 were recruited for the present study. Walking speed, stride length, and cadence were compared between groups while participants completed a goal-directed locomotion task under visually controlled (VC and visually noncontrolled conditions (VnC. Results. Significantly higher depression scores were found in PD comparing to healthy control groups. In PD, depression was associated with gait components in the VC wherein the place of the target was visible. In contrast, in healthy subjects the depression was associated with gait components in VnC wherein the location and image of the target were memorized and recalled. In patients with PD and depression, the visually deprived multitask augments the rate of cadence and diminishes stride length, while velocity remains relatively unchanged. The depression associated with gait characteristics as a comorbid affective factor in PD, and that impairs the coherence of gait pattern. Conclusion. The relationship between depression and gait parameters appears to indicate that PD not only is a neurological disease but also incorporates affective disturbances that associate with the regulation of gait characteristics.

  14. Association of Gait Characteristics and Depression in Patients with Parkinson's Disease Assessed in Goal-Directed Locomotion Task

    Science.gov (United States)

    Kincses, Péter; Karádi, Kázmér; Feldmann, Ádám; Dorn, Krisztina; Aschermann, Zsuzsanna; Szolcsányi, Tibor; Csathó, Árpád

    2017-01-01

    Introduction. In the genesis of Parkinson's disease (PD) clinical phenomenology the exact nature of the association between bradykinesia and affective variables is unclear. In the present study, we analyzed the gait characteristics and level of depression in PD and healthy volunteers. Methods. Patients with PD (n = 48) and healthy controls (n = 52) were recruited for the present study. Walking speed, stride length, and cadence were compared between groups while participants completed a goal-directed locomotion task under visually controlled (VC) and visually noncontrolled conditions (VnC). Results. Significantly higher depression scores were found in PD comparing to healthy control groups. In PD, depression was associated with gait components in the VC wherein the place of the target was visible. In contrast, in healthy subjects the depression was associated with gait components in VnC wherein the location and image of the target were memorized and recalled. In patients with PD and depression, the visually deprived multitask augments the rate of cadence and diminishes stride length, while velocity remains relatively unchanged. The depression associated with gait characteristics as a comorbid affective factor in PD, and that impairs the coherence of gait pattern. Conclusion. The relationship between depression and gait parameters appears to indicate that PD not only is a neurological disease but also incorporates affective disturbances that associate with the regulation of gait characteristics. PMID:28293444

  15. fMRI activities in the emotional cerebellum: a preference for negative stimuli and goal-directed behavior.

    Science.gov (United States)

    Schraa-Tam, Caroline K L; Rietdijk, Willem J R; Verbeke, Willem J M I; Dietvorst, Roeland C; van den Berg, Wouter E; Bagozzi, Richard P; De Zeeuw, Chris I

    2012-03-01

    Several studies indicate that the cerebellum might play a role in experiencing and/or controlling emphatic emotions, but it remains to be determined whether there is a distinction between positive and negative emotions, and, if so, which specific parts of the cerebellum are involved in these types of emotions. Here, we visualized activations of the cerebellum and extracerebellar regions using high-field fMRI, while we asked participants to observe and imitate images with pictures of human faces expressing different emotional states or with moving geometric shapes as control. The state of the emotions could be positive (happiness and surprise), negative (anger and disgust), or neutral. The positive emotional faces only evoked mild activations of crus 2 in the cerebellum, whereas the negative emotional faces evoked prominent activations in lobules VI and VIIa in its hemispheres and lobules VIII and IX in the vermis. The cerebellar activations associated with negative emotions occurred concomitantly with activations of mirror neuron domains such as the insula and amygdala. These data suggest that the potential role of the cerebellum in control of emotions may be particularly relevant for goal-directed behavior that is required for observing and reacting to another person's (negative) expressions.

  16. Bonsai trees in your head: how the pavlovian system sculpts goal-directed choices by pruning decision trees.

    Directory of Open Access Journals (Sweden)

    Quentin J M Huys

    Full Text Available When planning a series of actions, it is usually infeasible to consider all potential future sequences; instead, one must prune the decision tree. Provably optimal pruning is, however, still computationally ruinous and the specific approximations humans employ remain unknown. We designed a new sequential reinforcement-based task and showed that human subjects adopted a simple pruning strategy: during mental evaluation of a sequence of choices, they curtailed any further evaluation of a sequence as soon as they encountered a large loss. This pruning strategy was Pavlovian: it was reflexively evoked by large losses and persisted even when overwhelmingly counterproductive. It was also evident above and beyond loss aversion. We found that the tendency towards Pavlovian pruning was selectively predicted by the degree to which subjects exhibited sub-clinical mood disturbance, in accordance with theories that ascribe Pavlovian behavioural inhibition, via serotonin, a role in mood disorders. We conclude that Pavlovian behavioural inhibition shapes highly flexible, goal-directed choices in a manner that may be important for theories of decision-making in mood disorders.

  17. Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis.

    Science.gov (United States)

    Omidvari, K; de Boisblanc, B P; Karam, G; Nelson, S; Haponik, E; Summer, W

    1998-08-01

    Our objective was to compare therapeutic outcome and analyse cost-benefit of a 'conventional' (7-day course of i.v. antibiotic therapy) vs. an abbreviated (2-day i.v. antibiotic course followed by 'switch' to oral antibiotics) therapy for in-patients with community-acquired pneumonia (CAP). We used a multicenter prospective, randomized, parallel group with a 28 day follow-up, at the University-based teaching hospitals: The Medical Center of Louisiana in New Orleans, LA and hospitals listed in the acknowledgement. Ninety-five patients were randomized to receive either a 'conventional' course of intravenous antibiotic therapy with cefamandole 1 g i.v. every 6 h for 7 days (n = 37), or an abbreviated course of intravenous therapy with cefamandole (1 g i.v. every 6 h for 2 days) followed by oral therapy with cefaclor (500 mg every 8 h for 5 days). No difference was found in the clinical courses, cure rates, survival or the resolution of the chest radiograph abnormalities among the two groups. The mean duration of therapy (6.88 days for the conventional group compared to 7-30 days for the early oral therapy group) and the frequencies of overall symptomatic improvement (97% vs. 95%, respectively) were similar in both groups. Patients who received early oral therapy had shorter hospital stays (7.3 vs. 9.71 days, P = 0.01), and a lower total cost of care ($2953 vs. $5002, P < 0.05). It was concluded that early transition to an oral antibiotic after an abbreviated course of intravenous therapy in CAP is substantially less expensive and has comparable efficacy to conventional intravenous therapy. Altering physicians' customary management of hospitalized patients with CAP can reduce costs with no appreciable additional risk of adverse patient outcome.

  18. Reward Contingencies Improve Goal-Directed Behavior by Enhancing Posterior Brain Attentional Regions and Increasing Corticostriatal Connectivity in Cocaine Addicts.

    Science.gov (United States)

    Rosell-Negre, Patricia; Bustamante, Juan-Carlos; Fuentes-Claramonte, Paola; Costumero, Víctor; Llopis-Llacer, Juan-José; Barrós-Loscertales, Alfonso

    2016-01-01

    The dopaminergic system provides the basis for the interaction between motivation and cognition. It is triggered by the possibility of obtaining rewards to initiate the neurobehavioral adaptations necessary to achieve them by directing the information from motivational circuits to cognitive and action circuits. In drug addiction, the altered dopamine (DA) modulation of the meso-cortico-limbic reward circuitry, such as the prefrontal cortex (PFC), underlies the disproportionate motivational value of drug use at the expense of other non-drug reinforcers and the user's loss of control over his/her drug intake. We examine how the magnitude of the reward affects goal-directed processes in healthy control (HC) subjects and abstinent cocaine dependent (ACD) patients by using functional magnetic resonance imaging (fMRI) during a counting Stroop task with blocked levels of monetary incentives of different magnitudes (€0, €0.01, €0.5, €1 or €1.5). Our results showed that increasing reward magnitude enhances (1) performance facilitation in both groups; (2) left dorsolateral prefrontal cortex (DLPFC) activity in HC and left superior occipital cortex activity in ACD; and (3) left DLPFC and left putamen connectivity in ACD compared to HC. Moreover, we observed that (4) dorsal striatal and pallidum activity was associated with craving and addiction severity during the parametric increases in the monetary reward. In conclusion, the brain response to gradients in monetary value was different in HC and ACD, but both groups showed improved task performance due to the possibility of obtaining greater monetary rewards.

  19. Fast Track Open Partial Nephrectomy: Reduced Postoperative Length of Stay with a Goal-Directed Pathway Does Not Compromise Outcome

    Directory of Open Access Journals (Sweden)

    Bilal Chughtai

    2008-01-01

    Full Text Available Introduction. The aim of this study is to examine the feasibility of reducing postoperative hospital stay following open partial nephrectomy through the implementation of a goal directed clinical management pathway. Materials and Methods. A fast track clinical pathway for open partial nephrectomy was introduced in July 2006 at our institution. The pathway has daily goals and targets discharge for all patients on the 3rd postoperative day (POD. Defined goals are (1 ambulation and liquid diet on the evening of the operative day; (2 out of bed (OOB at least 4 times on POD 1; (3 removal of Foley catheter on the morning of POD 2; (4 removal of Jackson Pratt drain on the afternoon of POD 2; (4 discharge to home on POD 3. Patients and family are instructed in the fast track protocol preoperatively. Demographic data, tumor size, length of stay, and complications were captured in a prospective database, and compared to a control group managed consecutively immediately preceding the institution of the fast track clinical pathway. Results. Data on 33 consecutive patients managed on the fast track clinical pathway was compared to that of 25 control patients. Twenty two (61% out of 36 fast track patients and 4 (16% out of 25 control patients achieved discharge on POD 3. Overall, fast track patients had a shorter hospital stay than controls (median, 3 versus 4 days; P = .012. Age (median, 55 versus 57 years, tumor size (median, 2.5 versus 2.5 cm, readmission within 30 days (5.5% versus 5.1%, and complications (10.2% versus 13.8% were similar in the fast track patients and control, respectively. Conclusions. In the present series, a fast track clinical pathway after open partial nephrectomy reduced the postoperative length of hospital stay and did not appear to increase the postoperative complication rate.

  20. Goal-directed control with cortical units that are gated by both top-down feedback and oscillatory coherence

    Science.gov (United States)

    Kerr, Robert R.; Grayden, David B.; Thomas, Doreen A.; Gilson, Matthieu; Burkitt, Anthony N.

    2014-01-01

    The brain is able to flexibly select behaviors that adapt to both its environment and its present goals. This cognitive control is understood to occur within the hierarchy of the cortex and relies strongly on the prefrontal and premotor cortices, which sit at the top of this hierarchy. Pyramidal neurons, the principal neurons in the cortex, have been observed to exhibit much stronger responses when they receive inputs at their soma/basal dendrites that are coincident with inputs at their apical dendrites. This corresponds to inputs from both lower-order regions (feedforward) and higher-order regions (feedback), respectively. In addition to this, coherence between oscillations, such as gamma oscillations, in different neuronal groups has been proposed to modulate and route communication in the brain. In this paper, we develop a simple, but novel, neural mass model in which cortical units (or ensembles) exhibit gamma oscillations when they receive coherent oscillatory inputs from both feedforward and feedback connections. By forming these units into circuits that can perform logic operations, we identify the different ways in which operations can be initiated and manipulated by top-down feedback. We demonstrate that more sophisticated and flexible top-down control is possible when the gain of units is modulated by not only top-down feedback but by coherence between the activities of the oscillating units. With these types of units, it is possible to not only add units to, or remove units from, a higher-level unit's logic operation using top-down feedback, but also to modify the type of role that a unit plays in the operation. Finally, we explore how different network properties affect top-down control and processing in large networks. Based on this, we make predictions about the likely connectivities between certain brain regions that have been experimentally observed to be involved in goal-directed behavior and top-down attention. PMID:25152715

  1. Goal-directed control with cortical units that are gated by both top-down feedback and oscillatory coherence

    Directory of Open Access Journals (Sweden)

    Robert R. Kerr

    2014-08-01

    Full Text Available The brain is able to flexibly select behaviors that adapt to both its environment and its present goals. This cognitive control is understood to occur within the hierarchy of the cortex and relies strongly on the prefrontal and premotor cortices, which sit at the top of this hierarchy. Pyramidal neurons, the principal neurons in the cortex, have been observed to exhibit much stronger responses when they receive inputs at their soma/basal dendrites that are coincident with inputs at their apical dendrites. This corresponds to inputs from both lower-order regions (feedforward and higher-order regions (feedback, respectively. In addition to this, coherence between oscillations, such as gamma oscillations, in different neuronal groups has been proposed to modulate and route communication in the brain. In this paper, we develop a simple, but novel, neural mass model in which cortical units (or ensembles exhibit gamma oscillations when they receive coherent oscillatory inputs from both feedforward and feedback connections. By forming these units into circuits that can perform logic operations, we identify the different ways in which operations can be initiated and manipulated by top-down feedback. We demonstrate that more sophisticated and flexible top-down control is possible when the gain of units is modulated by not only top-down feedback but by coherence between the activities of the oscillating units. With these types of units, it is possible to not only add units to, or remove units from, a higher-level unit's logic operation using top-down feedback, but also to modify the type of role that a unit plays in the operation. Finally, we explore how different network properties affect top-down control and processing in large networks. Based on this, we make predictions about the likely connectivities between certain brain regions that have been experimentally observed to be involved in goal-directed behavior and top-down attention.

  2. Reward Contingencies Improve Goal-Directed Behavior by Enhancing Posterior Brain Attentional Regions and Increasing Corticostriatal Connectivity in Cocaine Addicts

    Science.gov (United States)

    Rosell-Negre, Patricia; Bustamante, Juan-Carlos; Fuentes-Claramonte, Paola; Costumero, Víctor; Llopis-Llacer, Juan-José; Barrós-Loscertales, Alfonso

    2016-01-01

    The dopaminergic system provides the basis for the interaction between motivation and cognition. It is triggered by the possibility of obtaining rewards to initiate the neurobehavioral adaptations necessary to achieve them by directing the information from motivational circuits to cognitive and action circuits. In drug addiction, the altered dopamine (DA) modulation of the meso-cortico-limbic reward circuitry, such as the prefrontal cortex (PFC), underlies the disproportionate motivational value of drug use at the expense of other non-drug reinforcers and the user’s loss of control over his/her drug intake. We examine how the magnitude of the reward affects goal-directed processes in healthy control (HC) subjects and abstinent cocaine dependent (ACD) patients by using functional magnetic resonance imaging (fMRI) during a counting Stroop task with blocked levels of monetary incentives of different magnitudes (€0, €0.01, €0.5, €1 or €1.5). Our results showed that increasing reward magnitude enhances (1) performance facilitation in both groups; (2) left dorsolateral prefrontal cortex (DLPFC) activity in HC and left superior occipital cortex activity in ACD; and (3) left DLPFC and left putamen connectivity in ACD compared to HC. Moreover, we observed that (4) dorsal striatal and pallidum activity was associated with craving and addiction severity during the parametric increases in the monetary reward. In conclusion, the brain response to gradients in monetary value was different in HC and ACD, but both groups showed improved task performance due to the possibility of obtaining greater monetary rewards. PMID:27907134

  3. Reward Contingencies Improve Goal-Directed Behavior by Enhancing Posterior Brain Attentional Regions and Increasing Corticostriatal Connectivity in Cocaine Addicts.

    Directory of Open Access Journals (Sweden)

    Patricia Rosell-Negre

    Full Text Available The dopaminergic system provides the basis for the interaction between motivation and cognition. It is triggered by the possibility of obtaining rewards to initiate the neurobehavioral adaptations necessary to achieve them by directing the information from motivational circuits to cognitive and action circuits. In drug addiction, the altered dopamine (DA modulation of the meso-cortico-limbic reward circuitry, such as the prefrontal cortex (PFC, underlies the disproportionate motivational value of drug use at the expense of other non-drug reinforcers and the user's loss of control over his/her drug intake. We examine how the magnitude of the reward affects goal-directed processes in healthy control (HC subjects and abstinent cocaine dependent (ACD patients by using functional magnetic resonance imaging (fMRI during a counting Stroop task with blocked levels of monetary incentives of different magnitudes (€0, €0.01, €0.5, €1 or €1.5. Our results showed that increasing reward magnitude enhances (1 performance facilitation in both groups; (2 left dorsolateral prefrontal cortex (DLPFC activity in HC and left superior occipital cortex activity in ACD; and (3 left DLPFC and left putamen connectivity in ACD compared to HC. Moreover, we observed that (4 dorsal striatal and pallidum activity was associated with craving and addiction severity during the parametric increases in the monetary reward. In conclusion, the brain response to gradients in monetary value was different in HC and ACD, but both groups showed improved task performance due to the possibility of obtaining greater monetary rewards.

  4. Dynamics of rapid dopamine release in the nucleus accumbens during goal-directed behaviors for cocaine versus natural rewards.

    Science.gov (United States)

    Cameron, Courtney M; Wightman, R Mark; Carelli, Regina M

    2014-11-01

    Electrophysiological studies show that distinct subsets of nucleus accumbens (NAc) neurons differentially encode information about goal-directed behaviors for intravenous cocaine versus natural (food/water) rewards. Further, NAc rapid dopamine signaling occurs on a timescale similar to phasic cell firing during cocaine and natural reward-seeking behaviors. However, it is not known whether dopamine signaling is reinforcer specific (i.e., is released during responding for only one type of reinforcer) within discrete NAc locations, similar to neural firing dynamics. Here, fast-scan cyclic voltammetry (FSCV) was used to measure rapid dopamine release during multiple schedules involving sucrose reward and cocaine self-administration (n = 8 rats) and, in a separate group of rats (n = 6), during a sucrose/food multiple schedule. During the sucrose/cocaine multiple schedule, dopamine increased within seconds of operant responding for both reinforcers. Although dopamine release was not reinforcer specific, more subtle differences were observed in peak dopamine concentration [DA] across reinforcer conditions. Specifically, peak [DA] was higher during the first phase of the multiple schedule, regardless of reinforcer type. Further, the time to reach peak [DA] was delayed during cocaine-responding compared to sucrose. During the sucrose/food multiple schedule, increases in dopamine release were also observed relative to operant responding for both natural rewards. However, peak [DA] was higher relative to responding for sucrose than food, regardless of reinforcer order. Overall, the results reveal the dynamics of rapid dopamine signaling in discrete locations in the NAc across reward conditions, and provide novel insight into the functional role of this system in reward-seeking behaviors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Of goals and habits: Age-related and individual differences in goal-directed decision-making

    Directory of Open Access Journals (Sweden)

    Ben eEppinger

    2013-12-01

    Full Text Available In this study we investigated age-related and individual differences in habitual (model-free and goal-directed (model-based decision-making. Specifically, we were interested in three questions. First, does age affect the balance between model-based and model-free decision mechanisms? Second, are these age-related changes due to age differences in working memory (WM capacity? Third, can model-based behavior be affected by manipulating the distinctiveness of the reward value of choice options? To answer these questions we used a two-stage Markov decision task in in combination with computational modeling to dissociate model-based and model-free decision mechanisms. To affect model-based behavior in this task we manipulated the distinctiveness of reward probabilities of choice options. The results show age-related deficits in model-based decision-making, which are particularly pronounced if unexpected reward indicates the need for a shift in decision strategy. In this situation younger adults explore the task structure, whereas older adults show perseverative behavior. Consistent with previous findings, these results indicate that older adults have deficits in the representation and updating of expected reward value. We also observed substantial individual differences in model-based behavior. In younger adults high WM capacity is associated with greater model-based behavior and this effect is further elevated when reward probabilities are more distinct. However, in older adults we found no effect of WM capacity. Moreover, age differences in model-based behavior remained statistically significant, even after controlling for WM capacity. Thus, factors other than decline in WM, such as deficits in the in the integration of expected reward value into strategic decisions may contribute to the observed impairments in model-based behavior in older adults.

  6. Development of a Combination Cell and Gene Therapy Approach for Early-Stage Breast Cancer

    National Research Council Canada - National Science Library

    Lewis, Michael T

    2005-01-01

    The unique biology of the breast presents the opportunity to these cell and gene therapy techniques in a way that circumvents many of these technical limitations for the treatment of early stage breast cancer...

  7. Gene therapy, early promises, subsequent problems, and recent breakthroughs.

    Science.gov (United States)

    Razi Soofiyani, Saeideh; Baradaran, Behzad; Lotfipour, Farzaneh; Kazemi, Tohid; Mohammadnejad, Leila

    2013-01-01

    Gene therapy is one of the most attractive fields in medicine. The concept of gene delivery to tissues for clinical applications has been discussed around half a century, but scientist's ability to manipulate genetic material via recombinant DNA technology made this purpose to reality. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. While gene therapy initially conceived as a way to treat life-threatening disorders (inborn errors, cancers) refractory to conventional treatment, to date gene therapy is considered for many non-life-threatening conditions including those adversely influence on a patient's quality of life. Gene therapy has made significant progress, including tangible success, although much slower than was initially predicted. Although, gene therapies still at a fairly primitive stage, it is firmly science based. There is justifiable hope that with enhanced pathobiological understanding and biotechnological improvements, gene therapy will be a standard part of clinical practice within 20 years.

  8. Gene Therapy, Early Promises, Subsequent Problems, and Recent Breakthroughs

    Directory of Open Access Journals (Sweden)

    Saeideh Razi Soofiyani

    2013-08-01

    Full Text Available Gene therapy is one of the most attractive fields in medicine. The concept of gene delivery to tissues for clinical applications has been discussed around half a century, but scientist’s ability to manipulate genetic material via recombinant DNA technology made this purpose to reality. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. While gene therapy initially conceived as a way to treat life-threatening disorders (inborn errors, cancers refractory to conventional treatment, to date gene therapy is considered for many non–life-threatening conditions including those adversely influence on a patient’s quality of life. Gene therapy has made significant progress, including tangible success, although much slower than was initially predicted. Although, gene therapies still at a fairly primitive stage, it is firmly science based. There is justifiable hope that with enhanced pathobiological understanding and biotechnological improvements, gene therapy will be a standard part of clinical practice within 20 years.

  9. Interpersonal processes affecting early alliance formation in experiential therapy for depression.

    Science.gov (United States)

    Wong, Karen; Pos, Alberta E

    2014-01-01

    This study examined the effects of in-session interpersonal process and pre-therapy interpersonal problems on session-one alliance formation for 32 clients who received short-term experiential therapy for depression. Interpersonal behavior measured by the Structural Analysis of Social Behavior, as well as clients' pre-therapy reports of interpersonal problems significantly related to session-one alliance scores. Greater client disclosure independently predicted a stronger session-one bond with the therapist. Both greater client disclosure (positively) and pre-therapy Social Inhibition (negatively) independently predicted early goal agreement. Findings suggest that client disclosure is a marker of early engagement in experiential therapy, as well as support this model's mandate to form interpersonally safe therapeutic environments from the first moments of therapy.

  10. Occupational Therapy Contributions in Early Intervention: Implications for Personnel Preparation and Interprofessional Practice

    Science.gov (United States)

    Muhlenhaupt, Mary; Pizur-Barnekow, Kris; Schefkind, Sandra; Chandler, Barbara; Harvison, Neil

    2015-01-01

    Occupational therapy provides a unique contribution in early intervention programs for families and their children from birth to 3 years old who are at risk for, or who have, identified disabilities. This article describes occupational therapy's distinct value and presents the profession's perspective on services to enhance families' caregiving…

  11. Early Intervention Stem Cell-Based Therapy (EISCBT) for Corneal Burns and Trauma

    Science.gov (United States)

    2016-10-01

    described in their manuscript fully available, without restriction and from the time of publication, with only rare exceptions to address legal and... aborting the early inflammatory response. Molecular therapy : the journal of the American Society of Gene Therapy. 2012;20(11):2143-52. Epub 2012/08/30

  12. Value of information: interim analysis of a randomized, controlled trial of goal-directed hemodynamic treatment for aged patients.

    Science.gov (United States)

    Bartha, Erzsebet; Davidson, Thomas; Brodtkorb, Thor-Henrik; Carlsson, Per; Kalman, Sigridur

    2013-07-09

    A randomized, controlled trial, intended to include 460 patients, is currently studying peroperative goal-directed hemodynamic treatment (GDHT) of aged hip-fracture patients. Interim efficacy analysis performed on the first 100 patients was statistically uncertain; thus, the trial is continuing in accordance with the trial protocol. This raised the present investigation's main question: Is it reasonable to continue to fund the trial to decrease uncertainty? To answer this question, a previously developed probabilistic cost-effectiveness model was used. That model depicts (1) a choice between routine fluid treatment and GDHT, given uncertainty of current evidence and (2) the monetary value of further data collection to decrease uncertainty. This monetary value, that is, the expected value of perfect information (EVPI), could be used to compare future research costs. Thus, the primary aim of the present investigation was to analyze EVPI of an ongoing trial with interim efficacy observed. A previously developed probabilistic decision analytic cost-effectiveness model was employed to compare the routine fluid treatment to GDHT. Results from the interim analysis, published trials, the meta-analysis, and the registry data were used as model inputs. EVPI was predicted using (1) combined uncertainty of model inputs; (2) threshold value of society's willingness to pay for one, quality-adjusted life-year; and (3) estimated number of future patients exposed to choice between GDHT and routine fluid treatment during the expected lifetime of GDHT. If a decision to use GDHT were based on cost-effectiveness, then the decision would have a substantial degree of uncertainty. Assuming a 5-year lifetime of GDHT in clinical practice, the number of patients who would be subject to future decisions was 30,400. EVPI per patient would be €204 at a €20,000 threshold value of society's willingness to pay for one quality-adjusted life-year. Given a future population of 30,400 individuals

  13. The Neuro-Mechanical Processes That Underlie Goal-Directed Medio-Lateral APA during Gait Initiation.

    Science.gov (United States)

    Honeine, Jean-Louis; Schieppati, Marco; Crisafulli, Oscar; Do, Manh-Cuong

    2016-01-01

    Gait initiation (GI) involves passing from bipedal to unipedal stance. It requires a rapid movement of the center of foot pressure (CoP) towards the future swing foot and of the center of mass (CoM) in the direction of the stance foot prior to the incoming step. This anticipatory postural adjustment (APA) allows disengaging the swing leg from the ground and establishing favorable conditions for stepping. This study aimed to describe the neuro-mechanical process that underlies the goal-directed medio-lateral (ML) APA. We hypothesized that controlled knee flexion of the stance leg contributes to the initial ML displacement of the CoP and to the calibration of the first step. Fourteen subjects initiated gait starting from three different initial stance widths of 15 cm (Small), 30 cm (Medium), and 45 cm (Large). Optoelectronic, force platform and electromyogram (EMG) measurements were performed. During APA, soleus activity diminished bilaterally, while tibialis anterior (TA) activity increased, more so in the stance leg than in the swing leg, and to a larger extent with increasing initial stance width. Knee flexion of the stance leg was observed during APA and correlated with the ML CoP displacement towards the swing leg. ML CoP and CoM displacements during APA increased with increasing stance width. The activity of stance-leg TA was correlated with the degree of knee flexion. Swing-leg tensor fasciae latae (TFL) was also active during APA. Across subjects, when stance-leg tibialis activity was low, TFL activity was large and vice versa. The modulation of the ML CoP position during APA allowed the gravity-driven torque to place the CoM just lateral to the stance foot during step execution. Accordingly, the gravity-driven torque, the ML CoM velocity during step execution, and the step width at foot contact (FC) were lower in the Small and greater in the Large condition. Consequently, the position of the stepping foot at FC remained close to the sagittal plane in all

  14. Slips of action and sequential decisions: a cross-validation study of tasks assessing habitual and goal-directed action control

    Directory of Open Access Journals (Sweden)

    Zsuzsika Sjoerds

    2016-12-01

    Full Text Available Instrumental learning and decision-making rely on two parallel systems: a goal-directed and a habitual system. In the past decade, several paradigms have been developed to study these systems in animals and humans by means of e.g. overtraining, devaluation procedures and sequential decision-making. These different paradigms are thought to measure the same constructs, but cross-validation has rarely been investigated. In this study we compared two widely used paradigms that assess aspects of goal-directed and habitual behavior. We correlated parameters from a two-step sequential decision-making task that assesses model-based and model-free learning with a slips-of-action paradigm that assesses the ability to suppress cue-triggered, learnt responses when the outcome has been devalued and is therefore no longer desirable. Model-based control during the two-step task showed a very moderately positive correlation with goal-directed devaluation sensitivity, whereas model-free control did not. Interestingly, parameter estimates of model-based and goal-directed behavior in the two tasks were positively correlated with higher-order cognitive measures (e.g. visual short-term memory. These cognitive measures seemed to (at least partly mediate the association between model-based control during sequential decision-making and goal-directed behavior after instructed devaluation. This study provides moderate support for a common framework to describe the propensity towards goal-directed behavior as measured with two frequently used tasks. However, we have to caution that the amount of shared variance between the goal-directed and model-based system in both tasks was rather low, suggesting that each task does also pick up distinct aspects of goal-directed behavior. Further investigation of the commonalities and differences between the model-free and habit systems as measured with these, and other, tasks is needed. Also, a follow-up cross-validation on the neural

  15. Some effects of radiation therapy during early childhood on facial growth and tooth development

    International Nuclear Information System (INIS)

    Harris, A.M.P.; Nortje, C.J.; Lucchesi, M.V.

    1986-01-01

    Case histories of the dental examinations of 2 children who were treated by radiation therapy for retinoblastomas in early childhood are discussed. The evidence presented here seems to indicate that in both patients early irradiation of the orbits and, as a result thereof, the jaws, could be partly responsible for the underdevelopment of this region

  16. The association between early menopause and risk of ischaemic heart disease: Influence of Hormone Therapy

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen Christine Leth; Andersen, Zorana Jovanovic; Heitmann, Berit Lilienthal

    2006-01-01

    Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether...... HT reduces this risk associated with early menopause....

  17. The early career researcher's toolkit:translating tissue engineering, regenerative medicine and cell therapy products

    OpenAIRE

    Rafiq, Qasim A.; Ortega, Ilida; Jenkins, Stuart I.; Wilson, Samantha L.; Patel, Asha K.; Barnes, Amanda L.; Adams, Christopher F.; Delcassian, Derfogail; Smith, David

    2015-01-01

    Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in...

  18. Dissociable corticostriatal circuits underlie goal-directed vs. cue-elicited habitual food seeking after satiation : Evidence from a multimodal MRI study

    NARCIS (Netherlands)

    van Steenbergen, H.; Watson, P.; Wiers, R.W.; Hommel, B.; de Wit, S.

    The present multimodal MRI study advances our understanding of the corticostriatal circuits underlying goal-directed vs. cue-driven, habitual food seeking. To this end, we employed a computerized Pavlovian-instrumental transfer paradigm. During the test phase, participants were free to perform

  19. Pharmacological Blockade of Adenosine A2A but Not A1 Receptors Enhances Goal-Directed Valuation in Satiety-Based Instrumental Behavior

    Directory of Open Access Journals (Sweden)

    Yan Li

    2018-04-01

    Full Text Available The balance and smooth shift between flexible, goal-directed behaviors and repetitive, habitual actions are critical to optimal performance of behavioral tasks. The striatum plays an essential role in control of goal-directed versus habitual behaviors through a rich interplay of the numerous neurotransmitters and neuromodulators to modify the input, processing and output functions of the striatum. The adenosine receptors (namely A2AR and A1R, with their high expression pattern in the striatum and abilities to interact and integrate dopamine, glutamate and cannabinoid signals in the striatum, may represent novel therapeutic targets for modulating instrumental behavior. In this study, we examined the effects of pharmacological blockade of the A2ARs and A1Rs on goal-directed versus habitual behaviors in different information processing phases of instrumental learning using a satiety-based instrumental behavior procedure. We found that A2AR antagonist acts at the coding, consolidation and expression phases of instrumental learning to modulate animals’ sensitivity to goal-directed valuation without modifying action-outcome contingency. However, pharmacological blockade and genetic knockout of A1Rs did not affect acquisition or sensitivity to goal-valuation of instrumental behavior. These findings provide pharmacological evidence for a potential therapeutic strategy to control abnormal instrumental behaviors associated with drug addiction and obsessive-compulsive disorder by targeting the A2AR.

  20. Applying the model of Goal-Directed Behavior, including descriptive norms, to physical activity intentions: A contribution to improving the Theory of Planned Behavior

    Science.gov (United States)

    The theory of planned behavior (TPB) has received its fair share of criticism lately, including calls for it to retire. We contributed to improving the theory by testing extensions such as the model of goal-directed behavior (MGDB, which adds desire and anticipated positive and negative emotions) ap...

  1. Intact goal-directed control in treatment-seeking drug users indexed by outcome-devaluation and Pavlovian to instrumental transfer: Critique of habit theory.

    Science.gov (United States)

    Hogarth, Lee; Lam-Cassettari, Christa; Pacitti, Helena; Currah, Tara; Mahlberg, Justin; Hartley, Lucie; Moustafa, Ahmed

    2018-05-22

    Animal studies have demonstrated that chronic exposure to drugs of abuse impairs goal-directed control over action selection indexed by the outcome-devaluation and specific Pavlovian to instrumental transfer procedures, suggesting this impairment might underpin addiction. However, there is currently only weak evidence for impaired goal-directed control in human drug users. Two experiments were undertaken in which treatment-seeking drug users and non-matched normative reference samples (controls) completed outcome-devaluation and specific Pavlovian to instrumental transfer procedures notionally translatable to animal procedures (Experiment 2 used a more challenging biconditional schedule). The two experiments found significant outcome-devaluation and specific Pavlovian to instrumental transfer effects overall and there was no significant difference between groups in the magnitude of these effects. Moreover, Bayes factor supported the null hypothesis for these group comparisons. Although limited by non-matched group comparisons and small sample sizes, the two studies suggest that treatment-seeking drug users have intact goal-directed control over action selection, adding uncertainty to already mixed evidence concerning the role of habit learning in human drug dependence. Neuro-interventions might seek to tackle goal-directed drug-seeking rather than habit formation in drug users. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

    DEFF Research Database (Denmark)

    Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred

    2015-01-01

    BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS: We randomly assigned HIV...... entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients...... in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells...

  3. Early insulin therapy in patients with type 2 diabetes mellitus

    African Journals Online (AJOL)

    Type 2 diabetes mellitus (T2DM) is an insulin-insufficient disease characterised ... complications.1–4 Early in the onset of T2DM there is development of relative insulin ..... position statement of the American Diabetes Association (ADA) and.

  4. The Underutilization of Occupational Therapy in Transdisciplinary Early Intervention Services

    Science.gov (United States)

    Minard, Carey

    2018-01-01

    Early intervention (EI) services are mandated by Part C of The Individuals with Disabilities Education Act (IDEA, 2004). The EI team, a multidisciplinary team overseen by individual states, is charged with providing family-centered services to support child development in the natural environment. This article examines the use of occupational…

  5. Serological analysis and therapy in patients with early syphilis

    International Nuclear Information System (INIS)

    Wu Zhifen

    2000-01-01

    Sixty one patients with early syphilis were treated with benzathine penicillin under guide of serological analysis, the results showed that benzathine penicilline was able to cure indurated chancre and skin rashes in a month, flat condyloma in one and a half month, and PRP were all negative in 18 month

  6. Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins.

    Directory of Open Access Journals (Sweden)

    Reinhard Meier

    Full Text Available Anticalins are a novel class of targeted protein therapeutics. The PEGylated Anticalin Angiocal (PRS-050-PEG40 is directed against VEGF-A. The purpose of our study was to compare the performance of diffusion weighted imaging (DWI, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI and positron emission tomography with the tracer [18F]fluorodeoxyglucose (FDG-PET for monitoring early response to antiangiogenic therapy with PRS-050-PEG40. 31 mice were implanted subcutaneously with A673 rhabdomyosarcoma xenografts and underwent DWI, DCE-MRI and FDG-PET before and 2 days after i.p. injection of PRS-050-PEG40 (n = 13, Avastin (n = 6 or PBS (n = 12. Tumor size was measured manually with a caliper. Imaging results were correlated with histopathology. In the results, the tumor size was not significantly different in the treatment groups when compared to the control group on day 2 after therapy onset (P = 0.09. In contrast the imaging modalities DWI, DCE-MRI and FDG-PET showed significant differences between the therapeutic compared to the control group as early as 2 days after therapy onset (P<0.001. There was a strong correlation of the early changes in DWI, DCE-MRI and FDG-PET at day 2 after therapy onset and the change in tumor size at the end of therapy (r = -0.58, 0.71 and 0.67 respectively. The imaging results were confirmed by histopathology, showing early necrosis and necroptosis in the tumors. Thus multimodality multiparametric imaging was able to predict therapeutic success of PRS-050-PEG40 and Avastin as early as 2 days after onset of therapy and thus promising for monitoring early response of antiangiogenic therapy.

  7. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jeppesen, Stefan Starup; Schytte, Tine; Jensen, Henrik R

    2013-01-01

    Abstract Introduction. Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single...... and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients....

  8. The results of radiation therapy for early glottic carcinoma

    International Nuclear Information System (INIS)

    Yamamoto, Michinori; Hada, Yoshihiro; Shirane, Makoto

    2000-01-01

    To analyze various parameters affect local control, we reviewed the results of radiotherapy for early glottic carcinoma. Between 1977 and 1997, 64 patients with untreated early glottic carcinoma and four patients with recurrent early glottic carcinoma were analyzed retrospectively. All tumors were classified as follows; T1 (n=56), T2 (n=12); well differentiated (n=33), moderately (n=25), poorly (n=1), unknown (n=9); very small tumor (VST) (n=46), small tumor (ST) (n=22). All patients were treated utilizing a cobalt-60 unit to a total dose that ranged from 56 Gy to 64 Gy (mean 60 Gy). The mean treatment time was 44 days (range 38-49). The local control rates at 2 years and 5 years for all patients were 85% and 78%, respectively. On univariate analysis, tumor size (p=0.0146) and recurrent or untreated tumor (p=0.0226) affected local control. On multivariate analysis, tumor size (p=0.0273) and recurrent or untreated tumor (p=0.0495) were also significant factors that affected local control. (author)

  9. Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors.

    Science.gov (United States)

    Martin, Donel M; Gálvez, Verònica; Loo, Colleen K

    2015-06-19

    Loss of personal memories experienced prior to receiving electroconvulsive therapy is common and distressing and in some patients can persist for many months following treatment. Improved understanding of the relationships between individual patient factors, electroconvulsive therapy treatment factors, and clinical indicators measured early in the electroconvulsive therapy course may help clinicians minimize these side effects through better management of the electroconvulsive therapy treatment approach. In this study we examined the associations between the above factors for predicting retrograde autobiographical memory changes following electroconvulsive therapy. Seventy-four depressed participants with major depressive disorder were administered electroconvulsive therapy 3 times per week using either a right unilateral or bitemporal electrode placement and brief or ultrabrief pulse width. Verbal fluency and retrograde autobiographical memory (assessed using the Columbia Autobiographical Memory Interview - Short Form) were tested at baseline and after the last electroconvulsive therapy treatment. Time to reorientation was measured immediately following the third and sixth electroconvulsive therapy treatments. Results confirmed the utility of measuring time to reorientation early during the electroconvulsive therapy treatment course as a predictor of greater retrograde amnesia and the importance of assessing baseline cognitive status for identifying patients at greater risk for developing later side effects. With increased number of electroconvulsive therapy treatments, older age was associated with increased time to reorientation. Consistency of verbal fluency performance was moderately correlated with change in Columbia Autobiographical Memory Interview - Short Form scores following right unilateral electroconvulsive therapy. Electroconvulsive therapy treatment techniques associated with lesser cognitive side effects should be particularly considered for

  10. Musical Play as Therapy in an Early Intervention Programme

    Directory of Open Access Journals (Sweden)

    Julie Wylie

    2013-07-01

    Full Text Available Effective therapeutic use of music for very young children with multi-system developmental disabilities involves engaging them and their parents/caregivers in musical play activities that can regulate the children’s (and parents’ physiological systems, strengthen parent-child relationships, and open children’s minds to physical, social emotional and intellectual learning and development; both in the context of music therapy and in response to goals set by a multi-disciplinary team. This article, based on a presentation given at the ISME conference in Greece in 2012, describes the therapy programmes at the Champion Centre in Christchurch, New Zealand and presents four case studies designed to illustrate the type and range of activities that have been shown to be effective over twenty years of experience. They show how when music practitioners follow the child’s lead, and draw the parents into the interaction as full partners, the well-being of children is enhanced and their parents are encouraged to engage in similar activities at home, thereby extending music’s therapeutic reach and effectiveness.

  11. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    Science.gov (United States)

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

  12. Results of primary radiation therapy in early vocal cord cancers

    International Nuclear Information System (INIS)

    Mehta, S.A.; Sarkar, S.; Mehta, M.S.; Marfatia, P.T.; Choudhary, A.J.; Mehta, A.R.

    1991-01-01

    Results of 74 patients treated by primary radiation therapy with curative intent at the Tata Memorial Hospital between January 1980 and December 1984 are reported. Thirty three (44.6%) were classified as TlaNO, twenty five (33.8%) as TlbNO, ten (13.5%) as T2NO and six(8.1%) as TisNO. The 5-year actuarial survival was 92% and disease-free survival was 85%. Thirteen patients (17.5%) failed locally, seven (53.8%) of whom were salvaged by surgery. Radiation side-effects were minimal and there were no long term complications. Anterior commissure involvement did not affect the local recurrence rates. (author). 19 refs., 1 tabs

  13. Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial

    Science.gov (United States)

    Brummel, N.E.; Girard, T.D.; Ely, E.W.; Pandharipande, P.P.; Morandi, A.; Hughes, C.G.; Graves, A.J.; Shintani, A.K.; Murphy, E.; Work, B.; Pun, B.T.; Boehm, L.; Gill, T.M.; Dittus, R.S.; Jackson, J.C.

    2013-01-01

    PURPOSE Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. METHODS We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3-months, we also assessed cognitive, functional and health-related quality of life outcomes. Data are presented as median [interquartile range] or frequency (%). RESULTS Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% [92–100%] of study days beginning 1.0 [1.0–1.0] day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients and 42/43 (98%) of cognitive plus physical therapy patients on 17% [10–26%], 67% [46–87%] and 75% [59–88%] of study days, respectively. Cognitive, functional and health-related quality of life outcomes did not differ between groups at 3-month follow-up. CONCLUSIONS This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment and benefits of cognitive therapy in the critically ill is needed. PMID:24257969

  14. Advances in gene therapy and early imaging monitoring for avascular necrosis of the femoral head

    International Nuclear Information System (INIS)

    Wang Peng; Lan Xiaoli; Zhang Yongxue; Qi Hongyan

    2012-01-01

    Gene therapy is a method that transfers foreign gene to target cells, so as to correct or compensate the disease which is caused by the gene defects and abnormalities. As a new technology, gene therapy has been used in many fields, such as cancer, cardiovascular and nervous system disease, and it brings some hope for patients with difficult and complicated disease. Avascular necrosis of femoral head is a refractory and common disease in clinical, but the traditional surgery therapy and conservative treatment both have many shortcomings,and the effect is unsatisfactory. As a new technology,gene therapy showed bright future in orthopedics ischemic disease, and its potential feasibility has been confirmed by many animal experiments. This article focuses on the research progress of gene therapy and early monitoring in the avascular necrosis of the femoral head. (authors)

  15. Early cessation of pressure garment therapy results in scar contraction and thickening.

    Directory of Open Access Journals (Sweden)

    Danielle M DeBruler

    Full Text Available Pressure garment therapy is often prescribed to improve scar properties following full-thickness burn injuries. Pressure garment therapy is generally recommended for long periods of time following injury (1-2 years, though it is plagued by extremely low patient compliance. The goal of this study was to examine the effects of early cessation of pressure garment therapy on scar properties. Full-thickness burn injuries were created along the dorsum of red Duroc pigs. The burn eschar was excised and wound sites autografted with split-thickness skin. Scars were treated with pressure garments within 1 week of injury and pressure was maintained for either 29 weeks (continuous pressure or for 17 weeks followed by cessation of pressure for an additional 12 weeks (pressure released; scars receiving no treatment served as controls. Scars that underwent pressure garment therapy were significantly smoother and less contracted with decreased scar height compared to control scars at 17 weeks. These benefits were maintained in the continuous pressure group until week 29. In the pressure released group, grafts significantly contracted and became more raised, harder and rougher after the therapy was discontinued. Pressure cessation also resulted in large changes in collagen fiber orientation and increases in collagen fiber thickness. The results suggest that pressure garment therapy effectively improves scar properties following severe burn injury; however, early cessation of the therapy results in substantial loss of these improvements.

  16. Early cessation of pressure garment therapy results in scar contraction and thickening.

    Science.gov (United States)

    DeBruler, Danielle M; Zbinden, Jacob C; Baumann, Molly E; Blackstone, Britani N; Malara, Megan M; Bailey, J Kevin; Supp, Dorothy M; Powell, Heather M

    2018-01-01

    Pressure garment therapy is often prescribed to improve scar properties following full-thickness burn injuries. Pressure garment therapy is generally recommended for long periods of time following injury (1-2 years), though it is plagued by extremely low patient compliance. The goal of this study was to examine the effects of early cessation of pressure garment therapy on scar properties. Full-thickness burn injuries were created along the dorsum of red Duroc pigs. The burn eschar was excised and wound sites autografted with split-thickness skin. Scars were treated with pressure garments within 1 week of injury and pressure was maintained for either 29 weeks (continuous pressure) or for 17 weeks followed by cessation of pressure for an additional 12 weeks (pressure released); scars receiving no treatment served as controls. Scars that underwent pressure garment therapy were significantly smoother and less contracted with decreased scar height compared to control scars at 17 weeks. These benefits were maintained in the continuous pressure group until week 29. In the pressure released group, grafts significantly contracted and became more raised, harder and rougher after the therapy was discontinued. Pressure cessation also resulted in large changes in collagen fiber orientation and increases in collagen fiber thickness. The results suggest that pressure garment therapy effectively improves scar properties following severe burn injury; however, early cessation of the therapy results in substantial loss of these improvements.

  17. Neuromodulatory adaptive combination of correlation-based learning in cerebellum and reward-based learning in basal ganglia for goal-directed behavior control.

    Science.gov (United States)

    Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus, in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms.

  18. Neonatal lesions of orbital frontal areas 11/13 in monkeys alter goal-directed behavior but spare fear conditioning and safety signal learning.

    Directory of Open Access Journals (Sweden)

    Andy M Kazama

    2014-03-01

    Full Text Available Recent studies in monkeys have demonstrated that damage to the lateral subfields of orbital frontal cortex (OFC areas 11/13 yields profound changes in flexible modulation of goal-directed behaviors and a lack in fear regulation. Yet, little consideration has been placed on its role in emotional and social development throughout life. The current study investigated the effects of neonatal lesions of the OFC on the flexible modulation of goal-directed behaviors and fear responses in monkeys. Infant monkeys received neonatal lesions of OFC areas 11/13 or sham-lesions during the first post-natal week. Modulation of goal-directed behaviors was measured with a devaluation task at 3-4 years and 6-7 years. Modulation of fear reactivity by safety signals was assessed with the AX+/BX- potentiated-startle paradigm at 6-7 years. Similar to adult-onset OFC lesions, selective neonatal lesions of OFC areas 11/13 yielded a failure to modulate behavioral responses guided by changes in reward value, but spared the ability to modulate fear responses in the presence of safety signals. These results suggest that these areas play a critical role in the development of behavioral adaptation during goal-directed behaviors, but not, or less so, in the development of the ability to process emotionally salient stimuli and to modulate emotional reactivity using environmental contexts, which could be supported by other OFC subfields, such as the most ventromedial subfields (i.e. areas 14/25. Given similar impaired decision-making abilities and spared modulation of fear followed both neonatal lesions of either OFC areas 11 and 13 or amygdala (Kazama et al., 2012; Kazama & Bachevalier, 2013, the present results suggest that interactions between these two neural structures play a critical role in the development of behavioral adaptation; an ability essential for the self-regulation of emotion and behavior that assures the maintenance of successful social relationships.

  19. Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

    Science.gov (United States)

    Nagasaka, Misako; Gadgeel, Shirish M

    2018-01-01

    Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

  20. Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients

    NARCIS (Netherlands)

    Karakullukcu, Baris; van Oudenaarde, Kim; Copper, Marcel P.; Klop, W. M. C.; van Veen, Robert; Wildeman, Maarten; Bing Tan, I.

    2011-01-01

    The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason is that the success rates are not well established. The current paper analyzes our institutional experience of early stage oral cavity and oropharynx neoplasms (Tis-T2) to

  1. Computed tomography assessment of early response to neoadjuvant therapy in colon cancer

    DEFF Research Database (Denmark)

    Dam, Claus; Lund-Rasmussen, Vera; Pløen, John

    2015-01-01

    INTRODUCTION: Using multidetector computed tomography, we aimed to assess the early response of neoadjuvant drug therapy for locally advanced colon cancer. METHODS: Computed tomography with IV contrast was acquired from 67 patients before and after up to three cycles of preoperative treatment. All...

  2. Prolonged Exposure Therapy for a Vietnam Veteran with PTSD and Early-Stage Dementia

    Science.gov (United States)

    Duax, Jeanne M.; Waldron-Perrine, Brigid; Rauch, Sheila A. M.; Adams, Kenneth M.

    2013-01-01

    Although prolonged exposure therapy (PE) is considered an evidence-based treatment for PTSD, there has been little published about the use of this treatment for older adults with comorbid early-stage dementia. As the number of older adults in the United States continues to grow, so will their unique mental health needs. The present article…

  3. Photodynamic therapy of early stage cancer of lung, esophagus, and stomach with two different photosensitizers

    Science.gov (United States)

    Chissov, Valery I.; Sokolov, Victor V.; Trakhtenberg, A. K.; Mamontov, A. S.; Vaschakmadze, L. A.; Frank, George A.; Filonenko, E. V.; Telegina, L. V.; Belous, T. A.; Gladunov, V. K.; Aristarkhova, E. I.; Zharkova, Natalia N.; Menenkov, V. D.

    1996-01-01

    The paper presents the results of photodynamic therapy (PDT) of early-stage cancer of lung (17 patients), esophagus (8 patients) and stomach (10 patients). Fifteen patients had second primary tumors. New drugs photoheme and photosens were used as photosensitizers. Complete remission was obtained in 87%. The patients are followed up without relapses to 2.5 years.

  4. Examining the effect of state anxiety on compensatory and strategic adjustments in the planning of goal-directed aiming.

    Science.gov (United States)

    Roberts, James W; Wilson, Mark R; Skultety, Jessica K; Lyons, James L

    2018-04-01

    The anxiety-perceptual-motor performance relationship may be enriched by investigations involving discrete manual responses due to the definitive demarcation of planning and control processes, which comprise the early and late portions of movement, respectively. To further examine the explanatory power of self-focus and distraction theories, we explored the potential of anxiety causing changes to movement planning that accommodate for anticipated negative effects in online control. As a result, we posed two hypotheses where anxiety causes performers to initially undershoot the target and enable more time to use visual feedback ("play-it-safe"), or fire a ballistic reach to cover a greater distance without later undertaking online control ("go-for-it"). Participants were tasked with an upper-limb movement to a single target under counter-balanced instructions to execute fast and accurate responses (low/normal anxiety) with non-contingent negative performance feedback (high anxiety). The results indicated that the previously identified negative impact of anxiety in online control was replicated. While anxiety caused a longer displacement to reach peak velocity and greater tendency to overshoot the target, there appeared to be no shift in the attempts to utilise online visual feedback. Thus, the tendency to initially overshoot may manifest from an inefficient auxiliary procedure that manages to uphold overall movement time and response accuracy. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. The discriminatory analysis about factors correlative with the early hypothyroidism after 131I therapy for hyperthyroidism

    International Nuclear Information System (INIS)

    Xiong Lingjing; Liang Changhua; Deng Haoyu; Li Xinhui; Hu Shuo

    2002-01-01

    Objective: To explore the factors correlative with the early hypothyroidism after 131 I therapy for Graves' hyperthyroidism so as to cure it and decrease the early hypothyroidism occurring and prevent it from becoming irreversible hypothyroidism. Methods: Logistic regression discriminatory analysis by introducing multiple factors from group data and forward stepwise selection of 11 independent variables of 240 hyperthyroidism patients from clinical data and 1 dependent variable from follow-up data after 131 I therapy was conducted. Univariate analysis of each observed factor was performed, too. Results: (1)The results of multivariate analysis showed that the age of patients, the weight of thyroid, the suffering situation, the curve of 131 I absorption rate and the giving 131 I dosage/g thyroid tissue were correlated to early hypothyroidism. The results of univariate analysis showed that the weight of thyroid, the highest absorption of 131 I, the total treatment dosage of 131 I were correlated to early hypothyroidism. (2) The logistic regression equation was statistically significant. (3) The positive and negative predicting accuracy of the early hypothyroidism occurring was 64.08 %, 78.83 %, respectively, the overall predicting accuracy was 72.50%. Conclusions: The dosage of 131 I for treatment of hyperthyroid is the key factor according to the five correlative factors which are relating to the early hypothyroidism and the discriminatory classification. Enhanced follow-up and in time supplement of thyroid hormone are important measures for preventing the early hypothyroidism from becoming irreversible hypothyroidism

  6. Radiation therapy and patient age in the survival from early-stage breast cancer

    International Nuclear Information System (INIS)

    Joslyn, Sue A.

    1999-01-01

    Purpose: To analyze the use of radiation therapy following local excision of invasive localized breast cancer and subsequent survival by 5-year age category. Methods: Data for 27,399 women diagnosed with localized stage of breast cancer and treated with local excision surgery from 1983 through 1992 were collected and provided by the national Surveillance, Epidemiology, and End Results (SEER) program. Use of radiation therapy was analyzed by race, ethnic background, geographic location, and age at diagnosis. Survival for women treated with local excision plus radiation therapy was compared to that of women treated with local excision alone for each 5-year age category. Results: Subjects in older age groups were significantly less likely (p < 0.001) to receive radiation following local excision compared to younger age groups. Statistically significant survival advantages were conferred on women receiving radiation therapy in each 5-year age category from age 35 to 84 years (ranging from p = 0.02 to p < 0.0001). Conclusion: While the use of radiation therapy following local excision of early-stage breast tumors drops significantly in older age groups, women aged 35-84 years receiving radiation therapy had significant reductions in mortality. These results did not appear to be influenced by the presence of mortal comorbid conditions. These results strongly suggest the need to consider carefully patient characteristics other than age in deciding the course of treatment for early-stage breast cancer

  7. Music therapy for early cognitive rehabilitation post-childhood TBI: an intrinsic mixed methods case study.

    Science.gov (United States)

    Bower, Janeen; Catroppa, Cathy; Grocke, Denise; Shoemark, Helen

    2014-10-01

    The primary aim of this case study was to explore the behavioural changes of a paediatric patient in post-traumatic amnesia (PTA) during a music therapy session. A secondary objective was to measure the effect of the music therapy intervention on agitation. Video data from pre, during and post-music therapy sessions were collected and analysed using video micro-analysis and the Agitated Behaviour Scale. The participant displayed four discrete categories of behaviours: Neutral, Acceptance, Recruitment and Rejection. Further analysis revealed brief but consistent and repeated periods of awareness and responsiveness to the live singing of familiar songs, which were classified as Islands of Awareness. Song offered an Environment of Potential to maximise these periods of emerging consciousness. The quantitative data analysis yielded inconclusive results in determining if music therapy was effective in reducing agitation during and immediately post the music therapy sessions. The process of micro-analysis illuminated four discrete participant behaviours not apparent in the immediate clinical setting. The results of this case suggest that the use of familiar song as a music therapy intervention may harness early patient responsiveness to foster cognitive rehabilitation in the early acute phase post-TBI.

  8. Early Change in Stroke Size Performs Best in Predicting Response to Therapy.

    Science.gov (United States)

    Simpkins, Alexis Nétis; Dias, Christian; Norato, Gina; Kim, Eunhee; Leigh, Richard

    2017-01-01

    Reliable imaging biomarkers of response to therapy in acute stroke are needed. The final infarct volume and percent of early reperfusion have been used for this purpose. Early fluctuation in stroke size is a recognized phenomenon, but its utility as a biomarker for response to therapy has not been established. This study examined the clinical relevance of early change in stroke volume and compared it with the final infarct volume and percent of early reperfusion in identifying early neurologic improvement (ENI). Acute stroke patients, enrolled between 2013 and 2014 with serial magnetic resonance imaging (MRI) scans (pretreatment baseline, 2 h post, and 24 h post), who received thrombolysis were included in the analysis. Early change in stroke volume, infarct volume at 24 h on diffusion, and percent of early reperfusion were calculated from the baseline and 2 h MRI scans were compared. ENI was defined as ≥4 point decrease in National Institutes of Health Stroke Scales within 24 h. Logistic regression models and receiver operator characteristics analysis were used to compare the efficacy of 3 imaging biomarkers. Serial MRIs of 58 acute stroke patients were analyzed. Early change in stroke volume was significantly associated with ENI by logistic regression analysis (OR 0.93, p = 0.048) and remained significant after controlling for stroke size and severity (OR 0.90, p = 0.032). Thus, for every 1 mL increase in stroke volume, there was a 10% decrease in the odds of ENI, while for every 1 mL decrease in stroke volume, there was a 10% increase in the odds of ENI. Neither infarct volume at 24 h nor percent of early reperfusion were significantly associated with ENI by logistic regression. Receiver-operator characteristic analysis identified early change in stroke volume as the only biomarker of the 3 that performed significantly different than chance (p = 0.03). Early fluctuations in stroke size may represent a more reliable biomarker for response to therapy than the

  9. Contributions to clinical Occupational Therapy in the area of early intervention in interdisciplinary team

    Directory of Open Access Journals (Sweden)

    Dani Laura Peruzzolo

    2015-07-01

    Full Text Available Introduction: Specialized care for infants considers that the sooner the intervention in risk and symptoms occurs, the greater the possibility of obtaining better results. Aims: To describe the process of early intervention provided by an extension program of graduate studies in Occupational Therapy and Hearing, Speech and Languages Science courses and also discuss the theoretical and practical paths in the care for infants and in the Occupational Therapy area. Method: Case report with convenience sample. The study was carried out through an assessment interpreted in light of psychomotor, occupational therapeutic, and speech, hearing and language contributions. The intervention was under the responsibility of an occupational therapist supported by an interdisciplinary team. It occurred once a week from August 2011 to January 2012 and from March 2012 to July 2012. Data analysis was carried out by comparing the entry assessment test and the final assessment test. Results: The boy had not developed concepts of body schema and body image that could sustain his relationship with objects, space and other persons. He presented little linguistic evolution. Considering the contributions of occupational therapy in psychomotor clinic, the boy reconstructed his family place in early intervention. The possibility of language functioning connected to the boy’s demands allowed access to symbolism. Conclusion: The proposal of early occupational therapy intervention with a single therapist supported by an interdisciplinary team was able to overcome the structural and instrumental obstacles to the boy’s development.

  10. Early response in cognitive-behavior therapy for syndromes of medically unexplained symptoms.

    Science.gov (United States)

    Kleinstäuber, Maria; Lambert, Michael J; Hiller, Wolfgang

    2017-05-25

    Early dramatic treatment response suggests a subset of patients who respond to treatment before most of it has been offered. These early responders tend to be over represented among those who are well at termination and at follow-up. Early response patterns in psychotherapy have been investigated only for a few of mental disorders so far. The main aim of the current study was to examine early response after five therapy-preparing sessions of a cognitive behavior therapy (CBT) for syndromes of medically unexplained symptoms (MUS). In the context of a randomized, waiting-list controlled trial 48 patients who suffered from ≥3 MUS over ≥6 months received 5 therapy-preparing sessions and 20 sessions of CBT for somatoform disorders. They completed self-report scales of somatic symptom severity (SOMS-7 T), depression (BDI-II), anxiety (BSI), illness anxiety and behavior (IAS) at pre-treatment, after 5 therapy-preparing sessions (FU-5P) and at therapy termination (FU-20 T). The current analyses are based on data from the treatment arm only. Repeated measure ANOVAs revealed a significant decrease of depression (d = 0.34), anxiety (d = 0.60), illness anxiety (d = 0.38) and illness behavior (d = 0.42), but no change of somatic symptom severity (d = -0.03) between pre-treatment and FU-5P. Hierarchical linear multiple regression analyses showed that symptom improvements between pre-treatment and FU-5P predict a better outcome at therapy termination for depression and illness anxiety, after controlling for pre-treatment scores. Mixed-effect ANOVAs revealed significant group*time interaction effects indicating differences in the course of symptom improvement over the therapy between patients who fulfilled a reliable change (i.e., early response) during the 5 therapy-preparing sessions and patients who did not reach an early reliable change. Demographic or clinical variables at pre-treatment were not significantly correlated with differential scores between pre

  11. Image-guided conformation arc therapy for prostate cancer: Early side effects

    International Nuclear Information System (INIS)

    Soete, Guy; Verellen, Dirk; Michielsen, Dirk; Rappe, Bernard; Keuppen, Frans; Storme, Guy

    2006-01-01

    Purpose: To evaluate early side effects in prostate cancer patients treated with image-guided conformation arc therapy (IGCAT) using a minimultileaf collimator and daily X-ray-assisted patient positioning. Methods and Materials: Between May 2000 and November 2004, 238 cT1-T3N0M0 tumors were treated with doses of 70 or 78 Gy. Seventy patients also received neoadjuvant or concurrent hormonal treatment. Median follow-up is 18 months (range, 4-55 months). Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer toxicity scoring system was used to evaluate early side effects. Results: Grade 1, 2, and >2 acute side effects occurred in 19, 6, and 0% (gastrointestinal) and 37, 16, and 0% (genitourinary) of the patients. No relation between radiation dose and early side effects was observed. Conclusion: Patients treated with image-guided conformation arc therapy experience a low rate of Grade 2 (i.e., requiring medication) early side effects. The definitive evaluation of late side effects and biochemical control requires further follow-up

  12. Counterfactual Processing of Economic Action-Outcome Alternatives in Obsessive-Compulsive Disorder: Further Evidence of Impaired Goal-Directed Behavior

    Science.gov (United States)

    Gillan, Claire M.; Morein-Zamir, Sharon; Kaser, Muzaffer; Fineberg, Naomi A.; Sule, Akeem; Sahakian, Barbara J.; Cardinal, Rudolf N.; Robbins, Trevor W.

    2014-01-01

    Background Obsessive-compulsive disorder (OCD) is a disorder of automatic, uncontrollable behaviors and obsessive rumination. There is evidence that OCD patients have difficulties performing goal-directed actions, instead exhibiting repetitive stimulus-response habit behaviors. This might result from the excessive formation of stimulus-response habit associations or from an impairment in the ability to use outcome value to guide behavior. We investigated the latter by examining counterfactual decision making, which is the ability to use comparisons of prospective action-outcome scenarios to guide economic choice. Methods We tested decision making (forward counterfactual) and affective responses (backward counterfactual) in 20 OCD patients and 20 matched healthy control subjects using an economic choice paradigm that previously revealed attenuation of both the experience and avoidance of counterfactual emotion in schizophrenia patients and patients with orbitofrontal cortex lesions. Results The use of counterfactual comparison to guide decision making was diminished in OCD patients, who relied primarily on expected value. Unlike the apathetic affective responses previously shown to accompany this decision style, OCD patients reported increased emotional responsivity to the outcomes of their choices and to the counterfactual comparisons that typify regret and relief. Conclusions Obsessive-compulsive disorder patients exhibit a pattern of decision making consistent with a disruption in goal-directed forward modeling, basing decisions instead on the temporally present (and more rational) calculation of expected value. In contrast to this style of decision making, emotional responses in OCD were more extreme and reactive than control subjects. These results are in line with an account of disrupted goal-directed cognitive control in OCD. PMID:23452663

  13. Inter-individual differences in decision-making, flexible and goal-directed behaviors: novel insights within the prefronto-striatal networks.

    Science.gov (United States)

    Fitoussi, Aurélie; Renault, Prisca; Le Moine, Catherine; Coutureau, Etienne; Cador, Martine; Dellu-Hagedorn, Françoise

    2018-03-01

    Inflexible behavior is a hallmark of several decision-making-related disorders such as ADHD and addiction. As in humans, a subset of healthy rats makes poor decisions and prefers immediate larger rewards despite suffering large losses in a rat gambling task (RGT). They also display a combination of traits reminiscent of addiction, notably inflexible behavior and perseverative responses. The goal of the present work was twofold: (1) to elucidate if behavioral inflexibility of poor decision-makers could be related to a lower quality of goal-directed behavior (action-outcome associations); (2) to uncover the neural basis of inter-individual differences in goal-directed behavior. We specifically assessed inter-individual differences in decision-making in the RGT, flexibility in the RGT-reversed version and goal-directed behavior in a contingency degradation test, i.e., response adaptation when dissociating reward delivery from the animal's action. The contributions of the medial prefrontal cortex and the dorsal striatum to action-outcome associations were assessed using Zif268 immunodetection. Inflexible behavior was related to a lower sensitivity to contingency degradation in all poor decision-makers and only in a few good decision-makers. This poorer sensitivity was associated with a lower immunoreactivity in prelimbic and infralimbic cortices and a higher one in the dorsomedial and dorsolateral striatum. These findings suggest that an imbalanced prefronto-striatal activity could underlie inaccurate goal representation in changing environments and may promote maladaptive habit formation among poor decision-makers. These data strengthen our previous work identifying biomarkers of vulnerability to develop psychiatric disorders and demonstrate the relevance of inter-individual differences to model maladaptive behaviors.

  14. Counterfactual processing of economic action-outcome alternatives in obsessive-compulsive disorder: further evidence of impaired goal-directed behavior.

    Science.gov (United States)

    Gillan, Claire M; Morein-Zamir, Sharon; Kaser, Muzaffer; Fineberg, Naomi A; Sule, Akeem; Sahakian, Barbara J; Cardinal, Rudolf N; Robbins, Trevor W

    2014-04-15

    Obsessive-compulsive disorder (OCD) is a disorder of automatic, uncontrollable behaviors and obsessive rumination. There is evidence that OCD patients have difficulties performing goal-directed actions, instead exhibiting repetitive stimulus-response habit behaviors. This might result from the excessive formation of stimulus-response habit associations or from an impairment in the ability to use outcome value to guide behavior. We investigated the latter by examining counterfactual decision making, which is the ability to use comparisons of prospective action-outcome scenarios to guide economic choice. We tested decision making (forward counterfactual) and affective responses (backward counterfactual) in 20 OCD patients and 20 matched healthy control subjects using an economic choice paradigm that previously revealed attenuation of both the experience and avoidance of counterfactual emotion in schizophrenia patients and patients with orbitofrontal cortex lesions. The use of counterfactual comparison to guide decision making was diminished in OCD patients, who relied primarily on expected value. Unlike the apathetic affective responses previously shown to accompany this decision style, OCD patients reported increased emotional responsivity to the outcomes of their choices and to the counterfactual comparisons that typify regret and relief. Obsessive-compulsive disorder patients exhibit a pattern of decision making consistent with a disruption in goal-directed forward modeling, basing decisions instead on the temporally present (and more rational) calculation of expected value. In contrast to this style of decision making, emotional responses in OCD were more extreme and reactive than control subjects. These results are in line with an account of disrupted goal-directed cognitive control in OCD. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Factors affecting osteoarthritis patients' self-reported goal-directed drug information-seeking behaviors after exposure to direct-to-consumer advertising from physicians and the internet.

    Science.gov (United States)

    Liu, Yifei; Farris, Karen B; Doucette, William R

    2011-10-01

    The objective of this study was to investigate appraisal of means (ie, self-efficacy, outcome expectancy, and affect) in predicting patients' goal-directed behaviors of direct-to-consumer advertising (DTCA)-prompted drug-information search from physicians and the internet. One thousand patients were randomly selected from a nationwide sample frame of 3000 osteoarthritis patients. A self-administered survey assessed exposure to DTCA, drug-information search as goal, self-efficacy, outcome expectancy, affect, and osteoarthritis pain. After 6 weeks, another survey measured the behavior of drug-information search for respondents to the first survey. Study subjects were those who were exposed to DTCA in the previous month, and who set drug-information search as their goal. For each information source, a multiple regression analysis was conducted in which drug-information search was the dependent variable, and self-efficacy, outcome expectancy, affect, and osteoarthritis pain were the independent variables. Among 454 patients who were exposed to DTCA, 174 patients set drug-information search as their goal and were the study subjects. The regression for physicians was not statistically significant. The regression for the internet was significant, accounting for 15% of behavior variance. Self-efficacy was a strong predictor of goal-directed drug-information search from the internet. Appraisal of means was useful to predict the goal-directed behavior of DTCA-prompted drug-information search from the internet. For patients who set drug-information search as a goal, actions to promote drug-information search from the internet need to focus on self-efficacy.

  16. Geographic access to radiation therapy facilities and disparities of early-stage breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Yan Lin

    2018-05-01

    Full Text Available Few studies of breast cancer treatment have focused on the Northern Plains of the United States, an area with a high mastectomy rate. This study examined the association between geographic access to radiation therapy facilities and receipt of breast cancer treatments among early-stage breast cancer patients in South Dakota. Based on 4,209 early-stage breast cancer patients diagnosed between 2001 and 2012 in South Dakota, the study measured geographic proximity to radiation therapy facilities using the shortest travel time for patients to the closest radiation therapy facility. Two-level logistic regression models were used to estimate for early stage cases i the odds of mastectomy versus breast conserving surgery (BCS; ii the odds of not receiving radiation therapy after BCS versus receiving follow-up radiation therapy. Covariates included race/ethnicity, age at diagnosis, tumour grade, tumour sequence, year of diagnosis, census tract-level poverty rate and urban/rural residence. The spatial scan statistic method was used to identify geographic areas with significantly higher likelihood of experiencing mastectomy. The study found that geographic accessibility to radiation therapy facilities was negatively associated with the likelihood of receiving mastectomy after adjustment for other covariates, but not associated with radiation therapy use among patients receiving BCS. Compared with patients travelling less than 30 minutes to a radiation therapy facility, patients travelling more than 90 minutes were about 1.5 times more likely to receive mastectomy (odds ratio, 1.51; 95% confidence interval, 1.08-2.11 and patients travelling more than 120 minutes were 1.7 times more likely to receive mastectomy (odds ratio, 1.70; 95% confidence interval, 1.19-2.42. The study also identified a statistically significant cluster of patients receiving mastectomy who were located in south-eastern South Dakota, after adjustment for other factors. Because

  17. Processing and Integration of Contextual Information in Monkey Ventrolateral Prefrontal Neurons during Selection and Execution of Goal-Directed Manipulative Actions.

    Science.gov (United States)

    Bruni, Stefania; Giorgetti, Valentina; Bonini, Luca; Fogassi, Leonardo

    2015-08-26

    The prefrontal cortex (PFC) is deemed to underlie the complexity, flexibility, and goal-directedness of primates' behavior. Most neurophysiological studies performed so far investigated PFC functions with arm-reaching or oculomotor tasks, thus leaving unclear whether, and to which extent, PFC neurons also play a role in goal-directed manipulative actions, such as those commonly used by primates during most of their daily activities. Here we trained two macaques to perform or withhold grasp-to-eat and grasp-to-place actions, depending on the combination of two subsequently presented cues: an auditory go/no-go cue (high/low tone) and a visually presented target (food/object). By varying the order of presentation of the two cues, we could segment and independently evaluate the processing and integration of contextual information allowing the monkey to make a decision on whether or not to act, and what action to perform. We recorded 403 task-related neurons from the ventrolateral prefrontal cortex (VLPFC): unimodal sensory-driven (37%), motor-related (21%), unimodal sensory-and-motor (23%), and multisensory (19%) neurons. Target and go/no-go selectivity characterized most of the recorded neurons, particularly those endowed with motor-related discharge. Interestingly, multisensory neurons appeared to encode a behavioral decision independently from the sensory modality of the stimulus allowing the monkey to make it: some of them reflected the decision to act or refraining from acting (56%), whereas others (44%) encoded the decision to perform (or withhold) a specific action (e.g., grasp-to-eat). Our findings indicate that VLPFC neurons play a role in the processing of contextual information underlying motor decision during goal-directed manipulative actions. We demonstrated that macaque ventrolateral prefrontal cortex (VLPFC) neurons show remarkable selectivity for different aspects of the contextual information allowing the monkey to select and execute goal-directed

  18. Primary radiation therapy for early breast cancer: the experience at the joint center for radiation therapy

    International Nuclear Information System (INIS)

    Harris, J.R.; Botnick, L.; Bloomer, W.D.; Chaffey, J.T.; Hellman, S.

    1981-01-01

    The results of primary radiation therapy in 176 consecutive patients with clinical State I and II carcinoma of the breast were reviewed. Median follow-up time was 47 months. The overall breast relapse rate was 7%. Patients undergoing interstitial implantation had a significantly lower breast relapse rate (1%) than patients not undergoing implantation (11%). Breast relapse was more common in patients undergoing incisional or needle biopsy (17%), compared to patients treated after excisional biopsy (5%). In patients undergoing excisional biopsy, but not interstitial implantation, breast relapse was related to external beam dose. Twelve percent of the patients who received less than 1600 ret dose relapsed in the breast, compared to none of the 19 patients who received more than 1700 ret dose. These results imply that supplemental irradiation to the primary tumor area is required following excisional biopsy of a primary breast cancer when 4500-5000 rad is delivered to the entire breast

  19. Outcome of intraoperative goal-directed therapy using Vigileo/FloTrac in high-risk patients scheduled for major abdominal surgeries: A prospective randomized trial

    Directory of Open Access Journals (Sweden)

    Mohammed A. Elgendy

    2017-07-01

    Conclusion: The applied protocol for intraoperative GDT provided significant reduction of PO morbidities, ICU and hospital LOS but couldn‘t significantly reduce mortality rates in high risk patients scheduled for major abdominal surgeries.

  20. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

    Science.gov (United States)

    de la Monte, Suzanne M

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

  1. [The importance of early exercise therapy in the treatment of Colles' fracture. A clinically controlled study].

    Science.gov (United States)

    Grønlund, B; Harreby, M S; Kofoed, R; Rasmussen, L

    1990-08-27

    Forty patients participated in a study of the importance of early occupational therapy for the prognosis in stable Colles' fractures. Seventeen patients were treated by an occupational therapist 1-3 days after the injury, and the need for appliances and home-care was estimated. Twenty-three patients completed the usual treatment. Five weeks after the injury, we found significantly (p less than 0.05) better function of the hand in the 17 patients with early occupational therapy. This difference in function could not be found after 13 weeks. The rate of complications was the same in the two groups. The results indicate that contact with the occupational therapist shortly after the injury is valuable in patients with stable Colles' fractures.

  2. Metacognitive Reflection and Insight Therapy for Early Psychosis: A preliminary study of a novel integrative psychotherapy.

    Science.gov (United States)

    Vohs, Jenifer L; Leonhardt, Bethany L; James, Alison V; Francis, Michael M; Breier, Alan; Mehdiyoun, Nikki; Visco, Andrew C; Lysaker, Paul H

    2018-05-01

    Poor insight impedes treatment in early phase psychosis (EPP). This manuscript outlines preliminary findings of an investigation of the novel metacognitively oriented integrative psychotherapy, Metacognitive Reflection and Insight Therapy, for individuals with early phase psychosis (MERIT-EP). Twenty adults with EPP and poor insight were randomized to either six months of MERIT-EP or treatment as usual (TAU). Therapists were trained and therapy was successfully delivered under routine, outpatient conditions. Insight, assessed before and after treatment, revealed significant improvement for the MERIT-EP, but not TAU, group. These results suggest MERIT-EP is feasible to deliver, accepted by patients, and leads to clinically significant improvements in insight. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A possible utilization of the mice forced swim test for modeling manic-like increase in vigor and goal-directed behavior.

    Science.gov (United States)

    Flaisher-Grinberg, Shlomit; Einat, Haim

    2009-01-01

    The lack of appropriate animal models for bipolar disorder (BPD) is a major factor hindering the research of its pathophysiology and the development of new drug treatments. In line with the notion that BPD might represent a heterogeneous group of disorders, it was suggested that models for specific domains of BPD should be developed. The present study tested the possible utilization of the forced swim test (FST) as a model for the heightened vigor and goal-directed behavior domain of mania, using mice with low baseline immobility. Black Swiss mice were previously identified to have low immobility in the FST but similar spontaneous activity levels compared with several other mice strains. Thus, spontaneous activity and behavior in the FST were evaluated following treatment with the mood stabilizer valproate and the antidepressant imipramine. The results indicated that valproate increased immobility in the FST without affecting spontaneous activity whereas imipramine had no effect in the FST but increased spontaneous activity. These findings suggest that in mice with low baseline immobility scores, the FST might be a useful model for the elevated vigor and goal-directed behavior domain of mania. As such, this test might be well integrated into a battery of models for different domains of BPD.

  4. Molecular Diagnostics of Copper-Transporting Protein Mutations Allows Early Onset Individual Therapy of Menkes Disease.

    Science.gov (United States)

    Králík, L; Flachsová, E; Hansíková, H; Saudek, V; Zeman, J; Martásek, P

    2017-01-01

    Menkes disease is a severe X-linked recessive disorder caused by a defect in the ATP7A gene, which encodes a membrane copper-transporting ATPase. Deficient activity of the ATP7A protein results in decreased intestinal absorption of copper, low copper level in serum and defective distribution of copper in tissues. The clinical symptoms are caused by decreased activities of copper-dependent enzymes and include neurodegeneration, connective tissue disorders, arterial changes and hair abnormalities. Without therapy, the disease is fatal in early infancy. Rapid diagnosis of Menkes disease and early start of copper therapy is critical for the effectiveness of treatment. We report a molecular biology-based strategy that allows early diagnosis of copper transport defects and implementation of individual therapies before the full development of pathological symptoms. Low serum copper and decreased activity of copperdependent mitochondrial cytochrome c oxidase in isolated platelets found in three patients indicated a possibility of functional defects in copper-transporting proteins, especially in the ATPA7 protein, a copper- transporting P-type ATPase. Rapid mutational screening of the ATP7A gene using high-resolution melting analysis of DNA indicated presence of mutations in the patients. Molecular investigation for mutations in the ATP7A gene revealed three nonsense mutations: c.2170C>T (p.Gln724Ter); c.3745G>T (p.Glu1249Ter); and c.3862C>T (p.Gln1288Ter). The mutation c.3745G>T (p.Glu1249Ter) has not been identified previously. Molecular analysis of the ATOX1 gene as a possible modulating factor of Menkes disease did not reveal presence of pathogenic mutations. Molecular diagnostics allowed early onset of individual therapies, adequate genetic counselling and prenatal diagnosis in the affected families.

  5. Heart Protection by Combination Therapy with Esmolol and Milrinone at Late-Ischemia and Early Reperfusion

    OpenAIRE

    Huang, Ming-He; Wu, Yewen; Nguyen, Vincent; Rastogi, Saurabh; McConnell, Bradley K.; Wijaya, Cori; Uretsky, Barry F.; Poh, Kian-Keong; Tan, Huay-Cheem; Fujise, Kenichi

    2011-01-01

    Introduction The present study determined whether late-ischemia/early reperfusion therapy with the β1-adrenergic receptor (AR) blocker esmolol and phosphodiesterase III inhibitor milrinone reduced left ventricular (LV) myocardial infarct size (IS). Methods and Results In an ischemia/reperfusion rat model (30-min ischemia/4-hr reperfusion), esmolol, milrinone or esmolol + milrinone were intravenous (IV) infused over 10 min (from the last 5min of ischemia to the first 5min of reperfusion). LV-I...

  6. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer’s disease therapeutics

    OpenAIRE

    de la Monte, Suzanne M.

    2012-01-01

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol. 2011 Sep 12. Alzheimer’s disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer’s, subsequent neurodegeneration might be prevented. ...

  7. Early effects of modern electroconvulsive therapy on subjective memory in patients with mania or depression

    OpenAIRE

    Bag, Sevda; Canbek, Ozge; Atagun, Ilhan Murat; Kutlar, Tarik Mehmet

    2016-01-01

    Context: Although electroconvulsive therapy (ECT) is considered a very effective tool for the treatment of psychiatric diseases, memory disturbances are among the most important adverse effects. Aims: This study aimed to assess prospectively early subjective memory complaints in depressive and manic patients due to bilateral, brief-pulse ECT, at different stages of the treatment, compare the associations between psychiatric diagnosis, sociodemographic characteristics, and ECT characteristics....

  8. Early use of negative pressure therapy in combination with silver dressings in a difficult breast abscess.

    Science.gov (United States)

    Richards, Alastair J; Hagelstein, Sue M; Patel, Girish K; Ivins, Nicola M; Sweetland, Helen M; Harding, Keith G

    2011-12-01

    Combining silver-based dressings with negative pressure therapy after radical excision of chronically infected breast disease is a novel application of two technologies. One patient with complex, chronic, infected breast disease underwent radical excision of the affected area and was treated early with a combination of silver-based dressings and topical negative pressure therapy. The wound was then assessed sequentially using clinical measurements of wound area and depth, pain severity scores and level of exudation. It is possible to combine accepted techniques with modern dressing technologies that result in a positive outcome. In this case, the combination of a silver-based dressing with negative pressure therapy following radical excision proved safe and was well tolerated by the patient. Full epithelisation of the wound was achieved and there was no recurrence of the infection for the duration of the treatment. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

  9. Indication for and frequency of early orthodontic therapy or interceptive measures.

    Science.gov (United States)

    Schopf, Peter

    2003-05-01

    The early treatment of nonskeletal and skeletal orthodontic anomalies in the deciduous and early mixed dentition is intended to prevent the development of pronounced anomalies in the late mixed and permanent dentition with the ultimate aim of reducing or even eliminating the need for later orthodontic treatment. There is a general consensus in the international literature that early therapy is indicated in cases of anterior and lateral crossbite and Class III malocclusion, and possibly for extreme forms of mandibular retrognathism (overjet > or =10 mm) and of open bite. However, evidence of the efficiency of early orthodontic measures is just as rare as studies providing serviceable information on the incidence of tooth malalignments and malocclusions in the deciduous and early mixed dentition, some of whose findings are in any case highly divergent. This makes it substantially more difficult to draw conclusions on the extent to which early orthodontic therapy may be indicated. In order to obtain information on the incidence of nonskeletal and skeletal orthodontic problems constituting a treatment need, 2326 first-year schoolchildren aged between 6 and 7 years were examined in Frankfurt am Main and in the Rural District of Offenbach. In only 14.7% of the children were no relevant orthodontic findings recorded. 77.2% displayed mild to severe dysgnathic symptoms, though without early orthodontic therapy being considered indicated. Treatment with orthodontic appliances was considered urgent for 187 of the children (8.04%). With 8.3% and 7.9% respectively, lateral and anterior crossbite were top of the list of anomalies with an urgent treatment need. Among the patients with lateral crossbite, the prognostically less favorable unilateral form was recorded approximately four times more often than the bilateral form. Markedly increased sagittal overjet > or =10 mm) was registered in only 1.4% of the children, and negative overjet (Class III) (with the exception of edge

  10. Information Needs of Older Women With Early-Stage Breast Cancer When Making Radiation Therapy Decisions.

    Science.gov (United States)

    Wang, Shi-Yi; Kelly, Gabrielle; Gross, Cary; Killelea, Brigid K; Mougalian, Sarah; Presley, Carolyn; Fraenkel, Liana; Evans, Suzanne B

    2017-07-15

    To identify the information older women with early-stage breast cancer need when making radiation therapy decisions, and who patients identify as the main decision maker. We surveyed (through face-to-face interview, telephone, or mail) women aged ≥65 years who received lumpectomy and were considering or receiving adjuvant radiation therapy for early-stage breast cancer. The survey instrument was constructed with input from patient and professional advisory committees, including breast cancer survivors, advocates of breast cancer care and aging, clinicians, and researchers. Participants rated the importance (on a 4-point scale) of 24 statements describing the benefits, side effects, impact on daily life, and other issues of radiation therapy in relation to radiation therapy decision making. Participants also designated who was considered the key decision maker. The response rate was 56.4% (93 of 165). Mean age was 72.5 years, ranging from 65 to 93 years. More than 96% of participants indicated they were the main decision maker on receiving radiation therapy. There was wide variation in information needs regarding radiation therapy decision making. Participants rated a mean of 18 (range, 3-24) items as "essential." Participants rated items related to benefits highest, followed by side effects. Participants who were older than 75 years rated 13.9 questions as essential, whereas participants aged ≤74 years rated 18.7 as essential (P=.018). Older women desire information and have more agency and input in the decision-making process than prior literature would suggest. The variation in information needs indicates that future decision support tools should provide options to select what information would be of interest to the participants. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient.

    Science.gov (United States)

    Darcy, Justin; Fang, Yimin; Hill, Cristal M; McFadden, Sam; Sun, Liou Y; Bartke, Andrzej

    2016-10-01

    Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not. Possible mechanisms by which early life growth hormone replacement therapy shortens longevity include deleterious effects on glucose homeostasis and energy metabolism, which are long lasting. A mechanism explaining why early life T4 replacement therapy does not shorten longevity remains elusive. Here, we look for a possible explanation as to why early life T4 replacement therapy does not impact longevity of Ames dwarf mice. We found that early life T4 replacement therapy increased body weight and advanced the age of sexual maturation. We also find that early life T4 replacement therapy does not impact glucose tolerance or insulin sensitivity, and any deleterious effects on oxygen consumption, respiratory quotient and heat production are transient. Lastly, we find that early life T4 replacement therapy has long-lasting effects on bone mineral density and bone mineral content. We suggest that the transient effects on energy metabolism and lack of effects on glucose homeostasis are the reasons why there is no shortening of longevity after early life T4 replacement therapy in Ames dwarf mice. © 2016 by the Society for Experimental Biology and Medicine.

  12. The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products.

    Science.gov (United States)

    Rafiq, Qasim A; Ortega, Ilida; Jenkins, Stuart I; Wilson, Samantha L; Patel, Asha K; Barnes, Amanda L; Adams, Christopher F; Delcassian, Derfogail; Smith, David

    2015-11-01

    Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization.

  13. [Early diagnosis and therapy in pulmonary hypertension--aspects of a vision].

    Science.gov (United States)

    Ewert, R; Olschewski, H; Ghofrani, H A; Opitz, C F

    2013-07-01

    In patients with pulmonary hypertension progressive vascular changes in the lung precede the clinical and hemodynamic manifestations of the disease. Therefore, early diagnosis and timely treatment of the disease are crucial. This has been the topic of an expert meeting in Greifswald, Germany in June 2012. The current definition of pulmonary hypertension requires a mean pulmonary artery pressure ≥ 25 mmHg at rest, a hemodynamic abnormality already reflecting pulmonary vascular changes beyond early disease. There is increasing evidence supporting the concept that a lower pressure threshold at rest or an abnormal pressure response with exercise better characterize early disease. While right heart catheterization at rest remains the diagnostic gold standard other methods for detecting early disease are explored with echocardiography being the most frequently used technique. Targeted therapy has been approved for patients with pulmonary arterial hypertension (PAH, WHO-group I) in functional class II-IV. Preliminary data in functional class I patients suggest therapeutic potential of theses drugs in early disease as well. Current guidelines propose therapeutic goals based on parameters with prognostic importance. However, these recommendations are based on mostly retrospective analyses of pre-treatment data obtained in patients with pulmonary hypertension in functional class II-IV. Therefore, evidence-based therapeutic goals for early interventions in functional class I patients are lacking. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Early Cutaneous Leishmaniasis Patients Infected With Leishmania braziliensis Express Increased Inflammatory Responses After Antimony Therapy.

    Science.gov (United States)

    Costa, Rúbia S; Carvalho, Lucas P; Campos, Taís M; Magalhães, Andréa S; Passos, Sara T; Schriefer, Albert; Silva, Juliana A; Lago, Ednaldo; Paixão, Camilla S; Machado, Paulo; Scott, Phillip; Carvalho, Edgar M

    2018-02-14

    Early cutaneous leishmaniasis (ECL) is characterized by a nonulcerated papular lesion and illness duration less than 30 days. Approximately 4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised to find that failure after antimony therapy (Sb5) is higher in ECL than CL. We hypothesize that the inflammatory response in ECL patients may increase during Sb5 therapy, which leads to treatment failure. A cohort of 44 ECL patients infected by Leishmania braziliensis was established to evaluate the response to Sb5 and to compare immunologic responses in ECL patients with CL and healthy subjects. A hierarchical clustering based on cytokine levels showed a weak positive correlation between proinflammatory cytokine levels and those patients that failed Sb5 treatment. Although Sb5 therapy decreased interferon-γ and tumor necrosis factor levels in CL patients, we were surprised to find that an increase in these cytokines was observed in ECL patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune responses in ECL. The enhanced production of proinflammatory cytokines, due in part to the decreased ability of IL-10 to down-modulate immune response during therapy in ECL, promotes the development and persistence of leishmania ulcer despite antimony therapy. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  15. Neuromodulatory Adaptive Combination of Correlation-based Learning in Cerebellum and Reward-based Learning in Basal Ganglia for Goal-directed Behavior Control

    DEFF Research Database (Denmark)

    Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational...... and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role...... in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We...

  16. Implementation of a Goal-Directed Mechanical Ventilation Order Set Driven by Respiratory Therapists Improves Compliance With Best Practices for Mechanical Ventilation.

    Science.gov (United States)

    Radosevich, Misty A; Wanta, Brendan T; Meyer, Todd J; Weber, Verlin W; Brown, Daniel R; Smischney, Nathan J; Diedrich, Daniel A

    2017-01-01

    Data regarding best practices for ventilator management strategies that improve outcomes in acute respiratory distress syndrome (ARDS) are readily available. However, little is known regarding processes to ensure compliance with these strategies. We developed a goal-directed mechanical ventilation order set that included physician-specified lung-protective ventilation and oxygenation goals to be implemented by respiratory therapists (RTs). We sought as a primary outcome to determine whether an RT-driven order set with predefined oxygenation and ventilation goals could be implemented and associated with improved adherence with best practice. We evaluated 1302 patients undergoing invasive mechanical ventilation (1693 separate episodes of invasive mechanical ventilation) prior to and after institution of a standardized, goal-directed mechanical ventilation order set using a controlled before-and-after study design. Patient-specific goals for oxygenation partial pressure of oxygen in arterial blood (Pao 2 ), ARDS Network [Net] positive end-expiratory pressure [PEEP]/fraction of inspired oxygen [Fio 2 ] table use) and ventilation (pH, partial pressure of carbon dioxide) were selected by prescribers and implemented by RTs. Compliance with the new mechanical ventilation order set was high: 88.2% compliance versus 3.8% before implementation of the order set ( P mechanical ventilation, intensive care unit (ICU) length of stay, and in-hospital or ICU mortality. A standardized best practice mechanical ventilation order set can be implemented by a multidisciplinary team and is associated with improved compliance to written orders and adherence to the ARDSNet PEEP/Fio 2 table.

  17. Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors.

    Science.gov (United States)

    Kometer, Michael; Schmidt, André; Bachmann, Rosilla; Studerus, Erich; Seifritz, Erich; Vollenweider, Franz X

    2012-12-01

    Serotonin (5-HT) 1A and 2A receptors have been associated with dysfunctional emotional processing biases in mood disorders. These receptors further predominantly mediate the subjective and behavioral effects of psilocybin and might be important for its recently suggested antidepressive effects. However, the effect of psilocybin on emotional processing biases and the specific contribution of 5-HT2A receptors across different emotional domains is unknown. In a randomized, double-blind study, 17 healthy human subjects received on 4 separate days placebo, psilocybin (215 μg/kg), the preferential 5-HT2A antagonist ketanserin (50 mg), or psilocybin plus ketanserin. Mood states were assessed by self-report ratings, and behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues. Psilocybin enhanced positive mood and attenuated recognition of negative facial expression. Furthermore, psilocybin increased goal-directed behavior toward positive compared with negative cues, facilitated positive but inhibited negative sequential emotional effects, and valence-dependently attenuated the P300 component. Ketanserin alone had no effects but blocked the psilocybin-induced mood enhancement and decreased recognition of negative facial expression. This study shows that psilocybin shifts the emotional bias across various psychological domains and that activation of 5-HT2A receptors is central in mood regulation and emotional face recognition in healthy subjects. These findings may not only have implications for the pathophysiology of dysfunctional emotional biases but may also provide a framework to delineate the mechanisms underlying psylocybin's putative antidepressant effects. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Cognitive loading affects motor awareness and movement kinematics but not locomotor trajectories during goal-directed walking in a virtual reality environment.

    Directory of Open Access Journals (Sweden)

    Oliver Alan Kannape

    Full Text Available The primary purpose of this study was to investigate the effects of cognitive loading on movement kinematics and trajectory formation during goal-directed walking in a virtual reality (VR environment. The secondary objective was to measure how participants corrected their trajectories for perturbed feedback and how participants' awareness of such perturbations changed under cognitive loading. We asked 14 healthy young adults to walk towards four different target locations in a VR environment while their movements were tracked and played back in real-time on a large projection screen. In 75% of all trials we introduced angular deviations of ±5° to ±30° between the veridical walking trajectory and the visual feedback. Participants performed a second experimental block under cognitive load (serial-7 subtraction, counter-balanced across participants. We measured walking kinematics (joint-angles, velocity profiles and motor performance (end-point-compensation, trajectory-deviations. Motor awareness was determined by asking participants to rate the veracity of the feedback after every trial. In-line with previous findings in natural settings, participants displayed stereotypical walking trajectories in a VR environment. Our results extend these findings as they demonstrate that taxing cognitive resources did not affect trajectory formation and deviations although it interfered with the participants' movement kinematics, in particular walking velocity. Additionally, we report that motor awareness was selectively impaired by the secondary task in trials with high perceptual uncertainty. Compared with data on eye and arm movements our findings lend support to the hypothesis that the central nervous system (CNS uses common mechanisms to govern goal-directed movements, including locomotion. We discuss our results with respect to the use of VR methods in gait control and rehabilitation.

  19. Cognitive loading affects motor awareness and movement kinematics but not locomotor trajectories during goal-directed walking in a virtual reality environment.

    Science.gov (United States)

    Kannape, Oliver Alan; Barré, Arnaud; Aminian, Kamiar; Blanke, Olaf

    2014-01-01

    The primary purpose of this study was to investigate the effects of cognitive loading on movement kinematics and trajectory formation during goal-directed walking in a virtual reality (VR) environment. The secondary objective was to measure how participants corrected their trajectories for perturbed feedback and how participants' awareness of such perturbations changed under cognitive loading. We asked 14 healthy young adults to walk towards four different target locations in a VR environment while their movements were tracked and played back in real-time on a large projection screen. In 75% of all trials we introduced angular deviations of ±5° to ±30° between the veridical walking trajectory and the visual feedback. Participants performed a second experimental block under cognitive load (serial-7 subtraction, counter-balanced across participants). We measured walking kinematics (joint-angles, velocity profiles) and motor performance (end-point-compensation, trajectory-deviations). Motor awareness was determined by asking participants to rate the veracity of the feedback after every trial. In-line with previous findings in natural settings, participants displayed stereotypical walking trajectories in a VR environment. Our results extend these findings as they demonstrate that taxing cognitive resources did not affect trajectory formation and deviations although it interfered with the participants' movement kinematics, in particular walking velocity. Additionally, we report that motor awareness was selectively impaired by the secondary task in trials with high perceptual uncertainty. Compared with data on eye and arm movements our findings lend support to the hypothesis that the central nervous system (CNS) uses common mechanisms to govern goal-directed movements, including locomotion. We discuss our results with respect to the use of VR methods in gait control and rehabilitation.

  20. The strategy of therapy of the axilla in early cancer. Surgery or radiotherapy

    International Nuclear Information System (INIS)

    Izuo, Masaru

    1998-01-01

    The therapy of the axillary lymph node in early breast cancer was assessed perspectively. Recently, axillary irradiation was carried out and compared with surgery. Radiotherapy was not evaluated more successful. To carry out in accordance with the present guide line, so called ''modern technique'' or ''modern dosage schedule'', radiotherapy of the axilla is effective as well as surgery. We have many agreements that the rate of incidence of complication associated with irradiation was decreased in accordance with ''modern technique''. It is reasonable to radiate additionally after the selection by the ''node sampling'' in the sense of decreasing unnecessary irradiation. But it is not sufficient in their reliability, it is hard to expect this method getting more popular than now. We cannot find any difference in the effect of the treatment itself between present dissection and radiotherapy. However we have many agreements that axillary dissection may give the information about n-stage, and the contribution to the suitable selection to the prognosis factor and adjuvant chemotherapy was not so less even in early cancer. Some early cancers (non-invasive carcinoma or micro carcinoma) will not need the axillary therapy. It is one of the options ''to combine mastectomy under local anesthesia and radiotherapy'' in close cooperation with the skilled radiologist. (K.H.) 120 refs

  1. A Longitudinal Assessment of Early Childhood Education with Integrated Speech Therapy for Children with Significant Language Impairment in Germany

    Science.gov (United States)

    Ullrich, Dieter; Ullrich, Katja; Marten, Magret

    2014-01-01

    Background: In Lower Saxony, Germany, pre-school children with language- and speech-deficits have the opportunity to access kindergartens with integrated language-/speech therapy prior to attending primary school, both regular or with integrated speech therapy. It is unknown whether these early childhood education treatments are helpful and…

  2. Early identification of risk factors for refractory secondary hyperparathyroidism in patients with long-term renal replacement therapy

    NARCIS (Netherlands)

    Jorna, Francisca Hillegonda; Tobe, TJM; Huisman, RM; de Jong, PE; Plukker, JTM; Stegeman, CA

    Background. Secondary hyperparathyroidism can complicate renal replacement therapy (RRT) in patients with end-stage renal disease. Current medical therapies often result in hypercalcaemia and fail to correct hyperparathyroidism, but might be more effective at an early stage of disease. The aim of

  3. Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA.

    Science.gov (United States)

    Santos, Helena; Eusébio, Mónica; Borges, Joana; Gonçalves, Diana; Ávila-Ribeiro, Pedro; Faria, Daniela Santos; Lopes, Carina; Rovisco, João; Águeda, Ana; Nero, Patrícia; Valente, Paula; Cravo, Ana Rita; Santos, Maria José

    2017-01-01

    Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with PsA) and those with ≥5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; PPsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids had no effect on PsARC response over 2 years of follow-up. Persistence on ADA was similar in both groups. Conclusion Early PsA patients had a greater chance of improvement after ADA therapy and better functional outcome, and

  4. Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy

    Directory of Open Access Journals (Sweden)

    F. A. Zeiler

    2015-01-01

    Full Text Available Background. Treatment of symptomatic delayed cerebral ischemia (DCI after subarachnoid hemorrhage (SAH is difficult. Recent studies suggest intravenous (IV high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm.

  5. Therapy of anorexia and Young’s early maladaptive schemas. Longitudinal study

    Directory of Open Access Journals (Sweden)

    Dorota Mącik

    2015-10-01

    Full Text Available Background Young’s early maladaptive schemas are defined as convictions about oneself acquired in childhood, formed by a child in response to deprivation of his or her basic needs, especially in the area of relationships. In the case of anorexia, the role of the family and relations is emphasized as crucial for the genesis of this disorder. The aim of the research was to investigate whether Young’s early maladaptive schemas change during the therapy, which would prognosticate higher treatment efficiency. Participants and procedure The study group included 30 women suffering from anorexia, starting their 6-week therapeutic program. The procedure included double measurement: during the administration and discharge. The respondents filled in the Young Schema Questionnaire in its short form (YSQ-S3 (twice, the Acceptance of Illness Scale (AIS adapted by Juczyński (twice, and a demographic chart (once. Results The intensity of all schemas decreased after completion of the therapeutic program; the differences were mostly statistically significant. The composition of the most intense schemas did not change significantly: unrelenting standards and abandonment were the highest during both measurements. What changed were the interrelations between the schemas. They are also connected with the acceptance of the illness (the weaker they are, the greater the acceptance, and the stronger the relations and with psychological well-being, especially during the post-therapy measurement. Conclusions The schemas seem to be significant from the perspective of understanding anorexia. They are susceptible to be changed by integrative therapies. Nevertheless, it seems that in order to achieve a durable change, schema therapy should be applied.

  6. Early detection by MRI and conservative therapy of lumbar spondylolysis in the growing period

    International Nuclear Information System (INIS)

    Yoshida, Tohru; Namba, Hiromichi; Kasai, Tsutomu; Ohta, Susumu

    1996-01-01

    Since 1991 the early cases of spondylolysis in the growing stage have been diagnosed with MRI and treated conservatively by the authors. The final results were obtained in 153 cases (207 arches). The fusion rate of the separated part of these arches was 82% of the total. Treatment consisted mainly of prohibition of exercise and wearing a hard brace. The brace was more effective when worn not only during the day but also throughout the night. On MRI T 1 -weighted images low signal intensity changes of the pars interarticularis proved that bony fusion had been attained with conservative therapy. (author)

  7. Early detection by MRI and conservative therapy of lumbar spondylolysis in the growing period

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Tohru; Namba, Hiromichi; Kasai, Tsutomu; Ohta, Susumu [Yoshida Orthopaedic Hospital, Toyota, Aichi (Japan)

    1996-07-01

    Since 1991 the early cases of spondylolysis in the growing stage have been diagnosed with MRI and treated conservatively by the authors. The final results were obtained in 153 cases (207 arches). The fusion rate of the separated part of these arches was 82% of the total. Treatment consisted mainly of prohibition of exercise and wearing a hard brace. The brace was more effective when worn not only during the day but also throughout the night. On MRI T{sub 1}-weighted images low signal intensity changes of the pars interarticularis proved that bony fusion had been attained with conservative therapy. (author)

  8. [The new concept of osteoporosis. Early diagnosis, prevention and therapy are possible today].

    Science.gov (United States)

    Hesch, R D; Harms, H; Rittinghaus, E F; Brabant, G

    1990-04-15

    A paradigma of osteoporosis pathology is discussed, at the center of which is the hormone-related disturbance of the osteoblast/osteoclast functional unit. A liberal replacement of estrogen-gestagen in post-menopausal women is advocated. Early diagnosis with the aid of quantitative computed tomography makes it possible to establish the indication for timely hormonal treatment in the future, which can result in a measureable increase in bone mass. Late therapy, that is, treatment initiated after the occurrence of fractures, has proven largely ineffective.

  9. Emerging Cardiac Imaging Modalities for the Early Detection of Cardiotoxicity Due to Anticancer Therapies.

    Science.gov (United States)

    López-Fernández, Teresa; Thavendiranathan, Paaladinesh

    2017-06-01

    The undeniable advances in the field of oncology have finally led to a decrease in overall cancer-related mortality. However, this population of long-term cancer survivors is now facing a shift toward a substantial increase in cardiovascular morbidity and mortality. Because the development of overt cardiotoxicity can be associated with poor outcomes, preclinical identification of cardiac toxicity is important. This will promote early instauration of treatments to prevent overt heart dysfunction and allow oncologists to continue cancer therapy in an uninterrupted manner. Surveillance strategies for the early detection of cardiac injury include cardiac imaging and biomarkers during treatment. In this review, we outline existing cardiac imaging modalities to detect myocardial changes in patients undergoing cancer treatment and in survivors, and their strengths and limitations. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Developing Singing Confidence in Early Childhood Teachers Using Acceptance and Commitment Therapy and Group Singing: A Randomized Trial

    Science.gov (United States)

    Swain, Nicola; Bodkin-Allen, Sally

    2017-01-01

    Early childhood teachers are often required to sing, which requires confidence. The purpose of the present study was to treat early childhood teachers who self-identified as uncertain singers using either a group singing (GS) approach, or a talking approach, based on Acceptance and Commitment Therapy (ACT). The aim of the study was to increase…

  11. Factors predlisposing to developing early hypothyroidism after 131I therapy in patients with Graves' disease

    International Nuclear Information System (INIS)

    Zhu Mingfeng; Wen Chijun; Qian Hong

    2006-01-01

    Objective: To explore the clinical meanings of changes of serum TRAb, TGA, TMA contents during treatment of Graves' disease with 131 I, especially in those patients developing early hypothyroidism. Methods: Serum levels of TRAb, TGA, TMA, TSH, T 3 , T 4 were measured in 167 patients with Graves' disease both before and six months after mi therapy. Results: Six months after 131 I treatment, the original 167 patients could be divided into three groups based apon their thyroid ruction statas: Group A, improved but remained hyperthyroid, n=91, Group B, enthyroid, n=48, Group C, developing early hypothyroidism, n=28. Average age in Group C (hypothyroid) was significantly lower than that in Group A (hyperthyroid) (P 131 I treatment in younger patients. (2) Patients with high TRAb levels before 131 I therapy were less likely to be rendered enthyroid after a single course of treatment while those with low TRAb levels were easily rendered hypothyroid. (3) Development of hypothyroidism after 131 I treatment was closely related to the increase of TGA, TMA levels. (authors)

  12. Effects of intensive therapy using gait trainer or floor walking exercises early after stroke.

    Science.gov (United States)

    Peurala, Sinikka H; Airaksinen, Olavi; Huuskonen, Pirjo; Jäkälä, Pekka; Juhakoski, Mika; Sandell, Kaisa; Tarkka, Ina M; Sivenius, Juhani

    2009-02-01

    To analyse the effects of gait therapy for patients after acute stroke in a randomized controlled trial. Fifty-six patients with a mean of 8 days post-stroke participated in: (i) gait trainer exercise; (ii) walking training over ground; or (iii) conventional treatment. Patients in the gait trainer exercise and walking groups practiced gait for 15 sessions over 3 weeks and received additional physiotherapy. Functional Ambulatory Category and several secondary outcome measures assessing gait and mobility were administered before and after rehabilitation and at 6-month follow-up. Patients also evaluated their own effort. Walking ability improved more with intensive walk training compared with conventional treatment; median Functional Ambulatory Category was zero in all patients at the start of the study, but it was 3 in both walk-training groups and 0.5 in the conventional treatment group at the end of the therapy. Median Functional Ambulatory Category was 4 in both walk-training groups and 2.5 in conventional treatment group at 6-month follow-up. Mean accomplished walking distance was not different between the gait trainer exercise and over ground walking groups. Borg scale indicated more effort in over ground walking. Secondary outcomes also indicated improvements. Exercise therapy with walking training improved gait function irrespective of the method used, but the time and effort required to achieve the results favour the gait trainer exercise. Early intensive gait training resulted in better walking ability than did conventional treatment.

  13. An overview of experimental and early investigational therapies for the treatment of polycystic kidney disease.

    Science.gov (United States)

    Santoro, Domenico; Pellicanò, Vincenzo; Visconti, Luca; Trifirò, Gianluca; Buemi, Michele; Cernaro, Valeria

    2015-01-01

    At present, treatment of autosomal dominant polycystic kidney disease (ADPKD) is essentially supportive as there is still no specific therapy. However, recent advances with ADPKD pathophysiology have stimulated research for new therapeutic strategies. The aim of this systematic review is to analyze the experimental and early investigational therapies currently under evaluation in this field. Data from completed clinical trials were retrieved from the currently available scientific literature and from the ClinicalTrials.gov website. Among the drugs currently being explored, mammalian target of rapamycin inhibitors reduce kidney volume enlargement but their role remains uncertain. The most promising drug is the V2 receptor antagonist tolvaptan, which reduces the increased rate of total kidney volume and slows down glomerular filtration rate decline. The main candidates for the treatment of cysts growth, both in the kidney and in the liver whenever present, are the somatostatin analogues, such as lanreotide and octreotide and more recently pasireotide. As for other therapies, some favorable results have been achieved but data are still not sufficient to establish if these approaches may be beneficial in slowing ADPKD progression in the future.

  14. Profiling persistent tubercule bacilli from patient sputa during therapy predicts early drug efficacy.

    Science.gov (United States)

    Honeyborne, Isobella; McHugh, Timothy D; Kuittinen, Iitu; Cichonska, Anna; Evangelopoulos, Dimitrios; Ronacher, Katharina; van Helden, Paul D; Gillespie, Stephen H; Fernandez-Reyes, Delmiro; Walzl, Gerhard; Rousu, Juho; Butcher, Philip D; Waddell, Simon J

    2016-04-07

    New treatment options are needed to maintain and improve therapy for tuberculosis, which caused the death of 1.5 million people in 2013 despite potential for an 86 % treatment success rate. A greater understanding of Mycobacterium tuberculosis (M.tb) bacilli that persist through drug therapy will aid drug development programs. Predictive biomarkers for treatment efficacy are also a research priority. Genome-wide transcriptional profiling was used to map the mRNA signatures of M.tb from the sputa of 15 patients before and 3, 7 and 14 days after the start of standard regimen drug treatment. The mRNA profiles of bacilli through the first 2 weeks of therapy reflected drug activity at 3 days with transcriptional signatures at days 7 and 14 consistent with reduced M.tb metabolic activity similar to the profile of pre-chemotherapy bacilli. These results suggest that a pre-existing drug-tolerant M.tb population dominates sputum before and after early drug treatment, and that the mRNA signature at day 3 marks the killing of a drug-sensitive sub-population of bacilli. Modelling patient indices of disease severity with bacterial gene expression patterns demonstrated that both microbiological and clinical parameters were reflected in the divergent M.tb responses and provided evidence that factors such as bacterial load and disease pathology influence the host-pathogen interplay and the phenotypic state of bacilli. Transcriptional signatures were also defined that predicted measures of early treatment success (rate of decline in bacterial load over 3 days, TB test positivity at 2 months, and bacterial load at 2 months). This study defines the transcriptional signature of M.tb bacilli that have been expectorated in sputum after two weeks of drug therapy, characterizing the phenotypic state of bacilli that persist through treatment. We demonstrate that variability in clinical manifestations of disease are detectable in bacterial sputa signatures, and that the changing M.tb m

  15. Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

    Science.gov (United States)

    Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

    2018-05-01

    Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

  16. Past, present and future of cyanide antagonism research: From the early remedies to the current therapies.

    Science.gov (United States)

    Petrikovics, Ilona; Budai, Marianna; Kovacs, Kristof; Thompson, David E

    2015-06-26

    This paper reviews milestones in antidotal therapies for cyanide (CN) spanning early remedies, current antidotal systems and research towards next generation therapies. CN has been a part of plant defense mechanisms for millions of years. It became industrially important in the nineteenth century with the advent of CN assisted gold mining and the use of CN as a pest control agent. The biochemical basis of CN poisoning was actively studied and key mechanisms were understood as early as 1929. These fundamental studies led to a variety of antidotes, including indirect CN binders that generate methemoglobin, direct CN binders such as hydroxocobalamin, and sulfur donors that convert CN to the less toxic thiocyanate. Research on blood gases at the end of the twentieth century shed new light on the role of nitric oxide (NO) in the body. The discovery of NO's ability to compete with CN for enzymatic binding sites provided a previously missed explanation for the rapid efficacy of NO generating antidotes such as the nitrites. Presently used CN therapies include: methemoglobin/NO generators (e.g., sodium nitrite, amyl nitrite, and dimethyl aminophenol), sulfur donors (e.g., sodium thiosulfate and glutathione), and direct binding agents [(e.g., hydroxocobalamin and dicobalt salt of ethylenediaminetetraacetic acid (dicobalt edetate)]. A strong effort is being made to explore novel antidotal systems and to formulate them for rapid administration at the point of intoxication in mass casualty scenarios. New antidotes, formulations, and delivery systems are enhancing bioavailability and efficacy and hold promise for a new generation of improved CN countermeasures.

  17. Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy.

    Science.gov (United States)

    Sabir, Adeel; Schor-Bardach, Rachel; Wilcox, Carol J; Rahmanuddin, Syed; Atkins, Michael B; Kruskal, Jonathan B; Signoretti, Sabina; Raptopoulos, Vassilios D; Goldberg, S Nahum

    2008-07-01

    The objective of our study was to determine whether perfusion CT can be used to detect early changes in therapeutic response to antiangiogenic therapy in an animal tumor model. Twenty-five rats implanted with R3230 mammary adenocarcinoma (diameter, 1.2-2.0 cm) randomly received 7.5 or 30 mg/kg of an antiangiogenic agent, sorafenib, by daily gavage for 4 (n = 4), 9 (n = 9), or 14 (n = 5) days. Seven untreated animals served as a control group. Perfusion MDCT was performed at days 0, 4, 9, and 14 with 0.4 mL of ioversol (350 mg/mL) and included four 5-mm slices covering the entire tumor volume. Changes in tumor growth were determined by volumetric analysis of CT data. Serial changes in tumor volume and blood flow were assessed and correlated with pathology findings. All control tumors grew larger (from 2.0 +/- 0.7 cm(3) at day 0 to 5.9 +/- 1.0 cm(3) at day 14), whereas all treated tumors shrank (from 2.5 +/- 1.1 to 2.1 +/- 1.0 cm(3)), with a statistically significant rate of growth or shrinkage in both groups (p histopathologic viability despite the fact that these tumors were shrinking in size from day 4 onward (day 4, 2.18 +/- 0.8 cm(3); day 9, 1.98 +/- 0.8 cm(3)). Perfusion MDCT can detect focal blood flow changes even when the tumor is shrinking, possibly indicating early reversal of tumor responsiveness to antiangiogenic therapy. Given that changes in tumor volume after antiangiogenic therapy do not necessarily correlate with true treatment response, physiologic imaging of tumor perfusion may be necessary.

  18. Early Outcomes From Three Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Mendenhall, Nancy P.; Li Zuofeng; Hoppe, Bradford S.; Marcus, Robert B.; Mendenhall, William M.; Nichols, R. Charles; Morris, Christopher G.; Williams, Christopher R.; Costa, Joseph; Henderson, Randal

    2012-01-01

    Purpose: To report early outcomes with image-guided proton therapy for prostate cancer. Methods and Materials: We accrued 211 prostate cancer patients on prospective Institutional Review Board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low–risk disease, dose escalation from 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel followed by androgen deprivation for high-risk disease. Minimum follow-up was 2 years. Results: One intermediate-risk patient and 2 high-risk patients had disease progression. Pretreatment genitourinary (GU) symptom management was required in 38% of patients. A cumulative 88 (42%) patients required posttreatment GU symptom management. Four transient Grade 3 GU toxicities occurred, all among patients requiring pretreatment GU symptom management. Multivariate analysis showed correlation between posttreatment GU 2+ symptoms and pretreatment GU symptom management (p < 0.0001) and age (p = 0.0048). Only 1 Grade 3+ gastrointestinal (GI) symptom occurred. The prevalence of Grade 2+ GI symptoms was 0 (0%), 10 (5%), 12 (6%), and 8 (4%) at 6, 12, 18, and 24 months, with a cumulative incidence of 20 (10%) patients at 2 years after proton therapy. Univariate and multivariate analyses showed significant correlation between Grade 2+ rectal bleeding and proctitis and the percentage of rectal wall (rectum) receiving doses ranging from 40 CGE (10 CGE) to 80 CGE. Conclusions: Early outcomes with image-guided proton therapy suggest high efficacy and minimal toxicity with only 1.9% Grade 3 GU symptoms and <0.5% Grade 3 GI toxicities.

  19. Early Outcomes From Three Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mendenhall, Nancy P., E-mail: menden@shands.ufl.edu [University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Li Zuofeng; Hoppe, Bradford S.; Marcus, Robert B.; Mendenhall, William M.; Nichols, R. Charles; Morris, Christopher G. [University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Williams, Christopher R.; Costa, Joseph [Division of Urology, College of Medicine, University of Florida, Jacksonville, FL (United States); Henderson, Randal [University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

    2012-01-01

    Purpose: To report early outcomes with image-guided proton therapy for prostate cancer. Methods and Materials: We accrued 211 prostate cancer patients on prospective Institutional Review Board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, dose escalation from 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel followed by androgen deprivation for high-risk disease. Minimum follow-up was 2 years. Results: One intermediate-risk patient and 2 high-risk patients had disease progression. Pretreatment genitourinary (GU) symptom management was required in 38% of patients. A cumulative 88 (42%) patients required posttreatment GU symptom management. Four transient Grade 3 GU toxicities occurred, all among patients requiring pretreatment GU symptom management. Multivariate analysis showed correlation between posttreatment GU 2+ symptoms and pretreatment GU symptom management (p < 0.0001) and age (p = 0.0048). Only 1 Grade 3+ gastrointestinal (GI) symptom occurred. The prevalence of Grade 2+ GI symptoms was 0 (0%), 10 (5%), 12 (6%), and 8 (4%) at 6, 12, 18, and 24 months, with a cumulative incidence of 20 (10%) patients at 2 years after proton therapy. Univariate and multivariate analyses showed significant correlation between Grade 2+ rectal bleeding and proctitis and the percentage of rectal wall (rectum) receiving doses ranging from 40 CGE (10 CGE) to 80 CGE. Conclusions: Early outcomes with image-guided proton therapy suggest high efficacy and minimal toxicity with only 1.9% Grade 3 GU symptoms and <0.5% Grade 3 GI toxicities.

  20. Predictive Value of Early Skin Rash in Cetuximab-Based Therapy of Advanced Biliary Tract Cancer.

    Science.gov (United States)

    Rubovszky, Gábor; Budai, Barna; Ganofszky, Erna; Horváth, Zsolt; Juhos, Éva; Madaras, Balázs; Nagy, Tünde; Szabó, Eszter; Pintér, Tamás; Tóth, Erika; Nagy, Péter; Láng, István; Hitre, Erika

    2018-04-01

    Randomized trials in advanced biliary tract cancer (BTC) did not show benefit of cetuximab addition over chemotherapy. This is probably due to the lack of predictive biomarkers. The aim of this study was to explore possible predictive factors. Between 2009 and 2014, 57 patients were treated in 3-week cycles with cetuximab (250 mg/m 2 /week, loading dose: 400 mg/m 2 ), gemcitabine (1000 mg/m 2 on day 1 and 8), and capecitabine (1300 mg/m 2 /day on days 1-14). The objective response rate (ORR), progression-free (PFS) and overall survival (OS) and the adverse events (AEs) were evaluated. An exploratory analysis was performed to find possible predictive factors on clinicopathological characteristics, routine laboratory parameters and early AEs, which occurred within 2 months from the beginning of treatment. The ORR was 21%. The median PFS and OS were 34 (95% CI: 24-40) and 54 (43-67) weeks, respectively. The most frequent AEs were skin toxicities. In univariate analysis performance status, previous stent implantation, thrombocyte count at the start of therapy, early neutropenia and skin rash statistically significantly influenced the ORR, PFS and/or OS. In multivariate Cox regression analysis only normal thrombocyte count at treatment start and early acneiform rash were independent markers of longer survival. In patients showing early skin rash compared to the others the median PFS was 39 vs. 13 weeks and the median OS was 67 vs. 26 weeks, respectively. It is suggested that early skin rash can be used as a biomarker to select patients who would benefit from the treatment with cetuximab plus chemotherapy.

  1. Adoption of Intensity Modulated Radiation Therapy For Early-Stage Breast Cancer From 2004 Through 2011

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Elyn H. [Yale School of Medicine, New Haven, Connecticut (United States); Mougalian, Sarah S. [Yale School of Medicine, New Haven, Connecticut (United States); Yale Cancer Center, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Soulos, Pamela R. [Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Smith, Benjamin D. [Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States); Haffty, Bruce G. [Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Gross, Cary P. [Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Yu, James B., E-mail: james.b.yu@yale.edu [Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States)

    2015-02-01

    Purpose: Intensity modulated radiation therapy (IMRT) is a newer method of radiation therapy (RT) that has been increasingly adopted as an adjuvant treatment after breast-conserving surgery (BCS). IMRT may result in improved cosmesis compared to standard RT, although at greater expense. To investigate the adoption of IMRT, we examined trends and factors associated with IMRT in women under the age of 65 with early stage breast cancer. Methods and Materials: We performed a retrospective study of early stage breast cancer patients treated with BCS followed by whole-breast irradiation (WBI) who were ≤65 years old in the National Cancer Data Base from 2004 to 2011. We used logistic regression to identify factors associated with receipt of IMRT (vs standard RT). Results: We identified 11,089 women with early breast cancer (9.6%) who were treated with IMRT and 104,448 (90.4%) who were treated with standard RT, after BCS. The proportion of WBI patients receiving IMRT increased yearly from 2004 to 2009, with 5.3% of WBI patients receiving IMRT in 2004 and 11.6% receiving IMRT in 2009. Further use of IMRT declined afterward, with the proportion remaining steady at 11.0% and 10.7% in 2010 and 2011, respectively. Patients treated in nonacademic community centers were more likely to receive IMRT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.30-1.43 for nonacademic vs academic center). Compared to privately insured patients, the uninsured patients (OR, 0.81; 95% CI, 0.70-0.95) and those with Medicaid insurance (OR, 0.87; 95% CI, 0.79-0.95) were less likely to receive IMRT. Conclusions: The use of IMRT rose from 2004 to 2009 and then stabilized. Important nonclinical factors associated with IMRT use included facility type and insurance status.

  2. Adoption of Intensity Modulated Radiation Therapy For Early-Stage Breast Cancer From 2004 Through 2011

    International Nuclear Information System (INIS)

    Wang, Elyn H.; Mougalian, Sarah S.; Soulos, Pamela R.; Smith, Benjamin D.; Haffty, Bruce G.; Gross, Cary P.; Yu, James B.

    2015-01-01

    Purpose: Intensity modulated radiation therapy (IMRT) is a newer method of radiation therapy (RT) that has been increasingly adopted as an adjuvant treatment after breast-conserving surgery (BCS). IMRT may result in improved cosmesis compared to standard RT, although at greater expense. To investigate the adoption of IMRT, we examined trends and factors associated with IMRT in women under the age of 65 with early stage breast cancer. Methods and Materials: We performed a retrospective study of early stage breast cancer patients treated with BCS followed by whole-breast irradiation (WBI) who were ≤65 years old in the National Cancer Data Base from 2004 to 2011. We used logistic regression to identify factors associated with receipt of IMRT (vs standard RT). Results: We identified 11,089 women with early breast cancer (9.6%) who were treated with IMRT and 104,448 (90.4%) who were treated with standard RT, after BCS. The proportion of WBI patients receiving IMRT increased yearly from 2004 to 2009, with 5.3% of WBI patients receiving IMRT in 2004 and 11.6% receiving IMRT in 2009. Further use of IMRT declined afterward, with the proportion remaining steady at 11.0% and 10.7% in 2010 and 2011, respectively. Patients treated in nonacademic community centers were more likely to receive IMRT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.30-1.43 for nonacademic vs academic center). Compared to privately insured patients, the uninsured patients (OR, 0.81; 95% CI, 0.70-0.95) and those with Medicaid insurance (OR, 0.87; 95% CI, 0.79-0.95) were less likely to receive IMRT. Conclusions: The use of IMRT rose from 2004 to 2009 and then stabilized. Important nonclinical factors associated with IMRT use included facility type and insurance status

  3. Low-Dose Consolidation Radiation Therapy for Early Stage Unfavorable Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Torok, Jordan A., E-mail: jordan.torok@dm.duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Wu, Yuan [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Prosnitz, Leonard R.; Kim, Grace J. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Beaven, Anne W.; Diehl, Louis F. [Division of Hematologic Malignancy and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Kelsey, Chris R. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2015-05-01

    Purpose: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. Methods and Materials: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achieve a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. Results: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. Conclusions: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.

  4. Proton Therapy for Craniopharyngioma - An Early Report from a Single European Centre.

    Science.gov (United States)

    Ajithkumar, T; Mazhari, A-L; Stickan-Verfürth, M; Kramer, P-H; Fuentes, C-S; Lambert, J; Thomas, H; Müller, H; Fleischhack, G; Timmermann, B

    2018-05-01

    Proton beam therapy (PBT) is being increasingly used for craniopharyngioma. We describe our early outcome of patients treated with PBT. Between August 2013 and July 2016, 18 patients with craniopharyngiomas were treated with 54 Cobalt Gray Equivalent (CGE) in 30 fractions over 6 weeks at our centre. The early outcome of 16 patients included in a registry study was analysed. Radiological response was assessed by RECIST criteria and the disease- and treatment-related toxicities were scored according to the CTCAE 4.0. All patients are alive at a median follow-up of 32.6 months (range 9.2-70.6 months) from initial diagnosis. The median age at PBT was 10.2 years (range 5.4-46.9 years). One patient progressed 8.7 months after PBT and subsequently had complete resection of the tumour. At a median follow-up of 18.4 months after PBT, five patients remained in complete remission, four in partial remission and seven with stable disease. The most common adverse effects during PBT were grade 1 (cutaneous in seven patients and fatigue in six patients). There were no treatment-related grade 3 toxicities. Our early results are encouraging and comparable with the limited literature on PBT for craniopharyngioma. Copyright © 2018. Published by Elsevier Ltd.

  5. Risk of Fatal Cerebrovascular Accidents after External Beam Radiation Therapy for Early Stage Glottic Larynx Cancer

    Science.gov (United States)

    Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O’Malley, Bert; Weinstein, Gregory S.; Bekelman, Justin E.

    2013-01-01

    Background This study compared the risk of fatal cerebrovascular accidents (CVA) in patients with early stage glottic larynx cancer receiving surgery or external beam radiation therapy (EBRT). Methods and Materials Using a competing risks survival analysis, we compared the risk of death due to CVA among patients with early stage glottic larynx cancer receiving surgery or EBRT in the SEER database. Results The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8 %; 95% CI 2.3%–3.4%) compared to surgery (1.5 %; 95% CI 0.8 %–2.3%, p= 0.024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted HR 1.75; 95% CI 1.04–2.96, p= 0.037). Conclusion Treatment of early stage glottic larynx cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. PMID:23595858

  6. MicroRNAs as biomarkers for early breast cancer diagnosis, prognosis and therapy prediction.

    Science.gov (United States)

    Nassar, Farah J; Nasr, Rihab; Talhouk, Rabih

    2017-04-01

    Breast cancer is a major health problem that affects one in eight women worldwide. As such, detecting breast cancer at an early stage anticipates better disease outcome and prolonged patient survival. Extensive research has shown that microRNA (miRNA) are dysregulated at all stages of breast cancer. miRNA are a class of small noncoding RNA molecules that can modulate gene expression and are easily accessible and quantifiable. This review highlights miRNA as diagnostic, prognostic and therapy predictive biomarkers for early breast cancer with an emphasis on the latter. It also examines the challenges that lie ahead in their use as biomarkers. Noteworthy, this review addresses miRNAs reported in patients with early breast cancer prior to chemotherapy, radiotherapy, surgical procedures or distant metastasis (unless indicated otherwise). In this context, miRNA that are mentioned in this review were significantly modulated using more than one statistical test and/or validated by at least two studies. A standardized protocol for miRNA assessment is proposed starting from sample collection to data analysis that ensures comparative analysis of data and reproducibility of results. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Early effects of boron neutron capture therapy on rat glioma models

    International Nuclear Information System (INIS)

    Nakagawa, N.; Akai, F.; Fukawa, N.; Taneda, M.; Ono, K.; Suzuki, M.

    2006-01-01

    Early effects of boron neutron capture therapy on malignant gliomas are characterized by reduction of the enhanced area regression of the peritumoral edema radiologically. The aim of this study is to investigate the early histological changes of tumors and inflammatory cells after BNCT in the rat brain. The rats were treated with BNCT using boronophenyialanine (BPA) 7 days after implantation of C6 glioma cells. The tumors were assessed their sizes and configurations with magnetic resonance imaging, then killed 4 days after BNCT. The mean tumor volumes were 39mm 3 in BNCT-treated group, and 138 mm 3 in the control group. In the histological examination, tumors of the BNCT group showed less pleomorphic appearance with atypical nuclei and mitotic figures, compared with the control group. Necrosis and edematous changes in the neuropile were negligible. There existed remnant tumors adjacent to the lateral ventricle. The reactions of the inflammatory cells were examined with ED-1 of macrophage marker. ED-1 positive cells and their processes were reduced in the marginal area of tumor in the BNCT group. BNCT reduce the tumor progression by suppression of the proliferation. Inhibition of the activated macrophages may reduce peritumoral edema in early phase. (author)

  8. The impact of early symptom change and therapeutic alliance on treatment outcome in cognitive-behavioural therapy for eating disorders.

    Science.gov (United States)

    Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily

    2015-10-01

    The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. External incentives and internal states guide goal-directed behavior via the differential recruitment of the nucleus accumbens and the medial prefrontal cortex.

    Science.gov (United States)

    Moscarello, J M; Ben-Shahar, O; Ettenberg, A

    2010-10-13

    Goal-directed behavior is governed by internal physiological states and external incentives present in the environment (e.g. hunger and food). While the role of the mesocorticolimbic dopamine (DA) system in behavior guided by environmental incentives has been well studied, the effect of relevant physiological states on the function of this system is less understood. The current study examined the role of the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAcc) in the kind of food-reinforced behaviors known to be sensitive to the internal state produced by food deprivation conditions. Operant lever-press reinforced on fixed ratio 1 (FR1) and progressive ratio (PR) schedules was tested after temporary inactivation of, or DA receptor blockade in, the prelimbic mPFC or NAcc core of rats with differing levels of food deprivation (0, 12 and 36-h). Food deprivation increased PR breakpoints, as well as the number of lever-presses emitted on the FR1 schedule. Both temporary inactivation and DA blockade of NAcc reduced breakpoints across deprivation conditions, while temporary inactivation and DA blockade of mPFC reduced breakpoints only in food-deprived rats. Neither manipulation of mPFC and NAcc had any effect on behavior reinforced on the FR1 schedule. Thus, mPFC and NAcc were differentially relevant to the behaviors tested-NAcc was recruited when the behavioral cost per reinforcer was rising or high regardless of food deprivation conditions, while mPFC was recruited when food-deprived animals behaved through periods of sparse reinforcement density in order to maximize available gain. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  10.  Effect of Thrombolytic Therapy on the Incidence of Early Left Ventricular Infarct Expansion in Acute Anterior Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Namir Ghanim Al-Tawil

    2011-11-01

    Full Text Available  Objectives: To determine the incidence of early left ventricular infarct expansion within five days after first anterior ST-segment elevation myocardial infarction and the effect of early thrombolytic therapy on the incidence of early infarct expansion compared with late thrombolytic therapy.Methods: In a prospective study of 101 patients (75males and 26 females, with the first attack of acute anterior myocardial infarction, their ages ranged from 40-80 years (mean age: 61.07±10.78 who had been admitted to the Coronary Care Unit of Hawler Teaching Hospital for the period from July 2007 through to September 2009. Those who received alteplase ≤3 hours of acute myocardial infarction were labelled as group-I (49 patients and those who received alteplase >3-12 hours were labelled as group-II (52 patients.Results: The incidence of early left ventricular infarct expansion was diagnosed by 2D-echocardiography and was found to be 17.8�20Group I patients had a lower incidence of early left ventricular infarct expansion (8.16�20compared with group-II (26.92�20 p=0.014. Patients with early left ventricular infarct expansion had a higher frequency rate of left ventricular systolic dysfunction (94.44�20compared to patients without early left ventricular infarct expansion (8.43�20p<0.001. There was a significant difference in the incidence of in-hospital mortality between the patients who developed early left ventricular infarct expansion (11.1�20compared with patients without early left ventricular infarct expansion (1.2�20p=0.025.Conclusion: Early reperfusion therapy in acute anterior myocardial infarction can decrease the incidence of early left ventricular infarct expansion, preserve left ventricular systolic function and decrease in-hospital mortality.

  11. Identification of early breast cancer patient cohorts who may benefit from lapatinib therapy

    DEFF Research Database (Denmark)

    Strasser-Weippl, Kathrin; Horick, Nora; Smith, Ian E

    2016-01-01

    with HER2+ early breast cancer not treated with trastuzumab. We performed subgroup analyses and number-needed-to-treat (NNT) calculations using patient and tumour associated predictors. Hormone receptor negative (HR-) patients on lapatinib had a significantly prolonged disease-free survival (DFS) compared...... 5 years) was between 5.9 (node positive patients trastuzumab for HR unselected patients (e.g. 15.6 for DFS at 4 years in HERA). In a subgroup analysis of the adjuvant TEACH trial, we show...... that anti-HER2 monotherapy with a TKI is beneficial as adjuvant therapy in a subgroup of patients. NNT in HER2+ HR- patients are in range with those reported from up-front adjuvant trastuzumab trials....

  12. Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cuaron, John J. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chon, Brian; Tsai, Henry; Goenka, Anuj; DeBlois, David [Procure Proton Therapy Center, Somerset, New Jersey (United States); Ho, Alice; Powell, Simon [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Hug, Eugen [Procure Proton Therapy Center, Somerset, New Jersey (United States); Cahlon, Oren, E-mail: cahlono@mskcc.org [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Procure Proton Therapy Center, Somerset, New Jersey (United States)

    2015-06-01

    Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

  13. A gene expression profile indicative of early stage HER2 targeted therapy response.

    Science.gov (United States)

    O'Neill, Fiona; Madden, Stephen F; Clynes, Martin; Crown, John; Doolan, Padraig; Aherne, Sinéad T; O'Connor, Robert

    2013-07-01

    Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor.Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents.

  14. Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis.

    Science.gov (United States)

    Georgopoulou, Antonia-Panagiota; Savva, Athina; Giamarellos-Bourboulis, Evangelos J; Georgitsi, Marianna; Raftogiannis, Maria; Antonakos, Nicolaos; Apostolidou, Efterpi; Carrer, Dionyssia-Pinelopi; Dimopoulos, George; Economou, Aggelos; Efthymiou, George; Galanakis, Nearchos; Galani, Labrini; Gargalianos, Panagiotis; Karaiskos, Ilias; Katsenos, Chrisostomos; Kavatha, Dimitra; Koratzanis, Evangelos; Labropoulos, Panagiotis; Lada, Malvina; Nakos, George; Paggalou, Evgenia; Panoutsopoulos, George; Paraschos, Michael; Pavleas, Ioannis; Pontikis, Konstantinos; Poulakou, Garyfallia; Prekates, Athanassios; Sybardi, Styliani; Theodorakopoulou, Maria; Trakatelli, Christina; Tsiaoussis, Panagiotis; Gogos, Charalambos; Giamarellou, Helen; Armaganidis, Apostolos; Meisner, Michael

    2011-06-01

    The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Longitudinal functional brain imaging study in early course schizophrenia before and after cognitive enhancement therapy.

    Science.gov (United States)

    Keshavan, Matcheri S; Eack, Shaun M; Prasad, Konasale M; Haller, Chiara S; Cho, Raymond Y

    2017-05-01

    Schizophrenia is characterized by impaired -social and non social cognition both of which lead to functional deficits. These deficits may benefit from cognitive remediation, but the neural underpinnings of such improvements have not been clearly delineated. We conducted a functional magnetic resonance (fMRI) study in early course schizophrenia patients randomly assigned to cognitive enhancement therapy (CET) or enriched supportive therapy (EST) and treated for two years. Imaging data over three time points including fMRI blood oxygen level dependent (BOLD) data were acquired during performance of a cognitive control paradigm, the Preparing to Overcome Prepotency (POP) task, and functional connectivity data, were analyzed. During the two years of treatment, CET patients showed a continual increase in BOLD activity in the right dorsolateral prefrontal cortex (DLPFC), whereas EST patients tended to show no change in prefrontal brain function throughout treatment. Increases in right DLPFC activity were modestly associated with improved neurocognition (β = .14, p = .041), but not social cognition. Functional connectivity analyses showed reduced connectivity between the DLPFC and the anterior cingulate cortex (ACC) in CET compared to EST over the two years of treatment, which was associated with neurocognitive improvement. These findings suggest that CET leads to enhanced neural activity in brain regions mediating cognitive control and increased efficiency in prefrontal circuits; such changes may be related to the observed therapeutic effects of CET on neurocognitive function. Copyright © 2017. Published by Elsevier Inc.

  16. Domestic dengue infection with hemophagocytic lymphohistiocytosis successfully treated by early steroid therapy.

    Science.gov (United States)

    Yoshifuji, Kota; Oshina, Takahiro; Sonokawa, Saeko; Noguchi, Yuma; Suzuki, Sayaka; Tanaka, Keisuke; Kumagai, Takashi

    2016-07-01

    A 34-year-old man, working at a park in Tokyo, Japan, was repeatedly bitten by mosquitoes while cutting grass. He was hospitalized with sudden fever, fatigue, and weakness. He was eventually diagnosed with dengue virus infection, detected using reverse transcription polymerase chain reaction for the genome and by the presence of nonstructural protein 1 in his peripheral blood. Symptomatic treatments such as acetaminophen for the fever were not effective. Moreover, peripheral blood examination showed drastically decreased white blood cells and platelets, as well as marked elevations of ferritin and soluble interleukin 2 receptor. Furthermore, bone marrow examination revealed increased macrophages with hemophagocytosis. Dengue infection with hemophagocytic lymphohistiocytosis (HLH) was ultimately diagnosed. Half-dose steroid pulse therapy for three days dramatically reduced his temperature, thereby ameliorating physical symptoms and restoring normal peripheral blood data. He was discharged 12 days after admission. Dengue infection with HLH is rare and this is the first report, to our knowledge, of domestic dengue infection with HLH in Japan. Early steroid therapy may be effective in such cases.

  17. Early MRI changes in glioblastoma in the period between surgery and adjuvant therapy.

    Science.gov (United States)

    Farace, Paolo; Amelio, Dante; Ricciardi, Giuseppe K; Zoccatelli, Giada; Magon, Stefano; Pizzini, Francesca; Alessandrini, Franco; Sbarbati, Andrea; Amichetti, Maurizio; Beltramello, Alberto

    2013-01-01

    To investigate the increase in MRI contrast enhancement (CE) occurring in glioblastoma during the period between surgery and initiation of chemo-radiotherapy, thirty-seven patients with newly diagnosed glioblastoma were analyzed by early post-operative magnetic resonance (EPMR) imaging within three days of surgery and by pre-adjuvant magnetic resonance (PAMR) examination before adjuvant therapy. Areas of new CE were investigated by use of EPMR diffusion-weighted imaging and PAMR perfusion imaging (by arterial spin-labeling). PAMR was acquired, on average, 29.9 days later than EPMR (range 20-37 days). During this period an increased area of CE was observed for 17/37 patients. For 3/17 patients these regions were confined to areas of reduced EPMR diffusion, suggesting postsurgical infarct. For the other 14/17 patients, these areas suggested progression. For 11/17 patients the co-occurrence of hyperperfusion in PAMR perfusion suggested progression. PAMR perfusion and EPMR diffusion did not give consistent results for 3/17 patients for whom small new areas of CE were observed, presumably because of the poor spatial resolution of perfusion imaging. Before initiation of adjuvant therapy, areas of new CE of resected glioblastomas are frequently observed. Most of these suggest tumor progression, according to EPMR diffusion and PAMR perfusion criteria.

  18. Analysis of radiation pneumonitis outside the radiation field in breast conserving therapy for early breast cancer

    International Nuclear Information System (INIS)

    Ogo, Etsuyo; Fujimoto, Kiminori; Hayabuchi, Naofumi

    2002-01-01

    In a retrospective study of radiation-induced pulmonary changes for patients with breast conserving therapy for early breast cancer, we sent questionnaires to the main hospitals in Japan. In this study, we analyzed pulmonary changes after tangential whole-breast irradiation. The purpose of this study was to determine the incidence and risk factors for radiation pneumonitis outside the radiation field. The questionnaires included patients data, therapy data, and lung injury information between August 1999 and May 2000. On the first questionnaires, answer letters were received from 107 institutions out of 158 (67.7%). On the second questionnaires, response rate (hospitals which had radiation pneumonitis outside the radiation field) was 21.7% (23/106). We could find no risk factors of this type of pneumonitis. We suggested that lung irradiation might trigger this type of pneumonitis which is clinically similar to BOOP (bronchiolitis obliterans organizing pneumonia). It developed in 1.5-2.1% among the patients with breast conserving surgery and tangential whole-breast irradiation. And it is likely appeared within 6 months after radiotherapy. (author)

  19. Monitoring early tumor response to drug therapy with diffuse optical tomography

    Science.gov (United States)

    Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

    2012-01-01

    Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

  20. Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

    Science.gov (United States)

    Denduluri, Neelima; Chavez-MacGregor, Mariana; Telli, Melinda L; Eisen, Andrea; Graff, Stephanie L; Hassett, Michael J; Holloway, Jamie N; Hurria, Arti; King, Tari A; Lyman, Gary H; Partridge, Ann H; Somerfield, Mark R; Trudeau, Maureen E; Wolff, Antonio C; Giordano, Sharon H

    2018-05-22

    Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

  1. Cancerous Tumour Model Analysis and Constructing schemes of Anti-angiogenesis Therapy at an Early Stage

    Directory of Open Access Journals (Sweden)

    O. Yu. Mukhomorova

    2015-01-01

    Full Text Available Anti-angiogenesis therapy is an alternative and successfully employed method for treatment of cancerous tumour. However, this therapy isn't widely used in medicine because of expensive drugs. It leads naturally to elaboration of such treatment regimens which use minimum amount of drugs.The aim of the paper is to investigate the model of development of illness and elaborate appropriate treatment regimens in the case of early diagnosis of the disease. The given model reflects the therapy at an intermediate stage of the disease treatment. Further treatment is aimed to destroy cancer cells and may be continued by other means, which are not reflected in the model.Analysis of the main properties of the model was carried out with consideration of two types of auxiliary systems. In the first case, the system is considered without control, as a model of tumour development in the absence of medical treatment. The study of the equilibrium point and determination of its type allowed us to describe disease dynamics and to determine tumour size resulting in death. In the second case a model with a constant control was investigated. The study of its equilibrium point showed that continuous control is not sufficient to support satisfactory patient's condition, and it is necessary to elaborate more complex treatment regimens. For this purpose, we used the method of terminal problems consisting in the search for such program control which forces system to a given final state. Selecting the initial and final states is due to medical grounds.As a result, we found two treatment regimens | one-stage treatment regimen and multi-stage one. The properties of each treatment regimen are analyzed and compared. The total amount of used drugs was a criterion for comparing these two treatment regimens. The theoretical conclusions obtained in this work are supported by computer modeling in MATLAB environment.

  2. Cognitive behavioural therapy attenuates the enhanced early facial stimuli processing in social anxiety disorders: an ERP investigation.

    Science.gov (United States)

    Cao, Jianqin; Liu, Quanying; Li, Yang; Yang, Jun; Gu, Ruolei; Liang, Jin; Qi, Yanyan; Wu, Haiyan; Liu, Xun

    2017-07-28

    Previous studies of patients with social anxiety have demonstrated abnormal early processing of facial stimuli in social contexts. In other words, patients with social anxiety disorder (SAD) tend to exhibit enhanced early facial processing when compared to healthy controls. Few studies have examined the temporal electrophysiological event-related potential (ERP)-indexed profiles when an individual with SAD compares faces to objects in SAD. Systematic comparisons of ERPs to facial/object stimuli before and after therapy are also lacking. We used a passive visual detection paradigm with upright and inverted faces/objects, which are known to elicit early P1 and N170 components, to study abnormal early face processing and subsequent improvements in this measure in patients with SAD. Seventeen patients with SAD and 17 matched control participants performed a passive visual detection paradigm task while undergoing EEG. The healthy controls were compared to patients with SAD pre-therapy to test the hypothesis that patients with SAD have early hypervigilance to facial cues. We compared patients with SAD before and after therapy to test the hypothesis that the early hypervigilance to facial cues in patients with SAD can be alleviated. Compared to healthy control (HC) participants, patients with SAD had more robust P1-N170 slope but no amplitude effects in response to both upright and inverted faces and objects. Interestingly, we found that patients with SAD had reduced P1 responses to all objects and faces after therapy, but had selectively reduced N170 responses to faces, and especially inverted faces. Interestingly, the slope from P1 to N170 in patients with SAD was flatter post-therapy than pre-therapy. Furthermore, the amplitude of N170 evoked by the facial stimuli was correlated with scores on the interaction anxiousness scale (IAS) after therapy. Our results did not provide electrophysiological support for the early hypervigilance hypothesis in SAD to faces, but

  3. Early severe morbidity and resource utilization in South African adults on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Meintjes Graeme A

    2009-12-01

    Full Text Available Abstract Background High rates of mortality and morbidity have been described in sub-Saharan African patients within the first few months of starting highly active antiretroviral therapy (HAART. There is limited data on the causes of early morbidity on HAART and the associated resource utilization. Methods A cross-sectional study was conducted of medical admissions at a secondary-level hospital in Cape Town, South Africa. Patients on HAART were identified from a register and HIV-infected patients not on HAART were matched by gender, month of admission, and age group to correspond with the first admission of each case. Primary reasons for admission were determined by chart review. Direct health care costs were determined from the provider's perspective. Results There were 53 in the HAART group with 70 admissions and 53 in the no-HAART group with 60 admissions. The median duration of HAART was 1 month (interquartile range 1-3 months. Median baseline CD4 count in the HAART group was 57 × 106 cells/L (IQR 15-115. The primary reasons for admission in the HAART group were more likely to be due to adverse drug reactions and less likely to be due to AIDS events than the no-HAART group (34% versus 7%; p Conclusions Causes of early morbidity are different and more complex in HIV-infected patients on HAART. This results in greater resource utilization of diagnostic and therapeutic services.

  4. Radiation therapy alone for early stage non-small cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Chun, Ha Chung; Lee, Myung Za

    2002-01-01

    To evaluate the outcome of early stage non-small cell lung cancer patients who were treated with radiation therapy along and define the optimal radiotherapeutic regimen for these patients. A retrospective review was performed on patients with sage I or II non-small cell carcinoma of the lung that were treated at our institution between June, 1987 and May, 2000. A total of 21 patients treated definitively with radiation therapy alone were included in this study. The age of the patients ranged from 53 to 81 years with a median of 66 years. All the patients were male. The medical reasons for inoperability were lack of pulmonary reserve, cardiovascular disease, poor performance status, old age, and patient refusal in the decreasing order. Pathological evidence was not adequate to characterize the non-small cell subtype in two patients. Of the remaining 19 patients, 16 had squamous cell carcinoma and 3 had adenocarcinoma. Treatment was given with conventional fractionation, once a day, five times a week. The doses to the primary site ranged from 56 Gy to 69 Gy. No patients were lost to follow-up. The overall survival rates for the entire group at 2, 3 and 5 years were 41, 30 and 21%, respectively. The cause specific survivals at 2, 3 and 5 years were 55, 36 and 25%, respectively. An intercurrent disease was the cause of death in two patients. The cumulative local failure rate at 5 years was 43%. Nine of the 21 patients had treatment failures after the curative radiotherapy was attempted. Local recurrences as the first site of failure were documented in 7 patients. Therefore, local failure alone represented 78% of the total failures. Those patients whose tumor sizes were less than 4 cm had a significantly better 5 year disease free survival than those with tumors greater than 4 cm (0% vs 36%). Those patients with a Karnofsky performance status less than 70 did not differ significantly with respect to actuarial survival when compared to those with a status greater than 70

  5. Cost-effectiveness of early initiation of first-line combination antiretroviral therapy in Uganda

    Directory of Open Access Journals (Sweden)

    Sempa Joseph

    2012-09-01

    Full Text Available Abstract Background Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART at CD4+ T cell (CD4 count below 350 cell/μl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250–350 cell/μl (early versus Methods Life expectancy of cART-treated patients, conditional on baseline CD4 count, was modeled based on published literature. First-line cART costs $192 annually, with an additional $113 for patient monitoring. Delaying initiation of cART until the CD4 count falls below 250 cells/μl would incur the cost of the bi-annual CD4 count tests and routine maintenance care at $85 annually. We compared lifetime treatment costs and disability adjusted life-expectancy between early vs. delayed cART for ten baseline CD4 count ranges from 250-350 cell/μl. All costs and benefits were discounted at 3% annually. Results Treatment delay varied from 6–18 months. Early cART initiation increased life expectancy from 1.5-3.5 years and averted 1.33–3.10 disability adjusted life years (DALY’s per patient. Lifetime treatment costs were $4,300–$5,248 for early initiation and $3,940–$4,435 for delayed initiation. The cost/DALY averted of the early versus delayed start ranged from $260–$270. Conclusions In HIV-positive patients presenting with CD4 count between 250-350 cells/μl, immediate initiation of cART is a highly cost-effective strategy using the recommended one-time per capita GDP threshold of $490 reported for Uganda. This would constitute an efficient use of scarce health care funds.

  6. Efficacy of breast conservation therapy in early stage bilateral breast cancer

    International Nuclear Information System (INIS)

    Lee, Misa M.; Chen, Luci M.; Heimann, Ruth; Powers, Claire; Weichselbaum, Ralph R.

    1996-01-01

    -up was 50 months for synchronous patients, 45 months for metachronous patients, and 52 months for unilateral patients. Local control and survival were analyzed in patients with (1) synchronous bilateral breast cancer (SBBC), (2) metachronous breast cancer (MBBC), (3) unilateral breast cancer (UBC). The interval to development of local recurrence and survival were calculated from the time of development of the second breast lesion in patients with metachronous breast cancer. RESULTS: There were no differences in survival and failure free survival in patients with SBBC, MBBC, or UBC. Five year overall survival by lifetable analysis was 76% for SBBC, 78% for MBBC, and 87% for UBC patients; the p-value was 0.32 by logrank analysis. The five year failure-free survival was 79% for SBBC, 73% for MBBC, and 85% for UBC patients; the p-value was 0.28 by logrank analysis. There were no significant differences in median age, tumor size, pathologic node status, tamoxifen use, chemotherapy use, or median total dose of radiation therapy for SBBC, MBBC, or UBC patients. A significant difference was found in the incidence of family history of breast cancer in patients with unilateral (28%) versus bilateral breast cancer (40%) (p=0.0028 by chi-square analysis). However, there was no difference seen in outcome of patients by family history of breast cancer. The local control was identical in both bilateral and UBC patients with a crude failure rate of 3%. CONCLUSION: In our patients, no differences were observed in both local control and overall survival. Therefore, breast conservation therapy in local-regional, early stage breast cancer is a rational treatment modality for patients with SBBC and MBBC as well as UBC

  7. Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Weijun Zhu

    Full Text Available BACKGROUND: Despite prolonged treatment with highly active antiretroviral therapy (HAART, the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS levels did not reveal any significant changes in the same treatment period. CONCLUSIONS/SIGNIFICANCE: Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.

  8. The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma

    DEFF Research Database (Denmark)

    Busse, William W; Pedersen, Søren; Pauwels, Romain A

    2008-01-01

    BACKGROUND: The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study enrolled 7241 patients aged 5 to 66 years with recent-onset, mild persistent asthma to assess early intervention with the inhaled corticosteroid budesonide on long-term asthma control. OBJECTIVE: The open......-label phase of the START study was included to determine the effect on lung function and asthma control of adding budesonide to the reference group patients who had not initially received inhaled corticosteroids. METHODS: Patients were randomized to double-blind treatment with budesonide, 200 mug (those aged...

  9. Social Learning Family Therapy and the Treatment of Conduct Disorder in Early Childhood: Premise, Procedures and Prospects.

    Science.gov (United States)

    Mpofu, Elias

    1997-01-01

    Discusses social learning family therapy hypotheses on the development and sustenance of conduct disorder in early childhood, together with treatment approaches that use parents as the primary agents of change. Reviews research showing that parent training procedures hold much promise for the treatment of conduct disorder in childhood. (JPB)

  10. Characterizing the protocol for early modified constraint-induced movement therapy in the EXPLICIT-stroke trial

    NARCIS (Netherlands)

    Nijland, R van; Wegen, E. van; Krogt, H. van der; Bakker, C.D.; Buma, F.; Klomp, A.; Kordelaar, J. van; Kwakkel, G.; Geurts, A.C.; Kuijk, A.A. van; Lindeman, E.; Visser-Meily, J.M.A.; Arendzen, H.J.; Meskers, C.G.; Helm, F.C.T. van der; Vlugt, E. de

    2013-01-01

    Constraint-induced movement therapy (CIMT) is a commonly used rehabilitation intervention to improve upper limb function after stroke. CIMT was originally developed for patients with a chronic upper limb paresis. Although there are indications that exercise interventions should start as early as

  11. Early Intervention in Children (0–6 Years with a Rare Developmental Disability: The Occupational Therapy Role

    Directory of Open Access Journals (Sweden)

    Lucy Dall'Alba

    2014-12-01

    Conclusion: Family-centred practice, play therapy, and individually tailored programmes are identified as key practice areas for this population. The important role occupational therapists play in early intervention teams is highlighted; however, further research is needed to develop the evidence base for best practice with particular rare developmental conditions.

  12. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury

    DEFF Research Database (Denmark)

    Karvellas, Constantine J; Farhat, Maha R; Sajjad, Imran

    2011-01-01

    Introduction: Our aim was to investigate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI). Methods: Systematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web ...

  13. Increasing Early Childhood Educators' Use of Communication-Facilitating and Language-Modelling Strategies: Brief Speech and Language Therapy Training

    Science.gov (United States)

    McDonald, David; Proctor, Penny; Gill, Wendy; Heaven, Sue; Marr, Jane; Young, Jane

    2015-01-01

    Intensive Speech and Language Therapy (SLT) training courses for Early Childhood Educators (ECEs) can have a positive effect on their use of interaction strategies that support children's communication skills. The impact of brief SLT training courses is not yet clearly understood. The aims of these two studies were to assess the impact of a brief…

  14. Aspirin and Statin Nonuse Associated With Early Biochemical Failure After Prostate Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zaorsky, Nicholas G. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Buyyounouski, Mark K., E-mail: mark.buyyounouski@fccc.edu [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Li, Tianyu [Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Horwitz, Eric M. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States)

    2012-09-01

    Purpose: To present the largest retrospective series investigating the effect of aspirin and statins, which are hypothesized to have antineoplastic properties, on biochemical failure (nadir plus 2 ng/mL) after prostate radiation therapy (RT). Methods and Materials: Between 1989 and 2006, 2051 men with clinically localized prostate cancer received definitive RT alone (median dose, 76 Gy). The rates of aspirin use and statin use (defined as any use at the time of RT or during follow-up) were 36% and 34%, respectively. The primary endpoint of the study was an interval to biochemical failure (IBF) of less than 18 months, which has been shown to be the single strongest predictor of distant metastasis, prostate cancer survival, and overall survival after RT. Patient demographic characteristics and tumor staging factors were assessed with regard to associations with the endpoint. Univariate analysis was performed with the {chi}{sup 2} test for categorical variables and the Wilcoxon test for continuous variables. Multivariable analysis was performed with a multiple logistic regression. Results: The median follow-up was 75 months. Univariate analysis showed that an IBF of less than 18 months was associated with aspirin nonuse (P<.0001), statin nonuse (P<.0001), anticoagulant nonuse (P=.0006), cardiovascular disease (P=.0008), and prostate-specific antigen (continuous) (P=.008) but not with Gleason score, age, RT dose, or T stage. On multivariate analysis, only aspirin nonuse (P=.0012; odds ratio, 2.052 [95% confidence interval, 1.328-3.172]) and statin nonuse (P=.0002; odds ratio, 2.465 [95% confidence interval, 1.529-3.974]) were associated with an IBF of less than 18 months. Conclusions: In patients who received RT for prostate cancer, aspirin or statin nonuse was associated with early biochemical failure, a harbinger of distant metastasis and death. Further study is needed to confirm these findings and to determine the optimal dosing and schedule, as well as the relative

  15. Aspirin and Statin Nonuse Associated With Early Biochemical Failure After Prostate Radiation Therapy

    International Nuclear Information System (INIS)

    Zaorsky, Nicholas G.; Buyyounouski, Mark K.; Li, Tianyu; Horwitz, Eric M.

    2012-01-01

    Purpose: To present the largest retrospective series investigating the effect of aspirin and statins, which are hypothesized to have antineoplastic properties, on biochemical failure (nadir plus 2 ng/mL) after prostate radiation therapy (RT). Methods and Materials: Between 1989 and 2006, 2051 men with clinically localized prostate cancer received definitive RT alone (median dose, 76 Gy). The rates of aspirin use and statin use (defined as any use at the time of RT or during follow-up) were 36% and 34%, respectively. The primary endpoint of the study was an interval to biochemical failure (IBF) of less than 18 months, which has been shown to be the single strongest predictor of distant metastasis, prostate cancer survival, and overall survival after RT. Patient demographic characteristics and tumor staging factors were assessed with regard to associations with the endpoint. Univariate analysis was performed with the χ 2 test for categorical variables and the Wilcoxon test for continuous variables. Multivariable analysis was performed with a multiple logistic regression. Results: The median follow-up was 75 months. Univariate analysis showed that an IBF of less than 18 months was associated with aspirin nonuse (P<.0001), statin nonuse (P<.0001), anticoagulant nonuse (P=.0006), cardiovascular disease (P=.0008), and prostate-specific antigen (continuous) (P=.008) but not with Gleason score, age, RT dose, or T stage. On multivariate analysis, only aspirin nonuse (P=.0012; odds ratio, 2.052 [95% confidence interval, 1.328-3.172]) and statin nonuse (P=.0002; odds ratio, 2.465 [95% confidence interval, 1.529-3.974]) were associated with an IBF of less than 18 months. Conclusions: In patients who received RT for prostate cancer, aspirin or statin nonuse was associated with early biochemical failure, a harbinger of distant metastasis and death. Further study is needed to confirm these findings and to determine the optimal dosing and schedule, as well as the relative

  16. Stereotactic body radiation therapy (S.B.R.T.) for early-stage lung cancer

    International Nuclear Information System (INIS)

    Hiraok, M.; Matsuo, Y.; Nagata, Y.

    2007-01-01

    Stereotactic body radiation therapy (SBRT) is a new treatment modality for early stage non-small-cell lung cancer, and has been developed in the United States, the European Union, and Japan. We started a feasibility study of this therapy in July 1998, using a stereotactic body frame. The eligibility criteria for primary lung cancer were: 1) solitary tumor less than 4 cm (T1-3NOM); 2) inoperable, or the patient refused operation; 3) no necessity for oxygen support; 4) performance status equal to or less than 2; 5) the peripheral tumor which dose constraints of mediastinal organs are maintained. A total dose of 48 Gy was delivered in four fractions in 2 weeks in most patients. Lung toxicity was minimal. No grade II toxicities for spinal cord, bronchus, pulmonary artery, or esophagus were observed. The 3 years overall survival for 32 patients with stage IA, and 13 patients with stage IB were 83% and 72%, respectively. Only one local recurrence was observed in a follow-up of 6 1 months. We retrospectively analyzed 241 patients from 13 Japanese institutions. The local recurrence rate was 20% when the biological equivalent dose (BED) was less than 100 Gy, and 6.5% when the BED was over 100 Gy. Overall survival at 3 years was 42% when the BED was less than 100 Gy, and 46% when it was over 100 Gy. In tumors, which received a BED of more than 100 Gy, overall survival at 3 years was 91% for operable patients, and 50% for inoperable patients. Long-term results, in terms of local control, regional recurrence, survival, and complications, are not yet evaluated. However, this treatment modality is highly expected to be a standard treatment for inoperable patients, and it may be an alternative to lobectomy for operative patients. A prospective trial, which is now ongoing, will, answer these questions. (author)

  17. Systemic therapy for HER2-positive early-stage breast cancer.

    Science.gov (United States)

    Mathew, Aju; Romond, Edward H

    The advent of the targeted monoclonal antbody trastuzumab for treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer marked a revolution in the understanding and management of mammary carcinoma and, in practice, separated this subtype from other kinds of primary breast malignancy. Long term follow-up from the initial large adjuvant trials continue to show remarkably positive results. Currently, at least four additional agents targeting this receptor, using different and complementary mechanisms of action compared with trastuzumab, have been incorporated into clinical trials. The small molecule tyrosine kinase inhibitors lapatinib and neratinib, in addition to the antibody pertuzumab and the antibody-drug conjugate trastuzumab-ematansine, have shown efficacy in metastatic breast cancer and are being evaluated both in neoadjuvant and adjuvant trials for early stage disease. The cytotoxic chemotherapy regimens used in combination with these agents also are evolving and different therapeutic approaches are emerging for patients depending on their relative level of risk from their cancers, thus moving clinical management toward individualized therapy. Much has been learned about managing the toxicities of treatment and pre-operative approaches have provided a means of assessing the sensitivity of individual patients' cancers to specific treatment regimens. This review traces the development of these studies and focuses on improvements in adjuvant and neoadjuvant therapy for patients with HER2-positive disease whose prognosis has changed in the last decade from dire to favorable. A path forward has been set by which the goal of cure is attainable for almost all patients faced with this aggressive form of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. [Early onset pneumonia after successful resuscitation : Incidence after mild invasive hypothermia therapy].

    Science.gov (United States)

    Erath, J W; Hodrius, J; Bushoven, P; Fichtlscherer, S; Zeiher, A M; Seeger, F H; Honold, J

    2017-09-01

    Targeted temperature management (TTM) represents an effective therapy to improve neurologic outcome in patients who survive an out-of-hospital cardiac arrest (OHCA). First publications about this therapy reported a higher incidence of infections in patients who underwent TTM induced by external cooling devices. Whether intravascular cooling devices are also associated with an increased infection rate has not been investigated so far. In a single center retrospective study, the incidence of early onset pneumonia (EOP) in OHCA patients with or without intravascular TTM at 33 °C target temperature for 24 h who survived at least 24 h after admission was analyzed. A total of 68 OHCA survivors (mean age 65 ± 15 years) were included in this analysis. The most common causes of OHCA were myocardial infarction (35 %), primary ventricular fibrillation (24 %), asystole (15 %), and pulmonary embolism (7 %). Of those, 32 patients (48 %) received TTM. The overall incidence of EOP was 38 %. Incidence of EOP did not differ significantly between groups, was more frequent in the group without TTM (42 % vs. 34 %, p = 0.57) and had no impact on mortality (hazard ratio = 1.02; 95 % confidence interval 0.25-4.16; p = 0.97). Intravascular TTM at 33 °C with a cooling catheter is not associated with more infective complications in OHCA patients. This finding underscores the safety of TTM.

  19. The effects of early antithyroid therapy for endogenous subclinical hyperthyroidism in clinical and heart abnormalities.

    Science.gov (United States)

    Sgarbi, José A; Villaça, Fábio G; Garbeline, Benito; Villar, Heloísa E; Romaldini, João H

    2003-04-01

    Subclinical hyperthyroidism has been associated with harmful cardiac effects, but its treatment remains controversial. This study was designed to assess the cardiac effects of the normalization of serum TSH concentration in patients with endogenous subclinical hyperthyroidism. Ten patients (median age, 59 yr; range, 16-72 yr) with normal serum free T(4) and free T(3) concentration and a stable suppression of serum TSH levels were evaluated by Doppler-echocardiography, by standard and 24-h electrocardiography monitoring (Holter), and by the clinical Wayne index. Ten subjects, matched for age and sex, were used as controls. Patients were reevaluated 6 months after achieving stabilized euthyroidism by using methimazole with a median initial dose of 20 mg daily (10-30 mg daily). After reaching euthyroidism, we found a significant decrease in the heart rate (P = 0.008), the total number of beats during 24 h (P = 0.004), and the number of atrial (P = 0.002) and ventricular (P = 0.003) premature beats. Echocardiographical data resulted in a reduction of the left ventricular mass index (P = 0.009), interventricular septum thickness (P = 0.008), and left ventricular posterior wall thickness (P = 0.004) at diastole. Furthermore, the early diastolic peak flow velocity deceleration rate was significantly higher (P = 0.02) in the untreated patients compared with controls. The Wayne clinical index was higher in patients than in controls (P = 0.001) and decreased after treatment (P = 0.004). Serum TSH concentration returned to normal values after 2.5 months (range, 1.0-7.0 months) on methimazole therapy (0.05 vs. 1.42 mU/liter; P = 0.002). Serum free T(4) values were normal in patients before treatment but significantly decreased after reaching the euthyroidism (16.9 vs. 11.5 pmol/liter; P = 0.002). In contrast, serum free T(3) concentration did not differ among the groups. In conclusion, our findings support that early antithyroid therapy should be considered in patients with

  20. Symptom fluctuations, self-esteem, and cohesion during group cognitive behaviour therapy for early psychosis.

    Science.gov (United States)

    Lecomte, Tania; Leclerc, Claude; Wykes, Til

    2018-03-01

    Group cohesion has been linked to positive changes in self-esteem and in symptoms during group psychotherapy in people with psychosis. These changes may be linked to changes in symptoms as fluctuations in self-esteem have been linked to symptom fluctuations. We aimed to determine the relationship between these three factors - group cohesion, self-esteem, and symptoms - during group cognitive behaviour therapy for psychosis (GCBTp). We hypothesized that group cohesion would precede changes in symptoms and self-esteem and that improvements in self-esteem would precede improvements in symptoms. This is an uncontrolled longitudinal study recruiting from a convenience sample within two early psychosis clinics. Sixty-six individuals from first episode of psychosis treatment programmes participated in this study and received 24 sessions of a validated GCBTp protocol. Participants answered a brief questionnaire at the end of each session, measuring their group cohesion, self-esteem, and perception of their symptoms as worse, same, or better than usual. Orthogonal polynomial contrasts for time effects were estimated with a mixed model for repeated measures with a random cluster effect and revealed a quartic trend regarding changes in symptoms over the 24 sessions. Self-esteem, symptoms, and group cohesion were strongly linked during a given session. Also, self-esteem changes predicted changes in symptoms up to two sessions later, and symptoms changes predicted self-esteem changes at the next session. Group cohesion preceded improvements in both self-esteem and symptoms; self-esteem also predicted improvements in group cohesion. These results suggest that self-esteem and symptoms influence each other during therapy, with improvements in one leading to improvements in the other. Group cohesion also appears to be an essential prerequisite to positive changes in self-esteem and symptoms during GCBTp. This study emphasizes the interrelation between self-esteem improvements and

  1. The Extraordinary Progress in Very Early Cancer Diagnosis and Personalized Therapy: The Role of Onco markers and Nano technology

    International Nuclear Information System (INIS)

    Fruscella, M.; Crema, A.; Carloni, G.; Fruscella, M.; Ponzetto, A.

    2016-01-01

    The impact of nano technology on oncology is revolutionizing cancer diagnosis and therapy and largely improving prognosis. This is mainly due to clinical translation of the most recent findings in cancer research, that is, the application of bio- and nano technologies. Cancer genomics and early diagnostics are increasingly playing a key role in developing more precise targeted therapies for most human tumors. In the last decade, accumulation of basic knowledge has resulted in a tremendous breakthrough in this field. Nano oncology, through the discovery of new genetic and epigenetic biomarkers, has facilitated the development of more sensitive biosensors for early cancer detection and cutting-edge multi functionalized nanoparticles for tumor imaging and targeting. In the near future, nano oncology is expected to enable a very early tumor diagnosis, combined with personalized therapeutic approaches.

  2. [Personalized cell therapy for early postoperative bullous keratopathy (experimental proof and clinical results)].

    Science.gov (United States)

    Kasparov, A A; Kasparova, Evg A; Fadeeva, L L; Subbot, A M; Borodina, N V; Kasparova, E A; Kobzova, M V; Musaeva, G M; Pavliuk, A S

    2013-01-01

    The article presents the results of a long-term research on development and clinical application of personalized cell therapy (PCT) for treatment of early postoperative (manifesting within the first 3 months after surgery) bullous keratopathy (BK). The method of intracameral PCT implies in vitro incubation of the patient's blood sample with poly(A:U) stimulator, separation of the serum with activated leukocytes, and injection of the final cell preparation into the anterior chamber. The fundamental part of the research was aimed at a detailed description of the cell preparation and investigation of its possible mechanisms of action. Cytokine and growth factor level in the cell preparation suggested that its high clinical efficacy might be due to its ability to improve regeneration of damaged corneal endothelium. The clinical study was conducted on a group of 52 patients with early BK. A significant effect (smoothing of the Descement's membrane folds, complete resorption of corneal edema, improvement of corneal transparency, reduction of corneal thickness and increase of visual acuity by 0.49 +/- 0.27) was achieved in 44.2% of patients, while partial effect was seen in 21.1% of patients. There was no clinical effect in 34.6% of patients. In those patients who developed significant or partial clinical effect after the PCT, many endotheliocytes appeared to have multiple nuclei (2 and more). In some patients polyploid nuclei persisted for 3-5 years after the treatment. Polyploidy results from incomplete mitosis which might be due to regenerative processes in the endothelium stimulated by the PCT. Obviously, high efficacy and relative simplicity of the method should promote its further clinical introduction.

  3. Emotion recognition in early Parkinson's disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants

    Directory of Open Access Journals (Sweden)

    Lindsey G. McIntosh

    2015-01-01

    Full Text Available Parkinson’s disease (PD is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits. In addition, contrasting this with a group of healthy aging individuals demonstrates changes in emotion processing specific to the degeneration of basal ganglia circuitry in PD. Early PD patients (EPD were recruited from a randomized clinical trial testing the safety and tolerability of deep brain stimulation of the subthalamic nucleus (STN-DBS in early-staged PD. EPD patients were previously randomized to receive optimal drug therapy only (ODT, or drug therapy plus STN-DBS (ODT+DBS. Matched healthy elderly controls (HEC and young controls (HYC also participated in this study. Participants completed two control tasks and three emotion recognition tests that varied in stimulus domain. EPD patients were impaired on all emotion recognition tasks compared to HEC. Neither therapy type (ODT or ODT+DBS nor therapy state (ON/OFF altered emotion recognition performance in this study. Finally, HEC were impaired on vocal emotion recognition relative to HYC, suggesting a decline related to healthy aging. This study supports the existence of impaired emotion recognition early in the PD course, implicating an early disruption of fronto-striatal loops mediating emotional function.

  4. Results of surgical treatment versus chemoradiation therapy in oropharyngeal early tumors

    Directory of Open Access Journals (Sweden)

    Chedid, Helma Maria

    2009-03-01

    Full Text Available Introduction: The epidermoid carcinoma of the upper aerodigestive tract is diagnosed in approximately 40% of the cases of advanced clinical stages. Objective: To evaluate the disease-free interval in patients with clinical stages I and II epidermoid carcinoma who were submitted to surgery or chemoradiation. Method: Retrospective study of the records of 139 patients treated for oropharyngeal epidermoid carcinoma submitted to treatment with curative intent. Among those patients, 38 were classified with early tumors clinical stages I and II. Twenty-seven (71.1% underwent surgical treatment whereas eleven (28.9% were treated with chemoradiation. The mean age was 56.4 years; 31 cases (81.6% were in men and seven (18.4% were in women. Results: Among the eleven patients who were submitted to chemoradiation, 72.7% obtained locoregional control of the disease and their disease-free survival was of 42%. Among the 27 patients operated, 19 remained in Clinical Stages I and II in the histological report and six underwent postoperative radiation therapy. The disease-free interval for two years was of 70%. Conclusion: The patients submitted to the surgery had a better disease-free interval as compared to those submitted to chemoradiation treatment.

  5. Animal-assisted therapy in early childhood schools in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Amanda O. Ferreira

    Full Text Available Abstract: Since ancient times, humans and animals have interacted for different purposes. Animal Assisted Therapy (AAT is used for the assistance and treatment in humans and educational projects where animals are used as co-therapists or co-educators. The use of animals facilitates the process of teaching and learning, and stimulates physical and therapeutic activities. So that knowledge on AAT could be expanded, current study analyzes the opinion of people directly involved in education on AAT implementation as an educational model in early childhood schools in São Paulo, Brazil. Questionnaires were handed out to 10 pedagogical coordinators, 32 teachers, 23 parents and 26 children aged 3-6 years. Results revealed that AAT is not well-known for most interviewees, including pedagogical coordinators, teachers and parents. However, interviewees believe in the benefits of child-pet interactions and are favorable to the implementation of AATs in schools. Projects should be interdisciplinary and must involve professionals from other areas, such as psychologists and veterinarians. Regarding the educational model, interviewees believe in the innovation capacity of AAT and in the possibilities of interdisciplinarity among teachers in the use of animals. Research also demonstrated that children like and support the use of animals in the school.

  6. Cytokines, Fatigue, and Cutaneous Erythema in Early Stage Breast Cancer Patients Receiving Adjuvant Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Vitaliana De Sanctis

    2014-01-01

    Full Text Available We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1 were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5% patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P<0.05. After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001 was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026. A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

  7. Breast cancer in the 21st century: from early detection to new therapies.

    Science.gov (United States)

    Merino Bonilla, J A; Torres Tabanera, M; Ros Mendoza, L H

    The analysis of the causes that have given rise to a change in tendency in the incidence and mortality rates of breast cancer in the last few decades generates important revelations regarding the role of breast screening, the regular application of adjuvant therapies and the change of risk factors. The benefits of early detection have been accompanied by certain adverse effects, even in terms of an excessive number of prophylactic mastectomies. Recently, several updates have been published on the recommendations in breast cancer screening at an international level. On the other hand, the advances in genomics have made it possible to establish a new molecular classification of breast cancer. Our aim is to present an updated overview of the epidemiological situation of breast cancer, as well as some relevant issues from the point of view of diagnosis, such as molecular classification and different strategies for both population-based and opportunistic screening. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Results and survival after photodynamic therapy in early-stage esophageal carcinoma

    Science.gov (United States)

    Spinelli, Pasquale; Mancini, Andrea; dal Fante, Marco; Meroni, Emmanuele; Jasinskas, Algirdas

    1996-01-01

    From January 1985 to December 1994, 23 early stage carcinomas of the esophagus were treated by photodynamic therapy in 21 patients. The stage of the tumors was assessed by esophagoscopy with multiple biopsies, CT scan and, from June 1991, also by endoscopic ultrasonography: 7 lesions were classified as carcinoma in situ (Tis) and 16 as invasive (T1). The photosensitizers used for PDT were hematoporphyrin derivative 3 mg/kg in 4 patients and dihematoporphyrin ether 2 mg/kg in 17. Light irradiation was performed using an Argon-dye laser system at a wavelength of 630 nm with an average energy of 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. A complete response was achieved in 17/23 (74%) tumors, 15/21 (71%) patients. In the follow-up period from 6 to 78 months (median 36 months) 3 recurrences occurred 6, 12, and 14 months after PDT, respectively. Seven patients died due to concomitant diseases, not related to tumor progression. The actuarial survival rate was 95%, 75% and 37% at 1, 3, and 5 years, respectively. Complications included 1 case of sunburn and 2 cases of esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage.

  9. Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

    Science.gov (United States)

    Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

    2017-06-28

    Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

  10. Cost-utility of COBRA-light versus COBRA therapy in patients with early rheumatoid arthritis: the COBRA-light trial

    NARCIS (Netherlands)

    ter Wee, Marieke M.; Coupé, Veerle M. H.; den Uyl, Debby; Blomjous, Birgit S.; Kooijmans, Esmee; Kerstens, Pit J. S. M.; Nurmohamed, Mike T.; van Schaardenburg, Dirkjan; Voskuyl, Alexandre E.; Boers, Maarten; Lems, Willem F.

    2017-01-01

    To evaluate if COmbinatie therapie Bij Reumatoïde Artritis (COBRA)-light therapy is cost-effective in treating patients with early rheumatoid arthritis (RA) compared with COBRA therapy. This economic evaluation was performed next to the open-label, randomised non-inferiority COBRA-light trial in 164

  11. Psychological morbidities in adolescent and young adult blood cancer patients during curative-intent therapy and early survivorship.

    Science.gov (United States)

    Muffly, Lori S; Hlubocky, Fay J; Khan, Niloufer; Wroblewski, Kristen; Breitenbach, Katherine; Gomez, Joseline; McNeer, Jennifer L; Stock, Wendy; Daugherty, Christopher K

    2016-03-15

    Adolescents and young adults (AYAs) with cancer face unique psychosocial challenges. This pilot study was aimed at describing the prevalence of psychological morbidities among AYAs with hematologic malignancies during curative-intent therapy and early survivorship and at examining provider perceptions of psychological morbidities in their AYA patients. Patients aged 15 to 39 years with acute leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma who were undergoing curative-intent therapy (on-treatment group) or were in remission within 2 years of therapy completion (early survivors) underwent a semistructured interview that incorporated measures of anxiety, depression, and posttraumatic stress (PTS). A subset of providers (n = 15) concomitantly completed a survey for each of the first 30 patients enrolled that evaluated their perception of each subject's anxiety, depression, and PTS. Sixty-one of 77 eligible AYAs participated. The median age at diagnosis was 26 years (range, 15-39 years), 64% were male, and 59% were non-Hispanic white. On-treatment demographics differed significantly from early-survivor demographics only in the median time from diagnosis to interview. Among the 61 evaluable AYAs, 23% met the criteria for anxiety, 28% met the criteria for depression, and 13% met the criteria for PTS; 46% demonstrated PTS symptomatology. Thirty-nine percent were impaired in 1 or more psychological domains. Psychological impairments were as frequent among early survivors as AYAs on treatment. Provider perceptions did not significantly correlate with patient survey results. AYAs with hematologic malignancies experience substantial psychological morbidities while they are undergoing therapy and during early survivorship, with more than one-third of the patients included in this study meeting the criteria for anxiety, depression, or traumatic stress. This psychological burden may not be accurately identified by their oncology providers. © 2016 American Cancer Society.

  12. Early orthopedic correction of skeletal Class III malocclusion using combined reverse twin block and face mask therapy

    Directory of Open Access Journals (Sweden)

    Vinay Kumar Chugh

    2015-01-01

    Full Text Available A 6-year 8-month-old girl presented with a moderate Class III malocclusion characterized by mid-face deficiency and an anterior cross bite. In the first phase, the patient was treated with combination of reverse twin block and facemask therapy. In phase two, fixed appliances were placed in the permanent dentition. The post treatment results were good and a favorable growth tendency could be observed. The correction of the Class III malocclusion occurred by a combination of skeletal and dental improvements. This report shows successful correction of skeletal Class III malocclusion in the early transitional dentition using combination therapy.

  13. Early experience of proton beam therapy combined with chemotherapy for locally advanced oropharyngeal cancer

    International Nuclear Information System (INIS)

    Ishikawa, Youjirou; Nakamura, Tatsuya; Takada, Akinori; Takayama, Kanako; Makita, Chiyoko; Suzuki, Motohisa; Azami, Yusuke; Kikuchi, Yasuhiro; Fuwa, Nobukazu

    2013-01-01

    Between 2009 and 2012, 10 patients with advanced oropharyngeal cancer underwent proton therapy combined with chemotherapy. The initial results of this therapy were 8 complete response (CR) and 2 partial response (PR), local recurrence was detected 1 patient. Proton beam therapy combined with chemotherapy is thought to be an effective treatment for locally advanced oropharyngeal cancer. (author)

  14. Predictors of receiving therapy among very low birth weight 2-year olds eligible for Part C early intervention in Wisconsin.

    Science.gov (United States)

    McManus, Beth Marie; Robert, Stephanie; Albanese, Aggie; Sadek-Badawi, Mona; Palta, Mari

    2013-07-11

    The Individuals with Disabilities Education Act (Part C) authorizes states to establish systems to provide early intervention services (e.g., therapy) for children at risk, with the incentive of federal financial support. This study examines family and neighborhood characteristics associated with currently utilizing physical, occupational, or speech therapy among very low birthweight (VLBW) 2-year-old children who meet Wisconsin eligibility requirements for early intervention services (EI) due to developmental delay. This cross-sectional analysis used data from the Newborn Lung Project, a regional cohort study of VLBW infants hospitalized in Wisconsin's newborn intensive care units during 2003-2004. We included the 176 children who were age two at follow-up, and met Wisconsin state eligibility requirements for EI based on developmental delay. Exact logistic regression was used to describe child and neighborhood socio-demographic correlates of parent-reported receipt of therapy. Among VLBW children with developmental delay, currently utilizing therapy was higher among children with Medicaid (aOR = 5.3, 95% CI: 1.3, 28.3) and concomitant developmental disability (aOR = 5.2, 95% CI: 2.1, 13.3) and lower for those living in a socially more disadvantaged neighborhood (aOR=0.48, 95% CI: 0.21, 0.98, per tertile). Among a sample of VLBW 2-year olds with developmental delays who are EI-eligible in WI, 4 out of 5 were currently receiving therapy, per parent report. Participation in Medicaid positively influences therapy utilization. Children with developmental difficulties who live in socially disadvantaged neighborhoods are at highest risk for not receiving therapy.

  15. Computerised mirror therapy with Augmented Reflection Technology for early stroke rehabilitation: clinical feasibility and integration as an adjunct therapy.

    Science.gov (United States)

    Hoermann, Simon; Ferreira Dos Santos, Luara; Morkisch, Nadine; Jettkowski, Katrin; Sillis, Moran; Devan, Hemakumar; Kanagasabai, Parimala S; Schmidt, Henning; Krüger, Jörg; Dohle, Christian; Regenbrecht, Holger; Hale, Leigh; Cutfield, Nicholas J

    2017-07-01

    New rehabilitation strategies for post-stroke upper limb rehabilitation employing visual stimulation show promising results, however, cost-efficient and clinically feasible ways to provide these interventions are still lacking. An integral step is to translate recent technological advances, such as in virtual and augmented reality, into therapeutic practice to improve outcomes for patients. This requires research on the adaptation of the technology for clinical use as well as on the appropriate guidelines and protocols for sustainable integration into therapeutic routines. Here, we present and evaluate a novel and affordable augmented reality system (Augmented Reflection Technology, ART) in combination with a validated mirror therapy protocol for upper limb rehabilitation after stroke. We evaluated components of the therapeutic intervention, from the patients' and the therapists' points of view in a clinical feasibility study at a rehabilitation centre. We also assessed the integration of ART as an adjunct therapy for the clinical rehabilitation of subacute patients at two different hospitals. The results showed that the combination and application of the Berlin Protocol for Mirror Therapy together with ART was feasible for clinical use. This combination was integrated into the therapeutic plan of subacute stroke patients at the two clinical locations where the second part of this research was conducted. Our findings pave the way for using technology to provide mirror therapy in clinical settings and show potential for the more effective use of inpatient time and enhanced recoveries for patients. Implications for Rehabilitation Computerised Mirror Therapy is feasible for clinical use Augmented Reflection Technology can be integrated as an adjunctive therapeutic intervention for subacute stroke patients in an inpatient setting Virtual Rehabilitation devices such as Augmented Reflection Technology have considerable potential to enhance stroke rehabilitation.

  16. Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia.

    Science.gov (United States)

    Saint-Laurent, Celine; Garcia, Stephanie; Sarrazy, Vincent; Dumas, Karine; Authier, Florence; Sore, Sophie; Tran, Albert; Gual, Philippe; Gennero, Isabelle; Salles, Jean-Pierre; Gouze, Elvire

    2018-01-01

    Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a major health problem in these patients, and is associated to life-threatening complications including increasing risk of cardiovascular pathologies. We have thus decided to study obesity in patients and to use the mouse model to evaluate if soluble FGFR3 therapy, an innovative treatment approach for achondroplasia, could also impact the development of this significant complication. To achieve this, we have first fully characterized the metabolic deregulations in these patients by conducting a longitudinal retrospective study, in children with achondroplasia Anthropometric, densitometric measures as well as several blood parameters were recorded and compared between three age groups ranging from [0-3], [4-8] and [9-18] years old. Our results show unexpected results with the development of an atypical obesity with preferential fat deposition in the abdomen that is remarkably not associated with classical complications of obesity such as diabetes or hypercholosterolemia. Because it is not associated with diabetes, the atypical obesity has not been studied in the past even though it is recognized as a real problem in these patients. These results were validated in a murine model of achondroplasia (Fgfr3ach/+) where similar visceral adiposity was observed. Unexpected alterations in glucose metabolism were highlighted during high-fat diet. Glucose, insulin or lipid levels remained low, without the development of diabetes. Very interestingly, in achondroplasia mice treated with soluble FGFR3 during the growth period (from D3 to D22), the development of these metabolic deregulations was prevented in adult animals (between 4 and 14 weeks of age). The lean-over-fat tissues ratio was

  17. Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia

    Science.gov (United States)

    Sarrazy, Vincent; Dumas, Karine; Authier, Florence; Sore, Sophie; Tran, Albert; Gual, Philippe; Gennero, Isabelle; Salles, Jean-Pierre; Gouze, Elvire

    2018-01-01

    Background Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a major health problem in these patients, and is associated to life-threatening complications including increasing risk of cardiovascular pathologies. We have thus decided to study obesity in patients and to use the mouse model to evaluate if soluble FGFR3 therapy, an innovative treatment approach for achondroplasia, could also impact the development of this significant complication. Methods and findings To achieve this, we have first fully characterized the metabolic deregulations in these patients by conducting a longitudinal retrospective study, in children with achondroplasia Anthropometric, densitometric measures as well as several blood parameters were recorded and compared between three age groups ranging from [0–3], [4–8] and [9–18] years old. Our results show unexpected results with the development of an atypical obesity with preferential fat deposition in the abdomen that is remarkably not associated with classical complications of obesity such as diabetes or hypercholosterolemia. Because it is not associated with diabetes, the atypical obesity has not been studied in the past even though it is recognized as a real problem in these patients. These results were validated in a murine model of achondroplasia (Fgfr3ach/+) where similar visceral adiposity was observed. Unexpected alterations in glucose metabolism were highlighted during high-fat diet. Glucose, insulin or lipid levels remained low, without the development of diabetes. Very interestingly, in achondroplasia mice treated with soluble FGFR3 during the growth period (from D3 to D22), the development of these metabolic deregulations was prevented in adult animals (between 4 and 14 weeks of age

  18. Mid-dose rate intracavitary therapy for uterine cervix cancer with a Selectron; An early experience of Osaka University

    Energy Technology Data Exchange (ETDEWEB)

    Teshima, Teruki; Inoue, Takehiro; Sasaki, Shigeru; Ohtani, Masatoshi; Kozuka, Takahiro; Inoue, Toshihiko; Ikeda, Hiroshi; Yamazaki, Hideya (Osaka Univ. (Japan). Faculty of Medicine); Murayama, Shigeyuki

    1993-05-01

    From May 1991 through September 1992, a total of 17 previously untreated patients with invasive uterine cervix cancer and with intact uterus were treated with mid-dose rate intracavitary therapy administered with a Selectron. Early primary tumor responses for all patients were complete. No acute or subacute radiation injury was observed except one patient with aplastic anemia who developed rectal ulcer. Two patients of Stage IIIb died from tumor because of local, paraaortic lymph node and distant metastases. Our early experience concluded that Selectron MDR can be used for cervix cancer patients as safely and effectively as our previously used high-dose rate machine. (author).

  19. Heart protection by combination therapy with esmolol and milrinone at late-ischemia and early reperfusion.

    Science.gov (United States)

    Huang, Ming-He; Wu, Yewen; Nguyen, Vincent; Rastogi, Saurabh; McConnell, Bradley K; Wijaya, Cori; Uretsky, Barry F; Poh, Kian-Keong; Tan, Huay-Cheem; Fujise, Kenichi

    2011-06-01

    The present study determined whether late-ischemia/early reperfusion therapy with the β(1)-adrenergic receptor (AR) blocker esmolol and phosphodiesterase III inhibitor milrinone reduced left ventricular (LV) myocardial infarct size (IS). In an ischemia/reperfusion rat model (30-min ischemia/4-hr reperfusion), esmolol, milrinone or esmolol + milrinone were intravenous (IV) infused over 10 min (from the last 5 min of ischemia to the first 5 min of reperfusion). LV-IS were 48.9 ± 8.9%, 41.5 ± 5.4%, 25.8 ± 7.7% and 16.8 ± 7.3% for saline, esmolol, milrinone, and esmolol + milrinone, respectively (n = 12/group). Esmolol + milrinone further reduced LV-IS compared with esmolol or milrinone alone (p milrinone was eliminated in the presence of protein kinase A-(PKA)-inhibitor (Rp-cAMPS) or Akt-inhibitor (AKT 1/2 kinase inhibitor). In mixed rat ventricular cardiomyocyte cultures, intra-ischemic application of esmolol, milrinone or esmolol + milrinone reduced myocyte death rates by 5.5%, 13.3%, and 16.8%, respectively, compared with saline (p milrinone was abrogated in the presence of PKA-inhibitor or Akt-inhibitor. Esmolol, milrinone or esmolol + milrinone increased myocardial PKA activity by 22%, 28% and 59%, respectively, compared with saline (n = 6, p milrinone or esmolol + milrinone, there were 1.7-, 2.7-, and 6-fold increase in tissue pAkt levels, respectively. This esmolol + milrinone induced pAkt activation was abolished in the presence of PKA inhibitor. Esmolol, milrinone and esmolol + milrinone reduced myocyte apoptosis rates by 22%, 37% and 60%, respectively, compared with saline (p milrinone additively reduces LV-IS associated with robust activation of myocardial PKA and subsequent Akt-antiapoptotic pathway.

  20. Prognosis for Mammographically Occult, Early-Stage Breast Cancer Patients Treated With Breast-Conservation Therapy

    International Nuclear Information System (INIS)

    Yang, Tzu-I. J.; Yang Qifeng; Haffty, Bruce G.; Moran, Meena S.

    2010-01-01

    Purpose: To compare mammographically occult (MamOcc) and mammographically positive (MamPos) early-stage breast cancer patients treated with breast-conservation therapy (BCT), to analyze differences between the two cohorts. Methods and Materials: Our two cohorts consisted of 214 MamOcc and 2168 MamPos patients treated with BCT. Chart reviews were conducted to assess mammogram reports and method of detection. All clinical-pathologic and outcome parameters were analyzed to detect differences between the two cohorts. Results: Median follow-up was 7 years. There were no differences in final margins, T stage, nodal status, estrogen/progesterone receptor status, or 'triple-negative' status. Significant differences included younger age at diagnosis (p o histology (p < 0.0001). At 10 years, the differences in overall survival, cause-specific survival, and distant relapse between the two groups did not differ significantly. The MamOcc cohort had more breast relapses (15% vs. 8%; p = 0.0357), but on multivariate analysis this difference was not significant (hazard ratio 1.0, 95% confidence interval 0.993-1.007, p = 0.9296). Breast relapses were mammographically occult in 32% of the MamOcc and 12% of the MamPos cohorts (p = 0.0136). Conclusions: Although our study suggests that there are clinical-pathologic variations for the MamOcc cohort vs. MamPos patients that may ultimately affect management, breast relapse after BCT was not significantly different. Breast recurrences were more often mammographically occult in the MamOcc cohort; consideration should be given to closer follow-up and alternative imaging strategies (ultrasound, breast MRI) for routine posttreatment examination. To our knowledge, this represents the largest series addressing the prognostic significance of MamOcc cancers treated with BCT.

  1. Early effects of modern electroconvulsive therapy on subjective memory in patients with mania or depression

    Science.gov (United States)

    Bag, Sevda; Canbek, Ozge; Atagun, Ilhan Murat; Kutlar, Tarik Mehmet

    2016-01-01

    Context: Although electroconvulsive therapy (ECT) is considered a very effective tool for the treatment of psychiatric diseases, memory disturbances are among the most important adverse effects. Aims: This study aimed to assess prospectively early subjective memory complaints in depressive and manic patients due to bilateral, brief-pulse ECT, at different stages of the treatment, compare the associations between psychiatric diagnosis, sociodemographic characteristics, and ECT characteristics. Settings and Design: This prospective study was done with patients undergoing ECT between November 2008 and April 2009 at a tertiary care psychiatry hospital of 2000 beds. Materials and Methods: A total of 140 patients, scheduled for ECT with a diagnosis of bipolar disorder (depressive or manic episode) or unipolar depression according to Diagnostic and Statistical Manual of Mental Disorders IV diagnostic criteria, were included in the study and invited to complete the Squire Subjective Memory Questionnaire (SSMQ) before ECT, after the first and third sessions and end of ECT treatment. Statistical Analysis: Mean values were compared with the Kruskal–Wallis test and comparison of the longitudinal data was performed with a nonparametric longitudinal data analysis method, F1_LD_F1 design. Results: SSMQ scores of the patients before ECT were zero. SSMQ scores showed a decrease after the first and third ECT sessions and before discharge, showing a memory disturbance after ECT and were significantly less severe in patients with mania in comparison to those with depression. Conclusions: These findings suggest an increasing degree of subjective memory complaints with bilateral brief-pulse ECT parallel to the increasing number of ECT sessions. PMID:27385854

  2. Molecular features of renal cell carcinoma: early diagnostics and perspectives for therapy

    Directory of Open Access Journals (Sweden)

    O. V. Kovaleva

    2014-01-01

    Full Text Available Kidney cancer (renal cell carcinoma is one of the major problems of modern urological oncology. In Russia renal cell carcinoma accountsfor 4.3 % of all cancers. The global incidence of renal cell carcinoma has increased over the past two decades. Worldwide renal cell carcinoma accounts for 3.6 % of all cancers and is 10th frequent malignancy. For some malignancies, for instance tumours of prostate, there are markers known that allowed improved early diagnostics. Kidney cancer, however, remains to be hard to diagnose and to treat, since the symptoms can be detected on advanced stages of the disease. In Russia 75.4 % of renal cell carcinoma cases detected at the stage of local and locally advanced disease. Though there are various target drugs on the market aimed to treat this disease, the results of renal cell carcinoma treatment did not reach any substantial success. Most of existing target drugs for kidney cancer treatment include inhibitors of a single signalingpathway regulated by VHL1, which expression is lost in the vast majority of renal-cell carcinomas. Till now existing drugs did not reach sufficient efficacy. Therefore, it is highly important to search for new signaling pathways, regulating such cellular processes as proliferation, migration and apoptosis. Further, prognostic markers and therapy targets identified so far are not sufficient and poorly specific. Therefore identification and validation of new markers, and especially new specific targets for the treatment of kindey oncopathologies is highly important and timely task.

  3. A Novel Therapy for People Who Attempt Suicide and Why We Need New Models of Suicide

    Directory of Open Access Journals (Sweden)

    Konrad Michel

    2017-03-01

    Full Text Available This paper presents a model of suicidal behaviour based on suicide as a goal-directed action, and its implications. An action theoretical model has guided the authors in the development of a brief therapy for individuals who attempt suicide (ASSIP—Attempted Suicide Short Intervention Program. Key elements are an early therapeutic alliance, narrative interviewing, psychoeducation, a joint case conceptualization, safety planning, and regular letters over 24 months. In a randomized controlled trial, ASSIP was highly effective in reducing the risk of suicide reattempts. The therapeutic elements in this treatment are described and possible implications for future directions in clinical suicide prevention discussed.

  4. Prospective randomized study of arthroscopic rotator cuff repair using an early versus delayed postoperative physical therapy protocol.

    Science.gov (United States)

    Cuff, Derek J; Pupello, Derek R

    2012-11-01

    This study evaluated patient outcomes and rotator cuff healing after arthroscopic rotator cuff repair using a postoperative physical therapy protocol with early passive motion compared with a delayed protocol that limited early passive motion. The study enrolled 68 patients (average age, 63.2 years) who met inclusion criteria. All patients had a full-thickness crescent-shaped tear of the supraspinatus that was repaired using a transosseous equivalent suture-bridge technique along with subacromial decompression. In the early group, 33 patients were randomized to passive elevation and rotation that began at postoperative day 2. In the delayed group, 35 patients began the same protocol at 6 weeks. Patients were monitored clinically for a minimum of 12 months, and rotator cuff healing was assessed using ultrasound imaging. Both groups had similar improvements in preoperative to postoperative American Shoulder and Elbow Surgeons scores (early group: 43.9 to 91.9, P rotator cuff healing, or range of motion between the early and delayed groups. Patients in the early group and delayed group both demonstrated very similar outcomes and range of motion at 1 year. There was a slightly higher rotator cuff healing rate in the delayed passive range of motion group compared with the early passive range of motion group (91% vs 85%). Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  5. Computer-assisted detection (CAD) methodology for early detection of response to pharmaceutical therapy in tuberculosis patients

    Science.gov (United States)

    Lieberman, Robert; Kwong, Heston; Liu, Brent; Huang, H. K.

    2009-02-01

    The chest x-ray radiological features of tuberculosis patients are well documented, and the radiological features that change in response to successful pharmaceutical therapy can be followed with longitudinal studies over time. The patients can also be classified as either responsive or resistant to pharmaceutical therapy based on clinical improvement. We have retrospectively collected time series chest x-ray images of 200 patients diagnosed with tuberculosis receiving the standard pharmaceutical treatment. Computer algorithms can be created to utilize image texture features to assess the temporal changes in the chest x-rays of the tuberculosis patients. This methodology provides a framework for a computer-assisted detection (CAD) system that may provide physicians with the ability to detect poor treatment response earlier in pharmaceutical therapy. Early detection allows physicians to respond with more timely treatment alternatives and improved outcomes. Such a system has the potential to increase treatment efficacy for millions of patients each year.

  6. Expectations and beliefs in science communication: Learning from three European gene therapy discussions of the early 1990s.

    Science.gov (United States)

    Meyer, Gitte

    2016-04-01

    There is widespread agreement that the potential of gene therapy was oversold in the early 1990s. This study, however, comparing written material from the British, Danish and German gene therapy discourses of the period finds significant differences: Over-optimism was not equally strong everywhere; gene therapy was not universally hyped. Against that background, attention is directed towards another area of variation in the material: different basic assumptions about science and scientists. Exploring such culturally rooted assumptions and beliefs and their possible significance to science communication practices, it is argued that deep beliefs may constitute drivers of hype that are particularly difficult to deal with. To participants in science communication, the discouragement of hype, viewed as a practical-ethical challenge, can be seen as a learning exercise that includes critical attention to internalised beliefs. © The Author(s) 2014.

  7. Early sensory re-education of the hand after peripheral nerve repair based on mirror therapy: a randomized controlled trial

    Science.gov (United States)

    Paula, Mayara H.; Barbosa, Rafael I.; Marcolino, Alexandre M.; Elui, Valéria M. C.; Rosén, Birgitta; Fonseca, Marisa C. R.

    2016-01-01

    BACKGROUND: Mirror therapy has been used as an alternative stimulus to feed the somatosensory cortex in an attempt to preserve hand cortical representation with better functional results. OBJECTIVE: To analyze the short-term functional outcome of an early re-education program using mirror therapy compared to a late classic sensory program for hand nerve repair. METHOD: This is a randomized controlled trial. We assessed 20 patients with median and ulnar nerve and flexor tendon repair using the Rosen Score combined with the DASH questionnaire. The early phase group using mirror therapy began on the first postoperative week and lasted 5 months. The control group received classic sensory re-education when the protective sensation threshold was restored. All participants received a patient education booklet and were submitted to the modified Duran protocol for flexor tendon repair. The assessments were performed by the same investigator blinded to the allocated treatment. Mann-Whitney Test and Effect Size using Cohen's d score were used for inter-group comparisons at 3 and 6 months after intervention. RESULTS: The primary outcome (Rosen score) values for the Mirror Therapy group and classic therapy control group after 3 and 6 months were 1.68 (SD=0.5); 1.96 (SD=0.56) and 1.65 (SD=0.52); 1.51 (SD=0.62), respectively. No between-group differences were observed. CONCLUSION: Although some clinical improvement was observed, mirror therapy was not shown to be more effective than late sensory re-education in an intermediate phase of nerve repair in the hand. Replication is needed to confirm these findings. PMID:26786080

  8. Early sensory re-education of the hand after peripheral nerve repair based on mirror therapy: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Mayara H. Paula

    2016-02-01

    Full Text Available BACKGROUND: Mirror therapy has been used as an alternative stimulus to feed the somatosensory cortex in an attempt to preserve hand cortical representation with better functional results. OBJECTIVE: To analyze the short-term functional outcome of an early re-education program using mirror therapy compared to a late classic sensory program for hand nerve repair. METHOD: This is a randomized controlled trial. We assessed 20 patients with median and ulnar nerve and flexor tendon repair using the Rosen Score combined with the DASH questionnaire. The early phase group using mirror therapy began on the first postoperative week and lasted 5 months. The control group received classic sensory re-education when the protective sensation threshold was restored. All participants received a patient education booklet and were submitted to the modified Duran protocol for flexor tendon repair. The assessments were performed by the same investigator blinded to the allocated treatment. Mann-Whitney Test and Effect Size using Cohen's d score were used for inter-group comparisons at 3 and 6 months after intervention. RESULTS: The primary outcome (Rosen score values for the Mirror Therapy group and classic therapy control group after 3 and 6 months were 1.68 (SD=0.5; 1.96 (SD=0.56 and 1.65 (SD=0.52; 1.51 (SD=0.62, respectively. No between-group differences were observed. CONCLUSION: Although some clinical improvement was observed, mirror therapy was not shown to be more effective than late sensory re-education in an intermediate phase of nerve repair in the hand. Replication is needed to confirm these findings.

  9. Assessment of Early Toxicity and Response in Patients Treated With Proton and Carbon Ion Therapy at the Heidelberg Ion Therapy Center Using the Raster Scanning Technique

    Energy Technology Data Exchange (ETDEWEB)

    Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna; Jensen, Alexandra [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Haberer, Thomas [Heidelberg Ion Therapy Center, Heidelberg (Germany); Jaekel, Oliver [Heidelberg Ion Therapy Center, Heidelberg (Germany); Department of Medical Physics, German Cancer Research Center (DKFZ), Heidelberg (Germany); Muenter, Marc W.; Welzel, Thomas; Debus, Juergen [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Combs, Stephanie E., E-mail: Stephanie.Combs@med.uni-hedielberg.de [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany)

    2011-12-01

    Puropose: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Patients and Methods: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. Results: In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Conclusions: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.

  10. Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Eric S Rosenberg

    2010-05-01

    Full Text Available An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG A5187 was a phase I/II, randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00-VP in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1 infection and had HIV-1 RNA<50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17-23 weeks after treatment discontinuation.Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo recipients were 3.5 and 3.7 log(10 HIV-1 RNA copies/mL, respectively.The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP was safe but poorly immunogenic in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo recipients following treatment interruption. However, median viral load set-points in both groups were lower than in historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and supporting the safety of

  11. Early changes of parotid density and volume predict modifications at the end of therapy and intensity of acute xerostomia

    International Nuclear Information System (INIS)

    Belli, Maria Luisa; Broggi, Sara; Scalco, Elisa; Rizzo, Giovanna; Sanguineti, Giuseppe; Fiorino, Claudio; Cattaneo, Giovanni Mauro; Dinapoli, Nicola; Valentini, Vincenzo; Ricchetti, Francesco

    2014-01-01

    To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer. Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients. A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher ''mean'' acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / 3 /day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia. (orig.) [de

  12. Person-Centered Therapy: A Philosophy to Support Early Childhood Education

    Science.gov (United States)

    Boyer, Wanda

    2016-01-01

    Person-centered therapy (PCT) comes from the experiential and relationship-oriented therapy tradition. It is considered to be a third force in therapeutic engagement, along with the psychoanalytic and behavioral approaches. PCT is based on faith in and empowerment of human beings to be joyful, creative, self-fulfilled and willing and able to…

  13. Hormone therapy and radiotherapy for early prostate cancer: A utility-adjusted number needed to treat (NNT) analysis

    International Nuclear Information System (INIS)

    Jani, Ashesh B.; Kao, Johnny; Heimann, Ruth; Hellman, Samuel

    2005-01-01

    Purpose: To quantify, using the number needed to treat (NNT) methodology, the benefit of short-term (≤6 months) hormone therapy adjuvant to radiotherapy in the group of patients with early (clinical stage T1-T2c) prostate cancer. Methods and materials: The absolute biochemical control benefit for the use of hormones adjuvant to radiotherapy in early-stage disease was determined by literature review. A model was developed to estimate the utility-adjusted survival detriment due to the side effects of hormone therapy. The NNTs before and after the incorporation of hormone sequelae were computed; the sign and magnitude of the NNTs were used to gauge the effect of the hormones. Results: The absolute NNT analysis, based on summarizing the results of 8 reports including a total of 3652 patients, demonstrated an advantage to the addition of hormones for the general early-stage prostate cancer population as well as for all prognostic groups. After adjustment for hormone-induced functional loss, the advantage of hormones remained considerable in the high- and intermediate-risk groups, with the utility-adjusted NNT becoming weakened in the low-risk group when the utility compromise from complications of hormones was assumed to be considerable. Conclusions: Short-term hormone therapy seems to be beneficial for selected early-stage prostate cancer patients. The advantage seems to be greatest in the intermediate- and high-risk groups; with current follow-up, the side effects of hormones may outweigh their benefit in certain clinical situations in the favorable group. The present investigation demonstrates the significant role of the NNT technique for oncologic and radiotherapeutic management decisions when treatment complications need to be considered and balanced with the beneficial effects of the treatment

  14. Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment.

    Science.gov (United States)

    Sinha, Sanjeev; Shekhar, Rahul C; Singh, Gurjeet; Shah, Nipam; Ahmad, Hafiz; Kumar, Narendra; Sharma, Surendra K; Samantaray, J C; Ranjan, Sanjai; Ekka, Meera; Sreenivas, Vishnu; Mitsuyasu, Ronald T

    2012-07-31

    For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. CTRI/2011/12/002260.

  15. Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment

    Directory of Open Access Journals (Sweden)

    Sinha Sanjeev

    2012-07-01

    Full Text Available Abstract Background For antiretroviral therapy (ART naive human immunodeficiency virus (HIV infected adults suffering from tuberculosis (TB, there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART after starting antituberculosis treatment (ATT, in order to minimize mortality, HIV disease progression, and adverse events. Methods In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART and 62 after 8-12 weeks (delayed ART of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045. Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05. Rates of adverse events were similar. Interpretation Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Trial registration CTRI/2011/12/002260

  16. Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.

    Science.gov (United States)

    Mall, Marcus A; Graeber, Simon Y; Stahl, Mirjam; Zhou-Suckow, Zhe

    2014-07-01

    Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Early Tissue Effects of Stereotactic Body Radiation Therapy for Spinal Metastases

    NARCIS (Netherlands)

    Steverink, Jasper G.; Willems, Stefan M.; Philippens, Marielle E.P.; Kasperts, Nicolien; Eppinga, Wietse S.C.; Versteeg, Anne L.; van der Velden, Joanne M.; Faruqi, Salman; Sahgal, Arjun; Verlaan, Jorrit Jan

    2018-01-01

    Purpose: Stereotactic body radiation therapy (SBRT) is a highly effective and potentially ablative treatment for complex spinal metastases. Recent data have suggested radiobiologic effects of SBRT that expand beyond the traditional concept of DNA damage. Antitumor immunity, vascular damage leading

  18. Bone metastases of differentiated thyroid cancer: the importance of early diagnosis and {sup 131}I therapy on prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Zanotti-Fregonara, P. [CEA, DSV, I2BM, SHFJ, UMNRC, Orsay (France); Rubello, D. [Santa Maria Misericordia Hosp, Rovigo (Italy); Hindie, E. [Hop StLouis, Paris (France)

    2008-07-01

    Complete text of publication follows: Distant metastases are found at diagnosis or during follow-up in 10%-15% of patients with differentiated thyroid cancer. Bone is the second most commonly involved site. Patients with bone metastases, whether isolated or associated with lung metastases, have a markedly poor prognosis. Ten-year survival rates range from 13% to 21%. Given such poor prognosis, the use of {sup 131}I therapy has been questioned. However, it might well be that poor prognosis of bone metastases can be overcome if {sup 131}I therapy is delivered at an early stage, when tumor burden is small, as previously demonstrated for pulmonary metastases. A review of a large series of patients showed that only rarely were bone metastases diagnosed at an early stage. Among 109 patients with bone metastases reported by Bernier et al., only 4 had both radioiodine uptake and a negative standard radiography examination. Similarly, Durante et al. reported that only 8 of 115 patients had negative radiography findings at presentation. Prognosis may improve if bone metastases are detected earlier. In a recent study, bone metastases were first detected by {sup 131}I scanning in 8 of 16 patients, when complementary radiologic studies were negative. Six of these patients showed an excellent response to {sup 131}I therapy. Today, the nuclear medicine community is well armed for this challenge toward earlier diagnosis. Postsurgery thyroid remnant ablation is more widely used. The {sup 131}I whole body scan associated with thyroid remnant ablation after thyroidectomy has a major role in early diagnosis of functioning distant metastases at a time when complementary imaging techniques (CT, MRI, bone scanning) are often still showing negative findings. Early diagnosis of specific {sup 131}I-avid bone foci will be improved with the advent and generalization of SPECT/CT. When early diagnosis is achieved, repeated {sup 131}I therapy can be effective by targeting not only visible

  19. Bone metastases of differentiated thyroid cancer: the importance of early diagnosis and 131I therapy on prognosis

    International Nuclear Information System (INIS)

    Zanotti-Fregonara, P.; Rubello, D.; Hindie, E.

    2008-01-01

    Complete text of publication follows: Distant metastases are found at diagnosis or during follow-up in 10%-15% of patients with differentiated thyroid cancer. Bone is the second most commonly involved site. Patients with bone metastases, whether isolated or associated with lung metastases, have a markedly poor prognosis. Ten-year survival rates range from 13% to 21%. Given such poor prognosis, the use of 131 I therapy has been questioned. However, it might well be that poor prognosis of bone metastases can be overcome if 131 I therapy is delivered at an early stage, when tumor burden is small, as previously demonstrated for pulmonary metastases. A review of a large series of patients showed that only rarely were bone metastases diagnosed at an early stage. Among 109 patients with bone metastases reported by Bernier et al., only 4 had both radioiodine uptake and a negative standard radiography examination. Similarly, Durante et al. reported that only 8 of 115 patients had negative radiography findings at presentation. Prognosis may improve if bone metastases are detected earlier. In a recent study, bone metastases were first detected by 131 I scanning in 8 of 16 patients, when complementary radiologic studies were negative. Six of these patients showed an excellent response to 131 I therapy. Today, the nuclear medicine community is well armed for this challenge toward earlier diagnosis. Postsurgery thyroid remnant ablation is more widely used. The 131 I whole body scan associated with thyroid remnant ablation after thyroidectomy has a major role in early diagnosis of functioning distant metastases at a time when complementary imaging techniques (CT, MRI, bone scanning) are often still showing negative findings. Early diagnosis of specific 131 I-avid bone foci will be improved with the advent and generalization of SPECT/CT. When early diagnosis is achieved, repeated 131 I therapy can be effective by targeting not only visible metastases but also those still too small

  20. CT in the assessment of early response to neoadjuvant therapy of colon

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael; Dam, Claus; Lund-Rasmussen, Vera

    tumour invasion and number and size of enlarged lymph nodes were measured before and after the therapy. Results: Mean tumour length was 7.8 cm (95% CI: 5.3–10.4) at baseline and 4.34 cm (95%, CI: 4.0–4.9) after therapy. Mean extramural tumour invasion was 10.6 mm (95% CI: 9.5–11.8) at baseline and 5.7 mm...

  1. Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

    Science.gov (United States)

    Yoo, S H; Kwon, J H; Nam, S W; Kim, H Y; Kim, C W; You, C R; Choi, S W; Cho, S H; Han, J-Y; Song, D S; Chang, U I; Yang, J M; Lee, H L; Lee, S W; Han, N I; Kim, S-H; Song, M J; Hwang, S; Sung, P S; Jang, J W; Bae, S H; Choi, J Y; Yoon, S K

    2018-04-16

    Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response. © 2018 John Wiley & Sons Ltd.

  2. [Clinical randomized controlled trial on ultrashort wave and magnetic therapy for the treatment of early stage distal radius fractures].

    Science.gov (United States)

    Wang, Guan-Jie; Liu, Jia

    2012-07-01

    To explore the effect of application of ultrashort wave and magnetic therapy instrument on the swelling regression in distal radius fractures treated by splint external fixation in initial stage. From March 2007 to May 2010,90 patients with distal radial fracture were treated by manual reduction and splint external fixation. After manual reduction and small splints external fixation, these patients were randomly divided into electrical physical therapy group, western medicine group and the control group by the order of calling number, with 30 cases each group. In control group, there were 9 males and 21 females with an average age of (61.29 +/- 1.97) years, the patients raised and exercise the limb and fingers only. The other two groups also carried out this treatment. In electrical physical therapy group, there were 9 males and 21 females with an average age of (62.37 +/- 2.48) years, the patients were treated with ultrashort wave and magnetic therapy instrument for early intervention, once a day, 5 days for a course of treatment and three cycle were operated. In western medicine group,there were 8 males and 22 females with an average age of (60.12 +/- 2.87) years, the patients were injected with beta-aescin (20 mg, intravenous injection,once a day) for 5 days, followed by Danshen injection (20 ml, intravenous injection, once a day) for 10 days. The limb swelling of patients were assessed every day for 20 days after manual reduction and small splints external fixation. The time of swelling regression in electrical physical therapy group, western medicine group and the control group were respectively (9.62 +/- 3.32), (10.05 +/- 3.05) and (14.57 +/- 2.93) days. Both of that in electrical physical therapy group and western medicine group were shorter than that in the control group (P0.05). The effective rate of swelling regression in electrical physical therapy group, western medicine group and the control group were 86.67%, 80.00%, 46.66% respectively. There was no

  3. Predictive value of early viriological response for sustained viriological response in chronic hepatitis c with conventional interferon therapy

    International Nuclear Information System (INIS)

    Awan, A.; Umar, M.; Khaar, H.T.B.; Kulsoom, A.; Minhas, Z.; Ambreen, S.; Habib, N.; Mumtaz, W.; Habib, F.

    2016-01-01

    Background: Hepatitis is a major public health problem in Pakistan due to its strong association with liver failure and hepatocellular carcinoma. In Pakistan, conventional interferon therapy along with Ribavirin is favoured especially in Government funded programs for treatment of Hepatitis C, over the more expensive Pegylated Interferon and Ribavirin combination therapy as recommended by Pakistan society of Gastroenterology and GI endoscopy due to its favourable results observed in genotype 3 which is the dominant genotype of this region. Objective of our study was to assess the viriological responses with standard interferon therapy and to determine the predictive values of early viriological response (EVR) for Sustained Viriological Response (SVR) in chronic hepatitis C patients treated with standard interferon therapy. Methods: A cross sectional study was conducted on patients with chronic hepatitis C having received standard interferon and ribavirin therapy for six months. EVR and SVR were noted for analysis. Positive and negative predictive values of EVR on SVR were calculated. Results: Out of the total sample (N=3075), 1946 (63.3 percentage) patients were tested for EVR. 1386 (71.2 percentage) were positive while 560 (28.8 percentage) were negative while 516 (16.8 percentage) were tested for SVR. Two hundred and eighty-five (55.2 percentage) were positive while 231 (44.8 percentage) were negative. EVR and SVR tested were N=117. Positive predictive value of EVR on SVR was 67.1 percentage and negative predictive value was 65.8 percentage. Statistically significant association between EVR and SVR was determined with Chi square statistic of 11.8 (p-value <0.0001). Conclusion: EVR is a good predictor of response of patients to standard interferon and ribavirin therapy. In the absence of an EVR, it seems imperative to stop further treatment. Virilogical responses with conventional interferon therapy are comparable to those of pegylated interferon therapy so

  4. 18F-FDG PET/CT-based early treatment response evaluation of nanoparticle-assisted photothermal cancer therapy.

    Science.gov (United States)

    Norregaard, Kamilla; Jørgensen, Jesper T; Simón, Marina; Melander, Fredrik; Kristensen, Lotte K; Bendix, Pól M; Andresen, Thomas L; Oddershede, Lene B; Kjaer, Andreas

    2017-01-01

    Within the field of nanoparticle-assisted photothermal cancer therapy, focus has mostly been on developing novel heat-generating nanoparticles with the right optical and dimensional properties. Comparison and evaluation of their performance in tumor-bearing animals are commonly assessed by changes in tumor volume; however, this is usually a late-occurring event. This study implements 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging to perform early evaluation of the treatment outcome of photothermal therapy. Silica-gold nanoshells (NS) are administered intravenously to nude mice bearing human neuroendocrine tumor xenografts and the tumors are irradiated by a near-infrared laser. The animals are positron emission tomography scanned with 2-deoxy-2-[F-18]fluoro-D-glucose one day before and one day after treatment. Using this setup, a significant decrease in tumor uptake of 2-deoxy-2-[F-18]fluoro-D-glucose is found already one day after therapy in the group receiving NS and laser treatment compared to control animals. At this time point no change in tumor volume can be detected. Moreover, the change in tumor uptake, is used to stratify the animals into responders and non-responders, where the responding group matched improved survival. Overall, these findings support the use of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging for preclinical and clinical evaluation and optimization of photothermal therapy.

  5. 18F-FDG PET/CT-based early treatment response evaluation of nanoparticle-assisted photothermal cancer therapy.

    Directory of Open Access Journals (Sweden)

    Kamilla Norregaard

    Full Text Available Within the field of nanoparticle-assisted photothermal cancer therapy, focus has mostly been on developing novel heat-generating nanoparticles with the right optical and dimensional properties. Comparison and evaluation of their performance in tumor-bearing animals are commonly assessed by changes in tumor volume; however, this is usually a late-occurring event. This study implements 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging to perform early evaluation of the treatment outcome of photothermal therapy. Silica-gold nanoshells (NS are administered intravenously to nude mice bearing human neuroendocrine tumor xenografts and the tumors are irradiated by a near-infrared laser. The animals are positron emission tomography scanned with 2-deoxy-2-[F-18]fluoro-D-glucose one day before and one day after treatment. Using this setup, a significant decrease in tumor uptake of 2-deoxy-2-[F-18]fluoro-D-glucose is found already one day after therapy in the group receiving NS and laser treatment compared to control animals. At this time point no change in tumor volume can be detected. Moreover, the change in tumor uptake, is used to stratify the animals into responders and non-responders, where the responding group matched improved survival. Overall, these findings support the use of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging for preclinical and clinical evaluation and optimization of photothermal therapy.

  6. A Randomized Controlled Trial on Very Early Speech and Language Therapy in Acute Stroke Patients with Aphasia

    Directory of Open Access Journals (Sweden)

    A.C. Laska

    2011-07-01

    Full Text Available Background: Aphasia affects one third of acute stroke patients. There is a considerable spontaneous recovery in aphasia, but impaired communication ability remains a great problem. Communication difficulties are an impediment to rehabilitation. Early treatment of the language deficits leading to increased communication ability would improve rehabilitation. The aim of this study is to elucidate the efficacy of very early speech and language therapy (SLT in acute stroke patients with aphasia. Methods: A prospective, open, randomized, controlled trial was carried out with blinded endpoint evaluation of SLT, starting within 2 days of stroke onset and lasting for 21 days. 123 consecutive patients with acute, first-ever ischemic stroke and aphasia were randomized. The SLT treatment was Language Enrichment Therapy, and the aphasia tests used were the Norsk grunntest for afasi (NGA and the Amsterdam-Nijmegen everyday language test (ANELT, both performed by speech pathologists, blinded for randomization. Results: The primary outcome, as measured by ANELT at day 21, was 1.3 in the actively treated patient group and 1.2 among controls. NGA led to similar results in both groups. Patients with a higher level of education (>12 years improved more on ANELT by day 21 than those with Conclusions: Very early intensive SLT with the Language Enrichment Therapy program over 21 days had no effect on the degree of aphasia in unselected acute aphasic stroke patients. In aphasic patients with more fluency, SLT resulted in a significant improvement as compared to controls. A higher educational level of >12 years was beneficial.

  7. The Results and Prognostic Factors of Postoperative Radiation Therapy in the Early Stages of Endometrial Cancer

    International Nuclear Information System (INIS)

    Lee, Kyung Ja

    2008-01-01

    To evaluate the results and prognostic factors for postoperative adjuvant radiation therapy in patients at stages I and II of endometrial cancer. Materials and Methods: Between January 1991 and December 2006, 35 patients with FIGO stages I and II disease, who received adjuvant radiation therapy following surgery for endometrial cancer at Ewha Womans University Hospital, were enrolled in this study. A total of 17 patients received postoperative pelvic external beam radiation therapy; whereas, 12 patients received vaginal brachytherapy alone, and 6 patients received both pelvic radiation therapy and vaginal brachytherapy. Results: The median follow-up period for all patients was 54 months. The 5-yr overall survival and disease-free survival rates for all patients were 91.4% and 81.7%, respectively. The 5-yr overall survival rates for low-risk, intermediate-risk, and high-risk groups were 100%, 100% and 55.6%, respectively. In addition, the 5-yr disease-free survival rates were 100%, 70.0%, and 45.7%, respectively. Although no locoregional relapses were identified, distant metastases were observed in 5 patients (14%). The most common site of distant metastases was the lung, followed by bone, liver, adrenal gland, and peritoneum. A univariate analysis revealed a significant correlation between distant metastases and risk-group (p=0.018), pathology type (p=0.001), and grade (p=0.019). A multivariate analysis also revealed that distant metastases were correlated with pathology type (p=0.009). Papillary, serous and clear cell carcinoma cases demonstrated a poor patient survival rate compared to cases of endometrioid adenocarcinoma or adenosquamous carcinoma. The most common complication of pelvic external beam radiation therapy was enteritis (30%), followed by proctitis, leucopenia, and lymphedema. All these complications were of RTOG grades 1 and 2; no grades 3 and 4 were observed. Conclusion: For the low-risk and intermediate-risk groups (stages 1 and 2) endometrial

  8. Endoscopic Management of Early Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus: Screening, Diagnosis, and Therapy.

    Science.gov (United States)

    di Pietro, Massimiliano; Canto, Marcia I; Fitzgerald, Rebecca C

    2018-01-01

    Because the esophagus is easily accessible with endoscopy, early diagnosis and curative treatment of esophageal cancer is possible. However, diagnosis is often delayed because symptoms are not specific during early stages of tumor development. The onset of dysphagia is associated with advanced disease, which has a survival at 5 years lower than 15%. Population screening by endoscopy is not cost-effective, but a number of alternative imaging and cell analysis technologies are under investigation. The ideal screening test should be inexpensive, well tolerated, and applicable to primary care. Over the past 10 years, significant progress has been made in endoscopic diagnosis and treatment of dysplasia (squamous and Barrett's), and early esophageal cancer using resection and ablation technologies supported by evidence from randomized controlled trials. We review the state-of-the-art technologies for early diagnosis and minimally invasive treatment, which together could reduce the burden of disease. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Mestre, Francisco [Service of Radiation Therapy, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Gutiérrez, Antonio, E-mail: antoniom.gutierrez@ssib.es [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Rodriguez, Jose [MD Anderson Cancer Center, Madrid (Spain); Ramos, Rafael [Service of Pathology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Garcia, Juan Fernando [Spanish National Cancer Research Centre, Madrid (Spain); Martinez-Serra, Jordi [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Casasus, Marta; Nicolau, Cristina [Service of Radiation Therapy, Policlinica Miramar, Palma de Mallorca (Spain); Bento, Leyre; Herraez, Ines [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Lopez-Perezagua, Paloma [Service of Radiology, IDISPA, Palma de Mallorca (Spain); Daumal, Jaime [Service of Nuclear Medicine, IDISPA, Palma de Mallorca (Spain); Besalduch, Joan [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain)

    2015-05-01

    Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.

  10. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Mestre, Francisco; Gutiérrez, Antonio; Rodriguez, Jose; Ramos, Rafael; Garcia, Juan Fernando; Martinez-Serra, Jordi; Casasus, Marta; Nicolau, Cristina; Bento, Leyre; Herraez, Ines; Lopez-Perezagua, Paloma; Daumal, Jaime; Besalduch, Joan

    2015-01-01

    Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2 + patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2 − patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2 + and COX-2 − patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT

  11. Predictors of premature termination from psychotherapy for anorexia nervosa: Low treatment credibility, early therapy alliance, and self-transcendence.

    Science.gov (United States)

    Jordan, Jennifer; McIntosh, Virginia V W; Carter, Frances A; Joyce, Peter R; Frampton, Christopher M A; Luty, Suzanne E; McKenzie, Janice M; Carter, Janet D; Bulik, Cynthia M

    2017-08-01

    Failure to complete treatment for anorexia nervosa (AN) is- common, clinically concerning but difficult to predict. This study examines whether therapy-related factors (patient-rated pretreatment credibility and early therapeutic alliance) predict subsequent premature termination of treatment (PTT) alongside self-transcendence (a previously identified clinical predictor) in women with AN. 56 women aged 17-40 years participating in a randomized outpatient psychotherapy trial for AN. Treatment completion was defined as attending 15/20 planned sessions. Measures were the Treatment Credibility, Temperament and Character Inventory, Vanderbilt Therapeutic Alliance Scale and the Vanderbilt Psychotherapy Process Scale. Statistics were univariate tests, correlations, and logistic regression. Treatment credibility and certain early patient and therapist alliance/process subscales predicted PTT. Lower self-transcendence and lower early process accounted for 33% of the variance in predicting PTT. Routine assessment of treatment credibility and early process (comprehensively assessed from multiple perspectives) may help clinicians reduce PTT thereby enhancing treatment outcomes. © 2017 Wiley Periodicals, Inc.

  12. Early changes of parotid density and volume predict modifications at the end of therapy and intensity of acute xerostomia.

    Science.gov (United States)

    Belli, Maria Luisa; Scalco, Elisa; Sanguineti, Giuseppe; Fiorino, Claudio; Broggi, Sara; Dinapoli, Nicola; Ricchetti, Francesco; Valentini, Vincenzo; Rizzo, Giovanna; Cattaneo, Giovanni Mauro

    2014-10-01

    To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer. Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients. A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher "mean" acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm(3)/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.

  13. The early changes of thyroid hormone concentrations after 131I therapy for graves' hyperthyroidism - the role of pretreatment with methimazole

    International Nuclear Information System (INIS)

    Pirnat, E.; Fidler, V.; Zaletel, K.; Gaberscek, S.; Hojker, S.

    2002-01-01

    Full text: 131 I therapy may cause exacerbation of hyperthyroidism due to leakage of previously formed thyroid hormones from damaged thyroid cells in Graves' patients. To avoid this complication pretreatment with antithyroid drugs is recommended. Otherwise, the use of antithyroid drugs prior to 131 I therapy may diminish the success of 131 I therapy and should therefore be discontinued. The aim of our prospective clinical study was to compare early changes of thyroid hormone concentrations after 131 I therapy in Graves' patients, pretreated or not pretreated with methimazole. 92 consecutive Graves' patients, 84 females and 8 males, aged 17 to 80 were treated with 555 MBq of 131 I. Absorbed dose of 131 I was calculated. In the first group of 22 patients treatment with methimazole (20 mg/day) was discontinued 7 days before 131 I therapy, the second group of 33 patients received methimazole until the day of 131 I therapy and the third group of 37 patients was not pretreated with methimazole before 131 I therapy. 7 and 2 days before 131 I therapy and 2, 5, 12 and 30 days after serum free T 4 (fT 4 ) and free T 3 (fT 3 ) concentrations were measured. In the first group a significant increase of fT 4 and fT 3 was observed 7 days after discontinuation of methimazole (fT 4 14.60 ± 4.10 vs. 18.25 ± 7.16; fT 3 5.45 ± 1.44 vs. 7.79 ± 5.27 pmol/l), while gradual decrease of fT 4 and fT 3 was observed after 131 I therapy. In the second group a significant increase of fT 4 and fT 3 after 131 I therapy peaking on day 5 was observed (fT 4 20.91 ± 13.70 vs. 27.85 ± 18.17; fT 3 7.81 ± 5.21 vs. 9.42 ± 6.21 pmol/l). In the third group significant decrease of fT 4 and fT 3 concentrations was observed after 131 I therapy (fT 4 36.12 ± 18.55 vs. on day 12th 27.49 ± 15.20; fT 3 12.66 ± 7.04 vs. on day 12th 8.31 ± 4.92 pmol/l). No correlation between absorbed dose of 131 I and changes of fT 4 and fT 3 concentrations was observed. Therefore, our results indicate that not 131 I

  14. Effectiveness of speech language therapy either alone or with add-on computer-based language therapy software (Malayalam version) for early post stroke aphasia: A feasibility study.

    Science.gov (United States)

    Kesav, Praveen; Vrinda, S L; Sukumaran, Sajith; Sarma, P S; Sylaja, P N

    2017-09-15

    This study aimed to assess the feasibility of professional based conventional speech language therapy (SLT) either alone (Group A/less intensive) or assisted by novel computer based local language software (Group B/more intensive) for rehabilitation in early post stroke aphasia. Comprehensive Stroke Care Center of a tertiary health care institute situated in South India, with the study design being prospective open randomised controlled trial with blinded endpoint evaluation. This study recruited 24 right handed first ever acute ischemic stroke patients above 15years of age affecting middle cerebral artery territory within 90days of stroke onset with baseline Western Aphasia Battery (WAB) Aphasia Quotient (AQ) score of aphasia. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Very preterm born children at early school age: Healthcare therapies and educational provisions

    NARCIS (Netherlands)

    van Veen, S.; Aarnoudse-Moens, C. S. H.; Oosterlaan, J.; Van Sonderen, L.; de Haan, T. R.; van Kaam, A. H.; van Wassenaer-Leemhuis, A. G.

    2017-01-01

    To explore changes in motor and cognitive outcomes in very preterm (VP; gestational age <30weeks) born children between ages five and six years, and to determine whether changes in these outcomes were associated with the use of healthcare therapies and educational provisions. Single-center

  16. Flavonoid-Based Therapies in the Early Management of Neurodegenerative Diseases12

    Science.gov (United States)

    Solanki, Isha; Parihar, Priyanka; Mansuri, Mohammad Lukman; Parihar, Mordhwaj S

    2015-01-01

    During the past several years, there has been enormous progress in the understanding of the causative factors that initiate neuronal damage in various neurodegenerative diseases, including Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease. Preventing neuronal damage and neuronal death will have a huge clinical benefit. However, despite major advances in causative factors that trigger these neurodegenerative diseases, to date there have been no therapies available that benefit patients who suffer from these diseases. Because most neurodegenerative diseases are late-onset and remain asymptomatic for most of the phases, the therapies initiated in advanced stages of the disease have limited value to patients. It may be possible to prevent or halt the disease progression to a great extent if therapies start at the initial stage of the disease. Such therapies may restore neuronal function by reducing or even eliminating the primary stressor. Flavonoids are key compounds for the development of a new generation of therapeutic agents that are clinically effective in treating neurodegenerative diseases. Regular consumption of flavonoids has been associated with a reduced risk of neurodegenerative diseases. In addition to their antioxidant properties, these polyphenolic compounds exhibit neuroprotective properties by their interaction with cellular signaling pathways followed by transcription and translation that mediate cell function under both normal and pathologic conditions. This review focuses on human intervention studies as well as animal studies on the role of various flavonoids in the prevention of neurodegenerative diseases. PMID:25593144

  17. Early stage cognitive impairment in Parkinson’s disease and the influence of dopamine replacement therapy

    NARCIS (Netherlands)

    Miah, I.P.; Olde Dubbelink, K.T.E.; Stoffers, D.; Deijen, J.B.; Berendse, H.W.

    2012-01-01

    Background and purpose: The aim of this study was to establish the cognitive profile of newly diagnosed untreated (de novo) patients with Parkinson's disease (PD) and more advanced, treated patients, and to determine the effects of dopamine (DA) replacement therapy. Methods: A cohort of 23 de novo

  18. Early and delayed results of radiotherapy and multimodality therapy of spinal hemangiomas

    International Nuclear Information System (INIS)

    Morozov, A.I.; Neretin, V.Ya.; Korshunov, A.I.; Nikolaeva, S.N.; Balkanov, A.S.; Marchenko, V.A.

    1988-01-01

    The authors described the results of therapy of 74 spinal hemangioma patients. The patients were divided into 2 groups: 1 - radiotherapy only; 2 - radiotherapy following surgical intervention for enhanced symptoms of spinal compression. γ-beam therapy was given 5 times a week at a single dose of 0.8-1.2 Gy. An integral dose delivered to the cervical spine was 26-32 Gy, to the thoracic spine 28-30 Gy, to the lumber spine - 30-34 Gy. Field sizes varied from 3x4 to 3x12 cm depending on lesion spreading. Therapy also included traction on a special platform bed. An analysis of delayed therapeutic results (from 3 to 13 yrs.) has shown that clinical convalescence with regained working capacity in the 1st group (40 patients) was observed in 21 patients, in the 2nd group (34 patients) - in 5 patients only. Partial functional restoration was observed in both groups (19 patients in each group). The therapy applied was ineffective in 10 patients of the 2nd group

  19. Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Neuhaus, Jacqueline; Babiker, Abdel G

    2016-01-01

    BACKGROUND:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts a...

  20. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

    NARCIS (Netherlands)

    Lodi, Sara; Del Amo, Julia; Moreno, Santiago; Bucher, Heiner C.; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Olson, Ashley; Van Sighem, Ard; Reiss, Peter; Sabin, Caroline; Jose, Sophie; Justice, Amy; Goulet, Joseph; Miró, José M.; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Vourli, Georgia; Antoniadou, Anastasia; Dabis, Francois; Vandenhede, Mari-Anne; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A.; Hernan, Miguel; Bansi, L.; Hill, T.; Sabin, C.; Dunn, D.; Porter, K.; Glabay, A.; Orkin, C.; Thomas, R.; Jones, K.; Fisher, M.; Perry, N.; Pullin, A.; Churchill, D.; Gazzard, B.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Delpech, V.; Anderson, J.; Munshi, S.; Post, F.; Easterbrook, P.; Khan, Y.; Patel, P.; Karim, F.; Duffell, S.; Gilson, R.; Man, S.-L.; Williams, I.; Gompels, M.; Dooley, D.; Schwenk, A.; Ainsworth, J.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Ismajani Puradiredja, D.; Bansi, L.; Hill, T.; Phillips, A.; Sabin, C.; Walsh, J.; Weber, J.; Kemble, C.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Bezemer, D.O.; Gras, L.A.J.; Kesselring, A.M.; Van Sighem, A.I.; Zaheri, S.; Van Twillert, G.; Kortmann, W.; Branger, J.; Prins, J.M.; Kuijpers, T.W.; Scherpbier, H.J.; Van Der Meer, J.T.M.; Wit, F.W.M.N.; Godfried, M.H.; Reiss, P.; Van Der Poll, T.; Nellen, F.J.B.; Lange, J.M.A.; Geerlings, S.E.; Van Vugt, M.; Pajkrt, D.; Bos, J.C.; van der Valk, M.; Grijsen, M.L.; Wiersinga, W.J.; Brinkman, K.; Blok, W.L.; Frissen, P.H.J.; Schouten, W.E.M.; Van Den Berk, G.E.L.; Veenstra, J.; Lettinga, K.D.; Mulder, J.W.; Vrouenraets, S.M.E.; Lauw, F.N.; Van Eeden, A.; Verhagen, D.W.M.; Van Agtmael, M.A.; Perenboom, R.M.; Claessen, F.A.P.; Bomers, M.; Peters, E.J.G.; Richter, C.; Van Der Berg, J.P.; Gisolf, E.H.; Schippers, E.F.; Van Nieuwkoop, C.; Van Elzakker, E.P.; Leyten, E.M.S.; Gelinck, L.B.S.; Pronk, M.J.H.; Bravenboer, B.; Kootstra, G.J.; Delsing, C.E.; Sprenger, H.G.; Doedens, R.; Scholvinck, E.H.; Van Assen, S.; Bierman, W.F.W.; Soetekouw, R.; Ten Kate, R.W.; Van Vonderen, M.G.A.; Van Houte, D.P.F.; Kroon, F.P.; Van Dissel, J.T.; Arend, S.M.; De Boer, M.G.J.; Jolink, H.; Ter Vollaard, H.J.M.; Bauer, M.P.; Weijer, S.; El Moussaoui, R.; Lowe, S.; Schreij, G.; Oude Lashof, A.; Posthouwer, D.; Koopmans, P.P.; Keuter, M.; Van Der Ven, A.J.A.M.; Ter Hofstede, H.J.M.; Dofferhoff, A.S.M.; Warris, A.; Van Crevel, R.; van der Ende, Marchina E.; De Vries-Sluijs, T.E.M.S.; Schurink, C.A.M.; Nouwen, J.L.; Nispen Tot Pannerden, M.H.; Verbon, A.; Rijnders, B.J.A.; Van Gorp, E.C.M.; Hassing, R.J.; Smeulders, A.W.M.; Hartwig, N.G.; Driessen, G.J.A.; Den Hollander, J.G.; Pogany, K.; Juttmann, J.R.; Van Kasteren, M.E.E.; Hoepelman, A.I.M.; Mudrikova, T.; Schneider, M.M.E.; Jaspers, C.A.J.J.; Ellerbroek, P.M.; Oosterheert, J.J.; Arends, J.E.; Wassenberg, M.W.M.; Barth, R.E.; Geelen, S.P.M.; Wolfs, T.F.W.; Bont, L.J.; Van Den Berge, M.; Stegeman, A.; Groeneveld, P.H.P.; Alleman, M.A.; Bouwhuis, J.W.; Barin, F.; Burty, C.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Khuong, M.A.; Mahamat, A.; Pilorgé, F.; Tattevin, P.; Salomon, Valérie; Jacquemet, N.; Abgrall, S.; Costagliola, D.; Grabar, S.; Guiguet, M.; Lanoy, E.; Lièvre, L.; Mary-Krause, M.; Selinger-Leneman, H.; Lacombe, J.M.; Potard, V.; Bricaire, F.; Herson, S.; Katlama, C.; Simon, A.; Desplanque, N.; Girard, P.M.; Meynard, J.L.; Meyohas, M.C.; Picard, O.; Cadranel, J.; Mayaud, C.; Pialoux, G.; Clauvel, J.P.; Decazes, J.M.; Gerard, L.; Molina, J.M.; Diemer, M.; Sellier, P.; Bentata, M.; Honoré, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Bouvet, E.; Crickx, B.; Ecobichon, J.L.; Matheron, S.; Picard-Dahan, C.; Yeni, P.; Berthé, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; De Truchis, P.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Gilquin, J.; Roudière, L.; Viard, J.P.; Boué, F.; Fior, R.; Delfraissy, J.F.; Goujard, C.; Jung, C.; Lesprit, Ph.; Vittecoq, D.; Fraisse, P.; Lang, J.M.; Rey, D.; Beck-Wirth, G.; Stahl, J.P.; Lecercq, P.; Gourdon, F.; Laurichesse, H.; Fresard, A.; Lucht, F.; Bazin, C.; Verdon, R.; Chavanet, P.; Arvieux, C.; Michelet, C.; Choutet, P.; Goudeau, A.; Maître, M.F.; Hoen, B.; Eglinger, P.; Faller, J.P.; Borsa-Lebas, F.; Caron, F.; Reynes, J.; Daures, J.P.; May, T.; Rabaud, C.; Berger, J.L.; Rémy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Thiercelin Legrand, M.F.; Pontonnier, G.; Viget, N.; Yasdanpanah, Y.; Dellamonica, P.; Pradier, C.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Tissot-Dupont, H.; Delmont, J.P.; Moreau, J.; Gastaut, J.A.; Poizot-Martin, I.; Retornaz, F.; Soubeyrand, J.; Galinier, A.; Ruiz, J.M.; Allegre, T.; Blanc, P.A.; Bonnet-Montchardon, D.; Lepeu, G.; Granet-Brunello, P.; Esterni, J.P.; Pelissier, L.; Cohen-Valensi, R.; Nezri, M.; Chadapaud, S.; Laffeuillade, A.; Billaud, E.; Raffi, F.; Boibieux, A.; Peyramond, D.; Livrozet, J.M.; Touraine, J.L.; Cotte, L.; Trepo, C.; Strobel, M.; Bissuel, F.; Pradinaud, R.; Sobesky, M.; Cabié, A.; Gaud, C.; Contant, M.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Haerry, D.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Hasse, B.; Hirsch, H.H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez De Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.; Casabona, J.; Gallois, A.; Esteve, A.; Podzamczer, D.; Murillas, J.; Gatell, J.M.; Manzardo, C.; Tural, C.; Clotet, B.; Ferrer, E.; Riera, M.; Segura, F.; Navarro, G.; Force, L.; Vilaró, J.; Masabeu, A.; García, I.; Guadarrama, M.; Cifuentes, C.; Dalmau, D.; Jaen, À.; Agustí, C.; Montoliu, A.; Pérez, I.; Gargoulas, Freyra; Blanco, J.L.; Garcia-Alcaide, F.; Martínez, E.; Mallolas, J.; López-Dieguez, M.; García-Goez, J.F.; Sirera, G.; Romeu, J.; Jou, A.; Negredo, E.; Miranda, C.; Capitan, M.C.; Saumoy, M.; Imaz, A.; Tiraboschi, J.M.; Murillo, O.; Bolao, F.; Peña, C.; Cabellos, C.; Masó, M.; Vila, A.; Sala, M.; Cervantes, M.; Jose Amengual, Ma.; Navarro, M.; Penelo, E.; Barrufet, P.; Bejarano, G.; Molina, J.; Guadarrama, M.; Alvaro, M.; Mercadal, J.; Fernandez, Juanse; Ospina, Jesus E.; Muñoz, M.A.; Caro-Murillo, A.M.; Sobrino, P.; Jarrín, I.; Gomez Sirvent, J.L.; Rodríguez, P.; Aleman, M.R.; Alonso, M.M.; Lopez, A.M.; Hernandez, M.I.; Soriano, V.; Labarga, P.; Barreiro, P.; Medrano, J.; Rivas, P.; Herrero, D.; Blanco, F.; Vispo, M.E.; Martín, L.; Ramírez, G.; De Diego, M.; Rubio, R.; Pulido, F.; Moreno, V.; Cepeda, C.; Hervás, Rl.; Iribarren, J.A.; Arrizabalaga, J.; Aramburu, M.J.; Camino, X.; Rodrí-guez-Arrondo, F.; Von Wichmann, M.A.; Pascual, L.; Goenaga, M.A.; Gutierrez, F.; Masia, M.; Ramos, J.M.; Padilla, S.; Sanchez-Hellín, V.; Bernal, E.; Escolano, C.; Montolio, F.; Peral, Y.; Berenguer, J.; Lopez, J.C.; Miralles, P.; Cosín, J.; Sanchez, M.; Gutierrez, I.; Ramírez, M.; Padilla, B.; Vidal, F.; Sanjuan, M.; Peraire, J.; Veloso, S.; Vilades, C.; Lopez-Dupla, M.; Olona, M.; Vargas, M.; Aldeguer, J.L.; Blanes, M.; Lacruz, J.; Salavert, M.; Montero, M.; Cuéllar, S.; De Los Santos, I.; Sanz, J.; Oteo, J.A.; Blanco, J.R.; Ibarra, V.; Metola, L.; Sanz, M.; Pérez-Martínez, L.; Sola, J.; Uriz, J.; Castiello, J.; Reparaz, J.; Arriaza, M.J.; Irigoyen, C.; Moreno, S.; Antela, A.; Casado, J.L.; Dronda, F.; Moreno, A.; Pérez, M.J.; López, D.; Gutiérrez, C.; Hernández, B.; Pumares, M.; Martí, P.; García, L.; Page, C.; García, F.; Hernández, J.; Peña, A.; Muñoz, L.; Parra, J.; Viciana, P.; Leal, M.; López-Cortés, L.F.; Trastoy, M.; Mata, R.; Justice, A.C.; Fiellin, D.A.; Rimland, D.; Jones-Taylor, C.; Oursler, K.A.; Titanji, R.; Brown, S.; Garrison, S.; Rodriguez-Barradas, M.; Masozera, N.; Goetz, M.; Leaf, D.; Simberkoff, M.; Blumenthal, D.; Leung, J.; Butt, A.; Hoffman, E.; Gibert, C.; Peck, R.; Mattocks, K.; Braithwaite, S.; Brandt, C.; Bryant, K.; Cook, R.; Conigliaro, J.; Crothers, K.; Chang, J.; Crystal, S.; Day, N.; Erdos, J.; Freiberg, M.; Kozal, M.; Gandhi, N.; Gaziano, M.; Gerschenson, M.; Good, B.; Gordon, A.; Goulet, J.L.; Hernán, M.A.; Kraemer, K.; Lim, J.; Maisto, S.; Miller, P.; Mole, L.; O'Connor, P.; Papas, R.; Robins, J.M.; Rinaldo, C.; Roberts, M.; Samet, J.; Tierney, B.; Whittle, J.; Babiker, A.; Brettle, R.; Darbyshire, J.; Gilson, R.; Goldberg, D.; Hawkins, D.; Jaffe, H.; Johnson, A.; McLean, K.; Pillay, D.; Cursley, Adam; Ewings, Fiona; Fairbrother, Keith; Louisa Gnatiuc, S.L.; Murphy, Brendan; Douglas, G.; Kennedy, N.; Pritchard, J.; Andrady, U.; Rajda, N.; Maw, R.; McKernan, S.; Drake, S.; Gilleran, G.; White, D.; Ross, J.; Toomer, S.; Hewart, R.; Wilding, H.; Woodward, R.; Dean, G.; Heald, L.; Horner, P.; Glover, S.; Bansaal, D.; Eduards, S.; Carne, C.; Browing, M.; Das, R.; Stanley, B.; Estreich, S.; Magdy, A.; O'Mahony, C.; Fraser, P.; Hayman, B.; Jebakumar, S.P.R.; Joshi, U.; Ralph, S.; Wade, A.; Mette, R.; Lalik, J.; Summerfield, H.; El-Dalil, A.; France, J.A.; White, C.; Robertson, R.; Gordon, S.; McMillan, S.; Morris, S.; Lean, C.; Vithayathil, K.; McLean, L.; Winter, A.; Gale, D.; Jacobs, S.; Tayal, S.; Short, L.; Roberts, M.; Green, S.; Williams, G.; Sivakumar, K.; Bhattacharyya, N.D.; Monteiro, E.; Minton, J.; Dhar, J.; Nye, F.; De Souza, C.B.; Isaksen, A.; McDonald, L.; McLean, K.; Franca, A.; Hawkins, D.; William, L.; Jendrulek, I.; Peters, B.; Shaunak, S.; El-Gadi, S.; Easterbrook, P.J.; Mazhude, C.; Gilson, R.; Johnstone, R.; Fakoya, A.; McHale, J.; Waters, A.; Kegg, S.; Mitchell, S.; Byrne, P.; Johnson, M.; Rice, P.; Fidler, S.; Mullaney, S.A.; McCormack, S.; David, D.; Melville, R.; Phillip, K.; Balachandran, T.; Mabey-Puttock, S.; Sukthankar, A.; Murphy, C.; Wilkins, E.; Ahmad, S.; Tayal, S.; Haynes, J.; Evans, E.; Ong, E.; Das, R.; Grey, R.; Meaden, J.; Bignell, C.; Loay, D.; Peacock, K.; Girgis, M.R.; Morgan, B.; Palfreeman, A.; Wilcox, J.; Tobin, J.; Tucker, L.; Saeed, A.M.; Chen, F.; Deheragada, A.; Williams, O.; Lacey, H.; Herman, S.; Kinghorn, D.; Devendra, V.S.; Wither, J.; Dawson, S.; Rowen, D.; Harvey, J.; Wilkins, E.; Bridgwood, A.; Singh, G.; Chauhan, M.; Kellock, D.; Young, S.; Dannino, S.; Kathir, Y.; Rooney, G.; Currie, J.; Fitzgerald, M.; Devendra, S.; Keane, F.; Booth, G.; Green, T.; Arumainayyagam, J.; Chandramani, S.; Rajamanoharan, S.; Robinson, T.; Curless, E.; Gokhale, R.; Tariq, A.; Roberts, M.; Williams, O.; Luzzi, G.; FitzGerald, M.; Fairley, I.; Wallis, F.; Smit, E.; Ward, F.; Molina, J.M.; Loze, B.; Morlat, P.; Bonarek, M.; Bonnet, F.; Nouts, C.; Louis, I.; Raffi, F.; Reliquet, V.; Sauser, F.; Biron, C.; Mounoury, O.; Hue, H.; Brosseau, D.; Delfraissy, J.F.; Goujard, C.; Ghosn, J.; Rannou, M.T.; Bergmann, J.F.; Badsi, E.; Rami, A.; Diemer, M.; Parrinello, M.; Girard, P.M.; Samanon-Bollens, D.; Campa, P.; Tourneur, M.; Desplanques, N.; Livrozet, J.M.; Jeanblanc, F.; Chiarello, P.; Makhloufi, D.; Blanc, A.P.; Allègre, T.; Reynes, J.; Baillat, V.; Lemoing, V.; Merle De Boever, C.; Tramoni, C.; Cabié, A.; Sobesky, G.; Abel, S.; Beaujolais, V.; Pialoux, G.; Slama, L.; Chakvetadze, C.; Berrebi, V.; Yeni, P.; Bouvet, E.; Fournier, I.; Gerbe, J.; Trepo, C.; Koffi, K.; Augustin-Normand, C.; Miailhes, P.; Thoirain, V.; Brochier, C.; Thomas, R.; Souala, F.; Ratajczak, M.; Beytoux, J.; Jacomet, C.; Gourdon, F.; Rouveix, E.; Morelon, S.; Dupont, C.; Olivier, C.; Lortholary, O.; Dupont, B.; Viard, J.P.; Maignan, A.; Ragnaud, J.M.; Raymond, I.; Leport, C.; Jadand, C.; Jestin, C.; Longuet, P.; Boucherit, S.; Sereni, D.; Lascoux, C.; Prevoteau, F.; Sobel, A.; Levy, Y.; Lelièvre, J.D.; Lascaux, A.S.; Dominguez, S.; Dumont, C.; Aumâitre, H.; Delmas, B.; Saada, M.; Medus, M.; Guillevin, L.; Salmon, D.; Tahi, T.; Yazdanpanah, Y.; Pavel, S.; Marien, M.C.; Drenou, B.; Beck-Wirth, G.; Beck, C.; Benomar, M.; Katlama, C.; Tubiana, R.; Ait Mohand, H.; Chermak, A.; Ben Abdallah, S.; Bentata, M.; Touam, F.; Hoen, B.; Drobacheff, C.; Folzer, A.; Massip, P.; Obadia, M.; Prudhomme, L.; Bonnet, E.; Balzarin, F.; Pichard, E.; Chennebault, J.M.; Fialaire, P.; Loison, J.; Galanaud, P.; Boué, F.; Bornarel, D.; Verdon, R.; Bazin, C.; Six, M.; Ferret, P.; Weiss, L.; Batisse, D.; Gonzales-Canali, G.; Tisne-Dessus, D.; Devidas, A.; Chevojon, P.; Turpault, I.; Lafeuillade, A.; Cheret, A.; Philip, G.; Morel, P.; Timsit, J.; Herson, S.; Amirat, N.; Simon, A.; Brancion, C.; Cabane, J.; Picard, O.; Tredup, J.; Stein, A.; Ravault, I.; Chavanet, C.; Buisson, M.; Treuvetot, S.; Choutet, P.; Nau, P.; Bastides, F.; May, T.; Boyer, L.; Wassoumbou, S.; Oksenhendeler, E.; Gérard, L.; Bernard, L.; De Truchis, P.; Berthé, H.; Domart, Y.; Merrien, D.; Greder Belan, A.; Gayraud, M.; Bodard, L.; Meudec, A.; Beuscart, C.; Daniel, C.; Pape, E.; Vinceneux, P.; Simonpoli, A.M.; Zeng, A.; Fournier, L.; Fuzibet, J.G.; Sohn, C.; Rosenthal, E.; Quaranta, M.; Dellamonica, P.; Chaillou, S.; Sabah, M.; Audhuy, B.; Schieber, A.; Moreau, P.; Niault, M.; Vaillant, O.; Huchon, G.; Compagnucci, A.; De Lacroix Szmania, I.; Richier, L.; Lamaury, I.; Saint-Dizier, F.; Garipuy, D.; Gastaut, J.A.; Drogoul, M.P.; Poizot Martin, I.; Fabre, G.; Lambert De Cursay, G.; Abraham, B.; Perino, C.; Lagarde, P.; David, F.; Roche-Sicot, J.; Saraux, J.L.; Leprêtre, A.; Fampin, B.; Uludag, A.; Morin, A.S.; Bletry, O.; Zucman, D.; Regnier, A.; Girard, J.J.; Quinsat, D.T.; Heripret, L.; Grihon, F.; Houlbert, D.; Ruel, M.; Chemlal, K.; Caron, F.; Debab, Y.; Tremollieres, F.; Perronne, V.; Lepeu, G.; Slama, B.; Perré, P.; Miodovski, C.; Guermonprez, G.; Dulioust, A.; Boudon, P.; Malbec, D.; Patey, O.; Semaille, C.; Deville, J.; Remy, G.; Béguinot, I.; Galanaud, P.; Boue, F.; Chambrin, V.; Pignon, C.; Estocq, G.A.; Levy, A.; Delfraissy, J.F.; Goujard, C.; Duracinsky, M.; Le Bras, P.; Ngussan, M.S.; Peretti, D.; Medintzeff, N.; Lambert, T.; Segeral, O.; Lezeau, P.; Laurian, Y.; Weiss, L.; Buisson, M.; Piketty, C.; Karmochkine, M.; Batisse, D.; Eliaszewitch, M.; Jayle, D.; Tisne-Dessus, D.; Kazatchkine, M.; Leport, C.; Colasante, U.; Jadand, C.; Jestin, C.; Duval, X.; Nouaouia, W.; Boucherit, S.; Vilde, J.L.; Girard, P.M.; Bollens, D.; Binet, D.; Diallo, B.; Meyohas, M.C.; Fonquernie, L.; Lagneau, J.L.; Salmon, D.; Guillevin, L.; Tahi, T.; Launay, O.; Pietrie, M.P.; Sicard, D.; Stieltjes, N.; Michot, J.; Sobel, A.; Levy, Y.; Bourdillon, F.; Lascaux, A.S.; Lelievre, J.D.; Dumont, C.; Dupont, B.; Obenga, G.; Viard, J.P.; Maignan, A.; Vittecoq, D.; Escaut, L.; Bolliot, C.; Bricaire, F.; Katlama, C.; Schneider, L.; Herson, S.; Simon, A.; Iguertsira, M.; Stein, A.; Tomei, C.; Ravaux, I.; Dhiver, C.; Tissot Dupont, H.; Vallon, A.; Gallais, J.; Gallais, H.; Gastaut, J.A.; Drogoul, M.P.; Fabre, G.; Dellamonica, P.; Durant, J.; Mondain, V.; Perbost, I.; Cassuto, J.P.; Karsenti, J.M.; Venti, H.; Fuzibet, J.G.; Rosenthal, E.; Ceppi, C.; Quaranta, M.; Krivitsky, J.A.; Bentata, M.; Bouchaud, O.; Honore, P.; Sereni, D.; Lascoux, C.; Delgado, J.; Rouzioux, C.; Burgard, M.; Boufassa, L.; Peynet, J.; Pérez-Hoyos, S.; Del Amo, J.; Alvarez, D.; Monge, S.; Muga, R.; Sanvisens, A.; Clotet, B.; Tor, J.; Bolao, F.; Rivas, I.; Vallecillo, G.; Del Romero, J.; Raposo, P.; Rodríguez, C.; Vera, M.; Hurtado, I.; Belda, J.; Fernandez, E.; Alastrue, I.; Santos, C.; Tasa, T.; Juan, A.; Trullen, J.; Garcia De Olalla, P.; Cayla, J.; Masdeu, E.; Knobel, H.; Mirò, J.M.; Sambeat, M.A.; Guerrero, R.; Rivera, E.; Guerrero, R.; Marco, A.; Quintana, M.; Gonzalez, C.; Castilla, J.; Guevara, M.; De Mendoza, C.; Zahonero, N.; Ortíz, M.; Paraskevis, D.; Touloumi, G.; Pantazis, N.; Bakoyannis, G.; Gioukari, V.; Antoniadou, A.; Papadopoulos, A.; Petrikkos, G.; Daikos, G.; Psichogiou, M.; Gargalianos-Kakolyris, P.; Xylomenos, G.; Katsarou, O.; Kouramba, A.; Ioannidou, P.; Kordossis, T.; Kontos, A.; Lazanas, M.; Chini, M.; Tsogas, N.; Panos, G.; Paparizos, V.; Leuow, K.; Kourkounti, S.; Sambatakou, H.; Mariolis, I.; Skoutelis, A.; Papastamopoulos, V.; Baraboutis, I.

    2014-01-01

    Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis,

  1. Immunological Analysis of Treatment Interruption After Early Highly Active Antiretroviral Therapy

    NARCIS (Netherlands)

    Schellens, Ingrid M. M.; Pogany, Katalin; Westerlaken, Geertje H. A.; Borghans, José A. M.; Miedema, Frank; van Valkengoed, Irene G. M.; Kroon, Frank P.; Lange, Joep M. A.; Brinkman, Kees; Prins, Jan M.; van Baarle, Debbie

    2010-01-01

    We longitudinally evaluated HIV-specific T-cell immunity after discontinuation of highly active antiretroviral therapy (HAART). After treatment interruption (TI), some individuals could maintain a low plasma viral load ( <15,000 copies/mL), whereas others could not (>50,000 copies/mL). Before HAART

  2. Effect of hormone replacement therapy on bone quality in early postmenopausal women

    DEFF Research Database (Denmark)

    Paschalis, E P; Boskey, A L; Kassem, M

    2003-01-01

    HRT is an effective prophylaxis against postmenopausal bone loss. Infrared imaging of paired iliac crest biopsies obtained at baseline and after 2 years of HRT therapy demonstrate an effect on the mineral crystallinity and collagen cross-links that may affect bone quality. Several studies have de...

  3. Skin carcinomas in organ-transplant recipients : from early oncogenic events to therapy

    NARCIS (Netherlands)

    Graaf, Ymke Grete Leontien de

    2008-01-01

    Skin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of this elevated carcinoma risk, starting from the earliest oncogenic events to the ultimate therapy.

  4. Does early change predict long-term (6 months) improvements in subjects who receive manual therapy for low back pain?

    Science.gov (United States)

    Cook, Chad; Petersen, Shannon; Donaldson, Megan; Wilhelm, Mark; Learman, Ken

    2017-09-01

    Early change is commonly assessed for manual therapy interventions and has been used to determine treatment appropriateness. However, current studies have only explored the relationship of between or within-session changes and short-/medium-term outcomes. The goal of this study was to determine whether pain changes after two weeks of pragmatic manual therapy could predict those participants with chronic low back pain who demonstrate continued improvements at 6-month follow-up. This study was a retrospective observational design. Univariate logistic regression analyses were performed using a 33% and a 50% pain change to predict improvement. Those who experienced a ≥33% pain reduction by 2 weeks had 6.98 (95% CI = 1.29, 37.53) times higher odds of 50% improvement on the GRoC and 4.74 (95% CI = 1.31, 17.17) times higher odds of 50% improvement on the ODI (at 6 months). Subjects who reported a ≥50% pain reduction at 2 weeks had 5.98 (95% CI = 1.56, 22.88) times higher odds of a 50% improvement in the GRoC and 3.99 (95% CI = 1.23, 12.88) times higher odds of a 50% improvement in the ODI (at 6 months). Future studies may investigate whether a change in plan of care is beneficial for patients who are not showing early improvement predictive of a good long-term outcome.

  5. Can early physical therapy positively affect the onset of independent walking in infants with Down syndrome? A retrospective cohort study.

    Science.gov (United States)

    Corrado, Bruno; Sommella, Nadia; Ciardi, Gianluca; Raiano, Enza; Scala, Iris; Strisciuglio, Pietro; Servodio Iammarrone, Clemente

    2018-02-19

    The development of both gross and fine motor skills in a child with Down syndrome is generally delayed. The most seriously affected stage is the achievement of independent walking ability, which influences the onset of all following motor and cognityive skills. The study objectives were (a) to assess the time taken to achieve independent walking ability in a cohort of children with Down syndrome, (b) to examine differences in walking onset by patient characteristics, (c) to verify the effect of early physical therapy (Neurodevelopmental Treatment on the basis of Bobath Concept practised within the first months of life) in the achievement of that skill. A retrospective study was carried out on a cohort of 86 children with Down Syndrome. The knowledge of the exact age of walking onset and information about comorobities and rehabilitation practised since birth were the eligibility criteria. The average age at which walking began in the sample was 26 months (Standard Deviation = 9.66). Some patient characteristics proved to be related negatively to the walking onset: gender male, trisomy 21, improved joint ligamentous laxity. When practised, early physical therapy was able to contrast the delay in walking. NDT-Bobath is a well-known and valid instrument for a child with Down syndrome to attain his highest possible psychomotor functioning level. This study pointed out for the first time ever its capability to contrast the delay on walking onset, which can influences positively the development of the following motor and cognitive skills.

  6. Cosmetic Outcome and Seroma Formation After Breast-Conserving Surgery With Intraoperative Radiation Therapy Boost for Early Breast Cancer

    International Nuclear Information System (INIS)

    Senthi, Sashendra; Link, Emma; Chua, Boon H.

    2012-01-01

    Purpose: To evaluate cosmetic outcome and its association with breast wound seroma after breast-conserving surgery (BCS) with targeted intraoperative radiation therapy (tIORT) boost for early breast cancer. Methods and Materials: An analysis of a single-arm prospective study of 55 patients with early breast cancer treated with BCS and tIORT boost followed by conventional whole breast radiation therapy (WBRT) between August 2003 and January 2006 was performed. A seroma was defined as a fluid collection at the primary tumor resection site identified clinically or radiologically. Cosmetic assessments using the European Organization for Research and Treatment of Cancer rating system were performed at baseline before BCS and 30 months after WBRT was completed. Results: Twenty-eight patients (51%) developed a seroma, with 18 patients (33%) requiring at least 1 aspiration. Tumor location was significantly associated with seroma formation (P=.001). Ten of 11 patients with an upper inner quadrant tumor developed a seroma. Excellent or good overall cosmetic outcome at 30 months was observed in 34 patients (62%, 95% confidence interval 53%-80%). Seroma formation was not associated with the overall cosmetic result (P=.54). Conclusion: BCS with tIORT boost followed by WBRT was associated with an acceptable cosmetic outcome. Seroma formation was not significantly associated with an adverse cosmetic outcome.

  7. Prospective Study of Local Control and Late Radiation Toxicity After Intraoperative Radiation Therapy Boost for Early Breast Cancer

    International Nuclear Information System (INIS)

    Chang, David W.; Marvelde, Luc te; Chua, Boon H.

    2014-01-01

    Purpose: To report the local recurrence rate and late toxicity of intraoperative radiation therapy (IORT) boost to the tumor bed using the Intrabeam System followed by external-beam whole-breast irradiation (WBI) in women with early-stage breast cancer in a prospective single-institution study. Methods and Materials: Women with breast cancer ≤3 cm were recruited between February 2003 and May 2005. After breast-conserving surgery, a single dose of 5 Gy IORT boost was delivered using 50-kV x-rays to a depth of 10 mm from the applicator surface. This was followed by WBI to a total dose of 50 Gy in 25 fractions. Patients were reviewed at regular, predefined intervals. Late toxicities were recorded using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring systems. Results: Fifty-five patients completed both IORT boost and external-beam WBI. Median follow-up was 3.3 years (range, 1.4-4.1 years). There was no reported locoregional recurrence or death. One patient developed distant metastases. Grade 2 and 3 subcutaneous fibrosis was detected in 29 (53%) and 8 patients (15%), respectively. Conclusions: The use of IORT as a tumor bed boost using kV x-rays in breast-conserving therapy was associated with good local control but a clinically significant rate of grade 2 and 3 subcutaneous fibrosis

  8. Early intervention in acute myocardial infarction: significance for myocardial salvage of immediate intravenous streptokinase therapy followed by coronary angioplasty

    International Nuclear Information System (INIS)

    Miller, H.I.; Almagor, Y.; Keren, G.

    1987-01-01

    Sixteen patients with acute myocardial infarction underwent treatment with streptokinase up to 3 hours after the onset of chest pain. Nine patients (group I) received streptokinase within 1 hour of the onset of pain, and seven patients (group II) received it within 2 to 3 hours. All underwent multigated radionuclide ventriculography after streptokinase therapy and 1 week later. Percutaneous transluminal coronary angioplasty of the infarct artery was performed within 24 hours in all patients. An effort-limited treadmill stress test was performed before discharge. There was no mortality or serious complication. Mean peak total creatine kinase was 521 +/- 289 mU/ml in group I, and 1,614 +/- 709 mU/ml in group II (p less than 0.05). The mean initial left ventricular ejection fraction was 47 +/- 11% in group I and 37 +/- 10% in group II. After early angioplasty (within 24 hours) and at 1 week recovery, left ventricular ejection fraction increased to 53 +/- 9% in group I (p less than 0.05) and to 40 +/- 7% in group II (p = NS). Seven of the nine patients in group I had normal radionuclide ventriculograms at discharge compared with none of the seven patients in group II. Thrombolytic therapy administered less than 1 hour after the onset of symptoms of acute myocardial infarction followed by angioplasty of the infarct artery results in preservation of left ventricular function, whereas therapy given after 2 hours has only a limited effect

  9. Evaluation of effects of early intravenous thrombolytic therapy in acute myocardial infarction with 99mTc-MIBI tomography imaging

    International Nuclear Information System (INIS)

    Zhang Zhongzheng; Xue Zheng; Qin Fuzhong

    1997-01-01

    PURPOSE: To evaluate the effects of early intravenous thrombolytic therapy in acute myocardial infarction (AMI) with 99m Tc-MIBI tomography imaging. METHODS: 22 patients with AMI were observed using 99m Tc-MIBI rest myocardial tomography imaging. The semiquantitative score of myocardial 99m Tc-MIBI uptake was expressed with a four point scoring system. RESULTS: The findings showed in patients in whom reperfusion was achieved, mean scores decreased from 9.1 +- 3.3 before thrombolytic therapy to 3.7 +- 2.2 (t 4.085, P 99m Tc-MIBI perfusion defect segments correlated with that of the ECG-determined infarct site. The comparison between the first and the second myocardial imaging in the non-thrombolytic-treatment group was statistically insignificant. CONCLUSION: The potential advantages of rest myocardial imaging in AMI before and after thrombolytic therapy not only provide an information for assessing the extent of improvement of myocardial ischemia but also provide an imaging basis for determining coronary artery reperfusion

  10. The alterations of serum FGF-21 levels, metabolic and body composition in early breast cancer patients receiving adjuvant endocrine therapy.

    Science.gov (United States)

    Akyol, Murat; Alacacioglu, Ahmet; Demir, Leyla; Kucukzeybek, Yuksel; Yildiz, Yasar; Gumus, Zehra; Kara, Mete; Salman, Tarik; Varol, Umut; Taskaynatan, Halil; Oflazoglu, Utku; Bayoglu, Vedat; Tarhan, Mustafa Oktay

    2017-01-01

    In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy. Each patient was followed-up over a period of 1 year. Changes in body composition and serum lipid profile, glucose and FGF-21 levels were evaluated. We recorded the type of hormonal therapy, body mass index, waist-to-hip ratio, lipid profile, and FGF-21 levels both at the beginning and after 12 months. There was a statistically significant decrease in serum FGF-21 levels after 12 months of adjuvant endocrine therapy (46 ± 19.21 pg/ml vs. 30.99 ± 13.81 pg/ml, pbody water (pbody composition, glucose, lipid profile and FGF-21 were similar in tamoxifen and aromatase inhibitor groups. A positive correlation was found between basal weight, fat mass, fat-free mass and serum FGF-21 levels; however, the correlation was maintained only for the fat-free mass at the 12th month. As part of the present study, we suggest that both tamoxifen and aromatase inhibitors can reduce FGF-21 levels independently of body compositions, and these drugs can provide antihyperlipidemic, antidiabetic and cardio-protective effects. We also recommend that serum FGF-21 level can be utilized as a tumor biomarker in early-stage breast cancer and for monitoring purposes. FGF-21 levels may help physicians estimate prognosis, too. Further studies with larger populations may shed light on the role of FGF-21 in breast cancer.

  11. Early-Stage Classic Hodgkin Lymphoma: The Utilization of Radiation Therapy and Its Impact on Overall Survival

    Energy Technology Data Exchange (ETDEWEB)

    Parikh, Rahul R., E-mail: rparikh@chpnet.org [Department of Radiation Oncology, Mount Sinai Beth Israel Medical Center and Mount Sinai St. Luke' s-Roosevelt Hospitals, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, New York, New York (United States); Grossbard, Michael L. [Division of Hematology-Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York (United States); Harrison, Louis B. [Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Yahalom, Joachim [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2015-11-01

    Purpose: To examine the association between radiation therapy (RT) utilization and overall survival (OS) for patients with early-stage Hodgkin lymphoma (HL). Methods and Materials: Using the National Cancer Database, we evaluated clinical features and survival outcomes among patients diagnosed with stage I/II HL from 1998 to 2011. The association between RT use, covariables, and outcome was assessed in a Cox proportional hazards regression model. Propensity score matching was performed to balance observed confounding factors. Survival was estimated using the Kaplan-Meier method. Results: Among the 41,943 patients in the National Cancer Database with stage I/II HL, 29,752 patients were analyzed for this study. Radiation therapy use was associated with younger age (≤40 years), favorable insured status, higher socioeconomic status (income, education), and treatment at comprehensive community cancer centers (all P<.05). Five-year OS for patients receiving RT was 94.5%, versus 88.9% for those not receiving RT (P<.01). Radiation therapy use was a significant predictor of OS in the “As-Treated” cohort (hazard ratio 0.53, 95% confidence interval 0.49-0.58, P<.01) and intention-to-treat analysis (P<.01). After propensity score matching based on clinicopathologic characteristics, RT use remained associated with improved OS (hazard ratio 0.46, 95% confidence interval 0.38-0.56, P<.01). Over the study period, RT utilization for this cohort decreased from 55% to 44%, most commonly because it was not part of the planned initial treatment strategy. Conclusions: Consolidation RT was associated with improved OS for patients with early-stage classic HL. We also have identified patient-specific variations in the use of RT that may be targeted to improve patient access to care.

  12. Allergic Rhinitis in Children: Principles of Early Diagnosis and Effective Therapy. Overview of Clinical Recommendations

    Directory of Open Access Journals (Sweden)

    Alexander A. Baranov

    2017-01-01

    Full Text Available The article briefly summarizes the key provisions of the clinical recommendations on medical care delivery for children with allergic rhinitis: modern approaches to diagnosis and therapy. The current document was developed by the professional association of pediatric specialists —the Union of Pediatricians of Russia — together with the leading experts of the Russian Association of Allergists and Clinical Immunologists. The recommendations are regularly updated due to the latest evidence-based results of effectiveness and safety of various medical interventions. The article presents information on the epidemiology of allergic rhinitis in children, specific diagnostic features which provide the opportunity for the timely and correct diagnosis and an effective therapy with personal approach.

  13. Therapies in early development for the treatment of urinary tract inflammation.

    Science.gov (United States)

    Zacchè, Martino Maria; Giarenis, Ilias

    2016-01-01

    Urinary tract inflammation is a very common clinical condition. It is caused by several pathogens and antibiotic treatment is the mainstay of therapy. Increasing antimicrobial resistance and high recurrence rates represent a challenge. Consequently, there is an unmet need for new therapeutic options. The authors discuss the rationale of emerging management strategies and current experimentation. Furthermore, they focus on both acute and recurrent urinary tract infections (UTIs) and examine a range of therapeutics, including new antibiotics, vaccines, mannosides, hyaluronic acid, probiotics, immunomodulant agents and novel compounds derived from nanotechnology. Basic science studies have elucidated the pathogenesis of UTIs and built up the ground for the development of new therapies. Evidence is mainly derived from animal studies on murine models of bacterial cystitis. However, clinical trials are scanty and cannot provide us with robust evidence. Hetereogeneity and virulence of uropathogens pose a threat that scientists and clinicians are struggling to overcome.

  14. The early development of transient and permanent hypothyroidism following radioiodine therapy for hyperthyroid Graves' disease

    International Nuclear Information System (INIS)

    Peden, N.R.; Hart, J.R.

    1984-01-01

    The outcome in 110 patients first treated with radioiodine (mean dose 6.56 mCi) for hyperthyroid Graves' disease in 1980 was reviewed. In 23 percent of the patients the disease had not been controlled by the initial dose after 3 months, and 17 percent were given one or two more doses. Within 2 years 65 percent of the patients required replacement thyroxine therapy. Although about half of the patients were biochemically hypothyroid 3 months after the last dose of iodine 131, this condition was transient in a third of them; five of these patients even became hyperthyroid again. Patients with transient, as opposed to permanent, hypothyroidism at 3 months tended to be clinically euthyroid but to have residual palpable thyroid tissue and only a modest reduction in the serum thyroxine level. It is therefore recommended that patients not overtly hypothyroid 3 months after treatment with 131 I be observed still longer before thyroxine replacement therapy is instituted

  15. Goal-Directed Resilience in Training (GRIT: A Biopsychosocial Model of Self-Regulation, Executive Functions, and Personal Growth (Eudaimonia in Evocative Contexts of PTSD, Obesity, and Chronic Pain

    Directory of Open Access Journals (Sweden)

    Martha Kent

    2015-06-01

    Full Text Available This paper presents a biopsychosocial model of self-regulation, executive functions, and personal growth that we have applied to Goal-Directed Resilience in Training (GRIT interventions for posttraumatic stress disorder (PTSD, obesity, and chronic pain. Implications of the training for the prevention of maladaptation, including psychological distress and health declines, and for promoting healthy development are addressed. Existing models of attention, cognition, and physiology were sourced in combination with qualitative study findings in developing this resilience skills intervention. We used qualitative methods to uncover life skills that are most salient in cases of extreme adversity, finding that goal-directed actions that reflected an individual’s values and common humanity with others created a context-independent domain that could compensate for the effects of adversity. The efficacy of the resilience skills intervention for promoting positive emotion, enhancing neurocognitive capacities, and reducing symptoms was investigated in a randomized controlled trial with a veteran population diagnosed with PTSD. The intervention had low attrition (8% and demonstrated improvement on symptom and wellbeing outcomes, indicating that the intervention may be efficacious for PTSD and that it taps into those mechanisms which the intervention was designed to address. Feasibility studies for groups with comorbid diagnoses, such as chronic pain and PTSD, also showed positive results, leading to the application of the GRIT intervention to other evocative contexts such as obesity and chronic pain.

  16. Complications of combined radical hysterectomy-postoperative radiation therapy in women with early stage cervical cancer

    International Nuclear Information System (INIS)

    Barter, J.F.; Soong, S.J.; Shingleton, H.M.; Hatch, K.D.; Orr, J.W. Jr.

    1989-01-01

    Fifty patients with cervical cancer were treated with radical hysterectomy and lymphadenectomy followed by postoperative radiation therapy for high risk factors (nodal metastases, lymphvascular space invasion, close or involved margins) at the University of Alabama at Birmingham Medical Center from 1969 to 1984. Fifteen (30%) of the patients treated had serious complications, 8 (16%) requiring an operation, and 1 (2%) dying as a result of treatment-related problems. This combined modality approach is associated with significant complications

  17. Evidence of Effectiveness of Current Therapies to Prevent and Treat Early Childhood Caries

    DEFF Research Database (Denmark)

    Twetman, Svante; Dhar, Vineet

    2015-01-01

    PURPOSE: The purpose of this paper was to systematically review the quality of evidence related to self-applied and professionally applied fluorides, antimicrobial agents, fissure sealants, temporary restorations, and restorative care for the prevention and management of early childhood caries (E...

  18. AMTA Monograph Series - Effective Clinical Practice in Music Therapy Early Childhood and School Age Educational Settings

    Science.gov (United States)

    Humpal, Marcia Earl, Ed.; Colwell, Cynthia, Ed.

    2006-01-01

    Educators, families, and media in increasing numbers are recognizing the unique role music plays in young children's development. More and more daycare, preschool, and early intervention centers offer employment opportunities that reflect the needs and attitudes of our ever-changing society. Furthermore, Federal and state regulations, a changing…

  19. Chemoradiation therapy with or without salvage surgery for early squamous cell carcinoma of the hypopharynx

    International Nuclear Information System (INIS)

    Nakamura, Katsumasa; Shioyama, Yoshiyuki; Sasaki, Tomonari; Ohga, Saiji; Saku, Madoka; Urashima, Yusuke; Yoshitake, Tadamasa; Nakashima, Torahiko; Kuratomi, Yuichiro; Komune, Shizuo; Terashima, Hiromi; Honda, Hiroshi

    2005-01-01

    Purpose: Early squamous cell carcinoma of the hypopharynx is a rare clinical entity. Our objective was to analyze the outcome of patients with early hypopharyngeal cancer treated with curative radiotherapy or the combination of preoperative radiotherapy with surgery. Methods and Materials: Forty-three patients with Stage I-II hypopharyngeal cancer were initially treated with 30-40 Gy of irradiation with or without chemotherapy. Thirty-two patients (74.4%) who demonstrated a complete response continued to receive further radiotherapy, with a median total dose of 61.2 Gy. Eleven other patients (25.6%) received surgery. Results: Local control with laryngeal voice preservation was achieved in 8 (88.9%) of 9 patients with Stage I disease, and in 23 (67.6%) of 34 patients with Stage II disease. The overall and disease-specific 5-year survival rates for all patients were 70.4% and 89.5%, respectively. The disease-specific survival rates according to the T-category were 100% for patients with T1 disease and 87.2% for patients with T2 disease (p = 0.32). Twenty patients (46.5%) had synchronous or metachronous cancers. Four patients died of hypopharyngeal cancer, and 5 died of second-primary esophageal cancer. Conclusions: A majority of patients with early hypopharyngeal cancer was curable. However, second malignancies influenced the overall outcome of patients with early hypopharyngeal cancer

  20. Effects of early changes in organ dysfunctions on the outcomes of critically ill patients in need of renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Elizabeth Maccariello

    2008-01-01

    Full Text Available INTRODUCTION: Acute kidney injury usually develops in critically ill patients in the context of multiple organ dysfunctions. OBJECTIVE: To evaluate the effect of changes in associated organ dysfunctions over the first three days of renal replacement therapy on the outcomes of patients with acute kidney injury. METHODS: Over a 19-month period, we evaluated 260 patients admitted to the intensive care units of three tertiary-care hospitals who required renal replacement therapy for > 48 h. Organ dysfunctions were evaluated by SOFA score (excluding renal points on the first (D1 and third (D3 days of renal replacement therapy. Absolute (A-SOFA and relative (D-SOFA changes in SOFA scores were also calculated. RESULTS: Hospital mortality rate was 75%. Organ dysfunctions worsened (A-SOFA>0 in 53%, remained unchanged (A-SOFA=0 in 17% and improved (A-SOFA<0 in 30% of patients; and mortality was lower in the last group (80% vs. 84% vs. 61%, p=0.003. SOFA on D1 (p<0.001, SOFA on D3 (p<0.001, A-SOFA (p=0.019 and D-SOFA (p=0.016 were higher in non-survivors. However, neither A-SOFA nor D-SOFA discriminated survivors from non-survivors on an individual basis. Adjusting for other covariates (including SOFA on D1, A-SOFA and D-SOFA were associated with increased mortality, and patients in whom SOFA scores worsened or remained unchanged had poorer outcomes. CONCLUSIONS: In addition to baseline values, early changes in SOFA score after the start of renal replacement therapy were associated with hospital mortality. However, no prognostic score should be used as the only parameter to predict individual outcomes.

  1. Long-term follow-up of testicular function following radiation therapy for early-stage Hodgkin's disease

    International Nuclear Information System (INIS)

    Kinsella, T.J.; Trivette, G.; Rowland, J.; Sorace, R.; Miller, R.; Fraass, B.; Steinberg, S.M.; Glatstein, E.; Sherins, R.J.

    1989-01-01

    Seventeen male patients with pathological staged I-IIIA1 Hodgkin's disease were followed prospectively for radiation damage to the testes from low-dose scattered irradiation. During conventionally fractionated radiation therapy, the testicular dose ranged from 6 to 70 cGy. Testicular function was measured in a prospective fashion by repeated analyses (every 6 to 12 months) of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Patients were also followed by serial semen analyses and by a questionnaire on fertility. The follow-up period ranged from 3 to 7 years after completion of radiation therapy. In patients receiving greater than or equal to 20 cGy, there was a dose-dependent increase in serum FSH values following irradiation, with the maximum difference at 6 months compared with pretreatment levels. All patients showed a return to normal FSH values within 12 to 24 months following irradiation. No significant changes in LH and testosterone were observed in this patient group. Eight patients with a normal pretreatment semen analysis provided serial semen samples and two patients showed transient oligospermia with complete recovery by 18 months following treatment. Four patients have fathered normal offspring following radiation therapy. We conclude that low doses (greater than 20 cGy) of scatter irradiation during treatment for Hodgkin's disease can result in transient injury to the seminiferous tubule as manifested by elevations of FSH for 6 to 24 months following treatment. Below 20 cGy, FSH values remained in the normal range. No evidence of Leydig cell injury (using LH and testosterone) was seen in this dose range (up to 70 cGy). Thus, patients with early-stage Hodgkin's disease can be treated with radiation therapy with little to no risk of irreversible testicular injury. Radiation treatment techniques to shield the testes are discussed

  2. Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age.

    Science.gov (United States)

    Visentin, Silvia; Manara, Renzo; Milanese, Laura; Da Roit, Anna; Forner, Gabriella; Salviato, Eleonora; Citton, Valentina; Magno, Fioretta Marciani; Orzan, Eva; Morando, Carla; Cusinato, Riccardo; Mengoli, Carlo; Palu, Giorgio; Ermani, Mario; Rinaldi, Roberto; Cosmi, Erich; Gussetti, Nadia

    2012-08-01

    Primary cytomegalovirus (CMV) infection during pregnancy is the leading infectious cause of congenital neurological disabilities. Early CMV infection carries a higher risk of adverse neonatal outcome (sensorineural hearing loss or neurological deficits). Intravenous hyperimmunoglobulin (HIG) therapy seems to be promising, but its efficacy needs further investigation. Since 2002, we have enrolled consecutively all pregnant women with early (ie, before gestational week 17) CMV infection. Beginning in 2007, all women were offered treatment with HIG (200 UI per kilogram of maternal weight, in a single intravenous administration). Outcome of infants was evaluated at the age of 1 year. Of the 592 women with early primary CMV infection, amniocentesis for CMV DNA detection was performed for 446. Of the 92 CMV-positive fetuses, pregnancy was terminated for 24, HIG was administered to mothers of 31, and no treatment was received by mothers of 37. Fetuses of treated mothers did not differ from fetuses of nontreated mothers according to mother's age, gestational week of infection, CMV load, or detection of abnormal ultrasonography findings. At the 1-year evaluation, 4 of 31 infants with treated mothers (13%; 95% confidence interval [CI], 1%-25%) and 16 of 37 infants with nontreated mothers (43%; 95% CI, 27%-59%) presented with poor outcomes (P primary CMV infection before gestational week 17.

  3. Risk of fatal cerebrovascular accidents after external beam radiation therapy for early-stage glottic laryngeal cancer.

    Science.gov (United States)

    Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O'Malley, Bert; Weinstein, Gregory S; Bekelman, Justin E

    2014-05-01

    This study compared the risk of fatal cerebrovascular accidents (CVAs) in patients with early-stage glottic laryngeal cancer receiving surgery or external beam radiation therapy (EBRT). Using a competing risks survival analysis, we compared the risk of death because of CVA among patients with early-stage glottic laryngeal cancer receiving surgery or EBRT in the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8%; 95% confidence interval [CI], 2.3% to 3.4%) compared to surgery (1.5%; 95% CI, 0.8% to 2.3%; p = .024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted hazard ratio [HR], 1.75; 95% CI, 1.04-2.96; p = .037). Treatment for early-stage glottic laryngeal cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. Copyright © 2013 Wiley Periodicals, Inc.

  4. Effect of antimicrobial photodynamic therapy on the counts of salivary Streptococcus mutans in children with severe early childhood caries.

    Science.gov (United States)

    Fekrazad, Reza; Seraj, Bahman; Chiniforush, Nasim; Rokouei, Mehrak; Mousavi, Niloofar; Ghadimi, Sara

    2017-06-01

    Antimicrobial photodynamic therapy (aPDT) is a novel technique for reduction of pathogenic microorganisms in dentistry. The aim of this study was to evaluate the effects of aPDT on Streptococcus mutans reduction in children with severe early childhood caries. Twenty-two children with severe early childhood caries aged 3-6 years were treated with toluoidine blue O (TBO) for 1min and irradiated by a Light Emitting Diode (LED; FotoSan, CMS Dental, Denmark) with the exposure time of 150s. Saliva samples were collected at baseline, 1h and 7 days after treatment. S. mutans counts were determined using the Dentocult SM Strip mutans. The counts of S. mutans in saliva decreased significantly after 1h (Pmutans counts in saliva was not significant between the baseline and 7 days after treatment (P>0.05). aPDT seems to be efficient to reduce salivary S. mutans immediately after treatment in children with severe early childhood caries. However, further research is needed to evaluate different doses and frequency of irradiation in combination with restoring carious teeth to find more durable results. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xi-Mei [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Ye-Xiong, E-mail: yexiong@yahoo.com [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Wang, Wei-Hu; Jin, Jing; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Fang, Hui; Ren, Hua [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Zhou, Li-Qiang [Department of Medical Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Liu, Xin-Fan; Yu, Zi-Hao [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China)

    2013-03-15

    Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival.

  6. Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

    International Nuclear Information System (INIS)

    Zhang, Xi-Mei; Li, Ye-Xiong; Wang, Wei-Hu; Jin, Jing; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Fang, Hui; Ren, Hua; Zhou, Li-Qiang; Liu, Xin-Fan; Yu, Zi-Hao

    2013-01-01

    Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival

  7. The Effect of Neoadjuvant Therapy on Early Complications of Esophageal Cancer Surgery

    Directory of Open Access Journals (Sweden)

    Mohammadtaghi Rajabi Mashhadi

    2015-07-01

    Full Text Available Introduction: Early diagnosis and appropriate treatment is required in esophageal cancer due to its invasive nature. The aim of this study was to evaluate early post-esophagectomy complications in patients with esophageal cancer who received neoadjuvant chemoradiotherapy (NACR.   Materials and Methods: This randomized clinical trial was carried out between 2009 and 2011. Patients with lower-third esophageal cancer were randomly assigned to one of two groups. The first group consisted of 50 patients receiving standard chemoradiotherapy (Group A and then undergoing surgery, and the second group consisted of 50 patients undergoing surgery only (Group B. Patients were evaluated with respect to age, gender, clinical symptoms, type of pathology, time of surgery, perioperative blood loss, and number of lymph nodes resected as well as early post-operative complicate including leakage at the anastomosis site, chylothorax and pulmonary complications, hospitalization period, and mortality rate within the first 30 days after surgery.   Results: The mean age of patients was 55 years. Seventy-two patients had squamous cell carcinoma (SCC and 28 patients had adenocarcinoma (ACC. There was no significant difference between the two groups with respect to age, gender, time of surgery, complications including anastomotic leakage, chylothorax, pulmonary complications, cardiac complications, deep venous thrombosis (DVT, or mortality. However, there was a significant difference between the two groups regarding hospital stay, time of surgery, perioperative blood loss, and number of lymph nodes resected.   Conclusion:  The use of NACR did not increase early post-operative complications or mortality among patients with esophageal cancer.

  8. Early carcinoma of the penis treated with radiation therapy: a preliminary report

    International Nuclear Information System (INIS)

    Sur, R.K.; Babaiah, M.; Sudarshan, G.; Shah, A.M.; Ranganathan, Vanieshree

    1994-01-01

    Four patients with stage 1 carcinoma of the penis were treated with radical external beam radiotherapy using individualized wax bolus. All patients are alive and doing well at the time of this report, 2 years after treatment. No patient had local recurrence and all had preservation of the organ and its function. Radiotherapy can be used as an alternative modality to surgery especially in the early stages of penile cancers. (author). 13 refs., 1 tab

  9. Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity

    International Nuclear Information System (INIS)

    Huang, Eugene; Teh, Bin S.; Strother, Douglas R.; Davis, Quillin G.; Chiu, J. Kam; Lu, Hsin H.; Carpenter, L. Steven; Mai Weiyuan; Chintagumpala, Murali M.; South, Michael; Grant, Walter H. III; Butler, E. Brian; Woo, Shiao Y.

    2002-01-01

    Purpose: The combination of cisplatin chemotherapy and radiation therapy for the treatment of medulloblastoma has been shown to cause significant ototoxicity, impairing a child's cognitive function and quality of life. Our purpose is to determine whether the new conformal technique of intensity-modulated radiation therapy (IMRT) can achieve lower rates of hearing loss by decreasing the radiation dose delivered to the cochlea and eighth cranial nerve (auditory apparatus). Patients and Methods: Twenty-six pediatric patients treated for medulloblastoma were retrospectively divided into two groups that received either conventional radiotherapy (Conventional-RT Group) or IMRT (IMRT Group). One hundred thirteen pure-tone audiograms were evaluated retrospectively, and hearing function was graded on a scale of 0 to 4 according to the Pediatric Oncology Group's toxicity criteria. Statistical analysis comparing the rates of ototoxicity was performed using Fisher's exact test with two-tailed analysis. Results: When compared to conventional radiotherapy, IMRT delivered 68% of the radiation dose to the auditory apparatus (mean dose: 36.7 vs. 54.2 Gy). Audiometric evaluation showed that mean decibel hearing thresholds of the IMRT Group were lower at every frequency compared to those of the Conventional-RT Group, despite having higher cumulative doses of cisplatin. The overall incidence of ototoxicity was lower in the IMRT Group. Thirteen percent of the IMRT Group had Grade 3 or 4 hearing loss, compared to 64% of the Conventional-RT Group (p<0.014). Conclusion: The conformal technique of IMRT delivered much lower doses of radiation to the auditory apparatus, while still delivering full doses to the desired target volume. Our findings suggest that, despite higher doses of cisplatin, and despite radiotherapy before cisplatin therapy, treatment with IMRT can achieve a lower rate of hearing loss

  10. Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

    Science.gov (United States)

    Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T.

    2018-01-01

    Introduction Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted. PMID:28271910

  11. Proton Therapy for Breast Cancer After Mastectomy: Early Outcomes of a Prospective Clinical Trial

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, Shannon M., E-mail: smacdonald@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Patel, Sagar A.; Hickey, Shea [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Specht, Michelle [Department of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Isakoff, Steven J. [Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Gadd, Michele; Smith, Barbara L. [Department of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Adams, Judith; DeLaney, Thomas F.; Kooy, Hanne; Lu, Hsiao-Ming; Taghian, Alphonse G. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2013-07-01

    Purpose: Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction. Methods and Materials: Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after the completion of therapy. All patients consented to have photographs taken for documentation of skin toxicity. Results: Eleven of 12 patients had left-sided breast cancer. One patient was treated for right-sided breast cancer with bilateral implants. Five women had permanent implants at the time of RT, and 7 did not have immediate reconstruction. All patients completed proton RT to a dose of 50.4 Gy (relative biological effectiveness [RBE]) to the chest wall and 45 to 50.4 Gy (RBE) to the regional lymphatics. No photon or electron component was used. The maximum skin toxicity during radiation was grade 2, according to the Common Terminology Criteria for Adverse Events (CTCAE). The maximum CTCAE fatigue was grade 3. There have been no cases of RT pneumonitis to date. Conclusions: Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT delivery using standard methods.

  12. Proton Therapy for Breast Cancer After Mastectomy: Early Outcomes of a Prospective Clinical Trial

    International Nuclear Information System (INIS)

    MacDonald, Shannon M.; Patel, Sagar A.; Hickey, Shea; Specht, Michelle; Isakoff, Steven J.; Gadd, Michele; Smith, Barbara L.; Yeap, Beow Y.; Adams, Judith; DeLaney, Thomas F.; Kooy, Hanne; Lu, Hsiao-Ming; Taghian, Alphonse G.

    2013-01-01

    Purpose: Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction. Methods and Materials: Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after the completion of therapy. All patients consented to have photographs taken for documentation of skin toxicity. Results: Eleven of 12 patients had left-sided breast cancer. One patient was treated for right-sided breast cancer with bilateral implants. Five women had permanent implants at the time of RT, and 7 did not have immediate reconstruction. All patients completed proton RT to a dose of 50.4 Gy (relative biological effectiveness [RBE]) to the chest wall and 45 to 50.4 Gy (RBE) to the regional lymphatics. No photon or electron component was used. The maximum skin toxicity during radiation was grade 2, according to the Common Terminology Criteria for Adverse Events (CTCAE). The maximum CTCAE fatigue was grade 3. There have been no cases of RT pneumonitis to date. Conclusions: Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT delivery using standard methods

  13. Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

    Science.gov (United States)

    Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T

    2017-04-01

    Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

  14. Prediction of transfusion therapy tactics for prophylaxis of early postoperative complications in coronary surgery

    Directory of Open Access Journals (Sweden)

    И. А. Мандель

    2015-10-01

    Full Text Available The study focuses on the tactics of transfusion therapy during coronary artery bypass surgery with cardiopulmonary bypass in patients with left ventricular ejection fraction higher or lower than 40%. To predict the tactics of intraoperative transfusion therapy, hypoxic tests were preoperatively conducted in the main group of patients. A traditional approach to blood transfusion was applied in the control group of patients. The analysis of clinical and laboratory data, hemodynamics and oxygen balance, as well as follow-up data allowed to prove the possibility of decreasing allogenic blood use by 48.8% (p = 0,02. Based on the hypoxic test data, criteria for lowering the intraoperative trigger hemoglobin level down to 70 g/l, including the patients with a low left ventricular ejection fraction. It was shown that our tactics of trigger hemoglobin level calculation allows for reducing artificial lung ventilation time, frequency of gastrointestinal complications, multiple organ failure, as well as duration of stay at ICU.

  15. Extending Parent–Child Interaction Therapy for Early Childhood Internalizing Problems: New Advances for an Overlooked Population

    Science.gov (United States)

    Puliafico, Anthony C.; Kurtz, Steven M. S.; Pincus, Donna B.; Comer, Jonathan S.

    2014-01-01

    Although efficacious psychological treatments for internalizing disorders are now well established for school-aged children, until recently there have regrettably been limited empirical efforts to clarify indicated psychological intervention methods for the treatment of mood and anxiety disorders presenting in early childhood. Young children lack many of the developmental capacities required to effectively participate in established treatments for mood and anxiety problems presenting in older children, making simple downward extensions of these treatments for the management of preschool internalizing problems misguided. In recent years, a number of research groups have successfully adapted and modified parent–child interaction therapy (PCIT), originally developed to treat externalizing problems in young children, to treat various early internalizing problems with a set of neighboring protocols. As in traditional PCIT, these extensions target child symptoms by directly reshaping parent–child interaction patterns associated with the maintenance of symptoms. The present review outlines this emerging set of novel PCIT adaptations and modifications for mood and anxiety problems in young children and reviews preliminary evidence supporting their use. Specifically, we cover (a) PCIT for early separation anxiety disorder; (b) the PCIT-CALM (Coaching Approach behavior and Leading by Modeling) Program for the full range of early anxiety disorders; (c) the group Turtle Program for behavioral inhibition; and (d) the PCIT-ED (Emotional Development) Program for preschool depression. In addition, emerging PCIT-related protocols in need of empirical attention—such as the PCIT-SM (selective mutism) Program for young children with SM—are also considered. Implications of these protocols are discussed with regard to their unique potential to address the clinical needs of young children with internalizing problems. Obstacles to broad dissemination are addressed, and we consider

  16. Extending parent-child interaction therapy for early childhood internalizing problems: new advances for an overlooked population.

    Science.gov (United States)

    Carpenter, Aubrey L; Puliafico, Anthony C; Kurtz, Steven M S; Pincus, Donna B; Comer, Jonathan S

    2014-12-01

    Although efficacious psychological treatments for internalizing disorders are now well established for school-aged children, until recently there have regrettably been limited empirical efforts to clarify indicated psychological intervention methods for the treatment of mood and anxiety disorders presenting in early childhood. Young children lack many of the developmental capacities required to effectively participate in established treatments for mood and anxiety problems presenting in older children, making simple downward extensions of these treatments for the management of preschool internalizing problems misguided. In recent years, a number of research groups have successfully adapted and modified parent-child interaction therapy (PCIT), originally developed to treat externalizing problems in young children, to treat various early internalizing problems with a set of neighboring protocols. As in traditional PCIT, these extensions target child symptoms by directly reshaping parent-child interaction patterns associated with the maintenance of symptoms. The present review outlines this emerging set of novel PCIT adaptations and modifications for mood and anxiety problems in young children and reviews preliminary evidence supporting their use. Specifically, we cover (a) PCIT for early separation anxiety disorder; (b) the PCIT-CALM (Coaching Approach behavior and Leading by Modeling) Program for the full range of early anxiety disorders; (c) the group Turtle Program for behavioral inhibition; and (d) the PCIT-ED (Emotional Development) Program for preschool depression. In addition, emerging PCIT-related protocols in need of empirical attention--such as the PCIT-SM (selective mutism) Program for young children with SM--are also considered. Implications of these protocols are discussed with regard to their unique potential to address the clinical needs of young children with internalizing problems. Obstacles to broad dissemination are addressed, and we consider

  17. Predictors of early change in bulimia nervosa after a brief psychoeducational therapy.

    Science.gov (United States)

    Fernàndez-Aranda, Fernando; Álvarez-Moya, Eva M; Martínez-Viana, Cristina; Sànchez, Isabel; Granero, Roser; Penelo, Eva; Forcano, Laura; Peñas-Lledó, Eva

    2009-06-01

    We aimed to examine baseline predictors of treatment response in bulimic patients. 241 seeking-treatment females with bulimia nervosa completed an exhaustive assessment and were referred to a six-session psychoeducational group. Regression analyses of treatment response were performed. Childhood obesity, lower frequency of eating symptomatology, lower body mass index, older age, and lower family's and patient's concern about the disorder were predictors of poor abstinence. Suicidal ideation, alcohol abuse, higher maximum BMI, higher novelty seeking and lower baseline purging frequency predicted dropouts. Predictors of early symptom changes and dropouts were similar to those identified in longer CBT interventions.

  18. Psychological aspects of breast conserving therapy (BCT) in early breast cancer

    International Nuclear Information System (INIS)

    Jeziorski, A.

    1994-01-01

    Psychological and social status of 40 women who underwent BCT in early cancer was compared with 40 women after radical mastectomy. Women in BCT group showed significantly less anxiety about overall body image. The majority of them reported adjustment to work or ability to carry out household tasks. Almost all returned to normal social activities and interpersonal relationships. The majority of patients treated with BCT were fully satisfied in spite of unsatisfactory cosmetic results achieved in some of them and in spite of long duration of combined modality treatment. (author)

  19. Conformal radiation therapy of localized prostate cancer: acute tolerance and early evaluation of effectiveness

    International Nuclear Information System (INIS)

    Zierhut, D.; Flentje, M.; Sroka-Perez, G.; Rudat, V.; Engenhart-Cabillic, R.; Wannenmacher, M.

    1997-01-01

    Aim: In a prospective trial early effectiveness and acute toxicity of conformal 3D-planned radiotherapy for localized prostate cancer was quantified using dose-volume-histogramms and evaluated with respect of treatment technique. Results: Eleven patients (of 32) had none, 15 mild (RTOG grade 1) and 6 moderate symptoms (RTOG grade 2, mainly diarrhoea, dysuria and polyuria). Acute complications leading to treatment interruption did not occur. In 16 patients symptoms disappeared within 6 weeks after radiotherapy. Only 2 men had symptoms which lasted longer than 3 months and were endoscopically examined. Up to now no late complications were detected. Incidence and severity of toxicity was significantly (p [de

  20. EVALUATION OF EARLY ISCHEMIC CHANGES IN STROKE PATIENTS TREATED WITH THROMBOLYTIC THERAPY

    OpenAIRE

    Kolevski Goran; Korneti-Pekevska Kostandina

    2016-01-01

    Introduction:The aim of this study is to evaluate early brain ischemic changes on CT scan in stroke patients in correlation with the clinical outcome, as well as to evaluate if there is prognostic and predictive features that can be used. Patients and methods: We examined 20 patients with acute ischemic stroke, from which 12 were male and 8 were female, at the age from 47 to 76 years. Results: The hyperdense medial artery (HMA) sign was present in 10 (50%) patients. Concerning the ASPECTS s...

  1. A case of deep venous thrombosis following protracted catatonic immobility recovered with electroconvulsive therapy: the relevance for an early intervention.

    Science.gov (United States)

    Medda, Pierpaolo; Fornaro, Michele; Fratta, Sara; Callari, Antonio; Manzo, Valerio; Ciaponi, Benedetta; Perugi, Giulio

    2012-01-01

    Catatonic patients often experience prolonged inactivity and dehydration, thus being prone to venous stasis leading to life-threatening thrombosis and pulmonary embolism (PE). When this occurs, the prescription of electroconvulsive therapy (ECT), actually irreplaceable in most life-threatening cases, remains controversial essentially due to an increased risk for PE and cerebral haemorrhage, with timing clinical decisions being as crucial as difficult to take. We report the case of a catatonic patient affected by malnutrition, deep venous thrombosis, severe pressure ulcers and septic syndrome resulting from previous untimely management, successfully treated with 16 well-tolerated ECT applications upon intensive supportive care. Although anecdotal, cases like this remind the relevance of early ECT to reduce the risk for potentially life-threatening complications due to prolonged catatonic inactivity, especially to those clinicians substantially disregarding this practice. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Antiretroviral therapy during pregnancy and early neonatal life: consequences for HIV-exposed, uninfected children

    Directory of Open Access Journals (Sweden)

    Patrícia El Beitune

    Full Text Available Women have emerged as the fastest growing human immunodeficiency virus (HIV infected population worldwide, mainly because of the increasing occurrence of heterosexual transmission. Most infected women are of reproductive age and one of the greatest concerns for both women and their physicians is that more than 1,600 infants become infected with HIV each day. Almost all infections are a result of mother-to-child transmission of HIV. With the advent of combination antiretroviral therapies, transmission rates lower than 2% have been achieved in clinical studies. Antiretroviral compounds differ from most other new pharmaceutical agents in that they have become widely prescribed in pregnancy in the absence of proof of safety. We reviewed antiretroviral agents used in pregnant women infected with human immunodeficiency virus, mother-to-child transmission, and their consequences for infants.

  3. Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Brasso, Klaus; Christensen, Ib J

    2015-01-01

    BACKGROUND: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. METHODS: A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non......-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). FINDINGS: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised...... disease (hazard ratios (HR)=0.77 (95% confidence interval (CI): 0.63-0.94, p=0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised...

  4. Stereotactic radiation therapy: a second gold standard in the treatment of early-stage lung cancer?

    International Nuclear Information System (INIS)

    Santini B, Alejandro; Valdez C, Cristian; Sepulveda A, Veronica; Baeza L, Ricardo; Bustos, Sergio

    2016-01-01

    Lung cancer is still the leading cause of cancer death in the world. Although in Chile this is not the case, the northern regions of the country show higher incidence and mortality rates than the other Chilean regions. In recent years screening guides for lung cancer with low-dose scanner have begun to be established, and most of the medical societies involved in this subject have already settled the selection criteria. At the same time new techniques of treatment for these patients have developed, with highly sophisticated radiotherapy such as SBRT (Stereotactic Body Radiotherapy) and SBART (Stereotactic ablative body radiation therapy) that are revealing extremely encouraging results and augur significant changes in the coming years. In the present review we analyze the current work, their results, and the future of this treatment modality

  5. Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

    International Nuclear Information System (INIS)

    Safdieh, Joseph; Schwartz, David; Weiner, Joseph; Weiss, Jeffrey P.; Madeb, Isaac; Rotman, Marvin; Schreiber, David; Rineer, Justin

    2014-01-01

    To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

  6. SU-F-R-55: Early Detection of Treatment Induced Bone Marrow Injury During Chemoradiation Therapy Using Quantitative CT

    Energy Technology Data Exchange (ETDEWEB)

    Chen, X; Song, Y; Erickson, B; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2016-06-15

    Purpose: Acute hematologic toxicity associated with bone marrow injury is a common complication of chemoradiation therapy (CRT) for pelvic malignancies. In this work, we investigate the feasibility of using quantitative CT to detect bone marrow injury during CRT. Methods: Daily CTs were acquired during routine CT-guided radiation therapy using a CT-on-rails for 15 cervical cancer patients. All patients treated with a radiation dose of 45.0 to 50.4 Gy in 1.8 Gy/fraction along with chemotherapy. For each patient, the contours of bone marrow were generated in L4, L5 and sacrum on the first daily CT and then populated to other daily CTs by rigid registration using MIM (MIM Software Inc., Cleveland, OH) with manual editing if possible. A series of CT texture parameters, including Hunsfield Unit (HU) histogram, mean HU, entropy, energy, in bone marrow contours were calculated using MATLAB on each daily CT and were correlated with the completed blood counts (CBC) collected weekly for each patient. The correlations were analyzed with Pearson correlation tests. Results: For all patient data analyzed, mean HU in bone marrow decreased during CRT delivery. From the first to the last fraction the average mean HU reduction is 58.1 ± 13.6 HU (P<0.01). This decrease can be observed as early as after first 5 fractions and is strongly associated with the changes of most CBC quantities, such as the reductions of white and blood cell counts (r=0.97, P=0.001). The reduction of HU is spatially varied. Conclusion: Chemoradiation induced bone marrow injury can be detected during the delivery of CRT using quantitative CT. Chemoradiation results in reductions in mean HU, which are strongly associated with the change in the pretrial blood cell counts. Early detection of bone marrow injury with commonly available CT opens a door to improve bone marrow sparing, reducing risk of hematologic toxicity.

  7. The failure of anxiolytic therapies in early clinical trials: what needs to be done.

    Science.gov (United States)

    Stewart, Adam Michael; Nguyen, Michael; Poudel, Manoj K; Warnick, Jason E; Echevarria, David J; Beaton, Elliott A; Song, Cai; Kalueff, Allan V

    2015-04-01

    Anxiety spectrum disorders (ASDs) are highly prevalent psychiatric illnesses that affect millions of people worldwide. Strongly associated with stress, common ASDs include generalized anxiety disorder, panic, social anxiety, phobias and drug-abuse-related anxiety. In addition to ASDs, several other prevalent psychiatric illnesses represent trauma/stressor-related disorders, such as post-traumatic stress disorder and acute stress disorder. Anxiolytic drugs, commonly prescribed to treat ASDs and trauma/stressor-related disorders, form a highly heterogenous group, modulating multiple neurotransmitters and physiological mechanisms. However, overt individual differences in efficacy and the potential for serious side-effects (including addiction and drug interaction) indicate a need for further drug development. Yet, over the past 50 years, there has been relatively little progress in the development of novel anxiolytic medications, especially when promising candidate drugs often fail in early clinical trials. Herein, the authors present recommendations of the Task Force on Anxiolytic Drugs of the International Stress and Behavior Society on how to improve anxiolytic drug discovery. These recommendations cover a wide spectrum of aspects, ranging from methodological improvements to conceptual insights and innovation. In order to improve the success of anxiolytic drugs in early clinical trials, the goals of preclinical trials may need to be adjusted from a clinical perspective and better synchronized with those of clinical studies. Indeed, it is important to realize that the strategic goals and approaches must be similar if we want to have a smoother transition between phases.

  8. Early environmental therapy rescues brain development in a mouse model of Down syndrome.

    Science.gov (United States)

    Begenisic, Tatjana; Sansevero, Gabriele; Baroncelli, Laura; Cioni, Giovanni; Sale, Alessandro

    2015-10-01

    Down syndrome (DS), the most common genetic disorder associated with intellectual disabilities, is an untreatable condition characterized by a number of developmental defects and permanent deficits in the adulthood. Ts65Dn mice, the major animal model for DS, display severe cognitive and synaptic plasticity defects closely resembling the human phenotype. Here, we employed a multidisciplinary approach to investigate, for the first time in developing Ts65Dn mice, the effects elicited by early environmental enrichment (EE) on brain maturation and function. We report that exposure to EE resulted in a robust increase in maternal care levels displayed by Ts65Dn mothers and led to a normalization of declarative memory abilities and hippocampal plasticity in trisomic offspring. The positive effects of EE on Ts65Dn phenotype were not limited to the cognitive domain, but also included a rescue of visual system maturation. The beneficial EE effects were accompanied by increased BDNF and correction of over-expression of the GABA vesicular transporter vGAT. These findings highlight the beneficial impact of early environmental stimuli and their potential for application in the treatment of major functional deficits in children with DS. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. A commentary on TREAT: The trial of early aggressive drug therapy in juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Baildam Eileen

    2012-06-01

    Full Text Available Abstract Polyarticular juvenile idiopathic arthritis (JIA is a category of JIA where multiple joints are affected by chronic inflammation, and where serious and lasting damage to joints is the expected natural history in untreated disease. There is evidence of response to disease-modifying antirheumatic and biologic drugs, but little evidence of permanent remission from any of the existing therapeutic trials. The TREAT trial by Wallace et al., recently published in Arthritis and Rheumatism, used a collaborative multicenter approach to studying early aggressive treatment of polyarticular JIA in an attempt to achieve full clinical inactive disease after 6 months of treatment. The study's main finding that the earlier in the disease course that treatment is started, the better the chance of disease control, has provided evidence that there is a 'window of opportunity' for treating JIA as there is in adult rheumatoid arthritis (RA. The study provides both a platform and an impetus for concentrating future treatment trials on early rather than established disease and investigating a standard of starting treatment within 10 to 12 weeks.

  10. Rescue localized intra-arterial thrombolysis for hyperacute MCA ischemic stroke patients after early non-responsive intravenous tissue plasminogen activator therapy

    International Nuclear Information System (INIS)

    Kim, Dong Joon; Kim, Dong Ik; Kim, Seo Hyun; Lee, Kyung Yeol; Heo, Ji Hoe; Han, Sang Won

    2005-01-01

    The outcome of patients who show no early response to intravenous (i.v.) tissue plasminogen activator (tPA) therapy is poor. The objective of this study was to evaluate the feasibility of rescue localized intra-arterial thrombolysis (LIT) therapy for acute ischemic stroke patients after an early non-responsive i.v. tPA therapy. Patients with proximal MCA occlusions who were treated by LIT (n=10) after failure of early response [no improvement or improvement of National Institute of Health Stroke Scale (NIHSS) scores of ≤3] to i.v. tPA therapy (0.9 mg/kg - 10% bolus and 90% i.v. infusion over 60 min) were selected. The recanalization rates, incidence of post-thrombolysis hemorrhage and clinical outcomes [baseline and discharge NIHSS scores, mortality, 3 months Barthel index (BI) and modified Rankin score (mRS)] were evaluated. Rescue LIT therapy was performed on ten MCA occlusion patients (male:female=3:7, mean age 71 years). The mean time between the initiation of i.v. tPA therapy and the initiation of intra-arterial urokinase (i.a. UK) was 117±25.0 min [time to i.v. tPA 137±32 min; time to digital subtraction angiography (DSA) 221±42 min; time to i.a. UK 260±46 min]. The baseline NIHSS scores showed significant improvement at discharge (median from 18 to 6). Symptomatic hemorrhage and, consequent, mortality were noted in 2/10 (20%) patients. Three months good outcome was noted in 4/10 (40%, mRS 0-2) and 3/10 (30%, BI ≥95). In conclusion, rescue LIT therapy can be considered as a treatment option for patients not showing early response to full dose i.v. tPA therapy. Larger scale studies for further validation of this protocol may be necessary. (orig.)

  11. Effect of Family Oriented Early Intervention Based on Localized Play Therapy on the Clinical Symptoms of Preschool Children with ADHD

    Directory of Open Access Journals (Sweden)

    سعید رحیمی پردنجانی

    2016-06-01

    Full Text Available Current study was aimed to investigate the effect of localized play therapy on reducing symptoms of attention deficiency and hyper activity/impulsivity in preschool children with ADHD. The method of this study was an applied semi-experimental study designed as pretest-posttest with control group. Twenty four mothers with ADHD children were selected through multi-stage sampling and randomly arranged in experimental or control groups. The experimental group participated in a 10 sessions Localized Play Therapy (LPT intervention program, while the control group was on the waiting list. Assessment tools were the Vanderbilt ADHD Teacher Rating Scale (Wolraich, et al., 1997 and a semiorganized clinical interview. Data were analyzed by using a repeated measure analysis of variance. The results showed that there were  significant differences between the control and experimental groups in attention deficiency and hyper activity/impulsivity scores of pre-test and post-test. In conclusion, it can be indicated that family oriented early intervention based on LPT is effective in reducing clinical symptoms of preschool children with ADHD. Therefore, this method can be considered as an effective therapeutic method for ADHD children by experts and parents

  12. Early effect of external beam radiation therapy on the anal sphincter: A study using anal manometry and transrectal ultrasound

    International Nuclear Information System (INIS)

    Birnbaum, E.H.; Dreznik, Z.; Myerson, R.J.; Lacey, D.L.; Fry, R.D.; Kodner, I.J.; Fleshman, J.W.

    1992-01-01

    The early of pelvic irradiation on the anal sphincter has not been previously investigated. This study prospectively evaluated the acute effect of preoperative radiation on anal function. Twenty patients with rectal carcinoma received 4,500 cGy of preoperative external beam radiation. The field of radiation included the sphincter in 10 patients and was delivered above the anorectal ring in 10 patients. Anal manometry and transrectal ultrasound were performed before and four weeks after radiotherapy. No significant difference in mean maximal squeeze or resting pressure was found after radiation therapy. An increase in mean minimal sensory threshold was significant. Histologic examination revealed minimal radiation changes at the distal margin in 8 of 10 patients who underwent low anterior resection and in 1 of 3 patients who underwent abdominoperineal resection. The authors conclude that preoperative radiation therapy has minimal immediate effect on the anal sphincter and is not a major contributing factor to postoperative incontinence in patients after sphincter-saving operations for rectal cancer

  13. Results of breast conserving therapy for early breast cancer and the role of mammographic follow-up

    International Nuclear Information System (INIS)

    Grosse, Antje; Schreer, Ingrid; Frischbier, Hans-Joachim; Maass, Heinrich; Loening, Thomas; Bahnsen, Jens

    1997-01-01

    Purpose: The following article is a review of 23 years of breast-conserving therapy in our hospital. This study was performed to assess and improve the follow-up care of women with early breast cancer and to evaluate whether or not biannual mammogram is useful. Methods and Materials: Between 1972 and December 1995, 3072 women with pathological size pT1 and pT2 breast cancer were treated with conservative surgery and radiation therapy. Eighty-five patients developed a recurrence in the treated breast as the first site of failure, 12 of which had positive axillary nodes. In the following patient study, those with an noninvasive recurrence were excluded. A retrospective assessment of the entire mammographic course was made, starting with the mammogram at the time of original diagnosis to the mammogram of the recurrence. Results: In our study group the probability for local failure ranged from 1 to 2% per year. At 5 and 10 years the actuarial rates were 5 and 10%. The median time to recurrence was 41 months (range 8-161). Twenty-six (31%) recurrences were detected by mammography alone, 10 (12%) by clinical examination only, and 35 (41%) by both methods. For the patients with an ipsilateral recurrence, the overall actuarial 5- and 10-year survival after treatment was 87 and 70%, respectively. The 5-year actuarial rate of survival from salvage mastectomy was 61%. Conclusion: Considering the high percentage of recurrences detectable by mammography and the possibility of detection within a short-term interval, we think biannual mammographic follow-up is appropriate for the first years following breast-conserving therapy

  14. [Clinical efficiency of Vasonat in neurometabolic therapy of patients with ischemic stroke at early rehabilitation period].

    Science.gov (United States)

    Abasova, G B; Tyksanbaeva, G U; Orazalieva, D B; Kasymova, S K

    2011-01-01

    Research of efficiency and safety of Vasonat has been carried out. 31 patients aged 46-75 years who had had hemispheric athero- thrombotic or hemodynamic schemic stroke with moderate severity and being treated in 2-5-month of early rehabilitation period have been observed. The control group of patients received placebo. Results of the study, 4 weeks treatment using Vasonat in the dosage of 500 mg/day have shown positive effect on common signs of the disease by decreasing headache intensity, dizziness, a nausea, and on focal neurological symptoms by decreasing hemiparesis degree; psychoemotional and mnestic activity (main memory and attention) improved as well. It was more distinct in patients with localization of the stroke in the right hemisphere of the brain. It was also noted more rapid improvement of motion function and quality of life of patients.

  15. STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction)

    DEFF Research Database (Denmark)

    Pels, A; Kenny, L C; Alfirevic, Z

    2017-01-01

    randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants......BACKGROUND: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate...... Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. METHODS: Five national/bi-national multicentre...

  16. Prediction of remission in Graves' disease after thionamide therapy by technetium-99m early uptake

    International Nuclear Information System (INIS)

    Misaki, Takashi; Dokoh, Shigeharu; Koh, Toshikiyo; Shimbo, Shin-ichiro; Hidaka, Akinari; Iida, Yasuhiro; Kasagi, Kanji; Konishi, Junji.

    1991-01-01

    In the clinical management of Graves' thyrotoxicosis, one of the most important subject is when to stop antithyroid drugs after achieving an euthyroid state. T 3 suppression test and other methods have been used to forecast the outcome after drug cessation, but the results were not always satisfactory. We have attempted to predict remission of Graves' disease by single measurement of early technetium uptake without administration of triiodothyronine. Drugs were discontinued in the seventy-five patients with Graves' disease on maintenance doses of either methimazole or propylthiouracil who showed normalized uptake (4.0% or less). Of 64 patients evaluable after twelve months, 55 (86%) remained euthyroid, 8 relapsed, and 1 became hypothyoid. With its accuracy in prediction of short-term remission comparable or superior to T 3 suppression test, this rapid and simple method seemed suitable for routine use in clinical practice. (author)

  17. A Randomized Trial of Time-Limited Antiretroviral Therapy in Acute/Early HIV Infection.

    Directory of Open Access Journals (Sweden)

    Joseph B Margolick

    Full Text Available It has been proposed that initiation of antiretroviral treatment (ART very soon after establishment of HIV infection may be beneficial by improving host control of HIV replication and delaying disease progression.People with documented HIV infection of less than 12 months' duration in Baltimore MD and seven Canadian sites were randomized to either a observation and deferred ART, or b immediate treatment with ART for 12 months. All subjects not receiving ART were followed quarterly and permanent ART was initiated according to contemporaneous treatment guidelines. The endpoint of the trial was total ART-free time from study entry until initiation of permanent ART.One hundred thirteen people were randomized, 56 to the observation arm and 57 to the immediate treatment arm. Twenty-three had acute (<2 months infection and 90 early (2-12 months infection. Of those randomized to the immediate treatment arm, 37 completed 12 months of ART according to protocol, 9 declined to stop ART after 12 months, and 11 were nonadherent to the protocol or lost to follow-up. Comparing those in the observation arm to either those who completed 12 months of ART or all 56 who were randomized to immediate ART, there was no significant difference between the arms in treatment-free interval after study entry, which was about 18 months in both arms.This study did not find a benefit from administration of a brief, time-limited (12-month course of ART in acute or early HIV infection.ClinicalTrials.gov NCT00106171.

  18. Variability of hepatitis C virus hypervariable region 1 (HVR-1) during the early phase of pegylated interferon and ribavirin therapy.

    Science.gov (United States)

    Caraballo Cortés, K; Laskus, T; Bukowska-Ośko, I; Pawełczyk, A; Berak, H; Horban, A; Fic, M; Radkowski, M

    2012-01-01

    Genetic variability of hepatitis C virus (HCV) is considered to be an important factor defining viral pathogenesis, persistence and resistance to treatment. The aim of the present study was to characterize HCV genetic heterogeneity within a hypervariable region 1 (HVR-1) before and during the early period of pegylated interferon alfa (PEG-IFN-α) and ribavirin treatment in correlation with treatment outcome. The study involved 24 patients treated with PEG-IFN-α and ribavirin whose sera were collected before (baseline) and at 7, 14, 21 28 and 56 day of treatment. HCV HVR-1 region was amplified by nested RT- PCR and subjected to SSCP (single strand conformational polymorphism) analysis. SSCP changes of HCV HVR-1 over time in each patient were compared to treatment outcome results. In 2/11 (18%) SVR+ and 8/13 (62%) SVR- treated patients, HVR-1 genetic changes manifested by new SSCP bands (new genetic variants) and were significantly more frequent in nonresponders (P HVR-1 variability during the early phase of PEG-IFN-α and ribavirin therapy may be predictive of treatment outcome.

  19. Findings of the analysis of antineoplastic therapy in patients with thyroid cancer at early stages of special treatment

    International Nuclear Information System (INIS)

    Vasil'jev, L. Ya.; Kulyinyich, G.V.; Radzyishevs'ka, Je.B.; Savchenko, A.S.

    2017-01-01

    The object of research is to estimate risks of development of early somatic neurological complications depending on the scheme of treatment of the thyroid according to the findings obtained due to analysis of 120 case histories of the patients. Research methods: nonparametric statistics methods, multivariance statistical analysis, hidden knowledge search technology. According to the accumulated data packages the frequency of unfavorable early somatic neurological consequences was ascertained, i.e. anemia - 15.8%, sialoadenitis - 27.5%, gastritis - 2.5%, heart beat disorder - 72.5%, polyneuropathy - 83,0%. The dependence of appearing on present concomitant pathology (hypoparathyrosis, hypocalcemia, peptic ulcer, diabetes mellitus, hypertension, cardiac failure, connective tissue diseases, varix dilatation of the lower extremities) and medical history data such as age, sex, disease stage, number of surgeries and radionuclide treatment courses, ECOG scale condition was clarified for the first time. The factors which affect appearing of immediate complications of radioactive iodine therapy at a statistically significant level were ascertained. It was specified that these factors include concomitant somatic diseases, involving cardiovascular, endocrine and nervous systems in particular. The further analysis of accumulated experience of treatment of thyroid cancer will make it possible to elaborate approaches to optimization choice appropriate treatment schemes and post-treatment monitoring of patients.

  20. Effectiveness of Lower Energy Density Extracorporeal Shock Wave Therapy in the Early Stage of Avascular Necrosis of the Femoral Head.

    Science.gov (United States)

    Han, Yong; Lee, June-Kyung; Lee, Bong-Yeon; Kee, Hoi-Sung; Jung, Kwang-Ik; Yoon, Seo-Ra

    2016-10-01

    To evaluate the effectiveness of lower energy flux density (EFD) extracorporeal shock wave therapy (ESWT) in the early stage of avascular necrosis (AVN) of the femoral head. Nineteen patients and 30 hips were enrolled. All subjects received 4 weekly sessions of ESWT, at different energy levels; group A (n=15; 1,000 shocks/session, EFD per shock 0.12 mJ/mm 2 ) and group B (n=15; 1,000 shocks/session, EFD per shock 0.32 mJ/mm 2 ). We measured pain by using the visual analog scale (VAS), and disability by using the Harris hip score, Hip dysfunction and Osteoarthritis Outcome Score (HOOS), and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). To determine the effect of the lower EFD ESWT, we assessed the VAS, Harris hip score, HOOS, WOMAC of the subjects before and at 1, 3, and 6 months. In both groups, the VAS, Harris hip score, HOOS, and WOMAC scores improved over time (p<0.05). Lower EFD ESWT may be an effective method to improve the function and to relieve pain in the early stage of AVN.

  1. Radionuclide bone scintigraphy in early detection of avascular osteonecrosis occurred in recovered SARS patients after hormone therapy

    International Nuclear Information System (INIS)

    Wang Qian; Huang Lili; Qin Shuling; Wang Yu; Nie Yuxin; Liang Tiejun; Zhang Caiqun; Zhao Yamei

    2005-01-01

    Objective: To analyze the characteristics of bone scintigraphy in patients who recovered from the severe acute respiratory syndrome (SARS), and to evaluate the clinical value of bone scintigraphy in the early diagnosis of avascular osteonecrosis (AVN) after hormone therapy. Methods: Bone scintigraphy was performed in 66 SARS patients. Among them 54 underwent MRI in bilateral hips and knees. Both images were compared and followed up clinically. Results: Abnormal scintigraphy was found in 30 (45.5%) of the 66 recovered SARS patients. Total 82 foci were found in hip, knee, ankle, elbow, shoulder, wrist and the middle of the tibia. Hip and knee joints were the most involved sites. 25 patients with 71 lesions were symptomatic, whereas 11 in 5 patients were asymptomatic, lesions in 8 patients were multifocal. The lesions found in scintigraphy and MRI were concordant in 92.6% of the joints. But more lesions could be detected by bone scintigraphy. Conclusions: SARS patients have a high occurrence of AVN, usually involved in multiple sites. Bone scintigraphy should be the first choice method used for early detection of AVN. (authors)

  2. PREMM: preterm early massage by the mother: protocol of a randomised controlled trial of massage therapy in very preterm infants.

    Science.gov (United States)

    Lai, Melissa M; D'Acunto, Giulia; Guzzetta, Andrea; Boyd, Roslyn N; Rose, Stephen E; Fripp, Jurgen; Finnigan, Simon; Ngenda, Naoni; Love, Penny; Whittingham, Koa; Pannek, Kerstin; Ware, Robert S; Colditz, Paul B

    2016-08-27

    Preterm infants follow an altered neurodevelopmental trajectory compared to their term born peers as a result of the influence of early birth, and the altered environment. Infant massage in the preterm infant has shown positive effects on weight gain and reduced length of hospital stay. There is however, limited current evidence of improved neurodevelopment or improved attachment, maternal mood or anxiety. The aim of this study is to investigate the effects of infant massage performed by the mother in very preterm (VPT) infants. Effects on the infant will be assessed at the electrophysiological, neuroradiological and clinical levels.  Effects on maternal mood, anxiety and mother-infant attachment will also be measured. A randomised controlled trial to investigate the effect of massage therapy in VPT infants. Sixty VPT infants, born at 28 to 32 weeks and 6 days gestational age, who are stable, off supplemental oxygen therapy and have normal cranial ultrasounds will be recruited and randomised to an intervention (infant massage) group or a control (standard care) group. Ten healthy term born infants will be recruited as a reference comparison group. The intervention group will receive standardised massage therapy administered by the mother from recruitment, until term equivalent age (TEA). The control group will receive care as usual (CAU). Infants and their mothers will be assessed at baseline, TEA, 12 months and 24 months corrected age (CA), with a battery of clinical, neuroimaging and electrophysiological measures, as well as structured questionnaires, psychoanalytic observations and neurodevelopmental assessments. Optimising preterm infant neurodevelopment is a key aim of neonatal research, which could substantially improve long-term outcomes and reduce the socio-economic impact of VPT birth. This study has the potential to give insights into the mother-baby relationship and any positive effects of infant massage on neurodevelopment. An early intervention

  3. Serum phosphate predicts early mortality in adults starting antiretroviral therapy in Lusaka, Zambia: a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Douglas C Heimburger

    Full Text Available BACKGROUND: Patients starting antiretroviral therapy (ART for acquired immunodeficiency syndrome (AIDS in sub-Saharan Africa have high rates of mortality in the initial weeks of treatment. We assessed the association of serum phosphate with early mortality among HIV-infected adults with severe malnutrition and/or advanced immunosuppression. METHODOLOGY/PRINCIPAL FINDINGS: An observational cohort of 142 HIV-infected adults initiating ART in Lusaka, Zambia with body mass index (BMI <16 kg/m(2 or CD4(+ lymphocyte count <50 cells/microL, or both, was followed prospectively during the first 12 weeks of ART. Detailed health and dietary intake history, review of systems, physical examination, serum metabolic panel including phosphate, and serum ferritin and high-sensitivity C-reactive protein (hsCRP were monitored. The primary outcome was mortality. Baseline serum phosphate was a significant predictor of mortality; participants alive at 12 weeks had a median value of 1.30 mmol/L (interquartile range [IQR]: 1.04, 1.43, compared to 1.06 mmol/L (IQR: 0.89, 1.27 among those who died (p<0.01. Each 0.1 mmol/L increase in baseline phosphate was associated with an incremental decrease in mortality (AHR 0.83; 95% CI 0.72 to 0.95. The association was independent of other metabolic parameters and known risk factors for early ART-associated mortality in sub-Saharan Africa. While participant attrition represented a limitation, it was consistent with local program experience. CONCLUSIONS/SIGNIFICANCE: Low serum phosphate at ART initiation was an independent predictor of early mortality among HIV patients starting ART with severe malnutrition or advanced immunosuppression. This may represent a physiologic phenomenon similar to refeeding syndrome, and may lead to therapeutic interventions that could reduce mortality.

  4. Risk of Cerebrovascular Events in Elderly Patients After Radiation Therapy Versus Surgery for Early-Stage Glottic Cancer

    International Nuclear Information System (INIS)

    Hong, Julian C.; Kruser, Tim J.; Gondi, Vinai; Mohindra, Pranshu; Cannon, Donald M.; Harari, Paul M.; Bentzen, Søren M.

    2013-01-01

    Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the cause of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients

  5. Decreased local control following radiation therapy alone in early-stage glottic carcinoma with anterior commissure extension

    International Nuclear Information System (INIS)

    Zouhair, A.; Azria, D.; Coucke, P.; Matzinger, O.; Mirimanoff, R.O.; Ozsahin, M.; Bron, L.; Moeckli, R.; Do, H.P.

    2004-01-01

    Purpose: to assess the patterns of failure in the treatment of early-stage squamous cell carcinoma of the glottic larynx. Patients and methods: between 1983-2000, 122 consecutive patients treated for early laryngeal cancer (UICC T1N0 and T2N0) by radical radiation therapy (RT) were retrospectively studied. Male-to-female ratio was 106: 16, and median age 62 years (35-92 years). There were 68 patients with T1a, 18 with T1b, and 36 with T2 tumors. Diagnosis was made by biopsy in 104 patients, and by laser vaporization or stripping in 18. Treatment planning consisted of three-dimensional (3-D) conformal RT in 49 (40%) patients including nine patients irradiated using arytenoid protection. A median dose of 70 Gy (60-74 Gy) was given (2 Gy/fraction) over a median period of 46 days (21-79 days). Median follow-up period was 85 months. Results: the 5-year overall, cancer-specific, and disease-free survival amounted to 80%, 94%, and 70%, respectively. 5-year local control was 83%. Median time to local recurrence in 19 patients was 13 months (5-58 months). Salvage treatment consisted of surgery in 17 patients (one patient refused salvage and one was inoperable; total laryngectomy in eleven, and partial laryngectomy or cordectomy in six patients). Six patients died because of laryngeal cancer. Univariate analyses revealed that prognostic factors negatively influencing local control were anterior commissure extension, arytenoid protection, and total RT dose < 66 Gy. Among the factors analyzed, multivariate analysis (cox model) demonstrated that anterior commissure extension, arytenoid protection, and male gender were the worst independent prognostic factors in terms of local control. Conclusion: for early-stage laryngeal cancer, outcome after RT is excellent. In case of anterior commissure extension, surgery or higher RT doses are warranted. Because of a high relapse risk, arytenoid protection should not be attempted. (orig.)

  6. Brief Report: Impact of Early Antiretroviral Therapy on the Performance of HIV Rapid Tests and HIV Incidence Assays.

    Science.gov (United States)

    Fogel, Jessica M; Piwowar-Manning, Estelle; Debevec, Barbara; Walsky, Tamara; Schlusser, Katherine; Laeyendecker, Oliver; Wilson, Ethan A; McCauley, Marybeth; Gamble, Theresa; Tegha, Gerald; Soko, Dean; Kumwenda, Johnstone; Hosseinipour, Mina C; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

    2017-08-01

    Antiretroviral therapy (ART) can downregulate antibody responses to HIV infection. We evaluated the impact of early vs. delayed ART on the performance of HIV diagnostic and incidence assays. Samples were obtained from 207 participants in the HPTN 052 trial, who were stably suppressed on ART for ≥4 years [Malawi sites; pre-ART CD4 cell count 350-550 cells/mm (early ART arm, N = 180) or ART arm, N = 27)]. Samples were tested with 2 HIV rapid tests and 2 HIV incidence assays; selected samples were also tested with two fourth-generation immunoassays and a Western blot (WB) assay. A pre-ART sample was analyzed if the follow-up sample had a false-negative or weakly-reactive rapid test result, or had an incidence assay result indicative of recent infection (false-recent result). Ten (4.8%) samples had a nonreactive or weakly-reactive rapid test result (7/180 early ART arm, 3/27 delayed ART arm, P = 0.13); one sample had nonreactive fourth-generation assay results and 3 had indeterminate WBs. Forty (18.9%) samples had a false-recent incidence assay result; 16 (7.8%) had false-recent results with both incidence assays. Baseline samples had stronger rapid test and WB bands, higher fourth-generation assay signal-to-cutoff values, and fewer HIV incidence assay results indicative of recent infection. False-negative/weakly-reactive HIV rapid tests and false-recent HIV incidence assay results were observed in virally-suppressed individuals, regardless of pre-ART CD4 cell count. Downregulation of the antibody response to HIV infection in the setting of ART may impact population-level surveys of HIV prevalence and incidence.

  7. Risk of Cerebrovascular Events in Elderly Patients After Radiation Therapy Versus Surgery for Early-Stage Glottic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Julian C.; Kruser, Tim J. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Gondi, Vinai [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Central Dupage Hospital Cancer Center, Warrenville, Illinois (United States); Mohindra, Pranshu; Cannon, Donald M.; Harari, Paul M. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Bentzen, Søren M., E-mail: bentzen@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States)

    2013-10-01

    Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the cause of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients.

  8. Delivery of intraoperative radiation therapy after pneumonectomy: experimental observations and early clinical results

    International Nuclear Information System (INIS)

    Pass, H.I.; Sindelar, W.F.; Kinsella, T.J.

    1987-01-01

    Intraoperative radiation therapy (IORT) is capable of delivering high doses of radiation to mediastinal structures while sparing lung parenchyma, heart, and other locoregional tissues. A canine model of pulmonary resection and IORT was investigated by performing a pneumonectomy in 15 adult foxhounds followed by 0 cGy, 2000 cGy, 3000 cGy, 4000 cGy. No clinical complications developed in 4 animals in the 2000-cGy group. However, 2 of the 8 animals given a high dose died of esophageal hemorrhage or carinal necrosis. Esophagitis occurred in 10 of 12 animals, and none of the animals experienced bronchial stump dehiscence. In a limited Phase I protocol, 4 patients with non-small cell lung cancer were treated with resection and 2500 cGy of IORT to two separate ports encompassing the superior and inferior mediastinum. Two patients experienced life-threatening bronchopleural fistulas, and 2 patients died as a consequence of esophageal problems. One patients had recurrence with brain metastases, and the 1 long-term survivor is free from disease. As opposed to the animal model of thoracic IORT, the clinical study demonstrated major toxicity with respiratory and esophageal morbidity. The therapeutic usefulness of thoracic IORT in the management of lung cancer must be questioned in view of this small but consistent series of patients. Further carefully designed clinical studies using lower doses of IORT are needed

  9. Photodynamic therapy for early malignancies in the lower female genital tract

    Science.gov (United States)

    Lobraico, Rocco V.

    1990-09-01

    A total of 14 patients who had failed all conventional modalities for cancer of the vulva vagina and perianal area were treated with photodynamic therapy PDT. The affinity of porphyrins to neopJ. astic tissue enables treatment to be concentrated at the tumor site. An Aurora FL Argon pumped dye laser (Cooper LaserSonics Inc. USA) was used to pump dicyanomethylene dye as an activating source for a red light at a wavelength of 630 nm. The combination of a tumor localizing photosensitizer and photoactivating red light produces a photo chemical reaction that is destructive to the cancerous lesion. The treatment time varied between 10-30 minutes. Vulvar sites ranged from 9-38 cm2. Delivered light doses were from 50-125 J/cm2 and power density from 50 to 75 mW/cm2. A complete response was obtained in 80 of the sites treated as evidenced by negative biopsies taken at 3 months post treatment. Adverse reactions to PDT included a transient cutaneous photosensitivity due to retention of the photosensitizers in the skin. This reaction usually persisted from 45-60 days. 1.

  10. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer

    International Nuclear Information System (INIS)

    Offersen, Birgitte V.; Boersma, Liesbeth J.; Kirkove, Carine; Hol, Sandra; Aznar, Marianne C.; Biete Sola, Albert; Kirova, Youlia M.; Pignol, Jean-Philippe; Remouchamps, Vincent; Verhoeven, Karolien; Weltens, Caroline; Arenas, Meritxell; Gabrys, Dorota; Kopek, Neil; Krause, Mechthild; Lundstedt, Dan; Marinko, Tanja

    2015-01-01

    Background and purpose: Delineation of clinical target volumes (CTVs) is a weak link in radiation therapy (RT), and large inter-observer variation is seen in breast cancer patients. Several guidelines have been proposed, but most result in larger CTVs than based on conventional simulator-based RT. The aim was to develop a delineation guideline obtained by consensus between a broad European group of radiation oncologists. Material and methods: During ESTRO teaching courses on breast cancer, teachers sought consensus on delineation of CTV through dialogue based on cases. One teacher delineated CTV on CT scans of 2 patients, followed by discussion and adaptation of the delineation. The consensus established between teachers was sent to other teams working in the same field, both locally and on a national level, for their input. This was followed by developing a broad consensus based on discussions. Results: Borders of the CTV encompassing a 5 mm margin around the large veins, running through the regional lymph node levels were agreed, and for the breast/thoracic wall other vessels were pointed out to guide delineation, with comments on margins for patients with advanced breast cancer. Conclusion: The ESTRO consensus on CTV for elective RT of breast cancer, endorsed by a broad base of the radiation oncology community, is presented to improve consistency

  11. Early postoperative physical therapy for improving short-term gross motor outcome in infants with cyanotic and acyanotic congenital heart disease.

    Science.gov (United States)

    Haseba, Sumihito; Sakakima, Harutoshi; Nakao, Syuhei; Ohira, Misaki; Yanagi, Shigefumi; Imoto, Yutaka; Yoshida, Akira; Shimodozono, Megumi

    2018-07-01

    We analysed the gross motor recovery of infants and toddlers with cyanotic and acyanotic congenital heart disease (CHD) who received early postoperative physical therapy to see whether there was any difference in the duration to recovery. This study retrospectively evaluated the influence of early physical therapy on postoperative gross motor outcomes of patients with CHD. The gross motor ability of patients with cyanotic (n = 25, average age: 376.4 days) and acyanotic (n = 26, average age: 164.5 days) CHD was evaluated using our newly developed nine-grade mobility assessment scale. Physical therapy was started at an average of five days after surgery, during which each patient's gross motor ability was significantly decreased compared with the preoperative level. Patients (who received early postoperative physical therapy) with cyanotic (88.0%) and acyanotic CHD (96.2%) showed improved preoperative mobility grades by the time of hospital discharge. However, patients with cyanotic CHD had a significantly prolonged recovery period compared to those with acyanotic CHD (p congenital heart disease are likely at greater risk of gross motor delays and have a prolonged recovery period of gross motor ability compared to those with acyanotic congenital heart disease. Early postoperative physical therapy for patients with congenital heart disease after cardiac surgery promoted gross motor recovery. The postoperative recovery period to preoperative mobility grade was affected by pre-, intra-, and postoperative factors. Rehabilitation experts should consider the risk of gross motor delays of patients with congenital heart disease after cardiac surgery and the early postoperative physical therapy to promote their gross motor recovery.

  12. Colloids versus crystalloids in objective-guided fluid therapy, systematic review and meta-analysis. Too early or too late to draw conclusions

    Directory of Open Access Journals (Sweden)

    Javier Ripollés

    2015-08-01

    Full Text Available INTRODUCTION: Several clinical trials on Goal directed fluid therapy (GDFT were carried out, many of those using colloids in order to optimize the preload. After the decision of European Medicines Agency, there is such controversy regarding its use, benefits, and possible contribution to renal failure. The objective of this systematic review and meta-analysis is to compare the use of last-generation colloids, derived from corn, with crystalloids in GDFT to determine associated complications and mortality.METHODS: A bibliographic research was carried out in MEDLINE PubMed, EMBASE and Cochrane Library, corroborating randomized clinical trials where crystalloids are compared to colloids in GDFT for major non-cardiac surgery in adults.RESULTS: One hundred thirty references were found and among those 38 were selected and 29 analyzed; of these, six were included for systematic review and meta-analysis, including 390 patients. It was observed that the use of colloids is not associated with the increase of complications, but rather with a tendency to a higher mortality (RR [95% CI] 3.87 [1.121-13.38]; I2 = 0.0%; p = 0.635.CONCLUSIONS: Because of the limitations of this meta-analysis due to the small number of randomized clinical trials and patients included, the results should be taken cautiously, and the performance of new randomized clinical trials is proposed, with enough statistical power, comparing balanced and unbalanced colloids to balanced and unbalanced crystalloids, following the protocols of GDFT, considering current guidelines and suggestions made by groups of experts.

  13. Early changes of parotid density and volume predict modifications at the end of therapy and intensity of acute xerostomia

    Energy Technology Data Exchange (ETDEWEB)

    Belli, Maria Luisa; Broggi, Sara [Ospedale San Raffaele Scientific Institute, Medical Physics, Milano (Italy); Scalco, Elisa; Rizzo, Giovanna [CNR, Istituto di Bioimmagini e Fisiologia Molecolare, Milano (Italy); Sanguineti, Giuseppe [Regina Elena National Cancer Institute, Department of Radiation Oncology, Rome (Italy); Fiorino, Claudio; Cattaneo, Giovanni Mauro [Ospedale San Raffaele Scientific Institute, Medical Physics, Milano (Italy); CNR, Istituto di Bioimmagini e Fisiologia Molecolare, Milano (Italy); Dinapoli, Nicola; Valentini, Vincenzo [Universita Cattolica del Sacro Cuore, Radiotherapy, Rome (Italy); Ricchetti, Francesco [Ospedale Sacro Cuore, Radiotherapy, Negrar (Italy)

    2014-11-15

    To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer. Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients. A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher ''mean'' acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / < 1.57 were -0.98 vs -0.22 HU/day respectively (p = 0.05). Early density and volume variations accurately predict final changes of parotid glands. A higher longitudinally assessed score of acute xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm{sup 3}/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia. (orig.) [German] Ziel der Studie ist die Untersuchung der praediktiven Aussagekraft von fruehen Veraenderungen in Volumen und Dichte der Ohrspeicheldruese in Bezug auf die finale Verformung zum Ende der Therapie sowie das Risiko von Xerostomie waehrend der intesitaetsmodulierten Strahlentherapie (IMRT) bei Kopf und Hals Tumoren. Die Studie

  14. Size, Composition, and Evolution of HIV DNA Populations during Early Antiretroviral Therapy and Intensification with Maraviroc.

    Science.gov (United States)

    Chaillon, Antoine; Gianella, Sara; Lada, Steven M; Perez-Santiago, Josué; Jordan, Parris; Ignacio, Caroline; Karris, Maile; Richman, Douglas D; Mehta, Sanjay R; Little, Susan J; Wertheim, Joel O; Smith, Davey M

    2018-02-01

    Residual viremia is common during antiretroviral therapy (ART) and could be caused by ongoing low-level virus replication or by release of viral particles from infected cells. ART intensification should impact ongoing viral propagation but not virion release. Eighteen acutely infected men were enrolled in a randomized controlled trial and monitored for a median of 107 weeks. Participants started ART with ( n = 9) or without ( n = 9) intensification with maraviroc (MVC) within 90 days of infection. Levels of HIV DNA and cell-free RNA were quantified by droplet digital PCR. Deep sequencing of C2-V3 env , gag , and pol (454 Roche) was performed on longitudinally collected plasma and peripheral blood mononuclear cell (PBMC) samples while on ART. Sequence data were analyzed for evidence of evolution by (i) molecular diversity analysis, (ii) nonparametric test for panmixia, and (iii) tip date randomization within a Bayesian framework. There was a longitudinal decay of HIV DNA after initiation of ART with no difference between MVC intensification groups (-0.08 ± 0.01 versus -0.09 ± 0.01 log 10 copies/week in MVC + versus MVC - groups; P = 0.62). All participants had low-level residual viremia (median, 2.8 RNA copies/ml). Across participants, medians of 56 (interquartile range [IQR], 36 to 74), 29 (IQR, 25 to 35), and 40 (IQR, 31 to 54) haplotypes were generated for env , gag , and pol regions, respectively. There was no clear evidence of viral evolution during ART and no difference in viral diversity or population structure from individuals with or without MVC intensification. Further efforts focusing on elucidating the mechanism(s) of viral persistence in various compartments using recent sequencing technologies are still needed, and potential low-level viral replication should always be considered in cure strategies. IMPORTANCE Residual viremia is common among HIV-infected people on ART. It remains controversial if this viremia is a consequence of propagating

  15. Early initiation of beta blockers following primary endoscopic therapy for bleeding esophageal varices in cirrhotics

    International Nuclear Information System (INIS)

    Salim, A.; Malik, K.; Farooq, M.O.; Butt, U.; Butt, A.K.

    2017-01-01

    Beta-blockers provide secondary prophylaxis following endoscopic therapy for variceal bleeding. Guidelines recommend starting beta-blockers 6 days after endoscopy to prevent masking hemodynamic signs of rebleeding. We aimed to see safety of earlier initiation of beta-blockers. Methods: Cirrhotic patients with upper GI bleed were given I.V vasoactive agents until undergoing endoscopy. Patients with only esophageal varices as source of bleed were recruited. Vasoactive agents were discontinued following variceal banding. The patients were observed for 12-18 hours, discharged on oral carvedilol 6.25 mg BID and monitored for 6 weeks for rebleeding and mortality. Results: 50 patients were included, 27 (54%) male and 23 (46%) female. Average age was 43+3 years. Etiology of cirrhosis was HCV in 42 (84%), HBV in 6 (12%), HCV and HBV in 2 (4%) and indeterminate in 1 (2%) patient. 17 (34%) patients had Child A, 22 (44%) Child B and 11 (22%) had Child C disease. Hospital stay was under 24 hours in 24 (48%), 24-48 hours in 15 (30%) and 48-72 hours in 11 (22%) patients. 5 (10%) patients underwent EGD within 6 hours of admission, 28 (56%) within 12 hours, 14 (28%) within 24 hours and 3 (6%) within 36 hours. No rebleeding, mortality or drug related adverse effects were noted during 6 weeks after discharge. Conclusions:Our study proves possibility of shorter management of variceal bleeding by having a 12-18 hour monitoring after endoscopic banding, followed by beta-blocker initiation and discharge. This will safely reduce physical and financial burden on health services. Background: Beta-blockers provide secondary prophylaxis following endoscopic therapy for variceal bleeding. Guidelines recommend starting beta-blockers 6 days after endoscopy to prevent masking hemodynamic signs of re-bleeding. We aimed to see safety of earlier initiation of beta-blockers. Methods: Cirrhotic patients with upper GI bleed were given intravenous vasoactive agents until undergoing endoscopy. Patients

  16. Radiation Therapy, Cardiac Risk Factors, and Cardiac Toxicity in Early-Stage Breast Cancer Patients

    International Nuclear Information System (INIS)

    Doyle, John J.; Neugut, Alfred I.; Jacobson, Judith S.; Wang Jian; McBride, Russell; Grann, Alison; Grann, Victor R.; Hershman, Dawn

    2007-01-01

    Purpose: The benefits of adjuvant radiation therapy (RT) for breast cancer may be counterbalanced by the risk of cardiac toxicity. We studied the cardiac effects of RT and the impact of pre-existing cardiac risk factors (CRFs) in a population-based sample of older patients with breast cancer. Methods and Materials: In the Surveillance, Epidemiology and End-Results (SEER)-Medicare database of women ≥65 years diagnosed with Stages I to III breast cancer from January 1, 1992 to December 31, 2000, we used multivariable logistic regression to model the associations of demographic and clinical variables with postmastectomy and postlumpectomy RT. Using Cox proportional hazards regression, we then modeled the association between treatment and myocardial infarction (MI) and ischemia in the 10 or more years after diagnosis, taking the predictors of treatment into account. Results: Among 48,353 women with breast cancer; 19,897 (42%) were treated with lumpectomy and 26,534 (55%) with mastectomy; the remainder had unknown surgery type (3%). Receipt of RT was associated with later year of diagnosis, younger age, fewer comorbidities, nonrural residence, and chemotherapy. Postlumpectomy RT was also associated with white ethnicity and no prior history of heart disease (HD). The RT did not increase the risk of MI. Presence of MI was associated with age, African American ethnicity, advanced stage, nonrural residence, more than one comorbid condition, a hormone receptor-negative tumor, CRFs and HD. Among patients who received RT, tumor laterality was not associated with MI outcome. The effect of RT on the heart was not influenced by HD or CRFs. Conclusion: It appears unlikely that RT would increase the risk of MI in elderly women with breast cancer, regardless of type of surgery, tumor laterality, or history of CRFs or HD, for at least 10 years

  17. Rationale and early outcomes for the management of thymoma with proton therapy.

    Science.gov (United States)

    Zhu, He J; Hoppe, Bradford S; Flampouri, Stella; Louis, Debbie; Pirris, John; Nichols, R Charles; Henderson, Randal H; Mercado, Catherine E

    2018-04-01

    Radiotherapy for thymic malignancies is technically challenging due to their close proximity to the heart, lungs, esophagus, and breasts, raising concerns about significant acute and late toxicities from conventional photon radiotherapy. Proton therapy (PT) may reduce the radiation dose to these vital organs, leading to less toxicity. We reviewed the dosimetry and outcomes among patients treated with PT for thymic malignancies at our institution. From January 2008 to March 2017, six patients with de novo Masaoka stages II-III thymic malignancies were treated with PT on an IRB-approved outcomes tracking protocol. Patients were evaluated weekly during treatment, then every 3 months for 2 years, then every 6 months for 3 more years, and then annually for CTCAE vs. four toxicities and disease recurrence. Comparison intensity-modulated radiotherapy (IMRT) plans were developed for each patient. Mean doses to the heart, esophagus, bilateral breasts, lungs, and V20 of bilateral lungs were evaluated for the two treatment plans. At last follow-up (median follow-up, 2.6 years), there were two patients with recurrences, including metastatic disease in the patient treated definitively with chemotherapy and PT without surgery and a local-regional recurrence in the lung outside the proton field in one of the post-operative cases. No patients with de novo disease experienced grade ≥3 toxicities after PT. The mean dose to the heart, lung, and esophagus was reduced on average by 36.5%, 33.5%, and 60%, respectively, using PT compared with IMRT (P<0.05 for each dose parameter). PT achieved superior dose sparing to the heart, lung, and esophagus compared to IMRT for thymic malignancies. Patients treated with PT had few radiation-induced toxicities and similar survival compared to historic proton data.

  18. An assessment of early Child Life Therapy pain and anxiety management: A prospective randomised controlled trial.

    Science.gov (United States)

    Hyland, Ela J; D'Cruz, Rachel; Harvey, John G; Moir, Jordyn; Parkinson, Christina; Holland, Andrew J A

    2015-12-01

    Burns remain extremely painful and distressing in young children. The consequences of poorly managed pain and anxiety can be life-long. Whilst Child Life Therapy (CLT) has been shown to be effective in many situations, few studies have looked at the effectiveness of CLT in regard to reducing pain and anxiety in children undergoing burn dressing changes. A prospective, randomised controlled trial was conducted, comparing CLT versus standard care in relation to pain and anxiety scores of children undergoing their initial burn dressing change. Pain and anxiety were assessed by an independent observer and questionnaires completed by the child, parent/caregiver and nursing staff. 50 subjects were recruited in each treatment group; median age 2.3 years (CLT) and 2.2 years (standard care). The median total body surface area (TBSA) burnt was 0.8% (CLT) and 0.5% (standard care). The majority were partial thickness dermal burns (88% CLT, 94% standard care). Rates of parent anxiety and pre-procedural child pain and anxiety were similar. Combined and scaled pain and anxiety scores in the CLT group were significantly less than in the standard treatment group (p=0.03). Whilst pain was significantly better in the CLT group (p=0.02), fear scores, wound outcomes and the need for skin grafting were not statistically different in either group. The presence of a Child Life Therapist, with their ability to adapt to the environment, the child and their family, significantly reduced the experience of pain during paediatric burn dressings. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  19. EVALUATION OF EARLY ISCHEMIC CHANGES IN STROKE PATIENTS TREATED WITH THROMBOLYTIC THERAPY

    Directory of Open Access Journals (Sweden)

    Kolevski Goran

    2016-07-01

    Full Text Available Introduction:The aim of this study is to evaluate early brain ischemic changes on CT scan in stroke patients in correlation with the clinical outcome, as well as to evaluate if there is prognostic and predictive features that can be used. Patients and methods: We examined 20 patients with acute ischemic stroke, from which 12 were male and 8 were female, at the age from 47 to 76 years. Results: The hyperdense medial artery (HMA sign was present in 10 (50% patients. Concerning the ASPECTS score, 5 patients (25% had normal score of 10 points, while 7 patients (35% had score of 7 points. 12 patients (60% had unfavorable outcome, while 8 patients (40% had favorable outcome. Our statistical analysis shows that age of more than 65 years, presence of 2 or more risk-factors, ASPECTS score of 7 and presence of HMA sign were all statistically significant predictors of unfavorable outcome in examined patients (p<0.05 each. The presence of the hyperdense medial artery sign was the most significant single predictor for unfavorable clinical outcome (p=0.0042, p<0.05. Conclusion:The presence of HMA sign is the most significant single predictor for unfavorable clinical outcome.

  20. Pneumonia, Acute Respiratory Distress Syndrome, and Early Immune-Modulator Therapy

    Directory of Open Access Journals (Sweden)

    Kyung-Yil Lee

    2017-02-01

    Full Text Available Acute respiratory distress syndrome (ARDS is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis. The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.

  1. [Ten years of early complex geriatric rehabilitation therapy in the DRG system].

    Science.gov (United States)

    Kolb, G; Breuninger, K; Gronemeyer, S; van den Heuvel, D; Lübke, N; Lüttje, D; Wittrich, A; Wolff, J

    2014-01-01

    Geriatric medicine, as a specialized form of treatment for the elderly, is gaining in importance due to demographic changes. Especially important for geriatric medicine is combining acute care with the need to maintain functionality and participation. This includes prevention of dependency on structured care or chronic disability and handicap by means of rehabilitation. Ten years ago, the German DRG system tried to incorporate procedures (e.g., "early rehabilitation in geriatric medicine") in the hospital reimbursement system. OPS 8-550.x, defined by structural quality, days of treatment, and number of therapeutic interventions, triggers 17 different geriatric DRGs, covering most of the fields of medicine. OPS 8-550.x had been revised continuously to give a clear structure to quality aspects of geriatric procedures. However, OPS 8-550.x is based on proven need of in-hospital treatment. In the last 10 years, no such definition has been produced taking aspects of the German hospital system into account as well as aspects of transparency and benefit in everyday work. The German DRG system covers just basic reimbursement aspects of geriatric medicine quite well; however, a practicable and patient-oriented definition of "hospital necessity" is still lacking, but is absolutely essential for proper compensation. A further problem concerning geriatric medicine reimbursement in the DRG system is due to the different structures of providing geriatric in-hospital care throughout Germany.

  2. Early detection and efficient therapy of cardiac angiosarcoma due to routine transesophageal echocardiography after cerebrovascular stroke

    Directory of Open Access Journals (Sweden)

    Dirk Vogelgesang

    2008-08-01

    Full Text Available Dirk Vogelgesang1, Johannes B Dahm2, Holm Großmann3, Andre Hippe4, Astrid Hummel5, Christian Lotze6, Silke Vogelgesang71Practice of Cardiology, Greifswald, 2Practice of Cardiology, Goettingen, 3Department of Cardiovascular Surgery, Herzzentrum Karlsburg, 4Department of Neurology, 5Department of Cardiology, 6Department of Haematology and Oncology, 7Department of Pathology, University of Greifswald, Greifswald, GermanyAbstract: Primary malignant cardiac tumors (cardiac angiosarcomas are exceedingly rare. Since there are initially nonspecific or missing symptoms, these tumors are usually diagnosed only in an advanced, often incurable stage, after the large tumor mass elicits hemodynamic obstructive symptoms. A 59-year-old female presented with symptoms of cerebral ischemia. A computed tomography (CT scan showed changes suggestive of stroke. Transesophageal echocardiography revealed an inhomogeneous, medium-echogenic, floating mass at the roof of the left atrium near the mouth of the right upper pulmonary vein, indicative of a thrombus. At surgery, a solitary tumor was completely enucleated. Histologically, cardiac angiosarcoma was diagnosed. The patient received adjuvant chemotherapy and was free of symptoms and recurrence of disease at 14 months follow-up. Due to the fortuitous appearance of clinical signs indicative of stroke, cardiac angiosarcoma was diagnosed and effectively treated at an early, nonmetastatic, and therefore potentially curable stage. Although cardiac angiosarcoma is a rare disease, it should be taken into consideration as a potential cause of cerebral embolic disease.Keywords: cardiac angiosarcoma, stroke, embolism

  3. Early detection of lung cancer recurrence after stereotactic ablative radiation therapy: radiomics system design

    Science.gov (United States)

    Dammak, Salma; Palma, David; Mattonen, Sarah; Senan, Suresh; Ward, Aaron D.

    2018-02-01

    Stereotactic ablative radiotherapy (SABR) is the standard treatment recommendation for Stage I non-small cell lung cancer (NSCLC) patients who are inoperable or who refuse surgery. This option is well tolerated by even unfit patients and has a low recurrence risk post-treatment. However, SABR induces changes in the lung parenchyma that can appear similar to those of recurrence, and the difference between the two at an early follow-up time point is not easily distinguishable for an expert physician. We hypothesized that a radiomics signature derived from standard-of-care computed tomography (CT) imaging can detect cancer recurrence within six months of SABR treatment. This study reports on the design phase of our work, with external validation planned in future work. In this study, we performed cross-validation experiments with four feature selection approaches and seven classifiers on an 81-patient data set. We extracted 104 radiomics features from the consolidative and the peri-consolidative regions on the follow-up CT scans. The best results were achieved using the sum of estimated Mahalanobis distances (Maha) for supervised forward feature selection and a trainable automatic radial basis support vector classifier (RBSVC). This system produced an area under the receiver operating characteristic curve (AUC) of 0.84, an error rate of 16.4%, a false negative rate of 12.7%, and a false positive rate of 20.0% for leaveone patient out cross-validation. This suggests that once validated on an external data set, radiomics could reliably detect post-SABR recurrence and form the basis of a tool assisting physicians in making salvage treatment decisions.

  4. Radiation therapy for early stage Hodgkin's disease: Australasian patterns of care

    Energy Technology Data Exchange (ETDEWEB)

    Barton, Michael; Boyages, John; Crennan, Elizabeth; Davis, Sidney; Fisher, Richard J; Hook, Carolyn; Johnson, Neva; Joseph, David; Liew, Kuen H; Morgan, Graeme; O' Brien, Peter; Pendlebury, Sue; Pratt, Gary; Quong, George; Thornton, Deborah; Walker, Quenten; Wallington, Margaret; Trotter, Grant

    1995-01-15

    Purpose: Analysis of treatment outcome for Stage I-IIA supradiaphragmatic Hodgkin's disease treated solely by irradiation in Australia and New Zealand. Methods and Materials: Patients with supradiaphragmatic Hodgkin's disease only who were treated by irradiation alone with curative intent between 1969 to 1988 were retrospectively reviewed. Ten radiation oncology departments in Australia and New Zealand contributed patient data to the study. Patient, tumor, and treatment variables were recorded. Disease-free interval, survival, and complications were analyzed. Results: Eight hundred and twenty patients were reviewed. The median age was 29 years. There were 437 men and 383 women. The distribution of 310 clinically staged patients was 170 stage IA, 5 IB, and 135 IIA. Five hundred and ten patients received laparotomies, and pathologic staging was as follows: IA 214, IB 13, IIA 283. The 10-year acturial disease-free rate was 69% and overall survival rate was 79%. Increasing age, male sex, higher number of involved sites, the use of involved field irradiation, no staging laparotomy, and earlier year of treatment were significantly associated with an increased risk of relapse and lower survival. Actuarial 10-year survival following recurrence was 48%. Acute complications requiring interruption to treatment occurred in 46 patients (6%), but < 1% had their treatment permanently suspended. Actuarial complication rates at 10 years were: cardiac 2%, pulmonary 3% and thyroid 5%. There were 44 second malignancies including 10 non-Hodgkin's lymphomas, 3 leukemias, 7 lung, and 6 breast cancers. Mean delay to the development of a second cancer was 6 years. The 10-year actuarial rate of second malignancy was 5%. Conclusions: The Australasian experience of early stage Hodgkin's disease is consistent with the results in the published literature and confirms that irradiation produces a high cure rate with minimal toxicity.

  5. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab

    International Nuclear Information System (INIS)

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2 + ) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2 + breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2 + breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients

  6. Radiation therapy for early stage Hodgkin's disease: Australasian patterns of care

    International Nuclear Information System (INIS)

    Barton, Michael; Boyages, John; Crennan, Elizabeth; Davis, Sidney; Fisher, Richard J.; Hook, Carolyn; Johnson, Neva; Joseph, David; Liew, Kuen H.; Morgan, Graeme; O'Brien, Peter; Pendlebury, Sue; Pratt, Gary; Quong, George; Thornton, Deborah; Walker, Quenten; Wallington, Margaret; Trotter, Grant

    1995-01-01

    Purpose: Analysis of treatment outcome for Stage I-IIA supradiaphragmatic Hodgkin's disease treated solely by irradiation in Australia and New Zealand. Methods and Materials: Patients with supradiaphragmatic Hodgkin's disease only who were treated by irradiation alone with curative intent between 1969 to 1988 were retrospectively reviewed. Ten radiation oncology departments in Australia and New Zealand contributed patient data to the study. Patient, tumor, and treatment variables were recorded. Disease-free interval, survival, and complications were analyzed. Results: Eight hundred and twenty patients were reviewed. The median age was 29 years. There were 437 men and 383 women. The distribution of 310 clinically staged patients was 170 stage IA, 5 IB, and 135 IIA. Five hundred and ten patients received laparotomies, and pathologic staging was as follows: IA 214, IB 13, IIA 283. The 10-year acturial disease-free rate was 69% and overall survival rate was 79%. Increasing age, male sex, higher number of involved sites, the use of involved field irradiation, no staging laparotomy, and earlier year of treatment were significantly associated with an increased risk of relapse and lower survival. Actuarial 10-year survival following recurrence was 48%. Acute complications requiring interruption to treatment occurred in 46 patients (6%), but < 1% had their treatment permanently suspended. Actuarial complication rates at 10 years were: cardiac 2%, pulmonary 3% and thyroid 5%. There were 44 second malignancies including 10 non-Hodgkin's lymphomas, 3 leukemias, 7 lung, and 6 breast cancers. Mean delay to the development of a second cancer was 6 years. The 10-year actuarial rate of second malignancy was 5%. Conclusions: The Australasian experience of early stage Hodgkin's disease is consistent with the results in the published literature and confirms that irradiation produces a high cure rate with minimal toxicity

  7. Quality of life following endoscopic resection or radio-therapy for early glottic cancer

    International Nuclear Information System (INIS)

    Bahannan, Abdulrahman A.; Zabrodsky, M.; Chovanec, M.; Cerny, L.; Lohynska, R.

    2007-01-01

    To compare post treatment quality of life (QoL) of patients treated by radiotherapy or endoscopic transoral endolaryngeal surgery using two quality of life scoring tools. From May 1998 to July 2005, 48 patients (11 women and 37 men) with early glottic cancer were treated with curative radiotherapy (18 patients) or laser cordectomy (30 patients), and retrospectively evaluated using QoL questionnaires; European Organization for Research and Treatment of Cancer (EORTC) - EORTC-QoL Core Questionnaire (QLQ-C30 version 2.0) and organ specific EORTC - QLQ, Head and Neck Module (QLQ-H and N35) at the University Hospital Motol, Czech Republic. Mean follow-up was 24 months. Only patients in complete remission were enrolled in the study. The overall score calculated separately for both questionnaires was not statistically different between both groups. Statistically significant differences were found only in specific group of questions focusing on saliva production (p=0.034) and sexuality performance (p=0.002). The majority of cases treated with cordectomy were Tis lesions. In the radiotherapy group, T1 lesions predominated (p=0.0001). Patients treated with radiotherapy were significantly older than those treated with cordectomy (p=0.027), which could explain the worsened score in sexuality questions. There were no significant differences found between genders allocated either to cordectomy or radiotherapy group. The overall QoL did not differ between patients treated with cordectomy or radiotherapy, despite the fact that patients treated with radiotherapy had more advanced disease and were older. There was significantly worse saliva and sexuality question score in the radiotherapy group. (author)

  8. Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial.

    Science.gov (United States)

    Kantarci, Kejal; Tosakulwong, Nirubol; Lesnick, Timothy G; Zuk, Samantha M; Lowe, Val J; Fields, Julie A; Gunter, Jeffrey L; Senjem, Matthew L; Settell, Megan L; Gleason, Carey E; Shuster, Lynne T; Bailey, Kent R; Dowling, N Maritza; Asthana, Sanjay; Jack, Clifford R; Rocca, Walter A; Miller, Virginia M

    2018-04-17

    The effects of 2 frequently used formulations of menopausal hormone therapy (mHT) on brain structure and cognition were investigated 3 years after the end of a randomized, placebo-controlled trial in recently menopausal women with good cardiovascular health. Participants (aged 42-56 years; 5-36 months past menopause) were randomized to one of the following: 0.45 mg/d oral conjugated equine estrogen (oCEE); 50 μg/d transdermal 17β-estradiol (tE2); or placebo pills and patch for 4 years. Oral progesterone (200 mg/d) was given to mHT groups for 12 days each month. MRIs were performed at baseline, at the end of 4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of participants also underwent Pittsburgh compound B-PET (n = 68). Ventricular volumes increased more in the oCEE group compared to placebo during the 4 years of mHT, but the increase in ventricular volumes was not different from placebo 3 years after the discontinuation of mHT. Increase in white matter hyperintensity volume was similar in the oCEE and tE2 groups, but it was statistically significantly greater than placebo only in the oCEE group. The longitudinal decline in dorsolateral prefrontal cortex volumes was less in the tE2 group compared to placebo, which correlated with lower cortical Pittsburgh compound B uptake. Rates of global cognitive change in mHT groups were not different from placebo. The effects of oCEE on global brain structure during mHT subside after oCEE discontinuation but white matter hyperintensities continue to increase. The relative preservation of dorsolateral prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may have long-term effects on the brain. This study provides Class III evidence that the rates of change in global brain volumes and cognitive function in recently menopausal women receiving mHT (tE2 or oCEE) were not significantly different from women receiving placebo, as measured 3 years after exposure to mHT. Copyright © 2018 The

  9. MRI-guided single fraction ablative radiotherapy for early-stage breast cancer : a brachytherapy versus volumetric modulated arc therapy dosimetry study

    NARCIS (Netherlands)

    Charaghvandi, Ramona K; den Hartogh, Mariska D; van Ommen, Anne-Mar L N; de Vries, Wilfred J H; Scholten, Vincent; Moerland, Rien; Philippens, Mariëlle E P; Schokker, Rogier I; van Vulpen, Marco; van Asselen, B; van den Bongard, Desirée H J G

    2015-01-01

    BACKGROUND AND PURPOSE: A radiosurgical treatment approach for early-stage breast cancer has the potential to minimize the patient's treatment burden. The dosimetric feasibility for single fraction ablative radiotherapy was evaluated by comparing volumetric modulated arc therapy (VMAT) with an

  10. Poor results of 5-aminolevulinic acid-photodynamic therapy for residual high-grade dysplasia and early cancer in barrett esophagus after endoscopic resection

    NARCIS (Netherlands)

    Peters, F.; Kara, M.; Rosmolen, W.; Aalders, M.; ten Kate, F.; Krishnadath, K.; van Lanschot, J.; Fockens, P.; Bergman, J.

    2005-01-01

    BACKGROUND AND STUDY AIMS: The aim of the study was to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of residual high-grade dysplasia or early cancer (HGD/EC) after endoscopic resection in Barrett esophagus. PATIENTS AND METHODS: Study patients were separated into group A,

  11. Influence of intestinal early enteral nutrition therapy on intestinal barrier function and immune response of patients with radiation enteritis

    International Nuclear Information System (INIS)

    Liu Guohui; Kang Xin; Chen Gong; Wang Guangyi

    2012-01-01

    Objective: To investigate the influence of early enteral nutrition therapy on the intestinal barrier function and immune response of the patients with radiation enteritis (ER) so as to find a relatively simple and effective method to treat RE. Methods: Fifty-six patients with radiation enteritis (RE) diagnosed by colonoscopy, X-rays, and pathology were randomly divided into 2 equal groups: experimental group undergoing enteral nutrition therapy, and control group undergoing conventional therapy only. Peripheral blood samples were collected 1, 11, and 21 days after admission. Plasma diamine oxidase (DAO), D-lactic acid, endotoxin, and lactulose/mannitol (L/M) ratio, and levels of IgG, IgM, and IgA, and CD4/CD8 ratio were examined. Five cases from the experimental group and 5 cases from the control group underwent second-time operation because of incomplete intestinal obstruction, intestinal stenosis, or recurrent tumor respectively. The biopsy specimens of the terminal ileum or distal descending colon taken during the first and second operations underwent pathological examination. Peripheral blood samples were collected 1, 11, and 21 days after admission. Plasma diamine oxidase (DAO), D-lactic acid, endotoxin, and lactulose/mannitol (L/M) ratio, and levels of IgG, IgM, and IgA, and CD4/CD8 ratio were examined. Results: There were no significant differences in the intestinal function and blood immunological indices between these 2 groups. The levels of DAO, D-lactic acid, and endotoxin,and the L/M ratio 11 days after admission of the experiment group were all significantly lower than those of the control group (t=2.568, 2.427, 2.143, 2.443, P<0.05), and all those indices 21 days after admission of the experiment group were all much more significantly lower in comparison with the control group (t=6.019, 12.834, 7.837, 7.997, P<0.01). The levels of IgG, IgM, and IgA, and CD4/CD8 ratio 11 days after admission of the experimental group were all significantly higher than

  12. Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Ju; Rhee, Woo Joong; Choi, Seo Hee; Kim, Gwi Eon; Kim, Yong Bae [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, EunJi; Kim, Sang Wun; Kim, Sung Hoon [Dept. of Radiation Oncology, Obstetrics and Gynecology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    significance in early uterine cervical cancer patients. More effective systemic treatments might be needed to reduce distant metastasis in