Inclusion of methods for early detection of chronic kidney disease in ...

African Journals Online (AJOL)

Background The burden and magnitude of chronic kidney disease (CKD) are enormous. The incidence and prevalence of chronic kidney disease are rising all over the world. Thus, there is the urgent and pressing need for methods of early detection of CKD, to be included in guidelines for management of noncommunicable ...

[Better pain management in chronic pancreatitis through early surgery?].

NARCIS (Netherlands)

Ahmed Ali, U.; Bruno, M.J.; Issa, Y.; Gooszen, H.G.; Fockens, P.; Boermeester, M.A.; Drenth, J.P.H.; Hesselink, E.J.; Goor, H. van; et al.,

2012-01-01

The most important symptom in patients with chronic pancreatitis is pain. This is often difficult to treat. The current treatment consists of, successively, optimal medical treatment, endoscopic intervention and finally surgical intervention. Previous research has indicated that early surgical

Early visceral pain predicts chronic pain after laparoscopic cholecystectomy

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Blichfeldt-Eckhardt, Morten Rune; Ording, Helle; Andersen, Claus

2014-01-01

Chronic pain after laparoscopic cholecystectomy is related to postoperative pain during the first postoperative week, but it is unknown which components of the early pain response is important. In this prospective study, 100 consecutive patients were examined preoperatively, 1week postoperatively...

Cartilage oligomeric matrix protein deficiency promotes early onset and the chronic development of collagen-induced arthritis

DEFF Research Database (Denmark)

Geng, Hui; Carlsen, Stefan; Nandakumar, Kutty

2008-01-01

ABSTRACT: INTRODUCTION: Cartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage. The development of arthritis, like collagen-induced arthritis (CIA), involves cartilage as a target tissue. We have investigated the development of CIA in COMP-deficient mice. METHODS: COMP......-deficient mice in the 129/Sv background were backcrossed for 10 generations against B10.Q mice, which are susceptible to chronic CIA. COMP-deficient and wild-type mice were tested for onset, incidence, and severity of arthritis in both the collagen and collagen antibody-induced arthritis models. Serum anti......-collagen II and anti-COMP antibodies as well as serum COMP levels in arthritic and wild-type mice were measured by enzyme-linked immunosorbent assay. RESULTS: COMP-deficient mice showed a significant early onset and increase in the severity of CIA in the chronic phase, whereas collagen II-antibody titers were...

Therapeutic misconception in early phase gene transfer trials.

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Henderson, Gail E; Easter, Michele M; Zimmer, Catherine; King, Nancy M P; Davis, Arlene M; Rothschild, Barbra Bluestone; Churchill, Larry R; Wilfond, Benjamin S; Nelson, Daniel K

2006-01-01

Many subjects in early phase clinical trials expect to benefit in some way from the research intervention. It is understandable that people hope for improvement in their condition, no matter what the evidence. Yet unreasonable expectation of medical benefit may reflect problems with informed consent: Investigators may not disclose clearly that direct medical benefit from an early phase experimental intervention is unlikely or impossible, or subjects may not appreciate the differences between treatment and research. This paper presents findings from recent interviews with researchers and subjects and analysis of consent forms in early phase gene transfer research, a cutting-edge technology often called 'gene therapy'. We use three variables to construct a composite measure of therapeutic misconception TM, tapping misconceptions about the purposes of early phase research and the potential for direct medical benefit in these trials. Our multivariate model demonstrates the importance of both subject- and study-level factors as predictors of this TM index: education, disease type, and communication by study personnel about the likelihood of benefit. We hope that this work will deepen the discussion of how to define and measure TM, and refine the specification of factors that are related to subjects' TM.

Modifications of the National Early Warning Score for patients with chronic respiratory disease

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Pedersen, N. E.; Rasmussen, L. S.; Petersen, J. A.

2018-01-01

System (CROS), the Chronic Respiratory Early Warning Score (CREWS) and the Salford NEWS (S-NEWS) affected NEWS total scores and NEWS performance. METHODS: In an observational study, we included patients with chronic respiratory disease. The frequency of use of CROS and the NEWS total score changes caused...... and specialist consultation' total score intervals to lower intervals. CONCLUSION: Capital Region of Denmark NEWS Override System was frequently used in patients with chronic respiratory disease. CROS, CREWS and S-NEWS reduced sensitivity for 48-h mortality and ICU admission. Using the methodology prevalent......BACKGROUND: The National Early Warning Score (NEWS) uses physiological variables to detect deterioration in hospitalized patients. However, patients with chronic respiratory disease may have abnormal variables not requiring interventions. We studied how the Capital Region of Denmark NEWS Override...

40 CFR 73.20 - Phase II early reduction credits.

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2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Phase II early reduction credits. 73.20 Section 73.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE ALLOWANCE SYSTEM Allowance Allocations § 73.20 Phase II early reduction credits...

First experience with early dynamic 18F-NaF-PET/CT in patients with chronic osteomyelitis

International Nuclear Information System (INIS)

Freesmeyer, M.; Stecker, F.F.; Schierz, J.-H.; Winkens, T.; Hofmann, G.O.

2014-01-01

This study investigates whether early dynamic positron emission tomography/computed tomography (ed-PET/CT) using 18 F-sodium fluoride-( 18 F-NaF) is feasible in depicting early phases of radiotracer distribution in patients with chronic osteomyelitis (COM). A total of 12 ed 18 F-NaF-PET/CT examinations were performed on 11 consecutive patients (2 female, 9 male; age 53 ± 12 years) in list mode over 5 min starting with radiopharmaceutical injection before standard late 18 F-NaF-PET/CT. Eight consecutive time intervals (frames) were reconstructed for each patient: four 15 s, then four 60 s. Several volumes of interest (VOI) were selected, representing the affected area as well as different reference areas within the bone and soft tissue. Maximum and mean ed standardized uptake values (edSUV max , edSUV mean , respectively) were calculated in each VOI during each frame to measure early fluoride influx and accumulation. Results were compared between affected and non-affected (contralateral) bones. Starting in the 31-45 s frame, the affected bone area showed significantly higher edSUV max and edSUV mean compared to the healthy contralateral region. The affected bone areas also significantly differed from non-affected contralateral regions in conventional late 18 F-NaF-PET/CT. This pilot study suggests that, in patients with COM, ed 18 F-NaF-PET offers additional information about early radiotracer distribution to standard 18 F-NaF-PET/CT, similar to a three-phase bone scan. The results should be validated in larger trials which directly compare ed 18 F-NaF-PET to a three-phase bone scan. (author)

Sex-specific impact of early-life adversity on chronic pain: a large population-based study in Japan

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Yamada K

2017-02-01

Full Text Available Keiko Yamada,1,2 Ko Matsudaira,3,4 Eizaburo Tanaka,1,5 Hiroyuki Oka,3 Junji Katsuhira,3,6 Hiroyasu Iso1 1Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 2Center for Pain Management, Osaka University Hospital, Suita, Osaka, 3Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Tokyo, 4Japan Labour Health & Welfare Organization, Tokyo, 5Hyogo Institute for Traumatic Stress, Kobe, 6Department of Prosthetics & Orthotics and Assistive Technology, Faculty of Medical Technology, Niigata University of Health and Welfare, Niigata, Japan Background: Responses to early-life adversity may differ by sex. We investigated the ­sex-specific impact of early-life adversity on chronic pain, chronic multisite pain, and somatizing tendency with chronic pain. Methods: We examined 4229 respondents aged 20–79 years who participated in the Pain Associated Cross-Sectional Epidemiological Survey in Japan. Outcomes were: 1 chronic pain prevalence, 2 multisite pain (≥3 sites prevalence, and 3 multiple somatic symptoms (≥3 symptoms among respondents with chronic pain related to the presence or absence of early-life adversity. Multivariable-adjusted odds ratios (ORs were calculated with 95% confidence intervals using a logistic regression model including age, smoking status, exercise routine, sleep time, body mass index, household expenditure, and the full distribution of scores on the Mental Health Inventory-5. We further adjusted for pain intensity when we analyzed the data for respondents with chronic pain. Results: The prevalence of chronic pain was higher among respondents reporting the presence of early-life adversity compared with those reporting its absence, with multivariable ORs of 1.62 (1.22–2.15, p<0.01 in men and 1.47 (1.13–1.90, p<0.01 in women. Among women with chronic pain, early

Family needs in the chronic phase after severe brain injury in Denmark

DEFF Research Database (Denmark)

Doser, Karoline; Norup, Anne

2014-01-01

Abstract Objective: This preliminary study aimed at investigating (1) changes in the status of family members between time of injury and follow-up in the chronic phase and (2) the most important needs within the family in the chronic phase and whether the needs were perceived as met. Participants......: The sample comprised 42 relatives (76% female, mean age = 53 years) of patients with severe brain injury, who had received intensive sub-acute rehabilitation. The relatives were contacted in the chronic phase after brain injury. Outcome measure: A set of questions about demographics and time spent caregiving...... for the patient was completed. The relatives completed the revised version of the Family Needs Questionnaire, a questionnaire consisting of 37 items related to different needs following brain injury. Results: Significant changes in status were found in employment (z = -3.464, p = 0.001) and co-habitation (z = -3...

Firstline treatment for chronic phase chronic myeloid leukemia patients should be based on a holistic approach.

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Breccia, Massimo; Alimena, Giuliana

2015-02-01

New selective and more potent drugs for the cure of chronic phase chronic myeloid leukemia patients are now available: physicians in some countries must decide the best option, selecting one of the drugs available. What the main prognostic factors are in order to make this selection remains a matter of discussion. Introducing a 'holistic approach' for the first time in chronic myeloid leukemia, as practiced in other diseases, and looking at the patient in a complete picture, considering several variables, such as comorbidities, age, concomitant drugs, lifestyle and patient expectations, may be of help to understand, patient by patient, the best therapeutic strategy.

Management of Advanced-Phase Chronic Myelogenous Leukemia.

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Radich, Jerald P

2016-05-01

Chronic myelogenous leukemia represents the poster child of successful precision medicine in cancer, with amazing survival results achieved with targeted tyrosine kinase inhibitors (TKIs) in many patients with chronic-phase disease. Unfortunately, however, this good news has not extended to patients in blast crisis, for whom survival has not clearly been improved with TKIs. During his presentation at the NCCN 21st Annual Conference, Jerald P. Radich, MD, briefly explored the biology behind advanced-stage disease and several of the molecular findings in disease progression. He also reviewed some of the therapeutic options in advanced disease, emphasizing that transplantation, although fraught with some difficulties, offers the best long-term prognosis for patients in blast crisis. Copyright © 2016 by the National Comprehensive Cancer Network.

Internalized stigma in adults with early phase versus prolonged psychosis.

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Firmin, Ruth L; Lysaker, Paul H; Luther, Lauren; Yanos, Philip T; Leonhardt, Bethany; Breier, Alan; Vohs, Jenifer L

2018-03-30

Although internalized stigma is associated with negative outcomes among those with prolonged psychosis, surprisingly little work has focused on when in the course of one's illness stigma is internalized and the impact of internalization on symptoms or social functioning over the course of the illness. Therefore, this study investigated whether (1) internalized stigma is greater among those later in the course of psychosis and (2) whether internalized stigma has a stronger negative relationship with social functioning or symptoms among those with prolonged compared to early phase psychosis. Individuals with early phase (n = 40) and prolonged psychosis (n = 71) who were receiving outpatient services at an early-intervention clinic and a VA medical center, respectively, completed self-report measures of internalized stigma and interview-rated measures of symptoms and social functioning. Controlling for education, race and sex differences, internalized stigma was significantly greater among those with prolonged psychosis compared to early phase. Internalized stigma was negatively related to social functioning and positively related to symptoms in both groups. Furthermore, the magnitude of the relationship between cognitive symptoms and internalized stigma was significantly greater among those with early phase. Stereotype endorsement, discrimination experiences and social withdrawal also differentially related to symptoms and social functioning across the 2 samples. Findings suggest that internalized stigma is an important variable to incorporate into models of early psychosis. Furthermore, internalized stigma may be a possible treatment target among those with early phase psychosis. © 2018 John Wiley & Sons Australia, Ltd.

Quantifying factors determining the rate of CTL escape and reversion during acute and chronic phases of HIV infection

Energy Technology Data Exchange (ETDEWEB)

Ganusov, Vitaly V [Los Alamos National Laboratory; Korber, Bette M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

2009-01-01

Human immunodeficiency virus (HIV) often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. However, the importance and quantitative details of CTL escape in humans are poorly understood. In part, this is because most studies looking at escape of HIV from CTL responses are cross-sectional and are limited to early or chronic phases of the infection. We use a novel technique of single genome amplification (SGA) to identify longitudinal changes in the transmitted/founder virus from the establishment of infection to the viral set point at 1 year after the infection. We find that HIV escapes from virus-specific CTL responses as early as 30-50 days since the infection, and the rates of viral escapes during acute phase of the infection are much higher than was estimated in previous studies. However, even though with time virus acquires additional escape mutations, these late mutations accumulate at a slower rate. A poor correlation between the rate of CTL escape in a particular epitope and the magnitude of the epitope-specific CTL response suggests that the lower rate of late escapes is unlikely due to a low efficacy of the HIV-specific CTL responses in the chronic phase of the infection. Instead, our results suggest that late and slow escapes are likely to arise because of high fitness cost to the viral replication associated with such CTL escapes. Targeting epitopes in which virus escapes slowly or does not escape at all by CTL responses may, therefore, be a promising direction for the development of T cell based HIV vaccines.

Quantitative phase imaging of platelets in patients with chronic renal failure treated with hemodialysis

Science.gov (United States)

Vasilenko, Irina; Vlasova, Elizaveta; Metelin, Vladislav; Kardasheva, Ziver

2018-02-01

The development of robust non-invasive laboratory screening methods for early diagnosis on the out-patient basis seems quite relevant for practical medicine. It is known, that platelet is an original biosensor, a detector of early changes in hemostasis condition. The aim of this study was to assess a potential of the quantitative phase imaging (QPI) technique for real time evaluation the influence of low-molecular weight and unfractionated heparin on platelets in patients with the end-stage of chronic renal failure, who were treated with program hemodialysis (PHD). The main group consisted of 21 patients who were administered a low-molecular weight heparin for hypocoagulation during the procedure of hemodialysis. The control group (15 patients) received unfractionated heparin. Morphodensitometric state of living platelets we evaluated by QPI using computer phase-interference microscope MIM (Moscow, Russia). We analyzed the optical-geometrical parameters and the morphological features of living platelets which reflected the degree of their activation at the beginning of PHD (before administration of heparin), in 15 minutes after it and at the end of the procedure. The results allow us to conclude that the use of low-molecular weight heparin provides better ratio of efficacy/safety and causes a reduction of the platelet activation during the hemodialysis procedure. Practical implementation of QPI for clinical monitoring of platelets makes it possible to obtain important information on hemostasis cell. It opens new opportunities to assess the efficacy of treatment, as well as for early diagnosis of complications for disease.

Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice.

Science.gov (United States)

Lopez, Marcelo F; Doremus-Fitzwater, Tamara L; Becker, Howard C

2011-06-01

Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2), and chronic variable stress (CVS) alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate housed (one mouse/cage) or group housed (four mice/cage) according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to CVS or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a two-bottle choice (ethanol 15% vol/vol vs. water) for a 2-h limited access procedure. Early social isolation resulted in greater ethanol intake compared with the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared with the corresponding group-housed mice (Experiment 2

Early diagnosis of chronic pancreatitis: understanding the factors associated with the development of chronic pancreatitis.

Science.gov (United States)

Yamabe, Akane; Irisawa, Atsushi; Shibukawa, Goro; Sato, Ai; Fujisawa, Mariko; Arakawa, Noriyuki; Yoshida, Yoshitsugu; Abe, Yoko; Igarashi, Ryo; Maki, Takumi; Yamamoto, Shogo

2017-04-28

The prognosis of advanced chronic pancreatitis (CP) is poor with the mortality rate approximately two-fold higher than the general population according to a survey of the prognosis of CP.　From this standpoint, the concept of early CP was propagated in Japan in 2009 to encourage the medical treatment for the earlier stages of CP.　That is, picking up the patients suspicious for early CP and then providing medical treatment for them are very important not only for patients, but also for health care economics.　In this review, we described some potential factors associated with the development of CP (alcohol, smoking, past history of acute pancreatitis, aging, gallstone, and gender) that are extremely important to discover patients with early-stage CP.

PTCH1 is a reliable marker for predicting imatinib response in chronic myeloid leukemia patients in chronic phase.

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Juan M Alonso-Dominguez

Full Text Available Patched homolog 1 gene (PTCH1 expression and the ratio of PTCH1 to Smoothened (SMO expression have been proposed as prognostic markers of the response of chronic myeloid leukemia (CML patients to imatinib. We compared these measurements in a realistic cohort of 101 patients with CML in chronic phase (CP using a simplified qPCR method, and confirmed the prognostic power of each in a competing risk analysis. Gene expression levels were measured in peripheral blood samples at diagnosis. The PTCH1/SMO ratio did not improve PTCH1 prognostic power (area under the receiver operating characteristic curve 0.71 vs. 0.72. In order to reduce the number of genes to be analyzed, PTCH1 was the selected measurement. High and low PTCH1 expression groups had significantly different cumulative incidences of imatinib failure (IF, which was defined as discontinuation of imatinib due to lack of efficacy (5% vs. 25% at 4 years, P = 0.013, probabilities of achieving a major molecular response (81% vs. 53% at first year, P = 0.02, and proportions of early molecular failure (14% vs. 43%, P = 0.015. Every progression to an advanced phase (n = 3 and CML-related death (n = 2 occurred in the low PTCH1 group (P<0.001 for both comparisons. PTCH1 was an independent prognostic factor for the prediction of IF. We also validated previously published thresholds for PTCH1 expression. Therefore, we confirmed that PTCH1 expression can predict the imatinib response in CML patients in CP by applying a more rigorous statistical analysis. Thus, PTCH1 expression is a promising molecular marker for predicting the imatinib response in CML patients in CP.

Radotinib and its clinical potential in chronic-phase chronic myeloid leukemia patients: an update.

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Eskazan, Ahmet Emre; Keskin, Dilek

2017-09-01

Although imatinib has dramatically improved major outcomes in patients with chronic myeloid leukemia (CML), there are newer tyrosine kinase inhibitors (TKIs) approved worldwide for the treatment of resistant cases, and two second-generation TKIs (dasatinib, nilotinib) are approved in some nations for treating patients in the upfront setting. Radotinib (IY5511HCL, Supect® ) is a novel and selective second-generation BCR-ABL1 TKI, which is currently approved in Korea for the treatment of patients with CML both in the upfront and salvage settings. This review mainly focuses on the clinical potential of radotinib in patients with CML in chronic phase in terms of efficacy and safety.

The Importance of Assessing Nutritional Status to Ensure Optimal Recovery during the Chronic Phase of Stroke

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Monica C. Serra

2018-01-01

Full Text Available Background. Despite evidence that many of the consequences of stroke that hinder recovery (i.e., obesity, muscle atrophy, and functional declines have nutritionally modifiable behavior components, little attention has been focused on the significance of nutrition beyond the acute phase of stroke. Objective. This literature review summarizes the evidence for and against the influence of nutrition on optimal recovery and rehabilitation in chronic (>6 months stroke. Results. The literature, which is mainly limited to cross-sectional studies, suggests that a suboptimal nutritional status, including an excess caloric intake, reduced protein intake, and micronutrient deficiencies, particularly the B-vitamins, vitamin D, and omega 3 fatty acids, may have deleterious effects on metabolic, physical, and psychological functioning in chronic stroke survivors. Conclusions. Careful evaluation of dietary intake, especially among those with eating disabilities and preexisting malnutrition, may aid in the identification of individuals at increased nutritional risk through which early intervention may benefit recovery and rehabilitation and prevent further complications after stroke.

The Importance of Assessing Nutritional Status to Ensure Optimal Recovery during the Chronic Phase of Stroke.

Science.gov (United States)

Serra, Monica C

2018-01-01

Despite evidence that many of the consequences of stroke that hinder recovery (i.e., obesity, muscle atrophy, and functional declines) have nutritionally modifiable behavior components, little attention has been focused on the significance of nutrition beyond the acute phase of stroke. This literature review summarizes the evidence for and against the influence of nutrition on optimal recovery and rehabilitation in chronic (>6 months) stroke. The literature, which is mainly limited to cross-sectional studies, suggests that a suboptimal nutritional status, including an excess caloric intake, reduced protein intake, and micronutrient deficiencies, particularly the B-vitamins, vitamin D, and omega 3 fatty acids, may have deleterious effects on metabolic, physical, and psychological functioning in chronic stroke survivors. Careful evaluation of dietary intake, especially among those with eating disabilities and preexisting malnutrition, may aid in the identification of individuals at increased nutritional risk through which early intervention may benefit recovery and rehabilitation and prevent further complications after stroke.

Dual phase helical CT: diagnosis value for early pancreatic carcinoma

International Nuclear Information System (INIS)

Shen Bingqi; Zhang Ling; Zheng Keguo; Xu Dasheng

2006-01-01

Objective: To study dual-phase helical CT for the evaluation of early pancreatic cacinoma. Methods: Dual-phase helical CT was performed on 21 patients with early pancreatic carcinoma. In the enhanced imaging the contrast material was intravenously injected in a dose of 1.5 ml/kg at a rate of 3 ml/s. The image acquisition of the lesion in pancreatic phase (PP) and portal venous phase (PVP) were started at 35 seconds and 65 seconds after the start of the injection respectively. The enhancement of normal pancreas and tumor during the two phases was observed and compared. All data were statistically analyzed. Results: Tumor-pancreas contrast was significantly greater in PP (45.16±113.23) HU than in PVP (23.15±12.44) HU (t=2.13, P<0.01). Conclusion: Dual-phase helical CT scan for pancreas, including the imaging of the pancreatic and portal , venous phase, can be applied as an optimal selection. It can delineate early pancreatic carcinoma clearly and provide more information for the diagnosis of the lesion. The tumor-pancreas contrast was much higher' in PP than in PVP. (authors)

Early- and later-phases satellite cell responses and myonuclear content with resistance training in young men.

Science.gov (United States)

Damas, Felipe; Libardi, Cleiton A; Ugrinowitsch, Carlos; Vechin, Felipe C; Lixandrão, Manoel E; Snijders, Tim; Nederveen, Joshua P; Bacurau, Aline V; Brum, Patricia; Tricoli, Valmor; Roschel, Hamilton; Parise, Gianni; Phillips, Stuart M

2018-01-01

Satellite cells (SC) are associated with skeletal muscle remodelling after muscle damage and/or extensive hypertrophy resulting from resistance training (RT). We recently reported that early increases in muscle protein synthesis (MPS) during RT appear to be directed toward muscle damage repair, but MPS contributes to hypertrophy with progressive muscle damage attenuation. However, modulations in acute-chronic SC content with RT during the initial (1st-wk: high damage), early (3rd-wk: attenuated damage), and later (10th-wk: no damage) stages is not well characterized. Ten young men (27 ± 1 y, 23.6 ± 1.0 kg·m-2) underwent 10-wks of RT and muscle biopsies (vastus-lateralis) were taken before (Pre) and post (48h) the 1st (T1), 5th (T2) and final (T3) RT sessions to evaluate fibre type specific SC content, cross-sectional area (fCSA) and myonuclear number by immunohistochemistry. We observed RT-induced hypertrophy after 10-wks of RT (fCSA increased ~16% in type II, P phase of RT than muscle hypertrophy resulted from 10-wks RT in young men. Chronic elevated SC pool size with RT is important providing proper environment for future stresses or larger fCSA increases.

Early histological and functional effects of chronic copper exposure in rat liver.

Science.gov (United States)

Cisternas, Felipe A; Tapia, Gladys; Arredondo, Miguel; Cartier-Ugarte, Denise; Romanque, Pamela; Sierralta, Walter D; Vial, María T; Videla, Luis A; Araya, Magdalena

2005-10-01

Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1,200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.

Tyrosine kinase inhibition: A therapeutic target for the management of chronic-phase chronic myeloid leukemia

Science.gov (United States)

Jabbour, Elias J; Cortes, Jorge E; Kantarjian, Hagop M

2014-01-01

Chronic myeloid leukemia (CML) is a hematologic neoplasm with a progressive, ultimately terminal, disease course. In most cases, CML arises owing to the aberrant formation of a chimeric gene for a constitutively active tyrosine kinase. Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target transforming the prognosis of patients with CML. New tyrosine kinase inhibitors (TKIs) continue to improve the management of CML, offering alternative options for those resistant to or intolerant of standard TKIs. Here we review the pathobiology of CML and explore emerging strategies to optimize the management of chronic-phase CML, particularly first-line treatment. PMID:24236822

Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study.

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Hochhaus, A; Masszi, T; Giles, F J; Radich, J P; Ross, D M; Gómez Casares, M T; Hellmann, A; Stentoft, J; Conneally, E; García-Gutiérrez, V; Gattermann, N; Wiktor-Jedrzejczak, W; le Coutre, P D; Martino, B; Saussele, S; Menssen, H D; Deng, W; Krunic, N; Bedoucha, V; Saglio, G

2017-07-01

The single-arm, phase 2 ENESTfreedom trial assessed the potential for treatment-free remission (TFR; i.e., the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with MR 4.5 (BCR-ABL1⩽0.0032% on the International Scale (BCR-ABL1 IS )) and ⩾2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase. Patients with loss of major molecular response (MMR; BCR-ABL1 IS ⩽0.1%) during the TFR phase reinitiated nilotinib. In total, 215 patients entered the consolidation phase, of whom 190 entered the TFR phase. The median duration of nilotinib before stopping treatment was 43.5 months. At 48 weeks after stopping nilotinib, 98 patients (51.6%; 95% confidence interval, 44.2-58.9%) remained in MMR or better (primary end point). Of the 86 patients who restarted nilotinib in the treatment reinitiation phase after loss of MMR, 98.8% and 88.4%, respectively, regained MMR and MR 4.5 by the data cutoff date. Consistent with prior reports of imatinib-treated patients, musculoskeletal pain-related events were reported in 24.7% of patients in the TFR phase (consolidation phase, 16.3%).

Two cases of chronic myelogenous leukemia (CML) treated with Iminitab (Glivec) in different phases

International Nuclear Information System (INIS)

Davoli, R.; Ciarlo, S.; Acosta, I.; Perez, S.; Lagorio, S.; Pratti, A.A.

2003-01-01

Full text: IMINITAB, inhibitor of cytoplasmic transduction signs, and hindering neoplastic cells growth, is a new therapeutic agent for chronic myelogenous leukemia (CML). It is a tyrosine kinase bcrabl inhibitor, inhibiting also the c-kit receptor protein in gastrointestinal neoplasia and small cells lung cancer. The aim of the present work was to evaluate the effect of this agent in CML patients in two different time-periods, namely the chronic phase and the acute one. We hereby present two patients: 1) a 48 years old patient with radioactive contamination history, and 2) a 19 years old patient. In both cases diagnosis was confirmed by BM and BM biopsy, neutrophile alkaline phosphatase, and Ph chromosome t(9;22) (q34;q11). There were non-compatible BM donors available. Both patients were treated with hydroxyurea, hydroxyurea plus interferon, and one of them adding ARAC. Since there was no favorable response an Iminitab course was started. Patient (2) with blastic crisis remitted for 12 month until subsequent relapse and death. Patient (1) treated during chronic phase is still in remission. Neither of them attained negative Ph chromosome. Up to now, current reports show a high percentage of relapse in patients treated during the acute phase, while the chronic ones present a smaller number of relapses. It is to be noted the importance of the follow up during the chronic phase, due to the short time drug utilization in our country (May 2001). Good tolerance and sustained remission in CML patients allows being optimistic regarding this therapeutic agent. (author)

Early life insults as determinants of chronic obstructive pulmonary disease in adult life

DEFF Research Database (Denmark)

Savran, Osman; Ulrik, Charlotte Suppli

2018-01-01

Background: Early life events may predispose to the development of chronic lung disease in adulthood. Aim: To provide an update on current knowledge of early nongenetic origins of COPD. Materials and methods: Systematic literature review was performed according to the Preferred Reporting Items...... in utero and early life is a risk factor for subsequent development of COPD. Furthermore, low birth weight, lower respiratory tract infections and asthma, including wheezy bronchitis, in childhood also seem to be important determinants for later development of COPD. Early life insults may, therefore...

Chronic Subdural Hematoma development in Accelerated phase of Chronic Myeloid Leukaemia presenting with seizure and rapid progression course with fatal outcome

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Raheja Amol

2015-06-01

Full Text Available Occurrence of chronic subdural hematoma (CSDH in leukemia is rare, and most reported cases occurred in relation with acute myeloid leukaemia; however, occurrence is extremely rare in accelerated phase of chronic myelogenous leukaemia (CML. Seizure as presentation of SDH development in CML cases is not reported in literature. Authors report an elderly male, who was diagnosed as CML, accelerated phase of developing SDH. Initially presented to local physician with seizure; urgent CT scan head was advised, but ignored and sensorium rapidly worsened over next day and reported to our emergency department in deeply comatose state, where imaging revealed chronic subdural hematoma with hypoxic brain injury with fatal outcome. Seizure, progressive worsening of headache, vomiting and papilloedema are harbinger of intracranial space occupying lesion and requires CT head in emergency medical department for exclusion, who are receiving treatment of haematological malignancy

Dual QCD and phase transition in early universe

International Nuclear Information System (INIS)

Ranjan, Akhilesh; Raina, P.K.; Nandan, Hemwati

2009-01-01

The quantum chromodynamics (QCD) vacuum with condensed monopoles/ dyons (i.e., a dual Ginzburg- Landau (DGL) type model of QCD or dual QCD) has been quite successful to describe the large-distance behavior of QCD vacuum. Further, such DGL theory of QCD at finite temperature is also found to be useful in studying the phase transition process as believed to occur in early universe. In the present article, we have used the DGL theory of QCD with dyons to study the hadronisation in early universe. The effective potential at finite temperature is calculated. The notions of the phase transition in the background of the dyonically condensed QCD vacuum has been investigated by calculating the critical temperature in view of the temperature dependent couplings

SU119. Internalized Stigma in Adults With Early-Phase vs Prolonged Psychosis

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Firmin, Ruth; Vohs, Jenifer; Luther, Lauren; Yanos, Philip; Leonhardt, Bethany; Lysaker, Paul

2017-01-01

Abstract Background: While internalized stigma is associated with negative outcomes among those with prolonged psychosis, surprisingly little work has focused on when in the course of one’s illness stigma is internalized and the impact of internalization on symptoms or quality of life over the course of the illness. Therefore, this study investigated whether (1) internalized stigma is greater among those later in the course of psychosis and (2) whether internalized stigma has a stronger negative relationship with quality of life or symptoms among those with prolonged compared to early-phase psychosis. Methods: Individuals with early-phase (n = 40) and prolonged psychosis (n = 71) who were receiving outpatient services at an early-intervention clinic and a VA medical center, respectively, completed self-report measures of internalized stigma and interview-rated measures of symptoms and quality of life. Results: Controlling for education, race, and sex differences, internalized stigma was significantly greater among those with prolonged compared to early-phase psychosis. Internalized stigma was negatively related to quality of life and positively related to symptoms in both groups. Furthermore, the magnitude of the relationship between cognitive symptoms and internalized stigma was significantly greater among those with early-phase psychosis. Stereotype endorsement, discrimination experiences, and social withdrawal also deferentially related to symptoms and quality of life across the 2 samples. Conclusion: Findings suggest that internalized stigma is an important variable to incorporate into models of early psychosis. Further, internalized stigma may be a possible treatment target among those in their early phase of psychosis.

Psychometric evaluation of a new instrument to measure disease self-management of the early stage chronic kidney disease patients.

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Lin, Chiu-Chu; Wu, Chia-Chen; Wu, Li-Min; Chen, Hsing-Mei; Chang, Shu-Chen

2013-04-01

This study aims to develop a valid and reliable chronic kidney disease self-management instrument (CKD-SM) for assessing early stage chronic kidney disease patients' self-management behaviours. Enhancing early stage chronic kidney disease patients' self-management plays a key role in delaying the progression of chronic kidney disease. Healthcare provider understanding of early stage chronic kidney disease patients' self-management behaviours can help develop effective interventions. A valid and reliable instrument for measuring chronic kidney disease patients' self-management behaviours is needed. A cross-sectional descriptive study collected data for principal components analysis with oblique rotation. Mandarin- or Taiwanese-speaking adults with chronic kidney disease (n=252) from two medical centres and one regional hospital in Southern Taiwan completed the CKD-SM. Construct validity was evaluated by exploratory factor analysis. Internal consistency and test-retest reliability were estimated by Cronbach's alpha and Pearson correlation coefficients. Four factors were extracted and labelled self-integration, problem-solving, seeking social support and adherence to recommended regimen. The four factors accounted for 60.51% of the total variance. Each factor showed acceptable internal reliability with Cronbach's alpha from 0.77-0.92. The test-retest correlations for the CKD-SM was 0.72. The psychometric quality of the CKD-SM instrument was satisfactory. Research to conduct a confirmatory factor analysis to further validate this new instrument's construct validity is recommended. The CKD-SM instrument is useful for clinicians who wish to identify the problems with self-management among chronic kidney disease patients early. Self-management assessment will be helpful to develop intervention tailored to the needs of the chronic kidney disease population. © 2013 Blackwell Publishing Ltd.

Conditional survival in patients with chronic myeloid leukemia in chronic phase in the era of tyrosine kinase inhibitors.

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Sasaki, Koji; Kantarjian, Hagop M; Jain, Preetesh; Jabbour, Elias J; Ravandi, Farhad; Konopleva, Marina; Borthakur, Gautam; Takahashi, Koichi; Pemmaraju, Naveen; Daver, Naval; Pierce, Sherry A; O'Brien, Susan M; Cortes, Jorge E

2016-01-15

Tyrosine kinase inhibitors (TKIs) significantly improve survival in patients with chronic myeloid leukemia in chronic phase (CML-CP). Conditional probability provides survival information in patients who have already survived for a specific period of time after treatment. Cumulative response and survival data from 6 consecutive frontline TKI clinical trials were analyzed. Conditional probability was calculated for failure-free survival (FFS), transformation-free survival (TFS), event-free survival (EFS), and overall survival (OS) according to depth of response within 1 year of the initiation of TKIs, including complete cytogenetic response, major molecular response, and molecular response with a 4-log or 4.5-log reduction. A total of 483 patients with a median follow-up of 99.4 months from the initiation of treatment with TKIs were analyzed. Conditional probabilities of FFS, TFS, EFS, and OS for 1 additional year for patients alive after 12 months of therapy ranged from 92.0% to 99.1%, 98.5% to 100%, 96.2% to 99.6%, and 96.8% to 99.7%, respectively. Conditional FFS for 1 additional year did not improve with a deeper response each year. Conditional probabilities of TFS, EFS, and OS for 1 additional year were maintained at >95% during the period. In the era of TKIs, patients with chronic myeloid leukemia in chronic phase who survived for a certain number of years maintained excellent clinical outcomes in each age group. Cancer 2016;122:238-248. © 2015 American Cancer Society. © 2015 American Cancer Society.

Long-term safety and efficacy of dasatinib in the treatment of chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib

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Shoumariyeh K

2014-09-01

Full Text Available Khalid Shoumariyeh, Nikolas von BubnoffDepartment of Hematology, Oncology and Stem Cell Transplantation, University Hospital Freiburg, Freiburg, Germany Abstract: Treatment of chronic myeloid leukemia (CML has undergone dramatic changes in the last decade. Dissecting the molecular pathways that lead to the development of this disease resulted in the development of targeted therapy against the molecular driver of CML, namely the aberrantly activated tyrosine kinase BCR-ABL1. By introducing the tyrosine kinase inhibitor imatinib to the treatment repertoire, the natural course of the disease has been dramatically altered and overall survival of patients with CML prolonged substantially. Nevertheless, a significant number of patients are primarily resistant, acquire resistance during the course of their disease, or do not tolerate the intake of imatinib due to adverse effects. Second-generation tyrosine kinase inhibitors were developed in an attempt to overcome these problems. Dasatinib is a potent oral kinase inhibitor that was originally developed as an Src-kinase inhibitor but exhibited promising potency against BCR-ABL1 as well. Phase I and II trials demonstrated efficacy in patients failing imatinib, and thus dasatanib was approved in 2006 for the treatment of imatinib-resistant or -intolerant patients with chronic-phase CML harboring the BCR-ABL1 fusion protein. It has since shown promising efficacy and good overall tolerability in subsequent clinical trials, including the Phase III first-line DASISION trial that led to the extension of its approval for first-line treatment of chronic-phase CML. The following review summarizes the available data on the long-term efficacy and safety of dasatinib as a second-line therapy in chronic-phase CML. Keywords: BCR-ABL1, TKI, CML-CP, second-line treatment

Early chronic obstructive pulmonary disease: definition, assessment, and prevention.

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Rennard, Stephen I; Drummond, M Bradley

2015-05-02

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD, however, is a heterogeneous collection of diseases with differing causes, pathogenic mechanisms, and physiological effects. Therefore a comprehensive approach to COPD prevention will need to address the complexity of COPD. Advances in the understanding of the natural history of COPD and the development of strategies to assess COPD in its early stages make prevention a reasonable, if ambitious, goal. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chronic phase of Chagas disease: why should it be treated? A comprehensive review

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José Rodrigues Coura

2011-09-01

Full Text Available The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii promote tissue regeneration to prevent fibrosis, (iii reverse existing fibrosis, (iv prevent cardiomyopathy, megaoesophagus and megacolon and (v reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis.

Accelerated phase chronic myeloid leukemia: evaluation of clinical criteria as predictors of survival, major cytogenetic response and progression to blast phase

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Vanessa Fiorini Furtado

2015-10-01

Full Text Available BACKGROUND: Published criteria defining the accelerated phase in chronic myeloid leukemia are heterogeneous and little is known about predictors of poor outcome.METHODS: This is a retrospective study of 139 subjects in the accelerated phase of chronic myeloid leukemia treated with imatinib at a single center in Brazil. The objective was to identify risk factors for survival, major cytogenetic response and progression to blast phase in this population. The factors analyzed were: blasts 10-29%, basophils ≥ 20%, platelets > 1 × 106/µL or 1 × 105/µL in the peripheral blood, as well as clonal evolution, splenomegaly, hemoglobin 12 months (p-value = 0.030.CONCLUSION: These data indicate that patients with the above risk factors have a worse prognosis. This information can guide the therapy to be used.

Spinal neuropeptide expression and neuropathic behavior in the acute and chronic phases after spinal cord injury: Effects of progesterone administration.

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Coronel, María F; Villar, Marcelo J; Brumovsky, Pablo R; González, Susana L

2017-02-01

Patients with spinal cord injury (SCI) develop chronic pain that severely compromises their quality of life. We have previously reported that progesterone (PG), a neuroprotective steroid, could offer a promising therapeutic strategy for neuropathic pain. In the present study, we explored temporal changes in the expression of the neuropeptides galanin and tyrosine (NPY) and their receptors (GalR1 and GalR2; Y1R and Y2R, respectively) in the injured spinal cord and evaluated the impact of PG administration on both neuropeptide systems and neuropathic behavior. Male rats were subjected to spinal cord hemisection at T13 level, received daily subcutaneous injections of PG or vehicle, and were evaluated for signs of mechanical and thermal allodynia. Real time PCR was used to determine relative mRNA levels of neuropeptides and receptors, both in the acute (1day) and chronic (28days) phases after injury. A significant increase in Y1R and Y2R expression, as well as a significant downregulation in GalR2 mRNA levels, was observed 1day after SCI. Interestingly, PG early treatment prevented Y1R upregulation and resulted in lower NPY, Y2R and GalR1 mRNA levels. In the chronic phase, injured rats showed well-established mechanical and cold allodynia and significant increases in galanin, NPY, GalR1 and Y1R mRNAs, while maintaining reduced GalR2 expression. Animals receiving PG treatment showed basal expression levels of galanin, NPY, GalR1 and Y1R, and reduced Y2R mRNA levels. Also, and in line with previously published observations, PG-treated animals did not develop mechanical allodynia and showed reduced sensitivity to cold stimulation. Altogether, we show that SCI leads to considerable changes in the spinal expression of galanin, NPY and their associated receptors, and that early and sustained PG administration prevents them. Moreover, our data suggest the participation of galaninergic and NPYergic systems in the plastic changes associated with SCI-induced neuropathic pain

Implementing Effective Mission Systems Engineering Practices During Early Project Formulation Phases

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Moton, Tryshanda

2016-01-01

Developing and implementing a plan for a NASA space mission can be a complicated process. The needs, goals, and objectives of any proposed mission or technology must be assessed early in the Project Life Cycle. The key to successful development of a space mission or flight project is the inclusion of systems engineering in early project formulation, namely during Pre-phase A, Phase A, and Phase B of the NASA Project Life Cycle. When a space mission or new technology is in pre-development, or "pre-Formulation", feasibility must be determined based on cost, schedule, and risk. Inclusion of system engineering during project formulation is key because in addition to assessing feasibility, design concepts are developed and alternatives to design concepts are evaluated. Lack of systems engineering involvement early in the project formulation can result in increased risks later in the implementation and operations phases of the project. One proven method for effective systems engineering practice during the pre-Formulation Phase is the use of a mission conceptual design or technology development laboratory, such as the Mission Design Lab (MDL) at NASA's Goddard Space Flight Center (GSFC). This paper will review the engineering process practiced routinely in the MDL for successful mission or project development during the pre-Formulation Phase.

Chronic early postnatal scream sound stress induces learning deficits and NMDA receptor changes in the hippocampus of adult mice.

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Hu, Lili; Han, Bo; Zhao, Xiaoge; Mi, Lihua; Song, Qiang; Wang, Jue; Song, Tusheng; Huang, Chen

2016-04-13

Chronic scream sounds during adulthood affect spatial learning and memory, both of which are sexually dimorphic. The long-term effects of chronic early postnatal scream sound stress (SSS) during postnatal days 1-21 (P1-P21) on spatial learning and memory in adult mice as well as whether or not these effects are sexually dimorphic are unknown. Therefore, the present study examines the performance of adult male and female mice in the Morris water maze following exposure to chronic early postnatal SSS. Hippocampal NR2A and NR2B levels as well as NR2A/NR2B subunit ratios were tested using immunohistochemistry. In the Morris water maze, stress males showed greater impairment in spatial learning and memory than background males; by contrast, stress and background females performed equally well. NR2B levels in CA1 and CA3 were upregulated, whereas NR2A/NR2B ratios were downregulated in stressed males, but not in females. These data suggest that chronic early postnatal SSS influences spatial learning and memory ability, levels of hippocampal NR2B, and NR2A/NR2B ratios in adult males. Moreover, chronic early stress-induced alterations exert long-lasting effects and appear to affect performance in a sex-specific manner.

Establishing a cost model when estimating product cost in early design phases

OpenAIRE

Jeppsson, Johanna; Sjöberg, Jessica

2017-01-01

About 75% of the total product cost is determined in the early design phase, which means that the possibilities to affect costs are relatively small when the design phase is completed. For companies, it is therefore vital to conduct reliable cost estimates in the early design phase, when selecting between different design choices. When conducting a cost estimate there are many uncertainties. The aim with this study is therefore to explore how uncertainties regarding product cost can be consid...

Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

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Alejandra Guillermina Miranda-Díaz

2016-01-01

Full Text Available The increase in the prevalence of diabetes mellitus (DM and the secondary kidney damage produces diabetic nephropathy (DN. Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day, including normal glomerular filtration rate (GFR or a mildly decreased GFR (60–89 mL/min/1.73 m2, with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is 300 mg/day. Chronic kidney disease (CKD is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β, producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS. The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase. The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.

Proteomic analysis of early phase of conidia germination in Aspergillus nidulans.

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Oh, Young Taek; Ahn, Chun-Seob; Kim, Jeong Geun; Ro, Hyeon-Su; Lee, Chang-Won; Kim, Jae Won

2010-03-01

In order to investigate proteins involved in early phase of conidia germination, proteomic analysis was performed using two-dimensional gel electrophoresis (2D-GE) in conjunction with MALDI-TOF mass spectrometry (MS). The expression levels of 241 proteins varied quantitatively with statistical significance (Pproteomic analysis of early phase of conidia germination and will contribute to a better understanding of the molecular events involved in conidia germination process. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Acute and "chronic" phase reaction-a mother of disease.

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Bengmark, Stig

2004-12-01

The world is increasingly threatened by a global epidemic of chronic diseases. Almost half of the global morbidity and almost two thirds of global mortality is due to these diseases-approximately 35 million die each year from chronic diseases. And they continue to increase. Increasing evidence suggest that these diseases are associated with lifestyle, stress, lack of physical exercise, over-consumption of calorie-condensed foods rich in saturated fat, sugar and starch, but also under-consumption of antioxidant-rich fruits and vegetables. As a result the function of the innate immune system is severe impaired. This review discusses the changes induced in response to mental and physical stress and their association with the subsequent development of metabolic syndrome, and its association with various chronic diseases. The endothelial cells and their function appears to be of great importance, and the function of their cellular membranes of special importance to the function of the underlying cells; their ability to obtain nutrients and antioxidants and to eliminate waste products. The abdominal adipocytes seen to play a key role, as they have the ability to in stressful situations release much of proinflammatory cytokines, PAI-1 and free fatty acids compared to elsewhere in the body. The load on the liver of these various substances in often of greater magnitude than the liver can handle. Some of the most common chronic diseases and their potential association with acute and "chronic" phase response, and with metabolic syndrome are discussed separately. The need for studies with lifestyle modifications is especially emphasized.

Generic features of vacuum phase transitions in the early universe

International Nuclear Information System (INIS)

Kephart, T.W.; Weiler, T.J.; Yuan, T.C.

1990-01-01

A simple Higgs model is utilized to show the occurrence of a four-phase pattern of vacuum symmetry. As temperature changes, an interplay of spontaneous symmetry breaking and spontaneous symmetry restoration ensues, and resonant field interchange occurs. The generality of models which may contain a sequence of vacuum phase transitions is emphasized. The laboratory for these multi-phase transitions is the early Universe. (orig.)

Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial.

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Lipton, Jeffrey H; Chuah, Charles; Guerci-Bresler, Agnès; Rosti, Gianantonio; Simpson, David; Assouline, Sarit; Etienne, Gabriel; Nicolini, Franck E; le Coutre, Philipp; Clark, Richard E; Stenke, Leif; Andorsky, David; Oehler, Vivian; Lustgarten, Stephanie; Rivera, Victor M; Clackson, Timothy; Haluska, Frank G; Baccarani, Michele; Cortes, Jorge E; Guilhot, François; Hochhaus, Andreas; Hughes, Timothy; Kantarjian, Hagop M; Shah, Neil P; Talpaz, Moshe; Deininger, Michael W

2016-05-01

Ponatinib has shown potent activity against chronic myeloid leukaemia that is resistant to available treatment, although it is associated with arterial occlusion. We investigated whether this activity and safety profile would result in superior outcomes compared with imatinib in previously untreated patients with chronic myeloid leukaemia. The Evaluation of Ponatinib versus Imatinib in Chronic Myeloid Leukemia (EPIC) study was a randomised, open-label, phase 3 trial designed to assess the efficacy and safety of ponatinib, compared with imatinib, in newly diagnosed patients with chronic-phase chronic myeloid leukaemia. Patients from 106 centres in 21 countries were randomly assigned (1:1, with stratification by Sokal score at diagnosis) using an interactive voice and web response system to receive oral ponatinib (45 mg) or imatinib (400 mg) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met. Eligible patients were at least 18 years of age, within 6 months of diagnosis, and Philadelphia chromosome-positive by cytogenetic assessment, with Eastern Cooperative Oncology Group performance status of 0-2, and had not previously been treated with tyrosine kinase inhibitors. The primary endpoint was major molecular response at 12 months. Patients who remained on study and had molecular assessments at specified timepoints were studied at those timepoints. Safety analyses included all treated patients, as per study protocol. This trial is registered with ClinicalTrials.gov, number NCT01650805. Between Aug 14, 2012, and Oct 9, 2013, 307 patients were randomly assigned to receive ponatinib (n=155) or imatinib (n=152). The trial was terminated early, on Oct 17, 2013, following concerns about vascular adverse events observed in patients given ponatinib in other trials. Trial termination limited assessment of the primary endpoint of major molecular response at 12 months, as only 13 patients in the imatinib group and ten patients in the

[Early exercise training after exacerbation in patients with chronic respiratory failure].

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Takahashi, Hiromitsu; Molleyres, Sandrine; Dousse, Nicolas; Contal, Olivier; Janssens, Jean-Paul

2011-11-23

Patients who suffered from an exacerbation of a chronic respiratory disorder are often very limited in terms of their exercise capacity because of severe dyspnea and amyotrophy of peripheral muscles. Early implementation of pulmonary rehabilitation may help these patients to avoid the complications of a prolonged bedridden period, and increase more rapidly their mobility. Early rehabilitation has become more frequent, but requires special skills from the care givers (chest therapists). Techniques which enhance muscular performance and motility of patients who are recovering from an exacerbation such as electromoystimulation or mobilisation under non-invasive ventilation, give encouraging results; their impact on length of hospital stay requires further studies.

Statistical controversies in clinical research: early-phase adaptive design for combination immunotherapies.

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Wages, N A; Slingluff, C L; Petroni, G R

2017-04-01

In recent years, investigators have asserted that the 3 + 3 design lacks flexibility, making its use in modern early-phase trial settings, such as combinations and/or biological agents, inefficient. More innovative approaches are required to address contemporary research questions, such as those posed in trials involving immunotherapies. We describe the implementation of an adaptive design for identifying an optimal treatment regimen, defined by low toxicity and high immune response, in an early-phase trial of a melanoma helper peptide vaccine plus novel adjuvant combinations. Operating characteristics demonstrate the ability of the method to effectively recommend optimal regimens in a high percentage of trials with reasonable sample sizes. The proposed design is a practical, early-phase, adaptive method for use with combined immunotherapy regimens. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of two small molecule inhibitors in relapsed/refractory mantle cell lymphoma. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Early monitoring of BCR-ABL transcript levels and cytogenetic in assessing the prognosis of chronic myeloid leukemia].

Science.gov (United States)

Huang, Qin; Zhang, Xiao-yan; Li, Yan; Wang, Xiao-min

2013-10-15

To explore the prognostic significance of early monitoring of BCR-ABL transcript levels and cytogenetic evaluations for chronic myeloid leukemia in chronic phase (CML-CP). From July 2007 to May 2012, 56 CML-CP patients received oral imatinib 400 mg/d. The BCR-ABL transcript levels were monitored and cytogenetic examinations performed after 3 and 6 months respectively. The median follow-up time was 48 months. The 3-month BCR-ABL transcript levels ≤ 10% of patients 5-year overall survival (OS) and progression-free survival (PFS) were better than BCR-ABL transcript levels >10% of patients (OS: 100% vs 84.6%, P = 0.011; PFS: 94.6% vs 67.7%, P = 0.045); cytogenetics: Ph(+) ≤ 35 % of patients 5-year OS and PFS better than Ph(+) > 35% of patients (OS: 100% vs 76.2%, P = 0.001; PFS: 95.2% vs 38.1%, P = 0.001); the 6-month BCR-ABL transcripts level ≤ 1% of patients 5-year OS and PFS also better than BCR-ABL transcript levels> 1% of patients (OS: 100% vs 71.4%, P = 0.000; PFS: 95.2% vs 47.6%, P = 0.001); Ph(+) = 0% and Ph(+)> 0% patients, 5-year OS and PFS were significantly different (OS: 100% vs 68.6%, P = 0.000; PFS: 95.3% vs 45.7%, P = 0.000). Early molecular biology and cytogenetics monitoring have some significance in the prognostic assessment of CML-CP. And individualized treatment strategies should be based upon the monitoring results in conjunctions with comprehensive judgments.

An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase.

Science.gov (United States)

Steegmann, Juan Luis; Colomer, Dolors; Gómez-Casares, Maria-Teresa; García-Gutiérrez, Valentín; Ortí, Guillermo; Ramírez-Payer, Angel; Olavarria, Eduardo; Vall-Llovera, Ferrán; Giraldo, Pilar; Conde, Eulogio; Vallansot, Rolando; López-Lorenzo, Jose Luis; Palomera, Luis; Álvarez-Larrán, Alberto; Conesa, Venancio; Bautista, Guiomar; Casas, Laura; Giles, Frank; Hochhaus, Andreas; Casado-Montero, Luis Felipe

2017-10-01

This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter. This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter). The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS ≤10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT ≤13 days was predictive of MMR at 12 months and MR4 at 18 months. The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.

Chronic ethanol intake alters circadian phase shifting and free-running period in mice.

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Seggio, Joseph A; Fixaris, Michael C; Reed, Jeffrey D; Logan, Ryan W; Rosenwasser, Alan M

2009-08-01

Chronic alcohol intake is associated with widespread disruptions in sleep and circadian rhythms in both human alcoholics and in experimental animals. Recent studies have demonstrated that chronic and acute ethanol treatments alter fundamental properties of the circadian pacemaker--including free-running period and responsiveness to photic and nonphotic phase-shifting stimuli--in rats and hamsters. In the present work, the authors extend these observations to the C57BL/6J mouse, an inbred strain characterized by very high levels of voluntary ethanol intake and by reliable and stable free-running circadian activity rhythms. Mice were housed individually in running-wheel cages under conditions of either voluntary or forced ethanol intake, whereas controls were maintained on plain water. Forced ethanol intake significantly attenuated photic phase delays (but not phase advances) and shortened free-running period in constant darkness, but voluntary ethanol intake failed to affect either of these parameters. Thus, high levels of chronic ethanol intake, beyond those normally achieved under voluntary drinking conditions, are required to alter fundamental circadian pacemaker properties in C57BL/6J mice. These observations may be related to the relative ethanol insensitivity displayed by this strain in several other phenotypic domains, including ethanol-induced sedation, ataxia, and withdrawal. Additional experiments will investigate chronobiological sensitivity to ethanol in a range of inbred strains showing diverse ethanol-related phenotypes.

The construction of a panel of serum amino acids for the identification of early chronic kidney disease patients.

Science.gov (United States)

Li, Rui; Dai, Jinna; Kang, Hui

2018-03-01

Serum creatinine, urea, and cystatin-c are standardly used for the evaluation of renal function in the clinic. However, some patients have chronic kidney disease but still retain kidney function; a conventional serum index in these patients can be completely normal. Serum amino acid levels can reflect subtle changes in metabolism and are closely related to renal function. Here, we investigated how amino acids change as renal impairment increases. Subjects were divided into three groups by renal function glomerular filtration rate: healthy controls, patients with chronic kidney disease with normal kidney function, and patients with chronic kidney disease with decreased kidney function group. We identified 11 amino acids of interest using LC-MS/MS on MRM (+) mode. Statistical analysis indicated that alanine (ALA), valine (VAL), and tyrosine (TYR) decrease with renal function impairment, whereas phenylalanine (PHE) and citrulline (CIT) increase. We tried to construct a diagnostic model utilizing a combination of amino acids capable of identifying early chronic kidney disease patients. The accuracy, specificity, and sensitivity of the combining predictors were 86.9%, 84.6%, and 90.9%, respectively, which is superior to the reported values for serum creatinine, urea, and cystatin-c. Our data suggest that serum amino acid levels may supply important information for the early detection of chronic kidney disease. We are the first to establish a diagnostic model utilizing serum levels of multiple amino acids for the diagnosis of patients with early-stage chronic kidney disease. © 2017 Wiley Periodicals, Inc.

Imaging Frontostriatal Function in Ultra-High-Risk, Early, and Chronic Schizophrenia During Executive Processing

Science.gov (United States)

Morey, Rajendra A.; Inan, Seniha; Mitchell, Teresa V.; Perkins, Diana O.; Lieberman, Jeffrey A.; Belger, Aysenil

2009-01-01

Context Individuals experiencing prodromal symptoms of schizophrenia (ultra-high-risk group) demonstrate impaired performance on tasks of executive function, attention, and working memory. The neurobiological underpinnings of such executive deficits in ultra-high-risk individuals remains unclear. Objective We assessed frontal and striatal functions during a visual oddball continuous performance task, in ultra-high-risk, early, and chronic schizophrenic patients with the use of functional magnetic resonance imaging. Design Cross-sectional case-control design. Setting Community; outpatient clinic. Patients Fifty-two individuals (control, n = 16; ultra-high risk, n = 10; early, n = 15; chronic, n = 11) from a referred clinical sample and age- and sex-matched control volunteers underwent scanning. Main Outcome Measures Percentage of active voxels and percentage signal change calculated for the anterior cingulate gyrus (ACG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), basal ganglia, and thalamus. Performance on the visual oddball task was measured with percentage of hits and d′ (a measure based on the hit rate and the false-alarm rate). Results The ultra-high-risk group showed significantly smaller differential activation between task-relevant and task-irrelevant stimuli in the frontal regions (ACG, IFG, MFG) than the control group. Frontostriatal activation associated with target stimuli in the early and chronic groups was significantly lower than the control group, while the ultra-high-risk group showed a trend toward the early group. Conclusions Our findings suggest that prefrontal function begins to decline before the onset of syndromally defined illness and hence may represent a vulnerability marker in assessing the risk of developing psychotic disorders among ultra-high-risk individuals. PMID:15753238

Imatinib mesylate is effective in children with chronic myelogenous leukemia in late chronic and advanced phase and in relapse after stem cell transplantation

NARCIS (Netherlands)

Millot, F; Guilhot, J; Nelken, B; Leblanc, T; De Bont, ES; Bekassy, AN; Gadner, H; Sufliarska, S; Stary, J; Gschaidmeier, H; Guilhot, F; Suttorp, M

A multicentric phase 2 study was conducted to determine the efficiency and the tolerance of imatinib mesylate in children with chronic myelogenous leukemia (CML) in advanced phase of the disease, in relapse after stem cell transplantation, or in case of failure to an interferon a-based regimen. In

EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery.

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Zhang, Shao-jie; Ke, Zheng; Li, Le; Yip, Shea-ping; Tong, Kai-yu

2013-04-01

Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague-Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely correlated with the neural

EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery

International Nuclear Information System (INIS)

Zhang, Shao-jie; Ke, Zheng; Tong, Kai-yu; Li, Le; Yip, Shea-ping

2013-01-01

Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague–Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely

Association between regular molecular monitoring and tyrosine kinase inhibitor therapy adherence in chronic myelogenous leukemia in the chronic phase.

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Guérin, Annie; Chen, Lei; Dea, Katherine; Wu, Eric Q; Goldberg, Stuart L

2014-07-01

Adherence with oral tyrosine kinase inhibitor (TKI) therapy over prolonged timeframes is required for successful outcomes among patients with chronic phase chronic myelogenous leukemia (CP-CML). Since quantitative polymerase chain reaction (qPCR) monitoring may identify early suboptimal responses, and thereby permit detection of non-adherence to therapy, we sought to assess the association between frequency of molecular monitoring and medication adherence. This is a retrospective cohort study design of diagnosed CP-CML obtained from two large US administrative claims databases. Patients were grouped into cohorts based on the number of qPCR tests they had. Adherence was assessed both by medication possession ratio (MPR) and proportion of days covered (PDC) and was compared between qPCR cohorts. A sensitivity analysis was performed by adjusting for the number of oncology outpatient visits not due to routine molecular monitoring. Over the 12 month study period, 1205 CML patients met the selection criteria; 41.0% had no qPCR tests, 31.9% had 1-2 tests, and 27.1% had 3-4 tests; 88.9% of patients were initiated on imatinib. Patients in the 3-4 qPCR tests cohort had an average MPR that was 10.22 (p sensitivity analysis were consistent with core analysis findings, excluding number of physician visits as a potential driver of adherence. These findings demonstrate an association, not causation, between molecular monitoring frequency and adherence. Frequent molecular monitoring (3-4 times per year as recommended in current guidelines) is associated with greater TKI treatment adherence for patients diagnosed with CML. Since TKI adherence >80% has been associated with better clinical outcomes, this study underscores the importance of molecular monitoring.

Early investigational antibiotics for the treatment of acute exacerbations of chronic bronchitis.

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Falagas, Matthew E; Georgiou, Maria

2017-03-01

Acute exacerbations in patients with chronic bronchitis are a leading cause of hospitalizations and death. Bacteria contribute significantly to such exacerbations. The aim of this review was to explore the potential role of investigational antibiotics in the treatment of these episodes. Areas covered: The available literature in PubMed database, in websites related to investigational drugs and in websites of the producing companies has been searched. The in vitro activity against pathogens involved in acute exacerbations of chronic bronchitis and the pharmacokinetic profile of antibiotics currently under development were taken into consideration for inclusion in the review. Expert opinion: Several novel antimicrobial agents have completed preclinical and Phase I studies and were well-tolerated. Further investigation is mandatory in order to evaluate their future in treatment of chronic bronchitis exacerbations and discover potential advantages compared to already approved antimicrobials.

Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections.

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S Gnanakaran

2011-09-01

Full Text Available Here we have identified HIV-1 B clade Envelope (Env amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor-binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413-415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response.

Branched chain amino acid profile in early chronic kidney disease

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M Anil Kumar

2012-01-01

Full Text Available The nutritional status in chronic kidney disease (CKD patients is a predictor of prognosis during the first period of dialysis. Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid profile. Of these, the plasma levels of branched chain amino acids (BCAA, especially valine and leucine, correlate well with nutritional status. Plasma BCAAs were evaluated along with albumin and C-reactive protein in 15 patients of early stages of CKD and 15 age- and sex-matched healthy controls. A significant decrease in plasma valine, leucine and albumin levels was observed in CKD patients when compared with the controls (P <0.05. No significant difference in C-reactive protein (CRP levels was observed between the two groups. Malnutrition seen in our CKD patients in the form of hypoalbuminemia and decreased concentrations of BCAA points to the need to evaluate the nutritional status in the early stages itself. Simple measures in the form of amino acid supplementation should be instituted early to decrease the morbidity and mortality before start of dialysis in these patients.

Gaia Science Alerts: Early Validation Phase Data from Gaia

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Walton, Nicholas; Hodgkin, Simon; van Leeuwen, Floor

2015-08-01

The ESA Gaia satellite launched Dec 2013, and after successful completion of its in orbit commissioning in July 2014, begun routine operations, with the aim to accurately measure the astrometric and astrophysical properties of more than a billion stars in our Milky Way.As a significant by product of its observational scanning law, where each point on the sky is observed multiple times (~80 revisits on average) over the nominal 5 year mission, Gaia has significant utility in detecting new transients, both flux (e.g. Supernovae, Flare stars) and positional (e.g. Asteroids).We will present the current status of the Gaia Photometric Science Alerts (PSA) system that has been developed within the Gaia DPAC. The PSA pipeline provides a quick look analysis of the daily data stream from Gaia, and identifies new photometric alerts, from analysis of the object photometric and the low resolution spectro-photometric data. Via a set of filters, those identified as astrophysical in nature, are published to the community. The information provided currently includes positional and flux information.The Gaia Alerts working group has organised a significant early stage followup campaign, providing access to a wide variety of followup facilities. These have been used to provide classification spectra of the Gaia alert candidates, with the early phase data confirming that the alerts issued are indeed largely astrophysical transients, with only a small contamination rate.The presentation will address the early phase issues that have been addressed in localising and classifying alerts in the early phase of Gaia observations (for instance, how lack of early knowledge of the sky as seen by Gaia was mitigated by reference to external image data), and how the alert rate published by the PSA will ramp up towards the end of 2015, with the availability of more Gaia sky data.Information concerning the Gaia alerts system can be found at http://gaia.ac.uk/selected-gaia-science-alerts

Acute versus chronic phase mechanisms in a rat model of CRPS.

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Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David

2016-01-19

Tibia fracture followed by cast immobilization in rats evokes nociceptive, vascular, epidermal, and bone changes resembling complex regional pain syndrome (CRPS). In most cases, CRPS has three stages. Over time, this acute picture, allodynia, warmth, and edema observed at 4 weeks, gives way to a cold, dystrophic but still painful limb. In the acute phase (at 4 weeks post fracture), cutaneous immunological and NK1-receptor signaling mechanisms underlying CRPS have been discovered; however, the mechanisms responsible for the chronic phase are still unknown. The purpose of this study is to understand the mechanisms responsible for the chronic phases of CRPS (at 16 weeks post fracture) at both the peripheral and central levels. We used rat tibial fracture/cast immobilization model of CRPS to study molecular, vascular, and nociceptive changes at 4 and 16 weeks post fracture. Immunoassays and Western blotting were carried out to monitor changes in inflammatory response and NK1-receptor signaling in the skin and spinal cord. Skin temperature and thickness were measured to elucidate vascular changes, whereas von Frey testing and unweighting were carried out to study nociceptive changes. All data were analyzed by one-way analysis of variance (ANOVA) followed by Neuman-Keuls multiple comparison test to compare among all cohorts. In the acute phase (at 4 weeks post fracture), hindpaw allodynia, unweighting, warmth, edema, and/or epidermal thickening were observed among 90 % fracture rats, though by 16 weeks (chronic phase), only the nociceptive changes persisted. The expression of the neuropeptide signaling molecule substance P (SP), NK1 receptor, inflammatory mediators TNFα, IL-1β, and IL-6 and nerve growth factor (NGF) were elevated at 4 weeks in sciatic nerve and/or skin, returning to normal levels by 16 weeks post fracture. The systemic administration of a peripherally restricted IL-1 receptor antagonist (anakinra) or of anti-NGF inhibited nociceptive behaviors at 4

Using virtual reality to assess theory of mind subprocesses and error types in early and chronic schizophrenia.

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Canty, Allana L; Neumann, David L; Shum, David H K

2017-12-01

Individuals with schizophrenia often demonstrate theory of mind (ToM) impairment relative to healthy adults. However, the exact nature of this impairment (first- vs. second-order ToM and cognitive vs. affective ToM) and the extent to which ToM abilities deteriorate with illness chronicity is unclear. Furthermore, little is known about the relationships between clinical symptoms and ToM error types (overmentalising, reduced mentalising and no ToM) in early and chronic schizophrenia. This study examined the nature and types of ToM impairment in individuals with early ( n  = 26) and chronic schizophrenia ( n  = 32) using a novel virtual reality task. Clinical participants and demographically-matched controls were administered the Virtual Assessment of Mentalising Ability, which provides indices of first- and second-order cognitive and affective ToM, and quantifies three different types of mentalising errors (viz., overmentalising, reduced mentalising, and no ToM). Individuals with early schizophrenia performed significantly poorer than healthy controls on first-order affective and second-order cognitive and affective ToM, but significantly higher than individuals with chronic schizophrenia on all ToM subscales. Whereas a lack of mental state concept was associated with negative symptoms, overmentalising was associated with positive symptoms. These findings suggest that ToM abilities selectively deteriorate with illness chronicity and error types are related to these individuals' presenting symptomology. An implication of the findings is that social-cognitive interventions for schizophrenia need to consider the nature, time course and symptomatology of the presenting patient.

Evaluation of early-phase [18F]-florbetaben PET acquisition in clinical routine cases

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Sonja Daerr

2017-01-01

Conclusions: Early-phase FBB acquisitions correlate on a relative quantitative and visual level with FDG PET scans, irrespective of the amyloid plaque density assessed in late FBB imaging. Thus, early-phase FBB uptake depicts a metabolism-like image, suggesting it as a valid surrogate marker for synaptic dysfunction, which could ultimately circumvent the need for additional FDG PET investigation in diagnosis of dementia.

Relationship between myocardial flow reserve by oxygen-15 water positron emission tomography in the subacute phase of myocardial infarction and left ventricular remodeling in the chronic phase

International Nuclear Information System (INIS)

Ohara, Minako; Yukiiri, Kazushi; Masugata, Hisashi

2008-01-01

The purposes of this study were to examine the effects of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) on myocardial flow reserve in patients with acute myocardial infarction (AMI) in the subacute phase using oxygen-15 positron emission tomography (PET) and to elucidate the relationship between the myocardial flow reserve and remodeling in the chronic phase. Sixty patients who had been treated with coronary angioplasty within 12 h after the onset of AMI were enrolled. Patients were divided into an enalapril (ACEI) group and a candesartan (ARB) group. The myocardial flow reserve was measured by oxygen-15 water PET in the subacute phase from the 20th to the 30th day after the onset of AMI. Left ventriculography was performed to measure the left ventricular ejection fraction in the chronic phase about 6 months after the onset. Ten patients (33%) in the enalapril group and 4 patients (13%) in the candesartan group stopped taking their respective medications within a few days of starting, because of side effects such as cough or hypotension. Thus, the prevalence of medication intolerance was higher in the enalapril group. The myocardial flow reserve in the subacute phase and the left ventricular ejection fraction in the chronic phase were lower in the enalapril group (2.08±0.30 and 42±6%) than in the candesartan group (2.25±0.20 and 49±5%) (p<0.05). The myocardial flow reserve significantly correlated with the left ventricular ejection fraction in all patients (r=0.45, p<0.01). The myocardial flow reserve assessed by PET in the subacute phase after AMI was found to be related to left ventricular remodeling in the chronic phase. (author)

Dental Hygienist-Led Chronic Disease Management System to Control Early Childhood Caries.

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Ng, Man Wai; Fida, Zameera

2016-06-01

Management of the complex chronic disease of early childhood caries requires a system of coordinated health care interventions which can be led by a dental hygienist and where patient self-care efforts are paramount. Even after receiving costly surgical treatment under general anesthesia in the operating room, many children develop new and recurrent caries after only 6-12 months, a sequela that can be prevented. This article describes the chronic disease management (CDM) of dental caries, a science-based approach that can prevent and control caries. In this article, we (1) introduce the concept of CDM of dental caries, (2) provide evidence that CDM improves oral health outcomes, and (3) propose a dental hygienist-led team-based oral health care approach to CDM. Although we will be describing the CDM approach for early childhood caries, CDM of caries is applicable in children, adolescents, and adults. Early childhood caries disease control requires meaningful engagement of patients and parents by the oral health care team to assist them with making behavioral changes in the unique context of their families and communities. The traditional dentist/hygienist/assistant model needs to evolve to a collaborative partnership between care providers and patients/families. This partnership will be focused on systematic risk assessment and behaviorally based management of the disease itself, with sensitivity toward the familial environment. Early pilot study results demonstrate reductions in the rates of new caries, dental pain, and referral to the operating room compared with baseline rates. Dental hygienists are the appropriate team members to lead this approach because of their expertise in behavior change and prevention. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Early Detection of Chronic Obstructive Pulmonary Disease in Primary Care.

Science.gov (United States)

Kobayashi, Seiichi; Hanagama, Masakazu; Yanai, Masaru

2017-12-01

Objective To evaluate the effectiveness of an early detection program for chronic obstructive pulmonary disease (COPD) in a primary care setting in Japan. Methods Participants of ≥40 years of age who regularly visited a general practitioner's clinic due to chronic disease were asked to complete a COPD screening questionnaire (COPD Population Screener; COPD-PS) and undergo simplified spirometry using a handheld spirometric device. Patients who showed possible COPD were referred to a respiratory specialist and underwent a detailed examination that included spirometry and chest radiography. Results A total of 111 patients with possible COPD were referred for close examination. Among these patients, 27 patients were newly diagnosed with COPD. The patients with COPD were older, had lower BMI values, and had a longer smoking history in comparison to non-COPD patients. COPD patients also had more comorbid conditions. A diagnosis of COPD was significantly associated with a high COPD-PS score (pearly detection of undiagnosed COPD in primary care.

Role of radio-aerosol and perfusion lung imaging in early detection of chronic obstructive lung disease

Energy Technology Data Exchange (ETDEWEB)

Garg, A; Pande, J N; Guleria, J S; Gopinath, P G

1983-04-01

The efficacy of radio-aerosol and perfusion lung imaging in the early detection of chronic obstructive lung disease was evaluated in 38 subjects. The subjects included 5 non-smokers, 21 smokers with minimal or no respiratory symptoms and 12 patients with chronic obstructive lung disease. Each subject consented to a respiratory questionaire, detailed physical examination, chest X-ray examinations, detailed pulmonary function tests and sup(99m)Tc-radioaerosol-inhalation lung imaging. Perfusion lung imaging with sup(99m)Tc-labelled macroaggregated albumin was performed in 22 subjects. A significant correlation (P<0.001) was observed between the degree of abnormalities on radio-aerosol imaging and pulmonary function tests (PFTs) including forced expiratory volume in 1 s, maximum midexpiratory flow rate and mean transit time analysis. Abnormal radio-aerosol patterns and deranged PFTs were observed in 21 subjects each. Of 21 subjects with abnormal radioaerosol pattern 8 had normal PFTs. Of 21 subjects with abnormal PFTs 8 had normal aerosol images. Aerosol lung images and PFTs were abnormal more frequently than perfusion lung images. The results suggest that radio-aerosol lung imaging is as sensitive an indicator as PFTs for early detection of chronic obstructive lung disease and can be usefully combined with PFTs for early detection of alteration in pulmonary physiology in smokers.

Early changes of lymphocyte RNA and serum immunoglobulins following chronic exposure to benzene

Energy Technology Data Exchange (ETDEWEB)

Chircu, V.; Ionescu, M.; Zgoan

Hematologic and immunochemical investigations carried out in 270 workers with chronic exposure to benzene demonstrated changes of the nucleologram and of the area of lymphocyte nucleoli as well as disorders of the humoral immune response revealed by radial immunodiffusion. The numerical rise of bi- and polynucleolated cells, of cells with irregular macronucleoli as well as an enlargement of the nucleolar area are assumed to reflect an increase of the endolymphocytic amounts of RNA. An increased capacity of immunoglobulin formation, particularly of IgM, was also observed. All these changes are considered as early signs of an enhanced immune reactivity following chronic exposure to benzene.

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

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Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

Emergency management in the early phase

International Nuclear Information System (INIS)

Crick, M.

2003-01-01

Full text: An overview of emergency management is provided from a systems approach with the aim of providing a common understanding for the diverse symposium participants of the elements of the management system required for preparedness and response for the early phase of an emergency at a nuclear installation. The systems approach starts with the recognition of response goals, and using detailed analyses of threats, past experience, international law and principles, a response strategy is developed. This step is illustrated with the case of severe accidents at PWRs and identifies the need for and nature of: emergency classification based an plant conditions; notification; radiological monitoring and assessment strategies; operational criteria for implementing protective action decisions; management of public information. From the strategy, detailed functional requirements can be defined addressing: establishing emergency management and operations; identifying, notifying and activating; taking mitigatory action; taking urgent protective action; providing information and issuing instructions and warnings to the public; protecting emergency workers; assessing the initial phase; managing the medical response; keeping the public informed; taking countermeasures against ingestion; mitigating the non-radiological consequences of the emergency and the response. Meeting these requirements necessitates decisions from competent authorities, the means to implement them, and mechanisms for response co-ordination, which need to be prepared in advance. These are supported by infrastructure, including: clear authorities; organization; coordinated plans and procedures; logistical support, facilities and tools; training and exercises; and a quality assurance programme. Some reflections an the key differences between response to emergencies arising from accidents and these arising from deliberate acts will be provided. An impression will be given of the level of preparedness and

Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants.

Science.gov (United States)

Halliday, H L; Ehrenkranz, R A; Doyle, L W

2003-01-01

Corticosteroids have been used late in the neonatal period to treat chronic lung disease (CLD) in preterm babies, and early to try to prevent it. CLD is likely to be the result of persisting inflammation in the lung and the use of powerful anti-inflammatory drugs like dexamethasone has some rationale. Early use tends to be associated with increased adverse effects so that studies of moderately early treatment (7-14 days postnatal) might have the dual benefits of fewer side effects and onset of action before chronic inflammation is established. To determine if moderately early (7-14 days) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the prevention and/or treatment of early chronic lung disease in the preterm infant. Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, Cochrane Database of Controlled Trials, MEDLINE (1966 - October 2002), hand searching paediatric and perinatal journals, examining previous review articles and information received from practicing neonatologists. Authors of all studies were contacted, where possible, to confirm details of reported follow-up studies, or to obtain any information about long-term follow-up where none had been reported. Randomised controlled trials of postnatal corticosteroid treatment from 7-14 days of birth in high risk preterm infants were selected for this review. Data regarding clinical outcomes including mortality, CLD (including late rescue with corticosteroids, or need for home oxygen therapy), death or CLD, failure to extubate, complications during the primary hospitalisation (including infection, hyperglycaemia, hypertension, hypertrophic cardiomyopathy, pneumothorax, severe intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), gastrointestinal bleeding, and severe retinopathy of prematurity (ROP)), and long term outcome (including blindness, deafness, cerebral palsy and major neurosensory

Early chronic kidney disease: diagnosis, management and models of care

Science.gov (United States)

Wouters, Olivier J.; O'Donoghue, Donal J.; Ritchie, James; Kanavos, Panos G.; Narva, Andrew S.

2015-01-01

Chronic kidney disease (CKD) is a prevalent condition in many countries, and it is estimated that over $1 trillion is spent globally on end-stage renal disease (ESRD) care. There is a clear clinical and economic rationale for designing timely and appropriate health system responses to limit progression from CKD to ESRD. This article reviews the gaps in our knowledge about which early CKD interventions are appropriate, the optimal time to intervene, and what model of care to adopt. The available diagnostic tests exhibit key limitations. Clinical care may improve if early-stage (1–3) CKD with risk for progression towards ESRD is differentiated from early CKD that is unlikely to advance. It is possible that CKD should be re-conceptualized as a part of primary care. Additional research is needed to better understand the risk factors for CKD progression. Systems modelling can be used to evaluate the impact of different care models on CKD outcomes and costs. The US Indian Health Service experience has demonstrated that an integrated, system-wide approach, even in an underfunded system, can produce significant benefits. PMID:26055354

Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance : Minimum 24-month follow-up

NARCIS (Netherlands)

Gambacorti-Passerini, Carlo; Brümmendorf, Tim H; Kim, Dong-Wook; Turkina, Anna G; Masszi, Tamas; Assouline, Sarit; Durrant, Simon; Kantarjian, Hagop M; Khoury, H Jean; Zaritskey, Andrey; Shen, Zhi-Xiang; Jin, Jie; Vellenga, Edo; Pasquini, Ricardo; Mathews, Vikram; Cervantes, Francisco; Besson, Nadine; Turnbull, Kathleen; Leip, Eric; Kelly, Virginia; Cortes, Jorge E

Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib

Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia

International Nuclear Information System (INIS)

McGlave, P.B.; Miller, W.J.; Hurd, D.D.; Arthur, D.C.; Kim, T.

1981-01-01

We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern or demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease

Early Intervention in Bipolar Disorder.

Science.gov (United States)

Vieta, Eduard; Salagre, Estela; Grande, Iria; Carvalho, André F; Fernandes, Brisa S; Berk, Michael; Birmaher, Boris; Tohen, Mauricio; Suppes, Trisha

2018-05-01

Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

Directory of Open Access Journals (Sweden)

Tokiko Ishida

Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

Changes in nucleosome repeat lengths precede replication in the early replicating metallothionein II gene region of cells synchronized in early S phase

International Nuclear Information System (INIS)

D'Anna, J.A.; Tobey, R.A.

1989-01-01

Previous investigations showed that inhibition of DNA synthesis by hydroxyurea, aphidicolin, or 5-fluorodeoxyuridine produced large changes in the composition and nucleosome repeat lengths of bulk chromatin. There the authors report results of investigations to determine whether the changes in nucleosome repeat lengths might be localized in the initiated replicons, as postulated. In most experiments, Chinese hamster (line CHO) cells were synchronized in G1, or they were synchronized in early S phase by allowing G1 cells to enter S phase in medium containing 1 mM hydroxyurea or 5 μg mL -1 aphidicolin, a procedure believed to produce an accumulation of initiated replicons that arise from normally early replicating DNA. Measurements of nucleosome repeat lengths of bulk chromatin, the early replicating unexpressed metallothionein II (MTII) gene region, and a later replicating repeated sequence indicate that the changes in repeat lengths occur preferentially in the early replicating MTII gene region as G1 cells enter and become synchronized in early S phase. During that time, the MTII gene region is not replicated nor is there any evidence for induction of MTII messenger RNA. Thus, the results are consistent with the hypothesis that changes in chromatin structure occur preferentially in the early replicating (presumably initiated) replicons at initiation or that changes in chromatin structure can precede replication during inhibition of DNA synthesis. The shortened repeat lengths that precede MTII replication are, potentially, reversible, because they become elongated when the synchronized early S-phase cells are released to resume cell cycle progression

Early phase in e-money development: from Edvard Bellamy to Frank Macknamary

Directory of Open Access Journals (Sweden)

O.S. Vysochan

2016-03-01

Full Text Available The article examines the phases of e-money development from the first mentioning of «a credit card» in literary sources to the appearance of Diners Club which preceded modern credit cards. The author has used the historical and geographic method for the decomposition of the early phase in the e-money development concerning the basic motives that induced emitters to develop and implement particular credit-payment systems. The article singles out three stages within the early phase of the e-money development, namely, the beginning of the ХХ-th century (supplying with short-term credits to obtain consumer’s goods, from 1920 to 1940 (guarantee of consumer’s loyalty to a brand, increasing the safety of clearing transactions by payer’s authorization, and 1950-ies (the use of the same credit for payment to various enterprises. It establishes the main features of the early phase in the e-money development; they are such as the absence of the necessary technical supply; emission, sale, guaranty on credits, on the cards issued take place outside the banking system; the lack of corporation credit card segment; the limitation of the application area; the low level of safety of the transactions accomplished.

Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

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Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

2016-01-01

The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment.

Early signaling, referral, and treatment of adolescent chronic pain: a study protocol

Directory of Open Access Journals (Sweden)

Voerman Jessica S

2012-06-01

Full Text Available Abstract Background Chronic pain is prevalent among young people and negatively influences their quality of life. Furthermore, chronic pain in adolescence may persist into adulthood. Therefore, it is important early on to promote the self-management skills of adolescents with chronic pain by improving signaling, referral, and treatment of these youngsters. In this study protocol we describe the designs of two complementary studies: a signaling study and an intervention study. Methods and design The signaling study evaluates the Pain Barometer, a self-assessed signaling instrument for chronic pain in adolescents. To evaluate the feasibility of the Pain Barometer, the experiences of youth-health care nurses will be evaluated in semi-structured interviews. Also, we will explore the frequencies of referral per health-care provider. The intervention study evaluates Move It Now, a guided self-help intervention via the Internet for teenagers with chronic pain. This intervention uses cognitive behavioural techniques, including relaxation exercises and positive thinking. The objective of the intervention is to improve the ability of adolescents to cope with pain. The efficacy of Move It Now will be examined in a randomized controlled trial, in which 60 adolescents will be randomly assigned to an experimental condition or a waiting list control condition. Discussion If the Pain Barometer is proven to be feasible and Move It Now appears to be efficacious, a health care pathway can be created to provide the best tailored treatment promptly to adolescents with chronic pain. Move It Now can be easily implemented throughout the Netherlands, as the intervention is Internet based. Trial registration Dutch Trial Register NTR1926

Assimilation of spatio-temporal distribution of radionuclides in early phase of radiation accident

Czech Academy of Sciences Publication Activity Database

Hofman, Radek; Šmídl, Václav

2010-01-01

Roč. 18, 7/8 (2010), s. 226-228 ISSN 1210-7085 R&D Projects: GA MŠk(CZ) 1M0572; GA ČR(CZ) GA102/07/1596 Institutional research plan: CEZ:AV0Z10750506 Keywords : decision support * early phase * Gaussian model * radioactive pollution transport Subject RIV: DL - Nuclear Waste, Radioactive Pollution ; Quality http://library.utia.cas.cz/separaty/2010/AS/hofman-assimilation of spatio-temporal distribution of radionuclides in early phase of radiation accident .pdf

Retaining older workers: the effect of phased retirement on delaying early retirement

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Åsmund Hermansen

2015-01-01

Full Text Available Introduction: Phased retirement involves reducing working time in the final years before retirement. The aim of phased retirement is to extend working careers and retain older workers who would otherwise opt for full early retirement. This article investigates the effect of offering phased retirement on early-retirement behaviour in Norway.Method: The data used in the analysis covers the period between 2000 and 2010 and comprises all employees between 61 and 62 years of age (N= 18 174 who were employed in any of the 442 companies that participated in a 2010 survey carried out by the Fafo Institute for Labour and Social Research and Respons Analyse AS, a Norwegian research firm. I use a difference-in-differences approach and logistic regression, which enables the measurement of changes in the individual relative risk of retiring full-time on the contractual pension (AFP, avtalefestet pensjon, contractual early-retirement pension, before and after the introduction of phased retirement as a retention measure.Results: The results show that working in a company that offers reduced working hours for older workers does not have an effect on the relative risk of a 61- or 62-year-old withdrawing a full contractual pension in the next two years of their employment. This result is evident both before and after controlling for a range of known individual risk factors, as well as after controlling for company characteristics.Discussion: In the search for suitable measures for retaining older workers, offering phased retirement may still be part of the answer. Though my analysis does not support the idea that more flexible working hours is a decisive factor for those who choose to opt for full early retirement, a possible next step could be to investigate the impact of offering flexible working hours on the employment duration of those who do remain in employment.

Betaxolol, a selective beta(1)-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats.

Science.gov (United States)

Rudoy, C A; Van Bockstaele, E J

2007-06-30

, treatment with betaxolol during early cocaine withdrawal significantly decreased beta(1)-adrenergic receptor protein expression in the amygdala to levels comparable to those of control animals. The present findings suggest that the anxiolytic-like effect of betaxolol on cocaine-induced anxiety may be related to its effect on amygdalar beta(1)-adrenergic receptors that are up-regulated during early phases of drug withdrawal. These data support the efficacy of betaxolol as a potential effective pharmacotherapy in treating cocaine withdrawal-induced anxiety during early phases of abstinence.

Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

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Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

2016-01-01

Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, poptimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (poptimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

Improving decision making in the early phases of configuration projects

DEFF Research Database (Denmark)

Mortensen, Niels Henrik; Harlou, Ulf; Haug, Anders

2008-01-01

During the early phases of configuration projects very important decisions are made which will heavily influence the performance of the company, benefits in different functional areas (production, sales, purchase, product development, service etc), maintenance of the configuration system...

Improving decision making in the early phases of configuration projects

DEFF Research Database (Denmark)

Mortensen, Niels Henrik; Hvam, Lars; Harlou, Ulf

2011-01-01

During the early phases of configuration projects very important decisions are made which will heavily influence the performance of the company, benefits in different functional areas (production, sales, purchase, product development, service etc), maintenance of the configuration system...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Early election for Group 1, Phase II boilers. 76.8 Section 76.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1...

Uptake of novel statistical methods for early-phase clinical studies in the UK public sector.

Science.gov (United States)

Jaki, Thomas

2013-04-01

In recent years, the success rate of confirmatory studies has been poor resulting in more emphasis on the conduct of exploratory studies. As one possibility to improve decision-making during the early stages of development, adaptive and Bayesian methods have been recommended. To investigate the current practice in designing early-phase studies in UK public sector research institutions and the use of adaptive and Bayesian methods in particular and to determine factors that hinder the penetration of methodological advances into practice. A questionnaire was sent to all UK clinical trials units (CTUs) to gauge their involvement in early-phase studies and to learn about the designs used in these studies. Follow-up visits to units conducting early-phase studies with round-table discussions around the methods used and the obstacles faced when using adaptive methods were undertaken. More than half of the CTUs are involved in early-phase studies, but conservatism in the methods used in these studies is present. Reasons for novel methodology not being used include a lack of expertise, incompatible funding and unit structure, and a lack of software. Information is collected from UK CTUs, which undertake a large portion (but not all) publicly funded trials. The use of adaptive and Bayesian methods for early-phase clinical studies in the UK public sector is at present limited. Various different initiatives aim to support and facilitate the use of these methods, however, so that an increased use of these methods can be anticipated in the future.

Prevention of organophosphate-induced chronic epilepsy by early benzodiazepine treatment.

Science.gov (United States)

Shrot, Shai; Ramaty, Erez; Biala, Yoav; Bar-Klein, Guy; Daninos, Moshe; Kamintsky, Lyn; Makarovsky, Igor; Statlender, Liran; Rosman, Yossi; Krivoy, Amir; Lavon, Ophir; Kassirer, Michael; Friedman, Alon; Yaari, Yoel

2014-09-02

Poisoning with organophosphates (OPs) may induce status epilepticus (SE), leading to severe brain damage. Our objectives were to investigate whether OP-induced SE leads to the emergence of spontaneous recurrent seizures (SRSs), the hallmark of chronic epilepsy, and if so, to assess the efficacy of benzodiazepine therapy following SE onset in preventing the epileptogenesis. We also explored early changes in hippocampal pyramidal cells excitability in this model. Adult rats were poisoned with the paraoxon (450μg/kg) and immediately treated with atropine (3mg/kg) and obidoxime (20mg/kg) to reduce acute mortality due to peripheral acetylcholinesterase inhibition. Electrical brain activity was assessed for two weeks during weeks 4-6 after poisoning using telemetric electrocorticographic intracranial recordings. All OP-poisoned animals developed SE, which could be suppressed by midazolam. Most (88%) rats which were not treated with midazolam developed SRSs, indicating that they have become chronically epileptic. Application of midazolam 1min following SE onset had a significant antiepileptogenic effect (only 11% of the rats became epileptic; p=0.001 compared to non-midazolam-treated rats). Applying midazolam 30min after SE onset did not significantly prevent chronic epilepsy. The electrophysiological properties of CA1 pyramidal cells, assessed electrophysiologically in hippocampal slices, were not altered by OP-induced SE. Thus we show for the first time that a single episode of OP-induced SE in rats leads to the acquisition of chronic epilepsy, and that this epileptogenic outcome can be largely prevented by immediate, but not delayed, administration of midazolam. Extrapolating these results to humans would suggest that midazolam should be provided together with atropine and an oxime in the immediate pharmacological treatment of OP poisoning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A Phase I Trial of Epstein-Barr Virus Gp350 Vaccine for Children With Chronic Kidney Disease Awaiting Transplantation

NARCIS (Netherlands)

Rees, L.; Tizard, E.J.; Morgan, A.J.; Cubitt, W.D.; Finerty, S.; Oyewole-Eletu, T.A.; Owen, K.; Royed, C.; Stevens, S.J.C.; Shroff, R.C.; Tanday, M.K.; Wilson, A.; Middeldorp, J.M.; Amlot, P.L.; Steven, N.M.

2009-01-01

Background. Vaccination against Epstein-Barr virus (EBV), inducing an antibody response to the envelope glycoprotein gp350, might protect EBV-negative children with chronic kidney disease from lymphoproliferative disease after transplantation. Methods. A phase I trial recruited children with chronic

Comparative efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for early onset chronic depression: design and rationale of a multisite randomized controlled trial

Science.gov (United States)

2011-01-01

Background Effective treatment strategies for chronic depression are urgently needed since it is not only a common and particularly disabling disorder, but is also considered treatment resistant by most clinicians. There are only a few studies on chronic depression indicating that traditional psycho- and pharmacological interventions are not as effective as in acute, episodic depression. Current medications are no more effective than those introduced 50 years ago whereas the only psychotherapy developed specifically for the subgroup of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), faired well in one large trial. However, CBASP has never been directly compared to a non-specific control treatment. Methods/Design The present article describes the study protocol of a multisite parallel-group randomized controlled trial in Germany. The purpose of the study is to estimate the efficacy of CBASP compared to supportive psychotherapy in 268 non-medicated early-onset chronically depressed outpatients. The intervention includes 20 weeks of acute treatment with 24 individual sessions followed by 28 weeks of continuation treatment with another 8 sessions. Depressive symptoms are evaluated 20 weeks after randomisation by means of the 24-item Hamilton Rating Scale of Depression (HRSD). Secondary endpoints are depressive symptoms after 12 and 48 weeks, and remission after 12, 20, and 48 weeks. Primary outcome will be analysed using analysis of covariance (ANCOVA) controlled for pre-treatment scores and site. Analyses of continuous secondary variables will be performed using linear mixed models. For remission rates, chi-squared tests and logistic regression will be applied. Discussion The study evaluates the comparative effects of a disorder-specific psychotherapy and a well designed non-specific psychological approach in the acute and continuation treatment phase in a large sample of early-onset chronically depressed patients. Trial

Dispositional optimism and therapeutic expectations in early-phase oncology trials.

Science.gov (United States)

Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P

2016-04-15

Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; Poptimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (Poptimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early-phase oncology research. © 2016 American Cancer Society.

Early-life adversity-induced long-term epigenetic programming associated with early onset of chronic physical aggression: Studies in humans and animals.

Science.gov (United States)

Chistiakov, Dimitry A; Chekhonin, Vladimir P

2017-06-05

To examine whether chronic physical aggression (CPA) in adulthood can be epigenetically programmed early in life due to exposure to early-life adversity. Literature search of public databases such as PubMed/MEDLINE and Scopus. Children/adolescents susceptible for CPA and exposed to early-life abuse fail to efficiently cope with stress that in turn results in the development of CPA later in life. This phenomenon was observed in humans and animal models of aggression. The susceptibility to aggression is a complex trait that is regulated by the interaction between environmental and genetic factors. Epigenetic mechanisms mediate this interaction. Subjects exposed to stress early in life exhibited long-term epigenetic programming that can influence their behaviour in adulthood. This programming affects expression of many genes not only in the brain but also in other systems such as neuroendocrine and immune. The propensity to adult CPA behaviour in subjects experienced to early-life adversity is mediated by epigenetic programming that involves long-term systemic epigenetic alterations in a whole genome.

Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype-4 chronic hepatitis C patients.

Science.gov (United States)

Helal, Gouda Kamel; Gad, Magdy Abdelmawgoud; Abd-Ellah, Mohamed Fahmy; Eid, Mahmoud Saied

2016-12-01

The therapeutic effect of pegylated interferon (peg-IFN) alfa-2a combined with ribavirin (RBV) on chronic hepatitis C Egyptian patients is low and further efforts are required to optimize this therapy for achievement of higher rates of virological response. This study aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) in combination with pegylated interferon plus ribavirin on early virological response (EVR) in chronic hepatitis C Egyptian patients. Naïve 120 Egyptian patients with chronic hepatitis C virus infection were divided into two groups. Group 1 have administered the standard of care therapy (pegylated interferon alfa-2a plus ribavirin) for 12 weeks, (n = 60). Group 2 have administered hydroxychloroquine plus standard of care therapy for 12 weeks, (n = 60). Therapeutics included hydroxychloroquine (200 mg) oral twice daily, peginterferon alfa-2a (160 μg) subcutaneous once weekly and oral weight-based ribavirin (1000-1200 mg/day). Baseline characteristics were similar in the two groups. The percentage of early virological response was significantly more in patients given the triple therapy than in patients given the standard of care [54/60 (90%) vs. 43/60 (71.7%); P = 0.011; respectively]. Biochemical response at week 12 was also significantly higher in patients given the triple therapy compared with the standard of care [58/60 (96.7%) vs. 42/60 (70%); P hydroxychloroquine to pegylated interferon plus ribavirin improves the rate of early virological and biochemical responses in chronic hepatitis C Egyptian patients without an increase in adverse events. J. Med. Virol. 88:2170-2178, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The role of early trabeculectomy in the control of chronic simple glaucoma.

Directory of Open Access Journals (Sweden)

Dastur Y

1994-04-01

Full Text Available Seventy patients of bilateral chronic simple glaucoma with a mean age of 59.7 years, an intra-ocular pressure over 25 mmg Hg, optic disc cupping, and without visual field loss were selected. The eye with higher intra-ocular pressure or the larger optic disc cup was treated by early trabeculectomy while the other eye of the same patient was subjected to medical therapy with topical beta blockers for 3 years (without any surgical treatment. Both the eyes of 70 patients were compared after 3 years. Eyes which had undergone trabeculectomy had a mean intra-ocular pressure of 11.7 mm Hg against 18 mm Hg in the medically treated eyes. Surgically treated eyes had decrease in the mean cup : disc ratio (from 0.54 : 1 to 0.48 : 1 whereas medically treated eyes showed an increase from 0.41:1 to 0.51: 1. Visual field loss occurred in 3/70 operated eyes and in 27/70 medically treated eyes. Twenty-one of 70 treated eyes developed cataract and 12 of these required cataract surgery. Only 18/70 medically treated eyes developed cataracts but none of these required cataract surgery. Early trabeculectomy in cases of chronic simple glaucoma resulted in a large reduction of intra-ocular pressure and consequently reduced the size of optic disc cup and the chances of visual field loss.

Chronic Disease Management Strategies of Early Childhood Caries: Support from the Medical and Dental Literature.

Science.gov (United States)

Edelstein, Burton L; Ng, Man Wai

2015-01-01

An Institute of Medicine report places chronic disease management (CDM) as an intervention on a treatment spectrum between prevention and acute care. CDM commonly focuses on conditions in which patient self-care efforts are significant. Framing early childhood caries (ECC) as such a chronic condition invites dentistry to reconsider its approach to caries management and shift gears from a strictly surgical approach to one that also incorporates a medical approach. This paper's purpose was to explore the definition of and concepts inherent in CDM. An explanatory model is introduced to describe the multiple factors that influence ECC-CDM strategies. Reviewed literature suggests that early evidence from ECC-CDM interventions, along with results of pediatric asthma and diabetes CDM, supports CDM of ECC as a valid approach that is independent of both prevention and repair. Early results of ECC-CDM endeavors have demonstrated a reduction in rates of new cavitation, dental pain, and referral to the operating room compared to baseline rates. ECC-CDM strategies hold strong promise to curtail caries activity while complementing dental repair when needed, thereby reducing disease progression and cavity recurrence. Institutionalizing ECC-CDM will both require and benefit from evolving health care delivery and financing systems that reward positive health outcomes.

Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer

Science.gov (United States)

Fitzpatrick, C. R. M.; Gordon, G. S. D.; Sawyer, T. W.; Wilkinson, T. D.; Bohndiek, S. E.

2018-02-01

Esophageal cancer has a 5-year survival rate below 20%, but can be curatively resected if it is detected early. At present, poor contrast for early lesions in white light imaging leads to a high miss rate in standard-of- care endoscopic surveillance. Early lesions in the esophagus, referred to as dysplasia, are characterized by an abundance of abnormal cells with enlarged nuclei. This tissue has a different refractive index profile to healthy tissue, which results in different light scattering properties and provides a source of endogenous contrast that can be exploited for advanced endoscopic imaging. For example, point measurements of such contrast can be made with scattering spectroscopy, while optical coherence tomography generates volumetric data. However, both require specialist interpretation for diagnostic decision making. We propose combining wide-field phase imaging with existing white light endoscopy in order to provide enhanced contrast for dysplasia and early-stage cancer in an image format that is familiar to endoscopists. Wide-field phase imaging in endoscopy can be achieved using coherent illumination combined with phase retrieval algorithms. Here, we present the design and simulation of a benchtop phase imaging system that is compatible with capsule endoscopy. We have undertaken preliminary optical modelling of the phase imaging setup, including aberration correction simulations and an investigation into distinguishing between different tissue phantom scattering coefficients. As our approach is based on phase retrieval rather than interferometry, it is feasible to realize a device with low-cost components for future clinical implementation.

Biomarkers in early phase development of central nervous system drugs : a conceptual framework

NARCIS (Netherlands)

Post, Jeroen-Paul van der

2006-01-01

The main objective of this thesis is to provide a conceptual framework for the use of Central Nervous System (CNS) biomarkers in early phase clinical drug development. In the Introduction the current use of biomarkers in early CNS drug development is discussed. A conceptual framework for the

Biomarkers in the early diagnosis of Parkinson's disease

Directory of Open Access Journals (Sweden)

CHEN Sheng-di

2013-08-01

Full Text Available Parkinson's disease (PD is a chronic and progressive neurodegenerative disorder. It has become clear that PD can have a preclinical phase, a period during which neurodegeneration has already begun years before the onset of typical motor symptoms. Consequently, if the early neurodegeneration in PD can be timely diagnosed, it will significantly slow down the progression of the disease and improve the quality of life. To date, there is no fully reliable and validated biomarker for the early diagnosis of PD, but some promising biomarker candidates exist.

Role of 123I-IMP SPET in the early diagnosis of borderline chronic hydrocephalus after aneurysmal subarachnoid haemorrhage

International Nuclear Information System (INIS)

Ohkuma, Hiroki; Tanaka, Masahiko; Suzuki, Shigeharu; Kondoh, Izumi

2000-01-01

Chronic hydrocephalus after aneurysmal subarachnoid haemorrhage (SAH) is easily diagnosed in most cases. However, the diagnosis is sometimes difficult in borderline cases, in which (a) pathognomonic clinical deterioration due to hydrocephalus is masked by the neurological deficits caused in the acute stage of SAH and (b) ventricular enlargement is not so marked on CT scan. The purpose of this study was to investigate whether or not iodine-123 labelled N-isopropyl-p-iodoamphetamine ( 123 I-IMP) single-photon emission tomography (SPET) is of value for the early diagnosis of borderline chronic hydrocephalus after SAH. Fifteen patients who met the criteria of borderline chronic hydrocephalus were selected for the study, and underwent a shunt operation. The patients were divided into a shunt-effective group and a shunt-ineffective group according to neurological improvement after the shunt operation. 123 I-IMP SPET was performed in the acute stage of SAH, within 1 week before the shunt operation, and 2 weeks after the shunt operation. Regional cerebral blood flow was estimated by the 123 I-IMP autoradiographic method. Pre-shunting periventricular low-perfusion areas showed statistically significant differences between the two groups (P 123 I-IMP SPET can be used for both the early diagnosis of borderline chronic hydrocephalus after SAH and the prediction of shunt effectiveness. (orig.)

Chronic sleep reduction in adolescents with Delayed Sleep Phase Disorder and effects of melatonin treatment

NARCIS (Netherlands)

van Maanen, Annette; Dewald-Kaufmann, Julia F.; Smits, Marcel G.; Oort, Frans J.; Meijer, Anne Marie

2013-01-01

Homeostatic and circadian changes that occur during adolescence can result in chronic sleep reduction. This may particularly be true for adolescents with Delayed Sleep Phase Disorder (DSPD), which is associated with late Dim Light Melatonin Onset (DLMO). This study assessed the influence of

Racial and gender discrimination, early life factors, and chronic physical health conditions in midlife.

Science.gov (United States)

McDonald, Jasmine A; Terry, Mary Beth; Tehranifar, Parisa

2014-01-01

Most studies of perceived discrimination have been cross-sectional and focused primarily on mental rather than physical health conditions. We examined the associations of perceived racial and gender discrimination reported in adulthood with early life factors and self-reported physician diagnosis of chronic physical health conditions. We used data from a racially diverse birth cohort of U.S. women (n = 168; average age, 41 years) with prospectively collected early life data (e.g., parental socioeconomic factors) and adult reported data on perceived discrimination, physical health conditions, and relevant risk factors. We performed modified robust Poisson regression owing to the high prevalence of the outcomes. Fifty percent of participants reported racial and 39% reported gender discrimination. Early life factors did not have strong associations with perceived discrimination. In adjusted regression models, participants reporting at least three experiences of gender or racial discrimination had a 38% increased risk of having at least one physical health condition (relative risk, 1.38; 95% confidence interval, 1.01-1.87). Using standardized regression coefficients, the magnitude of the association of having physical health condition(s) was larger for perceived discrimination than for being overweight or obese. Our results suggest a substantial chronic disease burden associated with perceived discrimination, which may exceed the impact of established risk factors for poor physical health. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Comparison of Direct Oral Anticoagulants and Warfarin in the Treatment of Deep Venous Thrombosis in the Chronic Phase.

Science.gov (United States)

Wakakura, Shingo; Hara, Fumihiko; Fujino, Tadashi; Hamai, Asami; Ohara, Hiroshi; Kabuki, Takayuki; Harada, Masahiko; Ikeda, Takanori

2018-01-27

We assessed the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of deep venous thrombosis (DVT) in the chronic phase through comparison with conventional warfarin therapy.A total of 807 consecutive patients who were diagnosed with having DVT in the chronic phase were included (484 patients to warfarin therapy and 323 patients to DOAC therapy). The condition of leg veins was assessed 3 to 6 months after starting the therapies by ultrasound examination. Major bleeding and mortality during the therapies were followed-up.There was no significant difference between the two groups in the thrombosis improvement rate (DOAC group: 91.2% versus warfarin group: 88.9%). There was no significant difference between the two groups in major bleeding (DOAC group: 1.8% versus warfarin group: 1.8%). In patients with active cancer, the DOAC group had a borderline higher thrombosis improvement rate than the warfarin group (92.1% versus 80.0%, P = 0.05). The proportion of major bleeding in the patients with active cancer was slightly higher in the warfarin group than in the DOAC group (4.3% versus 2.8%; P = 0.71). Active cancer was not an independent risk factor for major bleeding and recurrence in the DOAC group (OR 2.68, 95% CI 0.51-14.1; P = 0.24 and OR 0.65, 95% CI 0.20-2.07; P = 0.47).In treatment using oral anticoagulants for DVT in the chronic phase, DOACs exhibited equal efficacy and safety as warfarin did. Particularly DOACs appear to be an attractive therapeutic option for cancer-associated DVT in chronic phase, with relatively low anticipated rates of recurrence and major bleeding.

Modelling production system architectures in the early phases of product development

DEFF Research Database (Denmark)

Guðlaugsson, Tómas Vignir; Ravn, Poul Martin; Mortensen, Niels Henrik

2016-01-01

are needed and appropriate to enable determination of obtainable product quality. In order to meet this challenge, it is suggested that a visual modelling framework be adopted that clarifies which product and production features are known at a specific time of the project and which features will be worked...... on – leading to an improved basis for prioritizing activities in the project. Requirements for the contents of the framework are presented, and literature on production and system models is reviewed. The production system architecture modelling framework is founded on methods and approaches in literature......This article suggests a framework for modelling a production system architecture in the early phases of product development.The challenge in these phases is that the products to be produced are not completely defined and yet decisions need to be made early in the process on what investments...

'Real-life' study of imatinib therapy in chronic phase-chronic myeloid leukemia: A novel retrospective observational longitudinal analysis.

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Merante, Serena; Ferretti, Virginia; Elena, Chiara; Calvello, Celeste; Rocca, Barbara; Zappatore, Rita; Cavigliano, Paola; Orlandi, Ester

2017-01-01

Imatinib is a cornerstone of treatment of chronic myeloid leukemia. It remains unclear whether transient treatment discontinuation or dose changes affect outcome and this approach has not yet been approved for use outside clinical trials. We conducted a retrospective single-institution observational study to evaluate factors affecting response in 'real-life' clinical practice in 138 chronic myeloid leukemia patients in chronic phase treated with imatinib. We used a novel longitudinal data analytical model, with a generalized estimating equation model, to study BCR-ABL variation according to continuous standard dose, change in dose or discontinuation; BCR-ABL transcript levels were recorded. Treatment history was subdivided into time periods for which treatment was given at constant dosage (total 483 time periods). Molecular and cytogenetic complete response was observed after 154 (32%) and 358 (74%) time periods, respectively. After adjusting for length of time period, no association between dose and cytogenetic complete response rate was observed. There was a significantly lower molecular complete response rate after time periods at a high imatinib dosage. This statistical approach can identify individual patient variation in longitudinal data collected over time and suggests that changes in dose or discontinuation of therapy could be considered in patients with appropriate biological characteristics.

RODOS and decision conferencing on early phase protective actions in Finland

International Nuclear Information System (INIS)

Haemaelaeinen, R.P.; Lindstedt, M.; Salo, A.

1998-12-01

This work was undertaken in order to study the utilisation of decision conferencing and of the RODOS system when considering early phase protective actions in the case of a nuclear accident. Altogether four meetings with various people were organised. The meetings were attended by competent national safety authorities and technical level decision-makers, i.e., those who are responsible for preparing advice or making presentations of matters for decision-makers responsible for practical implementation of actions. In the first set of meetings the aim was to elicit the factors/attributes that have to be considered when making a decision on sheltering, evacuation and iodine tablets. No uncertainties nor a threat phase were considered but everything was assumed to happen as described in the given scenario. The theme in the second set of meetings was to study the implications of probabilities. All information was calculated with the support of the RODOS system. In the early phases of a nuclear accident time is limited. Prestructured generic value trees or a list of possible attributes can help to save time. A possible approach is to present a large generic value tree. Either the decision-makers select the attributes that are suitable for the case in hand or the facilitator offers a choice between more structured value trees. The decision-makers then just examine the suggested value trees, check the generic tree to make sure that no important factors have been omitted and choose the appropriate one. As in previous RODOS exercises, the participants felt that RODOS could be used for providing information but found it more problematic to use decision analysis methods when deciding on countermeasures in the early phase of a nuclear accident. Furthermore, it was noted that understanding the actual meaning of 'soft' attributes, such as socio-psychological impacts or political cost, was not a straightforward issue. Consequently, the definition of attributes in advance would be

RODOS and decision conferencing on early phase protective actions in Finland

Energy Technology Data Exchange (ETDEWEB)

Haemaelaeinen, R.P.; Lindstedt, M. [Helsinki Univ. of Technology, Espoo (Finland). Systems Analysis Lab.; Sinkko, K.; Ammann, M. [Radiation and Nuclear Safety Authority, Helsinki (Finland); Salo, A

1998-12-01

This work was undertaken in order to study the utilisation of decision conferencing and of the RODOS system when considering early phase protective actions in the case of a nuclear accident. Altogether four meetings with various people were organised. The meetings were attended by competent national safety authorities and technical level decision-makers, i.e., those who are responsible for preparing advice or making presentations of matters for decision-makers responsible for practical implementation of actions. In the first set of meetings the aim was to elicit the factors/attributes that have to be considered when making a decision on sheltering, evacuation and iodine tablets. No uncertainties nor a threat phase were considered but everything was assumed to happen as described in the given scenario. The theme in the second set of meetings was to study the implications of probabilities. All information was calculated with the support of the RODOS system. In the early phases of a nuclear accident time is limited. Prestructured generic value trees or a list of possible attributes can help to save time. A possible approach is to present a large generic value tree. Either the decision-makers select the attributes that are suitable for the case in hand or the facilitator offers a choice between more structured value trees. The decision-makers then just examine the suggested value trees, check the generic tree to make sure that no important factors have been omitted and choose the appropriate one. As in previous RODOS exercises, the participants felt that RODOS could be used for providing information but found it more problematic to use decision analysis methods when deciding on countermeasures in the early phase of a nuclear accident. Furthermore, it was noted that understanding the actual meaning of `soft` attributes, such as socio-psychological impacts or political cost, was not a straightforward issue. Consequently, the definition of attributes in advance would be

Catastrophic phase transitions and early warnings in a spatial ecological model

International Nuclear Information System (INIS)

Fernández, A; Fort, H

2009-01-01

Gradual changes in exploitation, nutrient loading, etc produce shifts between alternative stable states (ASS) in ecosystems which, quite often, are not smooth but abrupt or catastrophic. Early warnings of such catastrophic regime shifts are fundamental for designing management protocols for ecosystems. Here we study the spatial version of a popular ecological model, involving a logistically growing single species subject to exploitation, which is known to exhibit ASS. Spatial heterogeneity is introduced by a carrying capacity parameter varying from cell to cell in a regular lattice. Transport of biomass among cells is included in the form of diffusion. We investigate whether different quantities from statistical mechanics—like the variance, the two-point correlation function and the patchiness—may serve as early warnings of catastrophic phase transitions between the ASS. In particular, we find that the patch-size distribution follows a power law when the system is close to the catastrophic transition. We also provide links between spatial and temporal indicators and analyse how the interplay between diffusion and spatial heterogeneity may affect the earliness of each of the observables. We find that possible remedial procedures, which can be followed after these early signals, become more effective as the diffusion becomes lower. Finally, we comment on similarities of and differences between these catastrophic shifts and paradigmatic thermodynamic phase transitions like the liquid–vapour change of state for a fluid like water

Betaxolol, a selective β1-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats

Science.gov (United States)

Rudoy, C.A.; Van Bockstaele, E.J.

2007-01-01

. Furthermore, treatment with betaxolol during early cocaine withdrawal significantly decreased β1-adrenergic receptor protein expression in the amygdala to levels comparable to those of control animals. Conclusions The present findings suggest that the anxiolytic-like effect of betaxolol on cocaine-induced anxiety may be related to its effect on amygdalar β1-adrenergic receptors that are up-regulated during early phases of drug withdrawal. These data support the efficacy of betaxolol as a potential effective pharmacotherapy in treating cocaine withdrawal-induced anxiety during early phases of abstinence. PMID:17513029

Early and late oral features of chronic graft-versus-host disease

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Alessandra Oliveira Ferrari Gomes

2014-01-01

Full Text Available Background: Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. Objective: The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. Methods: This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year. Results: Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72% in the group with less than one year after transplantation, and 34 (77.27% in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. Conclusion: Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation.

Treating the chronic-phase chronic myeloid leukemia patient: which TKI, when to switch and when to stop?

Science.gov (United States)

Patel, Ami B; Wilds, Brandon W; Deininger, Michael W

2017-07-01

With the discovery of imatinib mesylate nearly 20 years ago, tyrosine kinase inhibitors (TKIs) were found to be effective in chronic myeloid leukemia (CML). TKI therapy has since revolutionized the treatment of CML and has served as a paradigm of success for targeted drug therapy in cancer. Several new TKIs for CML have been approved over the last two decades that exhibit improved potency over imatinib and have different off-target profiles, providing options for individualized therapy selection. Areas covered: Current management of chronic phase CML, including guidance on the sequential use of imatinib and newer-generation TKIs and evolving treatment strategies such as TKI discontinuation. Relevant literature was identified by searching biomedical databases (i.e. PubMed) for primary research material. Expert commentary: Although survival outcomes have drastically improved for CML patients, treatment for CML has grown more complex with the introduction of next-generation TKIs and the advent of treatment-free remissions (TFR). Goals of therapy have shifted accordingly, with increased focus on improving quality of life, managing patient expectations and optimizing patient adherence.

Autobiographical memory and structural brain changes in chronic phase TBI.

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Esopenko, Carrie; Levine, Brian

2017-04-01

Traumatic brain injury (TBI) is associated with a range of neuropsychological deficits, including attention, memory, and executive functioning attributable to diffuse axonal injury (DAI) with accompanying focal frontal and temporal damage. Although the memory deficit of TBI has been well characterized with laboratory tests, comparatively little research has examined retrograde autobiographical memory (AM) at the chronic phase of TBI, with no prior studies of unselected patients drawn directly from hospital admissions for trauma. Moreover, little is known about the effects of TBI on canonical episodic and non-episodic (e.g., semantic) AM processes. In the present study, we assessed the effects of chronic-phase TBI on AM in patients with focal and DAI spanning the range of TBI severity. Patients and socioeconomic- and age-matched controls were administered the Autobiographical Interview (AI) (Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002) a widely used method for dissociating episodic and semantic elements of AM, along with tests of neuropsychological and functional outcome. Measures of episodic and non-episodic AM were compared with regional brain volumes derived from high-resolution structural magnetic resonance imaging (MRI). Severe TBI (but not mild or moderate TBI) was associated with reduced recall of episodic autobiographical details and increased recall of non-episodic details relative to healthy comparison participants. There were no significant associations between AM performance and neuropsychological or functional outcome measures. Within the full TBI sample, autobiographical episodic memory was associated with reduced volume distributed across temporal, parietal, and prefrontal regions considered to be part of the brain's AM network. These results suggest that TBI-related distributed volume loss affects episodic autobiographical recollection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early-type galaxy core phase densities

International Nuclear Information System (INIS)

Carlberg, R. G.; Hartwick, F. D. A.

2014-01-01

Early-type galaxies have projected central density brightness profile logarithmic slopes, γ', ranging from about 0 to 1. We show that γ' is strongly correlated, r = 0.83, with the coarse grain phase density of the galaxy core, Q 0 ≡ ρ/σ 3 . The luminosity-γ' correlation is much weaker, r = –0.51. Q 0 also serves to separate the distribution of steep core profiles, γ' > 0.5, from shallow profiles, γ' < 0.3, although there are many galaxies of intermediate slope, at intermediate Q 0 , in a volume-limited sample. The transition phase density separating the two profile types is approximately 0.003 M ☉ pc –3 km –3 s 3 , which is also where the relation between Q 0 and core mass shows a change in slope, the rotation rate of the central part of the galaxy increases, and the ratio of the black hole to core mass increases. These relations are considered relative to the globular cluster inspiral core buildup and binary black hole core scouring mechanisms for core creation and evolution. Mass-enhanced globular cluster inspiral models have quantitative predictions that are supported by data, but no single model yet completely explains the correlations.

Multidisciplinary strategies in the management of early chronic kidney disease.

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Martínez-Ramírez, Héctor R; Cortés-Sanabria, Laura; Rojas-Campos, Enrique; Hernández-Herrera, Aurora; Cueto-Manzano, Alfonso M

2013-11-01

Chronic kidney disease (CKD) is a worldwide epidemic especially in developing countries, with clear deficiencies in identification and treatment. Better care of CKD requires more than only economic resources, utilization of health research in policy-making and health systems changes that produce better outcomes. A multidisciplinary approach may facilitate and improve management of patients from early CKD in the primary health-care setting. This approach is a strategy for improving comprehensive care, initiating and maintaining healthy behaviors, promoting teamwork, eliminating barriers to achieve goals and improving the processes of care. A multidisciplinary intervention may include educational processes guided by health professional, use of self-help groups and the development of a CKD management plan. The complex and fragmented care management of patients with CKD, associated with poor outcome, enhances the importance of implementing a multidisciplinary approach in the management of this disease from the early stages. Multidisciplinary strategies should focus on the needs of patients (to increase their empowerment) and should be adapted to the resources and health systems prevailing in each country; its systematic implementation can help to improve patient care and slow the progression of CKD. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

Numerical investigation of the early flight phase in ski-jumping.

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Gardan, N; Schneider, A; Polidori, G; Trenchard, H; Seigneur, J M; Beaumont, F; Fourchet, F; Taiar, R

2017-07-05

The purpose of this study is to develop a numerical methodology based on real data from wind tunnel experiments to investigate the effect of the ski jumper's posture and speed on aerodynamic forces in a wide range of angles of attack. To improve our knowledge of the aerodynamic behavior of the ski jumper and his equipment during the early flight phase of the ski jump, we applied CFD methodology to evaluate the influence of angle of attack (α=14°, 21.5°, 29°, 36.5° and 44°) and speed (u=23, 26 and 29m/s) on aerodynamic forces in the situation of stable attitude of the ski jumper's body and skis. The standard k-ω turbulence model was used to investigate both the influence of the ski jumper's posture and speed on aerodynamic performance during the early flight phase. Numerical results show that the ski jumper's speed has very little impact on the lift and drag coefficients. Conversely, the lift and drag forces acting on the ski jumper's body during the early flight phase of the jump are strongly influenced by the variations of the angle of attack. The present results suggest that the greater the ski jumper's angle of inclination, with respect to the relative flow, the greater the pressure difference between the lower and upper parts of the skier. Further studies will focus on the dependency of the parameters with both the angle of attack α and the body-ski angle β as control variables. It will be possible to test and optimize different ski jumping styles in different ski jumping hills and investigate different environmental conditions such as temperature, altitude or crosswinds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Line Evolution of the Nova V5587 Sgr from Early to Nebula Phase

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T. Kajikawa

2015-02-01

Full Text Available The spectral evolution of the nova V5587 Sgr has been monitored at Koyama Astronomical Observatory and Higashi-Hiroshima Observatory, Japan, from the early to nebula phase. The nova rebrightened several times. The spectra during the early phase showed emission lines of H α, H β, O I, He I, He II, N II, Fe II. Nova V5587 Sgr is classified into the Fe II type. The helium abundance of the nova is estimated as N(He/N(H = 0.134 ± 0.09. The light curve, the spectral evolution, and the helium abundance in V5587 Sgr are similar to those of the nova PW Vul.

Chronic headache and comorbidities: a two-phase, population-based, cross-sectional study.

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da Silva, Ariovaldo; Costa, Esther Coelho; Gomes, João Bosco; Leite, Frederico Motta; Gomez, Rodrigo Santiago; Vasconcelos, Luiz Paulo; Krymchantowski, Abouch; Moreira, Pedro; Teixeira, Antonio Lucio

2010-09-01

Studies using resources of a public family health program to estimate the prevalence of chronic daily headaches (CDH) are lacking. To estimate the 1-year prevalence of CDH, as well as the presence of associated psychiatric and temporomandibular disorders (TMD) comorbidities, on the entire population of a city representative of the rural area of Brazil. This was a cross-sectional, population-based, 2-phase study. In the first phase, health agents interviewed all individuals older than 10 years, in a rural area of Brazil. In the second stage, all individuals who reported headaches on 4 or more days per week were then evaluated by a multidisciplinary team. CDH were classified according to the second edition of the International Classification of Headache Disorders (ICHD-2). Medication overuse headache was diagnosed, as per the ICHD-2, after detoxification trials. Psychiatric comorbidities and TMD were diagnosed based on the DSM-IV and on the Research Diagnostic Criteria for Temporomandibular Disorders criteria, respectively. A total of 1631 subjects participated in the direct interviews. Of them, 57 (3.6%) had CDH. Chronic migraine was the most common of the CDH (21, 36.8%). Chronic tension-type headache (10, 17.5%), medication overuse headache (13, 22.8%) and probable medication overuse headache (10, 17.5%) were also common. Psychiatric disorders were observed in 38 (67.3%) of the CDH subjects. TMD were seen in 33 (58.1)% of them. The prevalence of CDH in the rural area of Brazil is similar to what has been reported in previous studies. A significant proportion of them have psychiatric comorbidities and/or TMD. In this sample, comorbidities were as frequent as reported in convenience samples from tertiary headache centers.

Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.

Science.gov (United States)

Winsauer, Peter J; Sutton, Jessie L

2014-02-01

This study examined whether chronic Δ(9)-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ(9)-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6 mg/kg of Δ(9)-THC i.p. for 40 days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ(9)-THC (0.56-10 mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ(9)-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ(9)-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ(9)-THC than the OVX groups irrespective of chronic Δ(9)-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ(9)-THC) and the dose of Δ(9)-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ(9)-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we

Skin manifestations in sulfur mustard exposed victims with ophthalmologic complications: Association between early and late phase

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Somayeh Hejazi, MD

Full Text Available Context: Sulfur mustard (SM was used during the Iraq-Iran war (1980–1988. Exposed veterans continue to suffer from its ocular, skin, and respiratory complications. Objective: We aimed to evaluate associations between early (at the time of acute exposure and decades later skin manifestations in individuals with severe ophthalmologic complications secondary to sulfur mustard exposure. Materials and methods: One hundred forty-nine veterans with severe ocular injuries were evaluated for acute and chronic skin complications. Logistic regression models were used to examine the associations between early and late skin manifestations. Results: Late skin complaints were observed in nearly all survivors who had early skin lesions (131 out of 137; 95.62%. Seven out of 12 patients (58.33% who did not have early skin lesions ultimately developed late skin complications. There was a significant relationship between the presence of lesions at the time of exposure and developing late skin complaints (two-sided Fisher's exact test, OR = 15.59, p < 0.001. There was an association between having at least one early skin lesion and occurrence of late skin complications. Survivors with blisters at the time of chemical exposure were more likely to complain of itching (95% CI: 3.63–25.97, p < 0.001, burning (OR = 11.16; 95% CI: 2.97–41.89, p < 0.001, pigmentation changes (OR = 10.17; 95% CI: 2.54–40.75, p = 0.001, dryness (OR = 6.71, 95% CI: 1.22–37.01, p = 0.03 or cherry angioma (OR = 2.59; 95% CI:1.21–5.55, p = 0.01 during the late phase. Using multivariate logistic models, early blisters remained significantly associated with latent skin complaints. Of note, the genitalia and great flexure areas were the most involved anatomical sites for both early and late skin lesions in SM exposed survivors. Conclusion: According to this study, the presence of blisters at the time of exposure to SM is the most important predictor of developing

Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial.

Science.gov (United States)

Ahmed Ali, Usama; Issa, Yama; Bruno, Marco J; van Goor, Harry; van Santvoort, Hjalmar; Busch, Olivier R C; Dejong, Cornelis H C; Nieuwenhuijs, Vincent B; van Eijck, Casper H; van Dullemen, Hendrik M; Fockens, Paul; Siersema, Peter D; Gouma, Dirk J; van Hooft, Jeanin E; Keulemans, Yolande; Poley, Jan W; Timmer, Robin; Besselink, Marc G; Vleggaar, Frank P; Wilder-Smith, Oliver H; Gooszen, Hein G; Dijkgraaf, Marcel G W; Boermeester, Marja A

2013-03-18

In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in terms of better pain control and preservation of pancreatic function. Therefore, we designed a randomized controlled trial to evaluate the benefits, risks and costs of early surgical intervention compared to the current stepwise practice for chronic pancreatitis. The ESCAPE trial is a randomized controlled, parallel, superiority multicenter trial. Patients with chronic pancreatitis, a dilated pancreatic duct (≥5 mm) and moderate pain and/or frequent flare-ups will be registered and followed monthly as potential candidates for the trial. When a registered patient meets the randomization criteria (i.e. need for opioid analgesics) the patient will be randomized to either early surgical intervention (group A) or optimal current step-up practice (group B). An expert panel of chronic pancreatitis specialists will oversee the assessment of eligibility and ensure that allocation to either treatment arm is possible. Patients in group A will undergo pancreaticojejunostomy or a Frey-procedure in case of an enlarged pancreatic head (≥4 cm). Patients in group B will undergo a step-up practice of optimal medical treatment, if needed followed by endoscopic interventions, and if needed followed by surgery, according to predefined criteria. Primary outcome is pain assessed with the Izbicki pain score during a follow-up of 18 months. Secondary outcomes include complications, mortality, total direct and indirect costs, quality of life, pancreatic insufficiency, alternative pain scales, length of hospital admission, number of interventions and pancreatitis flare-ups. For the sample size calculation we defined a minimal clinically relevant difference in the primary endpoint as a difference of at least

Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use.

Science.gov (United States)

Lucero, J; Harlow, B L; Barbieri, R L; Sluss, P; Cramer, D W

2001-10-01

To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). Cross-sectional study. Academic medical center. Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones. A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine. FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle. Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming or =500 mg of caffeine per day, about a 70% increase. Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

The retention of academics in the early career phase

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Coenraad Bester

2008-11-01

Full Text Available The purpose of the study was to determine to what extent academics in the early career phase at a South African higher education institution are committed to the institution in question and the impact which this commitment has on labour turnover. More than 21% of the original respondents left the institution while this research was still underway. Insufficient financial remuneration was the most important reason why the respondents considered leaving the institution.

Role of T2 weighted magnetic resonance image in chronic phase of head injured patients

International Nuclear Information System (INIS)

Uzura, Masahiko; Taguchi, Yoshio; Watanabe, Hiroyuki; Chiba, Syunmei; Matsuzawa, Motoshi

2002-01-01

In neuroimaging studies of head injury, addition of echo planar imaging (EPI) T2-weighted images (WI) to routine MR images has been useful in demonstrating small hemorrhagic lesions as magnetic susceptibility artifacts (MSAs). MSAs are often found in the acute or subacute phases of head injured patients with diffuse axonal injury. We studied MSAs in follow-up MR images of patients with diffuse brain injury and discuss the role of EPI T2-WI in patients with chronic phase of head injured patients. This series consisted of 20 patients with diffuse brain injury diagnosed clinically. Their head CT findings were classified into Diffuse Injury I or II according to the CT classification of Marshall et al. All patients underwent long-term follow-up MR examinations. MR findings in chronic phase were divided into three categories in terms of MSAs: group A, MSAs remaining even after disappearance of small traumatic lesions in both T2-WI and fluid attenuated inversion recovery (FLAIR) images (11 cases); group B, MSA (s) that disappeared in association with disappearance of small traumatic lesions (4 cases); and group C, MSAs that remained but could not be differentiated from non-traumatic lesions such as hemorrhagic lacunae or cavernoma (5 cases). Adding EPI T2-WI to routine MR images can provide useful information in visualizing old traumatic lesions of the brain in patients with diffuse brain injury even if no neuroimaging studies in acute or subacute phase. (author)

Characterisation of the maternal response to chronic phase shifts during gestation in the rat: implications for fetal metabolic programming.

Directory of Open Access Journals (Sweden)

Tamara J Varcoe

Full Text Available Disrupting maternal circadian rhythms through exposure to chronic phase shifts of the photoperiod has lifelong consequences for the metabolic homeostasis of the fetus, such that offspring develop increased adiposity, hyperinsulinaemia and poor glucose and insulin tolerance. In an attempt to determine the mechanisms by which these poor metabolic outcomes arise, we investigated the impact of chronic phase shifts (CPS on maternal and fetal hormonal, metabolic and circadian rhythms. We assessed weight gain and food consumption of dams exposed to either CPS or control lighting conditions throughout gestation. At day 20, dams were assessed for plasma hormone and metabolite concentrations and glucose and insulin tolerance. Additionally, the expression of a range of circadian and metabolic genes was assessed in maternal, placental and fetal tissue. Control and CPS dams consumed the same amount of food, yet CPS dams gained 70% less weight during the first week of gestation. At day 20, CPS dams had reduced retroperitoneal fat pad weight (-15%, and time-of-day dependent decreases in liver weight, whereas fetal and placental weight was not affected. Melatonin secretion was not altered, yet the timing of corticosterone, leptin, glucose, insulin, free fatty acids, triglycerides and cholesterol concentrations were profoundly disrupted. The expression of gluconeogenic and circadian clock genes in maternal and fetal liver became either arrhythmic or were in antiphase to the controls. These results demonstrate that disruptions of the photoperiod can severely disrupt normal circadian profiles of plasma hormones and metabolites, as well as gene expression in maternal and fetal tissues. Disruptions in the timing of food consumption and the downstream metabolic processes required to utilise that food, may lead to reduced efficiency of growth such that maternal weight gain is reduced during early embryonic development. It is these perturbations that may contribute to

Characterisation of the maternal response to chronic phase shifts during gestation in the rat: implications for fetal metabolic programming.

Science.gov (United States)

Varcoe, Tamara J; Boden, Michael J; Voultsios, Athena; Salkeld, Mark D; Rattanatray, Leewen; Kennaway, David J

2013-01-01

Disrupting maternal circadian rhythms through exposure to chronic phase shifts of the photoperiod has lifelong consequences for the metabolic homeostasis of the fetus, such that offspring develop increased adiposity, hyperinsulinaemia and poor glucose and insulin tolerance. In an attempt to determine the mechanisms by which these poor metabolic outcomes arise, we investigated the impact of chronic phase shifts (CPS) on maternal and fetal hormonal, metabolic and circadian rhythms. We assessed weight gain and food consumption of dams exposed to either CPS or control lighting conditions throughout gestation. At day 20, dams were assessed for plasma hormone and metabolite concentrations and glucose and insulin tolerance. Additionally, the expression of a range of circadian and metabolic genes was assessed in maternal, placental and fetal tissue. Control and CPS dams consumed the same amount of food, yet CPS dams gained 70% less weight during the first week of gestation. At day 20, CPS dams had reduced retroperitoneal fat pad weight (-15%), and time-of-day dependent decreases in liver weight, whereas fetal and placental weight was not affected. Melatonin secretion was not altered, yet the timing of corticosterone, leptin, glucose, insulin, free fatty acids, triglycerides and cholesterol concentrations were profoundly disrupted. The expression of gluconeogenic and circadian clock genes in maternal and fetal liver became either arrhythmic or were in antiphase to the controls. These results demonstrate that disruptions of the photoperiod can severely disrupt normal circadian profiles of plasma hormones and metabolites, as well as gene expression in maternal and fetal tissues. Disruptions in the timing of food consumption and the downstream metabolic processes required to utilise that food, may lead to reduced efficiency of growth such that maternal weight gain is reduced during early embryonic development. It is these perturbations that may contribute to the programming of

Early life influences on the development of chronic obstructive pulmonary disease.

Science.gov (United States)

Stocks, Janet; Sonnappa, Samatha

2013-06-01

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is not simply a disease of old age that is largely restricted to heavy smokers, but may be associated with insults to the developing lung during foetal life and the first few years of postnatal life, when lung growth and development are rapid. A better understanding of the long-term effects of early life factors, such as intrauterine growth restriction, prenatal and postnatal exposure to tobacco smoke and other pollutants, preterm delivery and childhood respiratory illnesses, on the subsequent development of chronic respiratory disease is imperative if appropriate preventive and management strategies to reduce the burden of COPD are to be developed. The extent to which insults to the developing lung are associated with increased risk of COPD in later life depends on the underlying cause, timing and severity of such derangements. Suboptimal conditions in utero result in aberrations of lung development such that affected individuals are born with reduced lung function, which tends to remain diminished throughout life, thereby increasing the risk both of wheezing disorders during childhood and subsequent COPD in genetically susceptible individuals. If the current trend towards the ever-increasing incidence of COPD is to be reversed, it is essential to minimize risks to the developing lung by improvements in antenatal and neonatal care, and to reduce prenatal and postnatal exposures to environmental pollutants, including passive tobacco smoke. Furthermore, adult physicians need to recognize that lung disease is potentially associated with early life insults and provide better education regarding diet, exercise and avoidance of smoking to preserve precious reserves of lung function in susceptible adults. This review focuses on factors that adversely influence lung development in utero and during the first 5 years of life, thereby predisposing to subsequent COPD.

Ductal Mucus Obstruction and Reduced Fluid Secretion Are Early Defects in Chronic Pancreatitis

Directory of Open Access Journals (Sweden)

Anita Balázs

2018-05-01

Full Text Available Objective: Defective mucus production in the pancreas may be an important factor in the initiation and progression of chronic pancreatitis (CP, therefore we aimed to (i investigate the qualitative and quantitative changes of mucus both in human CP and in an experimental pancreatitis model and (ii to correlate the mucus phenotype with epithelial ion transport function.Design: Utilizing human tissue samples and a murine model of cerulein induced CP we measured pancreatic ductal mucus content by morphometric analysis and the relative expression of different mucins in health and disease. Pancreatic fluid secretion in CP model was measured in vivo by magnetic resonance cholangiopancreatography (MRCP and in vitro on cultured pancreatic ducts. Time-changes of ductal secretory function were correlated to those of the mucin production.Results: We demonstrate increased mucus content in the small pancreatic ducts in CP. Secretory mucins MUC6 and MUC5B were upregulated in human, Muc6 in mouse CP. In vivo and in vitro fluid secretion was decreased in cerulein-induced CP. Analysis of time-course changes showed that impaired ductal ion transport is paralleled by increased Muc6 expression.Conclusion: Mucus accumulation in the small ducts is a combined effect of mucus hypersecretion and epithelial fluid secretion defect, which may lead to ductal obstruction. These results suggest that imbalance of mucus homeostasis may have an important role in the early-phase development of CP, which may have novel diagnostic and therapeutic implications.

Administration of Zinc plus Cyclo-(His-Pro Increases Hippocampal Neurogenesis in Rats during the Early Phase of Streptozotocin-Induced Diabetes

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Bo Young Choi

2017-01-01

Full Text Available The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro (ZC on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ-induced diabetes. ZC (27 mg/kg was administered by gavage once daily for one or six weeks from the third day after the STZ injection, and histological evaluation was performed at 10 (early phase or 45 (late phase days after STZ injection. We found that the proliferation of progenitor cells in STZ-induced diabetic rats showed an increase in the early phase. Additionally, ZC treatment remarkably increased the number of neural progenitor cells (NPCs and immature neurons in the early phase of STZ-induced diabetic rats. Furthermore, ZC treatment showed increased survival rate of newly generated cells but no difference in the level of neurogenesis in the late phase of STZ-induced diabetic rats. The present study demonstrates that zinc supplementation by ZC increases both NPCs proliferation and neuroblast production at the early phase of diabetes. Thus, this study suggests that zinc supplemented with a histidine/proline complex may have beneficial effects on neurogenesis in patients experiencing the early phase of Type 1 diabetes.

Strontium ranelate causes osteophytes overgrowth in a model of early phase osteoarthritis

OpenAIRE

Chu, Jian-Guo; Dai, Mu-Wei; Wang, Yu; Tian, Fa-Ming; Song, Hui-Ping; Xiao, Ya-Ping; Shao, Li-Tao; Zhang, Ying-Ze; Zhang, Liu

2017-01-01

Background Osteoarthritis (OA) involves cartilage changes as well as modifications of subchondral bone and synovial tissues. Strontium ranelate (SR), an anti-osteoporosis compound, which is currently in phase III clinical trial for treatment of OA. Evidences suggest that SR preferably deposited in osteophyte, other than in subchondral bone in early phase of OA. This phenomenon raises concern about its utility for OA treatment as a disease-modifying drug. To evaluate the effect of SR on cartil...

Imaging in early phase childhood cancer trials

International Nuclear Information System (INIS)

Adamson, Peter C.

2009-01-01

Advances made in the treatment of childhood malignancies during the last four decades have resulted in overall cure rates of approximately 80%, but progress has slowed significantly during the last 10 years, underscoring the need for more effective and less toxic agents. Current research is focused on development of molecularly targeted agents, an era ushered in with the discovery of imatinib mesylate for the treatment of chronic myelogenous leukemia. Since imatinib's introduction into the clinic, an increasing number of tyrosine kinase inhibitors have been developed and entered into clinical trials and practice. Parallel to the initial advances made in molecularly targeted agents has been the development of a spectrum of novel imaging modalities. Future goals for imaging in childhood cancer research thus include (1) patient identification based on target identification or other biologic characteristics of the tumor, (2) assessing pharmacokinetic-pharmacodynamic (PK-PD) effects, and (3) predictive value with an early indication of patient benefit. Development and application of novel imaging modalities for children with cancer can serve to streamline development of molecularly targeted agents. (orig.)

Paranasal Manifestations of Early Stage Chronic Lymphocytic Leukemia

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Ceren Günel

2015-04-01

Full Text Available OBJECTIVE: Chronic lymphocytic leukemia (CLL is the most common adult leukemia. A few studies have been reported about the relationship between CLL and paranasal sinuses. We aimed to investigate the paranasal manifestations of CLL and to determine the expression of nuclear factor-ĸB (NF-kB and tumor necrosis factor (TNF-α in the nasal mucosa in patients with CLL. MATERIALS AND METHODS: This study was a clinical trial that involved 40 patients. Group CLL (n=20 consisted of patients with early-stage CLL who were followed-up at the hematology clinic and who did not receive any treatment. The control group (n=20 consisted of patients who had undergone concha surgery because of nasal obstruction. Paranasal sinus computer tomography scans of all patients were taken, they were scored on the basis of the Lund–Mackay system, and sinusitis findings were recorded. The biopsy material taken from the inferior concha head of all patients was immunohistochemically stained with primary antibodies against NF-kB and TNF-α. RESULTS: There were no statistically significant differences between the two groups with respect to NF-κB (p=0.716 and TNF-α staining scores (p=1.000. The Lund–Mackay scores were significantly higher in the CLL group than in the control group (p=0.004. Fourteen patients had sinusitis at different locations, while the most common diagnosis was maxillary sinusitis (n=8 in the CLL group. CONCLUSION: This study showed that patients with early-stage CLL tend to have rhinosinusitis. However, NF-kB and TNF-α may not have a role in the inflammatory process involving the paranasal sinuses in patients with CLL.

Early assisted discharge with generic community nursing for chronic obstructive pulmonary disease exacerbations: Results of a randomised controlled trial

NARCIS (Netherlands)

C.M.A. Utens (Cecile); L.M.A. Goossens (Lucas); F.W.J.M. Smeenk (Frank); M.P.M.H. Rutten-van Mölken (Maureen); M. van Vliet (Monique); M.W. Braken (Maria); L. van Eijsden (Loes); O.C.P. Schayck (Onno)

2012-01-01

textabstractObjectives: To determine the effectiveness of early assisted discharge for chronic obstructive pulmonary disease (COPD) exacerbations, with home care provided by generic community nurses, compared with usual hospital care. Design: Prospective, randomised controlled and multicentre trial

Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

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Cui Zhi-Hua

2012-03-01

Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

Hemorrhagic intra splenic pseudocyst as a complication of chronic pancreatitis in acute phase - a case report

International Nuclear Information System (INIS)

Almeida, Fabiola Assuncao de; Marchiori, Edson; Mello, Walter de Assis; Nogueira, Aline Silva; Sales, Anderson Ribeiro; Martins, Renata Romano; Santos, Tereza Cristina C.R.S. dos

1999-01-01

The authors report a case of hemorrhagic intra splenic pseudocyst as a complication of chronic pancreatitis in acute phase. A 43-year-old woman, chronic alcoholic, who had pancreatitis 5 years ago, with symptoms of strong abdominal pain in the epigastrium, nausea and fever. Abdominal sonography showed a lesion contiguous to the spleen and computed tomography demonstrated an heterogeneous lesion of not well defined limits, in the lateral and posterior parts of the spleen. The patient was submitted to Roux-Y cystojejunostomy, he does not present any symptoms at the moment, and is undergoing clinical control. (author)

Treatment of chronic myelogenous leukemia with interleukin-2: a phase II study in 21 patients.

Science.gov (United States)

Vey, N; Blaise, D; Lafage, M; Olive, D; Viens, P; Baume, D; Camerlo, J; Stoppa, A M; Gabus, R; Brandely, M; Hercend, T; Maraninchi, D

1999-03-01

We designed a phase II study to assess the activity of recombinant interleukin-2 (rIL-2) in patients with chronic myelogenous leukemia (CML). Study population included 11 patients in the chronic phase of CML (6 in hematologic remission and 5 with active disease), 6 patients in the accelerated phase, and 4 in blastic phase of CML. Patients received three 5-day cycles administrated every other week. rIL-2 was given as intravenous bolus infusions of 8 x 10(6) IU/m2 three times a day during cycle 1 and twice a day during cycles 2 and 3. Response to rIL-2 was assessed on day 45. No hematologic response was achieved in the patients with evaluable disease. One patient in hematologic remission with rIL-2 achieved a major response (from 72% to 9% Ph+ metaphases), and two patients had some degree of reduction of Ph+ metaphases. Responses were short-lived (< 6 months), but two of these three patients achieved a new cytogenetic response with interferon given post-rIL-2. A significant immune activation was achieved with rIL-2 including a marked increase in CD3+/CD25+ cells, CD56+ cells, and in natural killer/lymphokine activated killer cell cytotoxic activity. These results confirm preclinical studies, which showed that IL-2 has antileukemic activity in CML. However, the responses observed were short lived and restricted to a subgroup of patients with low disease burden. This invites further studies testing its impact in situations of minimal disease or in combination with other cytokines.

The role of ambiguity and discrepancy in the early phases of innovation

DEFF Research Database (Denmark)

Laursen, Linda Nhu; Tollestrup, Christian H. T.

2015-01-01

Innovation literature mainly focuses on eliminating ambiguity and discrepancy from the early phases of innovation. This study questions this implicit assumption, as it may provide an oversimplified view on, how to attain proficiency. Instead of narrowly focusing on reducing ambiguity and discrepa...

Liver CT for vascular mapping during radioembolisation workup: comparison of an early and late arterial phase protocol

Energy Technology Data Exchange (ETDEWEB)

Hoven, Andor F. van den; Braat, Manon N.G.J.A.; Prince, Jip F.; Doormaal, Pieter J. van; Leeuwen, Maarten S. van; Lam, Marnix G.E.H.; Bosch, Maurice A.A.J. van den [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands)

2017-01-15

To compare right gastric (RGA) and segment 4 artery (A4) origin detection rates during radioembolisation workup between early and late arterial phase liver CT protocols. 100 consecutive patients who underwent liver CT between May 2012-January 2015 with early or late arterial phase protocol (n = 50 each, 10- vs. 20-s post-threshold delay) were included. RGA/A4 origin detection rates, assessed by two raters, and contrast-to-noise ratio (CNR) of the hepatic artery relative to the portal vein were compared between the protocols. The first-second rater scored the RGA origin as visible in 58-65 % (specific proportion of agreement 82 %, κ = 0.62); A4 origin in 96-89 % (94 %, κ = 0.54). Thirty-six percent of RGA origins not detectable by DSA were identified on CT. Origin detection rates were not significantly different for early/late arterial phases. Mean CNR was higher in the early arterial phase protocol (1.7 vs. 1.2, p < 0.001). A 10-s delay arterial phase CT protocol does not significantly improve detection of small intra- and extrahepatic branches. RGA origin detection requires further optimization, whereas A4/MHA origin detection is adequate, with good inter-rater reproducibility. CT remains important for preprocedural planning, because it may reveal arterial anatomy not discernible on DSA. (orig.)

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study

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Erick Huarcaya

2011-06-01

Full Text Available Human Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre- and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4+ and CD8+ T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-γ and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models.

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study.

Science.gov (United States)

Huarcaya, Erick; Best, Ivan; Rodriguez-Tafur, Juan; Maguiña, Ciro; Solórzano, Nelson; Menacho, Julio; Lopez De Guimaraes, Douglas; Chauca, Jose; Ventosilla, Palmira

2011-01-01

Human Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre- and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4(+) and CD8(+) T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-γ and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models.

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease

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Ewelina Łukaszyk

2015-06-01

Full Text Available Background/Aims: One of the most common causes of anemia of chronic disease (ACD is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. Methods: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP, creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6, hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR, growth differentiation factor-15 (GDF-15 and zonulin. Results: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. Conclusion: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency.

Early diagnosis of the Spondyloarthropathies

International Nuclear Information System (INIS)

Gonzalez Naranjo, Luis Alonso; Londono, John D; Valle, Rafael Raul

2005-01-01

Spondyloarthropathies are a cluster of chronic inflammatory diseases that primarily include ankylosing spondylitis, reactive arthritis, psoriatic arthritis; arthritis associated with inflammatory bowel diseases and undifferentiated spondyloarthropathies. The most common subgroups of spondyloarthropathies are ankylosing spondylitis and undifferentiated spondyloarthropathy. The diagnosis of ankylosing spondylitis is mainly based on unequivocal radiographic sacroiliitis of at least grade 2 bilaterally or grade 3 unilaterally. How ever, in the early phase of disease, conventional radiographs are often too insensitive to show sacroiliitis and it usually takes several years for definite radiographic sacroiliitis to evolve. Thus, the diagnosis of ankylosing spondylitis is a commonly delayed by 8 to 11 years after the onset of symptoms. As a result, diagnosing axial spondyloarthropathy in the absence of radiographic sacroiliitis is very difficult to rheumatologists. In the early phase of disease, HLA B27 test and magnetic resonance imaging of sacroiliac joints may be helpful to the early diagnosis. In the presence of chronic low back pain the probability of axial spondyloarthropathy is about 5% and is about 14% if the back pain is inflammatory. The presence of = 3 features of spondyloarthropathy (heel pain, uveitis, dactylitis, positive family history, alternating buttock pain, psoriasis, inflammatory bowel disease, asymmetrical arthritis, positive response to anti-inflammatory drugs) increase the probability of axial spondyloarthropathy to 90%. Both, the positive HLA B27 and magnetic resonance imaging with signs of sacroiliitis increase the probability of spondyloarthropathy, particularly in patients without spondyloarthropathies features or with only 1 or 2 features. Since ankylosing spondylitis in association with psoriasis and inflammatory bowel disease is often HLA B27 negative, this test is of limited value under theses circumstances. Is important to consider that

Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study

Science.gov (United States)

Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

2012-01-01

Background Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. Aim To explore processes underpinning the implementation of CKD management in primary care. Design and setting Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Method Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. Results A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Conclusion Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity. PMID:22520910

Early mortality estimates for different nuclear accidents. Final Phase I report, October 1977-April 1979

Energy Technology Data Exchange (ETDEWEB)

Hahn, F.F.

1979-08-01

Several studies have previously been made of the number of early deaths which might be expected in a population exposed to a cloud of radionuclides which could result from a nuclear accident. These analyses, however, have been limited to one accident scenario or to exposures involving limited numbers of radionuclides. The purpose of this Phase I study was to examine the existing data on the early health effects of inhaled radioactive materials and determined what, if any, new studies were needed to make reasonable estimates of early mortality after exposure of a population to a cloud of radionuclides of any type. The approach used in the Phase I project was to analyze the data bases available on the health effects of inhaled radioactive materials and document those which were adequate and useful. Using these data, a computer based simulation model was developed depicting exposure to a radioactive aerosol, the dose to an individual exposed to the aerosol and the probability of dying from early effects.

Early mortality estimates for different nuclear accidents. Final Phase I report, October 1977-April 1979

International Nuclear Information System (INIS)

Hahn, F.F.

1979-08-01

Several studies have previously been made of the number of early deaths which might be expected in a population exposed to a cloud of radionuclides which could result from a nuclear accident. These analyses, however, have been limited to one accident scenario or to exposures involving limited numbers of radionuclides. The purpose of this Phase I study was to examine the existing data on the early health effects of inhaled radioactive materials and determined what, if any, new studies were needed to make reasonable estimates of early mortality after exposure of a population to a cloud of radionuclides of any type. The approach used in the Phase I project was to analyze the data bases available on the health effects of inhaled radioactive materials and document those which were adequate and useful. Using these data, a computer based simulation model was developed depicting exposure to a radioactive aerosol, the dose to an individual exposed to the aerosol and the probability of dying from early effects

Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): Design and rationale of a randomized trial

NARCIS (Netherlands)

U. Ahmed Ali (Usama); Y. Issa (Yama); M.J. Bruno (Marco); H. van Goor (Harry); H.C. van Santvoort (Hjalmar); O.R.C. Busch (Olivier); C.H. Dejong (Cees); V.B. Nieuwenhuijs (Vincent); C.H.J. van Eijck (Casper); H.M. van Dullemen (Hendrik); P. Fockens (Paul); P.D. Siersema (Peter); D.J. Gouma (Dirk); J.E. van Hooft (Jeanin); Y. Keulemans (Yolande); J.-W. Poley (Jan-Werner); R. Timmer (Robin); M.G. Besselink (Marc); F.P. Vleggaar (Frank); O.H. Wilder-Smith (O.); H.G. Gooszen (Hein); M.G.W. Dijkgraaf (Marcel); M.A. Boermeester (Marja)

2013-01-01

textabstractBackground: In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits

78 FR 5816 - Guidance for Industry on Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical...

Science.gov (United States)

2013-01-28

.... The guidance provides recommendations on when and how genomic principles should be considered and... recommendations on when and how genomic principles should be considered and applied in early-phase clinical... the larger, later adequate, and well-controlled trials (phase 3) that are needed to support marketing...

Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE) : design and rationale of a randomized trial

NARCIS (Netherlands)

Ali, Usama Ahmed; Issa, Yama; Bruno, Marco J.; van Goor, Harry; van Santvoort, Hjalmar; Busch, Olivier R. C.; Dejong, Cornelis H. C.; Nieuwenhuijs, Vincent B.; van Eijck, Casper H.; van Dullemen, Hendrik M.; Fockens, Paul; Siersema, Peter D.; Gouma, Dirk J.; van Hooft, Jeanin E.; Keulemans, Yolande; Poley, Jan W.; Timmer, Robin; Besselink, Marc G.; Vleggaar, Frank P.; Wilder-Smith, Oliver H.; Gooszen, Hein G.; Dijkgraaf, Marcel G. W.; Boermeester, Marja A.

2013-01-01

Background: In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in

Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial

NARCIS (Netherlands)

Ahmed Ali, U.; Issa, Y.; Bruno, M.J.; Goor, H. van; Santvoort, H.C. van; Busch, O.R.; Dejong, C.H.; Nieuwenhuijs, V.B.; Eijck, C.H. van; Dullemen, H.M. van; Fockens, P.; Siersema, P.D.; Gouma, D.J.; Hooft, J.E. van; Keulemans, Y.; Poley, J.W.; Timmer, R.; Besselink, M.G.; Vleggaar, F.P.; Wilder-Smith, O.H.G.; Gooszen, H.G.; Dijkgraaf, M.G.; Boermeester, M.A.; et al.,

2013-01-01

BACKGROUND: In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in

Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib

Science.gov (United States)

Hochhaus, Andreas; le Coutre, Philipp D.; Rosti, Gianantonio; Pinilla-Ibarz, Javier; Jabbour, Elias; Gillis, Kathryn; Woodman, Richard C.; Blakesley, Rick E.; Giles, Francis J.; Kantarjian, Hagop M.; Baccarani, Michele

2011-01-01

Nilotinib has significant efficacy in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and in patients with CML-CP or CML in accelerated phase (CML-AP) after imatinib failure. We investigated the occurrence of cross-intolerance to nilotinib in imatinib-intolerant patients with CML. Only 1/75 (1%) patients with nonhematologic imatinib intolerance experienced a similar grade 3/4 adverse event (AE), and 3/75 (4%) experienced a similar persistent grade 2 nonhematologic AE on nilotinib. Only 7/40 (18%) patients with hematologic imatinib intolerance discontinued nilotinib, all because of grade 3/4 thrombocytopenia. Ninety percent of imatinib-intolerant patients with CML-CP who did not have complete hematologic response (CHR) at baseline (n = 52) achieved CHR on nilotinib. Nilotinib induced a major cytogenetic response in 66% and 41% of patients with imatinib-intolerant CML-CP and CML-AP (complete cytogenetic response in 51% and 30%), respectively. Minimal cross-intolerance was confirmed in patients with imatinib-intolerant CML. The favorable tolerability of nilotinib in patients with imatinib intolerance leads to alleviation of AE-related symptoms and significant and durable responses. In addition to its established clinical benefit in patients with newly diagnosed CML and those resistant to imatinib, nilotinib is effective and well-tolerated for long-term use in patients with imatinib intolerance. This study is registered at http://www.clinicaltrials.gov as NCT00471497 PMID:21467546

Comparison of parasite loads in serum and blood samples from patients in acute and chronic phases of Chagas disease.

Science.gov (United States)

Hernández, Carolina; Teherán, Aníbal; Flórez, Carolina; Ramírez, Juan David

2018-04-17

Molecular methods have been developed for the detection and quantification of Trypanosoma cruzi DNA in blood samples from patients with Chagas disease. However, aspects of sample processing necessary for quantitative real-time PCR (qPCR), such as the addition of guanidine hydrochloride to whole blood samples, may limit timely access to molecular diagnosis. We analysed 169 samples from serum and guanidine-EDTA blood (GEB) obtained from patients in acute and chronic phases of Chagas disease. We applied qPCR targeted to the satellite DNA region. Finally, we compared the parasite loads and cycle of threshold values of the qPCR. The results confirmed the usefulness of serum samples for the detection and quantification of parasite DNA in patients with Chagas disease, especially in the acute phase. However, the parasite loads detected in serum samples from patients in the chronic phase were lower than those detected in GEB samples. The epidemiological implications of the findings are herein discussed.

Production of Vibrio vulnificus metalloprotease VvpE begins during the early growth phase: usefulness of gelatin-zymography.

Science.gov (United States)

Kim, Choon-Mee; Kang, Sang-Mee; Jeon, Ho-Jong; Shin, Sung-Heui

2007-07-01

Recent studies have demonstrated that expression of the vvpE gene begins during the early growth phase albeit at low levels. However, we found that the traditional protease assay method that is used to measure caseinolytic activity in culture supernatants is not suitable for the measurement of extracellular VvpE that is produced at low levels during the early growth phase. By using gelatin-zymography in place of the protease assay, we could specifically detect only VvpE of several proteases produced by Vibrio vulnificus. Moreover, we could sensitively measure VvpE produced at low levels during the early growth phase, which was consistent with transcription of the vvpE gene. The extracellular production of VvpE was reduced or delayed by mutation of the pilD gene which encodes for the type IV leader peptidase/N-methyltransferase associated with the type II general secretion system; the delayed production of VvpE was recovered by in trans complementation of the wild-type pilD gene. These results indicate that VvpE begins to be produced during the early growth phase via the PilD-mediated type II general secretion system, and that the use of gelatin-zymography is recommended as a simple method for the sensitive and specific detection of VvpE production.

Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial

NARCIS (Netherlands)

Ahmed Ali, Usama; Issa, Yama; Bruno, Marco J.; van Goor, Harry; van Santvoort, Hjalmar; Busch, Olivier R. C.; Dejong, Cornelis H. C.; Nieuwenhuijs, Vincent B.; van Eijck, Casper H.; van Dullemen, Hendrik M.; Fockens, Paul; Siersema, Peter D.; Gouma, Dirk J.; van Hooft, Jeanin E.; Keulemans, Yolande; Poley, Jan W.; Timmer, Robin; Besselink, Marc G.; Vleggaar, Frank P.; Wilder-Smith, Oliver H.; Gooszen, Hein G.; Dijkgraaf, Marcel G. W.; Boermeester, Marja A.

2013-01-01

In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in terms of better

How does early maternal separation and chronic stress in adult rats affect the immunoreactivity of serotonergic neurons within the dorsal raphe nucleus?

Science.gov (United States)

Pollano, Antonella; Trujillo, Verónica; Suárez, Marta M

2018-01-01

Vulnerability to emotional disorders like depression derives from interactions between early and late environments, including stressful conditions. The serotonin (5HT) system is strongly affected by stress and chronic unpredictable stress can alter the 5HT system. We evaluated the distribution of active serotonergic neurons in the dorsal raphe nucleus (DR) through immunohistochemistry in maternally separated and chronically stressed rats treated with an antidepressant, tianeptine, whose mechanism of action is still under review. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50-74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle. We found an interaction between the effects of MS and chronic unpredictable stress on Fos-5HT immunoreactive cells at mid-caudal level of the DR. MS-chronically stressed rats showed an increase of Fos-5HT immunoreactive cells compared with AFR-chronically stressed rats. The ventrolateral (DRL/VLPAG) and dorsal (DRD) subdivisions of the DR were significantly more active than the ventral part (DRV). At the rostral level of the DR, tianeptine decreased the number of Fos-5HT cells in DR in the AFR groups, both unstressed and stressed. Overall, our results support the idea of a match in phenotype exhibited when the early and the adult environment correspond.

Evaluation of early phase nuclear accident clean-up procedures for Nordic residential areas

International Nuclear Information System (INIS)

Andersson, K.G.

1996-12-01

The work reported was carried out as a part of the EKO-5 project under the framework of the Nordic co-operative NKS programme. The project is aimed at giving guidelines relating to Nordic conditions for the reduction of external doses in the early phase of a major accidental airborne nuclear contamination (essentially with 137 Cs) situation in urban areas. The material in this report describes the expected effects, in terms of immediate dose rate reduction and of reduction of the integrated doses over 70 years, of implementation of the methods which were considered to be feasible for early phase treatment of contaminated urban surfaces. Also given are estimates of the integrated doses if no action were taken. The given estimates were based on the experience obtained through large amounts of in situ measurements on different types of surface, mainly since the Chernobyl accident in 1986. The computer model URGENT, was used to apply the information on the migration of the radioactive material with time, together with the results of Monte Carlo photon transport calculations, for the time-integrated dose estimates. 66 data sheets describe the beneficial effects, costs and disadvantages of application of a feasible method for cleaning in the early phase of a specific type of surface in one of five different urban or suburban environments. These data form the foundation for the recommendations on guidelines, which are the ultimate goal of the EKO-5 project. References are given to recommended supplementary reading. (EG)

Information about robustness, reliability and safety in early design phases

DEFF Research Database (Denmark)

Marini, Vinicius Kaster

methods, and an industrial case to assess how the use of information about robustness, reliability and safety as practised by current methods influences concept development. Current methods cannot be used in early design phases due to their dependence on detailed design information for the identification...... alternatives. This prompts designers to reuse working principles that are inherently flawed, as they are liable to disturbances, failures and hazards. To address this issue, an approach based upon individual records of early design issues consists of comparing failures and benefits from prior working...... principles, before making a decision, and improving the more suitable alternatives through this feedback. Workshops were conducted with design practitioners to evaluate the potential of the approach and to simulate decision-making and gain feedback on a proof-of-concept basis. The evaluation has demonstrated...

Tradeoff analysis for Dependable Real-Time Embedded Systems during the Early Design Phases

DEFF Research Database (Denmark)

Gan, Junhe

Embedded systems are becoming increasingly complex and have tight competing constraints in terms of performance, cost, energy consumption, dependability, flexibility, security, etc. The objective of this thesis is to propose design methods and tools for supporting the tradeoff analysis of competing...... to processing elements, as well as the processor voltage and frequency levels for executing each task, such that transient faults are tolerated, the real-time constraints of the application are satisfied, and the energy consumed is minimized. In this thesis, we target the early design phases, when decisions...... have a high impact on the subsequent implementation choices. However, due to a lack of information, the early design phases are characterized by uncertainties, e.g., in the worst-case execution times (WCETs), in the functionality requirements, or in the hardware component costs. In this context, we...

Changes in cerebral blood flow and psychometric indicators in veterans with early forms of chronic brain ischemia

Directory of Open Access Journals (Sweden)

Vasilenko Т.М.

2015-09-01

Full Text Available The goal is to study the cerebral blood flow and psychometric characteristics in veterans of Afghanistan with early forms of chronic brain ischemia. Material and Methods. The study included 74 veterans of the Afghan war aged from 45 to 55 years: group 1, 28 people with NPNKM; Group 2-28 patients with circulatory encephalopathy stage 1; group 3-18 healthy persons. Doppler examination of cerebral vessels was carried out on the unit «Smart-lite». Reactive and personal anxiety of patients was assessed using the scale of Spielberger, evaluation of the quality of life through the test SAN. Determining the level of neuroticism and psychoticism was conducted by the scale of neuroticism and psy-choticism. Results: The study of cerebral blood flow in the Afghan war veterans showed signs of insolvency of carotid and carotid-basilar anastomoses, hypoperfusion phenomenon with the depletion of autoregulation, violation of the outflow of venous blood at the level of the microvasculature, accompanied by cerebral arteries spasm. More than 40% of patients with early forms of chronic brain ischemia had high personal anxiety, low levels of well-being and activity, with maximum expression of dyscirculatory hypoxia. Conclusion. Readaptation of veterans of Afghanistan is accompanied by the changes in psychometric performance and the formation of the earliest forms of brain chronic ischemia associated with inadequate hemodynamics providing increased functional activity of the brain and the inefficiency of compensatory-adaptive reactions.

The cost of the nuclear energy-turnaround. An early nuclear phase-out and its consequences

International Nuclear Information System (INIS)

Baran, Metin

2013-01-01

The booklet on the consequences of an early nuclear phase-out includes a description of the value creation strategy in the electricity market and the basic relations of the electricity price formation and a survey and evaluation of selected studies. The analysis was performed for the following studies: Energy policy scenarios for a nuclear phase-out in Germany; Economic consequences of a nuclear phase-out in Germany; Transformation of the electricity production systems with a forced nuclear phase-out - a contribution on sustainable energy systems following the reactor accident of Fukushima; Cost of a nuclear phase-out until 2022 in Germany and Bavaria.

Integrating Pharmacoproteomics into Early-Phase Clinical Development: State-of-the-Art, Challenges, and Recommendations

Directory of Open Access Journals (Sweden)

Savita Nandal

2017-02-01

Full Text Available Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating. We review the history, technologies, current usage, challenges, and potential for future use, and conclude with recommendations for integration of pharmacoproteomic in early-phase drug development.

Proteomics portrait of archival lesions of chronic pancreatitis.

Directory of Open Access Journals (Sweden)

Sheng Pan

Full Text Available Chronic pancreatitis is a chronic inflammatory disorder of the pancreas. The etiology is multi-fold, but all lead to progressive scarring and loss of pancreatic function. Early diagnosis is difficult; and the understanding of the molecular events that underlie this progressive disease is limited. In this study, we investigated differential proteins associated with mild and severe chronic pancreatitis in comparison with normal pancreas and pancreatic cancer. Paraffin-embedded formalin-fixed tissues from five well-characterized specimens each of normal pancreas (NL, mild chronic pancreatitis (MCP, severe chronic pancreatitis (SCP and pancreatic ductal adenocarcinoma (PDAC were subjected to proteomic analysis using a "label-free" comparative approach. Our results show that the numbers of differential proteins increase substantially with the disease severity, from mild to severe chronic pancreatitis, while the number of dysregulated proteins is highest in pancreatic adenocarcinoma. Important functional groups and biological processes associated with chronic pancreatitis and cancer include acinar cell secretory proteins, pancreatic fibrosis/stellate cell activation, glycoproteins, and inflammatory proteins. Three differential proteins were selected for verification by immunohistochemistry, including collagen 14A1, lumican and versican. Further canonical pathway analysis revealed that acute phase response signal, prothrombin activation pathway, and pancreatic fibrosis/pancreatic stellate cell activation pathway were the most significant pathways involved in chronic pancreatitis, while pathways relating to metabolism were the most significant pathways in pancreatic adenocarcinoma. Our study reveals a group of differentially expressed proteins and the related pathways that may shed light on the pathogenesis of chronic pancreatitis and the common molecular events associated with chronic pancreatitis and pancreatic adenocarcinoma.

Early and late radiation response of human skin following chronic exposure of the hands

International Nuclear Information System (INIS)

Lenz, U.; Arndt, D.; Thormann, T.

1979-01-01

Clinical examinations on 45 radiation workers with chronical low-level exposures to their hands revealed that accumulated doses in the range of 15 to 30 Sv (1500 to 3000 rem) may already produce macroscopically unconspicuous early alterations of the vessel system within the corium as well as epidermal hyperplasia. Therefore, the annual permissible dose equivalent of 0.75 Sv (75 rem) recommended by ICRP for the skin of the extremities appears unjustifiably high and should be reduced to 0.30 Sv (30 rem), the limit valid for the remaining areas of skin. (author)

EVALUATION OF SYMMETRIC DIMETHYLARGININE AS AN EARLY BIOMARKER OF CHRONIC KIDNEY DISEASE IN CAPTIVE CHEETAHS (ACINONYX JUBATUS).

Science.gov (United States)

Lamglait, Benjamin; Vandenbunder-Beltrame, Marielle

2017-09-01

Symmetric dimethylarginine (SDMA) has been shown to be a valuable biomarker for early detection of chronic kidney disease (CKD) in canine and feline patients. Recognition of early (subclinical) kidney disease would be of value in cheetahs (Acinonyx jubatus) as prevalence of CKD is relatively high in this species in captivity. Fifty-eight banked serum and plasma samples from seven adult cheetahs that died of CKD were analyzed for creatinine, urea, and SDMA. A marked increase in SDMA was noted on five of the tested cheetahs earlier than the rise of serum creatinine and urea (estimated 8-35 mo; mean 21.4 mo; median 22 mo). SDMA appears as an early biomarker to evaluate renal function for the diagnosis of CKD in cheetahs regardless of the cause of this disease.

Impaired early visual response modulations to spatial information in chronic schizophrenia

Science.gov (United States)

Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

2011-01-01

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model*.

Science.gov (United States)

Nardini, Stefano; Annesi-Maesano, Isabella; Del Donno, Mario; Delucchi, Maurizio; Bettoncelli, Germano; Lamberti, Vincenzo; Patera, Carlo; Polverino, Mario; Russo, Antonio; Santoriello, Carlo; Soverina, Patrizio

2014-01-01

Respiratory diseases in Italy already now represent an emergency (they are the 3(rd) ranking cause of death in the world, and the 2(nd) if Lung cancer is included). In countries similar to our own, they result as the principal cause for a visit to the general practitioner (GP) and the second main cause after injury for recourse to Emergency Care. Their frequency is probably higher than estimated (given that respiratory diseases are currently underdiagnosed). The trend is towards a further increase due to epidemiologic and demographic factors (foremost amongst which are the widespread diffusion of cigarette smoking, the increasing mean age of the general population, immigration, and pollution). Within the more general problem of chronic disease care, chronic respiratory diseases (CRDs) constitute one of the four national priorities in that they represent an important burden for society in terms of mortality, invalidity, and direct healthcare costs. The strategy suggested by the World Health Organization (WHO) is an integrated approach consisting of three goals: inform about health, reduce risk exposure, improve patient care. The three goals are translated into practice in the three areas of prevention (1-primary, 2-secondary, 3-tertiary) as: 1) actions of primary (universal) prevention targeted at the general population with the aim to control the causes of disease, and actions of Predictive Medicine - again addressing the general population but aimed at measuring the individual's risk for disease insurgence; 2) actions of early diagnosis targeted at groups or - more precisely - subgroups identified as at risk; 3) continuous improvement and integration of care and rehabilitation support - destined at the greatest possible number of patients, at all stages of disease severity. In Italy, COPD care is generally still inadequate. Existing guidelines, institutional and non-institutional, are inadequately implemented: the international guidelines are not always adaptable

Chronicity of Anterior Cruciate Ligament Deficiency, Part 2: Radiographic Predictors of Early Graft Failure.

Science.gov (United States)

Tanaka, Yoshinari; Kita, Keisuke; Takao, Rikio; Amano, Hiroshi; Uchida, Ryohei; Shiozaki, Yoshiki; Yonetani, Yasukazu; Kinugasa, Kazutaka; Mae, Tatsuo; Horibe, Shuji

2018-02-01

Accumulating evidence suggests that long-term anterior cruciate ligament (ACL) deficiency can give rise to an abnormal tibiofemoral relationship and subsequent intra-articular lesions. However, the effects of chronic ACL deficiency (ACLD) on early graft failure after anatomic reconstruction remain unclear. We hypothesized that patients with long-term ACLD lasting more than 5 years would have a greater rate of early graft failure due to insufficient intraoperative reduction of the tibia and that the preoperative and immediately postoperative abnormal tibiofemoral relationship in the sagittal plane, such as anterior tibial subluxation (ATS), would correlate with the graft status on postoperative magnetic resonance imaging (MRI). Cohort study; Level of evidence, 3. A total of 358 patients who had undergone anatomic ACL reconstruction with hamstring grafts were divided into 5 groups based on chronicity of ACLD: (1) 0 to 6 months, (2) 6 months to 1 year, (3) 1 to 2 years, (4) 2 to 5 years, and (5) longer than 5 years. Preoperatively and immediately postoperatively, lateral radiographs in full extension were taken in all patients to evaluate the tibiofemoral relationship, specifically with regard to ATS, space for the ACL (sACL), and extension angle. All patients underwent MRI at 6 months to reveal graft status. Groups with a high rate of graft failure were further analyzed to compare demographic and radiographic factors between the intact and failure subgroups, followed by multivariate logistic regression analysis to identify predisposing factors. Graft failure without trauma was observed in 4 (1.8%), 0 (0%), 1 (3.7%), 3 (9.7%), and 8 patients (17.7%) in groups 1, 2, 3, 4, and 5, respectively. Of the 76 patients in groups 4 and 5, significant differences were noted between the failure and intact subgroups in preoperative ATS (4.9 vs 2.4 mm, respectively; P failure (odds ratio, 3.2; 95% CI, 1.37-7.46). Early graft failure at 6 months increased in patients with ACLD

PP22. PROGRESSING RADIOTHERAPY-DRUG COMBINATIONS TOWARDS EARLY PHASE CLINICAL TRIALS

Science.gov (United States)

Jones, Dr Hazel; Stock, Dr Julie; Chalmers, Prof Anthony

2017-01-01

Abstract The Radiotherapy-Drug Combinations consortium (RaDCom) works with UK-based investigators to design and deliver high quality preclinical projects evaluating specific radiotherapy-drug combinations. We have several collaborations with industry, from in vitro projects to understand the novel agent in the context of radiobiology, through to preclinical studies that will generate data to support the development of radiotherapy combination trials. RaDCom facilitates the coordination of industry interactions, triage new proposals, monitor active projects, and engages with the radiotherapy community to promote collaboration and networking (via a capability map). The CRUK New Agents Committee Preclinical Combination Grant scheme provides one of the funding options for these studies, with the potential to feed into early phase clinical trials via the ECMC Combinations Alliance. RaDCom also supports broader radiotherapy research initiatives, by working to improve preclinical quality assurance and identifying a route to registration for radiotherapy-drug treatments. These activities will place the UK at the forefront of radiotherapy-drug preclinical research and provide a significant incentive for pharmaceutical companies to invest in this area and utilise the RaDCom network. Further information can be found on our webpage: http://ctrad.ncri.org.uk/research-support/radiation-drug-combinations-radcom Successful projects from RaDCom can then move into early phase combinations trials within the Combinations Alliance. The Combinations Alliance supports early phase combination studies in the UK via the ECMC (Experimental Cancer Medicine Centres) network. It focuses on translational research, and enables clinical project teams to work with disease experts to set up investigator led trials. The CRUK Centre of Drug Development (CDD) supports these studies with further management and coordination ensuring more robust timelines and delivery. The Combinations Alliance framework

Beyond the "First Hit": Marked Inhibition by N-Acetyl Cysteine of Chronic Ethanol Intake But Not of Early Ethanol Intake. Parallel Effects on Ethanol-Induced Saccharin Motivation.

Science.gov (United States)

Quintanilla, María Elena; Rivera-Meza, Mario; Berríos-Cárcamo, Pablo; Salinas-Luypaert, Catalina; Herrera-Marschitz, Mario; Israel, Yedy

2016-05-01

A number of studies have shown that acetaldehyde synthesized in the brain is necessary to induce ethanol (EtOH) reinforcement in naïve animals (acquisition phase). However, after chronic intake is achieved (maintenance phase), EtOH intake becomes independent of acetaldehyde generation or its levels. Glutamate has been reported to be associated with the maintenance of chronic EtOH intake. The levels of brain extracellular glutamate are modulated by 2 glial processes: glutamate reabsorption via an Na(+) -glutamate transporter (GLT1) and a cystine-glutamate exchanger. Chronic EtOH intake lowers GLT1 levels and increases extracellular glutamate. The administration of N-acetyl cysteine (NAC), a precursor of cystine, has been shown to reduce the relapse of several drugs of abuse, while NAC has not been tested on chronic EtOH intake or on EtOH's influence on the motivation for another drug. These were investigated in the present study. (i) Rats bred for their high EtOH intake were allowed access to 10% EtOH and water up to 87 days. NAC was administered (30 and 60 mg/kg daily, intraperitoneally) for 14 consecutive days, either during the acquisition phase or the maintenance phase of EtOH drinking. (ii) In additional experiments, rats were allowed EtOH (10%) and water access for 61 days, after which EtOH was replaced by saccharin (0.3%) to determine both if chronic EtOH consumption influences saccharin intake and whether NAC modifies the post chronic EtOH saccharin intake. NAC did not influence the acquisition ("first hit") of chronic EtOH intake, but greatly inhibited (60 to 70%; p intake when NAC was administered to animals that were consuming EtOH chronically. NAC did not influence saccharin intake in naïve animals. In animals that had consumed EtOH chronically and were thereafter offered a saccharin solution (0.3%), saccharin intake increased over 100% versus that of EtOH-untreated animals, an effect that was fully suppressed by NAC. N-acetyl cysteine, a drug

Early endocrine alterations reflect prolonged stress and relate to one year functional outcome in patients with severe brain injury

DEFF Research Database (Denmark)

Marina, Djordje; Klose, Marianne; Nordenbo, Annette

2015-01-01

OBJECTIVE: Severe brain injury poses a risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective was to assess the pattern and prevalence...

Differential Efficacy of Ketamine in the Acute versus Chronic Stages of Complex Regional Pain Syndrome in Mice

Science.gov (United States)

Tajerian, Maral; Leu, David; Yang, Phillip; Huang, Ting Ting; Kingery, Wade S; Clark, J David

2015-01-01

Background Complex regional pain syndrome (CRPS) is a painful, disabling and often chronic condition, where many patients transition from an acute phase with prominent peripheral neurogenic inflammation to a chronic phase with evident central nervous system (CNS) changes. Ketamine is a centrally-acting agent believed to work through blockade of N-methyl-D-aspartate (NMDA) receptors and is being increasingly used for the treatment of refractory CRPS, although the basis for the drug’s effects and efficacy at different stages of the syndrome remain unclear. Methods We used a mouse model of CRPS (n=8–12/group) involving tibia fracture/cast immobilization to test the efficacy of ketamine (2 mg/kg/day; 7 days) or vehicle infusion during acute (3weeks [3w] post-fracture) and chronic (7w post-fracture) stages. Results Acute phase fracture mice displayed elevated limb temperature, edema and nociceptive sensitization that were not reduced by ketamine. Fracture mice treated with ketamine during the chronic phase showed reduced nociceptive sensitization that persisted beyond completion of the infusion. During this chronic phase, ketamine also reduced latent nociceptive sensitization and improved motor function at 18 weeks post-fracture. No side effects of the infusions were identified. These behavioral changes were associated with altered spinal astrocyte activation and expression of pain-related proteins including NMDA receptor 2b (NR2b), Ca2+/calmodulin-dependent protein kinase ii (CaMK2), and brain-derived neurotrophic factor (BNDF). Conclusions Collectively, these results demonstrate that ketamine is efficacious in the chronic, but not acute stages of CRPS, suggesting that the centrally-acting drug is relatively ineffective in early CRPS when peripheral mechanisms are more critical for supporting nociceptive sensitization. PMID:26492479

Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.

Science.gov (United States)

Tan, Shu-Yin; Hang, Fu; Purvarshi, Gowreesunkur; Li, Min-Qing; Meng, Da-Hua; Huang, Ling-Ling

2015-10-01

To evaluate the predictive value of three-dimensional (3D)-power Doppler sonography on recurrent miscarriage. The study patients were divided into a recurrent miscarriage group (30 cases) and a normal pregnancy group (21 cases). Measurement of endometrial thickness was performed using two-dimensional transvaginal ultrasound in the midluteal phase. The endometrial volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in midluteal and placenta volume, as well as the VI, FI, and VFI of early pregnancy were measured using Virtual Organ Computer-aided Analysis of 3D-power Doppler ultrasound. Endometrial thickness, endometrial volume, endometrial vascular data, VI, FI, and VFI of the midluteal phase were lower in the recurrent miscarriage group compared with the normal pregnancy group (p FI between the recurrent miscarriage and control groups during early pregnancy (p > 0.05). The predictive accuracy of endometrial thickness, endometrial volume, VI, FI, and VFI in the midluteal phase, and placenta volume, VI, FI, and VFI in early pregnancy as measured by the receiver operating characteristic curve to predict miscarriage before 12 gestational weeks in participants was 0.681, 0.876, 0.770, 0.720, 0.879, 0.771, 0.907, 0.592, respectively. The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage. Copyright © 2015. Published by Elsevier B.V.

Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia.

Science.gov (United States)

Rosshandler, Yasmin; Shen, Ann Q; Cortes, Jorge; Khoury, Hanna Jean

2016-05-01

Omacetaxine mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic myeloid leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of omacetaxine mepesuccinate. Omacetaxine mepesuccinate has activity in chronic myeloid leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine mepesuccinate has distinct but manageable adverse events profile. Omacetaxine mepesuccinate is a treatment option for a subset of patients with refractory chronic myeloid leukemia.

Bridging the gap between selection decisions of facade systems at the early design phase: Issues, challenges and solutions

Directory of Open Access Journals (Sweden)

Mohamad Kassema

2015-11-01

Full Text Available Building facade has a significant impact on the environmental and economic performance of buildings and projects. The specification of their elements at the early design phase depends on numerous technical, environmental and economic factors and involves several stakeholders. The procurement and delivery of the facade work package from the early design phase, through detailed design and manufacture, to installation is a process with several inherent risk factors due to the involved cost, technical and engineering complexities and its position on the critical path in all projects. This research investigates the process of selection and specification of building facade elements at the early design phases with the overarching aim of identifying the issues affecting specification decisions, their root causes and impact on projects. The research utilizes a mixed research approach which combines a retrospective case study and an industry survey as two research methods that build on each other. The findings suggest that the complexity of specification at the early design phases is exacerbated by factors such as the inadequate technical knowledge of stakeholders involved in the decision making process, the non-involvement of building facade consultants, the late involvement of specialist facade subcontractors, and in a few cases by some commercial exclusivity agreements that restricts specification decisions. 

The value of the phase analysis for the diagnosis of COPD complicated with early cor pulmonale

International Nuclear Information System (INIS)

Tang Binxiang; Zhang Qingxian; Wang Shujun

1993-01-01

The phase analysis was examined in 14 cases of COPD complicated with early cor pulmonale, 10 cases of coronary heart disease and 19 cases of normal subjects by the radionuclide gated blood pool imaging. Right heart catheterization was also performed in COPD group. It was shown that RVW (right ventricular phase angle width) in the COPD were significantly increased than that in the coronary heart disease group and the normal group, while LVW (left ventricular phase angle width) in the coronary heart disease group were significantly increased. It was worthy to be pointed out that in 3 of 4 cases of COPD with normal pulmonary artery pressure the RVW definitely prolonged. Therefore, it was suggested that RVW may be taken as an index for diagnosis of COPD complicated with early cor pulmonale

Impact of early diagnosis and control of chronic respiratory diseases on active and healthy ageing. A debate at the European Union Parliament.

Science.gov (United States)

Bousquet, J; Tanasescu, C C; Camuzat, T; Anto, J M; Blasi, F; Neou, A; Palkonen, S; Papadopoulos, N G; Antunes, J P; Samolinski, B; Yiallouros, P; Zuberbier, T

2013-01-01

A debate at the European Union Parliament was held on 13 November 2012 on the Impact of early diagnosis and control of chronic respiratory diseases on Active and Healthy Ageing (AHA). The debate was held under the auspices of the Cyprus Presidency of the European Union (2012) and represents a follow-up of the priorities of the Polish Presidency of the European Union (2011). It highlighted the importance of early life events on the occurrence of chronic respiratory diseases later in life and their impact on active and healthy ageing. Epidemiologic evidence was followed by actions that should be taken to prevent and manage chronic respiratory diseases in children. The debate ended by practical, feasible and achievable projects, demonstrating the strength of the political action in the field. Three projects will be initiated from this debate: The first will be a meeting sponsored by the Région Languedoc-Roussillon on the developmental origins of chronic diseases and ageing: from research to policies and value creation. The second project is being led by the WHO Collaborating Centre for Asthma and Rhinitis: Prevention of Asthma, Prevention of Allergy (PAPA). The third project is the GA(2)LEN sentinel network. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Statistical analysis of the early phase of SBO accident for PWR

Energy Technology Data Exchange (ETDEWEB)

Kozmenkov, Yaroslav, E-mail: y.kozmenkov@hzdr.de; Jobst, Matthias, E-mail: m.jobst@hzdr.de; Kliem, Soeren, E-mail: s.kliem@hzdr.de; Schaefer, Frank, E-mail: f.schaefer@hzdr.de; Wilhelm, Polina, E-mail: p.wilhelm@hzdr.de

2017-04-01

Highlights: • Best estimate model of generic German PWR is used in ATHLET-CD simulations. • Uncertainty and sensitivity analysis of the early phase of SBO accident is presented. • Prediction intervals for occurrence of main events are evaluated. - Abstract: A statistical approach is used to analyse the early phase of station blackout accident for generic German PWR with the best estimate system code ATHLET-CD as a computation tool. The analysis is mainly focused on the timescale uncertainties of the accident events which can be detected at the plant. The developed input deck allows variations of all input uncertainty parameters relevant to the case. The list of identified and quantified input uncertainties includes 30 parameters related to the simulated physical phenomena/processes. Time uncertainties of main events as well as the major contributors to these uncertainties are defined. The uncertainty in decay heat has the highest contribution to the uncertainties of the analysed events. A linear regression analysis is used for predicting times of future events from detected times of occurred/past events. An accuracy of event predictions is estimated and verified. The presented statistical approach could be helpful for assessing and improving existing or elaborating additional emergency operating procedures aimed to prevent severe damage of reactor core.

Liver CT for vascular mapping during radioembolisation workup : comparison of an early and late arterial phase protocol

NARCIS (Netherlands)

van den Hoven, Andor F; Braat, Manon N G J A; Prince, Jip F; van Doormaal, Pieter J; van Leeuwen, Maarten S; Lam, Marnix G E H; van den Bosch, Maurice A A J

OBJECTIVES: To compare right gastric (RGA) and segment 4 artery (A4) origin detection rates during radioembolisation workup between early and late arterial phase liver CT protocols. METHODS: 100 consecutive patients who underwent liver CT between May 2012-January 2015 with early or late arterial

Cosmological QCD phase transition in steady non-equilibrium dissipative Hořava–Lifshitz early universe

International Nuclear Information System (INIS)

Khodadi, M.; Sepangi, H.R.

2014-01-01

We study the phase transition from quark–gluon plasma to hadrons in the early universe in the context of non-equilibrium thermodynamics. According to the standard model of cosmology, a phase transition associated with chiral symmetry breaking after the electro-weak transition has occurred when the universe was about 1–10 μs old. We focus attention on such a phase transition in the presence of a viscous relativistic cosmological background fluid in the framework of non-detailed balance Hořava–Lifshitz cosmology within an effective model of QCD. We consider a flat Friedmann–Robertson–Walker universe filled with a non-causal and a causal bulk viscous cosmological fluid respectively and investigate the effects of the running coupling constants of Hořava–Lifshitz gravity, λ, on the evolution of the physical quantities relevant to a description of the early universe, namely, the temperature T, scale factor a, deceleration parameter q and dimensionless ratio of the bulk viscosity coefficient to entropy density (ξ)/s . We assume that the bulk viscosity cosmological background fluid obeys the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively. -- Highlights: •In this paper we have studied quark–hadron phase transition in the early universe in the context of the Hořava–Lifshitz model. •We use a flat FRW universe with the bulk viscosity cosmological background fluid obeying the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively

Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress

NARCIS (Netherlands)

Marit Arp, J; Ter Horst, Judith P; Loi, Manila; den Blaauwen, Jan; Bangert, Eline; Fernández, Guillén; Joëls, Marian; Oitzl, Melly S; Krugers, Harm

2016-01-01

Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

Science.gov (United States)

Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

2017-02-01

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

A propensity score matching analysis of dasatinib and nilotinib as a frontline therapy for patients with chronic myeloid leukemia in chronic phase.

Science.gov (United States)

Takahashi, Koichi; Kantarjian, Hagop M; Yang, Yulong; Sasaki, Koji; Jain, Preetesh; DellaSala, Sara; Ravandi, Farhad; Kadia, Tapan; Pemmaraju, Naveen; Daver, Naval; Borthakur, Gautam; Garcia-Manero, Guillermo; Jabbour, Elias; Cortes, Jorge E

2016-11-15

Both dasatinib and nilotinib are approved frontline therapy for chronic myeloid leukemia in chronic phase (CML-CP) based on randomized trials compared with imatinib. However, no head-to-head comparison of dasatinib and nilotinib has been conducted in patients with newly diagnosed CML-CP. The authors conducted a propensity score (PS) matched comparison of patients with CML-CP who received frontline therapy with either dasatinib (N = 102) or nilotinib (N = 104) under the respective phase 2 trials conducted in parallel. PS matching resulted in 87 patients from each trial being matched for pretreatment characteristics. The 3-month BCR-ABL1/ABL1 ratio treatment cohorts. The 3-year probability of event-free survival was 89% among the patients who received dasatinib and 87% among those who received nilotinib (P = .99), and the corresponding 3-year overall survival probabilities were 99% and 93%, respectively (P = .95). No statistical difference was observed between the dasatinib and nilotinib groups in any of the other survival endpoints. The treatment discontinuation rate also was similar between the 2 cohorts (dasatinib group, 18%; nilotinib group, 19%; P = .82). In a PS-matched cohort of patients with newly diagnosed CML-CP, dasatinib and nilotinib offer similar response and survival outcomes. Both drugs can be considered reasonable standard-of-care options as first-line therapy for patients with CML-CP. Cancer 2016;122:3336-3343. © 2016 American Cancer Society. © 2016 American Cancer Society.

The association between microhaemorrhages and post - traumatic functional outcome in the chronic phase after mild traumatic brain injury

Energy Technology Data Exchange (ETDEWEB)

Haan, S. de; Groot, J.C. de [University Medical Center Groningen, Department of Radiology, University of Groningen, Groningen (Netherlands); Jacobs, B.; Naalt, J. van der [University Medical Center Groningen, Department of Neurology, University of Groningen, Groningen (Netherlands)

2017-10-15

In the chronic phase after mild traumatic brain injury (mTBI), microhaemorrhages are frequently detected on magnetic resonance imaging (MRI). It is however unclear whether microhaemorrhages are associated with functional outcome and which MRI sequence is most appropriate to address this association. We aimed to determine the association between microhaemorrhages and functional outcome in the chronic posttraumatic phase after injury with the most suitable MRI sequence to address this association. One hundred twenty-seven patients classified with mTBI admitted to the outpatient clinic from 2008 to 2015 for persisting posttraumatic complaints were stratified according to the presence of MRI abnormalities (n = 63 (MRI+ group) and n = 64 without abnormalities (MRI- group)). For the detection of microhaemorrhages, susceptibility-weighted imaging (SWI) and T2* gradient recalled echo (T2*GRE) were used. The relation between the functional outcome (dichotomized Glasgow Outcome Scale Extended scores) and the number and localization of microhaemorrhages was analysed using binary logistic regression. SWI detected twice as many microhaemorrhages compared to T2*GRE: 341 vs. 179. Lesions were predominantly present in the frontal and temporal lobes. Unfavourable outcome was present in 67% of the MRI+ group with a significant association of total number of microhaemorrhages in the temporal cortical area on SWI (OR 0.43 (0.21-0.90) p = 0.02), with an explained variance of 44%. The number of microhaemorrhages was not correlated with the number of posttraumatic complaints. An unfavourable outcome in the chronic posttraumatic phase is associated with the presence and number of microhaemorrhages in the temporal cortical area. SWI is preferably used to detect these microhaemorrhages. (orig.)

The association between microhaemorrhages and post - traumatic functional outcome in the chronic phase after mild traumatic brain injury

International Nuclear Information System (INIS)

Haan, S. de; Groot, J.C. de; Jacobs, B.; Naalt, J. van der

2017-01-01

In the chronic phase after mild traumatic brain injury (mTBI), microhaemorrhages are frequently detected on magnetic resonance imaging (MRI). It is however unclear whether microhaemorrhages are associated with functional outcome and which MRI sequence is most appropriate to address this association. We aimed to determine the association between microhaemorrhages and functional outcome in the chronic posttraumatic phase after injury with the most suitable MRI sequence to address this association. One hundred twenty-seven patients classified with mTBI admitted to the outpatient clinic from 2008 to 2015 for persisting posttraumatic complaints were stratified according to the presence of MRI abnormalities (n = 63 (MRI+ group) and n = 64 without abnormalities (MRI- group)). For the detection of microhaemorrhages, susceptibility-weighted imaging (SWI) and T2* gradient recalled echo (T2*GRE) were used. The relation between the functional outcome (dichotomized Glasgow Outcome Scale Extended scores) and the number and localization of microhaemorrhages was analysed using binary logistic regression. SWI detected twice as many microhaemorrhages compared to T2*GRE: 341 vs. 179. Lesions were predominantly present in the frontal and temporal lobes. Unfavourable outcome was present in 67% of the MRI+ group with a significant association of total number of microhaemorrhages in the temporal cortical area on SWI (OR 0.43 (0.21-0.90) p = 0.02), with an explained variance of 44%. The number of microhaemorrhages was not correlated with the number of posttraumatic complaints. An unfavourable outcome in the chronic posttraumatic phase is associated with the presence and number of microhaemorrhages in the temporal cortical area. SWI is preferably used to detect these microhaemorrhages. (orig.)

Serum IgE and IgG4 against muscle larva excretory-secretory products during the early and late phases of human trichinellosis.

Science.gov (United States)

Calcagno, Marcela A; Forastiero, María A; Saracino, María P; Vila, Cecilia C; Venturiello, Stella M

2017-11-01

In human trichinellosis, the relevance of the presence and persistence of specific serum IgE and IgG4 during the early and late phases of infection is still controversial.The aim of this work was to determine the percentage of human sera presenting IgE and IgG4 against Trichinella spiralis muscle larvae excretory-secretory products as well as their levels during the early and late phases of the infection. The antigen recognition pattern by serum total immunoglobulins (IgGAM), IgE, and IgG4 was assessed over time. Serum samples during early and late phases were analyzed by ELISA and immunoelectrotransfer blot (IETB).Results showed that (a)-IgE and IgG4 are present at constant levels in both phases; (b)-IgE recognized the glycoproteins of ~ 45 and ~ 55 kDa and IgG4 only the ~ 45 kDa; (c)-in the late phase, the percentage of specific IgE positive sera was higher than that of specific IgG4 by IETB; while in serum samples taken during the early phase, no differences were found between both isotypes; (d)-both isotypes displayed different glycoprotein recognition patterns: the pattern corresponding to IgE was coincident with that of IgGAM, comprising seven glycoproteins (ranging from ~ 116 to ~ 29 kDa), whereas IgG4 revealed four glycoproteins (ranging from ~ 97 to ~ 45 kDa), showing a different sera recognition percentage depending on the phase studied.In conclusion, IgE and IgG4 cannot be considered exclusive isotypes of neither the early nor the late phase of infection and they are as useful as the detection of total antibodies in the early diagnosis.

Evaluation of the Safety of Imatinib Mesylate in 200 Iraqi Patients with Chronic Myeloid Leukemia in the Chronic Phase: Single-Center Study

Directory of Open Access Journals (Sweden)

Bassam Francis Matti

2013-12-01

Full Text Available OBJECTIVE: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML. During therapy, a few patients may develop hematological and non-hematological adverse effects. METHODS: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day. RESULTS: Two hundred CML patients in chronic phase were included in this study; the male: female ratio was 0.7: 1 with mean age 39.06±13.21 years (ranged from 15-81 years. The study showed that the commonest hematological side effects were grade 2 anemia (12.5% followed by leukopenia (8% and thrombocytopenia (4%, while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%, followed by musculoskeletal pain (35.5%, then gastro-intestinal symptoms (vomiting, diarrhea (19%. Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity. CONCLUSION: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectively.

Focus on Chronic Disease through Different Lenses of Expertise : Towards Implementation of Patient-Focused Decision Support Preventing Disability: The Example of Early Rheumatoid Arthritis

OpenAIRE

Dahlström, Örjan

2009-01-01

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Treatment strategies emphasize early multi-professional interventions to reduce disease activity and to prevent disability, but there is a lack of knowledge on how optimal treatment can be provided to each individual patient. Aim: To elucidate how clinical manifestations of early RA are associated to disease and disability outcomes, to strive for greater potential to establish prognosis in early RA, and to facilitate i...

Early life socioeconomic adversity is associated in adult life with chronic inflammation, carotid atherosclerosis, poorer lung function and decreased cognitive performance: a cross-sectional, population-based study

LENUS (Irish Health Repository)

Packard, Chris J

2011-01-17

Abstract Background Socioeconomic gradients in health persist despite public health campaigns and improvements in healthcare. The Psychosocial and Biological Determinants of Ill-health (pSoBid) study was designed to uncover novel biomarkers of chronic disease that may help explain pathways between socioeconomic adversity and poorer physical and mental health. Methods We examined links between indicators of early life adversity, possible intermediary phenotypes, and markers of ill health in adult subjects (n = 666) recruited from affluent and deprived areas. Classical and novel risk factors for chronic disease (lung function and atherosclerosis) and for cognitive performance were assessed, and associations sought with early life variables including conditions in the parental home, family size and leg length. Results Associations were observed between father\\'s occupation, childhood home status (owner-occupier; overcrowding) and biomarkers of chronic inflammation and endothelial activation in adults (C reactive protein, interleukin 6, intercellular adhesion molecule; P < 0.0001) but not number of siblings and leg length. Lung function (forced expiratory volume in 1 second) and cognition (Choice Reaction Time, the Stroop test, Auditory Verbal Learning Test) were likewise related to early life conditions (P < 0.001). In multivariate models inclusion of inflammatory variables reduced the impact and independence of early life conditions on lung function and measures of cognitive ability. Including variables of adult socioeconomic status attenuated the early life associations with disease biomarkers. Conclusions Adverse levels of biomarkers of ill health in adults appear to be influenced by father\\'s occupation and childhood home conditions. Chronic inflammation and endothelial activation may in part act as intermediary phenotypes in this complex relationship. Reducing the \\'health divide\\' requires that these life course determinants are taken into account.

Tyrosine kinase inhibitors induced immune thrombocytopenia in chronic myeloid leukemia?

Directory of Open Access Journals (Sweden)

Avital F. Barak

2011-12-01

Full Text Available The outcome and quality of life of chronic myeloid leukemia (CML patients has remarkably changed with the treatment of tyrosine kinase inhibitors (TKIs. Currently, hematopoietic stem cell transplantation (HSCT is considered mainly as a third line salvage therapy in cases of TKIs resistance or intolerance. Here we describe a patient with chronic phase CML who developed both resistance and late occurrence of s severe thrombocytopenia on first and second generation TKIs and eventually underwent HSCT. Although the mechanism of the myelosuppression is not fully understood, we showed for the first time the development of dose dependent platelet antibodies in the presence of TKIs, suggesting the possibility of TKIs induced thrombocytopenia. Our case emphasizes that late development of severe myelosuppression during imatinib treatment is probably an important indication for consideration of early HSCT.

Phase II study of palliative low-dose local radiotherapy in disseminated indolent non-Hodgkin's lymphoma and chronic lymphocytic leukemia

DEFF Research Database (Denmark)

Jóhannsson, Jakob; Specht, Lena; Mejer, Johannes

2002-01-01

Indolent non-Hodgkin's lymphoma (INHL) and chronic lymphocytic leukemia (CLL) are highly sensitive to radiotherapy (RT). Previous retrospective studies have shown high response rates after local palliative RT of 4 Gy in 2 fractions, which prompted this prospective Phase II trial of the palliative...

Imatinib mesylate in chronic myelogenous leukemia: a Congolese ...

African Journals Online (AJOL)

Major cytogenetic response was noticed in 87.18%. After a median follow up of 12 months, chronic myeloid leukemia had not progressed to the accelerated or blastic phase in an estimated 91.8% of patients and 86.6% were alive. Conclusion: Imatinib is effective in newly chronic phase chronic myeloid leukemia patient ...

Risk factors for and impact of respiratory failure on mortality in the early phase of acute pancreatitis

DEFF Research Database (Denmark)

Dombernowsky, Tilde; Kristensen, Marlene Østermark; Rysgaard, Sisse

2016-01-01

: Retrospective cohort study including 359 patients admitted with acute pancreatitis. Information was gathered from electronic patient records. We defined respiratory failure based on the modified Marshall scoring system in the revised Atlanta criteria. Predictors of respiratory failure were evaluated......, or pneumonia may develop respiratory failure, suggests that acute lung injury, possibly associated with systemic inflammation, may be important.......BACKGROUND: The incidence of respiratory failure and other respiratory complications in the early phase of acute pancreatitis (AP) is not well investigated. OBJECTIVE: To evaluate the incidence and risk factors of respiratory failure, and its impact on mortality in the early phase AP. METHODS...

Sustainability certification systems as guidelines for early-phase urban design processes

OpenAIRE

Jensen, Lotte Bjerregaard; Bjerre, Lærke; Mansfelt, Lise

2016-01-01

The German Sustainable Building Council (Deutsche Gesellschaft für Nachhaltiges Bauen or DGNB) has one of the most comprehensive sustainability certification systems for urban districts (UD). Their explicit aim is that the system should impact the very earliest design decisions. The Technical University of Denmark has tested the DGNB-UD system in two experimental design projects for similar locations to find out how it can be used in the early-phase design process. This paper describes these ...

Enabling Parametric Optimal Ascent Trajectory Modeling During Early Phases of Design

Science.gov (United States)

Holt, James B.; Dees, Patrick D.; Diaz, Manuel J.

2015-01-01

During the early phases of engineering design, the costs committed are high, costs incurred are low, and the design freedom is high. It is well documented that decisions made in these early design phases drive the entire design's life cycle. In a traditional paradigm, key design decisions are made when little is known about the design. As the design matures, design changes become more difficult -- in both cost and schedule -- to enact. Indeed, the current capability-based paradigm that has emerged because of the constrained economic environment calls for the infusion of knowledge acquired during later design phases into earlier design phases, i.e. bring knowledge acquired during preliminary and detailed design into pre-conceptual and conceptual design. An area of critical importance to launch vehicle design is the optimization of its ascent trajectory, as the optimal trajectory will be able to take full advantage of the launch vehicle's capability to deliver a maximum amount of payload into orbit. Hence, the optimal ascent trajectory plays an important role in the vehicle's affordability posture as the need for more economically viable access to space solutions are needed in today's constrained economic environment. The problem of ascent trajectory optimization is not a new one. There are several programs that are widely used in industry that allows trajectory analysts to, based on detailed vehicle and insertion orbit parameters, determine the optimal ascent trajectory. Yet, little information is known about the launch vehicle early in the design phase - information that is required of many different disciplines in order to successfully optimize the ascent trajectory. Thus, the current paradigm of optimizing ascent trajectories involves generating point solutions for every change in a vehicle's design parameters. This is often a very tedious, manual, and time-consuming task for the analysts. Moreover, the trajectory design space is highly non-linear and multi

Divided attention can enhance early-phase memory encoding: the attentional boost effect and study trial duration.

Science.gov (United States)

Mulligan, Neil W; Spataro, Pietro

2015-07-01

Divided attention during encoding typically produces marked reductions in later memory. The attentional boost effect (ABE) is a surprising variation on this phenomenon. In this paradigm, each study stimulus (e.g., a word) is presented along with a target or a distractor (e.g., different colored circles) in a detection task. Later memory is better for stimuli co-occurring with targets. The present experiments indicate that the ABE arises during an early phase of memory encoding that involves initial stimulus perception and comprehension rather than at a later phase entailing controlled, elaborative rehearsal. Experiment 1 demonstrated that the ABE was robust at a short study duration (700 ms) and did not increase with increasing study trial durations (1,500 ms and 4,000 ms). Furthermore, the target condition is boosted to the level of memory performance in a full-attention condition for the short duration but not the long duration. Both results followed from the early-phase account. This account also predicts that for very short study times (limiting the influence of late-phase controlled encoding and thus minimizing the usual negative effect of divided attention), the target condition will produce better memory than will the full-attention condition. Experiment 2 used a study time of 400 ms and found that words presented with targets lead to greater recognition accuracy than do either words presented with distractors or words in the full-attention condition. Consistent with the early-phase account, a divided attention condition actually produced superior memory than did the full-attention condition, a very unusual but theoretically predicted result. (c) 2015 APA, all rights reserved.

Maternal separation in early life modifies anxious behavior and Fos and glucocorticoid receptor expression in limbic neurons after chronic stress in rats: effects of tianeptine.

Science.gov (United States)

Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M

2016-01-01

Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life.

Acute and chronic whiplash disorders--a review.

Science.gov (United States)

Sterner, Ylva; Gerdle, Björn

2004-09-01

This review examines acute and chronic whiplash-associated disorders to facilitate assessment, treatment and rehabilitation for further research and evidence-based practices. A review of the literature. Whiplash-associated disorders account for a large proportion of the overall impairment and disability caused by traffic injuries. Rarely can a definite injury be determined in the acute (or chronic) phase. Crash-related factors have been identified, and several trauma mechanisms possibly causing different injuries have been described. Most whiplash trauma will not cause injury, and the majority of patients (92-95%) will return to work. Litigation is not a major factor. Cognitive impairments are not the same as brain injury. Variables such as pain intensity, restricted motion, neurological symptoms and signs, together with central nervous system symptoms can be used to predict a situation with risk of remaining complaints. Influences of other factors--the same as for other chronic pain conditions--also exist. Persistent/chronic pain is not merely acute pain that persists over time; changes occur at different levels of the pain transmission system. Chronic whiplash-associated disorders are associated with problems concerning social functioning, daily anxieties and satisfaction with different aspects of life. Adequate information, advice and pain medication together with active interventions might be more effective in the acute stage. Early multidisciplinary rehabilitation focusing on cognitive-behavioural changes might be of value. To develop specific treatment and rehabilitation, it is important to identify homogenous subgroups.

Efficient runner safety assessment during early design phase and root cause analysis

International Nuclear Information System (INIS)

Liang, Q W; Lais, S; Gentner, C; Braun, O

2012-01-01

Fatigue related problems in Francis turbines, especially high head Francis turbines, have been published several times in the last years. During operation the runner is exposed to various steady and unsteady hydraulic loads. Therefore the analysis of forced response of the runner structure requires a combined approach of fluid dynamics and structural dynamics. Due to the high complexity of the phenomena and due to the limitation of computer power, the numerical prediction was in the past too expensive and not feasible for the use as standard design tool. However, due to continuous improvement of the knowledge and the simulation tools such complex analysis has become part of the design procedure in ANDRITZ HYDRO. This article describes the application of most advanced analysis techniques in runner safety check (RSC), including steady state CFD analysis, transient CFD analysis considering rotor stator interaction (RSI), static FE analysis and modal analysis in water considering the added mass effect, in the early design phase. This procedure allows a very efficient interaction between the hydraulic designer and the mechanical designer during the design phase, such that a risk of failure can be detected and avoided in an early design stage.The RSC procedure can also be applied to a root cause analysis (RCA) both to find out the cause of failure and to quickly define a technical solution to meet the safety criteria. An efficient application to a RCA of cracks in a Francis runner is quoted in this article as an example. The results of the RCA are presented together with an efficient and inexpensive solution whose effectiveness could be proven again by applying the described RSC technics. It is shown that, with the RSC procedure developed and applied as standard procedure in ANDRITZ HYDRO such a failure is excluded in an early design phase. Moreover, the RSC procedure is compatible with different commercial and open source codes and can be easily adapted to apply for

Efficient runner safety assessment during early design phase and root cause analysis

Science.gov (United States)

Liang, Q. W.; Lais, S.; Gentner, C.; Braun, O.

2012-11-01

Fatigue related problems in Francis turbines, especially high head Francis turbines, have been published several times in the last years. During operation the runner is exposed to various steady and unsteady hydraulic loads. Therefore the analysis of forced response of the runner structure requires a combined approach of fluid dynamics and structural dynamics. Due to the high complexity of the phenomena and due to the limitation of computer power, the numerical prediction was in the past too expensive and not feasible for the use as standard design tool. However, due to continuous improvement of the knowledge and the simulation tools such complex analysis has become part of the design procedure in ANDRITZ HYDRO. This article describes the application of most advanced analysis techniques in runner safety check (RSC), including steady state CFD analysis, transient CFD analysis considering rotor stator interaction (RSI), static FE analysis and modal analysis in water considering the added mass effect, in the early design phase. This procedure allows a very efficient interaction between the hydraulic designer and the mechanical designer during the design phase, such that a risk of failure can be detected and avoided in an early design stage.The RSC procedure can also be applied to a root cause analysis (RCA) both to find out the cause of failure and to quickly define a technical solution to meet the safety criteria. An efficient application to a RCA of cracks in a Francis runner is quoted in this article as an example. The results of the RCA are presented together with an efficient and inexpensive solution whose effectiveness could be proven again by applying the described RSC technics. It is shown that, with the RSC procedure developed and applied as standard procedure in ANDRITZ HYDRO such a failure is excluded in an early design phase. Moreover, the RSC procedure is compatible with different commercial and open source codes and can be easily adapted to apply for

PRODROMAL PHASE IN THE DEVELOPMENT OF EARLY ONSET SCHIZOPHRENIC PSYCHOSIS - CASE REPORT

Directory of Open Access Journals (Sweden)

Jelena Kostić

2012-06-01

Full Text Available Schizophrenia and other mental disorders are often preceded by prodromal changes in behavior that can last from several days to several years, indicating the beginning of psychosis. If the disease starts at an earlier age, especially in adolescence, the prodromal phase is more non-specific and difficult to detect. There is a large number of operational instruments used for clinical assessment and quantification of prodromal symptoms and "at risk mental state", as well as the predictive potential for psychosis. This paper describes the prodromal phase in the development of early onset schizophrenic psychosis, with the emphasis on gradual, several-month psychopathological accumulation and evolution of nonspecific and subclinical, prodromal symptoms to florid schizophrenic symptoms.

Oppositional behavior and longitudinal predictions of early adulthood mental health problems in chronic tic disorders.

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Thériault, Marie-Claude G; Bécue, Jean-Cyprien; Lespérance, Paul; Chouinard, Sylvain; Rouleau, Guy A; Richer, Francois

2018-03-16

Chronic tic disorders (TD) are associated with a number of psychological problems such as attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive behavior (OCB), oppositional-defiant disorder (ODD) as well as anxious and depressive symptoms. ODD is often considered a risk factor for many psychological symptoms and recent work suggests that different ODD dimensions show independent predictions of later psychological problems. This study examined the longitudinal predictions between ODD dimensions of Irritability and Defiance and the most frequent comorbidities in TD from childhood to early adulthood. From an initial sample of 135, parent reports were obtained on 58 participants with TD using standard clinical questionnaires and semi-structured interviews. Defiance symptoms decreased from baseline to follow-up whereas Irritability symptoms were more stable over time. In multiple regressions, Irritability in childhood predicted anxiety and OCB in early adulthood while Defiance in childhood predicted ADHD and conduct disorder symptoms in early adulthood. No developmental link was found for depressive symptoms. Results indicate that ODD dimensions are developmentally linked to both internalizing and externalizing adult mental health symptoms in TD. Copyright © 2018. Published by Elsevier B.V.

Chronic Absenteeism in Tennessee's Early Grades

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Attridge, Jonathon

2016-01-01

Although the average daily attendance rate for Tennessee students is 95 percent, almost 45,000, or 10 percent, of Tennessee K-3 students missed at least a month's worth of school days during the 2014-15 school year. These "chronically absent" students present a particular problem for schools that are charged with developing foundational…

Phase III trial of high- vs. low-dose-rate interstitial radiotherapy for early mobile tongue cancer

International Nuclear Information System (INIS)

Inoue, Takehiro; Inoue, Toshihiko; Yoshida, Ken; Yoshioka, Yasuo; Shimamoto, Shigetoshi; Tanaka, Eiichi; Yamazaki, Hideya; Shimizutani, Kimishige; Teshima, Teruki; Furukawa, Souhei

2001-01-01

Purpose: Early mobile tongue cancer can be controlled with interstitial radiotherapy (ISRT). We carried out a Phase III trial to compare the treatment results of low-dose-rate (Ld) ISRT and high-dose-rate (HDR) ISRT for early mobile tongue cancer. Methods and Materials: From April 1992 through October 1996, 59 patients with cancer of the early mobile tongue were registered in this Phase III study. Eight patients were excluded from the evaluation because of violations of the requirements for this study. Of 51 eligible patients, 26 patients were treated with LDR-ISRT (70 Gy/4-9 days) and 25 patients with HDR-ISRT (60 Gy/10 fractions/1 week). For the hyperfractionated HDR-ISRT, the time interval between 2 fractions was more than 6 h. Results: Five-year local control rates of the LDR and HDR groups were 84% and 87% respectively. Nodal metastasis occurred in 6 patients in each group. Five-year nodal control rates of the LDR and HDR groups were 77% and 76%, respectively. Conclusion: Hyperfractionated HDR-ISRT for early mobile tongue cancer has the same local control compared with continuous LDR-ISRT. Hyperfractionated HDR-ISRT is an alternative treatment for continuous LDR-ISRT

The predictive value of early molecular response in chronic myeloid leukaemia patients treated with imatinib in a single real-world medical centre in a developing country.

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Bee, Ping Chong; Sekaran, Veera; Ng, Richard Rui Jie; Kweh, Ting Yi; Gan, Gin Gin

2017-03-01

The prognosis of patients with chronic myeloid leukaemia (CML) has improved since the introduction of imatinib. However, patients who do not achieve complete cytogenetic response (CCyR) and major molecular response (MMR) have poorer prognosis. Recent clinical trials have demonstrated that early and deeper cytogenetic and molecular responses predict a better long-term outcome. This study aimed to analyse the relationship between early molecular response and clinical outcome in a real-life setting. This retrospective study included all patients with CML, in chronic or accelerated phase, who were treated with imatinib at University of Malaya Medical Centre, Malaysia. A total of 70 patients were analysed. The median follow-up duration was 74 months, and the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%, respectively. Overall survival (OS) and event-free survival (EFS) at ten years were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had significantly better OS and EFS than those who did not. At six months, patients who had a BCR-ABL level ≤ 10% had significantly better OS and EFS than those who had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at 18 months showed no survival advantage in our patients. Our data showed that imatinib is still useful as first-line therapy. However, vigilant monitoring of patients who have a BCR-ABL level > 10% at six months of treatment should be implemented so that prompt action can be taken to provide the best outcome for these patients. Copyright: © Singapore Medical Association

How Is Chronic Myeloid Leukemia Diagnosed?

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... Myeloid Leukemia? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

[Abnormal processing characteristics to basic emotional faces in the early phase in children with autism spectrum disorder].

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Lin, Qiong-Xi; Wu, Gui-Hua; Zhang, Ling; Wang, Zeng-Jian; Pan, Ning; Xu, Cai-Juan; Jing, Jin; Jin, Yu

2018-02-01

To explore the recognition ability and abnormal processing characteristics to basic emotional faces in the early phase in children with autism spectrum disorders (ASD). Photos of Chinese static faces with four basic emotions (fearful, happy, angry and sad) were used as stimulus. Twenty-five ASD children and twenty-two age- and gender-matched typical developed children (normal controls) were asked to match the emotional faces with words. Event-related potential (ERP) data were recorded concurrently. N170 latencies for total emotion and fearful face in the left temporal region were faster than in the right one in normal controls (P<0.05), but the results were not noted in ASD children. Further, N170 latencies in the left temporal region of ASD children were slower than normal controls for total emotion, fearful and happy faces (P<0.05), and their N170 latencies in the right temporal region were prone to slower than normal controls for angry and fearful faces. The holistic perception speed of emotional faces in the early cognitive processing phase in ASD children is slower than normal controls. The lateralized response in the early phase of recognizing emotional faces may be aberrant in children with ASD.

Informing Early-Phase Technology Decisions in Paradigmatic Innovation

DEFF Research Database (Denmark)

Jensen, Ole Kjeldal; Ahmed-Kristensen, Saeema

2010-01-01

their knowledge-world in such a radical manner, they start facing problems with making efficient decisions as knowledge generated through experience is mainly useful when the future mimics the past, which is not the case for such radical changes. Therefore, a 3 year long research project within this industry has......The innovation activities of a company facing paradigmatic change with regard to both technology and business model includes taking many decisions, where the information available, as well as the decision makers’ ability to understand this information, is limited. Technology decisions in the very...... early phases of innovation have been explored in a Scandinavian energy-utilities company facing exactly these paradigmatic changes. In the company there are 5500 employees, with the major footprint in Denmark. The company has activities in the full energy value-chain including: production & trade of oil...

ChronicOnline: Implementing a mHealth solution for monitoring and early alerting in chronic obstructive pulmonary disease.

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Bitsaki, Marina; Koutras, Christos; Koutras, George; Leymann, Frank; Steimle, Frank; Wagner, Sebastian; Wieland, Matthias

2017-09-01

Lack of time or economic difficulties prevent chronic obstructive pulmonary disease patients from communicating regularly with their physicians, thus inducing exacerbation of their chronic condition and possible hospitalization. Enhancing Chronic patients' Health Online proposes a new, sustainable and innovative business model that provides at low cost and at significant savings to the national health system, a preventive health service for chronic obstructive pulmonary disease patients, by combining human medical expertise with state-of-the-art online service delivery based on cloud computing, service-oriented architecture, data analytics, and mobile applications. In this article, we implement the frontend applications of the Enhancing Chronic patients' Health Online system and describe their functionality and the interfaces available to the users.

Bone scintigraphy compared to MRI and ultrasound in the early diagnosis of arthritis

International Nuclear Information System (INIS)

Sandrock, D.

2006-01-01

Chronic inflammatory arthritis is recognized specifically by bone erosions, caused by characteristic pannus tissue. In the finger joints dynamic low-Tesla MRI is nearly double but not completely sensitive in the detection of erosions than conventional radiography, sonography takes an intermediate position. Less specific signs of synovitis and tenosynovitis are shown with high sensitivity by both 3(2)-phase bone scintigraphy and ultrasound, MRI is less sensitive in this respect. However, standard situation of inflammation in bone scintigraphy - positive finding in early as well as late phase - is of surprisingly low sensitivity, any singular finding in the early or late phase has to be regarded as positive. Specificity of these singular findings is nevertheless sufficiently high, acute inflammatory joint changes and even erosions are also seen with MRI in obviously healthy persons. Only 2-phase bone scintigraphy is easily able to present a simultaneous survey of all joints of the body. For this reason 2-phase bone scintigraphy is most suitable for exclusion but also for primary diagnosis of disease, specification must be done afterwards by other imaging modalities or by laboratory findings. (orig.)

Antigravity treadmill training during the early rehabilitation phase following unicompartmental knee arthroplasty: A case series.

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Huang, Chun-Hao; Schroeder, E Todd; Powers, Christopher

2018-02-26

Patients who have undergone unicompartmental knee arthroplasty (UKA) have been reported to exhibit altered gait 19-25 months post-surgery. The most common gait impairment in this population is inadequate knee flexion and a corresponding decrease in the knee extensor moment during loading response (i.e., quadriceps avoidance). The purpose of this case series was to determine whether incorporation of antigravity treadmill training into a standard physical therapy program can eliminate quadriceps avoidance gait during the early rehabilitation phase following UKA. Four females who underwent UKA were recruited for this study. Participants completed antigravity treadmill training three times per week for 12 weeks in addition to their standard physical therapy program. Instrumented gait analysis was performed at baseline (pre-intervention), week 6 (mid-intervention), and week 12 (post-intervention). We found that peak knee flexion and the peak knee extensor moment during the weight acceptance phase of gait increased to normal values following the 12-week intervention period (14.1 ± 6.5° to 20.6 ± 1.5° and 0.4 ± 0.3 to 0.7 ± 0.2 Nm/kg respectively). The findings of this case series suggest that a standard physical therapy program that incorporates early gait training using an antigravity treadmill may be beneficial in eliminating "quadriceps avoidance" during the early rehabilitation phase following UKA.

Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B).

Science.gov (United States)

Chan, Henry L Y; Ahn, Sang Hoon; Chang, Ting-Tsung; Peng, Cheng-Yuan; Wong, David; Coffin, Carla S; Lim, Seng Gee; Chen, Pei-Jer; Janssen, Harry L A; Marcellin, Patrick; Serfaty, Lawrence; Zeuzem, Stefan; Cohen, David; Critelli, Linda; Xu, Dong; Wind-Rotolo, Megan; Cooney, Elizabeth

2016-05-01

Peginterferon lambda-1a (lambda) is a Type-III interferon, which, like alfa interferons, has antiviral activity in vitro against hepatitis B virus (HBV) and hepatitis C virus (HCV); however, lambda has a more limited extra-hepatic receptor distribution. This phase 2b study (LIRA-B) evaluated lambda in patients with chronic HBV infection. Adult HBeAg+ interferon-naive patients were randomized (1:1) to weekly lambda (180 μg) or peginterferon alfa-2a (alfa) for 48 weeks. The primary efficacy endpoint was HBeAg seroconversion at week 24 post-treatment; lambda non-inferiority was demonstrated if the 80% confidence interval (80% CI) lower bound was >-15%. Baseline characteristics were balanced across groups (lambda N=80; alfa N=83). Early on-treatment declines in HBV-DNA and qHBsAg through week 24 were greater with lambda. HBeAg seroconversion rates were comparable for lambda and alfa at week 48 (17.5% vs. 16.9%, respectively); however lambda non-inferiority was not met at week 24 post-treatment (13.8% vs. 30.1%, respectively; lambda vs. alfa 80% CI lower bound -24%). Results for other key secondary endpoints (virologic, serologic, biochemical) and post hoc combined endpoints (HBV-DNA lambda). Most on-treatment flares occurred early (weeks 4-12), associated with HBV-DNA decline; all post-treatment flares were preceded by HBV-DNA rise. On-treatment, lambda showed greater early effects on HBV-DNA and qHBsAg, and comparable serologic/virologic responses at end-of-treatment. However, post-treatment, alfa-associated HBeAg seroconversion rates were higher, and key secondary results mostly favored alfa. ClinicalTrials.gov number: NCT01204762. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chronic pretrigeminal and cerveau isolé cats.

Science.gov (United States)

Slósarska, M; Zernicki, B

1973-01-01

Ten pretrigeminal and ten cerveau isole cats were observed chronically. During 24-36 h sessions EEG activity was continuously recorded and the EEG and ocular responses to visual and olfactory stimuli were studied. In the pretrigeminal cat acute and chronic stages were distinguished, and in the cerveau isole, acute, "early chronic" and "late chronic" stages. During the acute stage, the pretrigeminal cat is continuously awake, whereas the cerveau isole is comatose. During the "early chronic stage", which lasted at least about 3 weeks, the cerveau isole is semicomatose. During the chronic stage in the pretrigeminal cat and the "late chronic stage" in the cerveau isole, the sleep-waking cycle is present. In both preparations alert wakefulness, drowsiness, light .synchronized sleep and deep synchronized sleep occupy, respectively, about 30 percent, 45 percent, 15 percent and 10 percent of the time. Thus, synchronized sleep is strikingly reduced in comparison with an intact cat, while desynchronized sleep is absent.

BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase.

Science.gov (United States)

Hughes, T P; Saglio, G; Quintás-Cardama, A; Mauro, M J; Kim, D-W; Lipton, J H; Bradley-Garelik, M B; Ukropec, J; Hochhaus, A

2015-09-01

BCR-ABL1 mutations are a common, well-characterized mechanism of resistance to imatinib as first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). Less is known about mutation development during first-line treatment with dasatinib and nilotinib, despite increased use because of higher response rates compared with imatinib. Retrospective analyses were conducted to characterize mutation development in patients with newly diagnosed CML-CP treated with dasatinib (n=259) or imatinib (n=260) in DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML-CP), with 3-year minimum follow-up. Mutation screening, including patients who discontinued treatment and patients who had a clinically relevant on-treatment event (no confirmed complete cytogenetic response (cCCyR) and no major molecular response (MMR) within 12 months; fivefold increase in BCR-ABL1 with loss of MMR; loss of CCyR), yielded a small number of patients with mutations (dasatinib, n=17; imatinib, n=18). Dasatinib patients had a narrower spectrum of mutations (4 vs 12 sites for dasatinib vs imatinib), fewer phosphate-binding loop mutations (1 vs 9 mutations), fewer multiple mutations (1 vs 6 patients) and greater occurrence of T315I (11 vs 0 patients). This trial was registered at www.clinicaltrials.gov as NCT00481247.

Characteristics of the early flight phase in the Olympic ski jumping competition.

Science.gov (United States)

Virmavirta, Mikko; Isolehto, Juha; Komi, Paavo; Brüggemann, Gert-Peter; Müller, Erich; Schwameder, Hermann

2005-11-01

Early flight phase (approximately 40 m) of the athletes participating in the final round of the individual large hill ski jumping competition in Salt Lake City Olympics was filmed with two high-speed pan & tilt video cameras. The results showed that jumpers' steady flight position was almost completed within 0.5s. The most significant correlation with the length of the jump was found in the angle between the skis and body (r=.714, p.001 at 1.1s after the take-off). This particular phase seemed to be important because the ski angle of attack was also related to the jumping distance at the same phase. Although the more upright ski position relative to flight path resulted in longer jumping distance, the winner of the competition had significantly lower ski position as compared to the other good jumpers. This may be due to the high altitude (>2000 m) of the ski jumping stadium in this competition. Because of the low air density, the aerodynamic forces were also low and this probably caused less skillful jumpers to lean too much forward at this phase. Maintenance of speed seemed to be emphasized in this particular competition.

A Case Study of Idea Work in the Early Phases of Product Development

DEFF Research Database (Denmark)

Gish, Liv; Clausen, Christian; Hansen, Claus Thorp

2009-01-01

development. Based on our case we will point out four central findings: 1) Early idea work is a complex process and interlinked with many other activities both inside and outside the organization. 2) Ideas evolve,combine and change over time. 3) Idea work involves a wide range of actors. 4) Carrying ideas......Focus in this paper is on the early innovation activities, in particular idea work. Based on a case study from industrial practice on the development of a new circulator (the Alpha Pro circulator) we aim at getting a better understanding of the work with ideas in the early phases of product...... through demands continuous mobilization of support among a range of actors. We suggest that the actors involved in idea work and their interaction such as negotiating different understandings of what constitutes a qualified idea as well as the continuous mobilization of support to their ideas among...

Early rehabilitation exercise program for inpatients during an acute exacerbation of chronic obstructive pulmonary disease: a randomized controlled trial.

Science.gov (United States)

Tang, Clarice Y; Blackstock, Felicity C; Clarence, Michael; Taylor, Nicholas F

2012-01-01

To determine whether an early rehabilitation program was safe and feasible for patients during an acute exacerbation of chronic obstructive pulmonary disease (COPD). In this phase 1 randomized controlled trial, patients with an acute exacerbation of COPD admitted to the hospital were randomly allocated to a low-intensity exercise group, a moderate- to high-intensity exercise group, or a control group, who received routine physical therapy. In addition to routine physical therapy, patients in the exercise group had to participate in an exercise program. The program consisted of twice-daily aerobic and resistance exercise sessions. Primary outcomes were the number and classification of adverse events and program adherence. In 174 exercise sessions, there was 1 serious adverse event of arrhythmia in the low-intensity exercise group that resolved within 1 hour. There were 12 other minor adverse events involving 5 patients with no significant differences between groups. Patients completed an average of 80% of their scheduled sessions with no significant between-group differences. The exercise groups improved significantly in walking distance; however, no significant between-group differences were observed. There was preliminary evidence that it was safe and feasible to implement an exercise program for patients during an acute exacerbation of COPD. Additional studies with larger sample sizes are required to accurately evaluate program effectiveness.

Diffusion weighted EPI in early cerebral infarction and intracerebral hemorrhage

Energy Technology Data Exchange (ETDEWEB)

Okada, Susumu; Cho, Keiichi; Hosaka, Sumio; Ito, Koichiro; Tajima, Natsuki; Kobayashi, Shiro [Nippon Medical School (Japan). Chiba-Hokuso Hospital; Kumazaki, Tatsuo; Takahashi, Yoshiyuki

1997-11-01

Fifteen cases of early cerebral infarction and 14 cases of cerebral hemorrhage underwent diffusion weighted echo planar imaging. Increased intensity area was detected only 2 in 5 cases less than 3 hours from ictus, whereas infarction was correctly diagnosed in all cases over 3 hours. Infarcted area was increased on the follow-up study in 2 cases. Hematoma showed mixed intensity in hyper acute phase, very hypo in acute, mixed in subacute and very hyper in the chronic stage. High intensity area surrounded the hematoma. (author)

Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model.

Directory of Open Access Journals (Sweden)

Desirée L Salazar

2010-08-01

Full Text Available Traumatic spinal cord injury (SCI results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns were prospectively isolated based on fluorescence-activated cell sorting for a CD133(+ and CD24(-/lo population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein.The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the "window of opportunity" for intervention.

Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

International Nuclear Information System (INIS)

Okunieff, Paul; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

2006-01-01

Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-α, and lymphotoxin-β) or fibrogenic cytokines (transforming growth factor [TGF]-β) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-α, and lymphotoxin-β) and the fibrogenic cytokine, TGF-β, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy

Clinical symptoms predict concurrent social and global functioning in an early psychosis sample.

Science.gov (United States)

Cacciotti-Saija, Cristina; Langdon, Robyn; Ward, Philip B; Hickie, Ian B; Guastella, Adam J

2018-04-01

Although well established in chronic schizophrenia, the key determinants of functioning remain unknown during the early phase of a psychotic disorder. The aim of this study was to comprehensively examine the social cognitive, basic neurocognitive and clinical predictors of concurrent social functioning and global functioning in an early psychosis sample. This study examined the relationship between social cognition, basic neurocognition and clinical symptoms with concurrent functioning in 51 early psychosis individuals. Assessments included a range of self-report, observational and clinician-rated measures of cognitive, symptom severity and functioning domains. Results revealed a significant association between self-reported social function and lower levels of both social interaction anxiety and negative psychotic symptoms. A significant association was also observed between lower levels of negative psychotic symptoms and observed social functioning. Lastly, results demonstrated a significant association between reduced negative psychotic symptoms and clinician-rated global functioning. Clinical domains such as negative symptoms and social interaction anxiety significantly contribute to an optimal model predicting outcome during the early phase of a psychotic disorder. These clinical features may also provide useful markers of an individual's capacity for social participation. Clinical implications include the need for early targeted intervention to address social anxiety and negative psychotic symptoms to facilitate optimum patient outcome. © 2015 Wiley Publishing Asia Pty Ltd.

Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation

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Małgorzata Nita

2014-01-01

Full Text Available The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH and facilitates chronic inflammation mediated by C-reactive protein (CRP. Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2 and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages; however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages.

Improved detection of chronic myocardial infarction with Fourier amplitude and phase imaging in two projections

International Nuclear Information System (INIS)

Akins, E.W.; Scott, E.A.; Williams, C.M.

1987-01-01

Twenty-seven patients with 33 chronic myocaridal infarctions underwent MR imaging and radionuclide ventriculography at rest. The radionuclide ventriculographs, in left anterior oblique (LAO) and left posterior oblique (LPO) projections, were analyzed by two independent observers by visual inspection and combined Fourier-transformed amplitude and phase imaging. Only 15 (45%) of the 33 infarctions were detected by visual inspection, but 21 (64%) were detected on the LAO Fourier-transformed images along. Thirty (91%) were detected by using both LAO and LPO Fourier-transformed images. On MR imaging, 28 (85%) of the myocardial infarctions appeared as areas of focal wall thinning. Combined Fourier-transformed amplitude and phase imaging in both LAO and LPO views discloses more myocardial infarctions than visual inspection or LAO Fourier-transformed images alone because inferior infarctions, which are frequently missed in the LAO view, are easily seen in the LPO view

Clinical and laboratory characteristics of chronic hepatitis C on the early stages of development

Directory of Open Access Journals (Sweden)

N. S. Zhevnerova

2016-01-01

Full Text Available Aim of the research – to assess the clinical and laboratory parameters in patients with chronic hepatitis C (CHC on the early stages of development and their comparison with the level of galectin3. The study included 78 patients with oligosymptomatic course of the disease and minimal liver fibrosis in the most cases. In the most patients with stages of the disease exceeding 8 years, viral load was over a million copies/ml. In 10 % of patients on the early stages of the disease, changes corresponding to severe liver fibrosis and cirrhosis F3 and F4 were detected. Moderate correlation of ALT activity, viral load and low severity with the duration of the disease was identified. There is a trend towards a higher level of galectin3 in a long course of CHC in comparison with earlier stages of its development, with significantly higher average level of galectin-3 in patients with minimal liver fibrosis (F0–F1 as compared to advanced stages, suggesting its importance in the launching and initial mechanisms of fibrogenesis.

Phase Transitions in the Early Universe: The Cosmology of Non-Minimal Scalar Sectors

Science.gov (United States)

Kost, Jeffrey D.

Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically--such as during cosmological mass-generating phase transitions--the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this thesis, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system--often by many orders of magnitude--but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "re-overdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings. In the second part of this thesis, we proceed to study the early-universe cosmology of a Kaluza-Klein (KK

Impact of chronic maternal stress during early gestation on maternal-fetal stress transfer and fetal stress sensitivity in sheep.

Science.gov (United States)

Dreiling, Michelle; Schiffner, Rene; Bischoff, Sabine; Rupprecht, Sven; Kroegel, Nasim; Schubert, Harald; Witte, Otto W; Schwab, Matthias; Rakers, Florian

2018-01-01

Acute stress-induced reduction of uterine blood flow (UBF) is an indirect mechanism of maternal-fetal stress transfer during late gestation. Effects of chronic psychosocial maternal stress (CMS) during early gestation, as may be experienced by many working women, on this stress signaling mechanism are unclear. We hypothesized that CMS in sheep during early gestation augments later acute stress-induced decreases of UBF, and aggravates the fetal hormonal, cardiovascular, and metabolic stress responses during later development. Six pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At 110 dGA, ewes were chronically instrumented and underwent acute isolation stress. The acute stress decreased UBF by 19% in both the CMS and control groups (p stress-induced cortisol and norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary-adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal norepinephrine is endogenous as maternal catecholamines do not cross the placenta. Cortisol in the control but not in the CMS fetuses was correlated with maternal cortisol blood concentrations; these findings indicate: (1) no increased maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses when the HPA-axis is normally inactive, due to early maturation of the fetal HPA-axis. CMS fetuses were better oxygenated, without shift towards acidosis compared to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS enhances maternal-fetal stress transfer by prolonged reduction in UBF and increased fetal HPA responsiveness.

Distinct cytokine profiles of circulating mononuclear cells stimulated with Staphylococcus aureus enterotoxin A in vitro during early and late episodes of chronic osteomyelitis

Directory of Open Access Journals (Sweden)

Gabriella Freitas Ferreira

2012-05-01

Full Text Available We investigated the cytokine profile of peripheral mononuclear cells from chronic osteomyelitis (OST patients following in vitro stimulation with staphylococcal enterotoxin A (SEA. We demonstrate that stimulation with SEA induced prominent lymphocyte proliferation and high levels of tumour necrosis factor (TNF-α, interleukin (IL-4 and IL-10 secretion in both OST and non-infected individuals (NI. Even though stimulation with SEA had no impact on IL-6 production in either patient group, the baseline level of IL-6 production by cells from OST patients was always significantly less than that produced by cells from NI. After classifying the osteomyelitic episodes based on the time after the last reactivation event as "early" (1-4 months or "late" osteomyelitis (5-12 months, we found that increased levels of TNF-α and IL-4 in combination with decreased levels of IL-6 were observed in the early episodes. By contrast, increased levels of IL-10, IL-2 and IL-6 were hallmarks of late episodes. Our data demonstrate that early osteomyelitic episodes are accompanied by an increased frequency of "high producers" of TNF-α and IL-4, whereas late events are characterised by increased frequencies of "high producers" of IL-10, IL-6 and IL-2. These findings demonstrate the distinct cytokine profiles in chronic osteomyelitis, with a distinct regulation of IL-6 production during early and late episodes.

Therapy for chronic myeloid leukemia: Past, present and future

International Nuclear Information System (INIS)

Tothova, E.

2012-01-01

Although chronic myeloid leukemia (CML) was probably first described in the early nineteenth century, there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 1960. Subsequent important landmarks were the recognition that the Ph chromosome results from a t(9;22) translocation and subsequently of BCR-ABL fusion gene. Between 1980 and 2000, allo grafting, despite the risks of morbidity and mortality, was the recommended initial treatment for younger patients with HLA-matched donors. Therapy has now been „revolutionized“ by the introduction on imatinib mesylate (IM), the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998. This paper will attempt to define approaches to management of the newly diagnosed patient with CML in chronic phase that are favored in 2012, but it is most probable these recommendations will need to be updated as further experience in gained with the use of TKI. (author)

Analyses of the pathways involved in early- and late-phase induction of IFN-beta during C. muridarum infection of oviduct epithelial cells.

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Sishun Hu

Full Text Available We previously reported that the IFN-β secreted by Chlamydia muridarum-infected murine oviduct epithelial cells (OE cells was mostly dependent on the TLR3 signaling pathway. To further characterize the mechanisms of IFN-β synthesis during Chlamydia infection of OE cells in vitro, we utilized specific inhibitory drugs to clarify the roles of IRF3 and NF-κB on both early- and late-phase C. muridarum infections. Our results showed that the pathways involved in the early-phase of IFN-β production were distinct from that in the late-phase of IFN-β production. Disruption of IRF3 activation using an inhibitor of TBK-1 at early-phase Chlamydia infection had a significant impact on the overall synthesis of IFN-β; however, disruption of IRF3 activation at late times during infection had no effect. Interestingly, inhibition of NF-κB early during Chlamydia infection also had a negative effect on IFN-β production; however, its impact was not significant. Our data show that the transcription factor IRF7 was induced late during Chlamydia infection, which is indicative of a positive feedback mechanism of IFN-β synthesis late during infection. In contrast, IRF7 appears to play little or no role in the early synthesis of IFN-β during Chlamydia infection. Finally, we demonstrate that antibiotics that target chlamydial DNA replication are much more effective at reducing IFN-β synthesis during infection versus antibiotics that target chlamydial transcription. These results provide evidence that early- and late-phase IFN-β production have distinct signaling pathways in Chlamydia-infected OE cells, and suggest that Chlamydia DNA replication might provide a link to the currently unknown chlamydial PAMP for TLR3.

Association of phase angle on bioelectrical impedance analysis and dialysis frequency with survival of chronic hemodialysis patients

Science.gov (United States)

Muzasti, R. A.; Lubis, H. R.

2018-03-01

Phase angle, a parameter by Bioelectrical Impedance Analysis, can detect body composition changes, so it can be used as a prognostic indicator in some chronic conditions. This study was for determining the relationship between PhA and hemodiálisis frequency with the survival of chronic hemodiálisis patients. This longitudinal retrospective study involved 173 chronic hemodiálisis patients at Rasyida Renal Hospital. The Kaplan-Meier method is used to determine the survival. Cox proportional hazard analysis is used to determine which variables significantly increase mortality. During the study period, 89 patients underwent hemodiálysis 3x a week (4 hours/session), and 84 patients underwent HD 2x a week (5 hours/session). Demographic and clinical characteristics in both groups were similar. There was no difference in PhA value in groups of 3x a week and group 2x a week (4.02 ± 1.13 vs 4.25 ± 1.12). Patients with twice a week hemodiálisis had a shorter survival than the 3x week group (35.14 ± 2.76 vs 38.62 ± 3.03) although it was not statistically significant (p = 0.126).

Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia.

Science.gov (United States)

Weiss, Lukas; Melchardt, Thomas; Egle, Alexander; Grabmer, Christoph; Greil, Richard; Tinhofer, Inge

2011-05-15

Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression. T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data. The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028). Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia. 2010 American Cancer Society.

Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

DEFF Research Database (Denmark)

Saglio, Giuseppe; Kim, Dong-Wook; Issaragrisil, Surapol

2010-01-01

Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase.......Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase....

Blood responses under chronic low daily dose gamma irradiation: Pt.1

International Nuclear Information System (INIS)

Seed, T.M.; Carnes, B.A.; Tolle, D.V.; Fritz, T.E.

1989-01-01

Male beagles chronically exposed to low daily doses of 60 Co γ rays show one of three hematopoietic patterns, which reflect three different distinctly responding subgroups: (1) low radioresistance with progressing aplastic anemia and shortened survival ( -S -AA subgroup); (2) high radioresistance with a complex of progressing myeloproliferative disorders ( + R-MPD group); or (3) high radioresistance with other nonMPD syndromes ( + R-nonMPD group). Blood cell levels (granulocytes, monocytes, erythrocytes, lymphocytes, and platelets) were assessed and fitted to a flexible polynomial spline model. Results showed that relative to the overall magnitude of blood cell loss as well as to the maximum rate of suppression during the initial phase, the subgroups were generally ranked - S-AA >> + R-MPD > + R-nonMPD. Relative to the overall strength of the recovery response, the subgroups were generally ranked + R-MPD > + R-nonMPD >>> - S-AA. In terms of overall maintenance levels of circulating blood cells during the recovery phase, however, the + R-nonMPD subgroup consistently exhibited stronger responses than the + R-MPD subgroup. These results support our contention that selected subgroups of dogs have strong propensities to specific hematopathologies (i.e. aplastic anemia and myeloid leukemia) under chronic irradiation and that these pathology-prone animals exhibit a series of marked differential hematopoietic responses during early preclinical phases, which serve effectively to prognosticate subsequent pathological progression. (author)

Air pollution in early life and adult mortality from chronic rheumatic heart disease.

Science.gov (United States)

Phillips, David I W; Osmond, Clive; Williams, Martin L; Jones, Alexander

2017-08-01

Chronic rheumatic heart disease (RHD) remains a globally important cause of heart disease. The reasons for the continuing high prevalence of this disease are obscure, but it may have its origins in the poor social and economic conditions with which the disease has been consistently and strongly linked. Mortality studies from the UK have suggested the importance of adverse environmental factors in early life; these studies demonstrated specific geographical associations between high rates of chest infection during infancy and subsequent RHD. They raised the possibility that early air pollution, which is known to be strongly linked with chest infection during infancy, may predispose to RHD. We related estimates of air pollution and social conditions developed by Daly in 1951-52 for 78 urban areas in England and Wales to their subsequent RHD mortality rates at ages 35-74 in men and women during 1993-2012. There were strong relationships between domestic air pollution and RHD [relative risk per standard deviation (SD) increase in pollution 1.168, 95% confidence interval (CI): 1.128 to 1.210, P air pollution association was independent of these; only overcrowding was separately linked with RHD. We present the first evidence of an association between air pollution in early life and RHD. Although there are several limitations to this study, the strength and consistency of the results, together with their biological plausibility, suggest a causal link. This deserves attention because it may have important consequences for the control of RHD in resource-poor countries where widespread use of biomass fuels and domestic pollution remain a problem. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Analysis of Loss-of-Coolant Accidents in the NIST Research Reactor - Early Phase

Energy Technology Data Exchange (ETDEWEB)

Baek, Joo S.; Diamond, David

2016-12-06

A study of the fuel temperature during the early phase of a loss-of-coolant accident (LOCA) in the NIST research reactor (NBSR) was completed. Previous studies had been reported in the preliminary safety analysis report for the conversion of the NBSR from high-enriched uranium (HEU) fuel to low-enriched (LEU) fuel. Those studies had focused on the most vulnerable LOCA situation, namely, a double-ended guillotine break in the time period after reactor trip when water is drained from either the coolant channels inside the fuel elements or the region outside the fuel elements. The current study fills in a gap in the analysis which is the early phase of the event when there may still be water present but the reactor is at power or immediately after reactor trip and pumps have tripped. The calculations were done, for both the current HEU-fueled core and the proposed LEU core, with the TRACE thermal-hydraulic systems code. Several break locations and different break sizes were considered. In all cases the increase in the clad (or fuel meat) temperature was relatively small so that a large margin to the temperature threshold for blistering (the Safety Limit for the NBSR) remained.

Unknown loads affect force production capacity in early phases of bench press throws.

Science.gov (United States)

Hernández Davó, J L; Sabido Solana, R; Sarabia Marínm, J M; Sánchez Martos, Á; Moya Ramón, M

2015-10-01

Explosive strength training aims to improve force generation in early phases of movement due to its importance in sport performance. The present study examined the influence of lack of knowledge about the load lifted in explosive parameters during bench press throws. Thirteen healthy young men (22.8±2.0 years) participated in the study. Participants performed bench press throws with three different loads (30, 50 and 70% of 1 repetition maximum) in two different conditions (known and unknown loads). In unknown condition, loads were changed within sets in each repetition and participants did not know the load, whereas in known condition the load did not change within sets and participants had knowledge about the load lifted. Results of repeated-measures ANOVA revealed that unknown conditions involves higher power in the first 30, 50, 100 and 150 ms with the three loads, higher values of ratio of force development in those first instants, and differences in time to reach maximal rate of force development with 50 and 70% of 1 repetition maximum. This study showed that unknown conditions elicit higher values of explosive parameters in early phases of bench press throws, thereby this kind of methodology could be considered in explosive strength training.

Ongoing Oxidative Stress Causes Subclinical Neuronal Dysfunction in the Recovery Phase of EAE

Science.gov (United States)

Radbruch, Helena; Bremer, Daniel; Guenther, Robert; Cseresnyes, Zoltan; Lindquist, Randall; Hauser, Anja E.; Niesner, Raluca

2016-01-01

Most multiple sclerosis (MS) patients develop over time a secondary progressive disease course, characterized histologically by axonal loss and atrophy. In early phases of the disease, focal inflammatory demyelination leads to functional impairment, but the mechanism of chronic progression in MS is still under debate. Reactive oxygen species generated by invading and resident central nervous system (CNS) macrophages have been implicated in mediating demyelination and axonal damage, but demyelination and neurodegeneration proceed even in the absence of obvious immune cell infiltration, during clinical recovery in chronic MS. Here, we employ intravital NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX1–4, DUOX1, 2) and, thus, to identify the cellular source of oxidative stress in the CNS of mice affected by experimental autoimmune encephalomyelitis (EAE) in the remission phase of the disease. This directly affects neuronal function in vivo, as monitored by cellular calcium levels using intravital FRET–FLIM, providing a possible mechanism of disease progression in MS. PMID:27014271

Dealing with subjectivity in early product design phase: a systematic approch to exploit QFD potentials

NARCIS (Netherlands)

Raharjo, H.; Brombacher, A.C.; Xie, M.

2008-01-01

Quality Function Deployment (QFD), as a customer-driven tool, is generally used in the early phase of new or improved products/services design process, and therefore most of the input parameters are highly subjective in nature. The five major input components of the QFD, which are laid in the House

SECRETED KLOTHO AND CHRONIC KIDNEY DISEASE

Science.gov (United States)

Hu, Ming Chang; Kuro-o, Makoto; Moe, Orson W.

2013-01-01

Soluble Klotho (sKl) in the circulation can be generated directly by alterative splicing of the Klotho transcript or the extracellular domain of membrane Klotho can be released from membrane-anchored Klotho on the cell surface. Unlike membrane Klotho which functions as a coreceptor for fibroblast growth factor-23 (FGF23), sKl, acts as hormonal factor and plays important roles in anti-aging, anti-oxidation, modulation of ion transport, and Wnt signaling. Emerging evidence reveals that Klotho deficiency is an early biomarker for chronic kidney diseases as well as a pathogenic factor. Klotho deficiency is associated with progression and chronic complications in chronic kidney disease including vascular calcification, cardiac hypertrophy, and secondary hyperparathyroidism. In multiple experimental models, replacement of sKl, or manipulated up-regulation of endogenous Klotho protect the kidney from renal insults, preserve kidney function, and suppress renal fibrosis, in chronic kidney disease. Klotho is a highly promising candidate on the horizon as an early biomarker, and as a novel therapeutic agent for chronic kidney disease. PMID:22396167

An economic analysis of high-dose imatinib, dasatinib, and nilotinib for imatinib-resistant chronic phase chronic myeloid leukemia in China: A CHEERS-compliant article.

Science.gov (United States)

Wu, Bin; Liu, Maobai; Li, Te; Lin, Houwen; Zhong, Hua

2017-07-01

The aim of the study was to test the cost-effectiveness of dasatinib compared to high-dose imatinib and nilotinib in Chinese patients who were diagnosed with imatinib-resistant chronic myeloid leukemia in the chronic phase (CML-CP). A Markov model combined with clinical effectiveness, utility, and cost data was used. The sensitivity analyses were conducted to determine the robustness of the model outcomes. The impact of patient assistance programs (PAPs) was assessed. Treatment with dasatinib is expected to produce 3.65, 0.59, and 0.15 more quality-adjusted life years (QALYs) in comparison with high-dose imatinib (600 and 800 mg) and nilotinib, respectively. When a PAP was available, dasatinib yielded an incremental cost of $16,417 per QALY compared to imatinib (600 mg) and was cost-saving compared to imatinib (800 mg) and nilotinib. When PAP is available in the Chinese setting, dasatinib is likely to be a cost-effective strategy for patients with CML-CP standard-dose imatinib resistance. The results should be carefully explained due to the assumptions and limitations used in the study.

Clinical Efficacy and Safety of First-Line Dasatinib Therapy and the Relevance of Velocity of BCR-ABL1 Transcript Decline for Achievement of Molecular Responses in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Report from the Juntendo Yamanashi Cooperative Study Group.

Science.gov (United States)

Takaku, Tomoiku; Iriyama, Noriyoshi; Mitsumori, Toru; Sato, Eriko; Gotoh, Akihiko; Kirito, Keita; Noguchi, Masaaki; Koike, Michiaki; Sakamoto, Junichi; Oba, Koji; Komatsu, Norio

2018-01-01

The use of tyrosine kinase inhibitors led to an improvement in the prognoses of patients with chronic myeloid leukemia (CML). The aims of this study were to investigate the efficacy and safety of dasatinib in Japanese patients and to explore the factors that affect the achievement of molecular responses. The primary endpoint was a major molecular response (MMR) by 12 months. The halving time for BCR-ABL1 transcripts was calculated using transcript levels. Thirty-two patients with chronic-phase CML (CML-CP) were enrolled and 30 received 100 mg dasatinib once daily. At 24 months of follow-up, 21 (72%) and 24 (83%) patients achieved an MMR by 12 and 24 months, respectively; the rates of a deep molecular response (DMR) by 12 and 24 months were 48 and 59%, respectively. A shorter halving time of BCR-ABL1 transcripts (≤10.6 days) accurately predicted both an MMR and a DMR. The incidence of pleural effusion was 50%. Our study reconfirmed the efficacy and safety of dasatinib treatment in Japanese patients with newly diagnosed CML-CP. In addition, the usefulness of the halving time of BCR-ABL1 transcripts was validated. These data emphasize the significance of an early treatment response in achieving a DMR during dasatinib therapy. © 2017 S. Karger AG, Basel.

Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era.

Directory of Open Access Journals (Sweden)

Zafar Iqbal

Full Text Available BACKGROUND: BCR-ABL kinase domain mutations are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CML patients. Recent studies indicate the presence of pre-existing BCR-ABL mutations in a higher percentage of CML patients when CD34+ stem/progenitor cells are investigated using sensitive techniques, and these mutations are associated with imatinib resistance and disease progression. However, such studies were limited to smaller number of patients. METHODS: We investigated BCR-ABL kinase domain mutations in CD34+ cells from 100 chronic-phase CML patients by multiplex allele-specific PCR and sequencing at diagnosis. Mutations were re-investigated upon manifestation of imatinib resistance using allele-specific PCR and direct sequencing of BCR-ABL kinase domain. RESULTS: Pre-existing BCR-ABL mutations were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48, all patients with pre-existing BCR-ABL mutations exhibited imatinib resistance. Of the 68 patients without pre-existing BCR-ABL mutations, 24 developed imatinib resistance; allele-specific PCR and BCR-ABL kinase domain sequencing detected mutations in 22 of these patients. All 32 patients with pre-existing BCR-ABL mutations had the same mutations after manifestation of imatinib-resistance. In imatinib-resistant patients without pre-existing BCR-ABL mutations, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients except T315I and Y253F mutations responded to imatinib dose escalation. CONCLUSION: Pre-existing BCR-ABL mutations can be detected in a substantial number of chronic-phase CML patients by sensitive allele-specific PCR technique using CD34+ cells. These mutations are associated with imatinib resistance if affecting drug binding directly or indirectly. After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid

Auto-inhibitory regulation of angiotensin II functionality in hamster aorta during the early phases of dyslipidemia.

Science.gov (United States)

Pereira, Priscila Cristina; Pernomian, Larissa; Côco, Hariane; Gomes, Mayara Santos; Franco, João José; Marchi, Kátia Colombo; Hipólito, Ulisses Vilela; Uyemura, Sergio Akira; Tirapelli, Carlos Renato; de Oliveira, Ana Maria

2016-06-15

Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored. Knowing that hamsters and humans have a similar lipid profile, we investigated the effects of early and advanced dyslipidemia on angiotensin II-induced contraction. Cumulative concentration-response curves for angiotensin II (1.0pmol/l to 1.0µmol/l) were obtained in the hamster thoracic aorta. We also investigated the modulatory action of NAD(P)H oxidase on angiotensin II-induced contraction using ML171 (Nox-1 inhibitor, 0.5µmol/l) and VAS2870 (Nox-4 inhibitor, 5µmol/l). Early dyslipidemia was detected in hamsters treated with a cholesterol-rich diet for 15 days. Early dyslipidemia decreased the contraction induced by angiotensin II and the concentration of Nox-4-derived hydrogen peroxide. Advanced dyslipidemia, observed in hamsters treated with cholesterol-rich diet for 30 days, restored the contractile response induced by angiotensin II by compensatory mechanism that involves Nox-4-mediated oxidative stress. The hyporresponsiveness to angiotensin II may be an auto-inhibitory regulation of the angiotensinergic function during early dyslipidemia in an attempt to reduce the effects of the upregulation of the vascular RAS during the advanced stages of atherogenesis. The recovery of vascular angiotensin II functionality during the advanced phases of dyslipidemia is the result of the upregulation of redox-pro-inflammatory pathway that might be most likely involved in atherogenesis progression rather than in the recovery of vascular function. Taken together, our findings show the early phase of dyslipidemia may be the most favorable moment for effective atheroprotective therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical evaluation of RNFL and GCC for diagnosis in early stage of chronic primary angle-closure glaucoma

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Shi Liu

2015-08-01

Full Text Available AIM:To explore the diagnosis value of retina nerve fiber layer(RNFLand ganglion cell complex(GCCin the early stage of chronic primary angle-closure glaucoma(CPACG, and investigate their relationship with mean defect(MDof visual field.METHODS: Twenty-one patients with CPACG(38 eyes, 25 patients with suspected glaucoma(SG(46 eyesand 25 normal controls(49 eyeswere selected to perform SD-OCT. Statistical difference was analyzed the thickness of RNFL and GCC of average and all quadrants, and correlation between RNFL, GCC and MD of visual field. RESULTS:There were significant differences in average and all quadrant thickness of RNFL and GCC between CPACG group and control group(PPPPPr=0.65, GCC(r=0.72in CPACG group. CONCLUSION:RNFL and GCC are useful to diagnose and monitor the early stage of CPACG, and GCC may be more significant for the disease.

A PAF receptor antagonist inhibits acute airway inflammation and late-phase responses but not chronic airway inflammation and hyperresponsiveness in a primate model of asthma

Directory of Open Access Journals (Sweden)

R. H. Gundel

1992-01-01

Full Text Available We have examined the effects of a PAF receptor antagonist, WEB 2170, on several indices of acute and chronic airway inflammation and associated changes in lung function in a primate model of allergic asthma. A single oral administration WEB 2170 provided dose related inhibition of the release of leukotriene C4 (LTC4 and prostaglandin D2 (PGD2 recovered and quantified in bronchoalveolar lavage (BAL fluid obtained during the acute phase response to inhaled antigen. In addition, oral WEB 2170 treatment in dual responder primates blocked the acute influx of neutrophils into the airways as well as the associated late-phase airway obstruction occurring 6 h after antigen inhalation. In contrast, a multiple dosing regime with WEB 2170 (once a day for 7 consecutive days failed to reduce the chronic airway inflammation (eosinophilic and associated airway hyperresponsiveness to inhaled methacholine that is characteristic of dual responder monkeys. Thus, we conclude that the generation of PAF following antigen inhalation contributes to the development of lipid mediators, acute airway inflammation and associated late-phase airway obstruction in dual responder primates; however, PAF does not play a significant role in the maintenance of chronic airway inflammation and associated airway hyperresponsiveness in this primate model.

Chronic Meningococcaemia

African Journals Online (AJOL)

clinical features, complications, laboratory findings and treatment of this condition are discussed. The resemblance, both clinically and histologically, to allergic vasculitis is stressed. S. Air. Med. J., 48, 2154 (1974). Chronic meningococcaemia is an uncommon condition today, but was well recognised in the early decades of.

Do We Know What Causes Chronic Myeloid Leukemia?

Science.gov (United States)

... Be Prevented? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases

Directory of Open Access Journals (Sweden)

Shu-Yin Tan

2015-10-01

Conclusion: The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage.

Recurrent surgical site infection of the spine diagnosed by dual 18F-NaF-bone PET/CT with early-phase scan

International Nuclear Information System (INIS)

Shim, Jai-Joon; Lee, Jeong Won; Jeon, Min Hyok; Lee, Sang Mi

2016-01-01

We report a case of a 31-year-old man who showed recurrently elevated level of the serum inflammatory marker C-reactive protein (CRP) after spinal operation. He underwent 18 F-flurodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) and dual 18 F-sodium-fluoride ( 18 F-NaF) PET/CT with an additional early-phase scan to find a hidden inflammation focus. Only mildly increased 18 F-FDG was found at the surgical site of T11 spine on 18 F-FDG PET/CT. In contrast, dual 18 F-NaF bone PET/CT with early-phase scan demonstrated focal active inflammation at the surgical site of T11 spine. After a revision operation of the T11 spine, serum CRP level decreased to the normal range without any symptom or sign of inflammation. Inflammatory focus in the surgical site of the spine can be detected with using dual 18 F-NaF bone PET/CT scan with early-phase scan. (orig.)

ETIOLOGICAL FACTORS OF CHRONIC GASTRITIS IN CHILDREN

Directory of Open Access Journals (Sweden)

G.V. Volynets

2006-01-01

Full Text Available In the article the data on the study of the etiological factors of various types of chronic gastritis in children are presented. Based on revealing of the auto antibodies to parietal gastric cells in 40,0% of children autoimmune gastritis (a type gastritis is diagnosed. Helicobacterr pylori infection is revealed in 44,8% of children. In 27,6% of children type c gastritis is diagnosed. Autoimmune gastritis in children has been linked to the active phase of chronic epsteinbbarr virus infection. the etiological factors of nonautoimmune gastritis are Helicobacter pylori infection (type b gastritis and multiple duodenogastric refluxes (type c gastritis.Key words: children, chronic gastritis, etiological factors, autoimmune gastritis, nonautoimmune gastritis, active phase of chronic Epstein-Barr virus infection, Helicobacter pylori infection.

The differences in RCAS1 and DFF45 endometrial expression between late proliferative, early secretory, and mid-secretory cycle phases.

Directory of Open Access Journals (Sweden)

Jerzy Sikora

2008-04-01

Full Text Available RCAS1 expression is related to the regulation of activated immune cells and to connective tissue remodeling within the endometrium. DFF45 seems to play an important role in the apoptotic process, most likely by acting through the regulation of DNA fragmentation. Its expression changes within the endometrium seem to be related to the resistance of endometrial cells to apoptosis. The aim of the present study was to evaluate RCAS1 and DFF45 endometrial expressions during ovulation and the implantation period. RCAS1 and DFF45 expression was assessed by the Western-blot method in endometrial tissue samples obtained from 20 patients. The tissue samples were classified according to the menstrual cycle phases in which they were collected, with a division into three phases: late proliferative, early secretory, and mid-secretory. The lowest level of RCAS1 and the highest level of DFF45 endometrial expression was found during the early secretory cycle phase. Statistically significantly higher RCAS1 and statistically significantly lower DFF45 endometrial expression was identified in the endometrium during the late proliferative as compared to the early secretory cycle phase. Moreover, statistically significantly higher RCAS1 and statistically significantly lower DFF45 expression was found in the endometrium during the mid-secretory as compared to the early secretory cycle phase. The preparation for implantation process in the endometrium is preceded by dynamic changes in endometrial ECM and results from the proper interaction between endometrial and immune cells. The course of this process is conditioned by the immunomodulating activity of endometrial cells and their resistance to immune-mediated apoptosis. These dynamic changes are closely related to RCAS1 and DFF45 expression alterations.

Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

Science.gov (United States)

Wahner-Roedler, Dietlind L.; Thompson, Jeffrey M.; Luedtke, Connie A.; King, Susan M.; Cha, Stephen S.; Elkin, Peter L.; Bruce, Barbara K.; Townsend, Cynthia O.; Bergeson, Jody R.; Eickhoff, Andrea L.; Loehrer, Laura L.; Sood, Amit; Bauer, Brent A.

2011-01-01

Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated. PMID:18990724

Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual.

Science.gov (United States)

Massett, Holly A; Mishkin, Grace; Rubinstein, Larry; Ivy, S Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A; Abrams, Jeffrey S

2016-11-15

Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. ©2016 AACRSee related commentary by Mileham and Kim, p. 5397. ©2016 American Association for Cancer Research.

Phase angle as a nutritional evaluation tool in all stages of chronic liver disease.

Science.gov (United States)

Peres, W A F; Lento, D F; Baluz, K; Ramalho, A

2012-01-01

Malnutrition is commonly and frequently under-diagnosed in clinical settings in patients with chronic liver disease (CLD) due to the limitations of nutritional evaluation methods in this population. We hypothesized that the bioelectrical impedance analysis derived phase angle (BIA-derived PhA) might be considered as a nutritional indicator in CLD since it represents either cell death or malnutrition characterized by changes in cellular membrane integrity. The aim of this study was to evaluate the BIA-derived PhA as a nutritional evaluation tool in all stages of CLD, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). Liver-related death and survival were evaluated. A total of 66 patients were enrolled in a cross-sectional study. For the nutritional diagnosis, mid-arm circumference (MAC), triceps skinfold thickness (TST), mid-arm muscle circumference (MAMC) and Subject Global Assessment (SGA) were evaluated. Biochemical and clinical evaluations were performed. Our results showed that PhA was higher in well-nourished patients, according to SGA and in the patients without hepatic encephalopathy. PhA correlated significantly with MAMC, MAC and albumin and was inversely correlated with age. No correlation was found between PhA values and the Child-Pugh score and ascites. PhA was strongly associated with survival and PhA ≤ 5.18º with relative risk increase of 2.5 for death. We conclude that the BIA-derived PhA is a relevant nutritional evaluation tool in chronic hepatitis, liver cirrhosis and HCC and the role of PhA in the prediction of survival in CLD should be examined further in a controlled study.

Nutrition for Early Chronic Kidney Disease in Adults

Science.gov (United States)

... Disease (CKD) Eating Right Related Topics English English French Español Section Navigation Chronic Kidney Disease (CKD) What ... foods, instead of deep frying. Cook with nonstick cooking spray or a small amount of olive oil ...

Early Recognition of Chronic Traumatic Encephalopathy Through FDDNP PET Imaging

Science.gov (United States)

2017-10-01

characteristic distribution is felt to be the cardinal pathologic feature of Chronic Traumatic Encephalopathy. This project will examine whether FDDNP PET...chronic traumatic encephalopathy (CTE). Pathological series have indicated that a characteristic feature of CTE is accumulation of tau protein in the...3. Accomplishments: Major goals: Upon receiving approval from the Human Research Protection Office, enrollment of participants began in March , 2015

Showing up Matters: Newark Chronic Absenteeism in the Early Years

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Chen, Peter; Rice, Cynthia

2016-01-01

Based on a 180-day school year, any student who misses 18 days or more per year--or about two days per month--is considered chronically absent. An alarming 4,328 Newark students in grades kindergarten through 3rd grade were chronically absent during the 2013-14 school year. When young students miss too much school, they will likely struggle…

Early life socioeconomic adversity is associated in adult life with chronic inflammation, carotid atherosclerosis, poorer lung function and decreased cognitive performance: a cross-sectional, population-based study

Directory of Open Access Journals (Sweden)

Sattar Naveed

2011-01-01

Full Text Available Abstract Background Socioeconomic gradients in health persist despite public health campaigns and improvements in healthcare. The Psychosocial and Biological Determinants of Ill-health (pSoBid study was designed to uncover novel biomarkers of chronic disease that may help explain pathways between socioeconomic adversity and poorer physical and mental health. Methods We examined links between indicators of early life adversity, possible intermediary phenotypes, and markers of ill health in adult subjects (n = 666 recruited from affluent and deprived areas. Classical and novel risk factors for chronic disease (lung function and atherosclerosis and for cognitive performance were assessed, and associations sought with early life variables including conditions in the parental home, family size and leg length. Results Associations were observed between father's occupation, childhood home status (owner-occupier; overcrowding and biomarkers of chronic inflammation and endothelial activation in adults (C reactive protein, interleukin 6, intercellular adhesion molecule; P P Conclusions Adverse levels of biomarkers of ill health in adults appear to be influenced by father's occupation and childhood home conditions. Chronic inflammation and endothelial activation may in part act as intermediary phenotypes in this complex relationship. Reducing the 'health divide' requires that these life course determinants are taken into account.

Men Managing, Not Teaching Foundation Phase: Teachers, Masculinity and the Early Years of Primary Schooling

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Moosa, Shaaista; Bhana, Deevia

2017-01-01

In this article we argue that eliminating the divisions of labour between men and women could work towards counteracting gender inequality within professions. Globally women are over-represented in the teaching of young children in the early years of primary school, or Foundation Phase (FP), as it is known in South Africa. We are concerned to go…

The cost-effectiveness of using chronic kidney disease risk scores to screen for early-stage chronic kidney disease.

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Yarnoff, Benjamin O; Hoerger, Thomas J; Simpson, Siobhan K; Leib, Alyssa; Burrows, Nilka R; Shrestha, Sundar S; Pavkov, Meda E

2017-03-13

Better treatment during early stages of chronic kidney disease (CKD) may slow progression to end-stage renal disease and decrease associated complications and medical costs. Achieving early treatment of CKD is challenging, however, because a large fraction of persons with CKD are unaware of having this disease. Screening for CKD is one important method for increasing awareness. We examined the cost-effectiveness of identifying persons for early-stage CKD screening (i.e., screening for moderate albuminuria) using published CKD risk scores. We used the CKD Health Policy Model, a micro-simulation model, to simulate the cost-effectiveness of using CKD two published risk scores by Bang et al. and Kshirsagar et al. to identify persons in the US for CKD screening with testing for albuminuria. Alternative risk score thresholds were tested (0.20, 0.15, 0.10, 0.05, and 0.02) above which persons were assigned to receive screening at alternative intervals (1-, 2-, and 5-year) for follow-up screening if the first screening was negative. We examined incremental cost-effectiveness ratios (ICERs), incremental lifetime costs divided by incremental lifetime QALYs, relative to the next higher screening threshold to assess cost-effectiveness. Cost-effective scenarios were determined as those with ICERs less than $50,000 per QALY. Among the cost-effective scenarios, the optimal scenario was determined as the one that resulted in the highest lifetime QALYs. ICERs ranged from $8,823 per QALY to $124,626 per QALY for the Bang et al. risk score and $6,342 per QALY to $405,861 per QALY for the Kshirsagar et al. risk score. The Bang et al. risk score with a threshold of 0.02 and 2-year follow-up screening was found to be optimal because it had an ICER less than $50,000 per QALY and resulted in the highest lifetime QALYs. This study indicates that using these CKD risk scores may allow clinicians to cost-effectively identify a broader population for CKD screening with testing for albuminuria

Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or CTRC Gene Mutations.

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Giefer, Matthew J; Lowe, Mark E; Werlin, Steven L; Zimmerman, Bridget; Wilschanski, Michael; Troendle, David; Schwarzenberg, Sarah Jane; Pohl, John F; Palermo, Joseph; Ooi, Chee Y; Morinville, Veronique D; Lin, Tom K; Husain, Sohail Z; Himes, Ryan; Heyman, Melvin B; Gonska, Tanja; Gariepy, Cheryl E; Freedman, Steven D; Fishman, Douglas S; Bellin, Melena D; Barth, Bradley; Abu-El-Haija, Maisam; Uc, Aliye

2017-07-01

To assess whether the age of onset was associated with unique features or disease course in pediatric acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). Demographic and clinical information on children with ARP or CP was collected at INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE) centers. The Cochran-Armitage trend test and Jonckheere-Terpstra test were used to examine for differences between pediatric age groups (pancreatitis, 111 (32%) were 6-11 years of age, and 102 (30%) were ≥12 years of age. Early-onset disease was associated with mutations in cationic trypsinogen (PRSS1) (P pancreatitis (P = .02), family history of CP (P chronic renal failure (P = .02). Later-onset disease was more commonly present with hypertriglyceridemia (P = .04), ulcerative colitis (P = .02), autoimmune diseases (P pancreatitis is associated strongly with PRSS1 or CTRC mutations and family history of pancreatitis. Children with later-onset disease are more likely to have nongenetic risk factors. Future studies are needed to investigate whether the disease course, response to therapy, or clinical outcomes differ relative to the timing of disease onset. Copyright © 2017 Elsevier Inc. All rights reserved.

Decrease in Urinary Creatinine Excretion in Early Stage Chronic Kidney Disease

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Tynkevich, Elena; Flamant, Martin; Haymann, Jean-Philippe; Metzger, Marie; Thervet, Eric; Boffa, Jean-Jacques; Vrtovsnik, François; Houillier, Pascal; Froissart, Marc; Stengel, Bénédicte

2014-01-01

Background Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population. Methods We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by 51Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time. Results Baseline mean urinary creatinine excretion decreased from 15.3±3.1 to 12.1±3.3 mmol/24 h (0.20±0.03 to 0.15±0.04 mmol/kg/24 h) in men, with mGFR falling from ≥60 to creatinine excretion at baseline. Mean annual decline in mGFR was 1.53±0.12 mL/min/1.73 m2 per year and that of urinary creatinine excretion rate, 0.28±0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m2 had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass. Conclusions Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass. PMID:25401694

Ultra-Fast Flash Observatory: Fast Response Space Missions for Early Time Phase of Gamma Ray Bursts

DEFF Research Database (Denmark)

Park, I.H.; Ahmad, S.; Barrillon, P.

2013-01-01

One of the unexplored domains in the study of gamma-ray bursts (GRBs) is the early time phase of the optical light curve. We have proposed Ultra-Fast Flash Observatory (UFFO) to address this question through extraordinary opportunities presented by a series of small space missions. The UFFO...

The Low-luminosity Type IIP Supernova 2016bkv with Early-phase Circumstellar Interaction

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Nakaoka, Tatsuya; Kawabata, Koji S.; Maeda, Keiichi; Tanaka, Masaomi; Yamanaka, Masayuki; Moriya, Takashi J.; Tominaga, Nozomu; Morokuma, Tomoki; Takaki, Katsutoshi; Kawabata, Miho; Kawahara, Naoki; Itoh, Ryosuke; Shiki, Kensei; Mori, Hiroki; Hirochi, Jun; Abe, Taisei; Uemura, Makoto; Yoshida, Michitoshi; Akitaya, Hiroshi; Moritani, Yuki; Ueno, Issei; Urano, Takeshi; Isogai, Mizuki; Hanayama, Hidekazu; Nagayama, Takahiro

2018-06-01

We present optical and near-infrared observations of a low-luminosity (LL) Type IIP supernova (SN) 2016bkv from the initial rising phase to the plateau phase. Our observations show that the end of the plateau is extended to ≳140 days since the explosion, indicating that this SN takes one of the longest times to finish the plateau phase among Type IIP SNe (SNe IIP), including LL SNe IIP. The line velocities of various ions at the middle of the plateau phase are as low as 1000–1500 km s‑1, which is the lowest even among LL SNe IIP. These measurements imply that the ejecta mass in SN 2016bkv is larger than that of the well-studied LL IIP SN 2003Z. In the early phase, SN 2016bkv shows a strong bump in the light curve. In addition, the optical spectra in this bump phase exhibit a blue continuum accompanied by a narrow Hα emission line. These features indicate an interaction between the SN ejecta and the circumstellar matter (CSM) as in SNe IIn. Assuming the ejecta–CSM interaction scenario, the mass loss rate is estimated to be ∼ 1.7× {10}-2 {M}ȯ yr‑1 within a few years before the SN explosion. This is comparable to or even larger than the largest mass loss rate observed for the Galactic red supergiants (∼ {10}-3 {M}ȯ yr‑1 for VY CMa). We suggest that the progenitor star of SN 2016bkv experienced a violent mass loss just before the SN explosion.

Azacytidine in combination with tyrosine kinase inhibitors induced durable responses in patients with advanced phase chronic myelogenous leukemia.

Science.gov (United States)

Ruggiu, Mathilde; Oberkampf, Florence; Ghez, David; Cony-Makhoul, Pascale; Beckeriche, Florence; Cano, Isabelle; Taksin, Anne L; Benbrahim, Omar; Ghez, Stéphanie; Farhat, Hassan; Rigaudeau, Sophie; de Gunzburg, Noémie; Lara, Diane; Terre, Christine; Raggueneau, Victoria; Garcia, Isabel; Spentchian, Marc; De Botton, Stéphane; Rousselot, Philippe

2017-11-28

Although the tyrosine kinase inhibitor (TKI) era has brought great improvement in outcome in chronic myelogenous leukemia (CML), prognosis of accelerated phase or myeloid blast crisis patients or of de novo Philadelphia chromosome-positive acute myeloid leukemia remains poor. We conducted a retrospective study on patients with advanced phase disease treated with a TKI and azacytidine. Sixteen patients were eligible. Median age was 64.9 years, the median number of previous therapies was 2.5 lines, and median follow-up was 23.1 months. Hematologic response (HR) rate was 81.3%. Median overall survival (OS), event free survival and relapse-free survival (RFS) were 31.5, 23.3, and 32.2 months, respectively. All except one patient were treated as out-patients after the first cycle. Five patients were bridged to allogenic hematopoietic stem cells transplant. The combination of a TKI and azacytidine is a safe and efficient regiment for patients with CML patients in advanced phases.

Data assimilation in the early phase: Kalman filtering RIMPUFF

International Nuclear Information System (INIS)

Astrup, P.; Turcanu, C.; Puch, R.O.; Palma, C.R.; Mikkelsen, T.

2004-09-01

In the framework of the DAONEM project (Data Assimilation for Off-site Nuclear Emergency Management), a data assimilation module, ADUM (Atmospheric Dispersion Updating Module), for the mesoscale atmospheric dispersion program RIMPUFF (Risoe Mesoscale Puff model) part of the early-phase programs of RODOS (Realtime Online DecisiOn Support system for nuclear emergencies) has been developed. It is built on the Kalman filtering algorithm and it assimilates 10-minute averaged gamma dose rates measured at ground level stations. Since the gamma rates are non-linear functions of the state vector variables, the applied Kalman filter is the so-called Extended Kalman filter. In more ways the implementation is non standard: 1) the number of state vector variables varies with time, and 2) the state vector variables are prediction updated with 1-minute time steps but only Kalman filtered every 10 minutes, and this based on time averaged measurements. Given reasonable conditions, i.e. a spatially dense distribution of gamma monitors and a realistic wind field, the developed ADUM module is found to be able to enhance the prediction of the gamma dose field. Based on some of the Kalman filtering parameters, another module, ToDeMM, has been developed for providing the late-phase DeMM (Deposition Monitoring Module) of RODOS with an ensemble of fields of ground level air concentrations and wet deposited material. This accounts for the uncertainty estimation of this kind of quantities as calculated by RIMPUFF for use by DeMM. (au)

The early phase of /see symbol/ production development in adult Japanese learners of English.

Science.gov (United States)

Saito, Kazuya; Munro, Murray J

2014-12-01

Although previous research indicates that Japanese speakers' second language (L2) perception and production of English /see symbol/ may improve with increased L2 experience, relatively little is known about the fine phonetic details of their /see symbol/ productions, especially during the early phase of L2 speech learning. This cross-sectional study examined acoustic properties of word-initial /see symbol/ from 60 Japanese learners with a length of residence of between one month and one year in Canada. Their performance was compared to that of 15 native speakers of English and 15 low-proficiency Japanese learners of English. Formant frequencies (F2 and F3) and F1 transition durations were evaluated under three task conditions--word reading, sentence reading, and timed picture description. Learners with as little as two to three months of residence demonstrated target-like F2 frequencies. In addition, increased LOR was predictive of more target-like transition durations. Although the learners showed some improvement in F3 as a function of LOR, they did so mainly at a controlled level of speech production. The findings suggest that during the early phase of L2 segmental development, production accuracy is task-dependent and is influenced by the availability of L1 phonetic cues for redeployment in L2.

Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits

International Nuclear Information System (INIS)

Jirkovský, Eduard; Lenčová-Popelová, Olga; Hroch, Miloš; Adamcová, Michaela; Mazurová, Yvona; Vávrová, Jaroslava

2013-01-01

Despite incomplete understanding to its mechanism of action, dexrazoxane (DEX) is still the only clearly effective cardioprotectant against chronic anthracycline (ANT) cardiotoxicity. However, its clinical use is currently restricted to patients exceeding significant ANT cumulative dose (300 mg/m 2 ), although each ANT cycle may induce certain potentially irreversible myocardial damage. Therefore, the aim of this study was to compare early and delayed DEX intervention against chronic ANT cardiotoxicity and study the molecular events involved. The cardiotoxicity was induced in rabbits with daunorubicin (DAU; 3 mg/kg/week for 10 weeks); DEX (60 mg/kg) was administered either before the 1st or 7th DAU dose (i.e. after ≈300 mg/m 2 cumulative dose). While both DEX administration schedules prevented DAU-induced premature deaths and severe congestive heart failure, only the early intervention completely prevented the left ventricular dysfunction, myocardial morphological changes and mitochondrial damage. Further molecular analyses did not support the assumption that DEX cardioprotection is based and directly proportional to protection from DAU-induced oxidative damage and/or deletions in mtDNA. Nevertheless, DAU induced significant up-regulation of heme oxygenase 1 pathway while heme synthesis was inversely regulated and both changes were schedule-of-administration preventable by DEX. Early and delayed DEX interventions also differed in ability to prevent DAU-induced down-regulation of expression of mitochondrial proteins encoded by both nuclear and mitochondrial genome. Hence, the present functional, morphological as well as the molecular data highlights the enormous cardioprotective effects of DEX and provides novel insights into the molecular events involved. Furthermore, the data suggests that currently recommended delayed intervention may not be able to take advantage of the full cardioprotective potential of the drug

Nationwide epidemiological survey of early chronic pancreatitis in Japan.

Science.gov (United States)

Masamune, Atsushi; Kikuta, Kazuhiro; Nabeshima, Tatsuhide; Nakano, Eriko; Hirota, Morihisa; Kanno, Atsushi; Kume, Kiyoshi; Hamada, Shin; Ito, Tetsuhide; Fujita, Motokazu; Irisawa, Atsushi; Nakashima, Masanori; Hanada, Keiji; Eguchi, Takaaki; Kato, Ryusuke; Inatomi, Osamu; Shirane, Akio; Takeyama, Yoshifumi; Tsuji, Ichiro; Shimosegawa, Tooru

2017-08-01

The world's first diagnostic criteria for early CP were proposed in 2009 in Japan. This study aimed to clarify the clinico-epidemiological features of early CP in Japan. Patients with early CP who were diagnosed according to the diagnostic criteria for early CP and had visited the selected hospitals in 2011 were surveyed. The study consisted of two-stage surveys: the number of patients with early CP was estimated by the first questionnaire and their clinical features were assessed by the second questionnaire. The estimated number of early CP patients was 5410 (95% confidence interval 3675-6945), with an overall prevalence of 4.2 per 100,000 persons. The number of patients who were newly diagnosed with early CP was estimated to be 1330 (95% confidence interval 1058-1602), with an annual incidence of 1.0 per 100,000 persons. Detailed clinical information was obtained in 151 patients in the second survey. The male-to-female sex ratio was 1.32:1. The mean age was 60.4 and the mean age at disease onset was 55.4. Idiopathic (47.7%) and alcoholic (45.0%) were the two most common etiologies. Proportions of female and idiopathic cases were higher in early CP than in definite CP. Hyperechoic foci without shadowing and stranding were the most common findings on endoscopic ultrasonography. The clinical profiles of early CP patients who showed lobularity with honeycombing on endoscopic ultrasonography or previous episodes of acute pancreatitis were similar to those of definite CP patients. We clarified the current status of early CP in Japan.

Ultrastructural Complexity of Nuclear Components During Early Apoptotic Phases in Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Christian Castelli

2001-01-01

Full Text Available Fractal morphometry was used to investigate the ultrastructural features of the plasma membrane, perinuclear membrane and nuclear chromatin in SK‐BR‐3 human breast cancer cells undergoing apoptosis. Cells were incubated with 1 μM calcimycin (A23187 for 24 h. Cells in the early stage of apoptosis had fractal dimension (FD values indicating that their plasma membranes were less rough (lower FD than those of control cells, while their perinuclear membranes were unaffected. Changes of the chromatin texture within the entire nucleus and in selected nuclear domains were more pronounced in treated cells. This confirms that the morphological reorganization imputable to a loss of structural complexity (reduced FD occurs in the early stage of apoptosis, is accompanied by the inhibition of distinct enzymatic events and precedes the onset of conventional cellular markers, which can only be detected during the active phases of the apoptotic process.

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

Science.gov (United States)

Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

2016-03-01

Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

Maintenance phase in psoralen-ultraviolet A phototherapy of early-stage mycosis fungoides. A critically appraised topic.

Science.gov (United States)

Grandi, V; Delfino, C; Pileri, A; Pimpinelli, N

2017-08-01

A 65-year-old patient affected by mycosis fungoides (MF) stage IB achieved complete remission (CR) after a cycle of PUVA phototherapy. The U.S. Cutaneous Lymphoma Consortium (USCLC) guidelines suggest that the patient should be kept in the maintenance phase, defined as a 'period of gradual decrease of frequency of UVL [ultraviolet light] while in clinical remission before discontinuation of phototherapy' by slowly tapering the number of psoralen-ultraviolet A (PUVA) applications over time up to clinical relapse. The USCLC guidelines also suggest a standardized schedule for the maintenance phase. Alternatively, the patient could end PUVA therapy and go straight to follow-up. The aim of this critically appraised topic (CAT) was to determine if a maintenance phase gives a significant benefit in terms of relapse rate (RR) and RFI in patients affected by early-stage MF who had achieved CR under PUVA phototherapy. Embase, PubMed and TRIP databases were searched for 'mycosis fungoides' AND [('photochemotherapy' OR 'puva') OR 'psoralen'] in June 2016. Three articles matched our inclusion criteria and are discussed in this CAT. In this field of research the literature is poor and the reported level of evidence is low. Only one of the studies was conducted prospectively, and none were randomized. No significant difference in terms of reduction in relapse rate or increase in RFI in patients who underwent a PUVA maintenance phase emerged when compared with those who went for simple follow-up. Further randomized clinical trials (RCTs) are required in order to evaluate maintenance phase vs. no treatment before it can be favoured as the standard protocol of treatment in early-stage MF. At the time of writing this paper, we report an ongoing Austrian multicentre RCT (Clinical Trial.gov identifier: NCT01686594) that will hopefully give useful results in this topic. © 2017 British Association of Dermatologists.

Aggregation of MBP in chronic demyelination.

Science.gov (United States)

Frid, Kati; Einstein, Ofira; Friedman-Levi, Yael; Binyamin, Orli; Ben-Hur, Tamir; Gabizon, Ruth

2015-07-01

Misfolding of key disease proteins to an insoluble state is associated with most neurodegenerative conditions, such as prion, Parkinson, and Alzheimer's diseases. In this work, and by studying animal models of multiple sclerosis, we asked whether this is also the case for myelin basic protein (MBP) in the late and neurodegenerative phases of demyelinating diseases. To this effect, we tested whether MBP, an essential myelin component, present prion-like properties in animal models of MS, as is the case for Cuprizone-induced chronic demyelination or chronic phases of Experimental Autoimmune Encephalomyelitis (EAE). We show here that while total levels of MBP were not reduced following extensive demyelination, part of these molecules accumulated thereafter as aggregates inside oligodendrocytes or around neuronal cells. In chronic EAE, MBP precipitated concomitantly with Tau, a marker of diverse neurodegenerative conditions, including MS. Most important, analysis of fractions from Triton X-100 floatation gradients suggest that the lipid composition of brain membranes in chronic EAE differs significantly from that of naïve mice, an effect which may relate to oxidative insults and subsequently prevent the appropriate insertion and compaction of new MBP in the myelin sheath, thereby causing its misfolding and aggregation. Prion-like aggregation of MBP following chronic demyelination may result from an aberrant lipid composition accompanying this pathological status. Such aggregation of MBP may contribute to neuronal damage that occurs in the progressive phase of MS.

Early diagnosis of interferon-induced myocardial disorder in patients with chronic hepatitis C. Evaluation by myocardial imaging with 123I-BMIPP

International Nuclear Information System (INIS)

Kondo, Yuki; Yukinaka, Michiko; Nomura, Masahiro; Nakaya, Yutaka; Ito, Susumu

2000-01-01

Interferon (IFN) therapy for chronic hepatitis C is sometimes associated with cardiac complications. In the present study, we performed myocardial imaging with 123 I-labeled β-methyl-p-iodophenylpentadecanoic acid ( 123 I-BMIPP) in order to evaluate myocardial disorders caused by IFN. We studied 40 healthy subjects (H group) and 25 patients with chronic hepatitis C who had been treated with IFN (IFN group). A Holter electrocardiogram (ECG) was performed and the autonomic nervous function was assessed by analyzing the spectral variability and 1/f fluctuation of heart rate. Myocardial planner imaging with 123 I-BMIPP was performed to obtain the time activity curve for 20 min immediately after administration of 123 I-BMIPP (dynamic study). Early and delayed myocardial single photon emission computed tomography (SPECT) images were expressed as Bull's eyes and the myocardium was divided into four segments to calculate the washout rate for each segment on early and late SPECT images (early and late SPECT study). No significant differences in autonomic nervous function were observed between the two groups in heart rate variability. In a dynamic study, the reduction rate from the time activity curve was significantly higher in the IFN group compared with the H group (reduction rate, IFN group, 5.3±3.7% vs H group, 1.2±3.3%; P 123 I-BMIPP myocardial scintigraphy examination several months after IFN therapy. These results indicate that metabolic disorders of fatty acids caused by IFN therapy can be detected before abnormalities are observed by Holter-ECG or echocardiography. (author)

Early diagnosis of interferon-induced myocardial disorder in patients with chronic hepatitis C: evaluation by myocardial imaging with 123I-BMIPP.

Science.gov (United States)

Kondo, Y; Yukinaka, M; Nomura, M; Nakaya, Y; Ito, S

2000-01-01

Interferon (IFN) therapy for chronic hepatitis C is sometimes associated with cardiac complications. In the present study, we performed myocardial imaging with 123I-labeled beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) in order to evaluate myocardial disorders caused by IFN. We studied 40 healthy subjects (H group) and 25 patients with chronic hepatitis C who had been treated with IFN (IFN group). A Holter electrocardiogram (ECG) was performed and the autonomic nervous function was assessed by analyzing the spectral variability and 1/f fluctuation of heart rate. Myocardial planner imaging with 123I-BMIPP was performed to obtain the time activity curve for 20min immediately after administration of 123I-BMIPP (dynamic study). Early and delayed myocardial single photon emission computed tomography (SPECT) images were expressed as Bull's eyes and the myocardium was divided into four segments to calculate the washout rate for each segment on early and late SPECT images (early and late SPECT study). No significant differences in autonomic nervous function were observed between the two groups in heart rate variability. In a dynamic study, the reduction rate from the time activity curve was significantly higher in the IFN group compared with the H group (reduction rate, IFN group, 5.3 +/- 3.7% vs H group, 1.2 +/- 3.3%; P acids caused by IFN was reversed on the second 123I-BMIPP myocardial scintigraphy examination several months after IFN therapy. These results indicate that metabolic disorders of fatty acids caused by IFN therapy can be detected before abnormalities are observed by Holter-ECG or echocardiography.

Differential association with cellular substructures of pseudorabies virus DNA during early and late phases of replication

International Nuclear Information System (INIS)

Ben-Porat, T.; Veach, R.A.; Blankenship, M.L.; Kaplan, A.S.

1984-01-01

Pseudorabies virus DNA synthesis can be divided into two phases, early and late, which can be distinguished from each other on the basis of the structures of the replicating DNA. The two types of replicating virus DNA can also be distinguished from each other on the basis of the cellular substructures with which each is associated. Analysis by electron microscopic autoradiography showed that during the first round of replication, nascent virus DNA was found in the vicinity of the nuclear membrane; during later rounds of replication the nascent virus DNA was located centrally within the nucleus. The degree of association of virus DNA synthesized at early and late phases with the nuclear matrix fractions also differed; a larger proportion of late than of early nascent virus DNA was associated with this fraction. While nascent cellular DNA only was associated in significant amounts with the nuclear matrix fraction, a large part (up to 40%) of all the virus DNA remained associated with this fraction. However, no retention of specific virus proteins in this fraction was observed. Except for two virus proteins, which were preferentially extracted from the nuclear matrix, approximately 20% of all virus proteins remained in the nuclear matrix fraction. The large proportion of virus DNA associated with the nuclear fraction indicated that virus DNA may be intimately associated with some proteins

Cosmological phase transitions

International Nuclear Information System (INIS)

Kolb, E.W.

1993-10-01

If modern ideas about the role of spontaneous symmetry breaking in fundamental physics are correct, then the Universe should have undergone a series of phase transitions early in its history. The study of cosmological phase transitions has become an important aspect of early-Universe cosmology. In this lecture I review some very recent work on three aspects of phase transitions: the electroweak transition, texture, and axions

Radiological Emergency Preparedness after the Early Phase of an Accident : Focusing on an Air Contamination Event

International Nuclear Information System (INIS)

Jeong, Hyo Joon; Hwang, Won Tae; Kim, Eun Han; Han, Moon Hee

2010-01-01

Toxic materials in an urban area can be caused by a variety of events, such as accidental releases on industrial complexes, accidents during the transportation of hazardous materials and intentional explosions. Most governments around the world and their citizens have become increasingly worried about intentional accidents in urban area after the 911 terrorist attack in the United States of America. Even though there have been only a few attempted uses of Radiological Dispersal Devices (RDDs), accidental releases have occurred many times at commercial nuclear power plants and nuclear waste disposal sites. When an intentional release of radioactive materials occurs in an urban area, air quality for radioactive materials in the environment is of great importance to take action for countermeasures and environmental risk assessments. Atmospheric modeling is part of the decision making tasks and that it is particularly important for emergency managers as they often need to take actions quickly on very inadequate information(1). A simple model such as HOTSPOT required wind direction and source term would be enough to support the decision making in the early phase of an accident, but more sophisticated atmospheric modeling is required to adjust decontamination area and relocation etc after the early phase of an accidental event. In this study, we assume an explosion of 137 Cs using RDDs in the metropolitan area of Soul, South Korea. California Puff Model (CALPUFF) is used to calculate an atmospheric dispersion and transport for 137 Cs. Atmospheric dispersion and quantitative radiological risk analysis for 137 Cs were performed assuming an intentional explosion in the metropolitan area of Soul, South Korea after the early phase of emergency. These kinds of atmospheric modeling and risk analysis could provide a means for decision makers to take action on important issues such as the cleanup of the contaminated area and countermeasures to protect the public caused by

A tale of two timescales: Mixing, mass generation, and phase transitions in the early universe

Science.gov (United States)

Dienes, Keith R.; Kost, Jeff; Thomas, Brooks

2016-02-01

Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically—such as during cosmological mass-generating phase transitions—the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this paper, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system—often by many orders of magnitude—but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "reoverdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings.

Secretory activity and cell cycle alteration of alveolar type II cells in the early and late phase after irradiation

International Nuclear Information System (INIS)

Willner, Jochen; Vordermark, Dirk; Schmidt, Michael; Gassel, Andreamaria; Flentje, Michael; Wirtz, Hubert

2003-01-01

Purpose: Type II cells and the surfactant system have been proposed to play a central role in pathogenesis of radiation pneumonitis. We analyzed the secretory function and proliferation parameters of alveolar type II cells in the early (until 24 h) and late phase (1-5 weeks) after irradiation (RT) in vitro and in vivo. Methods and Materials: Type II cells were isolated from rats according to the method of Dobbs. Stimulation of secretion was induced with terbutaline, adenosine triphosphate (ATP), and 12-O-tetradecanoylphorbol-13-acetate (TPA) for a 2-h period. Determination of secretion was performed using 3 H-labeled phosphatidylcholine. For the early-phase analysis, freshly isolated and adherent type II cells were irradiated in vitro with 9-21 Gy (stepwise increase of 3 Gy). Secretion stimulation was initiated 1, 6, 24, and 48 h after RT. For late-phase analysis, type II cells were isolated 1-5 weeks after 18 Gy whole lung or sham RT. Each experiment was repeated at least fivefold. Flow cytometry was used to determine cell cycle distribution and proliferating cell nuclear antigen index. Results: During the early-phase (in vitro) analysis, we found a normal stimulation of surfactant secretion in irradiated, as well as unirradiated, cells. No change in basal secretion and no dose effect were seen. During the late phase, 1-5 weeks after whole lung RT, we observed enhanced secretory activity for all secretagogues and a small increase in basal secretion in Weeks 3 and 4 (pneumonitis phase) compared with controls. The total number of isolated type II cells, as well as the rate of viable cells, decreased after the second post-RT week. Cell cycle alterations suggesting an irreversible G 2 /M block occurred in the second post-RT week and did not resolve during the observation period. The proliferating cell nuclear antigen index of type II cells from irradiated rats did not differ from that of controls. Conclusion: In contrast to literature data, we observed no direct

ONGOING OXIDATIVE STRESS CAUSES SUBCLINICAL NEURONAL DYSFUNCTION IN THE RECOVERY PHASE OF EAE

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Helena eRadbruch

2016-03-01

Full Text Available Most multiple sclerosis patients develop over time a secondary progressive disease course, characterized histologically by axonal loss and atrophy. In early phases of the disease, focal inflammatory demyelination leads to functional impairment, but the mechanism of chronic progression in multiple sclerosis is still under debate. Reactive oxygen species generated by invading and resident central nervous system (CNS macrophages have been implicated in mediating demyelination and axonal damage, but demyelination and neurodegeneration proceed even in the absence of obvious immune cell infiltration, during clinical recovery in chronic multiple sclerosis. Here, we employ intravital NAD(PH fluorescence lifetime imaging to detect functional NADPH oxidases (NOX1-4, DUOX1,2 and, thus, to identify the cellular source of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE in the remission phase of the disease. This directly affects neuronal function in vivo, as monitored by cellular calcium levels using intravital FRET-FLIM, providing a possible mechanism of disease progression in multiple sclerosis.

Relationship between the use of inhaled steroids for chronic respiratory diseases and early outcomes in community-acquired pneumonia.

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Jordi Almirall

Full Text Available BACKGROUND: The role of inhaled steroids in patients with chronic respiratory diseases is a matter of debate due to the potential effect on the development and prognosis of community-acquired pneumonia (CAP. We assessed whether treatment with inhaled steroids in patients with chronic bronchitis, COPD or asthma and CAP may affect early outcome of the acute pneumonic episode. METHODS: Over 1-year period, all population-based cases of CAP in patients with chronic bronchitis, COPD or asthma were registered. Use of inhaled steroids were registered and patients were followed up to 30 days after diagnosis to assess severity of CAP and clinical course (hospital admission, ICU admission and mortality. RESULTS: Of 473 patients who fulfilled the selection criteria, inhaled steroids were regularly used by 109 (23%. In the overall sample, inhaled steroids were associated with a higher risk of hospitalization (OR=1.96, p = 0.002 in the bivariate analysis, but this effect disappeared after adjusting by other severity-related factors (adjusted OR=1.08, p=0.787. This effect on hospitalization also disappeared when considering only patients with asthma (OR=1.38, p=0.542, with COPD alone (OR=4.68, p=0.194, but a protective effect was observed in CB patients (OR=0.15, p=0.027. Inhaled steroids showed no association with ICU admission, days to clinical recovery and mortality in the overall sample and in any disease subgroup. CONCLUSIONS: Treatment with inhaled steroids is not a prognostic factor in COPD and asthmatic patients with CAP, but could prevent hospitalization for CAP in patients with clinical criteria of chronic bronchitis.

Early Factors Associated with the Development of Chronic Pain in Trauma Patients

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Raoul Daoust

2018-01-01

Full Text Available Objective. To identify factors, available at the time of trauma admission, associated with the development of chronic pain to allow testing of preventive approaches. Methods. In a retrospective observational cohort study, we included all patients ≥ 18 years old admitted for injury in 57 adult trauma centers in the province of Quebec (Canada between 2004 and 2014. Chronic pain was defined as follows: treated in a chronic pain clinic, diagnosed with chronic pain, or received at least 2 prescriptions of chronic pain medications 3 to 12 months postinjury. Results. A total of 95,134 patients were retained for analysis. Mean age was 59.8 years (±21.7, and 52% were men. The causes of trauma were falls (63% and motor vehicle accidents (22%. We identified 14,518 patients (15.3%; 95% CI: 15.1–15.5 who developed chronic pain. After controlling for confounding factors, the variables associated with chronic pain were spinal cord injury (OR = 3.9; 95% CI: 3.4–4.6, disc-vertebra trauma (OR = 1.6; 95% CI: 1.5–1.7, history of alcoholism (OR = 1.4; 95% CI: 1.2–1.7, history of anxiety (OR = 1.4; 95% CI: 1.2–1.5, history of depression (OR = 1.3; 95% CI: 1.1–1.4, and being female (OR = 1.3; 95% CI: 1.2–1.3. The area under the receiving operating characteristic curve derived from the model was 0.80. Conclusions. We identified risk factors present on hospital admission that can predict trauma patients who will develop chronic pain. These factors should be prospectively validated.

X-ray diagnosis of bronchial obstruction in chronic pneumonia

International Nuclear Information System (INIS)

Mamilyaev, R.M.

1981-01-01

Combined radiobronchological examination of patients with chronic pneumonia in the phase of reverse development of the disease has been performed. Severity, localization and extent of bronchial obstruction have been studied, depending on the phase of chronic pneumonia and aspects of lung tissue alterations. Bronchial lesions characteristic of chronic pneumonia were defined, as well as importance of x-ray examination methods for bronchial obstruction diagnosis. Three types of bronchial obstruction were distinguished: bronchoconstriction, bronchodilatation and their combination. With regard to the character and severity of bronchial and pulmonary tissue lesions 3 variants of chronic pneumonia are offered to be differentiated: bronchitic, bronchoectatic, and abscess-forming. The main significance in diagnosis of chronic pneumonia is attributed to combined x-ray examination, which also includes radiobronchological investigation in the first two variants of the disease [ru

Phase-based x-ray scattering—A possible method to detect cancer cells in a very early stage

Energy Technology Data Exchange (ETDEWEB)

Feye-Treimer, U., E-mail: feye-treimer@helmholtz-berlin.de; Treimer, W. [Department of Mathematics, Physics and Chemistry, University of Applied Sciences, D-13353 Berlin, Germany and Joint Department G-GTOMO, Helmholtz Zentrum fuer Materialien und Energie Berlin, D-14109 Berlin (Germany)

2014-05-15

Purpose: This theoretical work contains a detailed investigation of the potential and sensitivity of phase-based x-ray scattering for cancer detection in biopsies if cancer is in a very early stage of development. Methods: Cancer cells in their early stage of development differ from healthy ones mainly due to their faster growing cell nuclei and the enlargement of their densities. This growth is accompanied by an altered nucleus–plasma relation for the benefit of the cell nuclei, that changes the physical properties especially the index of refraction of the cell and the one of the cell nuclei. Interaction of radiation with matter is known to be highly sensitive to small changes of the index of refraction of matter; therefore a detection of such changes of volume and density of cell nuclei by means of high angular resolved phase-based scattering of x rays might provide a technique to distinguish malignant cells from healthy ones ifthe cell–cell nucleus system is considered as a coherent phase shifting object. Then one can observe from a thin biopsy which represents a monolayer of cells (no multiple scattering) that phase-based x-ray scattering curves from healthy cells differ from those of cancer cells in their early stage of development. Results: Detailed calculations of x-ray scattering patterns from healthy and cancer cell nuclei yield graphs and numbers with which one can distinguish healthy cells from cancer ones, taking into account that both kinds of cells occur in a tissue within a range of size and density. One important result is the role and the influence of the (lateral) coherence width of the radiation on the scattering curves and the sensitivity of phase-based scattering for cancer detection. A major result is that a larger coherence width yields a larger sensitivity for cancer detection. Further import results are calculated limits for critical sizes and densities of cell nuclei in order to attribute the investigated tissue to be healthy or

Catastrophic shifts in ecosystems: spatial early warnings and management procedures (Inspired in the physics of phase transitions)

Energy Technology Data Exchange (ETDEWEB)

Fort, H [Complex Systems Group, Instituto de Fisica, Facultad de Ciencias, Universidad de la Republica, Igua 4225, 11400 Montevideo (Uruguay); Mazzeo, N [Depto. de EcologIa, Facultad de Ciencias, Universidad de la Republica, Igua 4225, 11400 Montevideo (Uruguay); Scheffer, M; Nes, E van, E-mail: hugo@fisica.edu.u [Wageningen Agricultural University, Aquatic Ecology and Water Quality Management Group, PO Box 47, 6700 AA Wageningen (Netherlands)

2010-09-01

Ecosystems are complex systems which can respond to gradual changes of their conditions by a sudden shift to a contrasting regime or alternative stable state (ASS). Predicting such critical points before they are reached is extremely difficult and providing early warnings is fundamental to design management protocols for ecosystems. Here we study different spatial versions of popular ecological models which are known to exhibit ASS. The spatial heterogeneity is introduced by a local parameter varying from cell to cell in a regular lattice. Transport of biomass among cells occurs by simple diffusion. We investigate whether different quantities from statistical mechanics -like the variance, the two-point correlation function and the patchiness-may serve as early warnings of catastrophic phase transitions between the ASS. In particular, we find that the patch-size distribution follows a power law when the system is close to the catastrophic transition. We also provide links between spatial and temporal indicators and analyze how the interplay between diffusion and spatial heterogeneity may affect the earliness of each of the observables. Finally, we comment on similarities and differences between these catastrophic shifts and paradigmatic thermodynamic phase transitions like the liquid-vapor change of state for a fluid like water.

Catastrophic shifts in ecosystems: spatial early warnings and management procedures (Inspired in the physics of phase transitions)

International Nuclear Information System (INIS)

Fort, H; Mazzeo, N; Scheffer, M; Nes, E van

2010-01-01

Ecosystems are complex systems which can respond to gradual changes of their conditions by a sudden shift to a contrasting regime or alternative stable state (ASS). Predicting such critical points before they are reached is extremely difficult and providing early warnings is fundamental to design management protocols for ecosystems. Here we study different spatial versions of popular ecological models which are known to exhibit ASS. The spatial heterogeneity is introduced by a local parameter varying from cell to cell in a regular lattice. Transport of biomass among cells occurs by simple diffusion. We investigate whether different quantities from statistical mechanics -like the variance, the two-point correlation function and the patchiness-may serve as early warnings of catastrophic phase transitions between the ASS. In particular, we find that the patch-size distribution follows a power law when the system is close to the catastrophic transition. We also provide links between spatial and temporal indicators and analyze how the interplay between diffusion and spatial heterogeneity may affect the earliness of each of the observables. Finally, we comment on similarities and differences between these catastrophic shifts and paradigmatic thermodynamic phase transitions like the liquid-vapor change of state for a fluid like water.

Extension of quality-by-design concept to the early development phase of pharmaceutical R&D processes.

Science.gov (United States)

Csóka, Ildikó; Pallagi, Edina; Paál, Tamás L

2018-03-27

Here, we propose the extension of the quality-by-design (QbD) concept to also fit the early development phases of pharmaceuticals by adding elements that are currently widely applied, but not yet included in the QbD model in a structured way. These are the introduction of a 'zero' preformulation phase (i.e., selection of drug substance, possible dosage forms and administration routes based on the evaluated therapeutic need); building in stakeholders' (industry, patient, and regulatory) requirements into the quality target product profile (QTTP); and the use of modern quality management tools during the composition and process design phase [collecting critical quality attributes (CQAs) and selection of CPPs) for (still laboratory-scale) design space (DS) development. Moreover, during industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be changed; however, we recommend that the existing QbD elements are reconsidered and updated after this phase. Copyright © 2018 Elsevier Ltd. All rights reserved.

Correlation of early-phase 18F-florbetapir (AV-45/Amyvid) PET images to FDG images: preliminary studies

International Nuclear Information System (INIS)

Hsiao, Ing-Tsung; Hsieh, Chia-Ju; Wey, Shiaw-Pyng; Lin, Kun-Ju; Huang, Chin-Chang; Hsu, Wen-Chun; Yen, Tzu-Chen; Kung, Mei-Ping

2012-01-01

18 F-Florbetapir (AV-45/Amyvid) is a novel positron emission tomography (PET) tracer for imaging plaque pathology in Alzheimer's disease (AD), while PET images of fluorodeoxyglucose (FDG) for cerebral glucose metabolism can provide complementary information to amyloid plaque images for diagnosis of AD. The goal of this preliminary study was to investigate the perfusion-like property of relative cerebral blood flow estimates (R 1 ) and summed early-phase AV-45 images [perfusion AV-45 (pAV-45)] and optimize the early time frame for pAV-45. Dynamic AV-45 PET scans (0-180 min) were performed in seven subjects. pAV-45, late-phase AV-45, and FDG images were spatially normalized to the Montreal Neurological Institute template aided by individual MRI images, and the corresponding standardized uptake value ratio (SUVR) was computed. The R 1 images were derived from a simplified reference tissue model. Correlations between regional and voxelwise R 1 and the corresponding FDG images were calculated. An optimization of time frames of pAV-45 was conducted in terms of correlation to FDG images. The optimal early time frame was validated in a separate cohort. The regional distribution in the R 1 images correlated well (R = 0.91) to that of the FDG within subjects. Consistently high correlation was noted across a long range of time frames. The maximal correlation of pAV-45 to FDG SUVR of R = 0.95 was observed at the time frame of 1-6 min, while the peak correlation of R = 0.99 happened at 0-2 min between pAV-45 and R 1 . A similar result was achieved in the validation cohort. Preliminary results showed that the distribution patterns of R 1 and pAV-45 images are highly correlated with normalized FDG images, and the initial 5-min early time frame of 1-6 min is potentially useful in providing complementary FDG-like information to the amyloid plaque density by late-phase AV-45 images. (orig.)

Chronic comorbidity in patients with early rheumatoid arthritis: a descriptive study.

Science.gov (United States)

Kroot, E J; van Gestel, A M; Swinkels, H L; Albers, M M; van de Putte, L B; van Riel, P L

2001-07-01

To study the presence of chronic coexisting diseases in patients with rheumatoid arthritis (RA) and its effect on RA treatment, disease course, and outcome during the first years of the disease. From January 1985 to December 1990, 186 patients with recent onset RA were enrolled in a prospective longitudinal study. Between January 1991 and November 1992 patients were interviewed on the basis of a comorbidity questionnaire. For analysis the diseases were coded according to the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) medical diagnoses. Disease activity during the period of followup was measured by the Disease Activity Score. Outcome in terms of physical disability (Health Assessment Questionnaire) and radiological damage (Sharp's modified version) over 3 and 6 year periods was determined. In the group of 186 patients, with mean disease duration of 4.3 years at January 1991, 50 patients (27%) reported at least one chronic coexisting disease. The most frequently reported coexisting diseases were of cardiovascular (29%), respiratory (18%), or dermatological (11%) origin. For the major part (66%) chronic coexisting diseases were already present before onset of RA. No statistically significant differences in use of disease modifying antirheumatic drugs or corticosteroids were observed between RA patients with and without chronic coexisting diseases. No statistically significant differences were found in disease activity or in outcome in terms of physical disability and radiological damage over 3 and 6 year periods between the 2 groups with RA. The results showed that about 27% of patients with RA in this inception cohort had at least one chronic coexisting disease. Treatment, disease course, and outcome did not differ between patients with and without chronic coexisting diseases during the first years of the disease.

Decrease in early right alpha band phase synchronization and late gamma band oscillations in processing syntax in music.

Science.gov (United States)

Ruiz, María Herrojo; Koelsch, Stefan; Bhattacharya, Joydeep

2009-04-01

The present study investigated the neural correlates associated with the processing of music-syntactical irregularities as compared with regular syntactic structures in music. Previous studies reported an early ( approximately 200 ms) right anterior negative component (ERAN) by traditional event-related-potential analysis during music-syntactical irregularities, yet little is known about the underlying oscillatory and synchronization properties of brain responses which are supposed to play a crucial role in general cognition including music perception. First we showed that the ERAN was primarily represented by low frequency (music-syntactical irregularities as compared with music-syntactical regularities, were associated with (i) an early decrease in the alpha band (9-10 Hz) phase synchronization between right fronto-central and left temporal brain regions, and (ii) a late ( approximately 500 ms) decrease in gamma band (38-50 Hz) oscillations over fronto-central brain regions. These results indicate a weaker degree of long-range integration when the musical expectancy is violated. In summary, our results reveal neural mechanisms of music-syntactic processing that operate at different levels of cortical integration, ranging from early decrease in long-range alpha phase synchronization to late local gamma oscillations. 2008 Wiley-Liss, Inc.

78 FR 69690 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

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2013-11-20

... (referred to collectively as CGT products) with recommendations to assist in designing early-phase clinical... Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit written requests for single copies of the draft... 20852-1448. Send one self-addressed adhesive label to assist the office in processing your request. The...

78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

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2013-07-02

... collectively as CGT products) with recommendations to assist in designing early-phase clinical trials of CGT...-addressed adhesive label to assist the office in processing your requests. The draft guidance may also be...-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. FOR FURTHER...

Traumatic Brain Injury Pathophysiology and Treatments: Early, Intermediate, and Late Phases Post-Injury

Science.gov (United States)

Algattas, Hanna; Huang, Jason H.

2014-01-01

Traumatic Brain Injury (TBI) affects a large proportion and extensive array of individuals in the population. While precise pathological mechanisms are lacking, the growing base of knowledge concerning TBI has put increased emphasis on its understanding and treatment. Most treatments of TBI are aimed at ameliorating secondary insults arising from the injury; these insults can be characterized with respect to time post-injury, including early, intermediate, and late pathological changes. Early pathological responses are due to energy depletion and cell death secondary to excitotoxicity, the intermediate phase is characterized by neuroinflammation and the late stage by increased susceptibility to seizures and epilepsy. Current treatments of TBI have been tailored to these distinct pathological stages with some overlap. Many prophylactic, pharmacologic, and surgical treatments are used post-TBI to halt the progression of these pathologic reactions. In the present review, we discuss the mechanisms of the pathological hallmarks of TBI and both current and novel treatments which target the respective pathways. PMID:24381049

MCP/CCR2 signaling is essential for recruitment of mesenchymal progenitor cells during the early phase of fracture healing.

Directory of Open Access Journals (Sweden)

Masahiro Ishikawa

Full Text Available OBJECTIVE: The purpose of this study was to investigate chemokine profiles and their functional roles in the early phase of fracture healing in mouse models. METHODS: The expression profiles of chemokines were examined during fracture healing in wild-type (WT mice using a polymerase chain reaction array and histological staining. The functional effect of monocyte chemotactic protein-1 (MCP-1 on primary mouse bone marrow stromal cells (mBMSCs was evaluated using an in vitro migration assay. MCP-1-/- and C-C chemokine receptor 2 (CCR2-/- mice were fractured and evaluated by histological staining and micro-computed tomography (micro-CT. RS102895, an antagonist of CCR2, was continuously administered in WT mice before or after rib fracture and evaluated by histological staining and micro-CT. Bone graft exchange models were created in WT and MCP-1-/- mice and were evaluated by histological staining and micro-CT. RESULTS: MCP-1 and MCP-3 expression in the early phase of fracture healing were up-regulated, and high levels of MCP-1 and MCP-3 protein expression observed in the periosteum and endosteum in the same period. MCP-1, but not MCP-3, increased migration of mBMSCs in a dose-dependent manner. Fracture healing in MCP-1-/- and CCR2-/- mice was delayed compared with WT mice on day 21. Administration of RS102895 in the early, but not in the late phase, caused delayed fracture healing. Transplantation of WT-derived graft into host MCP-1-/- mice significantly increased new bone formation in the bone graft exchange models. Furthermore, marked induction of MCP-1 expression in the periosteum and endosteum was observed around the WT-derived graft in the host MCP-1-/- mouse. Conversely, transplantation of MCP-1-/- mouse-derived grafts into host WT mice markedly decreased new bone formation. CONCLUSIONS: MCP-1/CCR2 signaling in the periosteum and endosteum is essential for the recruitment of mesenchymal progenitor cells in the early phase of fracture healing.

Phase evolution during early stages of mechanical alloying of Cu–13 wt.% Al powder mixtures in a high-energy ball mill

International Nuclear Information System (INIS)

Dudina, Dina V.; Lomovsky, Oleg I.; Valeev, Konstantin R.; Tikhov, Serguey F.; Boldyreva, Natalya N.; Salanov, Aleksey N.; Cherepanova, Svetlana V.; Zaikovskii, Vladimir I.; Andreev, Andrey S.; Lapina, Olga B.; Sadykov, Vladislav A.

2015-01-01

Highlights: • Phase formation during early stages of Cu–Al mechanical alloying was studied. • The products of mechanical alloying are of highly non-equilibrium character. • X-ray amorphous phases are present in the products of mechanical alloying. • An Al-rich X-ray amorphous phase is distributed between the crystallites. - Abstract: We report the phase and microstructure evolution of the Cu–13 wt.% Al mixture during treatment in a high-energy planetary ball mill with a particular focus on the early stages of mechanical alloying. Several characterization techniques, including X-ray diffraction phase analysis, nuclear magnetic resonance spectroscopy, differential dissolution, thermal analysis, and electron microscopy/elemental analysis, have been combined to study the evolution of the phase composition of the mechanically alloyed powders and describe the microstructure of the multi-phase products of mechanical alloying at different length scales. The following reaction sequence has been confirmed: Cu + Al → CuAl 2 (+Cu) → Cu 9 Al 4 + (Cu) → Cu(Al). The phase evolution was accompanied by the microstructure changes, the layered structure of the powder agglomerates disappearing with milling time. This scheme is further complicated by the processes of copper oxidation, reduction of copper oxides by metallic aluminum, and by variation of the stoichiometry of Cu(Al) solid solutions with milling time. Substantial amounts of X-ray amorphous phases were detected as well. Differential dissolution technique has revealed that a high content of aluminum in the Cu(Al) solid solution-based powders is due to the presence of Al-rich phases distributed between the Cu(Al) crystallites

Early diagnosis of interferon-induced myocardial disorder in patients with chronic hepatitis C. Evaluation by myocardial imaging with {sup 123}I-BMIPP

Energy Technology Data Exchange (ETDEWEB)

Kondo, Yuki; Yukinaka, Michiko; Nomura, Masahiro; Nakaya, Yutaka; Ito, Susumu [Tokushima Univ. (Japan). School of Medicine

2000-02-01

Interferon (IFN) therapy for chronic hepatitis C is sometimes associated with cardiac complications. In the present study, we performed myocardial imaging with {sup 123}I-labeled {beta}-methyl-p-iodophenylpentadecanoic acid ({sup 123}I-BMIPP) in order to evaluate myocardial disorders caused by IFN. We studied 40 healthy subjects (H group) and 25 patients with chronic hepatitis C who had been treated with IFN (IFN group). A Holter electrocardiogram (ECG) was performed and the autonomic nervous function was assessed by analyzing the spectral variability and 1/f fluctuation of heart rate. Myocardial planner imaging with {sup 123}I-BMIPP was performed to obtain the time activity curve for 20 min immediately after administration of {sup 123}I-BMIPP (dynamic study). Early and delayed myocardial single photon emission computed tomography (SPECT) images were expressed as Bull's eyes and the myocardium was divided into four segments to calculate the washout rate for each segment on early and late SPECT images (early and late SPECT study). No significant differences in autonomic nervous function were observed between the two groups in heart rate variability. In a dynamic study, the reduction rate from the time activity curve was significantly higher in the IFN group compared with the H group (reduction rate, IFN group, 5.3{+-}3.7% vs H group, 1.2{+-}3.3%; P<0.05). In the early and delayed myocardial SPECT study, the washout rate for the IFN group was significantly increased in all myocardial areas compared to that in the H group. However, the metabolic disorder of fatty acids caused by IFN was reversed on the second {sup 123}I-BMIPP myocardial scintigraphy examination several months after IFN therapy. These results indicate that metabolic disorders of fatty acids caused by IFN therapy can be detected before abnormalities are observed by Holter-ECG or echocardiography. (author)

Early stages of bipolar disorder: characterization and strategies for early intervention

Directory of Open Access Journals (Sweden)

Adiel C. Rios

2015-12-01

Full Text Available Objective: To characterize the early stages of bipolar disorder (BD, defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. Methods: A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a characterized prodromal and first-episode stages of BD or b detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. Results: As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed or treatment phase. Conclusions: Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.

Psychosocial assessment and self-management of chronic pain

NARCIS (Netherlands)

J.S. Voerman (Jessica)

2015-01-01

markdownabstractAbstract Chronic pain is prevalent in both children and adults and has major negative consequences for their daily life, e.g. reduced participation in activities and depressive and anxious feelings. Therefore, it is important to early signal and treat chronic pain. This thesis

Strontium ranelate causes osteophytes overgrowth in a model of early phase osteoarthritis.

Science.gov (United States)

Chu, Jian-Guo; Dai, Mu-Wei; Wang, Yu; Tian, Fa-Ming; Song, Hui-Ping; Xiao, Ya-Ping; Shao, Li-Tao; Zhang, Ying-Ze; Zhang, Liu

2017-02-10

Osteoarthritis (OA) involves cartilage changes as well as modifications of subchondral bone and synovial tissues. Strontium ranelate (SR), an anti-osteoporosis compound, which is currently in phase III clinical trial for treatment of OA. Evidences suggest that SR preferably deposited in osteophyte, other than in subchondral bone in early phase of OA. This phenomenon raises concern about its utility for OA treatment as a disease-modifying drug. To evaluate the effect of SR on cartilage, subchondral bone mass and subchondral trabecular bone structure in medial meniscectomized (MNX) guinea pigs. Thirty-six 3-month-old male Dunkin Hartley albino guinea pigs received either sham or medial meniscectomy operations. One week after the procedure, meniscectomized animals began 12 weeks of SR (625 mg/kg, daily) treatment by oral gavage for MNX + SR group, or normal saline for MNX + V group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. Both OARSI scores (P = 0.523 for marcoscopic scores, P = 0.297 for histological scores) and Cartilage thickness (P = 0.335) in MNX + SR group were comparable to MNX + V group. However, osteophyte sizes were larger in MNX + SR group (P = 0.014), and collapsed osteophytes in MNX + SR group (7 by 12) were significantly more than in MNX + V group (1 by 12) (P = 0.027), while immunohistochemistry indicates catabolic changes in osteophyte/plateau junction. Micro-CT analysis showed bone mineral density (BMD) (P = 0.001), bone volume fraction (BV/TV) (P = 0.008), trabecular spacing (Tb.Sp) (P = 0.020), trabecular thickness (Tb.Th) (P = 0.012) and structure model index (SMI) (P = 0.005) levels to be significantly higher in the MNX + SR group than in the MNX + V group. SR (625 mg/kg/day) did not protect cartilage from degeneration in MNX guinea pigs but subchondral bone was significantly enhanced. In early

Bone marrow transplantation for patients with chronic myeloid leukemia

International Nuclear Information System (INIS)

Goldman, J.M.; Apperley, J.F.; Jones, L.

1986-01-01

Between February 1981 and December 1984 we treated 52 patients with chronic myeloid leukemia in the chronic phase and 18 patients with more advanced disease by high-dose chemoradiotherapy followed by allogeneic bone marrow transplantation using marrow cells from HLA-identical sibling donors. In addition, the 40 patients who had not previously undergone splenectomy received radiotherapy to the spleen. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with donor marrow depleted of T cells. Of the 52 patients treated in the chronic phase, 38 are alive after a median follow-up of 25 months (range, 7 to 50); the actuarial survival at two years was 72%, and the actuarial risk of relapse was 7%. Of the 18 patients with more advanced disease, 4 have survived; the actuarial two-year survival was 18%, and the actuarial risk of relapse was 42%. We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase of chronic myeloid leukemia. T-cell depletion may have reduced the incidence and severity of graft versus host disease. The value of irradiation to the spleen before transplantation has not been established

Intraerythrocytic sodium and potassium concentrations during acute and chronic digitalization.

Science.gov (United States)

Pedersen, K E; Koldkjaer, O; Berndtz, N H; Hvidt, S; Kjaer, K; Midtskov, C; Sanchez, G

1982-01-01

To assess the cellular effects of digoxin, intraerythrocytic sodium and potassium concentrations were measured in 17 patients during the early phase of digitalization, in 45 patients on long-term therapy and in 64 non-digitalized control patients. Acute digitalization raised intraerythrocytic sodium from 11.6 +/- 0.4 to 16.7 +/- 1.0 mmol/l (mean +/- SEM) (p less than 0.01) and reduced intraerythrocytic potassium from 100.1 +/- 1.3 to 95.9 +/- 1.8 mmol/l (p less than 0.01). These changes were strongly correlated with the steady-state plasma digoxin concentration. During a few weeks of digoxin therapy, the intraerythrocytic cation composition normalized gradually. In patients on chronic treatment, neither intraerythrocytic sodium (11.3 +/- 0.3 mmol/l) nor potassium concentrations (100.0 +/- 0.6 mmol/l) differed significantly from the values of the control group (11.4 +/- 0.2 and 99.9 +/- 0.5 mmol/l, respectively). The changes in intraerythrocytic cation concentrations, induced by acute digitalization, seem to disappear during chronic administration of the drug.

Theoretical model of the early phases of an underground explosion

International Nuclear Information System (INIS)

Cameron, I.G.; Scorgie, G.C.

1970-01-01

Introduction In the early phases of the intense underground explosions contemplated in peaceful applications the rock near the explosive exhibits fluid behaviour; at great distances its behaviour can usefully be investigated in terms of linear elasticity; and at intermediate distances we think of a solid exhibiting various inelastic effects including cracking and tensile fracture. The present paper outlines a mathematical model that attempts to include in some degree the main features of this range of behaviour. A more detailed treatment than is given here, and its relationship to the work of others, is given in a paper by the authors. A computer program ATHENE has been written based on this model and its use is illustrated by examining some aspects of two types of explosions. One is a chemical explosion which eventually formed a crater and the other a nuclear explosion which remained wholly contained

Theoretical model of the early phases of an underground explosion

Energy Technology Data Exchange (ETDEWEB)

Cameron, I G; Scorgie, G C [Atomic Weapons Research Establishment, Aldermaston, Berkshire (United Kingdom)

1970-05-01

Introduction In the early phases of the intense underground explosions contemplated in peaceful applications the rock near the explosive exhibits fluid behaviour; at great distances its behaviour can usefully be investigated in terms of linear elasticity; and at intermediate distances we think of a solid exhibiting various inelastic effects including cracking and tensile fracture. The present paper outlines a mathematical model that attempts to include in some degree the main features of this range of behaviour. A more detailed treatment than is given here, and its relationship to the work of others, is given in a paper by the authors. A computer program ATHENE has been written based on this model and its use is illustrated by examining some aspects of two types of explosions. One is a chemical explosion which eventually formed a crater and the other a nuclear explosion which remained wholly contained.

Effects of early childhood trauma on hypothalamic-pituitary-adrenal (HPA) axis function in patients with Chronic Fatigue Syndrome.

Science.gov (United States)

Kempke, Stefan; Luyten, Patrick; De Coninck, Sarah; Van Houdenhove, Boudewijn; Mayes, Linda C; Claes, Stephan

2015-02-01

There is a paucity of studies that have investigated the assumption that early childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction in Chronic Fatigue Syndrome (CFS). The current study is the first to simultaneously investigate relationships among early childhood trauma, cortisol activity, and cortisol stress reactivity to psychosocial stress in a sample of well-screened CFS patients. We also examined whether self-critical perfectionism (SCP) plays a mediating role in the potential relationship between early trauma and neurobiological stress responses. A total of 40 female patients diagnosed with CFS were asked to provide morning saliva cortisol samples (after awakening, 30min later, and 1h later) for seven consecutive days as a measure of cortisol activity. In addition, patients were exposed to the Trier Social Stress Test, a well-validated stress test, to investigate the relationship between early childhood trauma and cortisol stress reactivity. Before the start of the study, patients completed the Childhood Trauma Questionnaire-Short form (CTQ-SF) as a measure of early childhood trauma (i.e. sexual, physical and emotional traumatic experiences). SCP was measured with the Depressive Experiences Questionnaire (DEQ). Data were analyzed by calculating several indices of cortisol secretion (i.e. Cortisol Awakening Response and Area Under the Curve). There was no association between early childhood trauma and cortisol as measured over the 7-day period. However, emotional neglect was significantly negatively related to cortisol reactivity in the TSST. SCP did not significantly mediate this association. Findings of this study suggest that emotional neglect is associated with blunted HPA axis reactivity, congruent with the assumption that CFS may reflect loss of adaptability of the neuroendocrine stress response system in at least a subgroup of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

The long-term clinical implications of clonal chromosomal abnormalities in newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib mesylate.

Science.gov (United States)

Lee, Sung-Eun; Choi, Soo Young; Bang, Ju-Hee; Kim, Soo-Hyun; Jang, Eun-Jung; Byeun, Ji-Young; Park, Jin Eok; Jeon, Hye-Rim; Oh, Yun Jeong; Kim, Myungshin; Kim, Dong-Wook

2012-11-01

The aim of this study was to evaluate the long-term clinical significance of an additional chromosomal abnormality (ACA), variant Philadelphia chromosome (vPh) at diagnosis, and newly developed other chromosomal abnormalities (OCA) in patients with chronic myeloid leukemia (CML) on imatinib (IM) therapy. Sequential cytogenetic data from 281 consecutive new chronic phase CML patients were analyzed. With a median follow-up of 78.6 months, the 22 patients with vPh (P = 0.034) or ACA (P = 0.034) at diagnosis had more events of IM failure than did the patients with a standard Ph. The 5-year overall survival (OS), event-free survival (EFS), and failure-free survival (FFS) rates for patients with vPh at diagnosis were 77.8%, 75.0%, and 53.3%, respectively; for patients with ACA at diagnosis, 100%, 66.3%, and 52.1%, respectively; and for patients with a standard Ph, 96.0%, 91.3%, and 83.7%, respectively. During IM therapy, eight patients developed an OCA, which had no impact on outcomes as a time-dependent covariate in our Cox proportional hazards regression models. This study showed that vPh was associated with poor OS and FFS and that ACA had adverse effects on EFS and FFS. In addition, no OCA, except monosomy 7, had any prognostic impact, suggesting that the development of OCA may not require a change in treatment strategy. Copyright © 2012 Elsevier Inc. All rights reserved.

The Influence of Early Life Experience on Visceral Pain

Directory of Open Access Journals (Sweden)

Isabella M. Fuentes

2018-01-01

Full Text Available Pain is the most reported and troublesome symptom of nearly all functional disorders affecting the genitourinary and gastrointestinal organs. Patients with irritable bowel syndrome (IBS, interstitial cystitis/painful bladder syndrome (IC/PBS, vulvodynia, and/or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; collectively termed chronic pelvic pain syndromes report pain severe enough to impact quality of life and often suffer from symptoms of or are diagnosed with more than one of these syndromes. This increased comorbidity between chronic pelvic pain syndromes, and with pain disorders of disparate body regions, as well as with mood disorders, can be influenced by disruptions in the hypothalamic-pituitary-adrenal (HPA axis, which regulates the response to stress and influences the perception of pain. Experiencing trauma, neglect, or abuse in early life can permanently affect the functioning of the HPA axis. As such, a significant proportion of patients suffering from comorbid chronic pelvic pain syndromes report a history of early life stress or trauma. Here we will report on how these early life experiences influence chronic pelvic pain in patients. We will also discuss various rodent models that have been developed to study this phenomenon to understand the mechanisms underlying HPA axis dysfunction, as well as potential underlying mechanisms connecting these syndromes to one another.

Activity of toluene-degrading Pseudomonas putida in the early growth phase of a biofilm for waste gas treatment

DEFF Research Database (Denmark)

Pedersen, A.R.; Møller, S.; Molin, S.

1997-01-01

A biological trickling filter for treatment of toluene-containing waste gas was studied. The overall kinetics of the biofilm growth was followed in the early growth phase. A rapid initial colonization took place during the first three days. The biofilm thickness increased exponentially, whereas...

FLARE RIBBON ENERGETICS IN THE EARLY PHASE OF AN SDO FLARE

Energy Technology Data Exchange (ETDEWEB)

Fletcher, L.; Hannah, I. G.; Hudson, H. S. [School of Physics and Astronomy, SUPA, University of Glasgow, Glasgow, G12 8QQ (United Kingdom); Innes, D. E. [Max Planck Institute for Solar System Research, Max-Planck-Strasse 2, D-37191 Katlenburg-Lindau (Germany)

2013-07-10

The sites of chromospheric excitation during solar flares are marked by extended extreme ultraviolet ribbons and hard X-ray (HXR) footpoints. The standard interpretation is that these are the result of heating and bremsstrahlung emission from non-thermal electrons precipitating from the corona. We examine this picture using multi-wavelength observations of the early phase of an M-class flare SOL2010-08-07T18:24. We aim to determine the properties of the heated plasma in the flare ribbons, and to understand the partition of the power input into radiative and conductive losses. Using GOES, SDO/EVE, SDO/AIA, and RHESSI, we measure the temperature, emission measure (EM), and differential emission measure of the flare ribbons, and deduce approximate density values. The non-thermal EM, and the collisional thick target energy input to the ribbons are obtained from RHESSI using standard methods. We deduce the existence of a substantial amount of plasma at 10 MK in the flare ribbons, during the pre-impulsive and early-impulsive phase of the flare. The average column EM of this hot component is a few times 10{sup 28} cm{sup -5}, and we can calculate that its predicted conductive losses dominate its measured radiative losses. If the power input to the hot ribbon plasma is due to collisional energy deposition by an electron beam from the corona then a low-energy cutoff of {approx}5 keV is necessary to balance the conductive losses, implying a very large electron energy content. Independent of the standard collisional thick-target electron beam interpretation, the observed non-thermal X-rays can be provided if one electron in 10{sup 3}-10{sup 4} in the 10 MK (1 keV) ribbon plasma has an energy above 10 keV. We speculate that this could arise if a non-thermal tail is generated in the ribbon plasma which is being heated by other means, for example, by waves or turbulence.

Pyrexia-associated Relapse in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Case Report.

Science.gov (United States)

Ueda, Jun; Yoshimura, Hajime; Kohara, Nobuo

2018-04-27

Chronic inflammatory demyelinating polyradiculoneuropathy is a relapsing-remitting or chronic progressive demyelinating polyradiculoneuropathy. We report the case of a patient with chronic inflammatory demyelinating polyradiculoneuropathy who experienced relapses on four occasions after experiencing pyrexia and flu-like symptoms. Our patient showed characteristic features, such as relapse after pyrexia and flu-like symptoms, remission after pyretolysis without treatment, and the absence of remarkable improvement in a nerve conduction study in the remission phase. The serum level of tumor necrosis factor-α was elevated in the relapse phase and reduced in the remission phase; thus, the induction of cytokine release by viral infection might have caused the relapses.

Imatinib Intolerance Is Associated With Blastic Phase Development in Philadelphia Chromosome-Positive Chronic Myeloid Leukemia.

Science.gov (United States)

Ángeles-Velázquez, Jorge Luis; Hurtado-Monroy, Rafael; Vargas-Viveros, Pablo; Carrillo-Muñoz, Silvia; Candelaria-Hernández, Myrna

2016-08-01

Over the past years, the survival of patients with Philadelphia-positive chronic myeloid leukemia (CML Ph(+)) has increased as a result of therapy with tyrosin kinase inhibitors (TKIs). Intolerance to TKIs has been described in approximately 20% of patients receiving treatment. We studied the incidence of imatinib intolerance in patients with CML Ph(+) and their outcome in our CML reference site, as there is no information about the evolution of patients intolerant to TKIs. A group of 86 patients with CML Ph(+) receiving imatinib monotherapy who abandoned treatment were the basis for this study. We present the trends of their disease evolution. The median of age at diagnosis was 42 years. Within a year, 19 (22%) of 86 patients developed imatinib intolerance, all of them with grade III or IV disease that required imatinib dose reduction or discontinuation. Of these patients, 16 (84%) of 19 developed transformation to blastic phase. The cumulative incidences of blastic phase development were 47% in the nonintolerant group and 84% in the intolerant group. There was a relative risk for those with imatinib intolerance to develop blastic phase of 1.78 (95% confidence interval, 1.28 to 2.42) (P treatment is available. Future research should to determine whether the origin of this evolution is really due to the intolerance itself or whether it is due to a more aggressive form of the disease, perhaps related to genetic transformation. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic pancreatitis.

Science.gov (United States)

Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

2017-09-07

Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

Left atrial volume index as a predictor for persistent left ventricular dysfunction after aortic valve surgery in patients with chronic aortic regurgitation: the role of early postoperative echocardiography.

Science.gov (United States)

Cho, In-Jeong; Chang, Hyuk-Jae; Hong, Geu-Ru; Heo, Ran; Sung, Ji Min; Lee, Sang-Eun; Chang, Byung-Chul; Shim, Chi Young; Ha, Jong-Won; Chung, Namsik

2015-06-01

This study aimed to explore whether echocardiographic measurements during the early postoperative period can predict persistent left ventricular systolic dysfunction (LVSD) after aortic valve surgery in patients with chronic aortic regurgitation (AR). We prospectively recruited 54 patients (59 ± 12 years) with isolated chronic severe AR who subsequently underwent aortic valve surgery. Standard transthoracic echocardiography was performed before the operation, during the early postoperative period (≤2 weeks), and then 1 year after the surgery. Twelve patients with preoperative LVSD demonstrated LVSD at early after the surgery. Of the 42 patients without LVSD at preoperative echocardiography, 15 patients (36%) developed early postoperative LVSD after surgical correction. All 27 patients without LVSD at early postoperative echocardiography maintained LV function at 1 year after surgery. In the other 27 patients with postoperative LVSD, 17 patients recovered from LVSD and 10 patients did not at 1 year after surgery. Multiple logistic analysis demonstrated that postoperative left atrial volume index (LAVI) was the only independent predictor for persistent LVSD at 1 year after surgery in patients with postoperative LVSD (OR 1.180, 95% CI, 1.003-1.390, P = 0.046). The optimal LAVI cutoff value (>34.9 mL/m(2) ) had a sensitivity of 80% and a specificity of 88% for the prediction of persistent LVSD. Prevalence of early postoperative LVSD was relatively high, even in the patients without LVSD at preoperative echocardiography. Postoperative LAVI could be useful to predict persistent LVSD after aortic valve surgery in patients with early postoperative LVSD. © 2014, Wiley Periodicals, Inc.

Early detection of chronic obstructive pulmonary disease in apparently healthy attendants of tertiary care hospital and assessment of its severity

International Nuclear Information System (INIS)

Zubair, T.; Abbassi, A.; Khan, O. A.

2017-01-01

Objective: Early detection of Chronic Obstructive Pulmonary Disease in apparently healthy attendants of tertiary care hospital and assessment of its severity. Study Design: Cross-sectional, observational study. Place and Duration of Study: Study was conducted from January 2015 to July 2015 at Dow University Hospital, Ojha campus. Methodology: A screening method was designed for apparently healthy individuals including attendants of patients, hospital staff, faculty and students, belonging to age group 18-60 years after excluding severe obesity and already diagnosed respiratory and cardiovascular diseases by means of history. Each participant performed pulmonary function tests via spirometer after filling a questionnaire based on various risk factors and symptoms of chronic obstructive pulmonary disease (COPD). Data was entered and analysed by SPSS-20. Results: Out of the 517 participants, 122 (23.6%) were found to have COPD diagnosed by means of spirometry. Out of these, 23 (4.4%) had COPD stage I, 42 (8.1%) had COPD II, 34 (6.6%) had COPD III, and 23 (4.4%) had COPD IV. Exposure to smoking, wooden stoves, pesticides, biomass fuel, aerosol sprays, gas grill and vehicle exhaust were found to be statistically significant factors in relation to development of COPD. Conclusion: Apparently healthy individuals may have underlying COPD and active screening by means of spirometry plays vital role in early detection of COPD. Smoking and exposure to certain hazardous environmental pollutants are responsible for the development and progression of COPD. (author)

Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever

Science.gov (United States)

Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R.

2016-01-01

Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (1.5) in the serum, among which are two products of tryptophan metabolism–serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved the prognosis performance (AUC = 0.92, sensitivity = 77.8%, specificity = 95.8%), suggesting this duplex panel as accurate metrics for the early prognosis of DHF. PMID:27055163

A novel approach to population-based risk stratification, comprising individualized lifestyle intervention in Danish general practice to prevent chronic diseases

DEFF Research Database (Denmark)

Bruun Larsen, Lars; Søndergaard, Jens; Halling, Anders

2017-01-01

Early detection of patients at risk seems to be effective for reducing the prevalence of lifestyle-related chronic diseases. We aim to test the feasibility of a novel intervention for early detection of lifestyle-related chronic diseases based on a population-based stratification using a combinat......Early detection of patients at risk seems to be effective for reducing the prevalence of lifestyle-related chronic diseases. We aim to test the feasibility of a novel intervention for early detection of lifestyle-related chronic diseases based on a population-based stratification using...

Surgical Management of Chronic Pancreatitis.

Science.gov (United States)

Parekh, Dilip; Natarajan, Sathima

2015-10-01

Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.

Bacterial Contribution in Chronicity of Wounds.

Science.gov (United States)

Rahim, Kashif; Saleha, Shamim; Zhu, Xudong; Huo, Liang; Basit, Abdul; Franco, Octavio Luiz

2017-04-01

A wound is damage of a tissue usually caused by laceration of a membrane, generally the skin. Wound healing is accomplished in three stages in healthy individuals, including inflammatory, proliferative, and remodeling stages. Healing of wounds normally starts from the inflammatory phase and ends up in the remodeling phase, but chronic wounds remain in an inflammatory stage and do not show progression due to some specific reasons. Chronic wounds are classified in different categories, such as diabetic foot ulcer (DFU), venous leg ulcers (VLU) and pressure ulcer (PU), surgical site infection (SSI), abscess, or trauma ulcers. Globally, the incidence rate of DFU is 1-4 % and prevalence rate is 5.3-10.5 %. However, colonization of pathogenic bacteria at the wound site is associated with wound chronicity. Most chronic wounds contain more than one bacterial species and produce a synergetic effect that results in previously non-virulent bacterial species becoming virulent and causing damage to the host. While investigating bacterial diversity in chronic wounds, Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter, Stenotrophomonas, Finegoldia, and Serratia were found most frequently in chronic wounds. Recently, it has been observed that bacteria in chronic wounds develop biofilms that contribute to a delay in healing. In a mature biofilm, bacteria grow slowly due to deficiency of nutrients that results in the resistance of bacteria to antibiotics. The present review reflects the reasons why acute wounds become chronic. Interesting findings include the bacterial load, which forms biofilms and shows high-level resistance toward antibiotics, which is a threat to human health in general and particularly to some patients who have acute wounds.

Periodontitis in early and chronic rheumatoid arthritis: a prospective follow-up study in Finnish population.

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Äyräväinen, Leena; Leirisalo-Repo, Marjatta; Kuuliala, Antti; Ahola, Kirsi; Koivuniemi, Riitta; Meurman, Jukka H; Heikkinen, Anna Maria

2017-01-31

To investigate the association between rheumatoid arthritis (RA) and periodontitis with special emphasis on the role of antirheumatic drugs in periodontal health. Prospective follow-up study. Patients with early untreated RA and chronic active RA were examined at baseline and 16 months later. Controls were examined once. The study was conducted in Finland from September 2005 to May 2014 at the Helsinki University Hospital. Overall, 124 participants were recruited for dental and medical examinations: 53 were patients with early disease-modifying antirheumatic drug (DMARD) naїve RA (ERA), 28 were patients with chronic RA (CRA) with insufficient response to conventional DMARDs. After baseline examination, patients with ERA started treatment with synthetic DMARDs and patients with CRA with biological DMARDs. Controls were 43 age-matched, gender-matched and community-matched participants. Degree of periodontitis (defined according to the Center for Disease Control and Prevention and the American Academy of Periodontology). Prevalence of periodontal bacteria (analysed from plaque samples), clinical rheumatological status by Disease Activity Score, 28-joint count (DAS28), function by Health Assessment Questionnaire (HAQ) and treatment response by European League Against Rheumatism (EULAR) criteria. Moderate periodontitis was present in 67.3% of patients with ERA, 64.3% of patients with CRA and 39.5% of control participants (p=0.001). Further, patients with RA had significantly more periodontal findings compared with controls, recorded with common periodontal indexes. In the re-examination, patients with RA still showed poor periodontal health in spite of treatment with DMARDs after baseline examination. The prevalence of Porphyromonas gingivalis was higher in patients with ERA with periodontal probing depth ≥4 mm compared with patients with CRA and controls. Antirheumatic medication did not seem to affect the results. Moderate periodontitis was more frequent in

The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats.

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Maniam, Jayanthi; Antoniadis, Christopher P; Morris, Margaret J

2015-01-01

Early-life stress affects metabolic outcomes and choice of diet influences the development of metabolic disease. Here we tested the hypothesis that chronic sugar intake exacerbates metabolic deficits induced by early-life stress. Early-life stress was induced in Sprague-Dawley rats using limited nesting material in early lactation (LN, postnatal days 2-9), and siblings were given chow alone or with additional sucrose post weaning (n = 9-17 per group). Female control and LN siblings had unlimited access to either chow plus water, or chow and water plus 25% sucrose solution (Sucrose), from 3-15 weeks of age. Weekly body weight and food intake were measured. Glucose and insulin tolerance were tested at 13 and 14 weeks of age, respectively. Rats were killed at 15 weeks. Hepatic triglyceride and markers of lipid synthesis - fatty acid synthase, acetyl-CoA carboxylase alpha and oxidation - and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) were examined. Mediators of hepatic glucocorticoid metabolism, specifically 11-beta hydroxysteroid dehydrogenase-1 (11βHSD-1), 5-α reductase, and glucocorticoid and mineralocorticoid receptor mRNAs were also measured. Sucrose increased caloric intake in both groups, but overall energy intake was not altered by LN exposure. LN exposure had no further impact on sucrose-induced glucose intolerance and increased plasma and liver triglycerides. Hepatic markers of fat synthesis and oxidation were concomitantly activated and 11βHSD-1 mRNA expression was increased by 53% in LN-Sucrose versus Con-Sucrose rats. Adiposity was increased by 26% in LN-Sucrose versus Con-Sucrose rats. Thus, LN exposure had minimal adverse metabolic effects despite high-sugar diet postweaning.

Internal Dose from Food and Drink Ingestion in the Early Phase after the Accident

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Kawai, Masaki; Yoshizawa, Nobuaki; Hirakawa, Sachiko; Murakami, Kana; Takizawa, Mari; Sato, Osamu; Takagi, Shunji; Miyatake, Hirokazu; Takahashi, Tomoyuki; Suzuki, Gen

2017-09-01

Activity concentrations in food and drink, represented by water and vegetables, have been monitored continuously since the Fukushima Daiichi Nuclear Power Plant accident, with a focus on radioactive cesium. On the other hand, iodine-131 was not measured systematically in the early phase after the accident. The activity concentrations of iodine-131 in food and drink are important to estimate internal exposure due to ingestion pathway. When the internal dose from ingestion in the evacuation areas is estimated, water is considered as the main ingestion pathway. In this study, we estimated the values of activity concentrations in water in the early phase after the accident, using a compartment model as an estimation method. The model uses measurement values of activity concentration and deposition rate of iodine-131 onto the ground, which is calculated from an atmospheric dispersion simulation. The model considers how drinking water would be affected by radionuclides deposited into water. We estimated the activity concentrations of water on Kawamata town and Minamisouma city during March of 2011 and the committed effective doses were 0.08 mSv and 0.06 mSv. We calculated the transfer parameters in the model for estimating the activity concentrations in the areas with a small amount of measurement data. In addition, we estimated the committed effective doses from vegetables using atmospheric dispersion simulation and FARMLAND model in case of eating certain vegetables as option information.

Correlation of early-phase {sup 18}F-florbetapir (AV-45/Amyvid) PET images to FDG images: preliminary studies

Energy Technology Data Exchange (ETDEWEB)

Hsiao, Ing-Tsung; Hsieh, Chia-Ju; Wey, Shiaw-Pyng; Lin, Kun-Ju [Chang Gung Memorial Hospital, Department of Nuclear Medicine and Molecular Imaging Center, Taipei (China); Chang Gung University, Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, Taipei (China); Huang, Chin-Chang; Hsu, Wen-Chun [Chang Gung Memorial Hospital, Department of Neurology, Taipei (China); Yen, Tzu-Chen [Chang Gung Memorial Hospital, Department of Nuclear Medicine and Molecular Imaging Center, Taipei (China); Kung, Mei-Ping [Chang Gung Memorial Hospital, Department of Nuclear Medicine and Molecular Imaging Center, Taipei (China); Chang Gung University, Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, Taipei (China); University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States)

2012-04-15

{sup 18}F-Florbetapir (AV-45/Amyvid) is a novel positron emission tomography (PET) tracer for imaging plaque pathology in Alzheimer's disease (AD), while PET images of fluorodeoxyglucose (FDG) for cerebral glucose metabolism can provide complementary information to amyloid plaque images for diagnosis of AD. The goal of this preliminary study was to investigate the perfusion-like property of relative cerebral blood flow estimates (R{sub 1}) and summed early-phase AV-45 images [perfusion AV-45 (pAV-45)] and optimize the early time frame for pAV-45. Dynamic AV-45 PET scans (0-180 min) were performed in seven subjects. pAV-45, late-phase AV-45, and FDG images were spatially normalized to the Montreal Neurological Institute template aided by individual MRI images, and the corresponding standardized uptake value ratio (SUVR) was computed. The R{sub 1} images were derived from a simplified reference tissue model. Correlations between regional and voxelwise R{sub 1} and the corresponding FDG images were calculated. An optimization of time frames of pAV-45 was conducted in terms of correlation to FDG images. The optimal early time frame was validated in a separate cohort. The regional distribution in the R{sub 1} images correlated well (R = 0.91) to that of the FDG within subjects. Consistently high correlation was noted across a long range of time frames. The maximal correlation of pAV-45 to FDG SUVR of R = 0.95 was observed at the time frame of 1-6 min, while the peak correlation of R = 0.99 happened at 0-2 min between pAV-45 and R{sub 1}. A similar result was achieved in the validation cohort. Preliminary results showed that the distribution patterns of R{sub 1} and pAV-45 images are highly correlated with normalized FDG images, and the initial 5-min early time frame of 1-6 min is potentially useful in providing complementary FDG-like information to the amyloid plaque density by late-phase AV-45 images. (orig.)

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia.

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Yap, Christina; Pettitt, Andrew; Billingham, Lucinda

2013-07-03

As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon's two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics.

7T T-2*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease

NARCIS (Netherlands)

van Rooden, S.; Doan, N.T.; Versluis, M.J.; Goos, J.D.C.; Webb, A.G.; Oleksik, A.M.; van der Flier, W.M.; Scheltens, P.; Barkhof, F.; Weverlinge-Rynsburger, A.W.E.; Blauw, G. J.; Reiber, J.H.C.; van Buchem, M.A.; Milles, J.; van der Grond, J.

2015-01-01

The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T

Do mental health problems in childhood predict chronic physical conditions among males in early adulthood? Evidence from a community-based prospective study.

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Goodwin, R D; Sourander, A; Duarte, C S; Niemelä, S; Multimäki, P; Nikolakaros, G; Helenius, H; Piha, J; Kumpulainen, K; Moilanen, I; Tamminen, T; Almqvist, F

2009-02-01

Previous studies have documented associations between mental and physical health problems in cross-sectional studies, yet little is known about these relationships over time or the specificity of these associations. The aim of the current study was to examine the relationship between mental health problems in childhood at age 8 years and physical disorders in adulthood at ages 18-23 years. Multiple logistic regression analyses were used to examine the relationship between childhood mental health problems, reported by child, parent and teacher, and physical disorders diagnosed by a physician in early adulthood. Significant linkages emerged between childhood mental health problems and obesity, atopic eczema, epilepsy and asthma in early adulthood. Specifically, conduct problems in childhood were associated with a significantly increased likelihood of obesity and atopic eczema; emotional problems were associated with an increased likelihood of epilepsy and asthma; and depression symptoms at age 8 were associated with an increased risk of asthma in early adulthood. Our findings provide the first evidence of an association between mental health problems during childhood and increased risk of specific physical health problems, mainly asthma and obesity, during early adulthood, in a representative sample of males over time. These data suggest that behavioral and emotional problems in childhood may signal vulnerability to chronic physical health problems during early adulthood.

Early Clinical Effectiveness of ER:Yag Laser in Association with the Red Complex of Bacteria in the Initial Treatment of Moderate Chronic Periodontitis

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Yaneva Bl.

2014-06-01

Full Text Available Chronic periodontitis is a result of polymicrobial infection and its treatment aims removal of dental calculus and biofi lm from the periodontal pocket. Many hand and power-driven instruments are created for this purpose. In recent years, lasers are widely discussed tools for periodontal therapy. The aim of the present study is to evaluate the early microbiological and clinical effectiveness of the Er:YAG laser in the treatment of chronic periodontitis. 30 patients with moderate chronic periodontitis were enrolled in the study. Using a split-mouth design they were treated either with Er:YAG laser (chisel tip, 100 mJ, 15 Hz, 5-6 water spray-test group or with Gracey curettes- control group. Probing pocket depth (PPD, gingival recession (GR, clinical attachment level (CAL, bleeding on probing and plaque presence were evaluated at baseline and one month after the therapy. Microbiological samples were taken from the deepest four pockets of each quadrant from 20 randomly selected patients (n = 80. They were evaluated using real time PCR for periodontal pathogens from the red complex (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia. One month after therapy in the control group PPD decreased from 4.59 mm to 3.36 mm, the CAL gain was 1.09 mm and the reduction of bleeding and plaque - from 87.9% to 33.7% and from 75.9% to 40.9%, respectively. In the test group PPD decreased from 4.58 mm to 3.15 mm, the CAL gain was 1.37mm and the reduction of bleeding and plaque was from 85.6% to 25.9% one month after the treatment. The results were statistically significant in favour of the laser group (p < 0.05. Microbiological analysis revealed that the pathogens from the red complex decreased 3 times in the control and 6 times in the test group. Therefore, the Er:YAG laser demonstrate pronounced early effectiveness in chronic periodontitis treatment and would be appropriate alternative of the conventional periodontal therapy.

Imaging in the diagnosis of chronic pancreatitis

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Vasile D. Balaban

2014-12-01

Full Text Available Chronic pancreatitis is characterised by progressive and irreversible damage of the pancreatic parenchyma and ductal system, which leads to chronic pain, loss of endocrine and exocrine functions. Clinically, pancreatic exocrine insufficiency becomes apparent only after 90% of the parenchima has been lost. Despite the simple definition, diagnosing chronic pancreatitis remains a challenge, especially for early stage disease. Because pancreatic function tests can be normal until late stages and have significant limitations, there is an incresing interest in the role of imaging techniques for the diagnosis of chronic pancreatitis. In this article we review the utility and accuracy of different imaging methods in the diagnosis of chronic pancreatitis, focusing on the role of advanced imaging (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound.

Early symptoms in the prodromal phase of delirium: a prospective cohort study in elderly patients undergoing hip surgery.

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de Jonghe, Jos F M; Kalisvaart, Kees J; Dijkstra, Marty; van Dis, Huib; Vreeswijk, Ralph; Kat, Martin G; Eikelenboom, Piet; van der Ploeg, Tjeerd; van Gool, Willem A

2007-02-01

The authors investigated prodromal delirium symptoms in elderly patients undergoing hip surgery. This was a prospective cohort study in the setting of a large medical school-affiliated general hospital in Alkmaar, The Netherlands. Participants were patients undergoing hip surgery aged 70 and older at risk for delirium. Before surgery, patients were randomized to low-dose prophylactic haloperidol treatment or placebo. Daily assessments were based on patient interviews with the Mini-Mental State Examination and Digit Span test. The Delirium Rating Scale-Revised (DRS-R-98) was used to measure early symptoms during the prodromal phase before the onset of delirium. Data of 66 patients with delirium were compared with those of 35 at-risk patients who did not develop delirium: 14 of 66 patients (21%) had delirium on the day of surgery or early the day after, 32 of 66 (48%) on the second day, 14 of 66 on the third, and six of 66 (9%) on the fourth. The average DRS-R-98 total scores on day -4 to day -1 before delirium were 1.9 for the comparison group patients and 5.0, 4.3, 5.8, and 10.7 for patients with postoperative delirium. Multivariate analysis showed that the early symptoms memory impairments, incoherence, disorientation, and underlying somatic illness predict delirium. Most elderly patients undergoing hip surgery with postoperative delirium already have early symptoms in the prodromal phase of delirium. These findings are potentially useful for screening purposes and for optimizing prevention strategies targeted at reducing the incidence of postoperative delirium.

Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge

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Cristan Herbert

2013-03-01

Childhood exposure to environmental particulates increases the risk of development of asthma. The underlying mechanisms might include oxidant injury to airway epithelial cells (AEC. We investigated the ability of ambient environmental particulates to contribute to sensitization via the airways, and thus to the pathogenesis of childhood asthma. To do so, we devised a novel model in which weanling BALB/c mice were exposed to both ambient particulate pollutants and ovalbumin for sensitization via the respiratory tract, followed by chronic inhalational challenge with a low mass concentration of the antigen. We also examined whether these particulates caused oxidant injury and activation of AEC in vitro. Furthermore, we assessed the potential benefit of minimizing oxidative stress to AEC through the period of sensitization and challenge by dietary intervention. We found that characteristic features of asthmatic inflammation developed only in animals that received particulates at the same time as respiratory sensitization, and were then chronically challenged with allergen. However, these animals did not develop airway hyper-responsiveness. Ambient particulates induced epithelial injury in vitro, with evidence of oxidative stress and production of both pro-inflammatory cytokines and Th2-promoting cytokines such as IL-33. Treatment of AEC with an antioxidant in vitro inhibited the pro-inflammatory cytokine response to these particulates. Ambient particulates also induced pro-inflammatory cytokine expression following administration to weanling mice. However, early-life dietary supplementation with antioxidants did not prevent the development of an asthmatic inflammatory response in animals that were exposed to particulates, sensitized and challenged. We conclude that injury to airway epithelium by ambient environmental particulates in early life is capable of promoting the development of an asthmatic inflammatory response in sensitized and antigen-challenged mice. These

Early-Years Absenteeism Seen as Critical

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Sparks, Sarah D.

2010-01-01

While efforts to reduce chronic absenteeism typically focus on adolescents, experts say that the early grades are the place to start. Statistics show that rates of absenteeism in kindergarten and 1st grade can rival those in high school. An average of one in 10 pupils in grades K-12 nationwide is considered chronically absent, defined as missing…

Neurodegeneration severity can be predicted from early microglia alterations monitored in vivo in a mouse model of chronic glaucoma

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Alejandra Bosco

2015-05-01

Full Text Available Microglia serve key homeostatic roles, and respond to neuronal perturbation and decline with a high spatiotemporal resolution. The course of all chronic CNS pathologies is thus paralleled by local microgliosis and microglia activation, which begin at early stages of the disease. However, the possibility of using live monitoring of microglia during early disease progression to predict the severity of neurodegeneration has not been explored. Because the retina allows live tracking of fluorescent microglia in their intact niche, here we investigated their early changes in relation to later optic nerve neurodegeneration. To achieve this, we used the DBA/2J mouse model of inherited glaucoma, which develops progressive retinal ganglion cell degeneration of variable severity during aging, and represents a useful model to study pathogenic mechanisms of retinal ganglion cell decline that are similar to those in human glaucoma. We imaged CX3CR1+/GFP microglial cells in vivo at ages ranging from 1 to 5 months by confocal scanning laser ophthalmoscopy (cSLO and quantified cell density and morphological activation. We detected early microgliosis at the optic nerve head (ONH, where axonopathy first manifests, and could track attenuation of this microgliosis induced by minocycline. We also observed heterogeneous and dynamic patterns of early microglia activation in the retina. When the same animals were aged and analyzed for the severity of optic nerve pathology at 10 months of age, we found a strong correlation with the levels of ONH microgliosis at 3 to 4 months. Our findings indicate that live imaging and monitoring the time course and levels of early retinal microgliosis and microglia activation in glaucoma could serve as indicators of future neurodegeneration severity.

Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161(+)Th1 Cells) to CD161(+)Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients.

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Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161(+)Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.

Primary peak and chronic malaria infection levels are correlated in experimentally infected great reed warblers.

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Asghar, Muhammad; Westerdahl, Helena; Zehtindjiev, Pavel; Ilieva, Mihaela; Hasselquist, Dennis; Bensch, Staffan

2012-09-01

Malaria parasites often manage to maintain an infection for several months or years in their vertebrate hosts. In humans, rodents and birds, most of the fitness costs associated with malaria infections are in the short initial primary (high parasitaemia) phase of the infection, whereas the chronic phase (low parasitaemia) is more benign to the host. In wild birds, malaria parasites have mainly been studied during the chronic phase of the infection. This is because the initial primary phase of infection is short in duration and infected birds with severe disease symptoms tend to hide in sheltered places and are thus rarely caught and sampled. We therefore wanted to investigate the relationship between the parasitaemia during the primary and chronic phases of the infection using an experimental infection approach. We found a significant positive correlation between parasitaemia in the primary peak and the subsequent chronic phase of infection when we experimentally infected great reed warblers (Acrocephalus arundinaceus) with Plasmodium ashfordi. The reason for this association remains to be understood, but might arise from individual variation in exoerythrocytic parasite reservoirs in hosts, parasite antigenic diversity and/or host genetics. Our results suggest that the chronic phase parasitaemia can be used to qualitatively infer the parasitaemia of the preceding and more severe primary phase, which is a very important finding for studies of avian malaria in wild populations.

Modulation of Trypanosoma cruzi-specific T-cell responses after chemotherapy for chronic Chagas disease

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María Cecilia Albareda

2015-05-01

Full Text Available The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease. T-helper (Th1 and interleukin (IL-10 Trypanosoma cruzi-specific T-cells have been linked to the asymptomatic phase or to severe clinical forms of the disease, respectively or vice versa, depending on the T. cruzi antigen source, the patient’s location and the performed immunological assays. Parasite-specific T-cell responses are modulated after benznidazole (BZ treatment in chronically T. cruzi-infected subjects in association with a significant decrease in T. cruzi-specific antibodies. Accumulating evidence has indicated that treatment efficacy during experimental infection with T. cruzi results from the combined action of BZ and the activation of appropriate immune responses in the host. However, strong support of this interaction in T. cruzi-infected humans remains lacking. Overall, the quality of T-cell responses might be a key factor in not only disease evolution, but also chemotherapy responsiveness. Immunological parameters are potential indicators of treatment response regardless of achievement of cure. Providing tools to monitor and provide early predictions of treatment success will allow the development of new therapeutic options.

Earlier surgery improves outcomes from painful chronic pancreatitis

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Ke, Nengwen; Jia, Dan; Huang, Wei; Nunes, Quentin M.; Windsor, John A.; Liu, Xubao; Sutton, Robert

2018-01-01

Abstract The timing of surgery for painful chronic pancreatitis (CP) may affect outcomes. Clinical course, Izbicki pain scores, and pancreatic function were retrospectively compared and analyzed between patients undergoing either early or late surgery (pancreatic mass +/− ductal dilatation (47% vs 27%, P insufficiency (60% vs 72%, P = .034); there were no other significant differences. The early group had longer hospital stay (14.4 vs 12.2 days, P = .009), but no difference in complications. Significantly greater pain relief followed early surgery (complete 69% vs 47%, partial 22% vs 37%, none 8% vs 16%, P = .01) with lower rates of exocrine (60% vs 80%, P = .005) and endocrine insufficiency (36% vs 53%, P = .033). Our data indicate that early surgery results in higher rates of pain relief and pancreatic sufficiency than late surgery for chronic pancreatitis patients. Frey and Berne procedures showed better results than other surgical procedures. PMID:29742705

Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT

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2016-08-01

Geraghty, J. A. Seibert, and S. L. Wootton-Gorges, “Dose reduction in pediatric CT : A rational approach,” Radiology 228, 352–360 (2003). Medical...improvement in image quality can be quantified as large as 450 [Fig. 6(c)] and 350 [Fig. 6(d)] Hounsfield units (HUs), where the Hounsfield unit is defined...AWARD NUMBER: W81XWH-12-1-0138 TITLE: Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT PRINCIPAL INVESTIGATOR

Three-phase radionuclide bone imaging in sports medicine

International Nuclear Information System (INIS)

Rupani, H.D.; Holder, L.E.; Espinola, D.A.; Engin, S.I.

1985-01-01

Three-phase radionuclide bone (TPB) imaging was performed on 238 patients with sports-related injuries. A wide variety of lesions was encountered, but the most frequent lesions seen were stress fractures of the lower part of the leg at the junction of the middle and distal thirds of the posterior tibial cortex (42 of 79 lesions). There were no differences in the type, location, or distribution of lesions between males and females or between competitive and noncompetitive athletes. In 110 cases, bone stress lesions were often diagnosed when radiographs were normal, whereas subacute or chronic soft-tissue abnormalities had few specific scintigraphic features. TPB imaging provides significant early diagnostic information about bone stress lesions. Normal examination results (53 cases) exclude underlying osseous pathologic conditions

General practitioners' perspectives on management of early-stage chronic kidney disease: a focus group study.

Science.gov (United States)

van Dipten, Carola; van Berkel, Saskia; de Grauw, Wim J C; Scherpbier-de Haan, Nynke D; Brongers, Bouke; van Spaendonck, Karel; Wetzels, Jack F M; Assendelft, Willem J J; Dees, Marianne K

2018-06-06

Guideline adherence in chronic kidney disease management is low, despite guideline implementation initiatives. Knowing general practitioners' (GPs') perspectives of management of early-stage chronic kidney disease (CKD) and the applicability of the national interdisciplinary guideline could support strategies to improve quality of care. Qualitative focus group study with 27 GPs in the Netherlands. Three analysts open-coded and comparatively analysed the data. Mind-mapping sessions were performed after data-saturation. Five themes emerged: defining CKD, knowledge and awareness, patient-physician interaction, organisation of CKD care and value of the guideline. A key finding was the abstractness of the CKD concept. The GPs expressed various perspectives about defining CKD and interpreting estimated glomerular filtration rates. Views about clinical relevance influenced the decision-making, although factual knowledge seems lacking. Striving to inform well enough without creating anxiety and to explain suitably for the intellectual ability of the patient caused tension in the patient-physician interaction. Integration with cardiovascular disease-management programmes was mentioned as a way of implementing CKD care in the future. The guideline was perceived as a rough guide rather than a leading document. CKD is perceived as an abstract rather than a clinical concept. Abstractness plays a role in all formulated themes. Management of CKD patients in primary care is complex and is influenced by physician-bound considerations related to individual knowledge and perception of the importance of CKD. Strategies are needed to improve GPs' understanding of the concept of CKD by education, a holistic approach to guidelines, and integration of CKD care into cardiovascular programmes. Not applicable.

Breast cancer patients treated with chemotherapy reports more unmet supportive care needs in the early treatment phase, than patients treated only with radiotherapy

DEFF Research Database (Denmark)

Jensen-Johansen, Mikael Birkelund; Meldgaard, Anette; Henriksen, Jette

2016-01-01

of a large battery of selfadministered questionnaires, the women filled out at home, the Supportive Care Needs Survey (SCNS-SF34) together with demographic items (socioeconomic status, working hours, marital status etc.). The SCNS-SF34 includes 5 different domains of needs: Psychological-, Health system...... Aims: The purpose was to identify unmet supportive care needs in the early treatment phase of women treated for breast cancer and to investigate differences in needs between groups treated with chemo-therapy and radiationtherapy. If it is possible to identify early unmet needs, it may be possible...... to predict levels of unmet needs in the post-treatment phase and target an early rehabilitation to specific groups and with specific interventions. Population: Over a six-month period, 123 Danish women treated with mastectomy or lumpectomy, were assessed for eligibility in the midst of their primary...

F247. INTERNALIZED STIGMA HAS A STRONGER RELATIONSHIP WITH INTRINSIC MOTIVATION COMPARED TO AMOTIVATION IN EARLY PHASE AND PROLONGED SCHIZOPHRENIA

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Firmin, Ruth; Luther, Lauren; Lysaker, Paul; Vohs, Jennifer

2018-01-01

Abstract Background Motivation deficits predict decreased functioning in schizophrenia. Recent work suggests deficits reflect challenges in separate domains: intrinsic motivation (one’s internal drive to engage in a behavior out of enjoyment or interest) and amotivation (one’s broader decrease in motivated behavior linked to avolition and anhedonia). Internalized stigma is another determinant of functioning for people with schizophrenia that may impact motivation. However, little is known about these relationships, including which aspects of motivation it may impact nor when these links emerge. Identifying the link between these constructs may help to identify whether internalized stigma may be a novel treatment target to facilitate improvements in motivation. Methods Forty adults with early phase schizophrenia and 66 adults with prolonged schizophrenia completed measures of internalized stigma, intrinsic motivation, and amotivation. Pearson’s correlations were examined followed by Fischer’s r-to-z transformations to compare differences in the magnitude of associations between internalized stigma and intrinsic motivation and internalized stigma and amotivation among the first episode and prolonged samples. Next, we conducted stepwise regressions to examine whether internalized stigma was associated with intrinsic motivation above and beyond associations with amotivation in each sample. Results In the early phase sample, the association between internalized stigma was greater with intrinsic motivation (r=-0.48, p=.00) compared to amotivation (r=0.27, p=0.10). Associations with internalized stigma in the prolonged sample were also greater with intrinsic motivation (r=-0.30, p=0.02) versus amotivation (r=0.19, p=0.12). The magnitude of the associations between internalized stigma and intrinsic motivation (z=1.03, p=0.15) and between internalized stigma and amotivation (z=0.41, p = 0.34) did not significantly differ when comparing phase of illness. Regression

Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence.

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Chaby, Lauren E; Cavigelli, Sonia A; White, Amanda; Wang, Kayllie; Braithwaite, Victoria A

2013-01-01

Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid "stress" hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision-making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g., isolation, crowding, cage tilt) were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias [F (1, 12) = 5.000, P chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object [T (1, 14) = 2.240, P = 0.04; T (1, 14) = 2.419, P = 0.03, respectively]. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions.

The brain-derived neurotrophic factor pathway, life stress, and chronic multi-site musculoskeletal pain.

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Generaal, Ellen; Milaneschi, Yuri; Jansen, Rick; Elzinga, Bernet M; Dekker, Joost; Penninx, Brenda W J H

2016-01-01

Brain-derived neurotrophic factor (BDNF) disturbances and life stress, both independently and in interaction, have been hypothesized to induce chronic pain. We examined whether (a) the BDNF pathway (val(66)met genotype, gene expression, and serum levels), (b) early and recent life stress, and (c) their interaction are associated with the presence and severity of chronic multi-site musculoskeletal pain. Cross-sectional data are from 1646 subjects of the Netherlands Study of Depression and Anxiety. The presence and severity of chronic multi-site musculoskeletal pain were determined using the Chronic Pain Grade (CPG) questionnaire. The BDNF val(66)met polymorphism, BDNF gene expression, and BDNF serum levels were measured. Early life stress before the age of 16 was assessed by calculating a childhood trauma index using the Childhood Trauma Interview. Recent life stress was assessed as the number of recent adverse life events using the List of Threatening Events Questionnaire. Compared to val(66)val, BDNF met carriers more often had chronic pain, whereas no differences were found for BDNF gene expression and serum levels. Higher levels of early and recent stress were both associated with the presence and severity of chronic pain (p stress in the associations with chronic pain presence and severity. This study suggests that the BDNF gene marks vulnerability for chronic pain. Although life stress did not alter the impact of BDNF on chronic pain, it seems an independent factor in the onset and persistence of chronic pain. © The Author(s) 2016.

Decrease in urinary creatinine excretion in early stage chronic kidney disease.

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Elena Tynkevich

Full Text Available BACKGROUND: Little is known about muscle mass loss in early stage chronic kidney disease (CKD. We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population. METHODS: We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR by (51Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time. RESULTS: Baseline mean urinary creatinine excretion decreased from 15.3 ± 3.1 to 12.1 ± 3.3 mmol/24 h (0.20 ± 0.03 to 0.15 ± 0.04 mmol/kg/24 h in men, with mGFR falling from ≥ 60 to <15 mL/min/1.73 m(2, and from 9.6 ± 1.9 to 7.6 ± 2.5 (0.16 ± 0.03 to 0.12 ± 0.03 in women. In addition to mGFR, an older age, diabetes, and lower levels of body mass index, proteinuria, and protein intake assessed by urinary urea were associated with lower mean urinary creatinine excretion at baseline. Mean annual decline in mGFR was 1.53 ± 0.12 mL/min/1.73 m(2 per year and that of urinary creatinine excretion rate, 0.28 ± 0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m(2 had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass. CONCLUSIONS: Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass.

Pathological consequences of chronic low daily dose gamma irradiation

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Seed, T.M.; Miller, A.C.; Ramakrishnan, N. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States); Fritz, T.E.

2000-07-01

The quantitative relationships between the chronic radiation exposure parameters of dose-rate and total dose in relation to associated health risks was examined in dogs. At a dose-rate of 75, 128, and 263 mGy/d the incidence of acute lymphohematopoietic suppression (aplastic anemia) and associated septic complications was 73%, 87%, and 100%, respectively, and it increased in dose-dependent manner. By contrast, at dose-rates below 75 mGy/d, late cancers contributed significantly to the death of relatively long-lived animals, whose mean survival time was 1800 days. Myeloproliferative disease (MPD), mainly myeloid leukemia, was the dominant pathology seen at the higher daily dose-rates (18.8-75 mGy/d). When daily exposure was carried out continuously, the incidence of MPD was quite high. It should be noted that the induction radiation-induced MPD in this study was highly significant, because spontaneous MPD is exceedingly rare in the dog. However, when the daily dose-rate was reduced further or exposure was discontinued, the incidence of MPD declined significantly. At these lower dose-rates, solid tumors contributed heavily to the life-shortening effects of chronic irradiation. The induction and progression of these survival-compromising, late forms of pathology appeared to be driven by the degree of hematopoietic suppression that occurred early during the exposure phase, and in turn by the capacity of hematopoietic system to repair itself, recover, and to accommodate under chronic radiation stress. (K.H.)

Response to duloxetine in chronic low back pain: exploratory post hoc analysis of a Japanese Phase III randomized study

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Tsuji T

2017-09-01

Full Text Available Toshinaga Tsuji,1 Naohiro Itoh,1 Mitsuhiro Ishida,2 Toshimitsu Ochiai,3 Shinichi Konno4 1Medical Affairs Department, 2Clinical Research Development, 3Biostatistics Department, Shionogi & Co. Ltd, Osaka, 4Department of Orthopedic Surgery, Fukushima Medical University, Fukushima, Japan Purpose: Duloxetine is efficacious for chronic low back pain (CLBP. This post hoc analysis of a Japanese randomized, placebo-controlled trial (ClinicalTrials.gov, NCT01855919 assessed whether patients with CLBP with early pain reduction or treatment-related adverse events of special interest (TR-AESIs; nausea, somnolence, constipation have enhanced responses to duloxetine. Patients and methods: Patients (N = 456 with CLBP for ≥6 months and Brief Pain Inventory (BPI average pain severity score of ≥4 were randomized (1:1 to duloxetine 60 mg/day or placebo for 14 weeks. Primary outcome was change from baseline in BPI average pain severity score (pain reduction. Subgroup analyses included early pain reduction (≥30%, 10%–30%, or <10% at Week 4 and early TR-AESIs (with or without TR-AESIs by Week 2. Measures included changes from baseline in BPI average pain severity score and BPI Interference scores (quality of life; QOL, and response rate (≥30% or ≥50% pain reduction at Week 14. Results: Patients with ≥30% early pain reduction (n = 108 or early TR-AESIs (n = 50 had significantly greater improvements in pain and QOL than placebo-treated patients (n = 226, whereas patients with 10%–30% (n = 63 or <10% (n = 48 pain reduction did not; patients without early TR-AESIs (n = 180 had significant improvements in pain at Week 14. Response rates (≥30%/≥50% pain reduction were 94.4%/82.4%, 66.7%/49.2%, and 25.0%/18.8% for patients with ≥30%, 10%–30%, and <10% early pain reduction, respectively, 74.0%/64.0% for patients with early TR-AESIs, 67.2%/54.4% for patients without early TR-AESIs, and 52.2%/39.4% for placebo.Conclusion: Early pain reduction or TR

FIV establishes a latent infection in feline peripheral blood CD4+ T lymphocytes in vivo during the asymptomatic phase of infection

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Murphy Brian

2012-02-01

Full Text Available Abstract Background Feline immunodeficiency virus (FIV is a lentivirus of cats that establishes a lifelong persistent infection with immunologic impairment. Results In an approximately 2 year-long experimental infection study, cats infected with a biological isolate of FIV clade C demonstrated undetectable plasma viral loads from 10 months post-infection onward. Viral DNA was detected in CD4+CD25+ and CD4+CD25- T cells isolated from infected cats whereas viral RNA was not detected at multiple time points during the early chronic phase of infection. Viral transcription could be reactivated in latently infected CD4+ T cells ex vivo as demonstrated by detectable FIV gag RNA and 2-long terminal repeat (LTR circle junctions. Viral LTR and gag sequences amplified from peripheral blood mononuclear cells during early and chronic stages of infection demonstrated minimal to no viral sequence variation. Conclusions Collectively, these findings are consistent with FIV latency in peripheral blood CD4+ T cells isolated from chronically infected cats. The ability to isolate latently FIV-infected CD4+ T lymphocytes from FIV-infected cats provides a platform for the study of in vivo mechanisms of lentiviral latency.

7T T₂*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease.

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van Rooden, Sanneke; Doan, Nhat Trung; Versluis, Maarten J; Goos, Jeroen D C; Webb, Andrew G; Oleksik, Ania M; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Weverling-Rynsburger, Annelies W E; Blauw, Gerard Jan; Reiber, Johan H C; van Buchem, Mark A; Milles, Julien; van der Grond, Jeroen

2015-01-01

The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(∗)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p ≤ 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Proxy reporting in after-death interviews: the use of proxy respondents in retrospective assessment of chronic diseases and symptom burden in the terminal phase of life

NARCIS (Netherlands)

Klinkenberg, M.; Smit, J. H.; Deeg, D. J. H.; Willems, D. L.; Onwuteaka-Philipsen, B. D.; van der Wal, G.

2003-01-01

This study evaluates the quality of data obtained from after-death interviews with significant others of deceased older persons regarding the prevalence of chronic diseases and symptoms in the terminal phase of life. These data are compared with reports from physicians and earlier self-reports from

Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

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McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

2015-01-15

Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights reserved.

Chronic hepatitis B virus infection in Asian countries.

Science.gov (United States)

Merican, I; Guan, R; Amarapuka, D; Alexander, M J; Chutaputti, A; Chien, R N; Hasnian, S S; Leung, N; Lesmana, L; Phiet, P H; Sjalfoellah Noer, H M; Sollano, J; Sun, H S; Xu, D Z

2000-12-01

Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of

Alkyl PAH in crude oil cause chronic toxicity to early life stages of fish

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Hodson, P.V.; Khan, C.W.; Saravanabhavan, G.; Clarke, L.; Brown, R.S. [Queen' s Univ., Kingston, ON (Canada). School of Environmental Studies; Hollebone, B.; Wang, Z. [Environment Canada, Ottawa, ON (Canada). ; Short, J. [National Oceanic and Atmospheric Administration, Juneau, AK (United States). Auke Bay Lab; Lee, K.; King, T. [Fisheries and Oceans Canada, Dartmouth, NS (Canada). Centre for Offshore Oil and Gas Environmental Research

2007-07-01

In order to mitigate the risk to fisheries following an offshore oil spill, it is necessary to know the components of crude oil that are toxic. Chronic exposure of early life stages of fish to crude oil causes Blue Sac Disease, a syndrome characterized by induction of the cytochrome P450 (CYP1A) enzyme. In this study, effects-driven fractionation of Alaska North Slope Crude was used to identify the classes of compounds that cause CYP1A induction in juvenile rainbow trout and chronic toxicity to developing stages of Japanese medaka. Four fractions of compounds were created by low temperature vacuum distillation. This separated the constituents of oil according to their volatility within defined temperature ranges. The fractions were separated according to their boiling points. With a temperature range of 287-481 degrees C, fraction F3 was the only fraction as toxic as whole oil and induced CYPP1A enzymes of fish. Fractions containing specific classes of alkyl PAH were also collected. For all separations, the performance of the method was evaluated by the extent to which PAH were separated from aliphatics, resins and waxes, as well as by the quantitative recovery of mass in fractions and subfractions. The induction of CYP1A enzymes showed that PAH was present in all fractions that were highly toxic, but the toxicity tests indicated that not all fractions containing PAH were toxic. This research provided a scientific basis for comparing the risks of different crude oils based on chemical analyses that show the different proportions or amounts of PAH present. The results indicate which compounds of concern should be used to determine the extent and success of oil spill remediation, and provide a biological interpretation of chemical fingerprinting used to discriminate the sources of oil pollution. 15 refs., 1 tab.

Bone scintigraphy compared to MRI and ultrasound in the early diagnosis of arthritis; Skelettszintigraphie im Vergleich mit MRT und Sonographie beim Fruehnachweis der Arthritis

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Sandrock, D. [Klinikum Chemnitz gGmbH, Klinik fuer Nuklearmedizin, Chemnitz (Germany)

2006-12-15

Chronic inflammatory arthritis is recognized specifically by bone erosions, caused by characteristic pannus tissue. In the finger joints dynamic low-Tesla MRI is nearly double but not completely sensitive in the detection of erosions than conventional radiography, sonography takes an intermediate position. Less specific signs of synovitis and tenosynovitis are shown with high sensitivity by both 3(2)-phase bone scintigraphy and ultrasound, MRI is less sensitive in this respect. However, standard situation of inflammation in bone scintigraphy - positive finding in early as well as late phase - is of surprisingly low sensitivity, any singular finding in the early or late phase has to be regarded as positive. Specificity of these singular findings is nevertheless sufficiently high, acute inflammatory joint changes and even erosions are also seen with MRI in obviously healthy persons. Only 2-phase bone scintigraphy is easily able to present a simultaneous survey of all joints of the body. For this reason 2-phase bone scintigraphy is most suitable for exclusion but also for primary diagnosis of disease, specification must be done afterwards by other imaging modalities or by laboratory findings. (orig.)

[The impact of Glivec related side effects on daily life in Chinese patients with chronic myeloid leukemia in the chronic phase].

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Yu, L; Wang, H B; Huang, X J; Jiang, Q

2016-07-01

To explore the impact of Glivec related side effects on daily life in Chinese patients with chronic myeloid leukemia (CML) in the chronic phase (CP). From May to November in 2014, anonymous questionnaires were distributed to adult CML patients who were receiving tyrosine kinase inhibitors (TKI) treatment in China. The impact of TKI related side effects on daily life were assessed by the score of 1 (no impact) to 5 (high impact) from patient self- report. Data from 548 respondents in the CP on Glivec were collected. 303(55%) cases were male with the median age of 40 years (range, 18 to 88 years). 437 (80% ) cases started Glivec treatment within one year after diagnosis with a median treatment duration of 3 years (range, effects were edema (n=278, 51% ), fatigue (n=218, 40% ), gastrointestinal disorders (n=190, 35%), muscle cramps (n=118, 22%), skin color changes (n=118, 22%), weight gain (n=71, 13%), rash (n=60, 11%), hepatic function abnormality (n=55, 10%), and cytopenia (n=38, 7%). Among the 548 respondents, the mean score of Glivec-related side effects on daily life was 2.4±1.2. There was no negative impact of Glivec related side effects on daily life in 161(29%) respondents. 295 (54% ) and 92 (17% ) respondents reported slightly or moderately (2- 3 score) and significantly decreased (4-5 score) daily life, respectively. Multivariate analysis showed that Glivec treatment duration effects including fatigue (OR=2.9, 95% CI 2.1-4.1;Pnegative effect on daily life. Daily life was impaired seriously in a minority of Chinese CML patients who received Glivec, especially in the first 4 years of treatment. Fatigue, edema, gastrointestinal disorders, rash and hepatic function abnormality were side effects associated with negative impact on patients' daily life.

Home-based nerve stimulation to enhance effects of motor training in patients in the chronic phase after stroke: a proof-of-principle study.

Science.gov (United States)

Dos Santos-Fontes, Renata Laurenti; Ferreiro de Andrade, Karina Nocelo; Sterr, Annette; Conforto, Adriana Bastos

2013-01-01

Somatosensory stimulation in the form of repetitive peripheral nerve stimulation (RPSS) is a promising strategy to improve motor function of the upper limb in chronic stroke. Home-based RPSS may be an alternative to hospital-based RPSS. To investigate the feasibility and safety of an innovative program of home-based RPSS combined with motor training and to collect preliminary data on the efficacy of this program to enhance hand motor function in patients in the chronic phase after stroke. Twenty patients were randomized to either active or sham RPSS associated with daily motor training performed at home over 4 consecutive weeks. All the patients were able to perform tasks of the Jebsen-Taylor Test (JTT). The primary outcome measures were feasibility, evaluated by self-reported compliance with the intervention, and safety (adverse events). Secondary outcomes comprised improvements in hand function in the JTT after end of treatment and after a 4-month follow-up period. There were no relevant adverse events. Compliance with RPSS and motor training was significantly greater in the active group than in the sham group. Upper extremity performance improved significantly more in the active group compared with the sham group at the end of treatment. This difference remained significant 4 months later, even when differences in compliance with motor training were considered. Home-based active RPSS associated with motor training was feasible, was safe, and led to long-lasting enhancement of paretic arm performance in the chronic phase after stroke for those who can perform the JTT. These results point to the need for an efficacy trial.

Prevention of chronic PTSD with early cognitive behavioral therapy. A meta-analysis using mixed-effects modeling.

Science.gov (United States)

Kliem, Sören; Kröger, Christoph

2013-11-01

Post-traumatic stress disorder (PTSD) is of great interest to public health, due to the high burden it places on both the individual and society. We meta-analyzed randomized-controlled trials to examine the effectiveness of early trauma-focused cognitive-behavioral treatment (TFCBT) for preventing chronic PTSD. Systematic bibliographic research was undertaken to find relevant literature from on-line databases (Pubmed, PsycINFO, Psyndex, Medline). Using a mixed-effect approach, we calculated effect sizes (ES) for the PTSD diagnoses (main outcome) as well as PTSD and depressive symptoms (secondary outcomes), respectively. Calculations of ES from pre-intervention to first follow-up assessment were based on 10 studies. A moderate effect (ES = 0.54) was found for the main outcome, whereas ES for secondary outcomes were predominantly small (ES = 0.27-0.45). The ES for the main outcome decreased to small (ES = 0.34) from first follow-up to long-term follow-up assessment. The mean dropout rate was 16.7% pre- to post-treatment. There was evidence for the impact of moderators on different outcomes (e.g., the number of sessions on PTSD symptoms). Future studies should include survivors of other trauma types (e.g., burn injuries) rather than predominantly survivors of accidents and physical assault, and should compare early TFCBT with other interventions that previously demonstrated effectiveness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Once-Monthly Continuous Erythropoietin Receptor Activator (C.E.R.A.) in Patients with Hemodialysis-Dependent Chronic Kidney Disease: Pooled Data from Phase III Trials.

Science.gov (United States)

Locatelli, Francesco; Choukroun, Gabriel; Truman, Matt; Wiggenhauser, Alfons; Fliser, Danilo

2016-04-01

Erythropoiesis-stimulating agents and iron are commonly used in patients with chronic kidney disease with the aim of correcting anemia and maintaining stable hemoglobin levels. We analyzed pooled data from 13 studies with similar designs included in the Umbrella Continuous Erythropoietin Receptor Activator (C.E.R.A.) program to investigate the effects of continuous erythropoiesis receptor activator in clinically relevant subgroups of patients with chronic kidney disease and to determine whether the efficacy and safety outcomes demonstrated in the overall chronic kidney disease population are maintained in specific subgroups. Data from 13 Phase III trials set up with similar design were retrospectively pooled for this analysis. Patients with chronic kidney disease who had previously been receiving epoetin or darbepoetin were switched to continuous erythropoiesis receptor activator once-monthly after a 4- to 8-week screening period. Patients entered a 16-week continuous erythropoiesis receptor activator dose-titration period followed by an 8-week evaluation period. In total, 2060 patients were included in the analysis. Subgroups were defined based on: hemoglobin target range [lower (10.0-12.0 g/dL)/upper (10.5-13.0 g/dL)], gender (female/male), age (Basel, Switzerland.

Neurodegenerative properties of chronic pain: cognitive decline in patients with chronic pancreatitis.

Directory of Open Access Journals (Sweden)

Marijtje L A Jongsma

Full Text Available Chronic pain has been associated with impaired cognitive function. We examined cognitive performance in patients with severe chronic pancreatitis pain. We explored the following factors for their contribution to observed cognitive deficits: pain duration, comorbidity (depression, sleep disturbance, use of opioids, and premorbid alcohol abuse. The cognitive profiles of 16 patients with severe pain due to chronic pancreatitis were determined using an extensive neuropsychological test battery. Data from three cognitive domains (psychomotor performance, memory, executive functions were compared to data from healthy controls matched for age, gender and education. Multivariate multilevel analysis of the data showed decreased test scores in patients with chronic pancreatitis pain in different cognitive domains. Psychomotor performance and executive functions showed the most prominent decline. Interestingly, pain duration appeared to be the strongest predictor for observed cognitive decline. Depressive symptoms, sleep disturbance, opioid use and history of alcohol abuse provided additional explanations for the observed cognitive decline in some of the tests, but to a lesser extent than pain duration. The negative effect of pain duration on cognitive performance is compatible with the theory of neurodegenerative properties of chronic pain. Therefore, early and effective therapeutic interventions might reduce or prevent decline in cognitive performance, thereby improving outcomes and quality of life in these patients.

Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

Science.gov (United States)

Di Gioacchino, M; Perrone, A; Petrarca, C; Di Claudio, F; Mistrello, G; Falagiani, P; Dadorante, V; Verna, N; Braga, M; Ballone, E; Cavallucci, E

2008-01-01

The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (pallergoids are utilized.

SURVIVAL OF INTERSTELLAR MOLECULES TO PRESTELLAR DENSE CORE COLLAPSE AND EARLY PHASES OF DISK FORMATION

International Nuclear Information System (INIS)

Hincelin, U.; Wakelam, V.; Hersant, F.; Guilloteau, S.; Commerçon, B.

2013-01-01

An outstanding question of astrobiology is the link between the chemical composition of planets, comets, and other solar system bodies and the molecules formed in the interstellar medium. Understanding the chemical and physical evolution of the matter leading to the formation of protoplanetary disks is an important step for this. We provide some new clues to this long-standing problem using three-dimensional chemical simulations of the early phases of disk formation: we interfaced the full gas-grain chemical model Nautilus with the radiation-magnetohydrodynamic model RAMSES, for different configurations and intensities of the magnetic field. Our results show that the chemical content (gas and ices) is globally conserved during the collapsing process, from the parent molecular cloud to the young disk surrounding the first Larson core. A qualitative comparison with cometary composition suggests that comets are constituted of different phases, some molecules being direct tracers of interstellar chemistry, while others, including complex molecules, seem to have been formed in disks, where higher densities and temperatures allow for an active grain surface chemistry. The latter phase, and its connection with the formation of the first Larson core, remains to be modeled

A multidisciplinary network for the care of abnormal fatigue and chronic fatigue syndrome in the provinces of East and West Flanders in Belgium.

Science.gov (United States)

Tobback, E; Mariman, A; Heytens, S; Declercq, T; Bouwen, A; Spooren, D; Snoeck, P; Van Dessel, K; D'Hooghe, S; Rimbaut, S; Vogelaers, D

2014-10-01

The organization of care for patients with the chronic fatigue syndrome (CFS) in tertiary care referral centres from 2002 onwards, was negatively evaluated by the Belgian Health Care Knowledge Centre on the endpoint of socio-professional reintegration. Subsequently, the federal health authorities asked for the elaboration of a new and innovative model of stepped care, aiming at improved integration of diagnosis and treatment into primary care and between levels of health care for patients with CFS. The reference centre of the University Hospital Ghent took the initiative of recruiting partners in the Belgian provinces of East and West Flanders to guarantee the care for patients with medically unexplained symptoms, in particular abnormal fatigue and CFS. A new and innovative care model, in which general practitioners play a central role, emphasizes the importance of early recognition of the patient 'at risk', correct diagnosis and timely referral. Early detection and intervention is essential in order to avoid or minimize illness progression towards chronicity, to safeguard opportunities for significant health improvement as well as to enhance successful socio-professional reintegration. This approach covers both the large sample of patients developing somatic complaints without obvious disease in an early phase as well as the more limited group of patients with chronic illness, including CFS. Cognitive behavioural therapy and graded exposure/exercise therapy are the evidence based main components of therapy in the latter. A biopsychosocial model underlies the proposed path of care.

Nano-scale clusters formed in the early stage of phase decomposition of Al-Mg-Si alloys

Energy Technology Data Exchange (ETDEWEB)

Hirosawa, S.; Sato, T. [Dept. of Metallurgy and Ceramics Science, Tokyo Inst. of Tech. (Japan)

2005-07-01

The formation of nano-scale clusters (nanoclusters) prior to the precipitation of the strengthening {beta}'' phase significantly influences two-step aging behavior of Al-Mg-Si alloys. In this work, the existence of two kinds of nanoclusters has been verified in the early stage of phase decomposition by differential scanning calorimetry (DSC) and three-dimensional atom probe (3DAP). Pre-aging treatment at 373 K before natural aging was also found to form preferentially one of the two nanoclusters, resulting in the remarkable restoration of age-hardenability at paint-bake temperatures. Such microstructural control by means of optimized heat-treatments; i.e. nanocluster assist processing (NCAP), possesses great potential for enabling Al-Mg-Si alloys to be used more widely as a body-sheet material of automobiles. (orig.)

LONG-TERM RESULTS OF TARGET THERAPY WITH FIRST AND * SECOND-LINE TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

Directory of Open Access Journals (Sweden)

L. L. Vysotskaya

2015-01-01

Full Text Available Aim: To assess long-term efficacy of firstand second-line tyrosine kinase inhibitors in non-selected patients with chronic myeloid leukemia in a real-life clinical setting.Materials and methods: The assessment is based on long-term results of a prospective single center comparative clinical trial that was based on non-selected groups of 116 patients with various stages of chronic myeloid leukemia being treated with a first generation tyrosine kinase inhibitor imatinib, and of 44 patients being treated with a second generation tyrosine kinase inhibitor nilotinib. We analyzed all-cause mortality, progression-free survival from April 2005 to April 2013, with a median of the follow-up of 128 months.Results: In 116 patients with chronic myeloid leukemia treated with imatinib, the Kaplan-Meier survival estimate was 120 months. In 44 patients at an early chronic phase, 5-year overall survival and progression-free survival was 93.2% and 8-year overall and progression-free survival was 79.5%. In 44 patients at a late chronic stage, 5-year overall and progression-free survival was 95.5%, 8-year overall and progression-free survival, 72.7%. In 28 patients at acceleration phase, 5-years overall survival was 78.6% and 8-year overall survival, 46%. Median of overall survival in patients treated with nilotinib was not reached. During 78.6 months of combination treatment with cytotoxic agents, tyrosine kinase inhibitors of the first (imatinib and second line (nilotinib, overall survival was 100%.Conclusion: In clinical practice, inclusion of patients with chronic myeloid leukemia and imatinib resistance (disease relapse or imatinib intolerance into the treatment program with frontline therapy with general cytotoxic agents and thereafter with firstand second-line tyrosine kinase inhibitors significantly improves overall survival.

Hereditary chronic pancreatitis

Directory of Open Access Journals (Sweden)

Mössner Joachim

2007-01-01

Full Text Available Abstract Hereditary chronic pancreatitis (HCP is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2, the serine protease inhibitor, Kazal type 1 (SPINK1 and the cystic fibrosis transmembrane conductance regulator (CFTR have been found to be associated with chronic pancreatitis (idiopathic and hereditary as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

Some remarks on the transitional phase between Early Roman and Late Roman Periods in the region north of the Middle Danube

Czech Academy of Sciences Publication Activity Database

Tejral, Jaroslav

2015-01-01

Roč. 56, č. 2 (2015), s. 43-101 ISSN 1211-7250 Institutional support: RVO:68081758 Keywords : Early and Late Roman Period * transitional phase * Marcomanic Wars and their aftermath * ethnical and social backround of the B2/C1 phase Subject RIV: AC - Archeology, Anthropology, Ethnology http://prehled-vyzkumu.arub.avcr.cz/miranda2/export/sitesavcr/arub-prehled-vyzkumu/prehled-cisel-a-clanku/prehled-vydanych-cisel/files/PV56_2_Studie2_Tejral.pdf

Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukaemia: a phase 1-2 study

DEFF Research Database (Denmark)

Coiffier, Bertrand; Losic, Nedjad; Rønn, Birgitte Biilmann

2010-01-01

The purpose of this phase 1-2 study was to investigate the association between the pharmacokinetic properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukaemia receiving 4 weekly infusions of ofatumumab. The ofatumu...

Early Origins of Child Obesity: Bridging Disciplines and Phases of Development - September 30–October 1, 2010

Science.gov (United States)

Christoffel, Katherine Kaufer; Wang, Xiaobin; Binns, Helen J.

2012-01-01

This report summarizes a conference: “Early Origins of Child Obesity: Bridging Disciplines and Phases of Development”, held in Chicago on September 30–October 1, 2010. The conference was funded in part by the National Institutes of Health and the Williams Heart Foundation, to achieve the conference objective: forging a next-step research agenda related to the early origins of childhood obesity. This research agenda was to include working with an array of factors (from genetic determinants to societal ones) along a continuum from prenatal life to age 7, with an emphasis on how the developing child deals with the challenges presented by his/her environment (prenatal, parental, nutritional, etc.). The conference offered a unique opportunity to facilitate communication and planning of future work among a variety of researchers whose work separately addresses different periods in early life. Over the span of two days, speakers addressed existing, critical research topics within each of the most-studied age ranges. On the final day, workshops fostered the discussion needed to identify the highest priority research topics related to linking varied early factor domains. These are presented for use in planning future research and research funding. PMID:23443002

Review of hardware cost estimation methods, models and tools applied to early phases of space mission planning

Science.gov (United States)

Trivailo, O.; Sippel, M.; Şekercioğlu, Y. A.

2012-08-01

The primary purpose of this paper is to review currently existing cost estimation methods, models, tools and resources applicable to the space sector. While key space sector methods are outlined, a specific focus is placed on hardware cost estimation on a system level, particularly for early mission phases during which specifications and requirements are not yet crystallised, and information is limited. For the space industry, cost engineering within the systems engineering framework is an integral discipline. The cost of any space program now constitutes a stringent design criterion, which must be considered and carefully controlled during the entire program life cycle. A first step to any program budget is a representative cost estimate which usually hinges on a particular estimation approach, or methodology. Therefore appropriate selection of specific cost models, methods and tools is paramount, a difficult task given the highly variable nature, scope as well as scientific and technical requirements applicable to each program. Numerous methods, models and tools exist. However new ways are needed to address very early, pre-Phase 0 cost estimation during the initial program research and establishment phase when system specifications are limited, but the available research budget needs to be established and defined. Due to their specificity, for vehicles such as reusable launchers with a manned capability, a lack of historical data implies that using either the classic heuristic approach such as parametric cost estimation based on underlying CERs, or the analogy approach, is therefore, by definition, limited. This review identifies prominent cost estimation models applied to the space sector, and their underlying cost driving parameters and factors. Strengths, weaknesses, and suitability to specific mission types and classes are also highlighted. Current approaches which strategically amalgamate various cost estimation strategies both for formulation and validation

Alfuzosin and Symptoms of Chronic Prostatitis–Chronic Pelvic Pain Syndrome

Science.gov (United States)

Nickel, J. Curtis; Krieger, John N.; McNaughton-Collins, Mary; Anderson, Rodney U.; Pontari, Michel; Shoskes, Daniel A.; Litwin, Mark S.; Alexander, Richard B.; White, Paige C.; Berger, Richard; Nadler, Robert; O'Leary, Michael; Liong, Men Long; Zeitlin, Scott; Chuai, Shannon; Landis, J. Richard; Kusek, John W.; Nyberg, Leroy M.; Schaeffer, Anthony J.

2009-01-01

Background In men with chronic prostatitis–chronic pelvic pain syndrome, treatment with alpha-adrenergic receptor blockers early in the course of the disorder has been reported to be effective in some, but not all, relatively small randomized trials. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of alfuzosin, an alpha-adrenergic receptor blocker, in reducing symptoms in men with chronic prostatitis–chronic pelvic pain syndrome. Participation in the study required diagnosis of the condition within the preceding 2 years and no previous treatment with an alpha-adrenergic receptor blocker. Men were randomly assigned to treatment for 12 weeks with either 10 mg of alfuzosin per day or placebo. The primary outcome was a reduction of at least 4 points (from baseline to 12 weeks) in the score on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (range, 0 to 43; higher scores indicate more severe symptoms). A 4-point decrease is the minimal clinically significant difference in the score. Results A total of 272 eligible participants underwent randomization, and in both study groups, 49.3% of participants had a decrease of at least 4 points in their total NIH-CPSI score (rate difference associated with alfuzosin, 0.1%; 95% confidence interval, −11.2 to 11.0; P = 0.99). In addition, a global response assessment showed similar response rates at 12 weeks: 33.6% in the placebo group and 34.8% in the alfuzosin group (P = 0.90). The rates of adverse events in the two groups were also similar. Conclusions Our findings do not support the use of alfuzosin to reduce the symptoms of chronic prostatitis–chronic pelvic pain syndrome in men who have not received prior treatment with an alpha-blocker. PMID:19092152

The role of perfusion lung scanning and diffusion capacity for early diagnosis of micro circulatory disturbances in chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

Petrova, D.; Shoshlov, P.; Hadjikostova, H.

2002-01-01

The development of chronic obstructive pulmonary disease (COPD) and the frequent inflammatory exacerbations with development of respiratory failure lead to changes in the micro circulatory and an increased risk of lung thrombotic and thromboembolic complication. The aim of the study was to establish the possibility of the perfusion lung scanning and diffusion capacity for early diagnosis of pulmonary micro circulatory disturbances in COPD with mild and moderate respiratory failure. 59 COPD patients were investigated. The data presented significant segmental disorders. Only in 5 (8.47%) of them the perfusion lung scintigrams were normal. In 23 of the patients, single-breath diffusing capacity (DICO) and its two components: membranous component (Dm) and capillary blood component (Vc) were determined. DICO was lower especially Vc the mean sign of micro circulatory disorders. A relationship between the degree of hypoxaemia and the changes found in the perfusion scintigraphy was found. Changes in the pulmonary lung scanning and in the diffusion capacity in COPD with mild respiratory failure seem to be an early diagnostic test. The early anticoagulant and desaggregant prevention may decrease the risk of thrombotic complications in the development of the disease. (authors)

Dose-Volume Histogram Predictors of Chronic Gastrointestinal Complications After Radical Hysterectomy and Postoperative Concurrent Nedaplatin-Based Chemoradiation Therapy for Early-Stage Cervical Cancer

International Nuclear Information System (INIS)

Isohashi, Fumiaki; Yoshioka, Yasuo; Mabuchi, Seiji; Konishi, Koji; Koizumi, Masahiko; Takahashi, Yutaka; Ogata, Toshiyuki; Maruoka, Shintaroh; Kimura, Tadashi; Ogawa, Kazuhiko

2013-01-01

Purpose: The purpose of this study was to evaluate dose-volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in cervical cancer patients who underwent radical hysterectomy and postoperative concurrent nedaplatin-based chemoradiation therapy. Methods and Materials: This study analyzed 97 patients who underwent postoperative concurrent chemoradiation therapy. The organs at risk that were contoured were the small bowel loops, large bowel loop, and peritoneal cavity. DVH parameters subjected to analysis included the volumes of these organs receiving more than 15, 30, 40, and 45 Gy (V15-V45) and their mean dose. Associations between DVH parameters or clinical factors and the incidence of grade 2 or higher chronic GI complications were evaluated. Results: Of the clinical factors, smoking and low body mass index (BMI) (<22) were significantly associated with grade 2 or higher chronic GI complications. Also, patients with chronic GI complications had significantly greater V15-V45 volumes and higher mean dose of the small bowel loops compared with those without GI complications. In contrast, no parameters for the large bowel loop or peritoneal cavity were significantly associated with GI complications. Results of the receiver operating characteristics (ROC) curve analysis led to the conclusion that V15-V45 of the small bowel loops has high accuracy for prediction of GI complications. Among these parameters, V40 gave the highest area under the ROC curve. Finally, multivariate analysis was performed with V40 of the small bowel loops and 2 other clinical parameters that were judged to be potential risk factors for chronic GI complications: BMI and smoking. Of these 3 parameters, V40 of the small bowel loops and smoking emerged as independent predictors of chronic GI complications. Conclusions: DVH parameters of the small bowel loops may serve as predictors of grade 2 or higher chronic GI complications after postoperative

S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.

Science.gov (United States)

Bektik, Emre; Dennis, Adrienne; Pawlowski, Gary; Zhou, Chen; Maleski, Danielle; Takahashi, Satoru; Laurita, Kenneth R; Deschênes, Isabelle; Fu, Ji-Dong

2018-05-04

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of 5-ethynyl-20-deoxyuridine (EdU)⁺/α-myosin heavy chain (αMHC)-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP low cells. However, S-phase synchronization did not enhance the reprogramming with a polycistronic-viral vector, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

Differential involvement of IL-6 in the early and late phase of 1-methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis.

Science.gov (United States)

Sternak, Magdalena; Jakubowski, Andrzej; Czarnowska, Elzbieta; Slominska, Ewa M; Smolenski, Ryszard T; Szafarz, Malgorzata; Walczak, Maria; Sitek, Barbara; Wojcik, Tomasz; Jasztal, Agnieszka; Kaminski, Karol; Chlopicki, Stefan

2015-09-01

Exogenous 1-methylnicotinamide (MNA) displays anti-inflammatory activity. The aim of this work was to characterize the profile of release of endogenous MNA during the initiation and progression of murine hepatitis induced by Concanavalin A (ConA). In particular we aimed to clarify the role of interleukin-6 (IL-6) as well as the energy state of hepatocytes in MNA release in early and late phases of ConA-induced hepatitis in mice. Hepatitis was induced by ConA in IL-6(+/+) and IL-6(-/-) mice, and various parameters of liver inflammation and injury, as well as the energy state of hepatocytes, were analysed in relation to MNA release. The decrease in ATP/ADP and NADH/NAD ratios, cytokine release (IL-6, IFN-ɤ), acute phase response (e.g. haptoglobin) and liver injury (alanine aminotransaminase, ALT) were all blunted in ConA-induced hepatitis in IL-6(-/-) mice as compared to IL-6(+/+) mice. The release of MNA in response to Con A was also significantly blunted in IL-6(-/-) mice as compared to IL-6(+/+) mice in the early stage of ConA-induced hepatitis. In turn, nicotinamide N-methyltransferase (NNMT) and aldehyde oxidase (AO) activities were blunted in the liver and MNA plasma concentration was elevated to similar degree in the late stage after Concanavalin A in IL-6(+/+) and IL-6(-/-) mice. In conclusion, we demonstrated that in ConA-induced hepatitis, early, but not late MNA release was IL-6-dependent. Our results suggest that in the initiation and early hepatitis, MNA release is linked to the energy deficit/impaired redox status in hepatocytes, while in a later phase, MNA release is rather linked to the systemic inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

Volunteer navigation partnerships: Piloting a compassionate community approach to early palliative care.

Science.gov (United States)

Pesut, Barbara; Duggleby, Wendy; Warner, Grace; Fassbender, Konrad; Antifeau, Elisabeth; Hooper, Brenda; Greig, Madeleine; Sullivan, Kelli

2017-07-03

A compassionate community approach to palliative care provides important rationale for building community-based hospice volunteer capacity. In this project, we piloted one such capacity-building model in which volunteers and a nurse partnered to provide navigation support beginning in the early palliative phase for adults living in community. The goal was to improve quality of life by developing independence, engagement, and community connections. Volunteers received navigation training through a three-day workshop and then conducted in-home visits with clients living with advanced chronic illness over one year. A nurse navigator provided education and mentorship. Mixed method evaluation data was collected from clients, volunteer navigators, the nurse navigator, and other stakeholders. Seven volunteers were partnered with 18 clients. Over the one-year pilot, the volunteer navigators conducted visits in home or by phone every two to three weeks. Volunteers were skilled and resourceful in building connections and facilitating engagement. Although it took time to learn the navigator role, volunteers felt well-prepared and found the role satisfying and meaningful. Clients and family rated the service as highly important to their care because of how the volunteer helped to make the difficult experiences of aging and advanced chronic illness more livable. Significant benefits cited by clients were making good decisions for both now and in the future; having a surrogate social safety net; supporting engagement with life; and ultimately, transforming the experience of living with illness. Overall the program was perceived to be well-designed by stakeholders and meeting an important need in the community. Sustainability, however, was a concern expressed by both clients and volunteers. Volunteers providing supportive navigation services during the early phase of palliative care is a feasible way to foster a compassionate community approach to care for an aging population

Molecular effectors in the chronic exposure to arsenic as early and sensitive biomarkers in developing Rhinella arenarum toads

International Nuclear Information System (INIS)

Mardirosian, Mariana Noelia; Ceschin, Danilo Guillermo; Lascano, Cecilia Inés; Venturino, Andrés

2017-01-01

Highlights: • Arsenic early induces MAPK pathway in R. arenarum embryos and larvae. • The MAPKs MEK-ERK in turn upregulate the transcription factors c-FOS and c-JUN. • SOD, CAT and GST would be affected by ROS at synthesis and degradation level. • Low As levels inducing molecular biomarkers have high probabilities of exceedence. • Molecular biomarkers are most adequate to ascertain As impact in R. arenarum. - Abstract: Arsenic, a natural element of ecological relevance, is one of the most toxic elements present in various regions of the world. It can be found in natural water sources throughout Argentina in concentrations between 0.01 and 15 mg L"–"1. The Argentinean autochthonous toad Rhinella arenarum was selected to study the molecular mechanisms involved in the effects and response to the chronic As exposure along its embryonic and larval development. We evaluated the effects on MAPK signal transduction pathway and transcription factors c-FOS and c-JUN, and the regulation of the expression at protein levels of different antioxidant enzymes. Our results indicated that As is modulating the MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclear fraction along the embryonic development and mainly at the beginning of the larval stage. Through this pathway, As can upregulate transcription factors like c-FOS and c-JUN, impacting the antioxidant response of the exposed embryos and larvae through antioxidant enzymes and recycling of GSH. Arsenic triggered specifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. In particular, the expression levels of SOD, CAT and GST enzymes analyzed by Western blot showed a similar behavior to their enzymatic activities in our previous work. This fact suggests that not only the synthesis of these antioxidant enzymes but also their rapid degradation after inactivation would be regulated in response to ROS levels. Antioxidant enzymes may show dual responses of

Molecular effectors in the chronic exposure to arsenic as early and sensitive biomarkers in developing Rhinella arenarum toads

Energy Technology Data Exchange (ETDEWEB)

Mardirosian, Mariana Noelia; Ceschin, Danilo Guillermo; Lascano, Cecilia Inés; Venturino, Andrés, E-mail: a.venturino@conicet.gov.ar

2017-05-15

Highlights: • Arsenic early induces MAPK pathway in R. arenarum embryos and larvae. • The MAPKs MEK-ERK in turn upregulate the transcription factors c-FOS and c-JUN. • SOD, CAT and GST would be affected by ROS at synthesis and degradation level. • Low As levels inducing molecular biomarkers have high probabilities of exceedence. • Molecular biomarkers are most adequate to ascertain As impact in R. arenarum. - Abstract: Arsenic, a natural element of ecological relevance, is one of the most toxic elements present in various regions of the world. It can be found in natural water sources throughout Argentina in concentrations between 0.01 and 15 mg L{sup –1}. The Argentinean autochthonous toad Rhinella arenarum was selected to study the molecular mechanisms involved in the effects and response to the chronic As exposure along its embryonic and larval development. We evaluated the effects on MAPK signal transduction pathway and transcription factors c-FOS and c-JUN, and the regulation of the expression at protein levels of different antioxidant enzymes. Our results indicated that As is modulating the MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclear fraction along the embryonic development and mainly at the beginning of the larval stage. Through this pathway, As can upregulate transcription factors like c-FOS and c-JUN, impacting the antioxidant response of the exposed embryos and larvae through antioxidant enzymes and recycling of GSH. Arsenic triggered specifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. In particular, the expression levels of SOD, CAT and GST enzymes analyzed by Western blot showed a similar behavior to their enzymatic activities in our previous work. This fact suggests that not only the synthesis of these antioxidant enzymes but also their rapid degradation after inactivation would be regulated in response to ROS levels. Antioxidant enzymes may show dual responses of

Development and application of a biorelevant dissolution method using USP apparatus 4 in early phase formulation development.

Science.gov (United States)

Fang, Jiang B; Robertson, Vivian K; Rawat, Archana; Flick, Tawnya; Tang, Zhe J; Cauchon, Nina S; McElvain, James S

2010-10-04

Dissolution testing is frequently used to determine the rate and extent at which a drug is released from a dosage form, and it plays many important roles throughout drug product development. However, the traditional dissolution approach often emphasizes its application in quality control testing and usually strives to obtain 100% drug release. As a result, dissolution methods are not necessarily biorelevant and meaningful application of traditional dissolution methods in the early phases of drug product development can be very limited. This article will describe the development of a biorelevant in vitro dissolution method using USP apparatus 4, biorelevant media, and real-time online UV analysis. Several case studies in the areas of formulation selection, lot-to-lot variability, and food effect will be presented to demonstrate the application of this method in early phase formulation development. This biorelevant dissolution method using USP apparatus 4 provides a valuable tool to predict certain aspects of the in vivo drug release. It can be used to facilitate the formulation development/selection for pharmacokinetic (PK) and clinical studies. It may also potentially be used to minimize the number of PK studies, and to aid in the design of more efficient PK and clinical studies.

Low Cost Inkjet Printed Smart Bandage for Wireless Monitoring of Chronic Wounds

KAUST Repository

Farooqui, Muhammad Fahad

2016-06-29

Chronic wounds affect millions of patients around the world and their treatment is challenging as the early signs indicating their development are subtle. In addition, a type of chronic wound, known as pressure ulcer, develops in patients with limited mobility. Infection and frequent bleeding are indicators of chronic wound development. In this article, we present an unprecedented low cost continuous wireless monitoring system, realized through inkjet printing on a standard bandage, which can send early warnings for the parameters like irregular bleeding, variations in pH levels and external pressure at wound site. In addition to the early warnings, this smart bandage concept can provide long term wound progression data to the health care providers. The smart bandage comprises a disposable part which has the inkjet printed sensors and a reusable part constituting the wireless electronics. This work is an important step towards futuristic wearable sensors for remote health care applications.

Low Cost Inkjet Printed Smart Bandage for Wireless Monitoring of Chronic Wounds.

Science.gov (United States)

Farooqui, Muhammad Fahad; Shamim, Atif

2016-06-29

Chronic wounds affect millions of patients around the world and their treatment is challenging as the early signs indicating their development are subtle. In addition, a type of chronic wound, known as pressure ulcer, develops in patients with limited mobility. Infection and frequent bleeding are indicators of chronic wound development. In this article, we present an unprecedented low cost continuous wireless monitoring system, realized through inkjet printing on a standard bandage, which can send early warnings for the parameters like irregular bleeding, variations in pH levels and external pressure at wound site. In addition to the early warnings, this smart bandage concept can provide long term wound progression data to the health care providers. The smart bandage comprises a disposable part which has the inkjet printed sensors and a reusable part constituting the wireless electronics. This work is an important step towards futuristic wearable sensors for remote health care applications.

Low Cost Inkjet Printed Smart Bandage for Wireless Monitoring of Chronic Wounds

Science.gov (United States)

Farooqui, Muhammad Fahad; Shamim, Atif

2016-06-01

Chronic wounds affect millions of patients around the world and their treatment is challenging as the early signs indicating their development are subtle. In addition, a type of chronic wound, known as pressure ulcer, develops in patients with limited mobility. Infection and frequent bleeding are indicators of chronic wound development. In this article, we present an unprecedented low cost continuous wireless monitoring system, realized through inkjet printing on a standard bandage, which can send early warnings for the parameters like irregular bleeding, variations in pH levels and external pressure at wound site. In addition to the early warnings, this smart bandage concept can provide long term wound progression data to the health care providers. The smart bandage comprises a disposable part which has the inkjet printed sensors and a reusable part constituting the wireless electronics. This work is an important step towards futuristic wearable sensors for remote health care applications.

Low Cost Inkjet Printed Smart Bandage for Wireless Monitoring of Chronic Wounds

KAUST Repository

Farooqui, Muhammad Fahad; Shamim, Atif

2016-01-01

Chronic wounds affect millions of patients around the world and their treatment is challenging as the early signs indicating their development are subtle. In addition, a type of chronic wound, known as pressure ulcer, develops in patients with limited mobility. Infection and frequent bleeding are indicators of chronic wound development. In this article, we present an unprecedented low cost continuous wireless monitoring system, realized through inkjet printing on a standard bandage, which can send early warnings for the parameters like irregular bleeding, variations in pH levels and external pressure at wound site. In addition to the early warnings, this smart bandage concept can provide long term wound progression data to the health care providers. The smart bandage comprises a disposable part which has the inkjet printed sensors and a reusable part constituting the wireless electronics. This work is an important step towards futuristic wearable sensors for remote health care applications.

A Policy Analysis on the Proactive Prevention of Chronic Disease: Learnings from the Initial Implementation of Integrated Measurement for Early Detection (MIDO

Directory of Open Access Journals (Sweden)

Roberto Tapia-Conyer

2017-06-01

Full Text Available Mexico, like many low- and middle-income countries (LMICs, faces an epidemic of chronic non-communicable diseases (NCDs, specifically diabetes, hypertension, obesity, and lipid disorders. Many people with these NCDs may not be aware that they have a disease, pointing to the need for broader screening programs. The traditional prevention policy in Mexico was based on screening with a paper-based risk factor questionnaire. However, this was used to screen patients already seeking healthcare services at facilities, and screening goals were set as a function of the number of questionnaires applied, not number of individuals screened. Due to this, Fundación Carlos Slim developed Medición Integrada para la Detección Oportuna (MIDOTM, or Integrated Measurement for Early Detection, an NCD screening and proactive prevention policy. This document is a policy analysis based on early learnings from the initial implementation of MIDO in eight primary healthcare centers in two central Mexican states. MIDO was found to expand screening programs beyond clinic walls, systematize community screening strategies, emphasize the detection of pre-disease phases, incorporate lifestyle counseling, and propose screening goals based on population targets. In collaboration with the Mexican Ministry of Health, MIDO has successfully screened over 500 000 individuals—about 40% of whom would not have been screened under previous policies. Of these more than 500 000 screened individuals, 13.4% had pre-diabetes (fasting glucose between 100 and 125 mg/dL, and 5.8% had undiagnosed diabetes (defined as fasting glucose above 126 mg/dL or random glucose above 200 mg/dL. However, there is still room for improvement in linking positive results from screening with disease confirmation and with patient incorporation into disease management. The experience of implementing MIDO in Mexico suggests that primary and secondary prevention programs in other parts of the world should

Sympathetic arousal as a marker of chronicity in childhood stuttering.

Science.gov (United States)

Zengin-Bolatkale, Hatun; Conture, Edward G; Walden, Tedra A; Jones, Robin M

2018-01-01

This study investigated whether sympathetic activity during a stressful speaking task was an early marker for stuttering chronicity. Participants were 9 children with persisting stuttering, 23 children who recovered, and 17 children who do not stutter. Participants performed a stress-inducing picture-naming task and skin conductance was measured across three time points. Findings indicated that at the initial time point, children with persisting stuttering exhibited higher sympathetic arousal during the stressful speaking task than children whose stuttering recovered. Findings are taken to suggest that sympathetic activity may be an early marker of heightened risk for chronic stuttering.

Early and late surgical site infections in ear surgery.

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Bastier, P L; Leroyer, C; Lashéras, A; Rogues, A-M; Darrouzet, V; Franco-Vidal, V

2016-04-01

A retroauricular approach is routinely used for treating chronic otitis media. The incidence of surgical site infections after ear surgery is around 10% in contaminated or dirty procedures. This observational prospective study describes surgical site infections after chronic otitis media surgery with the retroauricular approach and investigated their potential predictive factors. This observational prospective study included patients suffering from chronic otitis media and eligible for therapeutic surgery with a retroauricular approach. During follow-up, surgical site infections were defined as "early" if occurring within 30 days after surgery or as "late" if occurring thereafter. The data of 102 patients were analysed. Concerning early surgical site infections, four cases were diagnosed (3.9%) and a significant association was found with preoperative antibiotic therapy, wet ear at pre-operative examination, class III (contaminated) in the surgical wound classification, NNIS (National Nosocomial Infection Surveillance) index > 1, and oral post-operative antibiotic use. Seven late surgical site infections were diagnosed (7.1%) between 90 and 160 days after surgery and were significantly correlated to otorrhoea during the 6 months before surgery, surgery duration ≤60 minutes, canal wall down technique and use of fibrin glue. Surgical site infections after chronic otitis media surgery seem to be associated with factors related to the inflammatory state of the middle ear at the time of surgery in early infections and with chronic inflammation in late infections. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

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Paulina Dumnicka

2017-02-01

Full Text Available Acute pancreatitis (AP is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1 we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2 we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

Brain viscoelasticity alteration in chronic-progressive multiple sclerosis.

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Kaspar-Josche Streitberger

Full Text Available INTRODUCTION: Viscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS. METHODS: We determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS. RESULTS: In chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001. CONCLUSIONS: Chronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation.

Measuring organizational readiness for knowledge translation in chronic care.

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Gagnon, Marie-Pierre; Labarthe, Jenni; Légaré, France; Ouimet, Mathieu; Estabrooks, Carole A; Roch, Geneviève; Ghandour, El Kebir; Grimshaw, Jeremy

2011-07-13

Knowledge translation (KT) is an imperative in order to implement research-based and contextualized practices that can answer the numerous challenges of complex health problems. The Chronic Care Model (CCM) provides a conceptual framework to guide the implementation process in chronic care. Yet, organizations aiming to improve chronic care require an adequate level of organizational readiness (OR) for KT. Available instruments on organizational readiness for change (ORC) have shown limited validity, and are not tailored or adapted to specific phases of the knowledge-to-action (KTA) process. We aim to develop an evidence-based, comprehensive, and valid instrument to measure OR for KT in healthcare. The OR for KT instrument will be based on core concepts retrieved from existing literature and validated by a Delphi study. We will specifically test the instrument in chronic care that is of an increasing importance for the health system. Phase one: We will conduct a systematic review of the theories and instruments assessing ORC in healthcare. The retained theoretical information will be synthesized in a conceptual map. A bibliography and database of ORC instruments will be prepared after appraisal of their psychometric properties according to the standards for educational and psychological testing. An online Delphi study will be carried out among decision makers and knowledge users across Canada to assess the importance of these concepts and measures at different steps in the KTA process in chronic care.Phase two: A final OR for KT instrument will be developed and validated both in French and in English and tested in chronic disease management to measure OR for KT regarding the adoption of comprehensive, patient-centered, and system-based CCMs. This study provides a comprehensive synthesis of current knowledge on explanatory models and instruments assessing OR for KT. Moreover, this project aims to create more consensus on the theoretical underpinnings and the

Measuring organizational readiness for knowledge translation in chronic care

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Ouimet Mathieu

2011-07-01

Full Text Available Abstract Background Knowledge translation (KT is an imperative in order to implement research-based and contextualized practices that can answer the numerous challenges of complex health problems. The Chronic Care Model (CCM provides a conceptual framework to guide the implementation process in chronic care. Yet, organizations aiming to improve chronic care require an adequate level of organizational readiness (OR for KT. Available instruments on organizational readiness for change (ORC have shown limited validity, and are not tailored or adapted to specific phases of the knowledge-to-action (KTA process. We aim to develop an evidence-based, comprehensive, and valid instrument to measure OR for KT in healthcare. The OR for KT instrument will be based on core concepts retrieved from existing literature and validated by a Delphi study. We will specifically test the instrument in chronic care that is of an increasing importance for the health system. Methods Phase one: We will conduct a systematic review of the theories and instruments assessing ORC in healthcare. The retained theoretical information will be synthesized in a conceptual map. A bibliography and database of ORC instruments will be prepared after appraisal of their psychometric properties according to the standards for educational and psychological testing. An online Delphi study will be carried out among decision makers and knowledge users across Canada to assess the importance of these concepts and measures at different steps in the KTA process in chronic care. Phase two: A final OR for KT instrument will be developed and validated both in French and in English and tested in chronic disease management to measure OR for KT regarding the adoption of comprehensive, patient-centered, and system-based CCMs. Discussion This study provides a comprehensive synthesis of current knowledge on explanatory models and instruments assessing OR for KT. Moreover, this project aims to create more

Early Life Exposure to Chronic Intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle During Adulthood

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Fiona B Mcdonald

2016-03-01

Full Text Available Intermittent hypoxia is a feature of apnea of prematurity, chronic lung disease and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH during postnatal development (pCIH causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 hours of delivery, pups and their respective dams were exposed to CIH: 90s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 hrs per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH, where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

Early life exposure to chronic intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle during adulthood.

LENUS (Irish Health Repository)

McDonald, Fiona B

2016-03-01

Intermittent hypoxia is a feature of apnea of prematurity (AOP), chronic lung disease, and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH) during postnatal development (pCIH) causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and\\/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 h of delivery, pups and their respective dams were exposed to CIH: 90 s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 h per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH), where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm) weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

Perceived Behavioral Changes in Early Multiple Sclerosis

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Fabiana Souza Lima

2007-01-01

Full Text Available Acquired behavioral changes have essentially been described in advanced multiple sclerosis (MS. The present study was designed to determine whether behavioral modifications specifically related to the MS pathological process could be identified in the initial phase of the disease, as compared to control patients with chronic, relapsing and progressive inflammatory disorders not involving the central nervous system (CNS. Eighty-eight early MS patients (Expanded Disability Status Scale score ≤ 2.5 and 48 controls were tested. Perceived changes by informants in behavioral control, goal-directed behavior, decision making, emotional expression, insight and interpersonal relationships were assessed using the Iowa Scale of Personality Change (ISPC. Executive behavioral disturbances were screened using the Dysexecutive Questionnaire (DEX. The mean change between the premorbid and postmorbid ISPC ratings was similar in the MS [12.2 (SD 15.6] and in the control [11.5 (SD 15.1] group. The perceived behavioral changes (PBCs most frequently reported in both groups were lack of stamina, lability/moodiness, anxiety, vulnerability to stress and irritability. Pathological scores in the DEX were also similar in both groups. Correlations between PBCs and DEX scores were different in MS and control groups. MS patients with cognitive impairment had a marginally higher number of PBCs than control patients (p = 0.056 and a significantly higher DEXp score (p = 0.04. These results suggest that (1 PBCs occurring in early MS patients were not different from those induced by comparable chronic non-CNS disorders, (2 qualitative differences in the relationship between behavioral symptoms and executive-behavioral changes may exist between MS and control groups, and (3 behavioral symptoms seem associated with cognitive deficits in MS. We further plan to assess these observations longitudinally.

Migration as a turning point in food habits: the early phase of dietary acculturation among women from South Asian, African, and Middle Eastern Countries living in Norway.

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Terragni, Laura; Garnweidner, Lisa M; Pettersen, Kjell Sverre; Mosdøl, Annhild

2014-01-01

This article explores the early phase of dietary acculturation after migration. South Asian, African and Middle Eastern women (N = 21) living in Norway were interviewed about their early experiences with food in a new context. The findings pointed to abrupt changes in food habits in the first period after migration. To various degrees, women reported unfamiliarity with foods in shops, uncertainty about meal formats and food preparation and fear of eating food prohibited by their religion. Their food consumption tended to be restricted to food items perceived as familiar or safe. Our findings indicate that the first period after migration represents a specific phase in the process of dietary acculturation. Early initiatives aimed at enhancing confidence in food and familiarity with the new food culture are recommended.

Chronic pain following total hip arthroplasty: a nationwide questionnaire study

DEFF Research Database (Denmark)

Nikolajsen, Lone; Brandsborg, Birgitte; Lucht, Ulf

2006-01-01

BACKGROUND: Chronic post-operative pain is a well-recognized problem after various types of surgery, but little is known about chronic pain after orthopedic surgery. Severe pre-operative pain is the primary indication for total hip arthroplasty (THA). Therefore, we examined the prevalence...... was 93.6%. Two hundred and ninety-four patients (28.1%) had chronic ipsilateral hip pain at the time of completion of the questionnaire, and pain limited daily activities to a moderate, severe or very severe degree in 12.1%. The chronic pain state was related to the recalled intensity of early post...

Transitions of Care Between Acute and Chronic Heart Failure: Critical Steps in the Design of a Multidisciplinary Care Model for the Prevention of Rehospitalization.

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Comín-Colet, Josep; Enjuanes, Cristina; Lupón, Josep; Cainzos-Achirica, Miguel; Badosa, Neus; Verdú, José María

2016-10-01

Despite advances in the treatment of heart failure, mortality, the number of readmissions, and their associated health care costs are very high. Heart failure care models inspired by the chronic care model, also known as heart failure programs or heart failure units, have shown clinical benefits in high-risk patients. However, while traditional heart failure units have focused on patients detected in the outpatient phase, the increasing pressure from hospital admissions is shifting the focus of interest toward multidisciplinary programs that concentrate on transitions of care, particularly between the acute phase and the postdischarge phase. These new integrated care models for heart failure revolve around interventions at the time of transitions of care. They are multidisciplinary and patient-centered, designed to ensure continuity of care, and have been demonstrated to reduce potentially avoidable hospital admissions. Key components of these models are early intervention during the inpatient phase, discharge planning, early postdischarge review and structured follow-up, advanced transition planning, and the involvement of physicians and nurses specialized in heart failure. It is hoped that such models will be progressively implemented across the country. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

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Montazeri, Mahbobeh; Ebrahimzadeh, Mohammad Ali; Ahmadpour, Ehsan; Sharif, Mehdi; Sarvi, Shahabeddin

2016-01-01

Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine. PMID:27645234

Additional chromosome abnormalities in chronic myeloid leukemia

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Hui-Hua Hsiao

2011-02-01

Full Text Available The Philadelphia (Ph chromosome and/or Breakpoint cluster region-Abelson leukemia virus oncogene transcript are unique markers for chronic myeloid leukemia (CML. However, CML demonstrates heterogeneous presentations and outcomes. We analyzed the cytogenetic and molecular results of CML patients to evaluate their correlation with clinical presentations and outcome. A total of 84 newly diagnosed CML patients were enrolled in the study. Patients were treated according to disease status. Bone marrow samples were obtained to perform cytogenetic and molecular studies. Clinical presentations, treatment courses, and survival were reviewed retrospectively. Among 84 patients, 72 had chronic phase and 12 had accelerated phase CML. Cytogenetic study showed 69 (82.1% with the classic Ph chromosome, 6 (7.2% with a variant Ph chromosome, and 9 (10.7% with additional chromosome abnormalities. Fifty-four (64.3% cases harbored b3a2 transcripts, 29 (34.5% had b2a2 transcript, and 1 had e19a2 transcript. There was no difference in clinical presentations between different cytogenetic and molecular groups; however, additional chromosome abnormalities were significantly associated with the accelerated phase. Imatinib therapy was an effective treatment, as measured by cytogenetic response, when administered as first- and second-line therapy in chronic phase patients. Survival analysis showed that old age, additional chromosome abnormalities, high Sokal score, and no cytogenetic response in second-line therapy had a significant poor impact (p<0.05. In conclusion, we presented the cytogenetic and molecular pattern of CML patients and demonstrated that the additional chromosome abnormality was associated with poor outcome.

Early Complete Molecular Response to First-Line Nilotinib in Two Patients with Chronic Myeloid Leukemia Carrying the p230 Transcript

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Marianna Greco

2013-01-01

Full Text Available Chronic myeloid leukemia (CML with the rare fusion gene e19a2, encoding a p230 protein, has been described in patients with typical or rather aggressive clinical course. Although tyrosine kinase inhibitors (TKIs induce a substantial cytogenetic and molecular response in all phases of CML, a minority of p230 positive patients have been treated with TKIs. We report two cases of CML patients carrying the p230 transcript, who achieved fast and deep complete molecular response (CMR after frontline treatment with nilotinib. Our results suggest the use of nilotinib as frontline agent for the treatment of this CML variant.

Chronic Absenteeism: A Key Indicator of Student Success. Policy Analysis

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Rafa, Alyssa

2017-01-01

Research shows that chronic absenteeism can affect academic performance in later grades and is a key early warning sign that a student is more likely to drop out of high school. Several states enacted legislation to address this issue, and many states are currently discussing the utility of chronic absenteeism as an indicator of school quality or…

Phase II drugs under clinical investigation for the treatment of chronic constipation.

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Mozaffari, Shilan; Didari, Tina; Nikfar, Shekoufeh; Abdollahi, Mohammad

2014-11-01

Chronic constipation (CC) is a common gastrointestinal (GI) motility disorder that significantly impairs the quality of life in affected subjects. As almost half of the patients suffering from CC are not satisfied with currently available medicines, there is a need to develop new molecules with better effectiveness and tolerability. The authors include all experimental and clinical trials (up to Phase II) about new investigational drugs for the treatment of CC. The article identifies nine new agents: mitemcinal, TD-8954, YKP10811, itopride, RM-131, KWA-0711, elobixibat, velusetrag, and naronapride. All nine agents have shown prokinetic effects in different stages of the development. The mechanisms of new developing drugs include: the activation of 5-hydroxytryptamine type-4 (5-HT4), ghrelin and motilin receptors, antagonizing dopamine type-2 (D2) receptors, inhibition of ileal bile acid reabsorption and acetylcholine esterase, as well as water absorption from the GI tract. At this current point in time, new generations of 5-HT4 receptor agonists (velusetrag, noranopride and YKP10811) are hoped to progress, further in the future, due to better efficiency and safety. However, it is not possible to make a concise conclusion at this current time due to a lack of evidence. Further clinical trials with a longer duration and a larger sample size are warranted.

Psychological Manifestations of Early Childhood Adversity in the Context of Chronic Hematologic Malignancy.

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McFarland, Daniel C; Shen, Megan Johnson; Polizzi, Heather; Mascarenhas, John; Kremyanskaya, Marina; Holland, Jimmie; Hoffman, Ronald

Myeloproliferative neoplasms (MPNs), a group of chronic hematologic malignancies, carry significant physical and psychological symptom burdens that significantly affect patients' quality of life. We sought to identify the relationship between early childhood adversity (ECA) and psychological distress in patients with MPNs, as ECA may compound symptom burden. Patients with MPNs were assessed for ECA (i.e., the Risky Families Questionnaire-subscales include abuse/neglect/chaotic home environment), distress (i.e., Distress Thermometer and Problem List), anxiety (i.e., Hospital Anxiety and Depression Scale-Anxiety [HADS-A]), depression (i.e., Hospital Anxiety and Depression Scale-Depression [HADS-D]), meeting standardized cutoff thresholds for distress (i.e., Distress Thermometer and Problem List≥ 4 or ≥ 7)/anxiety (HADS-A ≥8)/depression (HADS-D ≥ 8), and demographic factors. A total of 117 participants completed the study (78% response rate). ECA was associated with depression (p psychological outcomes. ECA was higher based on disease subtypes with greater symptom burden (other > polycythemia vera > myelofibrosis > essential thrombocythemia) (p = 0.047) and taking an antidepressant (p = 0.011). ECA is associated with psychological distress and meets screening criteria for anxiety and depression in patients with MPNs. ECA may help to explain individual patient trajectories, and further understanding may enhance patient-centered care among patients with MPNs. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Chronic Absenteeism and Its Effects on Students' Academic and Socioemotional Outcomes

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Gottfried, Michael A.

2014-01-01

Recent policy dialogue suggests that chronic absenteeism is not only underdocumented, but is also detrimental to the success of students as early as kindergarten. That said, almost no empirical research has examined the effects of chronic absenteeism on student outcomes. This study addresses this underresearched issue in more depth. Using a…

High temperature phase equilibria and phase diagrams

CERN Document Server

Kuo, Chu-Kun; Yan, Dong-Sheng

2013-01-01

High temperature phase equilibria studies play an increasingly important role in materials science and engineering. It is especially significant in the research into the properties of the material and the ways in which they can be improved. This is achieved by observing equilibrium and by examining the phase relationships at high temperature. The study of high temperature phase diagrams of nonmetallic systems began in the early 1900s when silica and mineral systems containing silica were focussed upon. Since then technical ceramics emerged and more emphasis has been placed on high temperature

Insights into Mechanisms of Chronic Neurodegeneration

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Abigail B. Diack

2016-01-01

Full Text Available Chronic neurodegenerative diseases such as Alzheimer’s disease (AD, Parkinson’s disease (PD, and prion diseases are characterised by the accumulation of abnormal conformers of a host encoded protein in the central nervous system. The process leading to neurodegeneration is still poorly defined and thus development of early intervention strategies is challenging. Unique amongst these diseases are Transmissible Spongiform Encephalopathies (TSEs or prion diseases, which have the ability to transmit between individuals. The infectious nature of these diseases has permitted in vivo and in vitro modelling of the time course of the disease process in a highly reproducible manner, thus early events can be defined. Recent evidence has demonstrated that the cell-to-cell spread of protein aggregates by a “prion-like mechanism” is common among the protein misfolding diseases. Thus, the TSE models may provide insights into disease mechanisms and testable hypotheses for disease intervention, applicable to a number of these chronic neurodegenerative diseases.

Chronic traumatic encephalopathy: The unknown disease.

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Martínez-Pérez, R; Paredes, I; Munarriz, P M; Paredes, B; Alén, J F

2017-04-01

Chronic traumatic encephalopathy is a neurodegenerative disease produced by accumulated minor traumatic brain injuries; no definitive premortem diagnosis and no treatments are available for chronic traumatic encephalopathy. Risk factors associated with chronic traumatic encephalopathy include playing contact sports, presence of the apolipoprotein E4, and old age. Although it shares certain histopathological findings with Alzheimer disease, chronic traumatic encephalopathy has a more specific presentation (hyperphosphorylated tau protein deposited as neurofibrillary tangles, associated with neuropil threads and sometimes with beta-amyloid plaques). Its clinical presentation is insidious; patients show mild cognitive and emotional symptoms before progressing to parkinsonian motor signs and finally dementia. Results from new experimental diagnostic tools are promising, but these tools are not yet available. The mainstay of managing this disease is prevention and early detection of its first symptoms. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

2,3-diphosphoglycerate, nucleotide phosophate, and organic and inorganic phosphate levels during the early phases of diabetic ketoacidosis.

Science.gov (United States)

Kanter, Y; Gerson, J R; Bessman, A N

1977-05-01

The relation between serum and red blood cell (RBC) inorganic phosphate levels, RBC 2,3-diphosphoglycerate (2,3-DPG) levels, RBC nucleotide phosphate (Pn), and RBC total phosphate (Pt) levels were studied during the early phases of treatment and recovery from diabetic ketoacidosis (DKA). A steady drop in serum inorganic phosphate was found during the first 24 hours of insulin treatment and was most profound at 24 hours. No statistically significant changes (P less than 0.05) were found in red cell inorganic phosphate or nucleotide phosphate levels during the 24-hour study period. The levels of total red cell phosphate were lower in this group of patients than in nonacidotic diabetic subjects and decreased slightly after 24 hours of treatment. The red cell 2,3-DPG levels were low at the initiation of therapy and remained low during the 24-hour study period. Glucose, bicarbonate, lactate, and ketone levels fell in linear patterns with treatment. In view of the current evidence for the effects of low 2,3-DPG on oxygen delivery and the relation of low serum phosphate levels to RBC glycolysis and 2,3-DPG formation, this study reemphasizes the need for phosphate replacement during the early phases of treatment of DKA.

Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

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van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

2016-02-01

Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (Ppreeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

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Dietlind L. Wahner-Roedler

2011-01-01

Full Text Available Most patients with fibromyalgia use complementary and alternative medicine (CAM. Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ and the Center for Epidemiologic Studies Depression Scale (CES-D at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02 and by 18% in the placebo group (P < .001. The difference in change in scores between the groups was not significant (P = .16. With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004 and in the placebo group by 15% (P = .05. The change in scores was similar in the groups (P = .83. Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated.

Substantial need for early diagnosis, rehabilitation and treatment of chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Lange, Peter; Marott, Jacob Louis; Dahl, Morten

2012-01-01

Our goal was to estimate the number of individuals with chronic obstructive pulmonary disease (COPD) in the Capital Region of Denmark and the need of resources required to implement the regional management programme for COPD.......Our goal was to estimate the number of individuals with chronic obstructive pulmonary disease (COPD) in the Capital Region of Denmark and the need of resources required to implement the regional management programme for COPD....

Evidence-based clinical practice guidelines for chronic pancreatitis 2015.

Science.gov (United States)

Ito, Tetsuhide; Ishiguro, Hiroshi; Ohara, Hirotaka; Kamisawa, Terumi; Sakagami, Junichi; Sata, Naohiro; Takeyama, Yoshifumi; Hirota, Morihisa; Miyakawa, Hiroyuki; Igarashi, Hisato; Lee, Lingaku; Fujiyama, Takashi; Hijioka, Masayuki; Ueda, Keijiro; Tachibana, Yuichi; Sogame, Yoshio; Yasuda, Hiroaki; Kato, Ryusuke; Kataoka, Keisho; Shiratori, Keiko; Sugiyama, Masanori; Okazaki, Kazuichi; Kawa, Shigeyuki; Tando, Yusuke; Kinoshita, Yoshikazu; Watanabe, Mamoru; Shimosegawa, Tooru

2016-02-01

Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

Updated estimates of survival and cost effectiveness for imatinib versus interferon-alpha plus low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukaemia.

Science.gov (United States)

Reed, Shelby D; Anstrom, Kevin J; Li, Yanhong; Schulman, Kevin A

2008-01-01

For trials in which participants are followed beyond the main study period to assess long-term outcomes, economic evaluations conducted using short-term data should be systematically updated to reflect new information. We used 60-month survival data from the IRIS (International Randomized study of Interferon vs STI571) trial to update previously published cost-effectiveness estimates, based on 19 months of follow-up, of imatinib versus interferon (IFN)-alpha plus low-dose cytarabine in patients with chronic-phase chronic myeloid leukaemia. For patients treated with imatinib, we used the 60-month data to calibrate the survival curves generated from the original cost-effectiveness model. We used historical data to model survival for patients randomized to IFNalpha. We updated costs for medical resources using 2006 Medicare reimbursement rates and applied average wholesale prices (AWPs) and wholesale acquisition costs (WACs) to study medications. Five-year survival for patients randomized to imatinib was better than predicted in the original model (89.4% vs 83.2%). We estimated remaining life expectancy with first-line imatinib to be 19.1 life-years (3.8 life-years over the original model) and 15.2 QALYs (3.1 QALYs over the original estimate). Estimates for IFNalpha remained at 9.1 life-years and 6.3 QALYs. When we applied AWPs to study medications, incremental cost-effectiveness ratios (ICERs) were $US 51,800-57,500 per QALY. When we applied WACs, ICERs were $US 42,000-46,200 per QALY. Although the analysis revealed that the original survival estimates were conservative, the updated cost-effectiveness ratios were consistent with, or slightly higher than, the original estimates, depending on the method for assigning costs to study medications.

Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response: a single center facing the dilemma.

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Iliakis, Theodoros; Papadopoulou, Vasiliki; Diamantopoulos, Panagiotis T; Panayiotidis, Panayiotis; Zervakis, Konstantinos; Giannakopoulou, Nefeli; Tilimidos, Gerassimos; Angelopoulou, Maria; Siakantaris, Marina P; Pangalis, Gerassimos; Mantzourani, Marina; Variami, Eleni; Viniou, Nora Athina

2013-08-01

Tyrosine kinase inhibitors (TKIs), namely imatinib mesylate (IM) and recently approved second-generation TKIs dasatinib and nilotinib, are currently considered the treatment of choice for newly-diagnosed chronic phase chronic myelogenous leukemia (CP-CML). Although treatment with TKIs has not yet been proven curative, it certainly accomplishes a sustained control of the disease in the vast majority of patients. More than a decade after the successful launching of IM in first-line treatment of CP-CML and the subsequent introduction of second-generation TKIs in this setting, the question of the possibility of TKI cessation in a specific subset of patients has emerged. Side-effects of TKIs, along with some patients' wish to abandon the drugs and the rising financial burden upon healthcare systems, have led to the dilemma whether IM can be safely withdrawn after achieving deep molecular remissions and which patients are suitable for this discontinuation. We examined the data of our patients with CML in search of potential canditates for cessation of TKI therapy and identified their characteristics. We also performed a thorough review of the relevant literature. Eight out of fifty patients were discriminated on grounds of sustained complete molecular response (CMR) exceeding 12 months, most of them with a low or intermediate Sokal score at diagnosis. The median interval from IM initiation to CMR was almost 2 years and the median duration of detected CMR reached 6.5 years. Based on the promising results of prospective clinical trials reporting successful cessation of treatment with TKIs on selected subgroups of patients, we decided to proceed to interruption of therapy in the specific subset of our patients and closely monitor their response.

Do telemonitoring projects of heart failure fit the Chronic Care Model?

Science.gov (United States)

Willemse, Evi; Adriaenssens, Jef; Dilles, Tinne; Remmen, Roy

2014-07-01

This study describes the characteristics of extramural and transmural telemonitoring projects on chronic heart failure in Belgium. It describes to what extent these telemonitoring projects coincide with the Chronic Care Model of Wagner. The Chronic Care Model describes essential components for high-quality health care. Telemonitoring can be used to optimise home care for chronic heart failure. It provides a potential prospective to change the current care organisation. This qualitative study describes seven non-invasive home-care telemonitoring projects in patients with heart failure in Belgium. A qualitative design, including interviews and literature review, was used to describe the correspondence of these home-care telemonitoring projects with the dimensions of the Chronic Care Model. The projects were situated in primary and secondary health care. Their primary goal was to reduce the number of readmissions for chronic heart failure. None of these projects succeeded in a final implementation of telemonitoring in home care after the pilot phase. Not all the projects were initiated to accomplish all of the dimensions of the Chronic Care Model. A central role for the patient was sparse. Limited financial resources hampered continuation after the pilot phase. Cooperation and coordination in telemonitoring appears to be major barriers but are, within primary care as well as between the lines of care, important links in follow-up. This discrepancy can be prohibitive for deployment of good chronic care. Chronic Care Model is recommended as basis for future.

THE FRAME NETWORK OF INTERDISCIPLINARY STAKEHOLDER COMPOSITIONS IN THE EARLY PHASES OF NEW PRODUCT DEVELOPMENT

DEFF Research Database (Denmark)

Andersen, Alexander Kjær; Nafei, Nadiim Mohamed Adel Abd El Fatta; Larsen, Michael Planck

2017-01-01

New Product Development (NPD) projects have continually become more complex over the years and now involve a diverse range of stakeholders, who have different disciplinary backgrounds, values, objectives, and experience. This makes them create different ‘frames’, which may represent conflicting p...... also identifies core activities and events of the framing process and propose a model describing an iterative cycle of six phases that stakeholders in New Product Development go through, which we in this article call ‘The Interdisciplinary Framing Loop’.......New Product Development (NPD) projects have continually become more complex over the years and now involve a diverse range of stakeholders, who have different disciplinary backgrounds, values, objectives, and experience. This makes them create different ‘frames’, which may represent conflicting...... in the early phases of NPD projects involving interdisciplinary stakeholders in organisational settings. The study indicates that stakeholders create isolated aspired values and working principles and from these form a ‘network’ of ‘partial frames’ before connecting them into ‘fully defined frames’. The study...

Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection

DEFF Research Database (Denmark)

Hansen, Susse Kirkelund; Rau, Martin Holm; Johansen, Helle Krogh

2012-01-01

that the paranasal sinuses constitute an important niche for the colonizing bacteria in many patients. The paranasal sinuses often harbor distinct bacterial subpopulations, and in the early colonization phases there seems to be a migration from the sinuses to the lower airways, suggesting that independent adaptation...... and evolution take place in the sinuses. Importantly, before the onset of chronic lung infection, lineages with mutations conferring a large fitness benefit in CF airways such as mucA and lasR as well as small colony variants and antibiotic-resistant clones are part of the sinus populations. Thus, the paranasal...

Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence

Directory of Open Access Journals (Sweden)

Lauren eChaby

2013-07-01

Full Text Available Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid stress hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g. isolation, crowding, cage tilt were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias (F1,12 = 5.000, P < 0.05, altered coping response (T1,14 = 2.216, P = 0.04, and accelerated decision making (T1,14 = 3.245, P = 0.01. Exposure to chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object (T1,14 = 2.240, P = 0.04; T1,14 = 2.419, P = 0.03, respectively. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions. Stress during adolescence also induced short-term changes in the way animals moved around a novel environment.

TRAVELLERS: a school-based early intervention programme helping young people manage and process change, loss and transition. Pilot phase findings.

Science.gov (United States)

Dickinson, Pauline; Coggan, Carolyn; Bennett, Sara

2003-06-01

This paper outlines the conceptual background and findings from the pilot phase of TRAVELLERS--an early intervention programme designed to enhance protective factors for young people experiencing change, loss and transition events and early signs of emotional distress. The pilot study aimed to determine whether TRAVELLERS was a feasible, acceptable and promising intervention for young people within secondary schools in Aotearoa/New Zealand. The conceptual origins of the TRAVELLERS programme are described in terms of: adolescent mental health concerns; emerging mental health promotion theory and practice; and prevention and early intervention models. The key elements of the TRAVELLERS programme are described. The programme was piloted in two secondary schools, one rural and one urban with 34 participants (females n = 24, males n = 10). Evaluation methods included: review of programme materials; identification of potential selection tools appropriate to Year 9 students; analysis of selection questionnaire; and conduct of feedback from participants, facilitators and parents/caregivers. The TRAVELLERS programme provides a means of identifying and selecting young people who may benefit from participating in an early intervention programme. The programme has achieved a statistically significant reduction in participants' distress (p Young people were overwhelmingly enthusiastic about most aspects of TRAVELLERS. School personnel reported that TRAVELLERS was an appropriate and acceptable programme to the school. Targeted interventions provided within a supportive school environment can contribute to enhancing protective factors such as personal and interpersonal coping strategies, increased help-seeking behaviour, and young people feeling more positive about themselves and their lives. The pilot programme has been amended and prepared for a two year trial phase in 10 secondary schools during 2002-2003.

Early-Time Solution of the Horizontal Unconfined Aquifer in the Buildup Phase

Science.gov (United States)

Gravanis, Elias; Akylas, Evangelos

2017-10-01

We derive the early-time solution of the Boussinesq equation for the horizontal unconfined aquifer in the buildup phase under constant recharge and zero inflow. The solution is expressed as a power series of a suitable similarity variable, which is constructed so that to satisfy the boundary conditions at both ends of the aquifer, that is, it is a polynomial approximation of the exact solution. The series turns out to be asymptotic and it is regularized by resummation techniques that are used to define divergent series. The outflow rate in this regime is linear in time, and the (dimensionless) coefficient is calculated to eight significant figures. The local error of the series is quantified by its deviation from satisfying the self-similar Boussinesq equation at every point. The local error turns out to be everywhere positive, hence, so is the integrated error, which in turn quantifies the degree of convergence of the series to the exact solution.

Orientation selection process during the early stage of cubic dendrite growth: A phase-field crystal study

International Nuclear Information System (INIS)

Tang Sai; Wang Zhijun; Guo Yaolin; Wang Jincheng; Yu Yanmei; Zhou Yaohe

2012-01-01

Using the phase-field crystal model, we investigate the orientation selection of the cubic dendrite growth at the atomic scale. Our simulation results reproduce how a face-centered cubic (fcc) octahedral nucleus and a body-centered cubic (bcc) truncated-rhombic dodecahedral nucleus choose the preferred growth direction and then evolve into the dendrite pattern. The interface energy anisotropy inherent in the fcc crystal structure leads to the fastest growth velocity in the 〈1 0 0〉 directions. New { 1 1 1} atomic layers prefer to nucleate at positions near the tips of the fcc octahedron, which leads to the directed growth of the fcc dendrite tips in the 〈1 0 0〉 directions. A similar orientation selection process is also found during the early stage of bcc dendrite growth. The orientation selection regime obtained by phase-field crystal simulation is helpful for understanding the orientation selection processes of real dendrite growth.

An unusual renal manifestation of chronic HBV infection.