Insights on the poster preparation and presentation process.

Science.gov (United States)

Moore, L W; Augspurger, P; King, M O; Proffitt, C

2001-05-01

Dissemination of research findings and effective clinical innovations is key to the growth and development of the nursing profession. Several avenues exist for the dissemination of information. One forum for communication that has gained increased recognition over the past decade is the poster presentation. Poster presentations are often a significant part of regional, national, and international nursing conferences. Although posters are frequently used to disseminate information to the nursing community, little is reported about actual poster presenters' experiences with preparation and presentation of their posters. The purpose of this article is to present insights derived from information shared by poster presenters regarding the poster preparation and presentation process. Such insights derived from the personal experiences of poster presenters may assist others to efficiently and effectively prepare and present scholarly posters that disseminate information to the nursing community. Copyright 2001 by W.B. Saunders Company

Adipose Derived Mesenchymal Stem Cells In Wound Healing: A Clinical Review

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Gunalp Uzun

2014-08-01

Full Text Available The aim of this article is to review clinical studies on the use of adipose derived mesenchymal stem cells in the treatment of chronic wounds. A search on PubMed was performed on April 30th, 2014 to identify the relevant clinical studies. We reviewed 13 articles that reported the use adipose derived stem cells in the treatment of different types of wounds. Adipose derived stem cells have the potential to be used in the treatment of chronic wounds. However, standard methods for isolation, storage and application of these cells are needed. New materials to transfer these stem cells to injured tissues should be investigated. [Dis Mol Med 2014; 2(4.000: 57-64

Nerve growth factor, brain-derived neurotrophic factor, and the chronobiology of mood: a new insight into the "neurotrophic hypothesis"

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Tirassa P

2015-10-01

Full Text Available Paola Tirassa,1 Adele Quartini,2 Angela Iannitelli2–4 1National Research Council (CNR, Institute of Cell Biology and Neurobiology (IBCN, 2Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine – "Sapienza" University of Rome, 3Italian Psychoanalytical Society (SPI, Rome, Italy; 4International Psychoanalytical Association (IPA, London, UKAbstract: The light information pathways and their relationship with the body rhythms have generated a new insight into the neurobiology and the neurobehavioral sciences, as well as into the clinical approaches to human diseases associated with disruption of circadian cycles. Light-based strategies and/or drugs acting on the circadian rhythms have widely been used in psychiatric patients characterized by mood-related disorders, but the timing and dosage use of the various treatments, although based on international guidelines, are mainly dependent on the psychiatric experiences. Further, many efforts have been made to identify biomarkers able to disclose the circadian-related aspect of diseases, and therefore serve as diagnostic, prognostic, and therapeutic tools in clinic to assess the different mood-related symptoms, including pain, fatigue, sleep disturbance, loss of interest or pleasure, appetite, psychomotor changes, and cognitive impairments. Among the endogenous factors suggested to be involved in mood regulation, the neurotrophins, nerve growth factor, and brain-derived neurotrophic factor show anatomical and functional link with the circadian system and mediate some of light-induced effects in brain. In addition, in humans, both nerve growth factor and brain-derived neurotrophic factor have showed a daily rhythm, which correlate with the morningness–eveningness dimensions, and are influenced by light, suggesting their potential role as biomarkers for chronotypes and/or chronotherapy. The evidences of the relationship between the diverse mood-related disorders

Gaining Insights on Nasopharyngeal Carcinoma Treatment Outcome Using Clinical Data Mining Techniques.

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Ghaibeh, A Ammar; Kasem, Asem; Ng, Xun Jin; Nair, Hema Latha Krishna; Hirose, Jun; Thiruchelvam, Vinesh

2018-01-01

The analysis of Electronic Health Records (EHRs) is attracting a lot of research attention in the medical informatics domain. Hospitals and medical institutes started to use data mining techniques to gain new insights from the massive amounts of data that can be made available through EHRs. Researchers in the medical field have often used descriptive statistics and classical statistical methods to prove assumed medical hypotheses. However, discovering new insights from large amounts of data solely based on experts' observations is difficult. Using data mining techniques and visualizations, practitioners can find hidden knowledge, identify interesting patterns, or formulate new hypotheses to be further investigated. This paper describes a work in progress on using data mining methods to analyze clinical data of Nasopharyngeal Carcinoma (NPC) cancer patients. NPC is the fifth most common cancer among Malaysians, and the data analyzed in this study was collected from three states in Malaysia (Kuala Lumpur, Sabah and Sarawak), and is considered to be the largest up-to-date dataset of its kind. This research is addressing the issue of cancer recurrence after the completion of radiotherapy and chemotherapy treatment. We describe the procedure, problems, and insights gained during the process.

Effects on cognitive and clinical insight with the use of Guided Self-Determination in outpatients with schizophrenia

DEFF Research Database (Denmark)

Jørgensen, Rikke; Licht, R W; Lysaker, P H

2015-01-01

with schizophrenia. The design was an open randomized trial. The primary hypothesis was cognitive insight would improve in those patients who received GSD-SZ+TAU as assessed by the BCIS. We additionally explored whether the intervention led to changes in clinical insight, self-perceived recovery, self-esteem, social...... their illness management, Guided Self-Determination (GSD), has been adapted for use in patients with schizophrenia (GSD-SZ). The purpose of this study was to investigate the effect on insight of GSD-SZ as a supplement to treatment as usual (TAU) as compared to TAU alone in outpatients diagnosed...

Milk-derived proteins and peptides in clinical trials

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Jolanta Artym

2013-08-01

Full Text Available Clinical trials are reviewed, involving proteins and peptides derived from milk (predominantly bovine, with the exception of lactoferrin, which will be the subject of another article. The most explored milk fraction is α-lactalbumin (LA, which is often applied with glycomacropeptide (GMP – a casein degradation product. These milk constituents are used in health-promoting infant and adult formulae as well as in a modified form (HAMLET to treat cancer. Lactoperoxidase (LCP is used as an additive to mouth hygiene products and as a salivary substitute. Casein derivatives are applied, in addition, in the dry mouth syndrome. On the other hand, casein hydrolysates, containing active tripeptides, found application in hypertension and in type 2 diabetes. Lysozyme is routinely used for food conservation and in pharmaceutical products. It was successfully used in premature infants with concomitant diseases to improve health parameters. When used as prophylaxis in patients with scheduled surgery, it significantly reduced the incidence of hepatitis resulting from blood transfusion. Lysozyme was also used in infected children as an antimicrobial agent showing synergistic effects in combination with different antibiotics. Proline-rich polypeptide (PRP was introduced to therapy of Alzheimer’s disease patients. The therapeutic value of PRP was proved in several clinical trials and supported by studies on its mechanism of action. Concentrated immunoglobulin preparations from colostrum and milk of hyperimmunized cows showed efficacy in prevention of infections by bacteria, viruses and protozoa. A nutrition formula with milk-derived TGF-β2 (Modulen IBD® found application in treatment of pediatric Crohn’s disease. In conclusion, the preparations containing milk-derived products are safe and effective measures in prevention and treatment of infections as well as autoimmune and neoplastic diseases.

Functional magnetic resonance imaging study of external source memory and its relation to cognitive insight in non-clinical subjects.

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Buchy, Lisa; Hawco, Colin; Bodnar, Michael; Izadi, Sarah; Dell'Elce, Jennifer; Messina, Katrina; Lepage, Martin

2014-09-01

Previous research has linked cognitive insight (a measure of self-reflectiveness and self-certainty) in psychosis with neurocognitive and neuroanatomical disturbances in the fronto-hippocampal neural network. The authors' goal was to use functional magnetic resonance imaging (fMRI) to investigate the neural correlates of cognitive insight during an external source memory paradigm in non-clinical subjects. At encoding, 24 non-clinical subjects travelled through a virtual city where they came across 20 separate people, each paired with a unique object in a distinct location. fMRI data were then acquired while participants viewed images of the city, and completed source recognition memory judgments of where and with whom objects were seen, which is known to involve prefrontal cortex. Cognitive insight was assessed with the Beck Cognitive Insight Scale. External source memory was associated with neural activity in a widespread network consisting of frontal cortex, including ventrolateral prefrontal cortex (VLPFC), temporal and occipital cortices. Activation in VLPFC correlated with higher self-reflectiveness and activation in midbrain correlated with lower self-certainty during source memory attributions. Neither self-reflectiveness nor self-certainty significantly correlated with source memory accuracy. By means of virtual reality and in the context of an external source memory paradigm, the study identified a preliminary functional neural basis for cognitive insight in the VLPFC in healthy people that accords with our fronto-hippocampal theoretical model as well as recent neuroimaging data in people with psychosis. The results may facilitate the understanding of the role of neural mechanisms in psychotic disorders associated with cognitive insight distortions. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Stronger default mode network connectivity is associated with poorer clinical insight in youth at ultra high-risk for psychotic disorders.

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Clark, Sarah V; Mittal, Vijay A; Bernard, Jessica A; Ahmadi, Aral; King, Tricia Z; Turner, Jessica A

2018-03-01

Impaired clinical insight (CI) is a common symptom of psychotic disorders and a promising treatment target. However, to date, our understanding of how variability in CI is tied to underlying brain dysfunction in the clinical high-risk period is limited. Developing a stronger conception of this link will be a vital first step for efforts to determine if CI can serve as a useful prognostic indicator. The current study investigated whether variability in CI is related to major brain networks in adolescents and young adults at ultra high-risk (UHR) of developing psychosis. Thirty-five UHR youth were administered structured clinical interviews as well as an assessment for CI and underwent resting-state magnetic resonance imaging scans. Functional connectivity was calculated in the default mode network (DMN) and fronto-parietal network (FPN), two major networks that are dysfunctional in psychosis and are hypothesized to affect insight. Greater DMN connectivity between the posterior cingulate/precuneus and ventromedial prefrontal cortex (DMN) was related to poorer CI (R 2 =0.399). There were no significant relationships between insight and the FPN. This is the first study to relate a major brain network to clinical insight before the onset of psychosis. Findings are consistent with evidence if a hyperconnected DMN in schizophrenia and UHR, and similar to a previous study of insight and connectivity in schizophrenia. Results suggest that a strongly connected DMN may be related to poor self-awareness of subthreshold psychotic symptoms in UHR adolescents and young adults. Copyright © 2017 Elsevier B.V. All rights reserved.

Bringing explicit insight into cognitive psychology features during clinical reasoning seminars: a prospective, controlled study.

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Nendaz, Mathieu R; Gut, Anne M; Louis-Simonet, Martine; Perrier, Arnaud; Vu, Nu V

2011-04-01

Facets of reasoning competence influenced by an explicit insight into cognitive psychology features during clinical reasoning seminars have not been specifically explored. This prospective, controlled study, conducted at the University of Geneva Faculty of Medicine, Switzerland, assessed the impact on sixth-year medical students' patient work-up of case-based reasoning seminars, bringing them explicit insight into cognitive aspects of their reasoning. Volunteer students registered for our three-month Internal Medicine elective were assigned to one of two training conditions: standard (control) or modified (intervention) case-based reasoning seminars. These seminars start with the patient's presenting complaint and the students must ask the tutor for additional clinical information to progress through case resolution. For this intervention, the tutors made each step explicit to students and encouraged self-reflection on their reasoning processes. At the end of their elective, students' performances were assessed through encounters with two standardized patients and chart write-ups. Twenty-nine students participated, providing a total of 58 encounters. The overall differences in accuracy of the final diagnosis given to the patient at the end of the encounter (control 63% vs intervention 74%, p = 0.53) and of the final diagnosis mentioned in the patient chart (61% vs 70%, p = 0.58) were not statistically significant. The students in the intervention group significantly more often listed the correct diagnosis among the differential diagnoses in their charts (75% vs 97%, p = 0.02). This case-based clinical reasoning seminar intervention, designed to bring students insight into cognitive features of their reasoning, improved aspects of diagnostic competence.

Unraveling interrelationships among psychopathology symptoms, cognitive domains and insight dimensions in chronic schizophrenia.

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Xavier, Rose Mary; Pan, Wei; Dungan, Jennifer R; Keefe, Richard S E; Vorderstrasse, Allison

2018-03-01

Insight in schizophrenia is long known to have a complex relationship with psychopathology symptoms and cognition. However, very few studies have examined models that explain these interrelationships. In a large sample derived from the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial (N=1391), we interrogated these interrelationships for potential causal pathways using structural equation modeling. Using the NIMH consensus model, latent variables were constructed for psychopathology symptom dimensions, including positive, negative, disorganized, excited and depressed from the Positive and Negative Syndrome Scale (PANSS) items. Neurocognitive variables were created from five predefined domains of working memory, verbal memory, reasoning, vigilance and processing speed. Illness insight and treatment insight were tested using latent variables constructed from the Illness and Treatment Attitude Questionnaire (ITAQ). Disorganized symptoms had the strongest effect on insight. Illness insight mediated the relationship of positive, depressed, and disorganized symptoms with treatment insight. Neurocognition mediated the relationship between disorganized and treatment insight and depressed symptoms and treatment insight. There was no effect of negative symptoms on either illness insight or treatment insight. Taken together, our results indicate overlapping and unique relational paths for illness and treatment insight dimensions, which could suggest differences in causal mechanisms and potential interventions to improve insight. Copyright © 2017 Elsevier B.V. All rights reserved.

Echocardiography Practice: Insights into Appropriate Clinical Use, Technical Competence and Quality Improvement Program

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Kossaify, Antoine; Grollier, Gilles

2014-01-01

Echocardiography accounts for nearly half of all cardiac imaging techniques. It is a widely available and adaptable tool, as well as being a cost-effective and mainly a non-invasive test. In addition, echocardiography provides extensive clinical data, which is related to the presence or advent of different modalities (tissue Doppler imaging, speckle tracking imaging, three-dimensional mode, contrast echo, etc.), different approaches (transesophageal, intravascular, etc.), and different applications (ie, heart failure/resynchronization studies, ischemia/stress echo, etc.). In view of this, it is essential to conform to criteria of appropriate use and to keep standards of competence. In this study, we sought to review and discuss clinical practice of echocardiography in light of the criteria of appropriate clinical use, also we present an insight into echocardiographic technical competence and quality improvement project. PMID:24516342

Insights From Pre-Clinical and Clinical Studies on the Role of Innate Inflammation in Atherosclerosis Regression

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Karishma Rahman

2018-05-01

Full Text Available Atherosclerosis, the underlying cause of coronary artery (CAD and other cardiovascular diseases, is initiated by macrophage-mediated immune responses to lipoprotein and cholesterol accumulation in artery walls, which result in the formation of plaques. Unlike at other sites of inflammation, the immune response becomes maladaptive and inflammation fails to resolve. The most common treatment for reducing the risk from atherosclerosis is low density lipoprotein cholesterol (LDL-C lowering. Studies have shown, however, that while significant lowering of LDL-C reduces the risk of heart attacks to some degree, there is still residual risk for the majority of the population. We and others have observed “residual inflammatory risk” of atherosclerosis after plasma cholesterol lowering in pre-clinical studies, and that this phenomenon is clinically relevant has been dramatically reinforced by the recent Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS trial. This review will summarize the role of the innate immune system, specifically macrophages, in atherosclerosis progression and regression, as well as the pre-clinical and clinical models that have provided significant insights into molecular pathways involved in the resolution of plaque inflammation and plaque regression. Partnered with clinical studies that can be envisioned in the post-CANTOS period, including progress in developing targeted plaque therapies, we expect that pre-clinical studies advancing on the path summarized in this review, already revealing key mechanisms, will continue to be essential contributors to achieve the goals of dampening plaque inflammation and inducing its resolution in order to maximize the therapeutic benefits of conventional risk factor modifications, such as LDL-C lowering.

Parental insightfulness: retrospect and prospect.

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Koren-Karie, Nina; Oppenheim, David

2018-06-01

We open this introductory paper to the special issue with the theoretical and clinical roots of the insightfulness concept. Next, the Insightfulness Assessment (IA) is presented, followed by a review of key empirical findings supporting the IA. The central points in the papers in this special issue are reviewed next. These include the use of the IA with parents of children ranging in age from infancy to adolescence, its applicability outside the parent-child relationship (e.g. insightfulness toward a close friend), its use with high-risk mothers, and the usefulness of insightfulness both as a continuous and a categorical measure. The clinical applications of the IA are discussed, and we close with future directions for IA research.

Linking FRRF Derived Photophysiology with Carbon-based Primary Productivity: Insights from Concepts of Cellular Energy Allocation

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Schuback, N.; Schallenberg, C.; Duckham, C.; Flecken, M.; Maldonado, M. T.; Tortell, P. D.

2016-02-01

Active chlorophyll a fluorescence approaches, including fast repetition rate fluorometry (FRRF), have the potential to provide estimates of phytoplankton primary productivity at unprecedented spatial and temporal resolution. FRRF-derived productivity rates are based on estimates of charge separation in photosystem II (ETRRCII), which must be converted into ecologically relevant units of carbon fixation. Understanding sources of variability in the coupling of ETRRCII and carbon fixation provides important physiological insight into phytoplankton photosynthesis, and is critical for the application of FRRF as a primary productivity measurement tool. We present data from a series of experiments during which we simultaneously measured phytoplankton carbon fixation and ETRRCII in the iron-limited NE subarctic Pacific. Our results show significant variability of the derived conversion factor (Ve:C/nPSII), with highest values observed under conditions of excess excitation pressure at the level of photosystem II, caused by high light and/or low iron. Our results will be discussed in the context of metabolic plasticity, which evolved in phytoplankton to simultaneously maximize growth and provide photoprotection under fluctuating light and limiting nutrient availabilities. Because the derived conversion factor is associated with conditions of excess light, it correlates with the expression of non-photochemical quenching (NPQ) in the pigment antenna, also derived from FRRF measurements. Our results demonstrate a significant correlation between NPQ and the conversion factor Ve:C/nPSII, and the potential of this relationship to improve FRRF-based estimates of phytoplankton carbon fixation rates is discussed.

Insight, Cognitive Insight and Sociodemographic Features in Obsessive Compulsive Disorder Presenting with Reactive and Autogeneus Features

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Katre ÇAMLI

2012-03-01

Full Text Available Objective: The aim of the present study was to test hypothesis that obsessive compulsive disorder (OCD patients who have autogenous obsessions and reactive obsessions show different sociodemographic and clinical characteristics with different insight and cognitive insight levels. Method: Sixty-one patients diagnosed as OCD according to the Structured Clinical Interview for DSM-III-R (SCID-I are recruited. 31 patients had reactive obsessions and 30 had autogenous obsessions. The sociodemographic characteristics of patients and the symptomatology were evaluated using psychiatric scales including SCID-I, Yale Brown Obsessive- Compulsive Scale (YBOCS, Yale Brown Obsessive-Compulsive Scale-Symptom Checklist (YBOCS-SC and Beck Insight Scale. Results: The percentage of women in reactive obsessive group was higher and also this group had significantly less antipsychotic medication prescribed than the autogenous obsessive group. No significant difference was found for the other demographic variables. No significant difference was identified for the Beck Insight Self-Reflectiveness subscale but for the Self-Certainty subscale, reactive obsessives had higher scores. Although there was no significant difference for the composit index points, which is the subtraction of the two subscales, the p value was close to the limit. On the other hand YBOCS item- 11 scores which evaluates insight were higher in autogenous obsessives meaning low levels of insight. Conclusion: For the sociodemographic and clinical characteristics; there was no significant difference between the groups except gender distribution and antipsychotic medication. Our data about insight seems inconsistent but insight and cognitive insight can be different entities which show different levels of insight. Further investigation with different obsession types is needed.

Effects on cognitive and clinical insight with the use of Guided Self-Determination in outpatients with schizophrenia: A randomized open trial.

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Jørgensen, R; Licht, R W; Lysaker, P H; Munk-Jørgensen, P; Buck, K D; Jensen, S O W; Hansson, L; Zoffmann, V

2015-07-01

Poor insight has a negative impact on the outcome in schizophrenia; consequently, poor insight is a logical target for treatment. However, neither medication nor psychosocial interventions have been demonstrated to improve poor insight. A method originally designed for diabetes patients to improve their illness management, Guided Self-Determination (GSD), has been adapted for use in patients with schizophrenia (GSD-SZ). The purpose of this study was to investigate the effect on insight of GSD-SZ as a supplement to treatment as usual (TAU) as compared to TAU alone in outpatients diagnosed with schizophrenia. The design was an open randomized trial. The primary hypothesis was cognitive insight would improve in those patients who received GSD-SZ+TAU as assessed by the BCIS. We additionally explored whether the intervention led to changes in clinical insight, self-perceived recovery, self-esteem, social functioning and symptom severity. Assessments were conducted at baseline, and at 3-, 6- and 12-month follow-up. Analysis was based on the principles of intention to treat and potential confounders were taken into account through applying a multivariate approach. A total of 101 participants were randomized to GSD-SZ+TAU (n=50) or to TAU alone (n=51). No statistically significant differences were found on the cognitive insight. However, at 12-month follow-up, clinical insight (measured by G12 from the Positive and Negative Syndrome Scale), symptom severity, and social functioning had statistically significantly improved in the intervention group as compared to the control group. "Improving insight in patients diagnosed with schizophrenia", NCT01282307, http://clinicaltrials.gov/. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Cognitive insight: A systematic review.

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Van Camp, L S C; Sabbe, B G C; Oldenburg, J F E

2017-07-01

Cognitive insight is the ability to re-evaluate thoughts and beliefs in order to make thoughtful conclusions. It differs from clinical insight, as it focuses on more general metacognitive processes. Therefore, it could be relevant to diverse disorders and non-clinical subjects. There is a growing body of research on cognitive insight in individuals with and without psychosis. This review has summarised the current state of the art regarding this topic. We conclude that while cognitive insight in its current form seems valid for use in individuals with psychosis, it is less so for individuals without psychosis. Additionally, higher cognitive insight not always leads to better psychological functioning. For instance, higher levels of self-reflection are often associated with depressive mood. We therefore recommend the sub-components of cognitive insight to be studied separately. Also, it is unclear what position cognitive insight takes within the spectrum of metacognitive processes and how it relates to other self-related concepts that have been defined previously in literature. Combining future and past research on cognitive insight and its analogue concepts will help in the formation of a uniform definition that fits all subjects discussed here. Copyright © 2017. Published by Elsevier Ltd.

Derivation of cell population kinetic parameters from clinical statistical data (program RAD3)

International Nuclear Information System (INIS)

Cohen, L.

1978-01-01

Cellular lethality models generally require up to 6 parameters to simulate a clinical course of fractionated radiation therapy and to derive an estimate of the cellular surviving fraction for a given treatment scheme. These parameters are the mean cellular lethal dose, the extrapolation number, the ratio of sublethal to irreparable events, the regeneration rate, the repopulation limit (cell cycles), and a field-size or tumor-volume factor. A computer program (RAD3) was designed to derive best-fitting values for these parameters in relation to available clinical data based on the assumption that if a number of different fractionation schemes yield similar reactions, the cellular surviving fractions will be about equal in each instance. Parameters were derived for a variety of human tissues from which realistic iso-effect functions could be generated

Insight in schizophrenia: a review.

Science.gov (United States)

Dam, Jesper

2006-01-01

The issue of insight in schizophrenia must be assumed to be one of the most important aspects of the clinical examination. Comprehensive studies have shown that between 50% and 80% of all patients suffering from schizophrenia do not believe that they have a disorder. In recent years, poor insight in schizophrenia has been the subject of increasing interest, as manifested in a number of studies discussed in the present review. Some of these studies focus on insight correlated to various parameters such as psychopathology, neuropsychology, clinical relevance and compliance. Other studies refer to more theoretical implications, among these the issue of defining the concept of insight: whether insight can be seen as a "primary" phenomenon in schizophrenia, and whether insight may be graduated, dimensioned or increased. Several authors have developed rating scales in an attempt to obtain a measure for the degree or dimension of insight. Here, the range of parameters employed gives an excellent impression of the complexity of the concept of insight. In the concluding discussion, a phenomenological aspect is brought in, in an attempt to place the concept of insight in relation to disturbances of the self in schizophrenia and to primary symptoms in schizophrenia, amongst these autism.

Insight and illness perception in Mexican patients with psychosis.

Science.gov (United States)

Gómez-de-Regil, Lizzette

2015-03-01

Insight and illness perception are two concepts of interest in the study of factors related to clinical outcome in patients with psychosis. Insight implies a risk of emotional distress for the patient. Illness perceptions, regardless of their accuracy, might be favorable or not to illness. Literature provides evidence of significant correlates of these factors with clinical outcome, but they are rarely included in a single study. 1) assessing insight and illness perception in a sample of Mexican patients who have experienced psychosis and, 2) analyzing how insight and illness perception relate to each other and how they relate to clinical status (i.e., positive, negative, and general psychopathology, depression, and anxiety). Sixty-one participants (55.7% females) were recruited from a public psychiatric hospital; insight and illness perceptions were assessed with the SUMD and the Brief-IPQ, respectively. Clinical status was assessed with the PANSS, CDS and BAI scales. Participants showed good insight, favorable illness perceptions for the cognitive and comprehension dimensions, but unfavorable for the emotional dimension. Clinical status of sample was characterized by mild symptoms. Poor insight related to positive symptoms and general psychopathology. Cognitive and emotional perceptions of illness were significantly associated to most clinical status parameters, whereas comprehension showed no significant results. The study not only replicates the significant association on insight and illness perception with clinical outcome, but shows how their patterns of interactions are different, reinforcing the idea that they are two distinct factors worthy of being habitually acknowledged in research and clinical practice.

Hypnosis in palliative care: from clinical insights to the science of self-regulation.

Science.gov (United States)

Landry, Mathieu; Stendel, Moriah; Landry, Michel; Raz, Amir

2018-01-01

Palliative care spans a wide-ranging spectrum: from pain-management to spiritual support. As the demand for end-of-life care increases, so does the demand for innovative, effective, interventions. Mind-body techniques seem especially advantageous in a palliative context. Here we show that hypnosis serves an excellent adjunct therapy in palliative care to boost the efficacy of standard treatments. With the overarching goal of bridging clinical and scientific insights, we outline how five core principles of hypnosis can benefit the diverse needs of palliative care.

Plant-derived immunomodulators: An insight on their preclinical evaluation and clinical trials

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Ibrahim eJantan

2015-08-01

Full Text Available The phagocyte-microbe interactions in the immune system is a defence mechanism but when excessively or inappropriately deployed can harm host tissues and participate in the development of different non-immune and immune chronic inflammatory diseases such as autoimmune problems, allergies, some rheumatoid disorders, cancers and others. Immunodrugs include organic synthetics, biological agents such as cytokines and antibodies acting on single targets or pathways have been used to treat immune-related diseases but with limited success. Most of immunostimulants and immunosuppressants in clinical use are the cytotoxic drugs which possess serious side effects. There is a growing interest to use herbal medicines as multi-component agents to modulate the complex immune system in the prevention of infections rather than treating the immune-related diseases. Many therapeutic effects of plant extracts have been suggested to be due to their wide array of immunomodulatory effects and influence on the immune system of the human body. Phytochemicals such as flavonoids, polysaccharides, lactones, alkaloids, diterpenoids and glycosides, present in several plants, have been reported to be responsible for the plants immunomodulating properties. Thus the search for natural products of plant origin as new leads for development of potent and safe immunosuppressant and immunostimulant agents is gaining much major research

Obesity Paradox in Lung Cancer Prognosis: Evolving Biological Insights and Clinical Implications.

Science.gov (United States)

Zhang, Xueli; Liu, Yamin; Shao, Hua; Zheng, Xiao

2017-10-01

The survival rate of lung cancer remains low despite the progress of surgery and chemotherapy. With the increasing comorbidity of obesity in patients with lung cancer, new challenges are emerging in the management of this patient population. A key issue of interest is the prognostic effect of obesity on surgical and chemotherapeutic outcomes in patients with lung cancer, which is fueled by the growing observation of survival benefits in overweight or obese patients. This unexpected inverse relationship between obesity and lung cancer mortality, called the obesity paradox, remains poorly understood. The evolving insights into the heterogeneity of obesity phenotypes and associated biological connections with lung cancer progression in recent years may help explain some of the seemingly paradoxical relationship, and well-designed clinical studies looking at the causal role of obesity-associated molecules are expected. Here, we examine potential biological mechanisms behind the protective effects of obesity in lung cancer. We highlight the need to clarify the clinical implications of this relationship toward an updated intervention strategy in the clinical care of patients with lung cancer and obesity. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Quantifying and visualizing site performance in clinical trials.

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Yang, Eric; O'Donovan, Christopher; Phillips, JodiLyn; Atkinson, Leone; Ghosh, Krishnendu; Agrafiotis, Dimitris K

2018-03-01

One of the keys to running a successful clinical trial is the selection of high quality clinical sites, i.e., sites that are able to enroll patients quickly, engage them on an ongoing basis to prevent drop-out, and execute the trial in strict accordance to the clinical protocol. Intuitively, the historical track record of a site is one of the strongest predictors of its future performance; however, issues such as data availability and wide differences in protocol complexity can complicate interpretation. Here, we demonstrate how operational data derived from central laboratory services can provide key insights into the performance of clinical sites and help guide operational planning and site selection for new clinical trials. Our methodology uses the metadata associated with laboratory kit shipments to clinical sites (such as trial and anonymized patient identifiers, investigator names and addresses, sample collection and shipment dates, etc.) to reconstruct the complete schedule of patient visits and derive insights about the operational performance of those sites, including screening, enrollment, and drop-out rates and other quality indicators. This information can be displayed in its raw form or normalized to enable direct comparison of site performance across studies of varied design and complexity. Leveraging Covance's market leadership in central laboratory services, we have assembled a database of operational metrics that spans more than 14,000 protocols, 1400 indications, 230,000 unique investigators, and 23 million patient visits and represents a significant fraction of all clinical trials run globally in the last few years. By analyzing this historical data, we are able to assess and compare the performance of clinical investigators across a wide range of therapeutic areas and study designs. This information can be aggregated across trials and geographies to gain further insights into country and regional trends, sometimes with surprising results. The

Stigma as a predictor of insight in schizophrenia.

Science.gov (United States)

Pruß, Linda; Wiedl, Karl Heinz; Waldorf, Manuel

2012-07-30

Insight in schizophrenia can be seen as a multifactorial phenomenon. Although multifactorial pathways have also been suggested for insight formation, motivational explanations have rarely been tested. The present study explores stigma as one possible determinant of a motivated lack of insight in integrated models of insight formation. It examines the contribution of socio-demographic and clinical variables, neurocognitive functions, symptoms, and stigma to the prediction of insight into illness. Patients diagnosed with schizophrenia spectrum disorders (N=111) participated in a comprehensive battery of instruments to measure insight dimensions, stigma, neurocognitive functions, symptoms, socio-demographic and clinical variables. Blockwise multiple regression analysis indicates significant association of variability in insight dimensions with gender (7%) and stigma (i. e., stereotype agreement: 5%). Our findings demonstrate an incremental validity of stigma, which indicates a motivational pathway of insight formation. This study enables better understanding of the multifactorial nature of insight, which should be considered in therapeutic interventions to improve insight. The roles of gender and neurocognitive functions in insight formation are also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Key principles for a national clinical decision support knowledge sharing framework: synthesis of insights from leading subject matter experts.

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Kawamoto, Kensaku; Hongsermeier, Tonya; Wright, Adam; Lewis, Janet; Bell, Douglas S; Middleton, Blackford

2013-01-01

To identify key principles for establishing a national clinical decision support (CDS) knowledge sharing framework. As part of an initiative by the US Office of the National Coordinator for Health IT (ONC) to establish a framework for national CDS knowledge sharing, key stakeholders were identified. Stakeholders' viewpoints were obtained through surveys and in-depth interviews, and findings and relevant insights were summarized. Based on these insights, key principles were formulated for establishing a national CDS knowledge sharing framework. Nineteen key stakeholders were recruited, including six executives from electronic health record system vendors, seven executives from knowledge content producers, three executives from healthcare provider organizations, and three additional experts in clinical informatics. Based on these stakeholders' insights, five key principles were identified for effectively sharing CDS knowledge nationally. These principles are (1) prioritize and support the creation and maintenance of a national CDS knowledge sharing framework; (2) facilitate the development of high-value content and tooling, preferably in an open-source manner; (3) accelerate the development or licensing of required, pragmatic standards; (4) acknowledge and address medicolegal liability concerns; and (5) establish a self-sustaining business model. Based on the principles identified, a roadmap for national CDS knowledge sharing was developed through the ONC's Advancing CDS initiative. The study findings may serve as a useful guide for ongoing activities by the ONC and others to establish a national framework for sharing CDS knowledge and improving clinical care.

Clinical Correlates of Computationally Derived Visual Field Defect Archetypes in Patients from a Glaucoma Clinic.

Science.gov (United States)

Cai, Sophie; Elze, Tobias; Bex, Peter J; Wiggs, Janey L; Pasquale, Louis R; Shen, Lucy Q

2017-04-01

To assess the clinical validity of visual field (VF) archetypal analysis, a previously developed machine learning method for decomposing any Humphrey VF (24-2) into a weighted sum of clinically recognizable VF loss patterns. For each of 16 previously identified VF loss patterns ("archetypes," denoted AT1 through AT16), we screened 30,995 reliable VFs to select 10-20 representative patients whose VFs had the highest decomposition coefficients for each archetype. VF global indices and patient ocular and demographic features were extracted retrospectively. Based on resemblances between VF archetypes and clinically observed VF patterns, hypotheses were generated for associations between certain VF archetypes and clinical features, such as an association between AT6 (central island, representing severe VF loss) and large cup-to-disk ratio (CDR). Distributions of the selected clinical features were compared between representative eyes of certain archetypes and all other eyes using the two-tailed t-test or Fisher exact test. 243 eyes from 243 patients were included, representative of AT1 through AT16. CDR was more often ≥ 0.7 among eyes representative of AT6 (central island; p = 0.002), AT10 (inferior arcuate defect; p = 0.048), AT14 (superior paracentral defect; p = 0.016), and AT16 (inferior paracentral defect; p = 0.016) than other eyes. CDR was more often 6D (p = 0.069). Shared clinical features between computationally derived VF archetypes and clinically observed VF patterns support the clinical validity of VF archetypal analysis.

Salicylic acid metabolites and derivatives inhibit CDK activity: Novel insights into aspirin's chemopreventive effects against colorectal cancer

Science.gov (United States)

Dachineni, Rakesh; Kumar, D. Ramesh; Callegari, Eduardo; Kesharwani, Siddharth S.; Sankaranarayanan, Ranjini; Seefeldt, Teresa; Tummala, Hemachand; Bhat, G. Jayarama

2017-01-01

Aspirin's potential as a drug continues to be evaluated for the prevention of colorectal cancer (CRC). Although multiple targets for aspirin and its metabolite, salicylic acid, have been identified, no unifying mechanism has been proposed to clearly explain its chemopreventive effects. Our goal here was to investigate the ability of salicylic acid metabolites, known to be generated through cytochrome P450 (CYP450) enzymes, and its derivatives as cyclin dependent kinase (CDK) inhibitors to gain new insights into aspirin's chemopreventive actions. Using in vitro kinase assays, for the first time, we demonstrate that salicylic acid metabolites, 2,3-dihydroxy-benzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA), as well as derivatives 2,4-dihydroxybenzoic acid (2,4-DHBA), 2,6-dihydroxybenzoic acid (2,6-DHBA), inhibited CDK1 enzyme activity. 2,3-DHBA and 2,6-DHBA did not inhibit CDK2 and 4; however, both inhibited CDK-6 activity. Interestingly, another derivative, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) was highly effective in inhibiting CDK1, 2, 4 and 6 activity. Molecular docking studies showed that these compounds potentially interact with CDK1. Immunoblotting experiments showed that aspirin acetylated CDK1, and pre-incubation with salicylic acid and its derivatives prevented aspirin-mediated CDK1 acetylation, which supported the data obtained from molecular docking studies. We suggest that intracellularly generated salicylic acid metabolites through CYP450 enzymes within the colonic epithelial cells, or the salicylic acid metabolites generated by gut microflora may significantly contribute to the preferential chemopreventive effect of aspirin against CRC through inhibition of CDKs. This novel hypothesis and mechanism of action in aspirin's chemopreventive effects opens a new area for future research. In addition, structural modification to salicylic acid derivatives may prove useful in the development of novel CDK inhibitors in cancer prevention and

Antimicrobial activity of some sulfonamide derivatives on clinical isolates of Staphylococus aureus

Directory of Open Access Journals (Sweden)

Bekdemir Yunus

2008-08-01

Full Text Available Abstract Background Staphylococcus aureus is a non-motile, gram positive, non-sporforming, facultative anaerobic microorganism. It is one of the important bacteria as a potential pathogen specifically for nosocomial infections. The sulfonamide derivative medicines are preferred to cure infection caused by S. aureus due to methicillin resistance. Methods Antimicrobial activity of four sulfonamide derivatives have been investigated against 50 clinical isolates of S. aureus and tested by using MIC and disc diffusion methods. 50 clinical isolate which collected from specimens of patients who are given medical treatment in Ondokuz Mayis University Medical School Hospital. A control strain of S. aureus ATCC 29213 was also tested. Results The strongest inhibition was observed in the cases of I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid], and II [N-(2-hydroxy-5-nitro-phenyl-4-methyl-benzensulfonamid] against S. aureus. Compound I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid] showed higher effect on 21 S. aureus MRSAisolates than oxacillin antibiotic. Introducing an electron withdrawing on the ring increased the antimicrobial activity remarkably. Conclusion This study may help to suggest an alternative possible leading compound for development of new antimicrobial agents against MRSA and MSSA resistant S. aureus. It was also shown here that that clinical isolates of 50 S. aureus have various resistance patterns against to four sulfonamide derivatives. It may also be emphasized here that in vitro antimicrobial susceptibility testing results for S. aureus need standardization with further studies and it should also have a correlation with in vivo therapeutic response experiments.

Australian OTC Derivatives Markets: Insights from the BIS Semiannual Survey

OpenAIRE

Jason Ahn; Mihovil Matic; Christian Vallence

2012-01-01

The Reserve Bank of Australia recently commenced surveying participants in Australian over-the-counter (OTC) derivatives markets as part of the Bank for International Settlements’ (BIS) semiannual global OTC derivatives survey. Australia’s contribution to the survey complements regulatory efforts to improve the resilience and transparency of Australia’s OTC derivatives markets. It also facilitates a higher frequency comparison of the Australian and foreign OTC derivatives markets. The survey ...

ATX-101 (Deoxycholic Acid Injection) Treatment in Men: Insights From Our Clinical Experience.

Science.gov (United States)

Shridharani, Sachin M; Behr, Kathleen L

2017-11-01

Excess submental fat (SMF), also called a double chin, is an area of concern for men that can be addressed clinically. ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada, Australia, and various European countries) is the first injectable approved for reduction of SMF. To share the authors' clinical experience using ATX-101 in men with submental fullness and offer insights regarding how this treatment may be presented to men as an option to improve their submental profile. Retrospective review of the authors' medical records for male patients treated with ATX-101. To allow for fewer ATX-101 treatments, it is recommended that a large surface area be treated at the first session. The positive changes and outcomes achieved with ATX-101 build confidence between the physician and patient, which often leads to male patients seeking other aesthetic treatments to improve their overall appearance. ATX-101 treatment is often an effective introduction to aesthetic medicine for men.

Human Amniotic Membrane-Derived Products in Sports Medicine: Basic Science, Early Results, and Potential Clinical Applications.

Science.gov (United States)

Riboh, Jonathan C; Saltzman, Bryan M; Yanke, Adam B; Cole, Brian J

2016-09-01

Amniotic membrane (AM)-derived products have been successfully used in ophthalmology, plastic surgery, and wound care, but little is known about their potential applications in orthopaedic sports medicine. To provide an updated review of the basic science and preclinical and clinical data supporting the use of AM-derived products and to review their current applications in sports medicine. Systematic review. A systematic search of the literature was conducted using the Medline, EMBASE, and Cochrane databases. The search term amniotic membrane was used alone and in conjunction with stem cell, orthopaedic, tissue engineering, scaffold, and sports medicine. The search identified 6870 articles, 80 of which, after screening of the titles and abstracts, were considered relevant to this study. Fifty-five articles described the anatomy, basic science, and nonorthopaedic applications of AM-derived products. Twenty-five articles described preclinical and clinical trials of AM-derived products for orthopaedic sports medicine. Because the level of evidence obtained from this search was not adequate for systematic review or meta-analysis, a current concepts review on the anatomy, physiology, and clinical uses of AM-derived products is presented. Amniotic membranes have many promising applications in sports medicine. They are a source of pluripotent cells, highly organized collagen, antifibrotic and anti-inflammatory cytokines, immunomodulators, and matrix proteins. These properties may make it beneficial when applied as tissue engineering scaffolds, improving tissue organization in healing, and treatment of the arthritic joint. The current body of evidence in sports medicine is heavily biased toward in vitro and animal studies, with little to no human clinical data. Nonetheless, 14 companies or distributors offer commercial AM products. The preparation and formulation of these products alter their biological and mechanical properties, and a thorough understanding of these

Extraction Socket Preservation Using Porcine-Derived Collagen Membrane Alone or Associated with Porcine-Derived Bone. Clinical Results of Randomized Controlled Study

Directory of Open Access Journals (Sweden)

Renzo Guarnieri

2017-03-01

Full Text Available Objectives: The aim of present randomized controlled clinical trial was to clinically evaluate hard tissue changes after extraction socket preservation procedures compared to natural spontaneous healing. Material and Methods: Thirty patients were enrolled in the present study and underwent single-tooth extraction in the premolar/molar areas. Ten sites were grafted with porcine-derived bone covered by collagen membrane, 10 covered by porcine-derived collagen membrane alone, and 10 underwent natural spontaneous healing. Vertical and horizontal bone changes after 3-month were evaluated at implant placement. Results: The vertical and horizontal bone changes at the extraction sockets treated with collagen membrane alone (vertical: -0.55 [SD 0.11] mm, and horizontal: -1.21 [SD 0.69] mm and collagen membrane plus porcine-derived bone (vertical: -0.37 [SD 0.7] mm, and horizontal: -0.91 [SD 0.53] mm were found significantly lower (P < 0.001, when compared to non-grafted sockets (vertical: -2.09 [SD 0.19] mm, and horizontal: -3.96 [SD 0.87] mm. In type 1 extraction sockets, in premolar sites, and in presence of vestibular bone thicknesses ≥ 1.5 mm, the use of collagen membrane alone revealed similar outcomes to those with additional graft material. Conclusions: At the re-entry surgery, extraction sockets grafted with porcine-derived bone and covered by collagen membrane, and extraction sockets covered by porcine-derived collagen membrane alone, showed significantly lower vertical and horizontal bone changes, compared to extraction sockets sites underwent natural spontaneous healing. However, a complete prevention of remodelling is not achievable, irrespective of the technique used.

Computational models of the pulmonary circulation: Insights and the move towards clinically directed studies

Science.gov (United States)

Tawhai, Merryn H.; Clark, Alys R.; Burrowes, Kelly S.

2011-01-01

Biophysically-based computational models provide a tool for integrating and explaining experimental data, observations, and hypotheses. Computational models of the pulmonary circulation have evolved from minimal and efficient constructs that have been used to study individual mechanisms that contribute to lung perfusion, to sophisticated multi-scale and -physics structure-based models that predict integrated structure-function relationships within a heterogeneous organ. This review considers the utility of computational models in providing new insights into the function of the pulmonary circulation, and their application in clinically motivated studies. We review mathematical and computational models of the pulmonary circulation based on their application; we begin with models that seek to answer questions in basic science and physiology and progress to models that aim to have clinical application. In looking forward, we discuss the relative merits and clinical relevance of computational models: what important features are still lacking; and how these models may ultimately be applied to further increasing our understanding of the mechanisms occurring in disease of the pulmonary circulation. PMID:22034608

[Informed consent process in clinical trials: Insights of researchers, patients and general practitioners].

Science.gov (United States)

Giménez, Nuria; Pedrazas, David; Redondo, Susana; Quintana, Salvador

2016-10-01

Adequate information for patients and respect for their autonomy are mandatory in research. This article examined insights of researchers, patients and general practitioners (GPs) on the informed consent process in clinical trials, and the role of the GP. A cross-sectional study using three questionnaires, informed consent reviews, medical records, and hospital discharge reports. GPs, researchers and patients involved in clinical trials. Included, 504 GPs, 108 researchers, and 71 patients. Consulting the GP was recommended in 50% of the informed consents. Participation in clinical trials was shown in 33% of the medical records and 3% of the hospital discharge reports. GPs scored 3.54 points (on a 1-10 scale) on the assessment of the information received by the principal investigator. The readability of the informed consent sheet was rated 8.03 points by researchers, and the understanding was rated 7.68 points by patients. Patient satisfaction was positively associated with more time for reflection. GPs were not satisfied with the information received on the participation of patients under their in clinical trials. Researchers were satisfied with the information they offered to patients, and were aware of the need to improve the information GPs received. Patients collaborated greatly towards biomedical research, expressed satisfaction with the overall process, and minimised the difficulties associated with participation. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Third-person Diagnostic Interview on the Cognitive Insight Level of Psychotic Patients with an Insight at the Denial Level.

Science.gov (United States)

Mehdizadeh, Mahsa; Rezaei, Omid

2016-01-01

According to the previous findings, the third-person technique improved the clinical insight of psychotic patients, therefore the present study aims to examine the effect of a third-person interview compared to a first-person interview on the level of cognitive insight of psychotic patients with an insight at the denial level. In this study, using interviews and questionnaires, a total number of 44 patients of Razi Psychiatric Educational and Treatment Center with an insight at the denial level being assessed using diagnostic interviews were divided randomly into two groups. Then, the two groups of patients' cognitive insights were evaluated using Beck Cognitive Insight Scale. The findings indicated that in psychotic patients with an insight at the denial level, the third-person technique of interview compared to the first-person had little effect on the improvement of overall cognitive insight and its components, including self-reflection and self-assurance; however, this effect was not strong enough to make a significant difference between the two groups of patients. According to the study findings, we can conclude that the third-person interview compared to the first-person interview has no effect on the improvement of the cognitive insight of psychotic patients with an insight at the denial level. This finding is consistent with the previous studies indicating that although the theory of mind has some correlations with the clinical insight of patients, it has no effect on their cognitive insight.

Genetic correlates of insight in schizophrenia.

Science.gov (United States)

Xavier, Rose Mary; Vorderstrasse, Allison; Keefe, Richard S E; Dungan, Jennifer R

2018-05-01

Insight in schizophrenia is clinically important as it is associated with several adverse outcomes. Genetic contributions to insight are unknown. We examined genetic contributions to insight by investigating if polygenic risk scores (PRS) and candidate regions were associated with insight. Schizophrenia case-only analysis of the Clinical Antipsychotics Trials of Intervention Effectiveness trial. Schizophrenia PRS was constructed using Psychiatric Genomics Consortium (PGC) leave-one out GWAS as discovery data set. For candidate regions, we selected 105 schizophrenia-associated autosomal loci and 11 schizophrenia-related oligodendrocyte genes. We used regressions to examine PRS associations and set-based testing for candidate analysis. We examined data from 730 subjects. Best-fit PRS at p-threshold of 1e-07 was associated with total insight (R 2 =0.005, P=0.05, empirical P=0.054) and treatment insight (R 2 =0.005, P=0.048, empirical P=0.048). For models that controlled for neurocognition, PRS significantly predicted treatment insight but at higher p-thresholds (0.1 to 0.5) but did not survive correction. Patients with highest polygenic burden had 5.9 times increased risk for poor insight compared to patients with lowest burden. PRS explained 3.2% (P=0.002, empirical P=0.011) of variance in poor insight. Set-based analyses identified two variants associated with poor insight- rs320703, an intergenic variant (within-set P=6e-04, FDR P=0.046) and rs1479165 in SOX2-OT (within-set P=9e-04, FDR P=0.046). To the best of our knowledge, this is the first study examining genetic basis of insight. We provide evidence for genetic contributions to impaired insight. Relevance of findings and necessity for replication are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Dimensions of insight in schizophrenia: Exploratory factor analysis of items from multiple self- and interviewer-rated measures of insight.

Science.gov (United States)

Konsztowicz, Susanna; Schmitz, Norbert; Lepage, Martin

2018-03-10

Insight in schizophrenia is regarded as a multidimensional construct that comprises aspects such as awareness of the disorder and recognition of the need for treatment. The proposed number of underlying dimensions of insight is variable in the literature. In an effort to identify a range of existing dimensions of insight, we conducted a factor analysis on combined items from multiple measures of insight. We recruited 165 participants with enduring schizophrenia (treated for >3years). Exploratory factor analysis was conducted on itemized scores from two interviewer-rated measures of insight: the Schedule for the Assessment of Insight-Expanded and the abbreviated Scale to assess Unawareness of Mental Disorder; and two self-report measures: the Birchwood Insight Scale and the Beck Cognitive Insight Scale. A five-factor solution was selected as the best-fitting model, with the following dimensions of insight: 1) awareness of illness and the need for treatment; 2) awareness and attribution of symptoms and consequences; 3) self-certainty; 4) self-reflectiveness for objectivity and fallibility; and 5) self-reflectiveness for errors in reasoning and openness to feedback. Insight in schizophrenia is a multidimensional construct comprised of distinct clinical and cognitive domains of awareness. Multiple measures of insight, both clinician- and self-rated, are needed to capture all of the existing dimensions of insight. Future exploration of associations between the various dimensions and their potential determinants will facilitate the development of clinically useful models of insight and effective interventions to improve outcome. Copyright © 2018 Elsevier B.V. All rights reserved.

Risk insights from seismic margin reviews

International Nuclear Information System (INIS)

Budnitz, R.J.

1990-01-01

This paper discusses the information that has been derived from the three seismic-margin reviews conducted so far, and the information that is potentially available from using the seismic-margin method more generally. There are two different methodologies for conducting seismic margin reviews of nuclear power plants, one developed under NRC sponsorship and one developed under sponsorship of the Electric Power Research Institute. Both methodologies will be covered in this paper. The paper begins with a summary of the steps necessary to complete a margin review, and will then outline the key technical difficulties that need to be addressed. After this introduction, the paper covers the safety and operational insights derived from the three seismic-margin reviews already completed: the NRC-sponsored review at Maine Yankee; the EPRI-sponsored review at Catawba; and the joint EPRI/NRC/utility effort at Hatch. The emphasis is on engineering insights, with attention to the aspects of the reviews that are easiest to perform and that provide the most readily available insights

Insight in seasonal affective disorder.

Science.gov (United States)

Ghaemi, S N; Sachs, G S; Baldassano, C F; Truman, C J

1997-01-01

Lack of insight complicates the evaluation and treatment of patients with psychotic and affective disorders. No studies of insight in seasonal affective disorder (SAD) have been reported. Thirty patients with SAD diagnosed by the Structured Clinical Interview for DSM-III-R but no other axis I conditions were treated short-term with light-therapy. Insight was measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) as modified by the authors to assess the self-report of insight into depressive symptoms. Increasing scores (1 to 5) indicated increasing unawareness of illness (i.e., less insight). SAD patients displayed a moderate amount of insight when depressed (mean SUMD score, 2.5). When recovered, they showed no significant change in insight into past depressive symptoms (mean SUMD score, 2.8). Greater insight into current depressive symptoms correlated with more depressive symptoms on the Hamilton Rating Scale for Depression score ([HRSD] r = .35, P depressive symptoms that does not change after recovery, a result in agreement with studies of insight in psychosis and mania. Further, in SAD, increased severity of illness may be associated with increased insight into depressive symptoms, consistent with the hypothesis of depressive realism.

Clinical potential of meningioma genomic insights: a practical review for neurosurgeons.

Science.gov (United States)

Karsy, Michael; Azab, Mohammed A; Abou-Al-Shaar, Hussam; Guan, Jian; Eli, Ilyas; Jensen, Randy L; Ormond, D Ryan

2018-06-01

Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell-like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.

The sights and insights of examiners in objective structured clinical examinations

Directory of Open Access Journals (Sweden)

Lauren Chong

2017-12-01

Full Text Available Purpose The objective structured clinical examination (OSCE is considered to be one of the most robust methods of clinical assessment. One of its strengths lies in its ability to minimise the effects of examiner bias due to the standardisation of items and tasks for each candidate. However, OSCE examiners’ assessment scores are influenced by several factors that may jeopardise the assumed objectivity of OSCEs. To better understand this phenomenon, the current review aims to determine and describe important sources of examiner bias and the factors affecting examiners’ assessments. Methods We performed a narrative review of the medical literature using Medline. All articles meeting the selection criteria were reviewed, with salient points extracted and synthesised into a clear and comprehensive summary of the knowledge in this area. Results OSCE examiners’ assessment scores are influenced by factors belonging to 4 different domains: examination context, examinee characteristics, examinee-examiner interactions, and examiner characteristics. These domains are composed of several factors including halo, hawk/dove and OSCE contrast effects; the examiner’s gender and ethnicity; training; lifetime experience in assessing; leadership and familiarity with students; station type; and site effects. Conclusion Several factors may influence the presumed objectivity of examiners’ assessments, and these factors need to be addressed to ensure the objectivity of OSCEs. We offer insights into directions for future research to better understand and address the phenomenon of examiner bias.

High frequency audiometry in prospective clinical research of ototoxicity due to platinum derivatives

NARCIS (Netherlands)

van der Hulst, R. J.; Dreschler, W. A.; Urbanus, N. A.

1988-01-01

The results of clinical use of routine high frequency audiometry in monitoring the ototoxic side effects of platinum and its derivatives are described in this prospective study. After demonstrating the reproducibility of the technique, we discuss the first results of an analysis of ototoxic side

Rare primary headaches: clinical insights.

Science.gov (United States)

Casucci, G; d'Onofrio, F; Torelli, P

2004-10-01

So-called "rare" headaches, whose prevalence rate is lower than 1% or is not known at all and have been reported in only a few dozen cases to date, constitute a very heterogeneous group. Those that are best characterised from the clinical point of view can be classified into forms with prominent autonomic features and forms with sparse or no autonomic features. Among the former are trigeminal autonomic cephalalgias (TACs) and hemicrania continua, while the latter comprise classical trigeminal neuralgia, hypnic headache, primary thunderclap headache, and exploding head syndrome. The major clinical discriminating factor for the differential diagnosis of TACs is the relationship between duration and frequency of attacks: the forms in which pain is shorter lived are those with the higher frequency of daily attacks. Other aspects to be considered are the time pattern of symptoms, intensity and timing of attacks, the patient's behaviour during the attacks, the presence of any triggering factors and of the refractory period after an induced attack, and response to therapy, especially with indomethacin. Often these are little known clinical entities, which are not easily detected in clinical practice. For some of them, e. g., thunderclap headache, it is always necessary to perform instrumental tests to exclude the presence of underlying organic diseases.

IPE data base structure and insights

International Nuclear Information System (INIS)

Lehner, J.; Youngblood, R.

1993-01-01

A data base (the ''IPE Insights Data Base''), has been developed that stores data obtained from the Individual Plant Examinations (IPEs) which licensees of nuclear power plants are conducting in response to the Nuclear Regulatory Commission's (NRC) Generic Letter GL88-20. The data base, which is a collection of linked dbase files, stores information about individual plant designs, core damage frequency, and containment performance in a uniform, structured way. This data base can be queried and used as a computational tool to derive insights regarding the plants for which data is stored. This paper sets out the objectives of the IPE Insights Data Base, describes its structure and contents, illustrates sample queries, and discusses possible future uses

A study of poor insight in social anxiety disorder.

Science.gov (United States)

Vigne, Paula; de Menezes, Gabriela B; Harrison, Ben J; Fontenelle, Leonardo F

2014-11-30

We investigated levels of insight among patients with Social Anxiety Disorder (SAD) as compared to patients with Obsessive-Compulsive Disorder (OCD) and evaluated whether levels of insight in SAD were related to specific sociodemographic and/or clinical features. Thirty-seven SAD patients and 51 OCD patients attending a tertiary obsessive-compulsive and anxiety disorders clinic were assessed with a sociodemographic and clinical questionnaire, a structured diagnostic interview, the Brown Assessment of Beliefs Scale (BABS), the Social Phobia Inventory (SPIN), the Beck Depression Inventory (BDI), the Sheehan Disability Scale (SDS), and the Treatment Adherence Survey-patient version (TAS-P). According to the BABS, SAD patients exhibited insight levels that were as low as those exhibited by OCD patients, with up to 29.7% of them being described as "poor insight" SAD. Although poor insight SAD patients were more frequently married, less depressed and displayed a statistical trend towards greater rates of early drop-out from cognitive-behavioral therapy, their insight levels were not associated with other variables of interest, including sex, age, employment, age at onset, duration of illness, associated psychiatric disorders, SPIN and SDS scores. Patients with poor insight SAD might perceive their symptoms as being less distressful and thus report fewer depressive symptoms and high rates of treatment non-adherence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Overcoming the bottleneck of platelet lysate supply in large-scale clinical expansion of adipose-derived stem cells

DEFF Research Database (Denmark)

Glovinski, Peter Viktor; Herly, Mikkel; Mathiasen, Anders B

2017-01-01

, we tested PLs prepared via three methods from outdated buffy coat-derived platelet concentrates (PCs) to establish an efficient and feasible expansion of ASCs for clinical use. METHODS: PLs were prepared by the freeze-thaw method from freshly drawn platelets or from outdated buffy coat-derived PCs...

New insights into the heterogeneity and functional diversity of human mesenchymal stem cells.

Science.gov (United States)

Han, Z C; Du, W J; Han, Z B; Liang, L

2017-01-01

Mesenchymal stem cells (MSCs) are being tested in several biological systems and clinical settings with the aim of exploring their therapeutic potentials for a variety of diseases. MSCs are also known to be heterogeneous populations with variable functions. In the context of this multidimensional complexity, a recurrent question is what source or population of MSCs is suitable for specific clinical indications. Here, we reported that the biological features of MSCs varied with the individual donor, the tissue source, the culture condition and the subpopulations. Placental chorionic villi (CV) derived MSCs exhibited superior activities of immunomodulation and pro-angiogenesis compared to MSCs derived from bone marrow (BM), adipose and umbilical cord (UC). We identified a subpopulation of CD106(VCAM-1)+MSCs, which are present richly in placental CV, moderately in BM, and lowly in adipose and UC. The CD106+MSCs possess significantly increased immunomodutory and pro-angiogenic activities compared to CD106-MSCs. Analysis of gene expression and cytokine secretion revealed that CD106+MSCs highly expressed several immnumodulatory and pro-angiogenic cytokines. Our data offer new insights on the identification and selection of suitable source or population of MSCs for clinical applications. Further efforts should be concentrated on standardizing methods which will ultimately allow the validation of MSC products with defined biomarkers as predictive of potency in suitable pre-clinical models and clinical settings.

IPE data base structure and insights

International Nuclear Information System (INIS)

Lehner, J.; Youngblood, R.

1994-01-01

A data base (the open-quotes IPE Insights Data Baseclose quotes), has been developed that stores data obtained from the Individual Plant Examinations (IPEs) which licensees of nuclear power plants are conducting in response to the Nuclear Regulatory Commission's (NRC) Generic Letter GL88-20. The data base, which is a collection of linked dBase files, stores information about individual plant designs, core damage frequency, and containment performance in a uniform, structured way. This data base can be queried and used as a computational tool to derive insights regarding the plants for which data is stored. This paper sets out the objectives of the IPE Insights Data Base, describes its structure and contents, illustrates sample queries, and discusses possible future uses

Mindfulness and Emotion Regulation: Insights from Neurobiological, Psychological, and Clinical Studies

Science.gov (United States)

Guendelman, Simón; Medeiros, Sebastián; Rampes, Hagen

2017-01-01

There is increasing interest in the beneficial clinical effects of mindfulness-based interventions (MBIs). Research has demonstrated their efficacy in a wide range of psychological conditions characterized by emotion dysregulation. Neuroimaging studies have evidenced functional and structural changes in a myriad of brain regions mainly involved in attention systems, emotion regulation, and self-referential processing. In this article we review studies on psychological and neurobiological correlates across different empirically derived models of research, including dispositional mindfulness, mindfulness induction, MBIs, and expert meditators in relation to emotion regulation. From the perspective of recent findings in the neuroscience of emotion regulation, we discuss the interplay of top-down and bottom-up emotion regulation mechanisms associated with different mindfulness models. From a phenomenological and cognitive perspective, authors have argued that mindfulness elicits a “mindful emotion regulation” strategy; however, from a clinical perspective, this construct has not been properly differentiated from other strategies and interventions within MBIs. In this context we propose the distinction between top-down and bottom-up mindfulness based emotion regulation strategies. Furthermore, we propose an embodied emotion regulation framework as a multilevel approach for understanding psychobiological changes due to mindfulness meditation regarding its effect on emotion regulation. Finally, based on clinical neuroscientific evidence on mindfulness, we open perspectives and dialogues regarding commonalities and differences between MBIs and other psychotherapeutic strategies for emotion regulation. PMID:28321194

Simulating clinical trial visits yields patient insights into study design and recruitment

Directory of Open Access Journals (Sweden)

Lim SS

2017-07-01

discussing SLE, emphasis on transportation and child care help during the visits, and concerns related to financial matters; and they placed greater importance on time commitment, understanding of potential personal benefit, trust, and confidentiality of patient data as factors for participation. Using these results, we present recommendations to improve study procedures to increase retention, recruitment, and compliance for clinical trials.Conclusion: Insights from these two studies can be applied to the development and implementation of future clinical trials to improve patient recruitment, retention, compliance, and advocacy. Keywords: systemic lupus erythematosus, lupus nephritis, clinical trial simulation, patient recruitment, patient retention

Effect modification, interaction and mediation: an overview of theoretical insights for clinical investigators

Directory of Open Access Journals (Sweden)

Corraini P

2017-06-01

Full Text Available Priscila Corraini,1 Morten Olsen,1 Lars Pedersen,1 Olaf M Dekkers,1,2 Jan P Vandenbroucke1–3 1Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Leiden University Medical Center, Leiden, the Netherlands; 3Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK Abstract: We revisited the three interrelated epidemiological concepts of effect modification, interaction and mediation for clinical investigators and examined their applicability when using research databases. The standard methods that are available to assess interaction, effect modification and mediation are explained and exemplified. For each concept, we first give a simple “best-case” example from a randomized controlled trial, followed by a structurally similar example from an observational study using research databases. Our explanation of the examples is based on recent theoretical developments and insights in the context of large health care databases. Terminology is sometimes ambiguous for what constitutes effect modification and interaction. The strong assumptions underlying the assessment of interaction, and particularly mediation, require clinicians and epidemiologists to take extra care when conducting observational studies in the context of health care databases. These strong assumptions may limit the applicability of interaction and mediation assessments, at least until the biases and limitations of these assessments when using large research databases are clarified. Keywords: methods, epidemiology, effect modifiers, stratified analyses, health care administrative claims

Chemical insight from density functional modeling of molecular adsorption: Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with molecular orbitals

Science.gov (United States)

Wyrick, Jonathan; Einstein, T. L.; Bartels, Ludwig

2015-03-01

We present a method of analyzing the results of density functional modeling of molecular adsorption in terms of an analogue of molecular orbitals. This approach permits intuitive chemical insight into the adsorption process. Applied to a set of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene, and 9,10-diselenonanthracene), we follow the electronic states of the molecules that are involved in the bonding process and correlate them to both the molecular adsorption geometry and the species' diffusive behavior. We additionally provide computational code to easily repeat this analysis on any system.

Stem Cell-Derived Exosome in Cardiovascular Diseases: Macro Roles of Micro Particles.

Science.gov (United States)

Yuan, Ye; Du, Weijie; Liu, Jiaqi; Ma, Wenya; Zhang, Lai; Du, Zhimin; Cai, Benzhi

2018-01-01

The stem cell-based therapy has emerged as the promising therapeutic strategies for cardiovascular diseases (CVDs). Recently, increasing evidence suggest stem cell-derived active exosomes are important communicators among cells in the heart via delivering specific substances to the adjacent/distant target cells. These exosomes and their contents such as certain proteins, miRNAs and lncRNAs exhibit huge beneficial effects on preventing heart damage and promoting cardiac repair. More importantly, stem cell-derived exosomes are more effective and safer than stem cell transplantation. Therefore, administration of stem cell-derived exosomes will expectantly be an alternative stem cell-based therapy for the treatment of CVDs. Furthermore, modification of stem cell-derived exosomes or artificial synthesis of exosomes will be the new therapeutic tools for CVDs in the future. In addition, stem cell-derived exosomes also have been implicated in the diagnosis and prognosis of CVDs. In this review, we summarize the current advances of stem cell-derived exosome-based treatment and prognosis for CVDs, including their potential benefits, underlying mechanisms and limitations, which will provide novel insights of exosomes as a new tool in clinical therapeutic translation in the future.

Review of Preclinical and Clinical Studies of Bone Marrow-Derived Cell Therapies for Intracerebral Hemorrhage

Directory of Open Access Journals (Sweden)

Paulo Henrique Rosado-de-Castro

2016-01-01

Full Text Available Stroke is the second leading cause of mortality worldwide, causing millions of deaths annually, and is also a major cause of disability-adjusted life years. Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a fatality rate of about 50% in the first 30 days, with limited treatment possibilities. In the past two decades, the therapeutic potential of bone marrow-derived cells (particularly mesenchymal stem cells and mononuclear cells has been intensively investigated in preclinical models of different neurological diseases, including models of intracerebral hemorrhage and subarachnoid hemorrhage. More recently, clinical studies, most of them small, unblinded, and nonrandomized, have suggested that the therapy with bone marrow-derived cells is safe and feasible in patients with ischemic or hemorrhagic stroke. This review discusses the available evidence on the use of bone marrow-derived cells to treat hemorrhagic strokes. Distinctive properties of animal studies are analyzed, including study design, cell dose, administration route, therapeutic time window, and possible mechanisms of action. Furthermore, clinical trials are also reviewed and discussed, with the objective of improving future studies in the field.

Neurobiological Basis of Insight in Schizophrenia: A Systematic Review.

Science.gov (United States)

Xavier, Rose Mary; Vorderstrasse, Allison

2016-01-01

Insight in schizophrenia is defined as awareness into illness, symptoms, and need for treatment and has long been associated with cognition, other psychopathological symptoms, and several adverse clinical and functional outcomes. However, the biological basis of insight is not clearly understood. The aim of this systematic review was to critically evaluate and summarize advances in the study of the biological basis of insight in schizophrenia and to identify gaps in this knowledge. A literature search of PubMed, CINAHL, PsycINFO, and EMBASE databases was conducted using search terms to identify articles relevant to the biology of insight in schizophrenia published in the last 6 years. Articles that focused on etiology of insight in schizophrenia and those that examined the neurobiology of insight in schizophrenia or psychoses were chosen for analysis. Articles on insight in conditions other than schizophrenia or psychoses and which did not investigate the neurobiological underpinnings of insight were excluded from the review. Twenty-six articles met the inclusion criteria for this review. Of the 26 articles, 3 focused on cellular abnormalities and 23 were neuroimaging studies. Preliminary data identify the prefrontal cortex, cingulate cortex, and regions of the temporal and parietal lobe (precuneus, inferior parietal lobule) and hippocampus as the neural correlates of insight. A growing body of literature attests to the neurobiological basis of insight in schizophrenia. Current evidence supports the neurobiological basis of insight in schizophrenia and identifies specific neural correlates for insight types and its dimensions. Further studies that examine the precise biological mechanisms of insight are needed to apply this knowledge to effective clinical intervention development.

Clinical impact of the immunome in lymphoid malignancies: the role of Myeloid-Derived Suppressor Cells

Directory of Open Access Journals (Sweden)

Calogero eVetro

2015-05-01

Full Text Available The better definition of the mutual sustainment between neoplastic cells and immune system has been translated from the bench to the bedside acquiring value as prognostic factor. Additionally, it represents a promising tool for improving therapeutic strategies. In this context, myeloid-derived suppressor cells have gained a central role in tumor developing with consequent therapeutic implications. In this review, we will focus on the biological and clinical impact of the study of myeloid-derived suppressor cells in the settings of lymphoid malignancies.

New Insights into the Surgical Management of Tetralogy of Fallot: Physiological Fundamentals and Clinical Relevance.

Science.gov (United States)

Bove, Thierry; François, Katrien; De Wolf, Daniel

2015-01-01

The surgical treatment of tetralogy of Fallot can be considered as a success story in the history of congenital heart diseases. Since the early outcome is no longer the main issue, the focus moved to the late sequelae of TOF repair, i.e. the pulmonary insufficiency and the secondary adaptation of the right ventricle. This review provides recent insights into the pathophysiological alterations of the right ventricle in relation to the reconstruction of the right ventricular outflow tract after repair of tetralogy of Fallot. Its clinical relevance is documented by addressing the policy changes regarding the optimal management at the time of surgical repair as well as properly defining criteria and timing for late pulmonary valve implantation.

Clinical insights into use of apomorphine in Parkinson's disease

DEFF Research Database (Denmark)

Henriksen, Tove

2014-01-01

is achieved a significant reduction of pre-existing levodopainduced dyskinesias is seen. The aim of this review is to give practical insight into apomorphine treatment, highlighting side effects, and complications and device-related problems are discussed with advice on how to prevent or handle these, should...

Relationship between insight and theory of mind in schizophrenia: A meta-analysis.

Science.gov (United States)

Bora, Emre

2017-12-01

Poor insight in schizophrenia has been associated with executive dysfunction and deficits in general cognitive ability. The overall outcome of available neurocognitive studies suggests that there is a significant but modest relationship between cognitive deficits and poor insight in schizophrenia. However, social cognitive abilities, particularly, theory of mind (ToM), might also play a role in poor insight in schizophrenia. A novel meta-analysis of the relationship between ToM and insight in schizophrenia was conducted. Current meta-analysis included 16 studies including 1085 patients with schizophrenia-spectrum disorders. There was a significant association between ToM and clinical insight (r=0.28, CI=0.20-0.36). By contrast, there was no significant relationship between ToM and cognitive insight. Current findings suggest that there is a small but significant relationship between ToM and clinical insight in schizophrenia. ToM impairment is one of the factors contributing to poor insight in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical outcomes after IVF or ICSI using human blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum.

Science.gov (United States)

Itoi, Fumiaki; Asano, Yukiko; Shimizu, Masashi; Nagai, Rika; Saitou, Kanako; Honnma, Hiroyuki; Murata, Yasutaka

2017-04-01

In this study the clinical and neo-natal outcomes after transfer of blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum (SER) were compared between IVF and intracytoplasmic sperm injection (ICSI) cycles. Clinical and neo-natal outcomes of blastocysts in cycles with at least one SER metaphase II oocyte (SER + MII; SER + cycles) did not significantly differ between the two insemination methods. When SER + MII were cultured to day 5/6, fertilization, embryo cleavage and blastocyst rates were not significantly different between IVF and ICSI cycles. In vitrified-warmed blastocyst transfer cycles, the clinical pregnancy rates from SER + MII in IVF and ICSI did not significantly differ. In this study, 52 blastocysts (27 IVF and 25 ICSI) derived from SER + MII were transferred, yielding 15 newborns (5 IVF and 10 ICSI) and no malformations. Moreover, 300 blastocysts (175 IVF and 125 ICSI) derived from SER-MII were transferred, yielding 55 newborns (24 IVF and 31 ICSI cycles). Thus, blastocysts derived from SER + cycles exhibited an acceptable ongoing pregnancy rate after IVF (n = 125) or ICSI (n = 117) cycles. In conclusion, blastocysts from SER + MII in both IVF and ICSI cycles yield adequate ongoing pregnancy rates with neo-natal outcomes that do not differ from SER-MII. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

A Multi-Center Prospective Derivation and Validation of a Clinical Prediction Tool for Severe Clostridium difficile Infection.

LENUS (Irish Health Repository)

Na, Xi

2015-04-23

Prediction of severe clinical outcomes in Clostridium difficile infection (CDI) is important to inform management decisions for optimum patient care. Currently, treatment recommendations for CDI vary based on disease severity but validated methods to predict severe disease are lacking. The aim of the study was to derive and validate a clinical prediction tool for severe outcomes in CDI.

Usefulness Of Derivative Instruments In Emerging Markets: Turkish Experience

OpenAIRE

Cem Saatcioglu; Iskender Karagul; Ara G. Volkan

2011-01-01

This article presents an overview of derivative markets, definitions of derivative investment instruments, development of global derivative markets and the applicability of derivative markets in Turkey, given their economic value added to the Turkish economy. Readers will acquire insight into investing in various investment instruments and hedging against risk. Turkish derivative markets will be described, supportive statistical data will be presented, and readers will be introduced to the de...

The geometrical precision of virtual bone models derived from clinical computed tomography data for forensic anthropology

NARCIS (Netherlands)

Colman, Kerri L.; Dobbe, Johannes G. G.; Stull, Kyra E.; Ruijter, Jan M.; Oostra, Roelof-Jan; van Rijn, Rick R.; van der Merwe, Alie E.; de Boer, Hans H.; Streekstra, Geert J.

2017-01-01

Almost all European countries lack contemporary skeletal collections for the development and validation of forensic anthropological methods. Furthermore, legal, ethical and practical considerations hinder the development of skeletal collections. A virtual skeletal database derived from clinical

Enhancement of human adipose-derived stem cell expansion and stability for clinical use

OpenAIRE

Krähenbühl, S. M.

2016-01-01

Co-culture techniques associating both dermal fibroblasts and epidermal keratinocytes have shown to have better clinical outcome than keratinocyte culture alone for the treatment of severe burns. Since fat grafting has been shown to improve scar remodelling, new techniques such as cell-therapy-assisted surgical reconstruction with isolated and expanded autologous adipose-derived stem cells (ASCs) would be of benefit to increase graft acceptation. Therefore, integrating ASCs into s...

Implementing the new clinical nurse leader role while gleaning insights from the past.

Science.gov (United States)

Moore, Linda Weaver; Leahy, Cathy

2012-01-01

This qualitative study explored the experiences of clinical nurse leaders (CNLs) as they implemented this new role. Twenty-four CNLs participated. Data were collected via an e-mail-distributed questionnaire. Data from open-ended questions were used to conduct a qualitative content analysis. Data were categorized according to question, key thoughts and phrases were established, and themes were determined. Findings revealed that nonsystematic role introduction was common. Two challenges to role implementation included role confusion and being overworked. The most positive aspect of the role was remaining close to the point of care. Participants noted that the overall response of the health care team to the role was positive despite participants' belief that the greatest roadblock to role success was the lack of support by nurse administrators. The support of nurse administrators and clear role expectations were viewed as essential for role sustain-ability. Understanding the experiences of CNLs as they launch this new role can provide insights for educators, administrators, CNLs, and other health care providers regarding the success and sustainability of the role. In addition, understanding the similarities between the clinical nurse specialist (CNS) role initiation in the past and the CNL role initiation today can foster the development of strategies for confronting the challenges of new role implementation. Copyright © 2012 Elsevier Inc. All rights reserved.

Role of Mesenchymal-Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical Metastases

Science.gov (United States)

2017-07-01

Clinical Metastases PRINCIPAL INVESTIGATOR: Rosandra Kaplan CONTRACTING ORGANIZATION: The Geneva Foundation Tacoma, WA 98402 REPORT DATE: July 2017...2017 4. TITLE AND SUBTITLE Role of Mesenchymal-Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical Metastases 5a...PRODUCTS:  publications, conference papers, and presentations ; Jennifer Zhu submitted an abstract and will present this work at the Annual

Role of Mesenchymal Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical Metastases

Science.gov (United States)

2017-07-01

Clinical Metastases PRINCIPAL INVESTIGATOR: Jeffrey Green CONTRACTING ORGANIZATION: The Geneva Foundation Tacoma, WA 98402 REPORT DATE: July 2017 TYPE...2016 - 14 June 2017 4. TITLE AND SUBTITLE Role of Mesenchymal-Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical ...and/or select agents. Nothing to report. 6. PRODUCTS: • publications, conference papers, and presentations ; Jennifer Zhu submitted an abstract and will

Empirical Derivation and Validation of a Clinical Case Definition for Neuropsychological Impairment in Children and Adolescents.

Science.gov (United States)

Beauchamp, Miriam H; Brooks, Brian L; Barrowman, Nick; Aglipay, Mary; Keightley, Michelle; Anderson, Peter; Yeates, Keith O; Osmond, Martin H; Zemek, Roger

2015-09-01

Neuropsychological assessment aims to identify individual performance profiles in multiple domains of cognitive functioning; however, substantial variation exists in how deficits are defined and what cutoffs are used, and there is no universally accepted definition of neuropsychological impairment. The aim of this study was to derive and validate a clinical case definition rule to identify neuropsychological impairment in children and adolescents. An existing normative pediatric sample was used to calculate base rates of abnormal functioning on eight measures covering six domains of neuropsychological functioning. The dataset was analyzed by varying the range of cutoff levels [1, 1.5, and 2 standard deviations (SDs) below the mean] and number of indicators of impairment. The derived rule was evaluated by bootstrap, internal and external clinical validation (orthopedic and traumatic brain injury). Our neuropsychological impairment (NPI) rule was defined as "two or more test scores that fall 1.5 SDs below the mean." The rule identifies 5.1% of the total sample as impaired in the assessment battery and consistently targets between 3 and 7% of the population as impaired even when age, domains, and number of tests are varied. The NPI rate increases in groups known to exhibit cognitive deficits. The NPI rule provides a psychometrically derived method for interpreting performance across multiple tests and may be used in children 6-18 years. The rule may be useful to clinicians and scientists who wish to establish whether specific individuals or clinical populations present within expected norms versus impaired function across a battery of neuropsychological tests.

Implications of Derived Rule Following of Roulette Gambling for Clinical Practice.

Science.gov (United States)

Wilson, Alyssa N; Grant, Tara

2015-05-01

Problem gambling is a global concern, and behavior analytic attention has increasingly focused on reasons for why problem gambling occurs and conditions under which it is maintained. However, limited knowledge currently exists on the process to which self-generated rules maintain gambling behaviors. Therefore, the current study assessed six recreational gamblers on a roulette game before and after discrimination training to establish a self-rule to wager on red or black. Following discrimination training, all six participants altered their response allocation among red or black and consistently responded according to the newly derived self-rule. Results maintained during 1-week follow-up sessions across all participants. Implications for clinical application of self-awareness and self-generated rule following are discussed. Implications for practice • Demonstration of how stimuli such as color can alter gambling behavior • Procedures to assist clients with changing self-rules about gambling behavior • Using self-generated rule formulation for more contextually appropriate target behaviors • Highlights how self-generated rules can be altered to change clinical target behaviors.

INSIGHT AGONISTES: A READING OF SOPHOCLES'S OEDIPUS THE KING.

Science.gov (United States)

Mahon, Eugene J

2015-07-01

In this reading of Sophocles's Oedipus the King, the author suggests that insight can be thought of as the main protagonist of the tragedy. He personifies this depiction of insight, calling it Insight Agonistes, as if it were the sole conflicted character on the stage, albeit masquerading at times as several other characters, including gods, sphinxes, and oracles. This psychoanalytic reading of the text lends itself to an analogy between psychoanalytic process and Sophocles's tragic hero. The author views insight as always transgressing against, always at war with a conservative, societal, or intrapsychic chorus of structured elements. A clinical vignette is presented to illustrate this view of insight. © 2015 The Psychoanalytic Quarterly, Inc.

The relationship between theory of mind and insight in obsessive-compulsive disorder.

Science.gov (United States)

Tulacı, Rıza Gökçer; Cankurtaran, Eylem Şahin; Özdel, Kadir; Öztürk, Nefise; Kuru, Erkan; Özdemir, İlker

2018-02-09

It is known that obsessive-compulsive disorder (OCD) patients with poor insight display more severe neuropsychological impairments than other patients with OCD. There are limited studies of OCD and theory of mind (ToM). To investigate ToM skills in patients with OCD and the relationship between insight and ToM skills by comparing OCD patients with good and poor insight. Eighty patients with OCD and 80 healthy controls completed the structured clinical interview for DSM-IV axis I disorders, the Yale Brown Obsessive-Compulsive Scale, the Beck Anxiety and Beck Depression Inventories, and the Brown Assessment of Beliefs Scale. To assess ToM skills, first- and second-order false-belief tests, a hinting test, a faux pas test, a reading the mind in the eyes test, and a double-bluff test were administered. Patients with OCD had poorer ToM abilities than healthy controls. All ToM scores were significantly lower in the poor insight group than in the good insight group (p insight than in OCD with good insight may contribute to the idea of OCD with poor insight being a subtype with different clinical and neuropsychological characteristics.

Hospitals - HOSPITALS_HAZUS_IN: Hospitals and Clinics in Indiana, Derived from HAZUS (Federal Emergency Management Agency, Point Shapefile)

Data.gov (United States)

NSGIC State | GIS Inventory — HOSPITALS_HAZUS_IN is a point shapefile that shows locations of hospitals and clinics in Indiana. HOSPITALS_HAZUS_IN was derived from the shapefile named "HOSPITAL."...

Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

Directory of Open Access Journals (Sweden)

Tetsuya Ishii

2014-10-01

Full Text Available Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.

How doctors learn: the role of clinical problems across the medical school-to-practice continuum.

Science.gov (United States)

Slotnick, H B

1996-01-01

The author proposes a theory of how physicians learn that uses clinical problem solving as its central feature. His theory, which integrates insights from Maslow, Schön, Norman, and others, claims that physicians-in-training and practicing physicians learn largely by deriving insights from clinical experience. These insights allow the learner to solve future problems and thereby address the learner's basic human needs for security, affiliation, and self-esteem. Ensuring that students gain such insights means that the proper roles of the teacher are (1) to select problems for students to solve and offer guidance on how to solve them, and (2) to serve as a role model of how to reflect on the problem, its solution, and the solution's effectiveness. Three principles guide instruction within its framework for learning: (1) learners, whether physicians-in-training or practicing physicians, seek to solve problems they recognize they have; (2) learners want to be involved in their own learning; and (3) instruction must both be time-efficient and also demonstrate the range of ways in which students can apply what they learn. The author concludes by applying the theory to an aspect of undergraduate education and to the general process of continuing medical education.

Insight and subjective measures of quality of life in chronic schizophrenia.

Science.gov (United States)

Siu, Cynthia O; Harvey, Philip D; Agid, Ofer; Waye, Mary; Brambilla, Carla; Choi, Wing-Kit; Remington, Gary

2015-09-01

Lack of insight is a well-established phenomenon in schizophrenia, and has been associated with reduced rater-assessed functional performance but increased self-reported well-being in previous studies. The objective of this study was to examine factors that might influence insight (as assessed by the Insight and Treatment Attitudes Questionnaire [ITAQ] or PANSS item G12) and subjective quality-of-life (as assessed by Lehman QoL Interview [LQOLI]), using the large National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset. Uncooperativeness was assessed by PANSS item G8 ("Uncooperativeness"). In the analysis, we found significant moderating effects for insight on the relationships of subjective life satisfaction assessment to symptom severity (as assessed by CGI-S score), objective everyday functioning (as assessed by rater-administered Heinrichs-Carpenter Quality of Life scale), clinically rated uncooperativeness (as assessed by PANSS G8), and discontinuation of treatment for all causes (all P > 0.05 for statistical interaction between insight and subject QoL). Patients with chronic schizophrenia who reported being "pleased" or "delighted" on LQOLI were found to have significantly lower neurocognitive reasoning performance and poorer insight (ITAQ total score). Our findings underscore the importance of reducing cognitive and insight impairments for both treatment compliance and improved functional outcomes.

How self-reflection and self-certainty are related to neurocognitive functioning: an examination of cognitive insight in bipolar disorder.

Science.gov (United States)

Van Camp, L S C; Oldenburg, J F E; Sabbe, B G C

2016-01-01

The pattern of associations between clinical insight, cognitive insight, and neurocognitive functioning was assessed in bipolar disorder patients. Data from 42 bipolar disorder patients were examined. Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS). The BCIS is a 15-item self-report instrument consisting of two subscales, self-reflectiveness and self-certainty. Clinical insight was measured by the use of the item G12 of the Positive and Negative Syndrome Scale. Neurocognitive functioning was assessed using the International Society for Bipolar Disorders-Battery for Assessment of Neurocognition. Correlation analyses revealed significant positive associations between self-reflectiveness and speed of processing, attention, working memory, visual learning, and reasoning and problem solving. The subscale self-certainty was negatively correlated to working memory, however, this correlation disappeared when we controlled for confounding variables. No correlations between clinical insight and neurocognition were found. In addition, there was no association between cognitive insight and clinical insight. Better neurocognitive functioning was more related to higher levels of self-reflectiveness than to diminished self-certainty.

Insight into mental illness and child maltreatment risk among mothers with major psychiatric disorders.

Science.gov (United States)

Mullick, M; Miller, L J; Jacobsen, T

2001-04-01

This study examined the relationship between insight into mental illness and current child maltreatment risk among mothers who had a major psychiatric disorder and who had lost custody of a child because of abuse, neglect, or having placed the child at risk of harm. Specifically, a measure of insight was examined in relation to systematically observed parenting behaviors known to be correlated with past child maltreatment and in relation to a comprehensive clinical determination of risk. Forty-four mothers who had a major psychiatric disorder were independently rated for their insight into their illness, the quality of mother-child interaction, and the overall clinical risk of maltreatment. Better insight into mental illness was associated with more sensitive mothering behavior and with lower assessed clinical risk of maltreatment. The association remained when mothers with current psychotic symptoms were excluded from the analyses. Better insight did not appear to be associated with past psychotic symptoms, maternal psychiatric diagnosis, or the mother's level of education. Insight into mental illness may function as a protective factor that influences the risk of child maltreatment in mothers with mental illness. Measures of insight could be usefully incorporated into comprehensive parenting assessments for mothers with psychiatric disorders.

Association of global weather changes with acute coronary syndromes: gaining insights from clinical trials data

Science.gov (United States)

Bakal, Jeffrey A.; Ezekowitz, Justin A.; Westerhout, Cynthia M.; Boersma, Eric; Armstrong, Paul W.

2013-05-01

The aim of this study was to develop a method for the identification of global weather parameters and patient characteristics associated with a type of heart attack in which there is a sudden partial blockage of a coronary artery. This type of heart attack does not demonstrate an elevation of the ST segment on an electrocardiogram and is defined as a non-ST elevation acute coronary syndrome (NSTE-ACS). Data from the Global Summary of the Day database was linked with the enrollment and baseline data for a phase III international clinical trial in NSTE-ACS in four 48-h time periods covering the week prior to the clinical event that prompted enrollment in the study. Meteorological events were determined by standardizing the weather data from enrollment dates against an empirical distribution from the month prior. These meteorological events were then linked to the patients' geographic region, demographics and comorbidities to identify potential susceptible populations. After standardization, changes in temperature and humidity demonstrated an association with the enrollment event. Additionally there appeared to be an association with gender, region and a history of stroke. This methodology may provide a useful global insight into assessing the biometeorologic component of diseases from international data.

The “Insight Paradox” in Schizophrenia: Magnitude, Moderators and Mediators of the Association Between Insight and Depression

Science.gov (United States)

Belvederi Murri, Martino; Amore, Mario; Calcagno, Pietro; Respino, Matteo; Marozzi, Valentina; Masotti, Mattia; Bugliani, Michele; Innamorati, Marco; Pompili, Maurizio; Galderisi, Silvana; Maj, Mario

2016-01-01

The so-called “insight paradox” posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia. PMID:27069064

Oligodendrocyte differentiation and implantation : new insights for remyelinating cell therapy

NARCIS (Netherlands)

Sher, Falak; Balasubramaniyan, Veerakumar; Boddeke, Erik; Copray, Sjef

2008-01-01

Purpose of review Recent research on oligodendrocyte development has yielded new insights on the involvement of morphogens and differentiation factors in oligodendrogenesis. This knowledge has improved strategies to control neural stem cell-derived oligodendrocyte differentiation and functional

Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system.

Science.gov (United States)

Adamson, Philip B; Magalski, Anthony; Braunschweig, Frieder; Böhm, Michael; Reynolds, Dwight; Steinhaus, David; Luby, Allyson; Linde, Cecilia; Ryden, Lars; Cremers, Bodo; Takle, Teri; Bennett, Tom

2003-02-19

This study examined the characteristics of continuously measured right ventricular (RV) hemodynamic information derived from an implantable hemodynamic monitor (IHM) in heart failure patients. Hemodynamic monitoring might improve the day-to-day management of patients with chronic heart failure (CHF). Little is known about the characteristics of long-term hemodynamic information in patients with CHF or how such information relates to meaningful clinical events. Thirty-two patients with CHF received a permanent RV IHM system similar to a single-lead pacemaker. Right ventricular systolic and diastolic pressures, heart rate, and pressure derivatives were continuously measured for nine months without using the data for clinical decision-making or management of patients. Data were then made available to clinical providers, and the patients were followed up for 17 months. Pressure characteristics during optimal volume, clinically determined volume-overload exacerbations, and volume depletion events were examined. The effect of IHM on hospitalizations was examined using the patients' historical controls. Long-term RV pressure measurements had either marked variability or minimal time-related changes. During 36 volume-overload events, RV systolic pressures increased by 25 +/- 4% (p < 0.05) and heart rate increased by 11 +/- 2% (p < 0.05). Pressure increases occurred in 9 of 12 events 4 +/- 2 days before the exacerbations requiring hospitalization. Hospitalizations before using IHM data for clinical management averaged 1.08 per patient year and decreased to 0.47 per patient-year (57% reduction, p < 0.01) after hemodynamic data were used. Long-term ambulatory pressure measurements from an IHM may be helpful in guiding day-to-day clinical management, with a potentially favorable impact on CHF hospitalizations.

Insight and illness perception in Mexican patients with psychosis

Directory of Open Access Journals (Sweden)

Lizzette Gómez-de-Regil

2015-03-01

Conclusions: The study not only replicates the significant association on insight and illness perception with clinical outcome, but shows how their patterns of interactions are different, reinforcing the idea that they are two distinct factors worthy of being habitually acknowledged in research and clinical practice.

Implicit and explicit self-related processing in relation to insight in patients with schizophrenia

NARCIS (Netherlands)

de Vos, Annerieke E.; Pijnenborg, Gerdina H. M.; Aleman, Andre; van der Meer, Lisette

2015-01-01

Introduction. Self-related processing (SRP) has been associated with clinical and cognitive insight. We investigated the relationship between implicit SRP (ISRP) and explicit SRP (ESRP) and insight. We first hypothesised that impaired insight is associated with the extent to which implicit feedback

Derivation of xeno-free and GMP-grade human embryonic stem cells--platforms for future clinical applications.

Directory of Open Access Journals (Sweden)

Shelly E Tannenbaum

Full Text Available Clinically compliant human embryonic stem cells (hESCs should be developed in adherence to ethical standards, without risk of contamination by adventitious agents. Here we developed for the first time animal-component free and good manufacturing practice (GMP-compliant hESCs. After vendor and raw material qualification, we derived xeno-free, GMP-grade feeders from umbilical cord tissue, and utilized them within a novel, xeno-free hESC culture system. We derived and characterized three hESC lines in adherence to regulations for embryo procurement, and good tissue, manufacturing and laboratory practices. To minimize freezing and thawing, we continuously expanded the lines from initial outgrowths and samples were cryopreserved as early stocks and banks. Batch release criteria included DNA-fingerprinting and HLA-typing for identity, characterization of pluripotency-associated marker expression, proliferation, karyotyping and differentiation in-vitro and in-vivo. These hESCs may be valuable for regenerative therapy. The ethical, scientific and regulatory methodology presented here may serve for development of additional clinical-grade hESCs.

Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo

OpenAIRE

Clémence Roux; Clémence Roux; Clémence Roux; Gaëlle Saviane; Gaëlle Saviane; Jonathan Pini; Jonathan Pini; Nourhène Belaïd; Nourhène Belaïd; Gihen Dhib; Gihen Dhib; Christine Voha; Christine Voha; Christine Voha; Lidia Ibáñez

2018-01-01

Despite mesenchymal stromal cells (MSCs) are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited in vitro expansion, absence of a full phenotypic characterization, few insights on their in vivo fate). Standardized MSCs derived in vitro from human-induced pluripotent stem (huIPS) cells, remediating part of these issues, are considered as well as a valuable tool for th...

[Poor insight and psychosis].

Science.gov (United States)

Giotakos, O

2017-01-01

A variety of phenomena might be considered as reflecting impaired insight in psychosis, like failure to recognize signs, symptoms or disease, failure to derive appropriate cognitive representations, despite recognition of the disease, and misattribution of the source or cause of the disease. The unawareness of tardive dyskinesia symptoms in schizophrenic patients points that self-awareness deficits in schizophrenia may be domain specific. Poor insight is an independent phenomenological and a prevalent feature in psychotic disorders in general, and in schizophrenia in particular, but we don't know yet if delusions in schizophrenia are the result of an entirely normal attempt to account for abnormal perceptual experiences or a product of abnormal experience but of normal reasoning. The theoretical approaches regarding impaired insight include the disturbed perceptual input, the impaired linkage between thought and emotion and the breakdown of the process of self-monitoring and error checking. The inability to distinguish between internally and externally generated mental events has been described by the metarepresentation theory. This theory includes the awareness of ones' goals, which leads to disorders of willed action, the awareness of intention, which leads to movement disorders, and the awareness of intentions of others, which leads to paranoid delusions. The theory of metarepresentation implies mainly output mechanisms, like the frontal cortex, while the input mechanism implies posterior brain systems, including the parietal lobe. There are many similarities between the disturbances of awareness seen in schizophrenia and those seen as a result of known neurological impairment. Neuropsychological models of impaired insight typically attribute the disturbance to any of a variety of core deficits in the processing of information. In this respect, lack of insight is on conceptual par with alogia, apraxia or aphasia in reflecting disturbed cognitive processing. In

The "Insight Paradox" in Schizophrenia: Magnitude, Moderators and Mediators of the Association Between Insight and Depression.

Science.gov (United States)

Belvederi Murri, Martino; Amore, Mario; Calcagno, Pietro; Respino, Matteo; Marozzi, Valentina; Masotti, Mattia; Bugliani, Michele; Innamorati, Marco; Pompili, Maurizio; Galderisi, Silvana; Maj, Mario

2016-09-01

The so-called "insight paradox" posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved

Clinical insights on Tolosa Hunt syndrome: A multidisciplinary approach on neurological-related symptomatology in maxillofacial region

Directory of Open Access Journals (Sweden)

Zafar Ali Khan

2018-02-01

Full Text Available Background Tolosa–Hunt syndrome (THS related neurological symptoms are described in literature as “unilateral”, “recurrent”, “episodic”, “intense”, “severe”, “lancinating” or “stabbing” pain on the upper face and forehead and may be misdiagnosed due to the similarity of few symptoms and a significant number of common characteristics between both conditions. Aims The aim of this brief report is to indicate some important clinical insights related to Tolosa Hunt syndrome, and to give a frank account on the multidisciplinary approach on neurological-related symptomatology in maxillofacial region. Methods We analysed a selection of patients with such clinical picture. To better describe the proper management of clinical cases, we report a 50-year-old female reporting an history of two years of recurrent, severe stabbing pain around the right eye, prominence of her cheek and forehead. Her general dentist first mistakenly diagnosed toothache and, thus, it was subsequently misdiagnosed the trigeminal neuropathy (TN. Results Reported exemplificative case presented a mild ptosis, diplopia of the right eye, corneal reflex loss, paresthesia and hyperesthesia of upper part of left side of face. Magnetic resonance imaging (MRI findings were suggestive of THS. Complete resolution of symptoms was achieved with oral Prednisolone and constant monitoring of symptoms. Conclusion THS may be added to the long list of differential diagnosis of TN and general dentist and oral surgeons should be informed about such rare causes of facial pain through continued medical education programs.

The relationship between cognitive insight and depression in psychosis and schizophrenia: a review and meta-analysis.

Science.gov (United States)

Palmer, Emma C; Gilleen, James; David, Anthony S

2015-08-01

Lack of insight is a commonly observed problem in patients with psychosis and schizophrenia. Clinical insight in patients has been associated with low mood. Cognitive insight is a recently defined concept, relating to the ability to self-reflect and the degree to which patients are over-confident regarding their interpretations of illness-related experiences, and is related to clinical insight. We therefore sought to investigate whether there is a positive relationship between cognitive insight and mood. A literature search identified 17 relevant papers published between 2004 and 2014. Our analysis indicated that there was a small but significant positive correlation between the composite index (CI) of the Beck Cognitive Insight Scale (BCIS) and depression scores, but this was driven by a significant positive relationship between depression and the BCIS self-reflection (SR) sub-scale, where low mood was related to higher SR scores. There was no significant relationship between the self-certainty sub-scale and depression. Post-hoc analysis indicated that different depression scales did not significantly affect the relationship with SR. Our results support the idea that cognitive insight is significantly related to mood in schizophrenia, and the effect size is similar to that between clinical insight and mood. Potential applications of this knowledge into treatment and rehabilitation are discussed and a model of cognitive insight is proposed. Copyright © 2015 Elsevier B.V. All rights reserved.

Exploring the link between clinical managers involvement in budgeting and performance: Insights from the Italian public health care sector.

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Macinati, Manuela S; Rizzo, Marco G

2016-01-01

The public health care sector has had an increase in initiatives, mostly inspired by New Public Management principles, aimed at assigning financial accountability to clinical managers. However, clinical managers might experience a scarce alignment between professional values and organizational requirements, which is a potentially important phenomena that may result in negative consequences on clinical managers' job performance. Building on Psychological Ownership Theory and adopting a psychology-based management accounting research approach, we focus on the managerial (nonmedical) role the clinical manager fulfills and explore the budgetary participation-performance link via the indirect effects of job-based psychological ownership, role clarity, and clinical managers' affective commitment toward managerial roles. The data were collected by a survey conducted in an Italian hospital. The research hypotheses were tested employing a path model. Our study revealed new insights that shed some light on underexplored processes through which mental states mediate the participation-performance link. Among these latter, the findings demonstrate that (a) budgetary participation has a direct effect on job-based psychological ownership; (b) role clarity mediates participation- and job-based psychological ownership link; (c) role clarity and job-based psychological ownership partially mediate the participation-commitment link; and (d) job-based psychological ownership, role clarity, and commitment fully mediate the participation-performance link. From a managerial viewpoint, an understanding of how clinical managers' feelings of ownership toward managerial roles could be enhanced is imperative in health care because ownership accounts for important attitudinal and organizational consequences. Results suggest that health care organizations that invest in budgetary participation will directly and indirectly affect clinical managers' psychological ownership, and this, along with

[Relationship of insight with depression and suicidal ideation in psychotic disorders].

Science.gov (United States)

Patelaros, E; Zournatzis, E; Kontstantakopoulos, G

2015-01-01

The associations of insight into psychosis (i.e., awareness of illness) with clinical variables have been examined by a great number of studies. Most of these studies revealed that the level of insight is negatively correlated with psychotic symptoms but positively correlated with depression and suicidal ideation. The aim of this study was to test these findings in a Greek sample of patients. Forty-three outpatients (30 men and 13 women) with schizophrenia or delusional disorder being followed up at the Mental Health Centre of Kavala took part in the study. Patients with bipolar or schizoaffective disorder were excluded. Patients' mean age was 40.7 years and the mean duration of illness was 18.67 years. All participants were under treatment and clinically stable at the time of the study. We used the Positive and Negative Syndrome Scale (PANSS) for the assessment of positive and negative symptoms, the Schedule for the Assessment of Insight-Expanded (SAI-E) to assess the insight into psychosis, and the Montgomery-Asberg Depression Rating Scale (MADRS) for the evaluation of depression recording separately the score for item 10 as an estimate of suicidal ideation. All the scales used have been adapted to Greek population. We used Spearman rho coefficient to assess the strength of correlations between the scales because the distributions of some scores were not normal. In order to assess the predictive value of insight for depression and suicidal ideation, we used hierarchical linear regression analysis. Correlation coefficients between SAI-E and the clinical scales of psychopathology, depression and suicide ideation was statistically significant at the pregression analysis showed that our model of positive and negative psychopathology and insight explained 47.4% of the variance of depression and 32.2% of the variance of suicidal ideation. The predictive value of insight was critically important, because only after the introduction of the SAI-E score in the analysis our

Insights from Human/Mouse genome comparisons

Energy Technology Data Exchange (ETDEWEB)

Pennacchio, Len A.

2003-03-30

Large-scale public genomic sequencing efforts have provided a wealth of vertebrate sequence data poised to provide insights into mammalian biology. These include deep genomic sequence coverage of human, mouse, rat, zebrafish, and two pufferfish (Fugu rubripes and Tetraodon nigroviridis) (Aparicio et al. 2002; Lander et al. 2001; Venter et al. 2001; Waterston et al. 2002). In addition, a high-priority has been placed on determining the genomic sequence of chimpanzee, dog, cow, frog, and chicken (Boguski 2002). While only recently available, whole genome sequence data have provided the unique opportunity to globally compare complete genome contents. Furthermore, the shared evolutionary ancestry of vertebrate species has allowed the development of comparative genomic approaches to identify ancient conserved sequences with functionality. Accordingly, this review focuses on the initial comparison of available mammalian genomes and describes various insights derived from such analysis.

Therapeutic alliance in schizophrenia: the role of recovery orientation, self-stigma, and insight.

Science.gov (United States)

Kvrgic, Sara; Cavelti, Marialuisa; Beck, Eva-Marina; Rüsch, Nicolas; Vauth, Roland

2013-08-30

The present study examined variables related to the quality of the therapeutic alliance in out-patients with schizophrenia. We expected recovery orientation and insight to be positively, and self-stigma to be negatively associated with a good therapeutic alliance. We expected these associations to be independent from age, clinical symptoms (i.e. positive and negative symptoms, depression), and more general aspects of relationship building like avoidant attachment style and the duration of treatment by the current therapist. The study included 156 participants with DSM-IV diagnoses of schizophrenia or schizoaffective disorder in the maintenance phase of treatment. Therapeutic alliance, recovery orientation, self-stigma, insight, adult attachment style, and depression were assessed by self-report. Symptoms were rated by interviewers. Hierarchical multiple regressions revealed that more recovery orientation, less self-stigma, and more insight independently were associated with a better quality of the therapeutic alliance. Clinical symptoms, adult attachment style, age, and the duration of treatment by current therapist were unrelated to the quality of the therapeutic alliance. Low recovery orientation and increased self-stigma might undermine the therapeutic alliance in schizophrenia beyond the detrimental effect of poor insight. Therefore in clinical settings, besides enhancing insight, recovery orientation, and self-stigma should be addressed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Noninvasive FFR derived from coronary CT angiography in the management of coronary artery disease: technology and clinical update

Directory of Open Access Journals (Sweden)

Nakanishi R

2016-06-01

Full Text Available Rine Nakanishi, Mathew J Budoff Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA Abstract: After a decade of clinical use of coronary computed tomographic angiography (CCTA to evaluate the anatomic severity of coronary artery disease, new methods of deriving functional information from CCTA have been developed. These methods utilize the anatomic information provided by CCTA in conjunction with computational fluid dynamics to calculate fractional flow reserve (FFR values from CCTA image data sets. Computed tomography-derived FFR (CT-FFR enables the identification of lesion-specific drop noninvasively. A three-dimensional CT-FFR modeling technique, which provides FFR values throughout the coronary tree (HeartFlow FFRCT analysis, has been validated against measured FFR and is now approved by the US Food and Drug Administration for clinical use. This technique requires off-site supercomputer analysis. More recently, a one-dimensional computational analysis technique (Siemens cFFR, which can be performed on on-site workstations, has been developed and is currently under investigation. This article reviews CT-FFR technology and clinical evidence for its use in stable patients with suspected coronary artery disease. Keywords: fractional flow reserve, coronary computed tomographic angiography, FFRCT, cFFR

Base-metal dental casting alloy biocompatibility assessment using a human-derived three-dimensional oral mucosal model.

LENUS (Irish Health Repository)

McGinley, E L

2012-01-01

Nickel-chromium (Ni-Cr) alloys used in fixed prosthodontics have been associated with type IV Ni-induced hypersensitivity. We hypothesised that the full-thickness human-derived oral mucosa model employed for biocompatibility testing of base-metal dental alloys would provide insights into the mechanisms of Ni-induced toxicity. Primary oral keratinocytes and gingival fibroblasts were seeded onto Alloderm™ and maintained until full thickness was achieved prior to Ni-Cr and cobalt-chromium (Co-Cr) alloy disc exposure (2-72 h). Biocompatibility assessment involved histological analyses with cell viability measurements, oxidative stress responses, inflammatory cytokine expression and cellular toxicity analyses. Inductively coupled plasma mass spectrometry analysis determined elemental ion release levels. We detected adverse morphology with significant reductions in cell viability, significant increases in oxidative stress, inflammatory cytokine expression and cellular toxicity for the Ni-Cr alloy-treated oral mucosal models compared with untreated oral mucosal models, and adverse effects were increased for the Ni-Cr alloy that leached the most Ni. Co-Cr demonstrated significantly enhanced biocompatibility compared with Ni-Cr alloy-treated oral mucosal models. The human-derived full-thickness oral mucosal model discriminated between dental alloys and provided insights into the mechanisms of Ni-induced toxicity, highlighting potential clinical relevance.

Biblical Leadership: Insights for Today's Managers

OpenAIRE

Friedman, Hershey H.; Friedman, Linda

2004-01-01

The scholarly literature in management has paid little attention to the study of Biblical figures as leaders. This paper aims to advance the effort to fill this gap by demonstrating that many insights about successful and unsuccessful leadership may be derived from the Bible. Successful leaders demonstrated a willingness to be different, a passion for justice, humility, and a concern for others. Unsuccessful leaders were sidetracked from their mission by the hunger for power or by lust and envy.

A cross-sectional study of insight and family accommodation in pediatric obsessive-compulsive disorder

Science.gov (United States)

2013-01-01

Background Factors predicting treatment outcome in pediatric patients with obsessive-compulsive disorder (OCD) include disease severity, functional impairment, comorbid disorders, insight, and family accommodation (FA). Treatment of pediatric OCD is often only partly successful as some of these predictors are not targeted with conventional therapy. Among these, insight and FA were identified to be modifiable predictors of special relevance to pediatric OCD. Despite their clinical relevance, insight and FA remain understudied in youth with OCD. This study examined the clinical correlates of insight and FA and determined whether FA mediates the relationship between symptom severity and functional impairment in pediatric OCD. Methods This was a cross-sectional, outpatient study. Thirty-five treatment-naive children and adolescentswith DSM-IV diagnosis of OCD (mean age: 13.11 ± 3.16; 54.3% males) were included. Standard questionnaires were administered for assessing the study variables. Insight and comorbidities were assessed based on clinician’s interview. Subjects were categorized as belonging to a high insight or a low insight group, and the differences between these two groups were analyzed using ANOVA. Pearson’s correlation coefficients were calculated for the remaining variables of interest. Mediation analysis was carried out using structural equation modeling. Results Relative to those in the high insight group, subjects in the low insight group were younger, had more severe disease and symptoms, and were accommodated to a greater extent by their families. In addition, comorbid depression was more frequent in subjects belonging to the low insight group. Family accommodation was positively related to disease severity, symptom severity, and functional impairment. Family accommodation totally mediated the relationship between symptom severity and functional impairment. Conclusions Results support the differences in the diagnostic criteria between adult and

Self-stigma and its relationship with insight, demoralization, and clinical outcome among people with schizophrenia spectrum disorders.

Science.gov (United States)

Cavelti, Marialuisa; Kvrgic, Sara; Beck, Eva-Marina; Rüsch, Nicolas; Vauth, Roland

2012-07-01

Paradoxically, insight is associated with positive outcomes, such as better treatment adherence and recovery, and negative outcomes, such as depression, hopelessness, low self-esteem, and quality of life. Self-stigma as a moderating variable can be decisive whether more insight leads to better or worse outcome. On the other hand, self-stigma can act as a mediator between insight and outcomes. We therefore examined self-stigma both as a moderator and a mediator. Insight, self-stigma, demoralization, symptoms, and functioning were assessed among 145 outpatients with schizophrenia spectrum disorders using questionnaires and structured interviews. Structural equation modeling was used to analyze the cross-sectional data. Results confirmed self-stigma as a moderator: The association of insight and demoralization was stronger as self-stigma increased. Self-stigma also partially mediated the positive relationship between insight and demoralization. Moreover, demoralization fully mediated the adverse associations of self-stigma with psychotic symptoms and global functioning. Given the decisive role of self-stigma regarding the detrimental consequences of insight, interventions should address self-stigma, particularly if psychoeducational or other interventions have increased insight. Therapeutic implications for changes of dysfunctional beliefs related to illness and self and change of self-concept in the context of recovery at the level of narrative identity are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Microbicide clinical trial adherence: insights for introduction.

Science.gov (United States)

Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena

2013-04-08

After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.

Nanotech-derived topical microbicides for HIV prevention: the road to clinical development.

Science.gov (United States)

Sánchez-Rodríguez, Javier; Vacas-Córdoba, Enrique; Gómez, Rafael; De La Mata, F Javier; Muñoz-Fernández, Ma Ángeles

2015-01-01

More than three decades since its discovery, HIV infection remains one of the most aggressive epidemics worldwide, with more than 35 million people infected. In sub-Saharan Africa, heterosexual transmissions represent nearly 80% of new infections, with 50% of these occurring in women. In an effort to stop the dramatic spread of the HIV epidemic, new preventive treatments, such as microbicides, have been developed. Nanotechnology has revolutionized this field by designing and engineering novel highly effective nano-sized materials as microbicide candidates. This review illustrates the most recent advances in nanotech-derived HIV prevention strategies, as well as the main steps required to translate promising in vitro results into clinical trials. Copyright © 2014 Elsevier B.V. All rights reserved.

Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment

NARCIS (Netherlands)

Molendijk, M.L.; Bus, B.A.A.; Spinhoven, P.; Penninx, B.W.J.H.; Kenis, G.; Prickaerts, J.; Voshaar, R.C.O.; Elzinga, B.M.

2011-01-01

Recent evidence supports 'the neurotrophin hypothesis of depression' in its prediction that brain-derived neurotrophic factor (BDNF) is involved in depression. However, some key questions remain unanswered, including whether abnormalities in BDNF persist beyond the clinical state of depression,

Insight into the chiral induction in supramolecular stacks through preferential chiral salvation

NARCIS (Netherlands)

George, S.J.; Tomovic, Z.; Schenning, A.P.H.J.; Meijer, E.W.

2011-01-01

Preferred handedness in the supramolecular chirality of self-assembled achiral oligo(p-phenylenevinylene) (OPV) derivatives is induced by chiral solvents and spectroscopic probing provides insight into the mechanistic aspects of this chiral induction through chiral solvation

Clinical Impact of the Immunome in Lymphoid Malignancies: The Role of Myeloid-Derived Suppressor Cells

Science.gov (United States)

Vetro, Calogero; Romano, Alessandra; Ancora, Flavia; Coppolino, Francesco; Brundo, Maria V.; Raccuia, Salvatore A.; Puglisi, Fabrizio; Tibullo, Daniele; La Cava, Piera; Giallongo, Cesarina; Parrinello, Nunziatina L.

2015-01-01

The better definition of the mutual sustainment between neoplastic cells and immune system has been translated from the bench to the bedside acquiring value as prognostic factor. Additionally, it represents a promising tool for improving therapeutic strategies. In this context, myeloid-derived suppressor cells (MDSCs) have gained a central role in tumor developing with consequent therapeutic implications. In this review, we will focus on the biological and clinical impact of the study of MDSCs in the settings of lymphoid malignancies. PMID:26052505

Effectiveness of bovine-derived xenograft versus bioactive glass with periodontally accelerated osteogenic orthodontics in adults: a randomized, controlled clinical trial.

Science.gov (United States)

Bahammam, Maha A

2016-11-30

Periodontally accelerated osteogenic orthodontics (PAOO) combines periodontal therapy with orthodontic therapy, which minimises treatment time. This study compared the effectiveness of a bovine-derived xenograft with that of bioactive glass when combined with PAOO for the treatment of adult patients with moderate crowding of the teeth. In this prospective, single-masked clinical trial, 33 orthodontic patients (20 women, 13 men; mean age 21.2 ± 1.43 [18 - 27] years), were randomly allocated to one of three groups. Group 1 underwent a modified corticotomy technique on the labial side only, whereas group 2 was treated with the same technique combined with PAOO using a bovine-derived xenograft and group 3 was treated in the same way but combining PAOO with bioactive glass. The total treatment duration was recorded from the start of active orthodontic treatment, immediately after corticotomy, and at the time of debonding. Probing depth was evaluated clinically and bone density and root length were evaluated radiographically on the day of surgery (baseline, T1), post-treatment at debonding (T2), and 9 months post-treatment (T3). The duration of orthodontic treatment was markedly reduced to an average of 11.4 ± 0.14 weeks in all groups. All probing depths were orthodontic treatment and periodontal surgery is an effective treatment for adult patients that decreases the duration of active treatment and reduces the risk of root resorption. Use of a bovine-derived xenograft with modified corticotomy provided superior benefits in terms of increased bone density than did the use of bioactive glass. The study was retrospectively registered at ClinicalTrials.gov under Clinical Trial Registration Number: NCT02796911 .

Recapitulation of Clinical Individual Susceptibility to Drug-Induced QT Prolongation in Healthy Subjects Using iPSC-Derived Cardiomyocytes

Directory of Open Access Journals (Sweden)

Tadahiro Shinozawa

2017-02-01

Full Text Available To predict drug-induced serious adverse events (SAE in clinical trials, a model using a panel of cells derived from human induced pluripotent stem cells (hiPSCs of individuals with different susceptibilities could facilitate major advancements in translational research in terms of safety and pharmaco-economics. However, it is unclear whether hiPSC-derived cells can recapitulate interindividual differences in drug-induced SAE susceptibility in populations not having genetic disorders such as healthy subjects. Here, we evaluated individual differences in SAE susceptibility based on an in vitro model using hiPSC-derived cardiomyocytes (hiPSC-CMs as a pilot study. hiPSCs were generated from blood samples of ten healthy volunteers with different susceptibilities to moxifloxacin (Mox-induced QT prolongation. Different Mox-induced field potential duration (FPD prolongation values were observed in the hiPSC-CMs from each individual. Interestingly, the QT interval was significantly positively correlated with FPD at clinically relevant concentrations (r > 0.66 in multiple analyses including concentration-QT analysis. Genomic analysis showed no interindividual significant differences in known target-binding sites for Mox and other drugs such as the hERG channel subunit, and baseline QT ranges were normal. The results suggest that hiPSC-CMs from healthy subjects recapitulate susceptibility to Mox-induced QT prolongation and provide proof of concept for in vitro preclinical trials.

Insight in psychosis: Standards, science, ethics and value judgment.

Science.gov (United States)

Jacob, K S

2017-06-01

The clinical assessment of insight solely employs biomedical perspectives and criteria to the complete exclusion of context and culture and to the disregard of values and value judgments. The aim of this discussion article is to examine recent research from India on insight and explanatory models in psychosis and re-examine the framework of assessment, diagnosis and management of insight and explanatory models. Recent research from India on insight in psychosis and explanatory models is reviewed. Recent research, which has used longitudinal data and adjusted for pretreatment variables, suggests that insight and explanatory models of illness at baseline do not predict course, outcome and treatment response in schizophrenia, which seem to be dependent on the severity and quality of the psychosis. It supports the view that people with psychosis simultaneously hold multiple and contradictory explanatory models of illness, which change over time and with the trajectory of the illness. It suggests that insight, like all explanatory models, is a narrative of the person's reality and a coping strategy to handle with the varied impact of the illness. This article argues that the assessment of insight necessarily involves value entailments, commitments and consequences. It supports a need for a broad-based approach to assess awareness, attribution and action related to mental illness and to acknowledge the role of values and value judgment in the evaluation of insight in psychosis.

Unraveling the insight paradox: One-year longitudinal study on the relationships between insight, self-stigma, and life satisfaction among people with schizophrenia spectrum disorders.

Science.gov (United States)

Chio, Floria H N; Mak, Winnie W S; Chan, Randolph C H; Tong, Alan C Y

2018-01-30

The promotion of insight among people with schizophrenia spectrum disorders has posed a dilemma to service providers as higher insight has been linked to positive clinical outcomes but negative psychological outcomes. The negative meaning that people attached to the illness (self-stigma content) and the recurrence of such stigmatizing thoughts (self-stigma process) may explain why increased insight is associated with negative outcomes. The present study examined how the presence of high self-stigma content and self-stigma process may contribute to the negative association between insight and life satisfaction. A total of 181 people with schizophrenia spectrum disorders were assessed at baseline. 130 and 110 participants were retained and completed questionnaire at 6-month and 1-year follow-up, respectively. Results showed that baseline insight was associated with lower life satisfaction at 6-month when self-stigma process or self-stigma content was high. Furthermore, baseline insight was predictive of better life satisfaction at 1-year follow-up when self-stigma process was low. Findings suggested that the detrimental effects of insight can be a result from both the presence of cognitive content and habitual process of self-stigma. Future insight promotion interventions should also address self-stigma content and process among people with schizophrenia spectrum disorders so as to maximize the beneficial effects of insight. Copyright © 2018 Elsevier B.V. All rights reserved.

The Neurocircuitry of Impaired Insight in Drug Addiction

Science.gov (United States)

Goldstein, Rita Z.; Craig, A. D. (Bud); Bechara, Antoine; Garavan, Hugh; Childress, Anna Rose; Paulus, Martin P.; Volkow, Nora D.

2010-01-01

More than 80% of addicted individuals fail to seek treatment, which might reflect impairments in recognition of severity of disorder. Considered by some as intentional deception, such `denial' might instead reflect dysfunction of brain networks subserving insight and selfawareness. Here we review the scant literature on insight in addiction and integrate this perspective with the role of: (i) the insula in interoception, self-awareness and drug craving; (ii) the anterior cingulate in behavioral monitoring and response selection (relevant to disadvantageous choices in addiction); (iii) the dorsal striatum in automatic habit formation; and (iv) drug related stimuli that predict emotional behavior in addicted individuals, even without conscious awareness. We discuss implications for clinical treatment including the design of interventions to improve insight into illness severity in addiction. PMID:19716751

The Neurocircuitry of Impaired Insight in Drug Addiction

Energy Technology Data Exchange (ETDEWEB)

Goldstein, R.Z.; Craig, A.D.; Bechara, A.; Garavan, H.; Childress, A.R.; Paulus, M.P.; Volkow, N.D.

2009-08-27

More than 80% of addicted individuals fail to seek treatment, which might reflect impairments in recognition of severity of disorder. Considered by some as intentional deception, such 'denial' might instead reflect dysfunction of brain networks subserving insight and self-awareness. Here we review the scant literature on insight in addiction and integrate this perspective with the role of: (i) the insula in interoception, self-awareness and drug craving; (ii) the anterior cingulate in behavioral monitoring and response selection (relevant to disadvantageous choices in addiction); (iii) the dorsal striatum in automatic habit formation; and (iv) drug-related stimuli that predict emotional behavior in addicted individuals, even without conscious awareness. We discuss implications for clinical treatment including the design of interventions to improve insight into illness severity in addiction.

Reduced Connectivity in the Self-Processing Network of Schizophrenia Patients with Poor Insight

NARCIS (Netherlands)

Liemburg, Edith J.; van der Meer, Lisette; Swart, Marte; Curcic-Blake, Branislava; Bruggeman, Richard; Knegtering, Henderikus; Aleman, Andre

2012-01-01

Lack of insight (unawareness of illness) is a common and clinically relevant feature of schizophrenia. Reduced levels of self-referential processing have been proposed as a mechanism underlying poor insight. The default mode network (DMN) has been implicated as a key node in the circuit for

Insight, Neurocognition, and Schizophrenia: Predictive Value of the Wisconsin Card Sorting Test

Science.gov (United States)

Yanos, Philip T.

2013-01-01

Lack of insight in schizophrenia is a key feature of the illness and is associated with both positive and negative clinical outcomes. Previous research supports that neurocognitive dysfunction is related to lack of insight, but studies have not examined how neurocognition relates to change in insight over time. Therefore, the current study sought to understand how performance on the Wisconsin Card Sorting Test (WCST) differed between participants with varying degrees of change in insight over a 6-month period. Fifty-two patients with schizophrenia or schizoaffective disorder were administered the WCST and Positive and Negative Syndrome Scale (PANSS) at baseline, and the PANSS was again administered at a 6-month follow-up assessment. Results indicated that while neurocognition was related to insight at baseline, it was not related to subsequent change in insight. The implications of findings for conceptualization and assessment of insight are discussed. PMID:24303216

Is good insight associated with depression among patients with schizophrenia? Systematic review and meta-analysis.

Science.gov (United States)

Belvederi Murri, Martino; Respino, Matteo; Innamorati, Marco; Cervetti, Alice; Calcagno, Pietro; Pompili, Maurizio; Lamis, Dorian A; Ghio, Lucio; Amore, Mario

2015-03-01

Among patients with schizophrenia, better insight may be associated with depression, but the findings on this issue are mixed. We examined the association between insight and depression in schizophrenia by conducting a systematic review and meta-analysis. The meta-analysis was based on 59 correlational studies and showed that global clinical insight was associated weakly, but significantly with depression (effect size r=0.14), as were the insight into the mental disorder (r=0.14), insight into symptoms (r=0.14), and symptoms' attributions (r=0.17). Conversely, neither insight into the social consequences of the disorder nor into the need for treatment was associated with symptoms of depression. Better cognitive insight was significantly associated with higher levels of depression. The exploratory meta-regression showed that methodological factors (e.g. the instrument used to assess depression and the phase of the illness) can significantly influence the magnitude of the association between insight and depression. Moreover, results from longitudinal studies suggest that the relation between insight and depression might be stronger than what is observed at the cross-sectional level. Finally, internalized stigma, illness perception, recovery attitudes, ruminative style, and premorbid adjustment seem to be relevant moderators and/or mediators of the association between insight and depression. In conclusion, literature indicates that among patients with schizophrenia, better insight is associated with higher levels of depressive symptoms. Thus, interventions aimed at promoting patients' insight should take into account the clinical implications of these findings. Copyright © 2015 Elsevier B.V. All rights reserved.

Modeling neurodegenerative diseases with patient-derived induced pluripotent cells: Possibilities and challenges.

Science.gov (United States)

Poon, Anna; Zhang, Yu; Chandrasekaran, Abinaya; Phanthong, Phetcharat; Schmid, Benjamin; Nielsen, Troels T; Freude, Kristine K

2017-10-25

The rising prevalence of progressive neurodegenerative diseases coupled with increasing longevity poses an economic burden at individual and societal levels. There is currently no effective cure for the majority of neurodegenerative diseases and disease-affected tissues from patients have been difficult to obtain for research and drug discovery in pre-clinical settings. While the use of animal models has contributed invaluable mechanistic insights and potential therapeutic targets, the translational value of animal models could be further enhanced when combined with in vitro models derived from patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls generated using CRISPR-Cas9 mediated genome editing. The iPSCs are self-renewable and capable of being differentiated into the cell types affected by the diseases. These in vitro models based on patient-derived iPSCs provide the opportunity to model disease development, uncover novel mechanisms and test potential therapeutics. Here we review findings from iPSC-based modeling of selected neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and spinocerebellar ataxia. Furthermore, we discuss the possibilities of generating three-dimensional (3D) models using the iPSCs-derived cells and compare their advantages and disadvantages to conventional two-dimensional (2D) models. Copyright © 2017 Elsevier B.V. All rights reserved.

Methodological inaccuracies in clinical aortic valve severity assessment: insights from computational fluid dynamic modeling of CT-derived aortic valve anatomy

Science.gov (United States)

Traeger, Brad; Srivatsa, Sanjay S.; Beussman, Kevin M.; Wang, Yechun; Suzen, Yildirim B.; Rybicki, Frank J.; Mazur, Wojciech; Miszalski-Jamka, Tomasz

2016-04-01

Aortic stenosis is the most common valvular heart disease. Assessing the contribution of the valve as a portion to total ventricular load is essential for the aging population. A CT scan for one patient was used to create one in vivo tricuspid aortic valve geometry and assessed with computational fluid dynamics (CFD). CFD simulated the pressure, velocity, and flow rate, which were used to assess the Gorlin formula and continuity equation, current clinical diagnostic standards. The results demonstrate an underestimation of the anatomic orifice area (AOA) by Gorlin formula and overestimation of AOA by the continuity equation, using peak velocities, as would be measured clinically by Doppler echocardiography. As a result, we suggest that the Gorlin formula is unable to achieve the intended estimation of AOA and largely underestimates AOA at the critical low-flow states present in heart failure. The disparity in the use of echocardiography with the continuity equation is due to the variation in velocity profile between the outflow tract and the valve orifice. Comparison of time-averaged orifice areas by Gorlin and continuity with instantaneous orifice areas by planimetry can mask the errors of these methods, which is a result of the assumption that the blood flow is inviscid.

Comparative Evaluation of the Antimicrobial Efficacy of Three Immersion Chemical Disinfectants on Clinically Derived Poly(Vinyl Siloxane) Impressions.

Science.gov (United States)

Jeyapalan, Vidhya; Krishnan, Chitra Shankar; Ramasubramanian, Hariharan; Sampathkumar, Jayakrishnakumar; Azhagarasan, N S; Krishnan, Madhusudan

2016-07-06

To comparatively evaluate the antimicrobial efficacy of freshly prepared electrolyzed oxidizing water (EOW) with that of 2.4% glutaraldehyde (GA) and 1% sodium hypochlorite (SH) on clinically derived poly vinyl siloxane (PVS) impressions. Four clinically derived PVS impressions each were obtained from 10 subjects. One impression from each subject was randomly kept as control (group I), without disinfection. The remaining three impressions were randomly disinfected by immersion in either 2.4% GA (group II), 1% SH (group III), or freshly prepared EOW (group IV). The samples were subjected to microbial culture individually on brain heart infusion (BHI) agar medium. The organisms isolated were confirmed by visual examination and gram staining. Mean colony forming units (CFU) were counted, log 10 reduction obtained and compared. Data were statistically analyzed using one-way ANOVA, followed by multiple comparisons using Tukey-HSD post hoc tests (p < 0.05). Streptococci, Staphylococci, Pseudomonas, Candida, Proteus, Klebsiella, and E. coli were isolated from all impressions including the controls, except those disinfected by EOW. All three disinfectants showed significant reduction in CFU and log 10 reduction values as compared to the controls. EOW showed significantly higher reduction in log 10 values compared to GA and SH, whereas GA and SH showed similar reductions. EOW, GA, and SH showed kill rates of 100%, 99.60%, and 99.82%, respectively. EOW showed significant antimicrobial efficacy as evidenced by reduction in log 10 values when used as an immersion disinfectant for PVS impressions when compared with the results obtained using GA and SH. These results need further investigation. EOW shows high antimicrobial efficacy when used as an immersion disinfectant as compared to GA and SH for clinically derived PVS impressions. © 2016 by the American College of Prosthodontists.

Insights from an overview of four PRAs

International Nuclear Information System (INIS)

Fitzpatrick, R.; Arrieta, L.; Teichmann, T.; Davis, P.

1987-01-01

This paper summarizes the findings of an investigation of four probabilistic risk assessments (PRAs), those for Millstone 3 Seabrook, Shoreham, and Oconee 3, performed by Brookhaven National Laboratory (BNL) for the Reliability and Risk Assessment branch of the U.S. Nuclear Regulatory Commission (NRC). This group of four PRAs was subjected to an overview process with the basic goal of ascertaining what insights might be gained (beyond those already documented within the individual PRAs) by an independent evaluation of the group with respect to nuclear plant safety and vulnerability. Specifically, the objectives of the study were 1) to identify and rank initiators, systems, components, and failure modes from dominant accident sequences according to their contribution to core melt probability and public risk; and 2) to derive from this process plant-specific and generic insights. The effort was not intended to verify the specific details and results of each PRA but rather - having accepted the results - to see what they might mean in a more global context. This paper also presents some comments and insights into the amenability of certain features of these PRAs to this type of overview process

Surveillance of illness associated with pandemic (H1N1) 2009 virus infection among adults using a global clinical site network approach: the INSIGHT FLU 002 and FLU 003 studies

DEFF Research Database (Denmark)

Dwyer, Dominic E; Gerstoft, Jan

2011-01-01

, with 1049 enrollments into the FLU 002 outpatient study and 316 into the FLU 003 hospitalization study. These 'in progress' INSIGHT influenza observational studies may act as a model for obtaining epidemiological, clinical and laboratory information in future international disease outbreaks....

Insights into the illegal trade of feline derivatives in Costa Rica

Directory of Open Access Journals (Sweden)

Jennifer Rebecca Kelly, Ph.D.

2018-01-01

Full Text Available Research has given the illegal trade of feline derivatives in Mexico as well as Central and South America little attention. The purpose of this article is to: 1 Begin a dialogue among human dimensions of wildlife scholars about the economic and cultural values of feline derivatives throughout Mexico, Central and South America; 2 Present the range of economic values that emerged in my interview and participant observation data from Costa Rica; 3 Offer an explanation of how sociological concepts influence the buying and selling of dead jaguars (Panthera onca, pumas (Puma concolor, and ocelots (Leopardus pardalis in Costa Rica. The principal results are: 1 The sociological concepts of social status and masculine identity interlace with and motivate the illegal trade; 2 The value of feline parts in Costa Rica ranges from $25 to $5000; 3 This value differs by culture and geographic residency of the seller (urban versus rural and diverged from values discovered in other countries; 4 The men who adorn their homes with illegal trophies are not necessarily the poachers. The value of jaguar skin has been recorded for as little as $100 in a 1983 study conducted in Belize and for as high as $600 in a study done in Venezuela in approximately 2011. Because of cultural differences, Cabécar sell a feline skin for as little as $25 and up to $400 if it includes teeth and nails, but Ticos, who are non-indigenous Costa Ricans, sell the skins from $500-$5000. Non-indigenous, wealthy urban men indicate prestige by the display of feline parts. My findings align with existing research that jaguar skins are sold to people in larger cities and that adornment of feline derivatives is a masculine tradition that can be linked with Amerindian cultures and ancient times. Historically jaguars have been associated with elitist symbolism and evidence in this study suggests this continues in today's culture as a sign of social status. Results suggest that money alone does not

Issues and insights of PRA methodology in nuclear and space applications

International Nuclear Information System (INIS)

Hsu, F.

2005-01-01

This paper presents some important issues and technical insights on the scope, conceptual framework, and essential elements of nuclear power plant Probabilistic Risk Assessments (PRAs) and that of the PRAs in general applications of the aerospace industry, such as the Space Shuttle PRA being conducted by NASA. Discussions are focused on various lessons learned in nuclear power plant PRA applications and their potential applicability to the PRAs in the aerospace and launch vehicle systems. Based on insights gained from PRA projects for nuclear power plants and from the current Space Shuttle PRA effort, the paper explores the commonalities and the differences between the conduct of the different PRAs and the key issues and risk insights derived from extensive modeling practices in both industries of nuclear and space. (author)

Narrative insight in psychosis: The relationship with spiritual and religious explanatory frameworks.

Science.gov (United States)

Marriott, Michael R; Thompson, Andrew R; Cockshutt, Graham; Rowse, Georgina

2018-03-25

When considering psychosis, the concept of narrative insight has been offered as an alternative to clinical insight in determining individuals' responses to their difficulties, as it allows for a more holistic and person-centred framework to be embraced within professional practice. This study aims to explore the validity of the narrative insight construct within a group of people who have experienced psychosis. Inductive qualitative methods were used to explore how eight participants utilized spiritual or religious explanatory frameworks for their experiences of psychosis and to consider these in relation to the construct of narrative insight. Semi-structured interviews were undertaken with individuals who identified themselves as interested in spiritual or religious ideas and whose self-reported experiences which were identified as akin to psychosis by experienced academic clinicians. Transcriptions from these interviews were subject to interpretative phenomenological analysis within a broader research question; a selection of themes and data from the resultant phenomenological structure are explored here for their relevance to narrative insight. Participants discussed spiritual and biological explanations for their experiences and were able to hold alternative potential explanations alongside each other. They were reflective regarding the origins of their explanations and would describe a process of testing and proof in relation to them. These findings suggest that the narrative insight construct has the potential to be a valid approach to understanding experiences of psychosis, and challenge the dominance of the clinical insight construct within clinical practice. Clinicians should value the explanatory framework for experiences which are provided by individuals experiencing psychosis, and encourage them to develop a framework which is coherent to their own world view rather than predominantly pursuing a biomedical explanation. Assessments of psychosis should

The relationship between insight and the level of expressed emotion in patients with obsessive-compulsive disorder.

Science.gov (United States)

Ozkiris, Ayse; Essizoglu, Altan; Gulec, Gulcan; Aksaray, Gokay

2015-04-01

The aim of this study is firstly to compare the obsessive-compulsive disorder (OCD) patients with good insight and OCD patients with poor insight in terms of socio-demographic and clinical features; to investigate the relation between insight and the level of the expressed emotion (EE) in the patients; and lastly to specify the factors that predict level of insight. OCD patients with good insight and patients with poor insight were compared in terms of clinical features and the perceived EE level of the patients and the individuals that they live with in order to specify the factors that predict the insight level, and to investigate the relationship between insight level and EE. It was found that the total Expressed Emotion Scale, total Level of Expressed Emotion (LEE), LEE-Emotional Response and LEE-Tolerance/Expectation subscale scores of the group comprised of patients with poor insight are higher than the other group. The results also show that the duration of illness and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score predict insight level. This study shows that the level of EE perceived by the patients with poor insight and the person that he/she lives with, is higher than the group with good insight. The studies that investigate the relationship between the factors of insight level and EE level, which are indicated to determine the level of the illness severity and its chronicity, will enable the researchers to understand the importance of the role of the family on the treatment processes of OCD.

A Cross-sectional, Comparative Study of Insight in Schizophrenia and Bipolar Patients in Remission.

Science.gov (United States)

Ramachandran, Arul Saravanan; Ramanathan, Rajkumar; Praharaj, Samir Kumar; Kanradi, Haridas; Sharma, Podila Satya Venkata Narasimha

2016-01-01

To study insight correlates in schizophrenia and bipolar mood disorder in remission among out-patients attending the Psychiatry Department of a Tertiary Care Hospital. In a cross-sectional, naturalistic study, adult patients with schizophrenia and bipolar mood disorder in remission (n = 80; schizophrenia-40, mania-20, bipolar depression-20) were compared on insight measures and clinical correlates. Scale to Assess the Unawareness of Mental Disorders (SUMD) was used as the main tool to assess current and past measures of insight. Hogan's Drug Attitude Inventory was used to assess the drug attitude and compliance. Positive and Negative Symptom Scale for Schizophrenia, Young's Mania Rating Scale, and HAMD were used to rate psychopathology. Clinical Global Improvement was used as a screening tool for remission. For comparison of the three clinical groups, analysis of variance and Chi-square test were used. In the post-hoc analysis, the Ryan-Einot-Gabriel-Welsch test was used to find the group difference. About 40% in the schizophrenia group were unaware of their mental illness as against none in the bipolar group. The awareness of mental disorder for the current period, the awareness of the achieved effects of medications, and the awareness of social consequence was better in the bipolar group. The drug attitude (compliant positive attitude) increased as the SUMD item scale decreased or in other words, as the insight improved. Insight, both current and retrospect, showed significant differences between the schizophrenia and bipolar patients. Insight is significantly correlated with the observed compliance and drug attitude of the patient groups.

Philosophers assess randomized clinical trials: the need for dialogue.

Science.gov (United States)

Miké, V

1989-09-01

In recent years a growing number of professional philosophers have joined in the controversy over ethical aspects of randomized clinical trials (RCTs). Morally questionable in their utilitarian approach, RCTs are claimed by some to be in direct violation of the second form of Kant's Categorical Imperative. But the arguments used in these critiques at times derive from a lack of insight into basic statistical procedures and the realities of the biomedical research process. Presented to physicians and other nonspecialists, including the lay public, such distortions can be harmful. Given the great complexity of statistical methodology and the anomalous nature of concepts of evidence, more sustained input into the interdisciplinary dialogue is needed from the statistical profession.

Clinical Insights Into Foveal Morphology in Albinism.

Science.gov (United States)

McCafferty, Brandon K; Wilk, Melissa A; McAllister, John T; Stepien, Kimberly E; Dubis, Adam M; Brilliant, Murray H; Anderson, Jennifer L; Carroll, Joseph; Summers, C Gail

2015-01-01

A hallmark of albinism is foveal hypoplasia. However, literature suggests variable foveal development. This study evaluates the association between ocular phenotype and foveal morphology to demonstrate the broad structural and functional spectrum. Best-corrected visual acuity (BCVA), nystagmus, angle kappa, stereoacuity, iris transillumination, macular melanin presence, foveal avascular zone, and annular reflex were recorded in 14 patients with albinism. Spectral-domain optical coherence tomography provided macular images. The clinical phenotype was broad, with BCVA varying from 20/20 to 20/100. Better BCVA was associated with a preserved foveal avascular zone, annular macular reflex, stereoacuity, and macular melanin. Imaging demonstrated a continuum of foveal development correlating with BCVA. Individuals with a rudimentary pit had normal inner and outer segment lengthening and better BCVA. The spectrum of ocular structure and visual function in albinism is broad, suggesting a possible diagnosis of albinism in a patient with an even more normal clinical presentation. Copyright 2015, SLACK Incorporated.

Electrophysiological properties and calcium handling of embryonic stem cell-derived cardiomyocytes

Directory of Open Access Journals (Sweden)

Jae Boum Youm

2016-03-01

Full Text Available Embryonic stem cell-derived cardiomyocytes (ESC-CMs hold great interest in many fields of research including clinical applications such as stem cell and gene therapy for cardiac repair or regeneration. ESC-CMs are also used as a platform tool for pharmacological tests or for investigations of cardiac remodeling. ESC-CMs have many different aspects of morphology, electrophysiology, calcium handling, and bioenergetics compared with adult cardiomyocytes. They are immature in morphology, similar to sinus nodal-like in the electrophysiology, higher contribution of trans-sarcolemmal Ca2+ influx to Ca2+ handling, and higher dependence on anaerobic glycolysis. Here, I review a detailed electrophysiology and Ca2+ handling features of ESC-CMs during differentiation into adult cardiomyocytes to gain insights into how all the developmental changes are related to each other to display cardinal features of developing cardiomyocytes.

Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening.

Science.gov (United States)

Sharma, Arun; Wu, Joseph C; Wu, Sean M

2013-12-24

Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. However, ongoing issues such as cell immaturity, scale of production, inter-line variability, and cell purity will need to be resolved before human clinical trials can begin. Meanwhile, the use of hiPSCs to explore cellular mechanisms of cardiovascular diseases in vitro has proven to be extremely valuable. For example, hiPSC-CMs have been shown to recapitulate disease phenotypes from patients with monogenic cardiovascular disorders. Furthermore, patient-derived hiPSC-CMs are now providing new insights regarding drug efficacy and toxicity. This review will highlight recent advances in utilizing hiPSC-CMs for cardiac disease modeling in vitro and as a platform for drug validation. The advantages and disadvantages of using hiPSC-CMs for drug screening purposes will be explored as well.

Insight and white matter fractional anisotropy in first-episode schizophrenia.

Science.gov (United States)

Asmal, Laila; du Plessis, Stefan; Vink, Matthijs; Fouche, Jean-Paul; Chiliza, Bonginkosi; Emsley, Robin

2017-05-01

Impaired insight is a hallmark feature of schizophrenia. Structural studies implicate predominantly prefrontal, cingulate, cuneus/precuneus, and inferior temporal brain regions. The cortical midline structures (CMS) are also implicated in functional studies primarily through self-reflective processing tasks. However, few studies have explored the relationship between white matter tracts and insight in schizophrenia, and none in first-episode schizophrenia (FES). Here, we examined for fractional anisotropy (FA) differences in 89 minimally treated FES patients and 98 matched controls, and identified those FA differences associated with impaired clinical insight in patients. We found widespread FA reduction in FES patients compared to controls. Poorer insight in patients was predicted by lower FA values in a number of white matter tracts with a predilection for tracts associated with cortical midline structures (fronto-occipital, cingulate, cingulate hippocampus, uncinate, anterior corona radiata), and more severe depressive symptoms. The association between FA abnormalities and insight was most robust for the awareness of symptoms and illness awareness domains. Our study implicates a network of tracts involved in impaired insight in schizophrenia with a predilection for the CMS. This study is a first step in delineating the white matter tracts involved in insight impairment in schizophrenia prior to chronicity. Copyright © 2016. Published by Elsevier B.V.

Clinical and morphological evaluation of snake venom derived fibrin glue on the tendon healing in dogs

Directory of Open Access Journals (Sweden)

G. C. Ferraro

2005-12-01

Full Text Available The aim of this study was to evaluate the effect of snake venom derived fibrin glue on the healing of the deep digital flexor tendon, during three periods. The tendon of the 2nd digit of 30 thoracic limbs of dogs was partially sectioned for glue application. Biopsies were performed 7, 15, and 30 days post surgery for the clinical and morphological study of tendons. Analysis of the results showed that 73.3% of the tendons showed stump retraction and 16.6% moderate to excessive adherence, which affected sliding. There was a significant difference in the number of inflammatory cells among the three studied periods, being the highest on day 15. The morphological analysis revealed a typical tendon healing process with a lower level of inflammation in the acute phase, facilitating the cicatricial maturation phase. Snake venom derived fibrin glue promotes the healing in dog flexor tendon.

O conceito do insight em pacientes com transtorno obsessivo-compulsivo The concept of insight in patients with obsessive-compulsive disorder

Directory of Open Access Journals (Sweden)

Júlia M. Fontenelle

2010-03-01

review of recent studies led us to identify some issues that cast doubts over the existence of a clear-cut poor insight subtype of obsessive-compulsive disorder. These issues include 1 an extremely variable prevalence of poor insight obsessive-compulsive disorder in categorical studies, 2 a significant degree of homogeneity in the phenotypical findings (i.e. greater severity associated with lower levels of insight in obsessive-compulsive disorder in both categorical and dimensional studies and, 3 a lack of studies investigating zones of rarity between poor and good insight obsessive-compulsive disorder. CONCLUSION: Although a categorical approach to the insight issue in obsessive-compulsive disorder is still important in clinical settings, where decision-making is often a critical issue, a dimensional approach seems to reflect levels of impairment in these patients more reliably.

Empirically derived personality subtyping for predicting clinical symptoms and treatment response in bulimia nervosa.

Science.gov (United States)

Haynos, Ann F; Pearson, Carolyn M; Utzinger, Linsey M; Wonderlich, Stephen A; Crosby, Ross D; Mitchell, James E; Crow, Scott J; Peterson, Carol B

2017-05-01

Evidence suggests that eating disorder subtypes reflecting under-controlled, over-controlled, and low psychopathology personality traits constitute reliable phenotypes that differentiate treatment response. This study is the first to use statistical analyses to identify these subtypes within treatment-seeking individuals with bulimia nervosa (BN) and to use these statistically derived clusters to predict clinical outcomes. Using variables from the Dimensional Assessment of Personality Pathology-Basic Questionnaire, K-means cluster analyses identified under-controlled, over-controlled, and low psychopathology subtypes within BN patients (n = 80) enrolled in a treatment trial. Generalized linear models examined the impact of personality subtypes on Eating Disorder Examination global score, binge eating frequency, and purging frequency cross-sectionally at baseline and longitudinally at end of treatment (EOT) and follow-up. In the longitudinal models, secondary analyses were conducted to examine personality subtype as a potential moderator of response to Cognitive Behavioral Therapy-Enhanced (CBT-E) or Integrative Cognitive-Affective Therapy for BN (ICAT-BN). There were no baseline clinical differences between groups. In the longitudinal models, personality subtype predicted binge eating (p = 0.03) and purging (p = 0.01) frequency at EOT and binge eating frequency at follow-up (p = 0.045). The over-controlled group demonstrated the best outcomes on these variables. In secondary analyses, there was a treatment by subtype interaction for purging at follow-up (p = 0.04), which indicated a superiority of CBT-E over ICAT-BN for reducing purging among the over-controlled group. Empirically derived personality subtyping appears to be a valid classification system with potential to guide eating disorder treatment decisions. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:506-514). © 2016 Wiley Periodicals, Inc.

Clinical and Radiographic Evaluation of the Effectiveness of Formocresol, Mineral Trioxide Aggregate, Portland Cement, and Enamel Matrix Derivative in Primary Teeth Pulpotomies: A Two Year Follow-Up.

Science.gov (United States)

Yildirim, Ceren; Basak, Feridun; Akgun, Ozlem Marti; Polat, Gunseli Guven; Altun, Ceyhan

2016-01-01

The aim of this study was to evaluate and to compare clinical and radiographic outcomes of 4 materials (formocresol, mineral trioxide aggregate (MTA), Portland cement and enamel matrix derivative) using in primary teeth pulpotomies. Sixty-five patients aged 5-9 years (32 female, 33 male) were included in this study. A total of 140 primary first and second molars with deep caries were treated with pulpotomy. All teeth were then restored with stainless steel crowns. The treated teeth were evaluated clinically and radiographically at 3, 6, 12, 18 and 24 months. At 24 months, the clinical success rates of formocresol, MTA, Portland cement, and enamel matrix derivative were 96.9%, 100%, 93.9%, and 93.3%, respectively. The corresponding radiographic success rates were 84.4%, 93.9%, 86.7% and 78.1%, respectively. Although there were no statistically significant differences in clinical and radiographic success rates among the 4 groups, MTA appears to be superior to formocresol, Portland cement, and enamel matrix derivative as a pulpotomy agent in primary teeth.

Students' Assessment and Self-assessment of Nursing Clinical Faculty Competencies: Important Feedback in Clinical Education?

Science.gov (United States)

Lovrić, Robert; Prlić, Nada; Zec, Davor; Pušeljić, Silvija; Žvanut, Boštjan

2015-01-01

The students' assessment of clinical faculty competencies and the faculty members' self-assessment can provide important information about nursing clinical education. The aim of this study was to identify the differences between the students' assessment of the clinical faculty member's competencies and the faculty member's self-assessment. These differences can reveal interesting insights relevant for improving clinical practice.

Aggregator: a machine learning approach to identifying MEDLINE articles that derive from the same underlying clinical trial.

Science.gov (United States)

Shao, Weixiang; Adams, Clive E; Cohen, Aaron M; Davis, John M; McDonagh, Marian S; Thakurta, Sujata; Yu, Philip S; Smalheiser, Neil R

2015-03-01

It is important to identify separate publications that report outcomes from the same underlying clinical trial, in order to avoid over-counting these as independent pieces of evidence. We created positive and negative training sets (comprised of pairs of articles reporting on the same condition and intervention) that were, or were not, linked to the same clinicaltrials.gov trial registry number. Features were extracted from MEDLINE and PubMed metadata; pairwise similarity scores were modeled using logistic regression. Article pairs from the same trial were identified with high accuracy (F1 score=0.843). We also created a clustering tool, Aggregator, that takes as input a PubMed user query for RCTs on a given topic, and returns article clusters predicted to arise from the same clinical trial. Although painstaking examination of full-text may be needed to be conclusive, metadata are surprisingly accurate in predicting when two articles derive from the same underlying clinical trial. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical Research

DEFF Research Database (Denmark)

Christensen, Irene

2016-01-01

This paper is about the logic of problem solving and the production of scientific knowledge through the utilisation of clinical research perspective. Ramp-up effectiveness, productivity, efficiency and organizational excellence are topics that continue to engage research and will continue doing so...... for years to come. This paper seeks to provide insights into ramp-up management studies through providing an agenda for conducting collaborative clinical research and extend this area by proposing how clinical research could be designed and executed in the Ramp- up management setting....

Searching for Clinically Relevant Biomarkers in Geriatric Oncology.

Science.gov (United States)

Katsila, Theodora; Patrinos, George P; Kardamakis, Dimitrios

2018-01-01

Ageing, which is associated with a progressive decline and functional deterioration in multiple organ systems, is highly heterogeneous, both inter- and intraindividually. For this, tailored-made theranostics and optimum patient stratification become fundamental, when decision-making in elderly patients is considered. In particular, when cancer incidence and cancer-related mortality and morbidity are taken into account, elderly patient care is a public health concern. In this review, we focus on oncogeriatrics and highlight current opportunities and challenges with an emphasis on the unmet need of clinically relevant biomarkers in elderly cancer patients. We performed a literature search on PubMed and Scopus databases for articles published in English between 2000 and 2017 coupled to text mining and analysis. Considering the top insights, we derived from our literature analysis that information knowledge needs to turn into knowledge growth in oncogeriatrics towards clinically relevant biomarkers, cost-effective practices, updated educational schemes for health professionals (in particular, geriatricians and oncologists), and awareness of ethical issues. We conclude with an interdisciplinary call to omics, geriatricians, oncologists, informatics, and policy-makers communities that Big Data should be translated into decision-making in the clinic.

The effects of aging on insight into illness in schizophrenia: a review†

Science.gov (United States)

Gerretsen, Philip; Plitman, Eric; Rajji, Tarek K.; Graff-Guerrero, Ariel

2015-01-01

Objectives Impaired insight into illness is a prevalent feature of schizophrenia, which negatively influences treatment adherence and clinical outcomes. Little is known about the effects of aging on insight impairment. We aimed to review the available research literature on the effects of aging on insight into illness in schizophrenia, in relation to positive, negative, and cognitive symptoms. Ultimately, we propose a trajectory of insight in schizophrenia across the lifespan. Method A systematic Medline® literature search was conducted, searching for English language studies describing the relationship of insight into illness in schizophrenia with aging. Results We identified 62 studies. Insight impairment is associated with illness severity, premorbid intellectual function (i.e. IQ), executive function, and memory. Insight impairment improves modestly during midlife, worsening again in late life. It tends to fluctuate with each episode of psychosis, likely in relation to worsening positive symptoms that improve with antipsychotic treatment. The relationship between insight impairment and cognitive dysfunction appears to attenuate with age, while the relationship with lower premorbid intellectual function is preserved. The association between impaired insight and negative symptoms is unclear. Conclusions The available literature suggests that the course of insight impairment follows a U-shaped curve, where insight impairment is severe during the first episode of psychosis, modestly improves over midlife, and declines again in late life. Future studies are required to investigate the trajectory of insight into illness and its core domains across the lifespan from prodromal phase to late life. PMID:25055980

Early insights into the characteristics and evolution of clinical parameters in a cohort of patients prescribed sacubitril/valsartan in Germany.

Science.gov (United States)

Wachter, Rolf; Viriato, Daniel; Klebs, Sven; Grunow, Stefanie S; Schindler, Matthias; Engelhard, Johanna; Proenca, Catia C; Calado, Frederico; Schlienger, Raymond; Dworak, Markus; Balas, Bogdan; Bruce Wirta, Sara

2018-04-01

This study aimed to provide early insights into sacubitril/valsartan (sac/val) prescription patterns and the demographic and clinical characteristics of patients prescribed sac/val in primary care and cardiology settings in Germany. The study used electronic medical records from the German IMS® Disease Analyzer database. Patients with ≥1 prescription for sac/val during 1 January-31 December 2016 (n = 1643) were identified and followed up for ≤12 months from first prescription. Patients with ≥1 heart failure (HF) diagnosis during the study period, ≥1 additional HF diagnosis in the full history of the database, and ≥1 prescription for an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and a β-blocker during the study period, without a prescription for sac/val (n = 25,264), were included as a reference cohort. Changes in clinical parameters in the 12 months before and after sac/val initiation were investigated and compared with those from the PARADIGM-HF study. The characteristics of patients prescribed sac/val more closely resembled those of patients enrolled in PARADIGM-HF (e.g. younger age, higher proportion of men than women, lower systolic blood pressure) than patients in the reference cohort. Most patients were initiated on the lowest dose of sac/val irrespective of clinical setting. Significant decreases (p < 0.001) in NT-proBNP and glycated haemoglobin levels were observed following sac/val initiation. Patients prescribed sac/val had similar baseline demographics and clinical characteristics to those from PARADIGM-HF, and most patients were initiated on the lowest dose. Changes in clinical parameters before and after initiation mirrored findings from the PARADIGM-HF study.

Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts.

Science.gov (United States)

Motté, Evi; Szepessy, Edit; Suenens, Krista; Stangé, Geert; Bomans, Myriam; Jacobs-Tulleneers-Thevissen, Daniel; Ling, Zhidong; Kroon, Evert; Pipeleers, Daniel

2014-11-01

β-Cells generated from large-scale sources can overcome current shortages in clinical islet cell grafts provided that they adequately respond to metabolic variations. Pancreatic (non)endocrine cells can develop from human embryonic stem (huES) cells following in vitro derivation to pancreatic endoderm (PE) that is subsequently implanted in immune-incompetent mice for further differentiation. Encapsulation of PE increases the proportion of endocrine cells in subcutaneous implants, with enrichment in β-cells when they are placed in TheraCyte-macrodevices and predominantly α-cells when they are alginate-microencapsulated. At posttransplant (PT) weeks 20-30, macroencapsulated huES implants presented higher glucose-responsive plasma C-peptide levels and a lower proinsulin-over-C-peptide ratio than human islet cell implants under the kidney capsule. Their ex vivo analysis showed the presence of single-hormone-positive α- and β-cells that exhibited rapid secretory responses to increasing and decreasing glucose concentrations, similar to isolated human islet cells. However, their insulin secretory amplitude was lower, which was attributed in part to a lower cellular hormone content; it was associated with a lower glucose-induced insulin biosynthesis, but not with lower glucagon-induced stimulation, which together is compatible with an immature functional state of the huES-derived β-cells at PT weeks 20-30. These data support the therapeutic potential of macroencapsulated huES implants but indicate the need for further functional analysis. Their comparison with clinical-grade human islet cell grafts sets references for future development and clinical translation. Copyright © 2014 the American Physiological Society.

Perspective: clinical communication education in the United Kingdom: some fresh insights.

Science.gov (United States)

Brown, Jo

2012-08-01

Clinical communication education is now part of the core curriculum of every medical school in the United Kingdom and the United States. It has emerged over 30 years because of various societal, political, and policy drivers and is supported by an impressive evidence base.For a variety of reasons, however, clinical communication has become separated from other parts of medical education and tends to be positioned in the early years of the curriculum, when students have limited experience of being in the clinical workplace and working with patients. The teachers of clinical communication, whether medical-school-based or clinically based, may not share learning goals for the subject and this may, therefore, provide a disintegrated learning experience for students.Clinical communication teachers need to inject fresh thinking into the teaching and learning of the subject to unite it with clinical practice in the authentic clinical workplace. Engaging with theories of workplace learning, which aim to overcome the theory/practice gap in vocational education, may be the way forward. The author suggests various ways that this might be achieved-for example, by situating clinical communication education throughout the whole undergraduate curriculum, by integrating the topic of clinical communication with other areas of medical education, by developing coteaching and curriculum design partnerships between medical school and clinical workplace, and by developing a greater range of postgraduate education that offers opportunities for professional development in clinical communication for qualified doctors that is complementary with what is taught in undergraduate education.

Intuition, insight, and the right hemisphere: Emergence of higher sociocognitive functions

Directory of Open Access Journals (Sweden)

Simon M McCrea

2010-03-01

Full Text Available Simon M McCreaDepartments of Neurology and Neuroophthalmology, University of British Columbia, Vancouver, British Columbia, CanadaAbstract: Intuition is the ability to understand immediately without conscious reasoning and is sometimes explained as a ‘gut feeling’ about the rightness or wrongness of a person, place, situation, temporal episode or object. In contrast, insight is the capacity to gain accurate and a deep understanding of a problem and it is often associated with movement beyond existing paradigms. Examples include Darwin, Einstein and Freud’s theories of natural selection, relativity, or the unconscious; respectively. Many cultures name these concepts and acknowledge their value, and insight is recognized as particularly characteristic of eminent achievements in the arts, sciences and politics. Considerable data suggests that these two concepts are more related than distinct, and that a more distributed intuitive network may feed into a predominately right hemispheric insight-based functional neuronal architecture. The preparation and incubation stages of insight may rely on the incorporation of domain-specific automatized expertise schema associated with intuition. In this manuscript the neural networks associated with intuition and insight are reviewed. Case studies of anomalous subjects with ability–achievement discrepancies are summarized. This theoretical review proposes the prospect that atypical localization of cognitive modules may enhance intuitive and insightful functions and thereby explain individual achievement beyond that expected by conventionally measured intelligence tests. A model and theory of intuition and insight’s neuroanatomical basis is proposed which could be used as a starting point for future research and better understanding of the nature of these two distinctly human and highly complex poorly understood abilities.Keywords: intuition, insight, nonverbal decoding, nonverbal sequencing

Structural insights into the recognition of phosphopeptide by the FHA domain of kanadaptin

DEFF Research Database (Denmark)

Xu, Qingping; Deller, Marc C; Nielsen, Tine K

2014-01-01

with a phosphopeptide mimic derived from a peptide segment from the N-terminus of a symmetry-related molecule as well as a sulfate bound to the structurally conserved phosphothreonine recognition cleft. This structure provides insights into the molecular recognition features utilized by this family of proteins...

Perampanel for focal epilepsy: insights from early clinical experience

OpenAIRE

Trinka, E.; Steinhoff, B. J.; Nikanorova, M.; Brodie, M. J.

2015-01-01

Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real-world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom-from-seizure rates in elderly vs younger patients. When using perampanel in elderly patients, special attention should be given to comorbidities and co-medication to avoid potenti...

Treating autoimmune disorders with venom-derived peptides.

Science.gov (United States)

Shen, Bingzheng; Cao, Zhijian; Li, Wenxin; Sabatier, Jean-Marc; Wu, Yingliang

2017-09-01

The effective treatment of autoimmune diseases remains a challenge. Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a new therapeutic target for treating autoimmune disease. Consequently, Kv1.3 channel-inhibiting venom-derived peptides are a prospective resource for new drug discovery and clinical application. Area covered: Preclinical and clinical studies have produced a wealth of information on Kv1.3 channel-inhibiting venom-derived peptides, especially from venomous scorpions and sea anemones. This review highlights the advances in screening and design of these peptides with diverse structures and potencies. It focuses on representative strategies for improving peptide selectivity and discusses the preclinical research on those venom-derived peptides as well as their clinical developmental status. Expert opinion: Encouraging results indicate that peptides isolated from the venom of venomous animals are a large resource for discovering immunomodulators that act on Kv1.3 channels. Since the structural diversity of venom-derived peptides determines the variety of their pharmacological activities, the design and optimization of venom-peptides for improved Kv1.3 channel-specificity has been advanced through some representative strategies, such as peptide chemical modification, amino acid residue truncation and binding interface modulation. These advances should further accelerate research, development and the future clinical application of venom-derived peptides selectively targeting Kv1.3 channels.

The impact of cognitive insight, self-stigma, and medication compliance on the quality of life in patients with schizophrenia.

Science.gov (United States)

Lien, Yin-Ju; Chang, Hsin-An; Kao, Yu-Chen; Tzeng, Nian-Sheng; Lu, Chien-Wen; Loh, Ching-Hui

2018-02-01

Impaired quality of life (QoL) is a common and clinically relevant feature of schizophrenia. In the present study, we attempted to formulate a model of QoL in the chronic stage of schizophrenia by including key variables-namely cognitive insight, self-stigma, insight into treatment, and medication compliance-that were proposed as its significant predictors in previous studies. We employed structural equation modeling (SEM) to simultaneously test the associations between these variables. A total of 170 community-dwelling patients with schizophrenia participated in this study. Cognitive insight, self-stigma, insight into treatment, medication compliance, and QoL were assessed through self-reporting. Symptoms were rated by interviewers. The influences of cognitive insight, stigma, insight into treatment, and medication compliance on QoL were supported using SEM. Our findings indicated that cognitive insight had a significant, positive, and direct effect on both self-stigma and insight into treatment; in contrast, it had a negative and direct effect on medication compliance. Notably, no evidence indicated a direct effect of cognitive insight on QoL. Thus, individuals with high cognitive insight reported low QoL because of stigma, low medication compliance, and their increased insight into treatment. In contrast, cognitive insight might indirectly ameliorate QoL mediated by the effect of insight into treatment on medication compliance. The findings provide additional support of the links between cognitive and clinical insight, self-stigma, medication compliance, and QoL in those with schizophrenia and suggest the need for screening and intervention services appropriate for this high-risk population.

Clinical reasoning-embodied meaning-making in physiotherapy.

Science.gov (United States)

Chowdhury, Anoop; Bjorbækmo, Wenche Schrøder

2017-07-01

This article examines physiotherapists' lived experience of practicing physiotherapy in primary care, focusing on clinical reasoning and decision-making in the case of a patient we call Eva. The material presented derives from a larger study involving two women participants, both with a protracted history of neck and shoulder pain. A total of eight sessions, all of them conducted by the first author, a professional physiotherapist, in his own practice room, were videotaped, after which the first author transcribed the sessions and added reflective notes. One session emerged as particularly stressful for both parties and is explored in detail in this article. In our analysis, we seek to be attentive to the experiences of physiotherapy displayed and to explore their meaning, significance and uniqueness from a phenomenological perspective. Our research reveals the complexity of integrating multiple theoretical perspectives of practice in clinical decision-making and suggests that a phenomenological perspective can provide insights into clinical encounters through its recognition of embodied knowledge. We argue that good physiotherapy practice demands tactfulness, sensitivity, and the desire to build a cooperative patient-therapist relationship. Informed by theoretical and practical knowledge from multiple disciplines, patient management can evolve and unfold beyond rehearsed routines and theoretical principles.

The geometrical precision of virtual bone models derived from clinical computed tomography data for forensic anthropology.

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Colman, Kerri L; Dobbe, Johannes G G; Stull, Kyra E; Ruijter, Jan M; Oostra, Roelof-Jan; van Rijn, Rick R; van der Merwe, Alie E; de Boer, Hans H; Streekstra, Geert J

2017-07-01

Almost all European countries lack contemporary skeletal collections for the development and validation of forensic anthropological methods. Furthermore, legal, ethical and practical considerations hinder the development of skeletal collections. A virtual skeletal database derived from clinical computed tomography (CT) scans provides a potential solution. However, clinical CT scans are typically generated with varying settings. This study investigates the effects of image segmentation and varying imaging conditions on the precision of virtual modelled pelves. An adult human cadaver was scanned using varying imaging conditions, such as scanner type and standard patient scanning protocol, slice thickness and exposure level. The pelvis was segmented from the various CT images resulting in virtually modelled pelves. The precision of the virtual modelling was determined per polygon mesh point. The fraction of mesh points resulting in point-to-point distance variations of 2 mm or less (95% confidence interval (CI)) was reported. Colour mapping was used to visualise modelling variability. At almost all (>97%) locations across the pelvis, the point-to-point distance variation is less than 2 mm (CI = 95%). In >91% of the locations, the point-to-point distance variation was less than 1 mm (CI = 95%). This indicates that the geometric variability of the virtual pelvis as a result of segmentation and imaging conditions rarely exceeds the generally accepted linear error of 2 mm. Colour mapping shows that areas with large variability are predominantly joint surfaces. Therefore, results indicate that segmented bone elements from patient-derived CT scans are a sufficiently precise source for creating a virtual skeletal database.

Transplantation of umbilical cord blood-derived cells for novel indications in regenerative therapy or immune modulation: a scoping review of clinical studies.

Science.gov (United States)

Iafolla, Marco A J; Tay, Jason; Allan, David S

2014-01-01

Although used mainly for transplantation of hematopoietic stem cells in the treatment of blood disorders, umbilical cord blood (UCB)-based therapies are now being used increasingly for novel applications in nonhematopoietic diseases and as a form of cellular regenerative therapy or immune modulation. We performed a systematic scoping review by searching Medline, EMBASE, and the Cochrane Library for published articles, and we searched www.clinicaltrials.com and the World Health Organization International Clinical Trials Registry Platform to describe the breadth of published studies and ongoing clinical activity in umbilical cord-based cellular therapy for regenerative therapy and immune modulation. The most commonly published area of expertise in the use of UCB-derived cellular transplantation for novel indications is for neurological disorders and this remains the most active area of study in ongoing registered trials. An increasingly broad range of disorders, however, are reflected in ongoing registered trials, which suggests greater activity, interest, and investment in UCB-derived cellular therapy. Interestingly, adult patients compose the majority of patients reported in published reports and registered ongoing clinical studies continue to enroll predominantly adult subjects. Geographically, Asian countries appear most active in UCB-derived cellular therapy and our analysis of ongoing studies suggests this trend will likely continue. Regular assessment of published and ongoing activity in UCB transplantation for emerging novel indications will be critical for informing UCB banking establishments and funding agencies to guide changes in banking practices related to emerging trends in cell therapy. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

National-scale strategic approaches for managing introduced plants: insights from Australian acacias in South Africa

CSIR Research Space (South Africa)

van Wilgen, BW

2011-09-01

Full Text Available A range of approaches and philosophies underpin national-level strategies for managing invasive alien plants. This study presents a strategy for the management of taxa that both have value and do harm. Insights were derived from examining Australian...

Clinical evaluation of the efficacy of removing microorganisms to disinfect patient-derived dental impressions.

Science.gov (United States)

Egusa, Hiroshi; Watamoto, Takao; Matsumoto, Takuya; Abe, Keiko; Kobayashi, Munemasa; Akashi, Yoshihiro; Yatani, Hirofumi

2008-01-01

Disinfection of dental impressions is an indispensable procedure for the control of cross-contamination; however, there is limited information on the efficacy of disinfection under clinical conditions. The objective of this study was to clinically evaluate the disinfection efficacy of commercially available agents in removing oral pathogens from patient-derived impressions. Impressions from 54 patients were divided into groups and either left undisinfected or underwent 1 of 5 disinfection treatments: (1) 2% glutaraldehyde (GA), (2) 1% sodium hypochlorite (SH), (3) 0.25% benzalkonium chloride (BC), (4) 1 ppm ozonated water (OW), or (5) the Hygojet/MD520 system (HJ). An impression culture technique using a brain heart infusion agar medium was used to visualize the microbial contamination on the surface of the impression cultures. The persistent presence of oral pathogens on the impression cultures was examined using selective isolation agar plates. The isolation frequencies of streptococci, staphylococci, Candida, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa species from undisinfected impressions were 100%, 55.6%, 25.9%, 25.9% and 5.6%, respectively. Disinfection with HJ and BC removed the microorganisms with the greatest efficacy, followed by GA, SH, and OW. Potential bacterial contamination could be detected even after disinfection had been performed. Combined use of BC plus GA or SH removed oral pathogens almost completely from dental impressions. This investigation showed that potential contaminants are still present, even after general disinfection procedures. Therefore, either HJ or the combined use of BC with GA or SH is recommended for clinical and laboratory use.

High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

Science.gov (United States)

Ocak, S; Sos, M L; Thomas, R K; Massion, P P

2009-08-01

During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

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

Science.gov (United States)

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

2018-05-01

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

CORRELATIONS BETWEEN AWARENESS OF ILLNESS (INSIGHT AND HISTORY OF ADDICTION IN HEROIN-ADDICTED PATIENTS

Directory of Open Access Journals (Sweden)

Angelo Giovanni Icro eMaremmani

2012-07-01

Full Text Available In a group of 1066 heroin addicts, who were seeking treatment for opioid agonist treatment, we looked for differences in historical, demographic and clinical characteristics, between patients with different levels of awareness of illness (insight. The results showed that, in the cohort studied, a majority of subjects lacked insight into their heroin-use behaviour. Compared with the impaired-insight group, those who possessed insight into their illness showed significantly greater awareness of past social, somatic and psychopathological impairments, and had a greater number of past treatment-seeking events for heroin addiction. In contrast with other psychiatric illnesses, the presence of awareness appears to be related to the passing of time and to the worsening of the illness. Methodologies to improve the insight of patients should, therefore, be targeted more directly on patients early in their history of heroin dependence, because the risk of lack of insight is greatest during this period.

Clinical psychology of religion. A training model

NARCIS (Netherlands)

Uden, M.H.F. van; Pieper, J.Z.T.

2003-01-01

In this paper we will show you a part of a course "Clinical Psychology of Religion" that has been developed in the Netherlands for introducing mental health professionals in the field of clinical psychology of religion. Clinical psychology of religion applies insights from general psychology of

Bolide Airbursts as a Seismic Source for the 2018 Mars InSight Mission

Science.gov (United States)

Stevanović, J.; Teanby, N. A.; Wookey, J.; Selby, N.; Daubar, I. J.; Vaubaillon, J.; Garcia, R.

2017-10-01

In 2018, NASA will launch InSight, a single-station suite of geophysical instruments, designed to characterise the martian interior. We investigate the seismo-acoustic signal generated by a bolide entering the martian atmosphere and exploding in a terminal airburst, and assess this phenomenon as a potential observable for the SEIS seismic payload. Terrestrial analogue data from four recent events are used to identify diagnostic airburst characteristics in both the time and frequency domain. In order to estimate a potential number of detectable events for InSight, we first model the impactor source population from observations made on the Earth, scaled for planetary radius, entry velocity and source density. We go on to calculate a range of potential airbursts from the larger incident impactor population. We estimate there to be {˜} 1000 events of this nature per year on Mars. To then derive a detectable number of airbursts for InSight, we scale this number according to atmospheric attenuation, air-to-ground coupling inefficiencies and by instrument capability for SEIS. We predict between 10-200 detectable events per year for InSight.

A Representation for Gaining Insight into Clinical Decision Models

Science.gov (United States)

Jimison, Holly B.

1988-01-01

For many medical domains uncertainty and patient preferences are important components of decision making. Decision theory is useful as a representation for such medical models in computer decision aids, but the methodology has typically had poor performance in the areas of explanation and user interface. The additional representation of probabilities and utilities as random variables serves to provide a framework for graphical and text insight into complicated decision models. The approach allows for efficient customization of a generic model that describes the general patient population of interest to a patient- specific model. Monte Carlo simulation is used to calculate the expected value of information and sensitivity for each model variable, thus providing a metric for deciding what to emphasize in the graphics and text summary. The computer-generated explanation includes variables that are sensitive with respect to the decision or that deviate significantly from what is typically observed. These techniques serve to keep the assessment and explanation of the patient's decision model concise, allowing the user to focus on the most important aspects for that patient.

Overlap and distinction between measures of insight and self-stigma.

Science.gov (United States)

Hasson-Ohayon, Ilanit

2018-05-24

Multiple studies on insight into one's illness and self-stigma among patients with serious mental illness and their relatives have shown that these constructs are related to one another and that they affect outcome. However, a critical exploration of the items used to assess both constructs raises questions with regard to the possible overlapping and centrality of items. The current study used five different samples to explore the possible overlap and distinction between insight and self-stigma, and to identify central items, via network analyses and principal component factor analysis. Findings from the network analyses showed overlap between insight and self-stigma exist with a relatively clearer observational distinction between the constructs among the two parent samples in comparison to the patient samples. Principal component factor analysis constrained to two factors showed that a relatively high percentage of items were not loaded on either factor, and in a few datasets, several insight items were loaded on the self-stigma scale and vice versa. The author discusses implications for research and calls for rethinking the way insight is assessed. Clinical implications are also discussed in reference to central items of social isolation, future worries and stereotype endorsement among the different study groups. Copyright © 2018 Elsevier B.V. All rights reserved.

Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application

Directory of Open Access Journals (Sweden)

Romilly E. Hodges

2015-01-01

Full Text Available Research into human biotransformation and elimination systems continues to evolve. Various clinical and in vivo studies have been undertaken to evaluate the effects of foods and food-derived components on the activity of detoxification pathways, including phase I cytochrome P450 enzymes, phase II conjugation enzymes, Nrf2 signaling, and metallothionein. This review summarizes the research in this area to date, highlighting the potential for foods and nutrients to support and/or modulate detoxification functions. Clinical applications to alter detoxification pathway activity and improve patient outcomes are considered, drawing on the growing understanding of the relationship between detoxification functions and different disease states, genetic polymorphisms, and drug-nutrient interactions. Some caution is recommended, however, due to the limitations of current research as well as indications that many nutrients exert biphasic, dose-dependent effects and that genetic polymorphisms may alter outcomes. A whole-foods approach may, therefore, be prudent.

Insightful practice: a reliable measure for medical revalidation

Science.gov (United States)

Guthrie, Bruce; Sullivan, Frank M; Mercer, Stewart W; Russell, Andrew; Bruce, David A

2012-01-01

Background Medical revalidation decisions need to be reliable if they are to reassure on the quality and safety of professional practice. This study tested an innovative method in which general practitioners (GPs) were assessed on their reflection and response to a set of externally specified feedback. Setting and participants 60 GPs and 12 GP appraisers in the Tayside region of Scotland, UK. Methods A feedback dataset was specified as (1) GP-specific data collected by GPs themselves (patient and colleague opinion; open book self-evaluated knowledge test; complaints) and (2) Externally collected practice-level data provided to GPs (clinical quality and prescribing safety). GPs' perceptions of whether the feedback covered UK General Medical Council specified attributes of a ‘good doctor’ were examined using a mapping exercise. GPs' professionalism was examined in terms of appraiser assessment of GPs' level of insightful practice, defined as: engagement with, insight into and appropriate action on feedback data. The reliability of assessment of insightful practice and subsequent recommendations on GPs' revalidation by face-to-face and anonymous assessors were investigated using Generalisability G-theory. Main outcome measures Coverage of General Medical Council attributes by specified feedback and reliability of assessor recommendations on doctors' suitability for revalidation. Results Face-to-face assessment proved unreliable. Anonymous global assessment by three appraisers of insightful practice was highly reliable (G=0.85), as were revalidation decisions using four anonymous assessors (G=0.83). Conclusions Unlike face-to-face appraisal, anonymous assessment of insightful practice offers a valid and reliable method to decide GP revalidation. Further validity studies are needed. PMID:22653078

Insight derived from molecular dynamics simulations into molecular motions, thermodynamics and kinetics of HIV-1 gp120.

Directory of Open Access Journals (Sweden)

Peng Sang

Full Text Available Although the crystal structures of the HIV-1 gp120 core bound and pre-bound by CD4 are known, the details of dynamics involved in conformational equilibrium and transition in relation to gp120 function have remained elusive. The homology models of gp120 comprising the N- and C-termini and loops V3 and V4 in the CD4-bound and CD4-unbound states were built and subjected to molecular dynamics (MD simulations to investigate the differences in dynamic properties and molecular motions between them. The results indicate that the CD4-bound gp120 adopted a more compact and stable conformation than the unbound form during simulations. For both the unbound and bound gp120, the large concerted motions derived from essential dynamics (ED analyses can influence the size/shape of the ligand-binding channel/cavity of gp120 and, therefore, were related to its functional properties. The differences in motion direction between certain structural components of these two forms of gp120 were related to the conformational interconversion between them. The free energy calculations based on the metadynamics simulations reveal a more rugged and complex free energy landscape (FEL for the unbound than for the bound gp120, implying that gp120 has a richer conformational diversity in the unbound form. The estimated free energy difference of ∼-6.0 kJ/mol between the global minimum free energy states of the unbound and bound gp120 indicates that gp120 can transform spontaneously from the unbound to bound states, revealing that the bound state represents a high-probability "ground state" for gp120 and explaining why the unbound state resists crystallization. Our results provide insight into the dynamics-and-function relationship of gp120, and facilitate understandings of the thermodynamics, kinetics and conformational control mechanism of HIV-1 gp120.

Surveillance of illness associated with pandemic (H1N1) 2009 virus infection among adults using a global clinical site network approach: the INSIGHT FLU 002 and FLU 003 studies

DEFF Research Database (Denmark)

Dwyer, Dominic E; Nielsen, Henrik Ib

2011-01-01

The novel pandemic influenza A (H1H1) 2009 virus spread rapidly around the world in 2009. The paucity of prospective international epidemiologic data on predictors of clinical outcomes with pandemic (H1N1) 2009 virus infection stimulated the INSIGHT network, an international network of community...... and hospital-based investigators, to commence two worldwide clinical observational studies to describe pandemic (H1N1) 2009 virus activity. The purpose of these two studies was to estimate the percent of adult patients with illness due to laboratory-confirmed pandemic (H1N1) 2009 virus infection...

Clinical Process Intelligence

DEFF Research Database (Denmark)

Vilstrup Pedersen, Klaus

2006-01-01

.e. local guidelines. From a knowledge management point of view, this externalization of generalized processes, gives the opportunity to learn from, evaluate and optimize the processes. "Clinical Process Intelligence" (CPI), will denote the goal of getting generalized insight into patient centered health...

Intermolecular interaction of thiosemicarbazone derivatives to solvents and a potential Aedes aegypti target

Science.gov (United States)

da Silva, João Bosco P.; Hallwass, Fernando; da Silva, Aluizio G.; Moreira, Diogo Rodrigo; Ramos, Mozart N.; Espíndola, José Wanderlan P.; de Oliveira, Ana Daura T.; Brondani, Dalci José; Leite, Ana Cristina L.; Merz, Kenneth M.

2015-08-01

DFT calculations were used to access information about structure, energy and electronic properties of series of phenyl- and phenoxymethyl-(thio)semicarbazone derivatives with demonstrated activity against the larvae of Aedes aegypti in stage L4. The way as the thiosemicarbazone derivatives can interact with solvents like DMSO and water were analyzed from the comparison between calculated and experimental 1H NMR chemical shifts. The evidences of thiosemicarbazone derivatives making H-bond interaction to solvent have provide us insights on how they can interact with a potential A. aegypti's biological target, the Sterol Carrier Protein-2.

Macrophages discriminate glycosylation patterns of apoptotic cell-derived microparticles.

Science.gov (United States)

Bilyy, Rostyslav O; Shkandina, Tanya; Tomin, Andriy; Muñoz, Luis E; Franz, Sandra; Antonyuk, Volodymyr; Kit, Yuriy Ya; Zirngibl, Matthias; Fürnrohr, Barbara G; Janko, Christina; Lauber, Kirsten; Schiller, Martin; Schett, Georg; Stoika, Rostyslav S; Herrmann, Martin

2012-01-02

Inappropriate clearance of apoptotic remnants is considered to be the primary cause of systemic autoimmune diseases, like systemic lupus erythematosus. Here we demonstrate that apoptotic cells release distinct types of subcellular membranous particles (scMP) derived from the endoplasmic reticulum (ER) or the plasma membrane. Both types of scMP exhibit desialylated glycotopes resulting from surface exposure of immature ER-derived glycoproteins or from surface-borne sialidase activity, respectively. Sialidase activity is activated by caspase-dependent mechanisms during apoptosis. Cleavage of sialidase Neu1 by caspase 3 was shown to be directly involved in apoptosis-related increase of surface sialidase activity. ER-derived blebs possess immature mannosidic glycoepitopes and are prioritized by macrophages during clearance. Plasma membrane-derived blebs contain nuclear chromatin (DNA and histones) but not components of the nuclear envelope. Existence of two immunologically distinct types of apoptotic blebs may provide new insights into clearance-related diseases.

Is Google Trends a reliable tool for digital epidemiology? Insights from different clinical settings.

Science.gov (United States)

Cervellin, Gianfranco; Comelli, Ivan; Lippi, Giuseppe

2017-09-01

Internet-derived information has been recently recognized as a valuable tool for epidemiological investigation. Google Trends, a Google Inc. portal, generates data on geographical and temporal patterns according to specified keywords. The aim of this study was to compare the reliability of Google Trends in different clinical settings, for both common diseases with lower media coverage, and for less common diseases attracting major media coverage. We carried out a search in Google Trends using the keywords "renal colic", "epistaxis", and "mushroom poisoning", selected on the basis of available and reliable epidemiological data. Besides this search, we carried out a second search for three clinical conditions (i.e., "meningitis", "Legionella Pneumophila pneumonia", and "Ebola fever"), which recently received major focus by the Italian media. In our analysis, no correlation was found between data captured from Google Trends and epidemiology of renal colics, epistaxis and mushroom poisoning. Only when searching for the term "mushroom" alone the Google Trends search generated a seasonal pattern which almost overlaps with the epidemiological profile, but this was probably mostly due to searches for harvesting and cooking rather than to for poisoning. The Google Trends data also failed to reflect the geographical and temporary patterns of disease for meningitis, Legionella Pneumophila pneumonia and Ebola fever. The results of our study confirm that Google Trends has modest reliability for defining the epidemiology of relatively common diseases with minor media coverage, or relatively rare diseases with higher audience. Overall, Google Trends seems to be more influenced by the media clamor than by true epidemiological burden. Copyright © 2017 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Reduced connectivity in the self-processing network of schizophrenia patients with poor insight.

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Edith J Liemburg

Full Text Available Lack of insight (unawareness of illness is a common and clinically relevant feature of schizophrenia. Reduced levels of self-referential processing have been proposed as a mechanism underlying poor insight. The default mode network (DMN has been implicated as a key node in the circuit for self-referential processing. We hypothesized that during resting state the DMN network would show decreased connectivity in schizophrenia patients with poor insight compared to patients with good insight. Patients with schizophrenia were recruited from mental health care centers in the north of the Netherlands and categorized in groups having good insight (n= 25 or poor insight (n = 19. All subjects underwent a resting state fMRI scan. A healthy control group (n = 30 was used as a reference. Functional connectivity of the anterior and posterior part of the DMN, identified using Independent Component Analysis, was compared between groups. Patients with poor insight showed lower connectivity of the ACC within the anterior DMN component and precuneus within the posterior DMN component compared to patients with good insight. Connectivity between the anterior and posterior part of the DMN was lower in patients than controls, and qualitatively different between the good and poor insight patient groups. As predicted, subjects with poor insight in psychosis showed decreased connectivity in DMN regions implicated in self-referential processing, although this concerned only part of the network. This finding is compatible with theories implying a role of reduced self-referential processing as a mechanism contributing to poor insight.

Overcoming the bottleneck of platelet lysate supply in large-scale clinical expansion of adipose-derived stem cells: A comparison of fresh versus three types of platelet lysates from outdated buffy coat-derived platelet concentrates.

Science.gov (United States)

Glovinski, Peter V; Herly, Mikkel; Mathiasen, Anders B; Svalgaard, Jesper D; Borup, Rehannah; Talman, Maj-Lis M; Elberg, Jens J; Kølle, Stig-Frederik T; Drzewiecki, Krzysztof T; Fischer-Nielsen, Anne

2017-02-01

Platelet lysates (PL) represent a promising replacement for xenogenic growth supplement for adipose-derived stem cell (ASC) expansions. However, fresh platelets from human blood donors are not clinically feasible for large-scale cell expansion based on their limited supply. Therefore, we tested PLs prepared via three methods from outdated buffy coat-derived platelet concentrates (PCs) to establish an efficient and feasible expansion of ASCs for clinical use. PLs were prepared by the freeze-thaw method from freshly drawn platelets or from outdated buffy coat-derived PCs stored in the platelet additive solution, InterSol. Three types of PLs were prepared from outdated PCs with platelets suspended in either (1) InterSol (not manipulated), (2) InterSol + supplemented with plasma or (3) plasma alone (InterSol removed). Using these PLs, we compared ASC population doubling time, cell yield, differentiation potential and cell surface markers. Gene expression profiles were analyzed using microarray assays, and growth factor concentrations in the cell culture medium were measured using enzyme-linked immunosorbent assay (ELISA). Of the three PL compositions produced from outdated PCs, removal of Intersol and resuspension in plasma prior to the first freezing process was overall the best. This specific outdated PL induced ASC growth kinetics, surface markers, plastic adherence and differentiation potentials comparable with PL from fresh platelets. ASCs expanded in PL from fresh versus outdated PCs exhibited different expressions of 17 overlapping genes, of which 10 were involved in cellular proliferation, although not significantly reflected by cell growth. Only minor differences in growth factor turnover were observed. PLs from outdated platelets may be an efficient and reliable source of human growth supplement allowing for large-scale ASC expansion for clinical use. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights

Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging

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Meenakshi Gaur

2017-01-01

Full Text Available Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology.

An integrated model for the effects of self-reflection and clinical experiential learning on clinical nursing performance in nursing students: A longitudinal study.

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Pai, Hsiang-Chu

2016-10-01

The use of clinical simulation in undergraduate nursing programs in Taiwan has gradually increased over the past 5years. Previous research has shown that students' experience of anxiety during simulated laboratory sessions influences their self-reflection and learning effectiveness. Thus, further study that tracks what influences students' clinical performance in actual clinical sites is vital. The aim of the study is to develop an integrated model that considers the associations among anxiety, self-reflection, and learning effectiveness and to understand how this model applies to student nurses' clinical performance while on clinical placement. This study used a correlational and longitudinal study design. The 80 nursing students, who ranged in age from 19 to 21 (mean=20.38, SD=0.56), were recruited from a nursing school in southern Taiwan. Data were collected during three phases of implementation using four questionnaires. During the first phase, the State-Trait Anxiety Inventory (STAI), Simulation Learning Effectiveness Scale (SLES), and Self-Reflection and Insight Scale (SRIS) were used after students completed the simulation course in the school simulation laboratory. Nursing students also completed the Holistic Nursing Competence Scale at 2months (Phase 2) and 4months (Phase 3) after clinical practice experience. In Phase 3, students again completed the STAI and SRIS. Partial least squares (PLS), a structural equation modeling (SEM) procedure, was used to test the research model. The findings showed that: (1) at the start of the simulation laboratory, anxiety had a significant negative effect on students' simulation learning effectiveness (SLE; β=-0.14, pself-reflection with insight (SRI; β=-0.52, pSelf-reflection also had a significant positive effect on simulation learning effectiveness (β=0.37, pself-reflection and insight also had a significant positive effect on nursing competence during the first 2months of practice in a clinical site (β=0.13; β=0

Ethnographic nexus analysis in clinical nursing education

DEFF Research Database (Denmark)

Kjær, Malene

2016-01-01

Purpose/aim(s): Internationally, student nurses' attrition after clinical practice is an increasing problem (Hamshire, Willgoss, & Wibberley, 2012; Pilegård Jensen, 2006). A better understanding of 'becoming a nurse' as situated practice in the hospital wards might help avoid pitfalls...... in the clinical practice. Thus a thorough insight into the field is necessary in order to change it. The purpose of this paper is to show and discuss how it is possible methodologically to do ethnographic research in clinical education and how the field of clinical nursing education in the hospital wards might...... be improved after insights obtained through ethnographic research. Methods: Using nexus analysis (Scollon & Scollon, 2004, 2007) as an ethnographic framework in four Danish hospital wards, a study of the development of a professional identity among student nurses in Denmark was conducted. Scollon and Scollon...

Connecting Classroom, Clinic, and Context: Clinical Reasoning Strategies for Clinical Instructors and Academic Faculty.

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Furze, Jennifer; Kenyon, Lisa K; Jensen, Gail M

2015-01-01

Clinical reasoning is an essential skill in pediatric physical therapist (PT) practice. As such, explicit instruction in clinical reasoning should be emphasized in PT education. This article provides academic faculty and clinical instructors with an overview of strategies to develop and expand the clinical reasoning capacity of PT students within the scope of pediatric PT practice. Achieving a balance between deductive reasoning strategies that provide a framework for thinking and inductive reasoning strategies that emphasize patient factors and the context of the clinical situation is an important variable in educational pedagogy. Consideration should be given to implementing various teaching and learning approaches across the curriculum that reflect the developmental level of the student(s). Deductive strategies may be helpful early in the curriculum, whereas inductive strategies are often advantageous after patient interactions; however, exposure to both is necessary to fully develop the learner's clinical reasoning abilities. For more insights from the authors, see Supplemental Digital Content 1, available at http://links.lww.com/PPT/A87.

Annuity factors, duration and convexity : insights from a financial engineering perspective

OpenAIRE

Ekern, Steinar

1998-01-01

This paper applies a unified and integrative financial engineering perspective to key derived concepts in traditional fixed income analysis, with the purpose of enhancing conceptual insights and motivating computational applications. The emphasis on annuity factors and their impact on duration and convexity differs from the focus prevailing in related discussions. By decomposing the cashflow streams of a coupon bond into different, specific, and clearly defined portfolios of component bonds w...

Insight into DEG/ENaC channel gating from genetics and structure.

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Eastwood, Amy L; Goodman, Miriam B

2012-10-01

The founding members of the superfamily of DEG/ENaC ion channel proteins are C. elegans proteins that form mechanosensitive channels in touch and pain receptors. For more than a decade, the research community has used mutagenesis to identify motifs that regulate gating. This review integrates insight derived from unbiased in vivo mutagenesis screens with recent crystal structures to develop new models for activation of mechanically gated DEGs.

Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

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Mold, Matthew; Shardlow, Emma; Exley, Christopher

2016-08-12

Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

Integrating research, clinical care, and education in academic health science centers.

Science.gov (United States)

King, Gillian; Thomson, Nicole; Rothstein, Mitchell; Kingsnorth, Shauna; Parker, Kathryn

2016-10-10

Purpose One of the major issues faced by academic health science centers (AHSCs) is the need for mechanisms to foster the integration of research, clinical, and educational activities to achieve the vision of evidence-informed decision making (EIDM) and optimal client care. The paper aims to discuss this issue. Design/methodology/approach This paper synthesizes literature on organizational learning and collaboration, evidence-informed organizational decision making, and learning-based organizations to derive insights concerning the nature of effective workplace learning in AHSCs. Findings An evidence-informed model of collaborative workplace learning is proposed to aid the alignment of research, clinical, and educational functions in AHSCs. The model articulates relationships among AHSC academic functions and sub-functions, cross-functional activities, and collaborative learning processes, emphasizing the importance of cross-functional activities in enhancing collaborative learning processes and optimizing EIDM and client care. Cross-functional activities involving clinicians, researchers, and educators are hypothesized to be a primary vehicle for integration, supported by a learning-oriented workplace culture. These activities are distinct from interprofessional teams, which are clinical in nature. Four collaborative learning processes are specified that are enhanced in cross-functional activities or teamwork: co-constructing meaning, co-learning, co-producing knowledge, and co-using knowledge. Practical implications The model provides an aspirational vision and insight into the importance of cross-functional activities in enhancing workplace learning. The paper discusses the conceptual and empirical basis to the model, its contributions and limitations, and implications for AHSCs. Originality/value The model's potential utility for health care is discussed, with implications for organizational culture and the promotion of cross-functional activities.

Rheumatology outpatient nurse clinics: a valuable addition?

NARCIS (Netherlands)

Temmink, D.; Hutten, J.B.F.; Francke, A.L.; Rasker, J.J.; Huijer Abu-Saad, H.; Zee, J. van der

2001-01-01

Objectives: "Transmural rheumatology nurse clinics," where nursing care is provided under the joint responsibility of a home care organization and a hospital, were recently introduced into Dutch health care. This article gives insight into outcomes of the transmural rheumatology nurse clinics.

Rheumatology outpatient nurse clinics: a valuable addition?

NARCIS (Netherlands)

Temmink, Denise; Hutten, Jack B.F.; Francke, Anneke L.; Rasker, Johannes J.; Abu-Saad, Huda Huijer

2001-01-01

Objectives: Transmural rheumatology nurse clinics, where nursing care is provided under the joint responsibility of a home care organization and a hospital, were recently introduced into Dutch health care. This article gives insight into outcomes of the transmural rheumatology nurse clinics. -

Experimental and Theoretical Insights into the Inhibition Mechanism of Prion Fibrillation by Resveratrol and its Derivatives.

Science.gov (United States)

Li, Lanlan; Zhu, Yongchang; Zhou, Shuangyan; An, Xiaoli; Zhang, Yan; Bai, Qifeng; He, Yong-Xing; Liu, Huanxiang; Yao, Xiaojun

2017-12-20

Resveratrol and its derivatives have been shown to display beneficial effects to neurodegenerative diseases. However, the molecular mechanism of resveratrol and its derivatives on prion conformational conversion is poorly understood. In this work, the interaction mechanism between prion and resveratrol as well as its derivatives was investigated using steady-state fluorescence quenching, Thioflavin T binding assay, Western blotting, and molecular dynamics simulation. Protein fluorescence quenching method and Thioflavin T assay revealed that resveratrol and its derivatives could interact with prion and interrupt prion fibril formation. Molecular dynamics simulation results indicated that resveratrol can stabilize the PrP 127-147 peptide mainly through π-π stacking interactions between resveratrol and Tyr128. The hydrogen bonds interactions between resveratrol and the PrP 127-147 peptide could further reduce the flexibility and the propensity to aggregate. The results of this study not only can provide useful information about the interaction mechanism between resveratrol and prion, but also can provide useful clues for further design of new inhibitors inhibiting prion aggregation.

Insight Is Not in the Problem: Investigating Insight in Problem Solving across Task Types.

Science.gov (United States)

Webb, Margaret E; Little, Daniel R; Cropper, Simon J

2016-01-01

The feeling of insight in problem solving is typically associated with the sudden realization of a solution that appears obviously correct (Kounios et al., 2006). Salvi et al. (2016) found that a solution accompanied with sudden insight is more likely to be correct than a problem solved through conscious and incremental steps. However, Metcalfe (1986) indicated that participants would often present an inelegant but plausible (wrong) answer as correct with a high feeling of warmth (a subjective measure of closeness to solution). This discrepancy may be due to the use of different tasks or due to different methods in the measurement of insight (i.e., using a binary vs. continuous scale). In three experiments, we investigated both findings, using many different problem tasks (e.g., Compound Remote Associates, so-called classic insight problems, and non-insight problems). Participants rated insight-related affect (feelings of Aha-experience, confidence, surprise, impasse, and pleasure) on continuous scales. As expected we found that, for problems designed to elicit insight, correct solutions elicited higher proportions of reported insight in the solution compared to non-insight solutions; further, correct solutions elicited stronger feelings of insight compared to incorrect solutions.

Engineering the Pores of Biomass-Derived Carbon: Insights for Achieving Ultrahigh Stability at High Power in High-Energy Supercapacitors.

Science.gov (United States)

Thangavel, Ranjith; Kaliyappan, Karthikeyan; Ramasamy, Hari Vignesh; Sun, Xueliang; Lee, Yun-Sung

2017-07-10

Electrochemical supercapacitors with high energy density are promising devices due to their simple construction and long-term cycling performance. The development of a supercapacitor based on electrical double-layer charge storage with high energy density that can preserve its cyclability at higher power presents an ongoing challenge. Herein, we provide insights to achieve a high energy density at high power with an ultrahigh stability in an electrical double-layer capacitor (EDLC) system by using carbon from a biomass precursor (cinnamon sticks) in a sodium ion-based organic electrolyte. Herein, we investigated the dependence of EDLC performance on structural, textural, and functional properties of porous carbon engineered by using various activation agents. The results demonstrate that the performance of EDLCs is not only dependent on their textural properties but also on their structural features and surface functionalities, as is evident from the electrochemical studies. The electrochemical results are highly promising and revealed that the porous carbon with poor textural properties has great potential to deliver high capacitance and outstanding stability over 300 000 cycles compared with porous carbon with good textural properties. A very low capacitance degradation of around 0.066 % per 1000 cycles, along with high energy density (≈71 Wh kg -1 ) and high power density, have been achieved. These results offer a new platform for the application of low-surface-area biomass-derived carbons in the design of highly stable high-energy supercapacitors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative Evaluation of Child Behavior Checklist-derived Scales in Children Clinically Referred for Emotional and Behavioural Dysregulation

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Efstathios Papachristou

2016-08-01

Full Text Available Background: We recently developed the Child Behavior Checklist-Mania Scale (CBCL-MS, a novel and short instrument for the assessment of mania-like symptoms in children and adolescents derived from the CBCL item pool and have demonstrated its construct validity and temporal stability in a longitudinal general population sample. Objective: The aim of this study was to evaluate the construct validity of the 19-item CBCL-MS in a clinical sample and to compare its discriminatory ability to that of the 40-item CBCL-Dysregulation Profile (CBCL-DP and the 34-item CBCL-Externalizing Scale. Methods: The study sample comprised 202 children, aged 7-12 years, diagnosed with DSM-defined Attention Deficit Hyperactivity Disorder (ADHD, Conduct Disorder (CD, Oppositional Defiant Disorder (ODD and mood and anxiety disorders based on the Diagnostic Interview Schedule for Children. The construct validity of the CBCL-MS was tested by means of a confirmatory factor analysis. Receiver operating characteristics (ROC curves and logistic regression analyses adjusted for sex and age were used to assess the discriminatory ability relative to that of the (CBCL-DP and the CBCL-Externalizing Scale. Results: The CBCL-MS had excellent construct validity (CFI=0.97; TLI=0.96; RMSEA=0.04. Despite similar overall performance across scales, the clinical-range scores of the CBCL-DP and the CBCL-Externalizing Scale were associated with higher odds for ODD and CD while the clinical range scores for CBCL-MS were associated with higher odds for mood disorders. The overlap amongst the children who scored within the clinical range of each scale was over 90%. Conclusion: CBCL-MS has good construct validity in general population and clinical samples and is therefore suitable for both clinical practice and research.

Clinical and Biological Insights from the University of California San Francisco Prospective and Longitudinal Cohort.

Science.gov (United States)

Benn, Bryan S; Lehman, Zoe; Kidd, Sharon A; Ho, Melissa; Sun, Sara; Ramstein, Joris; Arger, Nicholas K; Nguyen, Christine P; Su, Robert; Gomez, Antonio; Gelfand, Jeffrey M; Koth, Laura L

2017-10-01

Sarcoidosis is a systemic inflammatory disease characterized by non-necrotizing granulomas in involved organs, most commonly the lung. Description of patient characteristics in the Western United States is limited. Furthermore, blood-based measures that relate to clinical sarcoidosis phenotypes are lacking. We present an analysis of a prospective, longitudinal sarcoidosis cohort at a Northern Californian academic medical center. We enrolled 126 sarcoidosis subjects and 64 healthy controls and recorded baseline demographic and clinical characteristics. We used regression models to identify factors independently associated with pulmonary physiology. We tested whether blood transcript levels at study entry could relate to longitudinal changes in pulmonary physiology. White, non-Hispanics composed ~70% of subjects. Hispanics and Blacks had a diagnostic biopsy at an age ~7 years younger than whites. Obstructive, but not restrictive, physiology characterized Scadding Stage IV patients. Subjects reporting use of immunosuppression had worse FEV1%p, FVC%p, and DLCO%p compared to subjects never treated, regardless of Scadding stage. We defined sarcoidosis disease activity by a drop in pulmonary function over 36 months and found that subjects meeting this definition had significant repression of blood gene transcripts related to T cell receptor signaling pathways, referred to as the "TCR factor." Obstructive pulmonary physiology defined Stage IV patients which were mostly white, non-Hispanics. Genes comprising the composite gene expression score, TCR factor, may represent a blood-derived measure of T-cell activity and an indirect measure of active sarcoidosis inflammation. Validation of this measure could translate into individualized treatment for sarcoidosis patients.

High-resolution mutational profiling suggests the genetic validity of glioblastoma patient-derived pre-clinical models.

Directory of Open Access Journals (Sweden)

Shawn E Yost

Full Text Available Recent advances in the ability to efficiently characterize tumor genomes is enabling targeted drug development, which requires rigorous biomarker-based patient selection to increase effectiveness. Consequently, representative DNA biomarkers become equally important in pre-clinical studies. However, it is still unclear how well these markers are maintained between the primary tumor and the patient-derived tumor models. Here, we report the comprehensive identification of somatic coding mutations and copy number aberrations in four glioblastoma (GBM primary tumors and their matched pre-clinical models: serum-free neurospheres, adherent cell cultures, and mouse xenografts. We developed innovative methods to improve the data quality and allow a strict comparison of matched tumor samples. Our analysis identifies known GBM mutations altering PTEN and TP53 genes, and new actionable mutations such as the loss of PIK3R1, and reveals clear patient-to-patient differences. In contrast, for each patient, we do not observe any significant remodeling of the mutational profile between primary to model tumors and the few discrepancies can be attributed to stochastic errors or differences in sample purity. Similarly, we observe ∼96% primary-to-model concordance in copy number calls in the high-cellularity samples. In contrast to previous reports based on gene expression profiles, we do not observe significant differences at the DNA level between in vitro compared to in vivo models. This study suggests, at a remarkable resolution, the genome-wide conservation of a patient's tumor genetics in various pre-clinical models, and therefore supports their use for the development and testing of personalized targeted therapies.

Controversies in Cardiovascular Research: Induced pluripotent stem cell-derived cardiomyocytes – boutique science or valuable arrhythmia model?

Science.gov (United States)

Knollmann, Björn C

2013-01-01

As part of the series on Controversies in Cardiovascular Research, the article reviews the strengths and limitations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as models of cardiac arrhythmias. Specifically, the article attempts to answer the following questions: Which clinical arrhythmias can be modeled by iPSC-CM? How well can iPSC-CM model adult ventricular myocytes? What are the strengths and limitations of published iPSC-CM arrhythmia models? What new mechanistic insight has been gained? What is the evidence that would support using iPSC-CM to personalize anti-arrhythmic drug therapy? The review also discusses the pros and cons of using the iPSC-CM technology for modeling specific genetic arrhythmia disorders such as long QT syndrome, Brugada Syndrome or Catecholaminergic Polymorphic Ventricular Tachycardia. PMID:23569106

Amphetamine derivative related deaths.

Science.gov (United States)

Lora-Tamayo, C; Tena, T; Rodríguez, A

1997-02-28

Amphetamine its methylendioxy (methylendioxyamphetamine methylenedioxymethylamphetamine, methylenedioxyethylamphetamine) and methoxy derivatives (p-methoxyamphetamine and p-methoxymethylamphetamine) are widely abused in Spanish society. We present here the results of a systematic study of all cases of deaths brought to the attention of the Madrid department of the Instituto Nacional de Toxicologia from 1993 to 1995 in which some of these drugs have been found in the cadaveric blood. The cases were divided into three categories: amphetamine and derivatives, amphetamines and alcohol, amphetamines and other drugs. Data on age, sex, clinical symptoms, morphological findings, circumstances of death, when known, and concentration of amphetamine derivatives, alcohol and other drugs in blood are given for each group. The information provided here may prove to be useful for the forensic interpretation of deaths which are directly or indirectly related to abuse of amphetamine derivatives.

Insight Into Illness and Cognition in Schizophrenia in Earlier and Later Life.

Science.gov (United States)

Gerretsen, Philip; Voineskos, Aristotle N; Graff-Guerrero, Ariel; Menon, Mahesh; Pollock, Bruce G; Mamo, David C; Mulsant, Benoit H; Rajji, Tarek K

2017-04-01

Impaired insight into illness in schizophrenia is associated with illness severity and deficits in premorbid intellectual function, executive function, and memory. A previous study of patients aged 60 years and older found that illness severity and premorbid intellectual function accounted for variance in insight impairment. As such, we aimed to test whether similar relationships would be observed in earlier life. A retrospective analysis was performed on 1 large sample of participants (n = 171) with a DSM-IV-TR diagnosis of schizophrenia aged 19 to 79 years acquired from 2 studies: (1) a psychosocial intervention trial for older persons with schizophrenia (June 2008 to May 2014) and (2) a diffusion tensor imaging and genetics study of psychosis across the life span (February 2007 to December 2013). We assessed insight into illness using the Positive and Negative Syndrome Scale (PANSS) item G12 and explored its relationship to illness severity (PANSS total modified), premorbid intellectual function (Wechsler Test of Adult Reading [WTAR]), and cognition. Insight impairment was more severe in later life (≥ 60 years) than in earlier years (t = -3.75, P insight was explained by PANSS total modified (Exp[B] = 1.070, P insight, they did not independently contribute to its variance. However, the relationships between impaired insight and illness severity and between impaired insight and cognition, particularly working memory, were stronger in later life than in earlier life. These results suggest an opportunity for intervention may exist with cognitive-enhancing neurostimulation or medications to improve insight into illness in schizophrenia across the life span. Original study registered on ClinicalTrials.gov (identifier: NCT00832845). © Copyright 2017 Physicians Postgraduate Press, Inc.

Unanticipated Insights into Biomedicine from the Study of Acupuncture.

Science.gov (United States)

MacPherson, Hugh; Hammerschlag, Richard; Coeytaux, Remy R; Davis, Robert T; Harris, Richard E; Kong, Jiang-Ti; Langevin, Helene M; Lao, Lixing; Milley, Ryan J; Napadow, Vitaly; Schnyer, Rosa N; Stener-Victorin, Elisabet; Witt, Claudia M; Wayne, Peter M

2016-02-01

Research into acupuncture has had ripple effects beyond the field of acupuncture. This paper identifies five exemplars to illustrate that there is tangible evidence of the way insights gleaned from acupuncture research have informed biomedical research, practice, or policy. The first exemplar documents how early research into acupuncture analgesia has expanded into neuroimaging research, broadening physiologic understanding and treatment of chronic pain. The second describes how the acupuncture needle has become a tool to enhance biomedical knowledge of connective tissue. The third exemplar, which illustrates use of a modified acupuncture needle as a sham device, focuses on emergent understanding of placebo effects and, in turn, on insights into therapeutic encounters in treatments unrelated to acupuncture. The fourth exemplar documents that two medical devices now in widespread use were inspired by acupuncture: transcutaneous electrical nerve stimulators for pain control and antinausea wrist bands. The final exemplar describes how pragmatic clinical trial designs applied in acupuncture research have informed current general interest in comparative effectiveness research. In conclusion, these exemplars of unanticipated outcomes of acupuncture research comprise an additional rationale for continued support of basic and clinical research evaluating acupuncture and other under-researched therapies.

Automated interpretable computational biology in the clinic: a framework to predict disease severity and stratify patients from clinical data

Directory of Open Access Journals (Sweden)

Soumya Banerjee

2017-10-01

Full Text Available We outline an automated computational and machine learning framework that predicts disease severity and stratifies patients. We apply our framework to available clinical data. Our algorithm automatically generates insights and predicts disease severity with minimal operator intervention. The computational framework presented here can be used to stratify patients, predict disease severity and propose novel biomarkers for disease. Insights from machine learning algorithms coupled with clinical data may help guide therapy, personalize treatment and help clinicians understand the change in disease over time. Computational techniques like these can be used in translational medicine in close collaboration with clinicians and healthcare providers. Our models are also interpretable, allowing clinicians with minimal machine learning experience to engage in model building. This work is a step towards automated machine learning in the clinic.

The triphasics: insights for effective clinical use.

Science.gov (United States)

Youngkin, E Q; Miller, L G

1987-02-01

Three triphasic oral contraceptive preparations are currently being widely used in the United States. These are Ortho-Novum 7/7/7 (Ortho Pharmaceutical), Tri-Norinyl (Syntex) and Triphasil (Wyeth). The hormone manipulation in these formulations more closely mimics the normal menstrual cycle and decreases the total amount of hormone delivered. These drugs were formulated to decrease menstrual irregularities and nuisance side effects and increase menstrual control, while maintaining efficacy and safety. This article describes these products, their mechanisms of action, efficacy and selected areas of concern for clinical practice in relation to side effects, safety and menstrual control. Findings and suggestions related to the therapeutic administration, patient use, counseling and management of these newer oral contraceptives will assist the nurse practitioner in providing optimum care to the consumer.

Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour

Energy Technology Data Exchange (ETDEWEB)

Moeller, S.J.; Moeller, S.J.; Maloney, T.; Parvaz, M.A.; Alia-Klein, N.; Woicik, P.A.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

2010-04-15

Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes.

Clinical Significance and Mechanistic Insights into Ovarian Cancer Mitochondrial Dysfunction

Science.gov (United States)

2017-05-01

the grant period. Dr Shin has also benefitted from mentorship of Dr. H.G. Wang, a collaborator on the project, and has taken advantage of career ...Grant 193394 Genetech Gynecologic Cancer (Phaeton) 4/01/2017 - 3/31/2018 0.24 cal mths Young Investigator Career Development Award $135,000...Ca(2)(+) toolkit in endothelial progenitor cells derived from cancer patients suggest alternative targets for anti-angiogenic treatment? Biochim

Donor Derived Candida stellimalicola in a Clinical Specimen: Preservation Fluid Contamination During Pancreas Procurement.

Science.gov (United States)

Dupont, Damien; Huguenin, Antoine; Tisserand, Elodie; Reiter, Véronique; Morelon, Emmanuel; Badet, Lionel; Villena, Isabelle; Wallon, Martine; Toubas, Dominique

2017-07-05

We report here a case of possible donor-derived Candida stellimalicola infection after pancreas transplantation. Candida stellimalicola, an environmental non-filamentous yeast, was isolated from both the peritoneal fluid of the graft donor and the preservation fluid of the transplanted pancreas. Interestingly, this strain exhibited high minimum inhibitory concentrations to azoles. These results justified the use of echinocandins as therapy instead of fluconazole. This switch permitted a favorable outcome. To our knowledge, this is the first report of C. stellimalicola from clinical samples and therefore the first reported case of a possible human infection. This case report highlights the need for standardized microbiological procedures in solid organ transplant settings. Moreover, it underlines the importance of using molecular identification technique when routine techniques do not allow successful identification of the pathogen. It is of utmost importance to determine sensitivity profile, even in the absence of species-level identification, because resistance to fluconazole is not uncommon, especially in emergent species.

Isolation and expansion of adipose-derived stem cells for tissue engineering

DEFF Research Database (Denmark)

Fink, Trine; Rasmussen, Jeppe Grøndahl; Lund, Pia

2011-01-01

For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs for subseq......For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs...

Balancing Ethical Pros and Cons of Stem Cell Derived Gametes.

Science.gov (United States)

Segers, Seppe; Mertes, Heidi; de Wert, Guido; Dondorp, Wybo; Pennings, Guido

2017-07-01

In this review we aim to provide an overview of the most important ethical pros and cons of stem cell derived gametes (SCD-gametes), as a contribution to the debate about reproductive tissue engineering. Derivation of gametes from stem cells holds promising applications both for research and for clinical use in assisted reproduction. We explore the ethical issues connected to gametes derived from embryonic stem cells (both patient specific and non-patient specific) as well as those related to gametes derived from induced pluripotent stem cells. The technology of SCD-gametes raises moral concerns of how reproductive autonomy relates to issues of embryo destruction, safety, access, and applications beyond clinical infertility.

Effect of video self-observations vs. observations of others on insight in psychotic disorders.

Science.gov (United States)

David, Anthony S; Chis Ster, Irina; Zavarei, Hooman

2012-04-01

Improving insight in patients with schizophrenia and related disorders is a worthwhile goal. Previous work has suggested that patients' insight may improve if they see videos of themselves taken when ill. Our aim was to test the hypothesis that schizophrenia patients improve their insight after viewing videos of themselves when unwell more so than after viewing an actor. Forty patients admitted with an acute psychotic disorder underwent a videotaped recording of a clinical interview. The patients were then randomized to viewing this or a "control" video of a same-sex actor displaying psychotic symptoms approximately 3 weeks later. Insight, psychopathology, and mood were assessed before and 24 to 48 hours after viewing the videos. All participants showed general improvement across all measures. There was a trend for scores on the Schedule for the Assessment of Insight to improve more in those who viewed themselves when ill, but there were no clear statistically significant differences between the "self" and "other" video groups. In conclusion, video self-confrontation seems to be a safe and potentially effective means of enhancing insight, but evidence for a specific effect is lacking.

Extracellular matrix-derived hydrogels for dental stem cell delivery

OpenAIRE

Viswanath, Aiswarya; Vanacker, Julie; Germain, Loic; Leprince, Julien G.; Diogenes, Anibal; Shakesheff, Kevin M.; White, Lisa J.; des Rieux, Anne

2016-01-01

Decellularised mammalian extracellular matrices (ECM) have been widely accepted as an ideal substrate for repair and remodelling of numerous tissues in clinical and pre-clinical studies. Recent studies have demonstrated the ability of ECM scaffolds derived from site-specific homologous tissues to direct cell differentiation. The present study investigated the suitability of hydrogels derived from different source tissues: bone, spinal cord and dentine, as suitable carriers to deliver human ap...

Clinical Study of New Tetravalent (Type A, B, E, and F) Botulinum Toxoid Vaccine Derived from M Toxin in Japan.

Science.gov (United States)

Torii, Yasushi; Sugimoto, Nakaba; Kohda, Tomoko; Kozaki, Shunji; Morokuma, Kazunori; Horikawa, Yoshikane; Ginnaga, Akihiro; Yamamoto, Akihiko; Takahashi, Motohide

2017-07-24

Botulinum toxin is the most poisonous substance known, and is believed to be a highly lethal as a biological weapon; researchers of the toxin are exposed to this hazard. Botulinum toxoid vaccines have been produced and used in Japan. However, since clinical studies involving these vaccines were conducted before establishment of the Ethical Guidelines for Clinical Research in Japan, their immunogenicity and safety were not systematically assessed. In this study, we produced a new tetravalent (type A, B, E, and F) botulinum toxoid vaccine, the first ever to be derived from M toxin, and conducted quality control tests with reference to the Minimum Requirements in Japan for adsorbed tetanus toxoid vaccine. Subsequently, a clinical study using the new vaccine in 48 healthy adult volunteers was conducted according to the guidelines in Japan. No clinically serious adverse event was noted. Neutralizing antibody titers for each type of toxin in the participants' sera, 1 month after the 4th injection were more than 0.25 IU/mL, indicating sufficient protection. This study demonstrated that the vaccine has marked immunogenicity and is safe for use in humans.

Theoretical insights on the antioxidant activity of edaravone free radical scavengers derivatives

Science.gov (United States)

Cerón-Carrasco, José P.; Roy, Hélène M.; Cerezo, Javier; Jacquemin, Denis; Laurent, Adèle D.

2014-04-01

The prediction of antioxidant properties is not straightforward due to the complexity of the in vivo systems. Here, we use theoretical descriptors, including the potential of ionization, the electrodonating power and the spin density distribution, to characterize the antioxidant capacity of edaravone (EDV) derivatives. Our computations reveal the relationship between these parameters and their potential bioactivity as free radical scavengers. We conclude that more efficient antioxidants could be synthesized by tuning the R1 and R2 positions of the EDV structure, rather than modifying the R3 group. Such modifications might improve the antioxidant activity in neutral and deprotonated forms.

The way we measure: comparison of methods to derive radial surface brightness profiles

NARCIS (Netherlands)

Peters, S. P. C.; van der Kruit, P. C.; de Jong, R. S.

The breaks and truncations in the luminosity profile of face-on spiral galaxies offer valuable insights in their formation history. The traditional method of deriving the surface photometry profile for face-on galaxies is to use elliptical averaging. In this paper, we explore the question whether

Students' approaches to learning in a clinical practicum: A psychometric evaluation based on item response theory.

Science.gov (United States)

Zhao, Yue; Kuan, Hoi Kei; Chung, Joyce O K; Chan, Cecilia K Y; Li, William H C

2018-07-01

The investigation of learning approaches in the clinical workplace context has remained an under-researched area. Despite the validation of learning approach instruments and their applications in various clinical contexts, little is known about the extent to which an individual item, that reflects a specific learning strategy and motive, effectively contributes to characterizing students' learning approaches. This study aimed to measure nursing students' approaches to learning in a clinical practicum using the Approaches to Learning at Work Questionnaire (ALWQ). Survey research design was used in the study. A sample of year 3 nursing students (n = 208) who undertook a 6-week clinical practicum course participated in the study. Factor analyses were conducted, followed by an item response theory analysis, including model assumption evaluation (unidimensionality and local independence), item calibration and goodness-of-fit assessment. Two subscales, deep and surface, were derived. Findings suggested that: (a) items measuring the deep motive from intrinsic interest and deep strategies of relating new ideas to similar situations, and that of concept mapping served as the strongest discriminating indicators; (b) the surface strategy of memorizing facts and details without an overall picture exhibited the highest discriminating power among all surface items; and, (c) both subscales appeared to be informative in assessing a broad range of the corresponding latent trait. The 21-item ALWQ derived from this study presented an efficient, internally consistent and precise measure. Findings provided a useful psychometric evaluation of the ALWQ in the clinical practicum context, added evidence to the utility of the ALWQ for nursing education practice and research, and echoed the discussions from previous studies on the role of the contextual factors in influencing student choices of different learning strategies. They provided insights for clinical educators to measure

Perampanel for focal epilepsy: insights from early clinical experience.

Science.gov (United States)

Trinka, E; Steinhoff, B J; Nikanorova, M; Brodie, M J

2016-03-01

Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real-world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom-from-seizure rates in elderly vs younger patients. When using perampanel in elderly patients, special attention should be given to comorbidities and co-medication to avoid potential interactions or adverse events. Slower titration is generally recommended, and seizure control should be reassessed at a dose of 4 mg before further dose increases. Perampanel efficacy is similar in adolescents and adults; however, somnolence, nasopharyngitis, and aggression are more frequent in adolescents vs the overall population. Individualized and slow-dose titration can minimize adverse events. Low serum concentrations of perampanel may occur in patients also receiving some enzyme-inducing anti-epileptic drugs; a perampanel dose increase may be required. Adverse events of importance with perampanel include dizziness; anger, aggression, and hostile behavior (particularly in adolescents); and falls (particularly in patients >65 years). An individualized approach to dosing, including slower up-titration and bedtime dosing, reduces dizziness risk. Other drugs may cause or aggravate dizziness; reducing concomitant drugs may be necessary when up-titrating perampanel. It would seem clinically appropriate to give due consideration to avoiding use in patients with a history of anger or hostile/aggressive behavior. The possibility of such behaviors should be discussed with patients before starting perampanel, with monitoring during up-titration. Slower up-titration of perampanel in older patients helps reduce fall risk. © 2015 The Authors. Acta Neurologica Scandinavica Published by John Wiley & Sons Ltd.

The new final Clinical Skills examination in human medicine in Switzerland: Essential steps of exam development, implementation and evaluation, and central insights from the perspective of the national Working Group

Directory of Open Access Journals (Sweden)

Berendonk, Christoph

2015-10-01

Full Text Available Objective: Since 2011, the new national final examination in human medicine has been implemented in Switzerland, with a structured clinical-practical part in the OSCE format. From the perspective of the national Working Group, the current article describes the essential steps in the development, implementation and evaluation of the Federal Licensing Examination Clinical Skills (FLE CS as well as the applied quality assurance measures. Finally, central insights gained from the last years are presented. Methods: Based on the principles of action research, the FLE CS is in a constant state of further development. On the foundation of systematically documented experiences from previous years, in the Working Group, unresolved questions are discussed and resulting solution approaches are substantiated (planning, implemented in the examination (implementation and subsequently evaluated (reflection. The presented results are the product of this iterative procedure.Results: The FLE CS is created by experts from all faculties and subject areas in a multistage process. The examination is administered in German and French on a decentralised basis and consists of twelve interdisciplinary stations per candidate. As important quality assurance measures, the national Review Board (content validation and the meetings of the standardised patient trainers (standardisation have proven worthwhile. The statistical analyses show good measurement reliability and support the construct validity of the examination. Among the central insights of the past years, it has been established that the consistent implementation of the principles of action research contributes to the successful further development of the examination.Conclusion: The centrally coordinated, collaborative-iterative process, incorporating experts from all faculties, makes a fundamental contribution to the quality of the FLE CS. The processes and insights presented here can be useful for others planning a

Characterization of buffy coat-derived granulocytes for clinical use: a comparison with granulocyte colony-stimulating factor/dexamethasone-pretreated donor-derived products.

Science.gov (United States)

van de Geer, A; Gazendam, R P; Tool, A T J; van Hamme, J L; de Korte, D; van den Berg, T K; Zeerleder, S S; Kuijpers, T W

2017-02-01

Buffy coat-derived granulocytes have been described as an alternative to the apheresis product from donors pretreated with dexamethasone and granulocyte colony-stimulating factor (G-CSF). The latter is - dependent on the local and national settings - obtained following a demanding and time-consuming procedure, which is undesirable in critically ill septic patients. In contrast, buffy coat-derived products have a large volume and are often heavily contaminated with red cells and platelets. We developed a new pooled buffy coat-derived product with high purity and small volume, and performed a comprehensive functional characterization of these granulocytes. We pooled ten buffy coats following the production of platelet concentrates. Saline 0·9% was added to decrease the viscosity and the product was split into plasma, red cells and a 'super' buffy coat. Functional data of the granulocytes were compared to those obtained with granulocytes from healthy controls and G-CSF/dexamethasone-pretreated donors. Buffy coat-derived granulocytes showed adhesion, chemotaxis, reactive oxygen species production, degranulation, NETosis and in vitro killing of Staphylococcus aureus, Escherichia coli and Aspergillus species comparable to control and G-CSF/dexamethasone-derived granulocytes. Candida killing was superior compared to G-CSF/dexamethasone-derived granulocytes. Immunophenotyping was normal; especially no signs of activation in the buffy coat-derived granulocytes were seen. Viability was reduced. Buffy coats are readily available in the regular blood production process and would take away the concerns around the apheresis product. The product described appears a promising alternative for transfusion purposes. © 2017 International Society of Blood Transfusion.

Cognitive insight in psychosis: the relationship between self-certainty and self-reflection dimensions and neuropsychological measures.

Science.gov (United States)

Cooke, Michael A; Peters, Emmanuelle R; Fannon, Dominic; Aasen, Ingrid; Kuipers, Elizabeth; Kumari, Veena

2010-07-30

Cognitive insight in schizophrenia encompasses the evaluation and reinterpretation of distorted beliefs and appraisals. We investigated the neuropsychological basis of cognitive insight in psychosis. It was predicted that, like clinical insight, cognitive insight would be associated with a wide range of neuropsychological functions, but would be most strongly associated with measures of executive function. Sixty-five outpatients with schizophrenia or schizoaffective disorder were assessed on tests of intelligence quotient (IQ), executive function, verbal fluency, attention and memory, and completed the Beck Cognitive Insight Scale, which includes two subscales, self-certainty and self-reflection. Higher self-certainty scores reflect greater certainty about being right and more resistant to correction (poor insight), while higher self-reflection scores indicate the expression of introspection and the willingness to acknowledge fallibility (good insight). The self-certainty dimension of poor cognitive insight was significantly associated with lower scores on the Behavioural Assessment of Dysexecutive Syndrome; this relationship was not mediated by IQ. There were no relationships between self-reflection and any neuropsychological measures. We conclude that greater self-certainty (poor cognitive insight) is modestly associated with poorer executive function in psychotic individuals; self-reflection has no association with executive function. The self-certainty and self-reflection dimensions of cognitive insight have differential correlates, and probably different mechanisms, in psychosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Depot-medication compliance for patients with psychotic disorders: the importance of illness insight and treatment motivation.

Science.gov (United States)

Noordraven, Ernst L; Wierdsma, André I; Blanken, Peter; Bloemendaal, Anthony Ft; Mulder, Cornelis L

2016-01-01

Noncompliance is a major problem for patients with a psychotic disorder. Two important risk factors for noncompliance that have a severe negative impact on treatment outcomes are impaired illness insight and lack of motivation. Our cross-sectional study explored how they are related to each other and their compliance with depot medication. Interviews were conducted in 169 outpatients with a psychotic disorder taking depot medication. Four patient groups were defined based on low or high illness insight and on low or high motivation. The associations between depot-medication compliance, motivation, and insight were illustrated using generalized linear models. Generalized linear model showed a significant interaction effect between motivation and insight. Patients with poor insight and high motivation for treatment were more compliant (94%) (95% confidence interval [CI]: 1.821, 3.489) with their depot medication than patients with poor insight and low motivation (61%) (95% CI: 0.288, 0.615). Patients with both insight and high motivation for treatment were less compliant (73%) (95% CI: 0.719, 1.315) than those with poor insight and high motivation. Motivation for treatment was more strongly associated with depot-medication compliance than with illness insight. Being motivated to take medication, whether to get better or for other reasons, may be a more important factor than having illness insight in terms of improving depot-medication compliance. Possible implications for clinical practice are discussed.

Challenges of assessing critical thinking and clinical judgment in nurse practitioner students.

Science.gov (United States)

Gorton, Karen L; Hayes, Janice

2014-03-01

The purpose of this study was to determine whether there was a relationship between critical thinking skills and clinical judgment in nurse practitioner students. The study used a convenience, nonprobability sampling technique, engaging participants from across the United States. Correlational analysis demonstrated no statistically significant relationship between critical thinking skills and examination-style questions, critical thinking skills and scores on the evaluation and reevaluation of consequences subscale of the Clinical Decision Making in Nursing Scale, and critical thinking skills and the preceptor evaluation tool. The study found no statistically significant relationships between critical thinking skills and clinical judgment. Educators and practitioners could consider further research in these areas to gain insight into how critical thinking is and could be measured, to gain insight into the clinical decision making skills of nurse practitioner students, and to gain insight into the development and measurement of critical thinking skills in advanced practice educational programs. Copyright 2014, SLACK Incorporated.

Proofs that Develop Insight

Science.gov (United States)

Weber, Keith

2010-01-01

Many mathematics educators have noted that mathematicians do not only read proofs to gain conviction but also to obtain insight. The goal of this article is to discuss what this insight is from mathematicians' perspective. Based on interviews with nine research-active mathematicians, two sources of insight are discussed. The first is reading a…

Insight and psychosis: Functional and anatomical brain connectivity and self-reflection in Schizophrenia.

Science.gov (United States)

Ćurčić-Blake, Branislava; van der Meer, Lisette; Pijnenborg, Gerdina H M; David, Anthony S; Aleman, André

2015-12-01

Impaired insight into illness, associated with worse treatment outcome, is common in schizophrenia. Insight has been related to the self-reflective processing, centred on the medial frontal cortex. We hypothesized that anatomical and functional routes to and from the ventromedial prefrontal cortex (vmPFC) would differ in patients according to their degree of impaired insight. Forty-five schizophrenia patients and 19 healthy subjects performed a self-reflection task during fMRI, and underwent diffusion tensor imaging. Using dynamic causal modelling we observed increased effective connectivity from the posterior cingulate cortex (PCC), inferior parietal lobule (IPL), and dorsal mPFC (dmPFC) towards the vmPFC with poorer insight and decrease from vmPFC to the IPL. Stronger connectivity from the PCC to vmPFC during judgment of traits related to self was associated with poorer insight. We found small-scale significant changes in white matter integrity associated with clinical insight. Self-reflection may be influenced by synaptic changes that lead to the observed alterations in functional connectivity accompanied by the small-scale but measurable alterations in anatomical connections. Our findings may point to a neural compensatory response to an impairment of connectivity between self-processing regions. Similarly, the observed hyper-connectivity might be a primary deficit linked to inefficiency in the component cognitive processes that lead to impaired insight. We suggest that the stronger cognitive demands placed on patients with poor insight is reflected in increased effective connectivity during the task in this study. © 2015 Wiley Periodicals, Inc.

Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour

Science.gov (United States)

Maloney, Thomas; Parvaz, Muhammad A.; Alia-Klein, Nelly; Woicik, Patricia A.; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D.; Goldstein, Rita Z.

2010-01-01

Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects’ self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes. PMID:20395264

Clinical pitfalls in the diagnosis of ataque de nervios: a case study.

Science.gov (United States)

Lizardi, Dana; Oquendo, Maria A; Graver, Ruth

2009-09-01

Ataque de nervios (attack of nerves) is an idiom of distress generally thought of in relation to Caribbean Hispanics. The following case study discusses the presentation of ataque de nervios in a Colombian female. This case study provides insight into a different presentation of ataque de nervios in a new population that clinicians should be aware of in order to ensure accurate diagnosis. Ataque de nervios is a distinct syndrome that does not fully correspond with any single DSM-IV diagnosis. However, there is overlap between symptoms in this condition and those in conventional clinical diagnoses. Common problems in deriving an accurate differential diagnosis are discussed. Implications for treatment are also reviewed, with an emphasis on a comprehensive approach to treatment that supports the client's norms and values.

A deeper view of insight in schizophrenia: Insight dimensions, unawareness and misattribution of particular symptoms and its relation with psychopathological factors.

Science.gov (United States)

Pousa, Esther; Ochoa, Susana; Cobo, Jesús; Nieto, Lourdes; Usall, Judith; Gonzalez, Beatriz; Garcia-Ribera, Carles; Pérez Solà, Victor; Ruiz, Ada-I; Baños, Iris; Cobo, Jesús; García-Ribera, Carles; González, Beatriz; Massons, Carmina; Nieto, Lourdes; Monserrat, Clara; Ochoa, Susana; Pousa, Esther; Ruiz, Ada-Inmaculada; Ruiz, Isabel; Sanchez-Cabezudo, Dolores; Usall, Judith

2017-11-01

1. To describe insight in a large sample of schizophrenia subjects from a multidimensional point of view, including unawareness of general insight dimensions as well as unawareness and misattribution of particular symptoms. 2. To explore the relationship between unawareness and clinical and socio-demographic variables. 248 schizophrenia patients were assessed with the Positive and Negative Syndrome Scale (PANSS, five factor model of Lindenmayer) and the full Scale of Unawareness of Mental Disorder (SUMD). Bivariate associations and multiple linear regression analyses were used to investigate the relationship between unawareness, symptoms and socio-demographic variables. Around 40% of the sample showed unawareness of mental disorder, of the need for medication and of the social consequences. Levels of unawareness and misattribution of particular symptoms varied considerably. General unawareness dimensions showed small significant correlations with positive, cognitive and excitement factors of psychopathology, whereas these symptom factors showed higher correlations with unawareness of particular symptoms. Similarly, regression models showed a small significant predictive value of positive symptoms in the three general unawareness dimensions while a moderate one in the prediction of particular symptoms. Misattribution showed no significant correlations with any symptom factors. Results confirm that insight in schizophrenia is a multi-phased phenomenon and that unawareness into particular symptoms varies widely. The overlap between unawareness dimensions and psychopathology is small and seems to be restricted to positive and cognitive symptoms, supporting the accounts from cognitive neurosciences that suggest that besides basic cognition poor insight may be in part a failure of self-reflection or strategic metacognition. Copyright © 2017 Elsevier B.V. All rights reserved.

Automation in Clinical Microbiology

Science.gov (United States)

Ledeboer, Nathan A.

2013-01-01

Historically, the trend toward automation in clinical pathology laboratories has largely bypassed the clinical microbiology laboratory. In this article, we review the historical impediments to automation in the microbiology laboratory and offer insight into the reasons why we believe that we are on the cusp of a dramatic change that will sweep a wave of automation into clinical microbiology laboratories. We review the currently available specimen-processing instruments as well as the total laboratory automation solutions. Lastly, we outline the types of studies that will need to be performed to fully assess the benefits of automation in microbiology laboratories. PMID:23515547

Perioperative leadership: managing change with insights, priorities, and tools.

Science.gov (United States)

Taylor, David L

2014-07-01

The personal leadership of the perioperative director is a critical factor in the success of any change management initiative. This article presents an approach to perioperative nursing leadership that addresses obstacles that prevent surgical departments from achieving high performance in clinical and financial outcomes. This leadership approach consists of specific insights, priorities, and tools: key insights include self-understanding of personal barriers to leadership and accuracy at understanding economic and strategic considerations related to the OR environment; key priorities include creating a customer-centered organization, focusing on process improvement, and concentrating on culture change; and key tools include using techniques (e.g., direct engagement, collaborative leadership) to align surgical organizations with leadership priorities and mitigate specific perioperative management risks. Included in this article is a leadership development plan for perioperative directors. Copyright © 2014 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Derivation and characterisation of hESC lines from supernumerary embryos, experience from Odense, Denmark

DEFF Research Database (Denmark)

Harkness, Linda; Rasmussen, Iben Anne; Erb, Karin

2010-01-01

The derivation and characterisation of human embryonic stem cells provides a source of pluripotent stem cells with potential for clinical applications. Utilising locally sourced embryos from two IVF clinics, we derived and characterised five new cell lines for use in a non-clinical setting. Analy...

Pinostrobin Derivatives from PrenylationReaction and their Antibacterial Activity against Clinical Bacteria

Science.gov (United States)

Marliyana, S. D.; Mujahidin, D.; Syah, Y. M.

2018-04-01

Kaempferia pandurata (syn. Boesenbergia rotunda, B. pandurata (Roxb.)Schltr), locally known as "TemuKunci"in Indonesia, is one of the medicinal plants of the family Zingiberaceae. Phytochemical studies on the rhizome of K. pandurata showed the presence of flavonoid derivative, namely flavanones, which constitute as the main components of this plant. Bioactivity studies on this species exhibited various biological activities, such as antibacteria, anti-inflammatory, antitumor, antidiarrhea, antidisentri, anti-HIV, antioxidant, antipyretic, analgesic and insecticides. Among the biological activities, the antibacterial activity results are important as an attempt to answer the emergence of resistance of some bacteria against existing drugs, as well as the emergence of a number of outbreaks of disease caused by bacteria. Therefore, a search to find new compounds that are potential as an antibacterial is an urgent matter. The present study was aimed at the chemical transformation of pinostrobin (1) from K. pandurata rhizome and an antibacterial activity.The chemical transformation was performed through a prenylation reaction of pinostrobin (1) which is the main component of K. pandurata rhizome. The prenylation reaction was carried out by reacting pinostrobin (1) with prenyl bromide and potassium carbonat (K2CO3). The purification of product was done using the radial chromatography with mix solvent n-hexane and ethyl acetate (97.5:2.5; 9.5:0.5; 9.0:1.0.; 8.0:2.0). The purity test of isolated compound was analysedby TLC using different types of eluent. The identification of compounds was determined based on NMR data and mass spectra analysis. Five compounds were obtained from the prenylation reaction, i.e. monooxyprenylated pinostrobin (2), monooxyprenylated chalcone (3), diprenylated chalcone (4), triprenylated chalcone (5), and triprenylated cyclohexene chalcone (6). These compounds were tested for antibacterial activities against four clinical bacteria, namely

Clinical proteomics

DEFF Research Database (Denmark)

Albrethsen, Jakob; Frederiksen, Hanne; Johannsen, Trine Holm

2018-01-01

Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS)-platforms...... standards and calibrants. The present challenge is to examine if targeted proteomics of IGF-I can truly measure up to the routine performance that must be expected from a clinical testing platform.......Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS......)-platforms already implemented in many clinical laboratories for routine quantitation of small molecules (i.e. uHPLC coupled to triple-quadrupole MS). Progress in targeted proteomics of circulating insulin-like growth factor 1 (IGF-I) have provided valuable insights about tryptic peptides, transitions, internal...

The Effect of a Self-Reflection and Insight Program on the Nursing Competence of Nursing Students: A Longitudinal Study.

Science.gov (United States)

Pai, Hsiang-Chu

2015-01-01

Nurses have to solve complex problems for their patients and their families, and as such, nursing care capability has become a focus of attention. The aim of this longitudinal study was to develop a self-reflection practice exercise program for nursing students to be used during clinical practice and to evaluate the effects of this program empirically and longitudinally on change in students' clinical competence, self-reflection, stress, and perceived teaching quality. An additional aim was to determine the predictors important to nursing competence. We sampled 260 nursing students from a total of 377 practicum students to participate in this study. A total of 245 students nurse completed 4 questionnaires, Holistic Nursing Competence Scale, Self-Reflection and Insight Scale, Perceived Stress Scale, and Clinical Teaching Quality Scale, at 2, 4, and 6 months after clinical practice experience. Generalized estimating equation models were used to examine the change in scores on each of the questionnaires. The findings showed that, at 6 months after clinical practice, nursing competence was significantly higher than at 2 and 4 months, was positively related to self-reflection and insight, and was negatively related to practice stress. Nursing students' competence at each time period was positively related to clinical teachers' instructional quality at 4 and 6 months. These results indicate that a clinical practice program with self-reflection learning exercise improves nursing students' clinical competence and that nursing students' self-reflection and perceived practice stress affect their nursing competence. Nursing core competencies are enhanced with a self-reflection program, which helps nursing students to improve self-awareness and decrease stress that may interfere with learning. Further, clinical practice experience, self-reflection and insight, and practice stress are predictors of nursing students' clinical competence. Copyright © 2015 Elsevier Inc. All

Transcriptomic analysis of monocytes and macrophages derived from CLL patients which display differing abilities to respond to therapeutic antibody immune complexes

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M. Burgess

2016-03-01

Full Text Available Chronic lymphocytic leukemia (CLL is the most common adult leukemia. While therapeutic antibodies show clinical activity in CLL patients, resistance inevitably develops resulting in treatment failure. Identifying mechanisms of antibody resistance and methods to reduce resistance would be valuable in managing CLL. Monocyte derived cells (MDCs, also known as nurse like cells (NLCs in CLL [1,2], are known to be crucial components of the CLL microenvironment network and following “maturation” in in vitro culture systems are able to provide support for the survival of the malignant B cells from CLL patients. In addition to their protective role, MDCs are key effector cells in mediating responses to therapeutic antibody therapies [3]. We have determined that macrophages from patients with early stable CLL are able to elicit superior cytotoxic response to therapeutic antibodies than macrophages derived from patients with progressive CLL. We have exploited this unique finding to gain insight into antibody resistance. Thus, we have profiled monocytes on day 0 and MDCs on day 7 from antibody sensitive and antibody resistant CLL patients (GEO accession number GEO: GSE71409. We show that there are no significant differences in transcriptomes from the monocytes or MDCs derived from sensitive or resistant patient samples. However, we show that MDCs acquire an M2-like macrophage transcriptomic signature following 7 days culture regardless of whether they were derived from sensitive or resistant patient samples. Keywords: Chronic lymphocytic leukemia, Monocyte derived cells, Antibody resistance, Microarray

Children's self reported discomforts as participants in clinical research

NARCIS (Netherlands)

Staphorst, Mira S.; Hunfeld, Joke A. M.; van de Vathorst, Suzanne; Passchier, Jan; van Goudoever, Johannes B.

2015-01-01

There is little empirical evidence on children's subjective experiences of discomfort during clinical research procedures. Therefore, Institutional Review Boards have limited empirical information to guide their decision-making on discomforts for children in clinical research. To get more insight

Copy number variation and autism: New insights and clinical implications

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Brian Hon-Yin Chung

2014-07-01

Full Text Available Genomic research can lead to discoveries of copy number variations (CNVs which can be a susceptibility factor for autism spectrum disorder (ASD. The clinical translation is that this can improve the care of children with ASD. Chromosome microarray is now the first-tiered genetic investigation for ASD, with a detection rate exceeding conventional cytogenetics and any single gene testing. However, interpretation of the results is challenging and there is no consensus on “what” and “how much” to disclose. In this article, we will review how CNV studies have improved our understanding of ASD, the clinical applications, and related counseling issues. Future direction of autism genetic research is also discussed.

Illness Insight and Recovery: How Important is Illness Insight in Peoples’ Recovery Process?

DEFF Research Database (Denmark)

Korsbek, Lisa

2013-01-01

. Sources Used:The writing is based on research literature related to illness insight and on personal recovery experiences.Conclusions and Implications for Practice: It is helpful to consider the integration of the issue of illness insight when addressing the questions and consequences of diagnosis......Topic: This account reflects on the topic of illness insight and recovery. Purpose: The purpose of the account is to clarify our understanding about the importance of illness insight in peoples’ recovery process, especially when relating the question of illness insight to the question of identity......, and to assist individuals to work through the false analogy between illness and identity while supporting the transformation from patient to person. It is also necessary for clinicians to develop a clear understanding of peoples’ actual needs and gain more knowledge about peoples’ own views and experiences...

IgG4-related disease -Mechanistic insights from both clinical and immunologic understanding of this condition.

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Maehara, Takashi

2017-01-01

IgG4-related disease (IgG4-RD) is a chronic inflammatory disease characterized by tumescent lesions with characteristic storiform fibrosis, obliterative phlebitis and a marked lymphoplasmacytic infiltrate that includes a large number of IgG4 positive plasma cells. It's widely accepted that rituximab-mediated B cell depletion therapy is effective for this disease. Important mechanistic insights correlated with the pathogenesis of IgG4-RD have been gradually disclosed from studies of patients treated by B cell depletion. 1) IgG4-RD patients have the large clonal expansion of activated plasmablasts and CD4 + CTLs, so this disease might be antigen-driven. 2) CD4 + CTLs are the dominant population in affected tissues, on the other hands direct examination of T H1 and T H2 cells in tissues reveal that these subsets are sparse. 3) CD4 + CTLs into affected lesions secret cytotoxic, inflammatory, and pro-fibrotic cytokines, indicating reactivation by antigen in tissue sites. 4) The decline in CD4 + CTLs number by B cell depletion is associated with clinical remission of IgG4-RD patients. 5) CD4 + CXCR5 + T FH cells that express IL-4 are located outside germinal centers and specialized T FH cells that expanded dramatically in conditions with polarized class switching to IgG4. These results suggested that the disease pathogenesis might be based on orchestrating of activated plasmablasts, CD4 + CTLs, and T FH cells.

Incorporating evolutionary insights to improve ecotoxicology for freshwater species

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Brady, Steven P.; Richardson, Jonathan L.; Kunz, Bethany K.

2017-01-01

Ecotoxicological studies have provided extensive insights into the lethal and sublethal effects of environmental contaminants. These insights are critical for environmental regulatory frameworks, which rely on knowledge of toxicity for developing policies to manage contaminants. While varied approaches have been applied to ecotoxicological questions, perspectives related to the evolutionary history of focal species or populations have received little consideration. Here, we evaluate chloride toxicity from the perspectives of both macroevolution and contemporary evolution. First, by mapping chloride toxicity values derived from the literature onto a phylogeny of macroinvertebrates, fish, and amphibians, we tested whether macroevolutionary relationships across species and taxa are predictive of chloride tolerance. Next, we conducted chloride exposure tests for two amphibian species to assess whether potential contemporary evolutionary change associated with environmental chloride contamination influences chloride tolerance across local populations. We show that explicitly evaluating both macroevolution and contemporary evolution can provide important and even qualitatively different insights from those obtained via traditional ecotoxicological studies. While macroevolutionary perspectives can help forecast toxicological end points for species with untested sensitivities, contemporary evolutionary perspectives demonstrate the need to consider the environmental context of exposed populations when measuring toxicity. Accounting for divergence among populations of interest can provide more accurate and relevant information related to the sensitivity of populations that may be evolving in response to selection from contaminant exposure. Our data show that approaches accounting for and specifically examining variation among natural populations should become standard practice in ecotoxicology.

Assess the discrimination of Achilles InSight calcaneus quantitative ultrasound device for osteoporosis in Chinese women: Compared with dual energy X-ray absorptiometry measurements

Energy Technology Data Exchange (ETDEWEB)

Jin Ningning, E-mail: ningning_jin@163.com [Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100032 (China); Lin Shouqing, E-mail: Shouqing_Lin2003@yahoo.com.cn [Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100032 (China); Zhang Ying, E-mail: steel_lee@sina.com.cn [Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100032 (China); Chen Fengling, E-mail: bjzqk@126.com [Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100032 (China)

2010-11-15

Since the implementation of quantitative ultrasound (QUS) technology may become a part of future clinical decision making to identify osteoporosis and prevent fractures, this study was initiated to evaluate the correlations of QUS parameters and axial bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) and to assess the discrimination of QUS measurements for osteoporosis and osteopenia defined by WHO criteria. 106 native Chinese women (aged 50.2 {+-} 10.9 SD, 21-74 years) were involved. Each subject received both QUS measurements at left calcaneus with Achilles InSight and DXA measurements with DPX-L at lumbar spine (L{sub 2-4}), total hip and femoral neck. Achilles InSight provided the stiffness index (SI) which derived from Broadband Ultrasound Attenuation (BUA) and Speed of Sound (SOS), and the T-scores of SI were calculated. We found that the QUS parameter SI was statistically significant but medium correlated (r = 0.458-0.587) with DXA at the lumbar spine, total hip and femoral neck (P < 0.0001 for all correlations). With ROC analysis, the area under the ROC curve of diagnosis of osteoporosis and osteopenia were 0.933 and 0.796, respectively. To identify osteoporosis, when the T-score threshold of SI was defined as -1.4, the sensitivity was 100%, and the specificity was 73.7%. Our study confirmed that QUS measurements performed with Achilles InSight were capable to identify osteoporosis defined by axial BMD using DXA in Chinese women.

Assess the discrimination of Achilles InSight calcaneus quantitative ultrasound device for osteoporosis in Chinese women: Compared with dual energy X-ray absorptiometry measurements

International Nuclear Information System (INIS)

Jin Ningning; Lin Shouqing; Zhang Ying; Chen Fengling

2010-01-01

Since the implementation of quantitative ultrasound (QUS) technology may become a part of future clinical decision making to identify osteoporosis and prevent fractures, this study was initiated to evaluate the correlations of QUS parameters and axial bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) and to assess the discrimination of QUS measurements for osteoporosis and osteopenia defined by WHO criteria. 106 native Chinese women (aged 50.2 ± 10.9 SD, 21-74 years) were involved. Each subject received both QUS measurements at left calcaneus with Achilles InSight and DXA measurements with DPX-L at lumbar spine (L 2-4 ), total hip and femoral neck. Achilles InSight provided the stiffness index (SI) which derived from Broadband Ultrasound Attenuation (BUA) and Speed of Sound (SOS), and the T-scores of SI were calculated. We found that the QUS parameter SI was statistically significant but medium correlated (r = 0.458-0.587) with DXA at the lumbar spine, total hip and femoral neck (P < 0.0001 for all correlations). With ROC analysis, the area under the ROC curve of diagnosis of osteoporosis and osteopenia were 0.933 and 0.796, respectively. To identify osteoporosis, when the T-score threshold of SI was defined as -1.4, the sensitivity was 100%, and the specificity was 73.7%. Our study confirmed that QUS measurements performed with Achilles InSight were capable to identify osteoporosis defined by axial BMD using DXA in Chinese women.

Are privacy-enhancing technologies for genomic data ready for the clinic? A survey of medical experts of the Swiss HIV Cohort Study.

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Raisaro, Jean-Louis; McLaren, Paul J; Fellay, Jacques; Cavassini, Matthias; Klersy, Catherine; Hubaux, Jean-Pierre

2018-03-01

Protecting patient privacy is a major obstacle for the implementation of genomic-based medicine. Emerging privacy-enhancing technologies can become key enablers for managing sensitive genetic data. We studied physicians' attitude toward this kind of technology in order to derive insights that might foster their future adoption for clinical care. We conducted a questionnaire-based survey among 55 physicians of the Swiss HIV Cohort Study who tested the first implementation of a privacy-preserving model for delivering genomic test results. We evaluated their feedback on three different aspects of our model: clinical utility, ability to address privacy concerns and system usability. 38/55 (69%) physicians participated in the study. Two thirds of them acknowledged genetic privacy as a key aspect that needs to be protected to help building patient trust and deploy new-generation medical information systems. All of them successfully used the tool for evaluating their patients' pharmacogenomics risk and 90% were happy with the user experience and the efficiency of the tool. Only 8% of physicians were unsatisfied with the level of information and wanted to have access to the patient's actual DNA sequence. This survey, although limited in size, represents the first evaluation of privacy-preserving models for genomic-based medicine. It has allowed us to derive unique insights that will improve the design of these new systems in the future. In particular, we have observed that a clinical information system that uses homomorphic encryption to provide clinicians with risk information based on sensitive genetic test results can offer information that clinicians feel sufficient for their needs and appropriately respectful of patients' privacy. The ability of this kind of systems to ensure strong security and privacy guarantees and to provide some analytics on encrypted data has been assessed as a key enabler for the management of sensitive medical information in the near future

Determining criminal responsibility: How relevant are insight and personal attitudes to mock jurors?

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Jung, Sandy

2015-01-01

High levels of insight are interpreted as indications of a treatment compliance and good outcome by clinical professionals. However, it is unclear whether a defendant's insight plays a role in the decision-making of jurors when determining criminal responsibility. It may be the case that personal biases and attitudes toward the mentally ill and the insanity defense are more relevant in such decisions. This study examines the influence of two core dimensions of insight and personal attitudes on juror decision-making. Participants read trial scenarios describing a defendant who is accused of a violent crime and is diagnosed with schizophrenia. Assigning a verdict of not criminally responsible to the defendant was not influenced by insight, but instead, by supportive attitudes of the insanity defense and higher attributions of blame to external factors and to psychological factors. These findings highlight the need for continued investigation in the area of extra-legal factors that guide legal decision-making when defendants have a mental disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

The skeletal endocannabinoid system: clinical and experimental insights.

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Raphael, Bitya; Gabet, Yankel

2016-05-01

Recently, there has been a rapidly growing interest in the role of cannabinoids in the regulation of skeletal remodeling and bone mass, addressed in basic, translational and clinical research. Since the first publications in 2005, there are more than 1000 publications addressing the skeletal endocannabinoid system. This review focuses on the roles of the endocannabinoid system in skeletal biology via the cannabinoid receptors CB1, CB2 and others. Endocannabinoids play important roles in bone formation, bone resorption and skeletal growth, and are sometimes age, gender, species and strain dependent. Controversies in the literature and potential therapeutic approaches targeting the endocannabinoid system in skeletal disorders are also discussed.

The Impact of the Brain-Derived Neurotrophic Factor Gene on Trauma and Spatial Processing

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Jessica K. Miller

2017-11-01

Full Text Available The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF gene, given its impact on the integrity of the hippocampal memory system. Research into human navigation also considers the BDNF gene in relation to hippocampal dependent spatial processing. This speculative paper brings together trauma and spatial processing for the first time and presents exploratory research into their interactions with BDNF. We propose that quantifying the impact of BDNF on trauma and spatial processing is critical and may well explain individual differences in clinical trauma treatment outcomes and in navigation performance. Research has already shown that the BDNF gene influences PTSD severity and prevalence as well as navigation behaviour. However, more data are required to demonstrate the precise hippocampal dependent processing mechanisms behind these influences in different populations and environmental conditions. This paper provides insight from recent studies and calls for further research into the relationship between allocentric processing, trauma processing and BDNF. We argue that research into these neural mechanisms could transform PTSD clinical practice and professional support for individuals in trauma-exposing occupations such as emergency response, law enforcement and the military.

The Impact of the Brain-Derived Neurotrophic Factor Gene on Trauma and Spatial Processing.

Science.gov (United States)

Miller, Jessica K; McDougall, Siné; Thomas, Sarah; Wiener, Jan

2017-11-27

The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD) continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF) gene, given its impact on the integrity of the hippocampal memory system. Research into human navigation also considers the BDNF gene in relation to hippocampal dependent spatial processing. This speculative paper brings together trauma and spatial processing for the first time and presents exploratory research into their interactions with BDNF. We propose that quantifying the impact of BDNF on trauma and spatial processing is critical and may well explain individual differences in clinical trauma treatment outcomes and in navigation performance. Research has already shown that the BDNF gene influences PTSD severity and prevalence as well as navigation behaviour. However, more data are required to demonstrate the precise hippocampal dependent processing mechanisms behind these influences in different populations and environmental conditions. This paper provides insight from recent studies and calls for further research into the relationship between allocentric processing, trauma processing and BDNF. We argue that research into these neural mechanisms could transform PTSD clinical practice and professional support for individuals in trauma-exposing occupations such as emergency response, law enforcement and the military.

Dreaming and insight

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Edwards, Christopher L.; Ruby, Perrine M.; Malinowski, Josie E.; Bennett, Paul D.; Blagrove, Mark T.

2013-01-01

This paper addresses claims that dreams can be a source of personal insight. Whereas there has been anecdotal backing for such claims, there is now tangential support from findings of the facilitative effect of sleep on cognitive insight, and of REM sleep in particular on emotional memory consolidation. Furthermore, the presence in dreams of metaphorical representations of waking life indicates the possibility of novel insight as an emergent feature of such metaphorical mappings. In order to assess whether personal insight can occur as a result of the consideration of dream content, 11 dream group discussion sessions were conducted which followed the Ullman Dream Appreciation technique, one session for each of 11 participants (10 females, 1 male; mean age = 19.2 years). Self-ratings of deepened self-perception and personal gains from participation in the group sessions showed that the Ullman technique is an effective procedure for establishing connections between dream content and recent waking life experiences, although wake life sources were found for only 14% of dream report text. The mean Exploration-Insight score on the Gains from Dream Interpretation questionnaire was very high and comparable to outcomes from the well-established Hill (1996) therapist-led dream interpretation method. This score was associated between-subjects with pre-group positive Attitude Toward Dreams (ATD). The need to distinguish “aha” experiences as a result of discovering a waking life source for part of a dream, from “aha” experiences of personal insight as a result of considering dream content, is discussed. Difficulties are described in designing a control condition to which the dream report condition can be compared. PMID:24550849

Solving the puzzle of pluripotent stem cell-derived cardiomyocyte maturation: piece by piece.

Science.gov (United States)

Lundy, David J; Lee, Desy S; Hsieh, Patrick C H

2017-03-01

There is a growing need for in vitro models which can serve as platforms for drug screening and basic research. Human adult cardiomyocytes cannot be readily obtained or cultured, and so pluripotent stem cell-derived cardiomyocytes appear to be an attractive option. Unfortunately, these cells are structurally and functionally immature-more comparable to foetal cardiomyocytes than adult. A recent study by Ruan et al ., provides new insights into accelerating the maturation process and takes us a step closer to solving the puzzle of pluripotent stem cell-derived cardiomyocyte maturation.

Insight in Psychosis : Relationship With Neurocognition, Social Cognition and Clinical Symptoms Depends on Phase of Illness

NARCIS (Netherlands)

Quee, P.J.; van der Meer, L.; Bruggeman, R.; de Haan, L.; Krabbendam, L.; Cahn, W.; Mulder, N.C.; Wiersma, D.; Aleman, A.

Reduced insight has been reported in a majority of patients with a psychotic disorder. Most studies have focused on associations with neurocognition, neglecting relations with social cognition. Two hundred seventy patients with nonaffective psychosis participated in this study, which was part of the

Insight in Psychosis: Relationship With Neurocognition, Social Cognition and Clinical Symptoms Depends on Phase of Illness

NARCIS (Netherlands)

Quee, Piotr J.; van der Meer, Lisette; Bruggeman, Richard; de Haan, Lieuwe; Krabbendam, Lydia; Cahn, Wiepke; Mulder, Niels C. L.; Wiersma, Durk; Aleman, André

2011-01-01

Reduced insight has been reported in a majority of patients with a psychotic disorder. Most studies have focused on associations with neurocognition, neglecting relations with social cognition. Two hundred seventy patients with nonaffective psychosis participated in this study, which was part of the

Plant-Derived Antimicrobials: Insights into Mitigation of Antimicrobial Resistance

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Shun-Kai Yang

2018-07-01

Full Text Available Antibiotic resistance had first been reported not long after the discovery of the first antibiotic and has remained a major public health issue ever since. Challenges are constantly encountered during the mitigation process of antibiotic resistance in the clinical setting; especially with the emergence of the formidable superbug, a bacteria with multiple resistance towards different antibiotics; this resulted in the term multidrug resistant (MDR bacteria. This rapid evolution of the resistance phenomenon has propelled researchers to continuously uncover new antimicrobial agents in a bid to hopefully, downplay the rate of evolution despite a drying pipeline. Recently, there has been a paradigm shift in the mining of potential antimicrobials; in the past, targets for drug discovery were from microorganisms and at current, the focus has moved onto plants, this is mainly due to the beneficial attributes that plants are able to confer over that of microorganisms. This review will briefly discuss antibiotic resistance mechanisms employed by resistant bacteria followed by a detailed expository regarding the use of secondary metabolites from plants as a potential solution to the MDR pathogen. Finally, future prospects recommending enhancements to the usage of plant secondary metabolites to directly target antibiotic resistant pathogens will be discussed.

The Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) study.

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Paul, Ian M; Williams, Jennifer S; Anzman-Frasca, Stephanie; Beiler, Jessica S; Makova, Kateryna D; Marini, Michele E; Hess, Lindsey B; Rzucidlo, Susan E; Verdiglione, Nicole; Mindell, Jodi A; Birch, Leann L

2014-07-18

Because early life growth has long-lasting metabolic and behavioral consequences, intervention during this period of developmental plasticity may alter long-term obesity risk. While modifiable factors during infancy have been identified, until recently, preventive interventions had not been tested. The Intervention Nurses Starting Infants Growing on Healthy Trajectories (INSIGHT). Study is a longitudinal, randomized, controlled trial evaluating a responsive parenting intervention designed for the primary prevention of obesity. This "parenting" intervention is being compared with a home safety control among first-born infants and their parents. INSIGHT's central hypothesis is that responsive parenting and specifically responsive feeding promotes self-regulation and shared parent-child responsibility for feeding, reducing subsequent risk for overeating and overweight. 316 first-time mothers and their full-term newborns were enrolled from one maternity ward. Two weeks following delivery, dyads were randomly assigned to the "parenting" or "safety" groups. Subsequently, research nurses conduct study visits for both groups consisting of home visits at infant age 3-4, 16, 28, and 40 weeks, followed by annual clinic-based visits at 1, 2, and 3 years. Both groups receive intervention components framed around four behavior states: Sleeping, Fussy, Alert and Calm, and Drowsy. The main study outcome is BMI z-score at age 3 years; additional outcomes include those related to patterns of infant weight gain, infant sleep hygiene and duration, maternal responsiveness and soothing strategies for infant/toddler distress and fussiness, maternal feeding style and infant dietary content and physical activity. Maternal outcomes related to weight status, diet, mental health, and parenting sense of competence are being collected. Infant temperament will be explored as a moderator of parenting effects, and blood is collected to obtain genetic predictors of weight status. Finally, second

Hydroxyurea derivatives of irofulven with improved antitumor efficacy.

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Staake, Michael D; Kashinatham, Alisala; McMorris, Trevor C; Estes, Leita A; Kelner, Michael J

2016-04-01

Irofulven is a semi-synthetic derivative of Illudin S, a toxic sesquiterpene isolated from the mushroom Omphalotus illudens. Irofulven has displayed significant antitumor activity in various clinical trials but displayed a limited therapeutic index. A new derivative of irofulven was prepared by reacting hydroxyurea with irofulven under acidic conditions. Acetylation of this new compound with acetic anhydride produced a second derivative. Both of these new derivatives displayed significant antitumor activity in vitro and in vivo comparable to or exceeding that of irofulven. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cross-cultural psychometric assessment of the VAGUS insight into psychosis scale - Spanish version.

Science.gov (United States)

de León, Patricia Ponce; Gerretsen, Philip; Shah, Parita; Saracco-Alvarez, Ricardo; Graff-Guerrero, Ariel; Fresán, Ana

2018-01-01

Impaired insight into illness, a core feature of schizophrenia with negative clinical implications, is a multidimensional phenomenon existing on a continuum. However, the degree to which illness perception in distinct cultures influences the appraisal of insight into illness in schizophrenia remains unclear. As such, we aimed to determine if the psychometric properties of the VAGUS insight into psychosis scale (www.vagusonline.com), which was originally assessed in English speaking Canadians, were similar in a sample of Latino Mexican Spanish speaking patients with schizophrenia. To accomplish this, the VAGUS - Self-Report (SR) version was translated from English to Spanish and psychometrically evaluated in 95 participants. The Spanish version of the VAGUS-SR was internally consistent (ᾳ = 0.713), and demonstrated good convergent and discriminant validity with the subscales of the Positive and Negative Syndrome Scale. Factor analysis identified two components of insight, congruent with two of the components of the English version of the VAGUS-SR. In conclusion, the VAGUS-SR is a brief, novel, and valid measure of insight into illness in schizophrenia, which demonstrated similar psychometric properties in two culturally and linguistically distinct samples with schizophrenia. Future studies should assess whether the VAGUS demonstrates similar psychometric properties in non-Western cultures. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical and histologic evaluation of non-surgical periodontal therapy with enamel matrix derivative: a report of four cases.

Science.gov (United States)

Mellonig, James T; Valderrama, Pilar; Gregory, Holly J; Cochran, David L

2009-09-01

Enamel matrix derivative (EMD) is a composite of proteins that was demonstrated histologically to work as an adjunct to periodontal regenerative surgical therapy. The purpose of this study was to evaluate the clinical and histologic effects of EMD as an adjunct to scaling and root planing. Four patients with severe chronic periodontitis and scheduled to receive complete dentures were accrued. Probing depth and clinical attachment levels were obtained. Unlimited time was allowed for hand and ultrasonic instrumentation. A notch was placed in the root >or=1 to 2 mm from the apical extent of root planing. EMD was inserted into the pocket, and a periodontal dressing was placed. Patients were seen every 2 weeks for plaque control. At 6 months post-treatment, soft tissue measurements were repeated, and the teeth were removed en bloc and prepared for histomorphologic analysis. Probing depth reduction and clinical attachment level gain were obtained in three-fourths of the specimens. Three of the four specimens analyzed histologically demonstrated new cementum, bone, periodontal ligament, and connective tissue attachment coronal to the notch. In one specimen, the gingival margin had receded below the notch. The results were unexpected and may represent an aberration. However, the substantial reduction in deep probing depths and clinical attachment level gain in three of four specimens, in addition to the histologic findings of new cementum, new bone, a new periodontal ligament, and a new connective tissue attachment, suggest that EMD may be useful as an adjunct to scaling and root planing in single-rooted teeth.

Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats - A possible new hydrogen resource for clinical use.

Science.gov (United States)

Cui, Jin; Chen, Xiao; Zhai, Xiao; Shi, Dongchen; Zhang, Rongjia; Zhi, Xin; Li, Xiaoqun; Gu, Zhengrong; Cao, Liehu; Weng, Weizong; Zhang, Jun; Wang, Liping; Sun, Xuejun; Ji, Fang; Hou, Jiong; Su, Jiacan

2016-10-29

Hydrogen is a kind of noble gas with the character to selectively neutralize reactive oxygen species. Former researches proved that low-concentration of hydrogen can be used to ameliorating cerebral ischemia/reperfusion injury. Hydrogen electrolyzed from water has a hydrogen concentration of 66.7%, which is much higher than that used in previous studies. And water electrolysis is a potential new hydrogen resource for regular clinical use. This study was designed and carried out for the determination of safety and neuroprotective effects of water electrolysis-derived hydrogen. Sprague-Dawley rats were used as experimental animals, and middle cerebral artery occlusion was used to make cerebral ischemia/reperfusion model. Pathologically, tissues from rats in hydrogen inhalation group showed no significant difference compared with the control group in HE staining pictures. The blood biochemical findings matched the HE staining result. TTC, Nissl, and TUNEL staining showed the significant improvement of infarction volume, neuron morphology, and neuron apoptosis in rat with hydrogen treatment. Biochemically, hydrogen inhalation decreased brain caspase-3, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine-positive cells and inflammation factors concentration. Water electrolysis-derived hydrogen inhalation had neuroprotective effects on cerebral ischemia/reperfusion injury in rats with the effect of suppressing oxidative stress and inflammation, and it is a possible new hydrogen resource to electrolyze water at the bedside clinically. Copyright © 2016. Published by Elsevier Ltd.

NCCN Guidelines® Insights Bladder Cancer, Version 2.2016 Featured Updates to the NCCN Guidelines

Science.gov (United States)

Clark, Peter E.; Spiess, Philippe E.; Agarwal, Neeraj; Bangs, Rick; Boorjian, Stephen A.; Buyyounouski, Mark K.; Efstathiou, Jason A.; Flaig, Thomas W.; Friedlander, Terence; Greenberg, Richard E.; Guru, Khurshid A.; Hahn, Noah; Herr, Harry W.; Hoimes, Christopher; Inman, Brant A.; Kader, A. Karim; Kibel, Adam S.; Kuzel, Timothy M.; Lele, Subodh M.; Meeks, Joshua J.; Michalski, Jeff; Montgomery, Jeffrey S.; Pagliaro, Lance C.; Pal, Sumanta K.; Patterson, Anthony; Petrylak, Daniel; Plimack, Elizabeth R.; Pohar, Kamal S.; Porter, Michael P.; Sexton, Wade J.; Siefker-Radtke, Arlene O.; Sonpavde, Guru; Tward, Jonathan; Wile, Geoffrey; Dwyer, Mary A.; Smith, Courtney

2017-01-01

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice. PMID:27697976

Do Simulation-Based Skill Exercises and Post-Encounter Notes Add Additional Value to a Standardized Patient-Based Clinical Skills Examination?

Directory of Open Access Journals (Sweden)

Michael D. Prislin

2011-01-01

Full Text Available Background. Standardized patient (SP clinical assessments have limited utility in assessing higher-level clinical competencies. This study explores the value of including simulation exercises and postencounter notes in an SP clinical skills examination. Methods. Two exercises involving cardiac auscultation and ophthalmic funduscopy simulations along with written post encounter notes were added to an SP-based performance examination. Descriptive analyses of students' performance and correlations with SP-based performance measures were obtained. Results. Students' abilities to detect abnormalities on physical exam were highly variable. There were no correlations between SP-based and simulation-derived measures of physical examination competency. Limited correlations were found between students' abilities to perform and document physical examinations and their formulation of appropriate differential diagnoses. Conclusions. Clinical simulation exercises add depth to SP-based assessments of performance. Evaluating the content of post encounter notes offers some insight into students' integrative abilities, and this appears to be improved by the addition of simulation-based post encounter skill exercises. However, further refinement of this methodology is needed.

Dermatology discharge continuity clinic enhances resident autonomy and insight into transitions-of-care competencies: a cross-sectional survey study.

Science.gov (United States)

Rana, Jasmine; Mostaghimi, Arash

2017-05-15

Dermatology residents perform consults on hospitalized patients, but are often limited in their ability to follow-up with these patients after discharge, leading to inadequate follow-up and understanding of post-discharge transitions of care. In 2013, a discharge continuity clinic (DCC) staffed by the inpatient consult dermatology resident and attending dermatologist was established at one of the four adult hospital sites residents rotate through in the Harvard Combined Dermatology Residency Program. Resident perceptions about the DCC and their educational experience on inpatient consult rotations with a DCC and without a DCC were obtained using a cross-sectional survey instrument in June 2016. Self-reported data from a multi-year cohort of dermatology residents (n = 14 of 20, 70% response rate) reveals that the DCC enabled resident autonomy and resident satisfaction in care of their patients,insight into the disease-related challenges and the broader social context during transitions of care from inpatient to outpatient settings, and more enriching learning experiences than inpatient consult rotations without a DCC. Dermatology residents self-report participation in an inpatient consult rotation with aDCC supports their autonomy and achievement of post-discharge transitions-of-care competencies.

Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model

DEFF Research Database (Denmark)

Rasmussen, Jeppe; Frøbert, Ole; Holst-Hansen, Claus

2014-01-01

Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were...

What are System Dynamics Insights?

OpenAIRE

Stave, K.; Zimmermann, N. S.; Kim, H.

2016-01-01

This paper explores the concept of system dynamics insights. In our field, the term “insight” is generally understood to mean dynamic insight, that is, a deep understanding about the relationship between structure and behavior. We argue this is only one aspect of the range of insights possible from system dynamics activities, and describe a broader range of potential system dynamics insights. We also propose an initial framework for discussion that relates different types of system dynamics a...

Insight and Lessons Learned on Organizational Factors and Safety Culture from the Review of Human Error-related Events of NPPs in Korea

International Nuclear Information System (INIS)

Kim, Ji Tae; Lee, Dhong Hoon; Choi, Young Sung

2014-01-01

Event investigation is one of the key means of enhancing nuclear safety deriving effective measures and preventing recurrences. However, it is difficult to analyze organizational factors and safety culture. This paper tries to review human error-related events from perspectives of organizational factors and safety culture, and to derive insights and lessons learned in developing the regulatory infrastructure of plant oversight on safety culture

Insight and Lessons Learned on Organizational Factors and Safety Culture from the Review of Human Error-related Events of NPPs in Korea

Energy Technology Data Exchange (ETDEWEB)

Kim, Ji Tae; Lee, Dhong Hoon; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2014-08-15

Event investigation is one of the key means of enhancing nuclear safety deriving effective measures and preventing recurrences. However, it is difficult to analyze organizational factors and safety culture. This paper tries to review human error-related events from perspectives of organizational factors and safety culture, and to derive insights and lessons learned in developing the regulatory infrastructure of plant oversight on safety culture.

[Exploring the relationship between internalized stigma, insight and depression for inpatients with schizophrenia].

Science.gov (United States)

Bouvet, C; Bouchoux, A

2015-10-01

depression decreased moderately with CDSS and with small intensity with SAIQ, but clearly. So, ISMI is probably a mediating variable between IS and BDI-CDSS. In conclusion, internalized stigma could be a mediating variable between insight and depression. This validates our second hypothesis. Our results suggest that the relationship between insight and depression is mediated by internalized stigma. Patients with good insight who internalize stigma seem to be more depressed than those who don't. This result could have important consequences in clinical practice: improving insight level should be completed by a specific attention to the level and evolution of internalized stigma to avoid increasing depression. Further studies need to be conducted to confirm these results. Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Mechanism of Platinum Derivatives Induced Kidney Injury

Directory of Open Access Journals (Sweden)

Feifei YAN

2015-09-01

Full Text Available Platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors, lung cancer, and colorectal cancer. Two major problems exist, however, in the clinic use of platinum derivatives. One is the development of tumor resistance to the drug during therapy, leading to treatment failure. The other is the drug’s toxicity such as the cisplatin’s nephrotoxicity, which limits the dose that can be administered. This paper describes the mechanism of platinum derivatives induced kidney injury.

Biologic Rhythms Derived from Siberian Mammoths Hairs

Energy Technology Data Exchange (ETDEWEB)

M Spilde; A Lanzirotti; C Qualls; G Phillips; A Ali; L Agenbroad; O Appenzeller

2011-12-31

Hair is preserved for millennia in permafrost; it enshrines a record of biologic rhythms and offers a glimpse at chronobiology as it was in extinct animals. Here we compare biologic rhythms gleaned from mammoth's hairs with those of modern human hair. Four mammoths' hairs came from varying locations in Siberia 4600 km, four time zones, apart ranging in age between 18,000 and 20,000 years before present. We used two contemporaneous human hairs for comparison. Power spectra derived from hydrogen isotope ratios along the length of the hairs gave insight into biologic rhythms, which were different in the mammoths depending on location and differed from humans. Hair growth for mammoths was {approx}31 cms/year and {approx}16 cms/year for humans. Recurrent annual rhythms of slow and fast growth varying from 3.4 weeks/cycles to 8.7 weeks/cycles for slow periods and 1.2 weeks/cycles to 2.2 weeks/cycles for fast periods were identified in mammoth's hairs. The mineral content of mammoth's hairs was measured by electron microprobe analysis (k-ratios), which showed no differences in sulfur amongst the mammoth hairs but significantly more iron then in human hair. The fractal nature of the data derived from the hairs became evident in Mandelbrot sets derived from hydrogen isotope ratios, mineral content and geographic location. Confocal microscopy and scanning electron microscopy showed varied degrees of preservation of the cuticle largely independent of age but not location of the specimens. X-ray fluorescence microprobe and fluorescence computed micro-tomography analyses allowed evaluation of metal distribution and visualization of hollow tubes in the mammoth's hairs. Seasonal variations in iron and copper content combined with spectral analyses gave insights into variation in food intake of the animals. Biologic rhythms gleaned from power spectral plots obtained by modern methods revealed life style and behavior of extinct mega-fauna.

Biologic rhythms derived from Siberian mammoths' hairs.

Directory of Open Access Journals (Sweden)

Mike Spilde

Full Text Available Hair is preserved for millennia in permafrost; it enshrines a record of biologic rhythms and offers a glimpse at chronobiology as it was in extinct animals. Here we compare biologic rhythms gleaned from mammoth's hairs with those of modern human hair. Four mammoths' hairs came from varying locations in Siberia 4600 km, four time zones, apart ranging in age between 18,000 and 20,000 years before present. We used two contemporaneous human hairs for comparison. Power spectra derived from hydrogen isotope ratios along the length of the hairs gave insight into biologic rhythms, which were different in the mammoths depending on location and differed from humans. Hair growth for mammoths was ∼31 cms/year and ∼16 cms/year for humans. Recurrent annual rhythms of slow and fast growth varying from 3.4 weeks/cycles to 8.7 weeks/cycles for slow periods and 1.2 weeks/cycles to 2.2 weeks/cycles for fast periods were identified in mammoth's hairs. The mineral content of mammoth's hairs was measured by electron microprobe analysis (k-ratios, which showed no differences in sulfur amongst the mammoth hairs but significantly more iron then in human hair. The fractal nature of the data derived from the hairs became evident in Mandelbrot sets derived from hydrogen isotope ratios, mineral content and geographic location. Confocal microscopy and scanning electron microscopy showed varied degrees of preservation of the cuticle largely independent of age but not location of the specimens. X-ray fluorescence microprobe and fluorescence computed micro-tomography analyses allowed evaluation of metal distribution and visualization of hollow tubes in the mammoth's hairs. Seasonal variations in iron and copper content combined with spectral analyses gave insights into variation in food intake of the animals. Biologic rhythms gleaned from power spectral plots obtained by modern methods revealed life style and behavior of extinct mega-fauna.

Insights from advanced analytics at the Veterans Health Administration.

Science.gov (United States)

Fihn, Stephan D; Francis, Joseph; Clancy, Carolyn; Nielson, Christopher; Nelson, Karin; Rumsfeld, John; Cullen, Theresa; Bates, Jack; Graham, Gail L

2014-07-01

Health care has lagged behind other industries in its use of advanced analytics. The Veterans Health Administration (VHA) has three decades of experience collecting data about the veterans it serves nationwide through locally developed information systems that use a common electronic health record. In 2006 the VHA began to build its Corporate Data Warehouse, a repository for patient-level data aggregated from across the VHA's national health system. This article provides a high-level overview of the VHA's evolution toward "big data," defined as the rapid evolution of applying advanced tools and approaches to large, complex, and rapidly changing data sets. It illustrates how advanced analysis is already supporting the VHA's activities, which range from routine clinical care of individual patients--for example, monitoring medication administration and predicting risk of adverse outcomes--to evaluating a systemwide initiative to bring the principles of the patient-centered medical home to all veterans. The article also shares some of the challenges, concerns, insights, and responses that have emerged along the way, such as the need to smoothly integrate new functions into clinical workflow. While the VHA is unique in many ways, its experience may offer important insights for other health care systems nationwide as they venture into the realm of big data. Project HOPE—The People-to-People Health Foundation, Inc.

Translating epithelial mesenchymal transition markers into the clinic: Novel insights from proteomics

Directory of Open Access Journals (Sweden)

Vergara Daniele

2016-03-01

Full Text Available The growing understanding of the molecular mechanisms underlying epithelial-to-mesenchymal transition (EMT may represent a potential source of clinical markers. Despite EMT drivers have not yet emerged as candidate markers in the clinical setting, their association with established clinical markers may improve their specificity and sensitivity. Mass spectrometry-based platforms allow analyzing multiple samples for the expression of EMT candidate markers, and may help to diagnose diseases or monitor treatment efficiently. This review highlights proteomic approaches applied to elucidate the differences between epithelial and mesenchymal tumors and describes how these can be used for target discovery and validation.

Clinical expectations: what facilitators expect from ESL students on clinical placement.

Science.gov (United States)

San Miguel, Caroline; Rogan, Fran

2012-03-01

Many nursing students for whom English is a second language (ESL) face challenges related to communication on clinical placement and although clinical facilitators are not usually trained language assessors, they are often in a position of needing to assess ESL students' clinical language performance. Little is known, however, about the particular areas of clinical performance facilitators focus on when they are assessing ESL students. This paper discusses the results of a study of facilitators' written assessment comments about the clinical performance of a small group of ESL nursing students over a two and a half year period. These comments were documented on students' clinical assessment forms at the end of each placement. The results provide a more detailed insight into facilitators' expectations of students' language performance and the particular challenges faced by ESL students and indicate that facilitators have clear expectations of ESL students regarding communication, learning styles and professional demeanour. These findings may help both ESL students and their facilitators better prepare for clinical placement. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pooled human platelet lysate versus fetal bovine serum—investigating the proliferation rate, chromosome stability and angiogenic potential of human adipose tissue-derived stem cells intended for clinical use

DEFF Research Database (Denmark)

Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter V

2013-01-01

Because of an increasing focus on the use of adipose-derived stem cells (ASCs) in clinical trials, the culture conditions for these cells are being optimized. We compared the proliferation rates and chromosomal stability of ASCs that had been cultured in Dulbecco's modified Eagle's Medium (DMEM) ......) supplemented with either pooled human platelet lysate (pHPL) or clinical-grade fetal bovine serum (FBS) (DMEM(pHPL) versus DMEM(FBS))....

Insight, self-stigma and psychosocial outcomes in Schizophrenia: a structural equation modelling approach.

Science.gov (United States)

Lien, Y-J; Chang, H-A; Kao, Y-C; Tzeng, N-S; Lu, C-W; Loh, C-H

2018-04-01

Poor insight is prevalent in patients with schizophrenia and has been associated with acute illness severity, medication non-adherence and poor treatment outcomes. Paradoxically, high insight has been associated with various undesirable outcomes, including low self-esteem, depression and low subjective quality of life (QoL) in patients with schizophrenia. Despite the growing body of studies conducted in Western countries supporting the pernicious effects of improved insight in psychosis, which bases on the level of self-stigma, the effects are unclear in non-Western societies. The current study examined the role of self-stigma in the relationship between insight and psychosocial outcomes in a Chinese population. A total of 170 outpatients with schizophrenia spectrum disorders were recruited from two general university hospitals. Sociodemographic data and clinical variables were recorded and self-report scales were employed to measure self-stigma, depression, insight, self-esteem and subjective QoL. Structural equation modelling (SEM) was used to analyse the cross-sectional data. High levels of self-stigma were reported by 39% of the participants (n = 67). The influences of insight, self-stigma, self-esteem and depression on subjective QoL were confirmed by the SEM results. Our model with the closest fit to the data (χ 2 = 33.28; df = 20; p = 0.03; χ 2/df = 1.66; CFI = 0.98; TLI = 0.97; RMSEA = 0.06) demonstrated that self-stigma might fully mediate the association of insight with low self-esteem, depression and poor subjective QoL. High insight into illness contributed to self-stigma, which caused low self-esteem and depression and, consequently, low QoL. Notably, insight did not directly affect self-esteem, depression or QoL. Furthermore, the association of insight with poor psychosocial outcomes was not moderated by self-stigma. Our findings support the mediating model of insight relevant to the poor psychosocial outcomes of individuals diagnosed with

The 6-chromanol derivate SUL-109 enables prolonged hypothermic storage of adipose tissue-derived stem cells

NARCIS (Netherlands)

Hajmousa, Ghazaleh; Vogelaar, Pieter; Brouwer, Linda A.; Graaf, Adrianus Cornelis van der; Henning, Robert H.; Krenning, Guido

Encouraging advances in cell therapy research with adipose derived stem cells (ASC) require an effective short-term preservation method that provides time for quality control and transport of cells from their manufacturing facility to their clinical destination. Hypothermic storage of cells in their

Multiple myeloma in Nigeria: An insight to the clinical, laboratory ...

African Journals Online (AJOL)

... the clinician to investigate along the lines of MM. Majority of patients have osteolytic lesions on X‑ray and pathological fractures, and benefit from melphalan based combinations in situations where facilities for transplant are not available. Key words: Clinical features, chemotherapy, laboratory features, multiple myeloma, ...

Listening with a narrative ear: Insights from a study of fall stories in older adults.

Science.gov (United States)

Pereles, Laurie; Jackson, Roberta; Rosenal, Tom; Nixon, Lara

2017-01-01

To determine the value of adding a patient narrative to the clinical assessment of falls in the elderly. Qualitative study of interviews. A fall prevention clinic in Calgary, Alta. Fifteen older adults on a wait list for assessment by the fall clinic and the physiotherapists who assessed them. Participants' stories were audiorecorded and later transcribed and summarized. Stories were collected using open-ended questions, first inviting participants to tell the interviewer about themselves, and then the circumstances of their falls and their reflections on them. In a subsequent visit, transcriptions or summaries were returned to patients for member checking. Narratives were read and analyzed by all 4 investigators using a narrative approach and a close-reading technique. With the patients' additional consent, stories were shared with the fall prevention team for their insights and reactions. Interviews with physiotherapists were audiorecorded and transcribed. The narrative analysis provided new insights into the attitudes about and perceptions of the causes of falls, their effects, and rehabilitation. Close reading exposed presentation of self, locus of control, and underlying social and emotional issues. The addition of patient narratives to clinical assessments offers clinicians an understanding of patients' perspectives, which can be used to better engage patients in rehabilitation. Copyright© the College of Family Physicians of Canada.

Global Positioning System Derived Performance Measures Are Responsive Indicators of Physical Activity, Disease and the Success of Clinical Treatments in Domestic Dogs

Science.gov (United States)

Bruno, Elizabeth A.; Guthrie, James W.; Ellwood, Stephen A.; Mellanby, Richard J.; Clements, Dylan N.

2015-01-01

Objective To assess the use of Global Positioning System receiver (GPS) derived performance measures for differentiating between: 1) different outdoor activities in healthy dogs; 2) healthy dogs and those with osteoarthritis; 3) osteoarthritic dogs before and after treatment with non-steroidal anti-inflammatory analgesia. Design Prospective study. Animals Ten healthy dogs and seven dogs with osteoarthritis of the elbow joint (OA dogs). Procedure Healthy dogs were walked on a standard route on-lead, off-lead and subjected to playing activity (chasing a ball) whilst wearing a GPS collar. Each dog was walked for five consecutive days. Dogs with OA were subjected to a single off-lead walk whilst wearing a GPS collar, and then administered oral Carprofen analgesia daily for two weeks. OA dogs were then subjected to the same walk, again wearing a GPS collar. Results GPS derived measures of physical performance could differentiate between on-lead activity, off-lead activity and playing activity in healthy dogs, and between healthy dogs and OA dogs. Variation in the performance measures analysed was greater between individual dogs than for individual dogs on different days. Performance measures could differentiate healthy dogs from OA dogs. OA Dogs treated with Carprofen analgesia showed improvements in their physical performance, which returned to values indistinguishable from those of healthy dogs on nearly all the measures assessed. Conclusions and Clinical Relevance GPS derived measures of physical performance in dogs are objective, easy to quantify, and can be used to gauge the effects of disease and success of clinical treatments. Specific stimuli can be used to modulate physical performance beyond the self-governed boundaries that dogs will naturally express when allowed to exercise freely without stimulation. PMID:25692761

Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

Directory of Open Access Journals (Sweden)

Simon Turcotte

2007-10-01

Full Text Available Prostate-derived Ets transcription factor (PDEF has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1. Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001, moderate to good differentiation (less than grade III, P = .01, dissemination to axillary lymph nodes (P = .002. PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002. It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001. Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis.

Science.gov (United States)

Sevillano, Alejandro M; Fernández-Borges, Natalia; Younas, Neelam; Wang, Fei; R Elezgarai, Saioa; Bravo, Susana; Vázquez-Fernández, Ester; Rosa, Isaac; Eraña, Hasier; Gil, David; Veiga, Sonia; Vidal, Enric; Erickson-Beltran, Melissa L; Guitián, Esteban; Silva, Christopher J; Nonno, Romolo; Ma, Jiyan; Castilla, Joaquín; R Requena, Jesús

2018-01-01

Very solid evidence suggests that the core of full length PrPSc is a 4-rung β-solenoid, and that individual PrPSc subunits stack to form amyloid fibers. We recently used limited proteolysis to map the β-strands and connecting loops that make up the PrPSc solenoid. Using high resolution SDS-PAGE followed by epitope analysis, and mass spectrometry, we identified positions ~116/118, 133-134, 141, 152-153, 162, 169 and 179 (murine numbering) as Proteinase K (PK) cleavage sites in PrPSc. Such sites likely define loops and/or borders of β-strands, helping us to predict the threading of the β-solenoid. We have now extended this approach to recombinant PrPSc (recPrPSc). The term recPrPSc refers to bona fide recombinant prions prepared by PMCA, exhibiting infectivity with attack rates of ~100%. Limited proteolysis of mouse and bank vole recPrPSc species yielded N-terminally truncated PK-resistant fragments similar to those seen in brain-derived PrPSc, albeit with varying relative yields. Along with these fragments, doubly N- and C-terminally truncated fragments, in particular ~89/97-152, were detected in some recPrPSc preparations; similar fragments are characteristic of atypical strains of brain-derived PrPSc. Our results suggest a shared architecture of recPrPSc and brain PrPSc prions. The observed differences, in particular the distinct yields of specific PK-resistant fragments, are likely due to differences in threading which result in the specific biochemical characteristics of recPrPSc. Furthermore, recombinant PrPSc offers exciting opportunities for structural studies unachievable with brain-derived PrPSc.

Combining clinical practice and academic work in nursing: a qualitative study about perceived importance, facilitators and barriers regarding clinical academic careers for nurses in university hospitals.

NARCIS (Netherlands)

Oostveen, C.J. van; Goedhart, N.S.; Francke, A.L.; Vermeulen, H.

2017-01-01

Aims and objectives: To obtain in-depth insight into the perceptions of nurse aca- demics and other stakeholders regarding the importance, facilitators and barriers for nurses combining clinical and academic work in university hospitals. Background: Combining clinical practice and academic work

Some remarks on Romanian reflexive verbs derived by the prefix "în"

Directory of Open Access Journals (Sweden)

Veronica Tomescu

2008-01-01

Full Text Available The paper discusses a small group of Romanian reflexive verbs, denominals derived by means of the prefix în, as well as a group of transitive verbs which are reflexivized. Their behaviour will be briefly considered. A search on the Internet has also been made alongside the dictionary study in order to gain an insight into the frequency of use of certain forms.

Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.

Science.gov (United States)

Macias, Alba T; Williamson, Douglas S; Allen, Nicola; Borgognoni, Jenifer; Clay, Alexandra; Daniels, Zoe; Dokurno, Pawel; Drysdale, Martin J; Francis, Geraint L; Graham, Christopher J; Howes, Rob; Matassova, Natalia; Murray, James B; Parsons, Rachel; Shaw, Terry; Surgenor, Allan E; Terry, Lindsey; Wang, Yikang; Wood, Mike; Massey, Andrew J

2011-06-23

78 kDa glucose-regulated protein (Grp78) is a heat shock protein (HSP) involved in protein folding that plays a role in cancer cell proliferation. Binding of adenosine-derived inhibitors to Grp78 was characterized by surface plasmon resonance and isothermal titration calorimetry. The most potent compounds were 13 (VER-155008) with K(D) = 80 nM and 14 with K(D) = 60 nM. X-ray crystal structures of Grp78 bound to ATP, ADPnP, and adenosine derivative 10 revealed differences in the binding site between Grp78 and homologous proteins.

Reflective journaling for clinical judgment development and evaluation.

Science.gov (United States)

Lasater, Kathie; Nielsen, Ann

2009-01-01

Reflective journaling is a strategy used often in clinical education to gain insight into students' clinical thinking; however, studies indicate that students may benefit from guided reflections. Numerous tools have been used to structure student reflection with varying results. This article describes the outcomes from using the Guide for Reflection based on Tanner's Clinical Judgment Model. The Lasater Clinical Judgment Rubric, created from the Model, is used to evaluate development of clinical judgment and provides language to communicate about clinical thinking with students. Senior immersion course competencies, also developed with language from Tanner's Clinical Judgment Model,offer a comprehensive package that fosters students' clinical judgment development, faculty-student communication about clinical judgment, and evaluation of students' clinical thinking.

Recruiting Dementia Caregivers Into Clinical Trials: Lessons Learnt From the Australian TRANSCENDENT Trial.

Science.gov (United States)

Leach, Matthew J; Ziaian, Tahereh; Francis, Andrew; Agnew, Tamara

2016-01-01

The burden on those caring for a person with dementia is substantial. Although quality research assists in addressing the needs of these caregivers, recruiting caregivers into clinical studies is often problematic. This investigation explores the difficulties and successes in recruiting dementia caregivers into community-based clinical research by reporting the findings of a mixed-method substudy of a multicenter randomized controlled trial involving 40 community-dwelling dementia caregivers living in Adelaide, South Australia. Data for the substudy were derived from standardized trial monitoring documentation and structured telephone interviews. From a total of 16 distinct methods used across a 12-month recruitment campaign, the most cost-effective strategy was the distribution of flyers through a single study site. This approach generated the greatest number of enrollments of all methods used, achieving a 67% recruitment yield. The least cost-effective strategy, with a 0% recruitment yield, was the publication of a newspaper advertisement. Themes that emerged from the interviews pointed toward 5 key facilitators and 3 barriers to future trial recruitment. This study has generated new insights into the effective recruitment of dementia caregivers into clinical trials. We anticipate that these lessons learnt will assist in shaping the recruitment strategies of future studies of dementia caregivers.

Understanding latent structures of clinical information logistics: A bottom-up approach for model building and validating the workflow composite score.

Science.gov (United States)

Esdar, Moritz; Hübner, Ursula; Liebe, Jan-David; Hüsers, Jens; Thye, Johannes

2017-01-01

Clinical information logistics is a construct that aims to describe and explain various phenomena of information provision to drive clinical processes. It can be measured by the workflow composite score, an aggregated indicator of the degree of IT support in clinical processes. This study primarily aimed to investigate the yet unknown empirical patterns constituting this construct. The second goal was to derive a data-driven weighting scheme for the constituents of the workflow composite score and to contrast this scheme with a literature based, top-down procedure. This approach should finally test the validity and robustness of the workflow composite score. Based on secondary data from 183 German hospitals, a tiered factor analytic approach (confirmatory and subsequent exploratory factor analysis) was pursued. A weighting scheme, which was based on factor loadings obtained in the analyses, was put into practice. We were able to identify five statistically significant factors of clinical information logistics that accounted for 63% of the overall variance. These factors were "flow of data and information", "mobility", "clinical decision support and patient safety", "electronic patient record" and "integration and distribution". The system of weights derived from the factor loadings resulted in values for the workflow composite score that differed only slightly from the score values that had been previously published based on a top-down approach. Our findings give insight into the internal composition of clinical information logistics both in terms of factors and weights. They also allowed us to propose a coherent model of clinical information logistics from a technical perspective that joins empirical findings with theoretical knowledge. Despite the new scheme of weights applied to the calculation of the workflow composite score, the score behaved robustly, which is yet another hint of its validity and therefore its usefulness. Copyright © 2016 Elsevier Ireland

Pharmacogenetics in the oncological clinical practice

International Nuclear Information System (INIS)

Gruber, S.

2004-01-01

The genetic control of drug metabolism allows new insights into the bioavailability, toxicity, and efficacy of chemotherapy. In addition, molecular expression profiles of tumors offers the potential for targeted therapy to be directed more specifically to the biologic behavior of the cancer. Together these strategies are likely to change the practice of clinical oncology. However, appropriate clinical trials will be required to demonstrate the utility of these approaches before they are broadly implemented the biologic behavior of the cancer. Together these strategies are likely to change the practice of clinical oncology. However, appropriate clinical trials will be required to demonstrate the utility of these approaches before they are broadly implemented

Quality of outpatient clinical notes: a stakeholder definition derived through qualitative research

Directory of Open Access Journals (Sweden)

Hanson Janice L

2012-11-01

Full Text Available Abstract Background There are no empirically-grounded criteria or tools to define or benchmark the quality of outpatient clinical documentation. Outpatient clinical notes document care, communicate treatment plans and support patient safety, medical education, medico-legal investigations and reimbursement. Accurately describing and assessing quality of clinical documentation is a necessary improvement in an increasingly team-based healthcare delivery system. In this paper we describe the quality of outpatient clinical notes from the perspective of multiple stakeholders. Methods Using purposeful sampling for maximum diversity, we conducted focus groups and individual interviews with clinicians, nursing and ancillary staff, patients, and healthcare administrators at six federal health care facilities between 2009 and 2011. All sessions were audio-recorded, transcribed and qualitatively analyzed using open, axial and selective coding. Results The 163 participants included 61 clinicians, 52 nurse/ancillary staff, 31 patients and 19 administrative staff. Three organizing themes emerged: 1 characteristics of quality in clinical notes, 2 desired elements within the clinical notes and 3 system supports to improve the quality of clinical notes. We identified 11 codes to describe characteristics of clinical notes, 20 codes to describe desired elements in quality clinical notes and 11 codes to describe clinical system elements that support quality when writing clinical notes. While there was substantial overlap between the aspects of quality described by the four stakeholder groups, only clinicians and administrators identified ease of translation into billing codes as an important characteristic of a quality note. Only patients rated prioritization of their medical problems as an aspect of quality. Nurses included care and education delivered to the patient, information added by the patient, interdisciplinary information, and infection alerts as important

Quality of outpatient clinical notes: a stakeholder definition derived through qualitative research.

Science.gov (United States)

Hanson, Janice L; Stephens, Mark B; Pangaro, Louis N; Gimbel, Ronald W

2012-11-19

There are no empirically-grounded criteria or tools to define or benchmark the quality of outpatient clinical documentation. Outpatient clinical notes document care, communicate treatment plans and support patient safety, medical education, medico-legal investigations and reimbursement. Accurately describing and assessing quality of clinical documentation is a necessary improvement in an increasingly team-based healthcare delivery system. In this paper we describe the quality of outpatient clinical notes from the perspective of multiple stakeholders. Using purposeful sampling for maximum diversity, we conducted focus groups and individual interviews with clinicians, nursing and ancillary staff, patients, and healthcare administrators at six federal health care facilities between 2009 and 2011. All sessions were audio-recorded, transcribed and qualitatively analyzed using open, axial and selective coding. The 163 participants included 61 clinicians, 52 nurse/ancillary staff, 31 patients and 19 administrative staff. Three organizing themes emerged: 1) characteristics of quality in clinical notes, 2) desired elements within the clinical notes and 3) system supports to improve the quality of clinical notes. We identified 11 codes to describe characteristics of clinical notes, 20 codes to describe desired elements in quality clinical notes and 11 codes to describe clinical system elements that support quality when writing clinical notes. While there was substantial overlap between the aspects of quality described by the four stakeholder groups, only clinicians and administrators identified ease of translation into billing codes as an important characteristic of a quality note. Only patients rated prioritization of their medical problems as an aspect of quality. Nurses included care and education delivered to the patient, information added by the patient, interdisciplinary information, and infection alerts as important content. Perspectives of these four stakeholder

The SafeBoosC Phase II Randomised Clinical Trial : A Treatment Guideline for Targeted Near-Infrared-Derived Cerebral Tissue Oxygenation versus Standard Treatment in Extremely Preterm Infants

NARCIS (Netherlands)

Pellicer, Adelina; Greisen, Gorm; Benders, Manon; Claris, Olivier; Dempsey, Eugene; Fumagalli, Monica; Gluud, Christian; Hagmann, Cornelia; Hellstroem-Westas, Lena; Hyttel-Sorensen, Simon; Lemmers, Petra; Naulaers, Gunnar; Pichler, Gerhard; Roll, Claudia; van Bel, Frank; van Oeveren, Wim; Skoog, Maria; Wolf, Martin; Austin, Topun

2013-01-01

Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin (rSto(2)) reflects venous oxygen saturation. If cerebral metabolism is stable, rSto(2) can be used as an estimate of cerebral oxygen delivery. The SafeBoosC phase II randomised clinical trial hypothesises that the

Quinoxaline derivatives: a patent review (2006--present).

Science.gov (United States)

González, Mercedes; Cerecetto, Hugo

2012-11-01

Quinoxaline scaffold is included in a large number of therapeutic agents because of its physicochemical properties that make the difference between them and the carbono analogue, naphthalene. This review of patented products presents the quinoxaline heterocycle as part of the structural patent claims from a medicinal chemistry perspective. We centred our discussion in the various drug patent applications of the quinoxaline and its derivatives. The applications are based firstly in the specific enzyme target with very low development in the disease treatment. Only for cancer and antimicrobial agents they were specifically determined but little is mentioned in order to insight in the last development activities.

Assigning clinical codes with data-driven concept representation on Dutch clinical free text.

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Scheurwegs, Elyne; Luyckx, Kim; Luyten, Léon; Goethals, Bart; Daelemans, Walter

2017-05-01

Clinical codes are used for public reporting purposes, are fundamental to determining public financing for hospitals, and form the basis for reimbursement claims to insurance providers. They are assigned to a patient stay to reflect the diagnosis and performed procedures during that stay. This paper aims to enrich algorithms for automated clinical coding by taking a data-driven approach and by using unsupervised and semi-supervised techniques for the extraction of multi-word expressions that convey a generalisable medical meaning (referred to as concepts). Several methods for extracting concepts from text are compared, two of which are constructed from a large unannotated corpus of clinical free text. A distributional semantic model (i.c. the word2vec skip-gram model) is used to generalize over concepts and retrieve relations between them. These methods are validated on three sets of patient stay data, in the disease areas of urology, cardiology, and gastroenterology. The datasets are in Dutch, which introduces a limitation on available concept definitions from expert-based ontologies (e.g. UMLS). The results show that when expert-based knowledge in ontologies is unavailable, concepts derived from raw clinical texts are a reliable alternative. Both concepts derived from raw clinical texts perform and concepts derived from expert-created dictionaries outperform a bag-of-words approach in clinical code assignment. Adding features based on tokens that appear in a semantically similar context has a positive influence for predicting diagnostic codes. Furthermore, the experiments indicate that a distributional semantics model can find relations between semantically related concepts in texts but also introduces erroneous and redundant relations, which can undermine clinical coding performance. Copyright © 2017. Published by Elsevier Inc.

The prognostic value of temporal in vitro and in vivo derived hypoxia gene-expression signatures in breast cancer

International Nuclear Information System (INIS)

Starmans, Maud H.W.; Chu, Kenneth C.; Haider, Syed; Nguyen, Francis; Seigneuric, Renaud; Magagnin, Michael G.; Koritzinsky, Marianne; Kasprzyk, Arek; Boutros, Paul C.; Wouters, Bradly G.

2012-01-01

Background and purpose: Recent data suggest that in vitro and in vivo derived hypoxia gene-expression signatures have prognostic power in breast and possibly other cancers. However, both tumour hypoxia and the biological adaptation to this stress are highly dynamic. Assessment of time-dependent gene-expression changes in response to hypoxia may thus provide additional biological insights and assist in predicting the impact of hypoxia on patient prognosis. Materials and methods: Transcriptome profiling was performed for three cell lines derived from diverse tumour-types after hypoxic exposure at eight time-points, which include a normoxic time-point. Time-dependent sets of co-regulated genes were identified from these data. Subsequently, gene ontology (GO) and pathway analyses were performed. The prognostic power of these novel signatures was assessed in parallel with previous in vitro and in vivo derived hypoxia signatures in a large breast cancer microarray meta-dataset (n = 2312). Results: We identified seven recurrent temporal and two general hypoxia signatures. GO and pathway analyses revealed regulation of both common and unique underlying biological processes within these signatures. None of the new or previously published in vitro signatures consisting of hypoxia-induced genes were prognostic in the large breast cancer dataset. In contrast, signatures of repressed genes, as well as the in vivo derived signatures of hypoxia-induced genes showed clear prognostic power. Conclusions: Only a subset of hypoxia-induced genes in vitro demonstrates prognostic value when evaluated in a large clinical dataset. Despite clear evidence of temporal patterns of gene-expression in vitro, the subset of prognostic hypoxia regulated genes cannot be identified based on temporal pattern alone. In vivo derived signatures appear to identify the prognostic hypoxia induced genes. The prognostic value of hypoxia-repressed genes is likely a surrogate for the known importance of

Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity

Directory of Open Access Journals (Sweden)

Gayatri Gundannavar

2013-01-01

Full Text Available This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

Approaching the Distinction between Intuition and Insight.

Science.gov (United States)

Zhang, Zhonglu; Lei, Yi; Li, Hong

2016-01-01

Intuition and insight share similar cognitive and neural basis. Though, there are still some essential differences between the two. Here in this short review, we discriminated between intuition, and insight in two aspects. First, intuition, and insight are toward different aspects of information processing. Whereas intuition involves judgment about "yes or no," insight is related to "what" is the solution. Second, tacit knowledge play different roles in between intuition and insight. On the one hand, tacit knowledge is conducive to intuitive judgment. On the other hand, tacit knowledge may first impede but later facilitate insight occurrence. Furthermore, we share theoretical, and methodological views on how to access the distinction between intuition and insight.

Insights into business student's book

CERN Document Server

Lannon, Michael; Trappe, Tonya

1993-01-01

With Challenging reading and listening texts from a range of authentic business sources, New Insights into Business will really engage your students. The thorough language and vocabulary syllabus together with the strong focus on business skills development gives students everything they need to function effectively in the workplace. New Insights into Business is a self-contained course and is also an ideal follow-on to First Insights into Business.

In Search of Insight.

Science.gov (United States)

Kaplan, Craig A.; Simon, Herbert A.

1990-01-01

Attaining the insight needed to solve the Mutilated Checkerboard problem, which requires discovery of an effective problem representation (EPR), is described. Performance on insight problems can be predicted from the availability of generators and constraints in the search for an EPR. Data for 23 undergraduates were analyzed. (TJH)

Extracellular matrix-derived hydrogels for dental stem cell delivery.

Science.gov (United States)

Viswanath, Aiswarya; Vanacker, Julie; Germain, Loïc; Leprince, Julian G; Diogenes, Anibal; Shakesheff, Kevin M; White, Lisa J; des Rieux, Anne

2017-01-01

Decellularized mammalian extracellular matrices (ECM) have been widely accepted as an ideal substrate for repair and remodelling of numerous tissues in clinical and pre-clinical studies. Recent studies have demonstrated the ability of ECM scaffolds derived from site-specific homologous tissues to direct cell differentiation. The present study investigated the suitability of hydrogels derived from different source tissues: bone, spinal cord and dentine, as suitable carriers to deliver human apical papilla derived mesenchymal stem cells (SCAP) for spinal cord regeneration. Bone, spinal cord, and dentine ECM hydrogels exhibited distinct structural, mechanical, and biological characteristics. All three hydrogels supported SCAP viability and proliferation. However, only spinal cord and bone derived hydrogels promoted the expression of neural lineage markers. The specific environment of ECM scaffolds significantly affected the differentiation of SCAP to a neural lineage, with stronger responses observed with spinal cord ECM hydrogels, suggesting that site-specific tissues are more likely to facilitate optimal stem cell behavior for constructive spinal cord regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 319-328, 2017. © 2016 Wiley Periodicals, Inc.

Properties and clinical relevance of osteoinductive biomaterials

NARCIS (Netherlands)

Habibovic, Pamela

2005-01-01

This thesis had two main goals: (¿) to investigate parameters influencing osteoinductive potential of biomaterials in order to unravel the mechanism underlying osteoinduction and (¿¿) to investigate performance of osteoinductive biomaterials orthotopically in order to get insight into their clinical

Deriving a clinical prediction rule to target sexual healthcare to women attending British General Practices.

Science.gov (United States)

Edelman, N L; Cassell, J A; Mercer, C H; Bremner, S A; Jones, C I; Gersten, A; deVisser, R O

2018-07-01

Some women attending General Practices (GPs) are at higher risk of unintended pregnancy (RUIP) and sexually transmitted infections (STI) than others. A clinical prediction rule (CPR) may help target resources using psychosocial questions as an acceptable, effective means of assessment. The aim was to derive a CPR that discriminates women who would benefit from sexual health discussion and intervention. Participants were recruited to a cross-sectional survey from six GPs in a city in South-East England in 2016. On arrival, female patients aged 16-44 years were invited to complete a questionnaire that addressed psychosocial factors, and the following self-reported outcomes: 2+ sexual partners in the last year (2PP) and RUIP. For each sexual risk, psychosocial questions were retained from logistic regression modelling which best discriminated women at risk using the C-statistic. Sensitivity and specificity were established in consultation with GP staff. The final sample comprised N = 1238 women. 2PP was predicted by 11 questions including age, binge-drinking weekly, ever having a partner who insulted you often, current smoking, and not cohabiting (C-statistic = 0.83, sensitivity = 73% and specificity = 77%). RUIP was predicted by 5 questions including sexual debut years, and emergency contraception use in the last 6 months (C-statistic = 0.70, sensitivity = 69% and specificity = 57%). 2PP was better discriminated than RUIP but neither to a clinically-useful degree. The finding that different psychosocial factors predicted each outcome has implications for prevention strategies. Further research should investigate causal links between psychosocial factors and sexual risk. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Adipose-Derived Stem Cells in Aesthetic Surgery: A Mixed Methods Evaluation of the Current Clinical Trial, Intellectual Property, and Regulatory Landscape.

Science.gov (United States)

Arshad, Zeeshaan; Halioua-Haubold, Celine-Lea; Roberts, Mackenna; Urso-Baiarda, Fulvio; Branford, Oliver A; Brindley, David A; Davies, Benjamin M; Pettitt, David

2018-02-17

Adipose tissue, which can be readily harvested via a number of liposuction techniques, offers an easily accessible and abundant source of adipose-derived stem cells (ASCs). Consequently, ASCs have become an increasingly popular reconstructive option and a novel means of aesthetic soft tissue augmentation. This paper examines recent advances in the aesthetic surgery field, extending beyond traditional review formats to incorporate a comprehensive analysis of current clinical trials, adoption status, and the commercialization pathway. Keyword searches were carried out on clinical trial databases to search for trials using ASCs for aesthetic indications. An intellectual property landscape was created using commercial software (Thomson Reuters Thomson Innovation, New York, NY). Analysis of who is claiming what in respect of ASC use in aesthetic surgery for commercial purposes was analyzed by reviewing the patent landscape in relation to these techniques. Key international regulatory guidelines were also summarized. Completed clinical trials lacked robust controls, employed small sample sizes, and lacked long-term follow-up data. Ongoing clinical trials still do not address such issues. In recent years, claims to intellectual property ownership have increased in the "aesthetic stem cell" domain, reflecting commercial interest in the area. However, significant translational barriers remain including regulatory challenges and ethical considerations. Further rigorous randomized controlled trials are required to delineate long-term clinical efficacy and safety. Providers should consider the introduction of patient reported outcome metrics to facilitate clinical adoption. Robust regulatory and ethical policies concerning stem cells and aesthetic surgery should be devised to discourage further growth of "stem cell tourism." © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

The structural coherence of clinically derived dynamic indicators of reoffending risk

NARCIS (Netherlands)

Philipse, Martien W. G.; Koeter, Maarten W. J.; van den Brink, Wim; van der Staak, Cees P. F.

2004-01-01

BACKGROUND: Forensic psychiatrists aim to reduce the risk of reoffending through treatment. With few exceptions, research evidence tends to favour risk assessment aids reliant on fixed historical rather than clinical data, but transparency in the making of clinical judgements is lacking. AIMS: To

The potential of tumor-derived exosomes for noninvasive cancer monitoring.

Science.gov (United States)

Whiteside, Theresa L

2015-01-01

Tumor-derived exosomes (TEX) are emerging as a new type of cancer biomarker. TEX are membrane-bound, virus-size vesicles of endocytic origin present in all body fluids of cancer patients. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by tumor cells and cancer cell-specific molecular and genetic contents, TEX are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of tumor cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma of cancer patients responding to therapies appear to correlate with clinical endpoints. However, methods for TEX isolation and separation from the bulk of human plasma-derived exosomes are not yet established and their role as biomarkers remains to be confirmed. Further development and validation of TEX as noninvasive, liquid equivalents of tumor biopsies are necessary to move this effort forward.

Umbilical Cord-Derived Mesenchymal Stem Cells for Hematopoietic Stem Cell Transplantation

Directory of Open Access Journals (Sweden)

Yu-Hua Chao

2012-01-01

Full Text Available Hematopoietic stem cell transplantation (HSCT is becoming an effective therapeutic modality for a variety of diseases. Mesenchymal stem cells (MSCs can be used to enhance hematopoietic engraftment, accelerate lymphocyte recovery, reduce the risk of graft failure, prevent and treat graft-versus-host disease, and repair tissue damage in patients receiving HSCT. Till now, most MSCs for human clinical application have been derived from bone marrow. However, acquiring bone-marrow-derived MSCs involves an invasive procedure. Umbilical cord is rich with MSCs. Compared to bone-marrow-derived MSCs, umbilical cord-derived MSCs (UCMSCs are easier to obtain without harm to the donor and can proliferate faster. No severe adverse effects were noted in our previous clinical application of UCMSCs in HSCT. Accordingly, application of UCMSCs in humans appears to be feasible and safe. Further studies are warranted.

Social Withdrawal Among Individuals Receiving Psychiatric Care: Derivation of a Scale Using Routine Clinical Assessment Data to Support Screening and Outcome Measurement.

Science.gov (United States)

Rios, Sebastian; Perlman, Christopher M

2017-04-24

Social withdrawal is a symptom experienced by individuals with an array of mental health conditions, particularly those with schizophrenia and mood disorders. Assessments of social withdrawal are often lengthy and may not be routinely integrated within the comprehensive clinical assessment of the individual. This study utilized item response and classical test theory methods to derive a Social Withdrawal Scale (SWS) using items embedded within a routine clinical assessment, the RAI-Mental Health (RAI-MH). Using data from 60,571 inpatients in Ontario, Canada, a common factor analysis identified seven items from the RAI-MH that measure social withdrawal. A graded response model found that six items had acceptable discrimination parameters: lack of motivation, reduced interaction, decreased energy, flat affect, anhedonia, and loss of interest. Summing these items, the SWS was found to have strong internal consistency (Cronbach's alpha = 0.82) and showed a medium to large effect size (d = 0.77) from admission to discharge. Fewer individuals with high SWS scores participated in social activity or reported having a confidant compared to those with lower scores. Since the RAI-MH is available across clinical subgroups in several jurisdictions, the SWS is a useful tool for screening, clinical decision support, and evaluation.

The influence of current mood state, number of previous affective episodes and predominant polarity on insight in bipolar disorder.

Science.gov (United States)

de Assis da Silva, Rafael; Mograbi, Daniel C; Camelo, Evelyn Vieira Miranda; Peixoto, Ursula; Santana, Cristina Maria Teixeira; Landeira-Fernandez, Jesus; Morris, Robin G; Cheniaux, Elie

2017-11-01

Although many studies have explored the effect of current affective episodes on insight into bipolar disorder, the potential interaction between current mood state and previous affective episodes has not been consistently investigated. To explore the influence of dominant polarity, number of previous affective episodes and current affective state on insight in bipolar disorder patients in euthymia or mania. A total of 101 patients with bipolar disorder were recruited for the study, including 58 patients in euthymia (30 with no defined predominant polarity and 28 with manic predominant polarity) and 43 in mania (26 with no defined predominant polarity and 17 with manic predominant polarity). Patients underwent a clinical assessment and insight was evaluated through the Insight Scale for Affective Disorders. Bipolar disorder patients in mania had worse insight than those in euthymia, with no effect of dominant polarity. In addition, positive psychotic symptoms showed a significant effect on insight and its inclusion as a covariate eliminated differences related to mood state. Finally, the number of previous manic or depressive episodes did not correlate with insight level. Mania is a predictor of loss of insight into bipolar disorder. However, it is possible that its contribution is linked to the more frequent presence of psychotic symptoms in this state. Dominant polarity and number/type of previous affective episodes have a limited impact on insight.

Systemic lupus erythematosus: Clinical and experimental aspects

International Nuclear Information System (INIS)

Smolen, J.S.

1987-01-01

This text covers questions related to the history, etiology, pathogenesis, clinical aspects and therapy of systematic lupus erythematosus (SLE). Both animal models and human SLE are considered. With regard to basic science, concise information on cellular immunology, autoantibodies, viral aspects and molecular biology in SLE is provided. Clinical topics then deal with medical, dermatologic, neurologic, radiologic, pathologic, and therapeutic aspects. The book not only presents the most recent information on clinical and experimental insights, but also looks at future aspects related to the diagnosis and therapy of SLE

Parkinson disease: α-synuclein mutational screening and new clinical insight into the p.E46K mutation.

Science.gov (United States)

Pimentel, Márcia M G; Rodrigues, Fabíola C; Leite, Marco Antônio A; Campos Júnior, Mário; Rosso, Ana Lucia; Nicaretta, Denise H; Pereira, João S; Silva, Delson José; Della Coletta, Marcus V; Vasconcellos, Luiz Felipe R; Abreu, Gabriella M; Dos Santos, Jussara M; Santos-Rebouças, Cíntia B

2015-06-01

Amongst Parkinson's disease-causing genetic factors, missense mutations and genomic multiplications in the gene encoding α-synuclein are well established causes of the disease, although genetic data in populations with a high degree of admixture, such as the Brazilian one, are still scarce. In this study, we conducted a molecular screening of α-synuclein point mutations and copy number variation in the largest cohort of Brazilian patients with Parkinson's disease (n = 549) and also in twelve Portuguese and one Bolivian immigrants. Genomic DNA was isolated from peripheral blood leukocytes or saliva, and the mutational screening was performed by quantitative and qualitative real-time PCR. The only alteration identified was the p.E46K mutation in a 60-year-old man, born in Bolivia, with a familial history of autosomal dominant Parkinson's disease. This is the second family ever reported, in which this rare pathogenic mutation is segregating. The same mutation was firstly described ten years ago in a Spanish family with a neurodegenerative syndrome combining parkinsonism, dementia and visual hallucinations. The clinical condition of our proband reveals a less aggressive phenotype than previously described and reinforces that marked phenotypic heterogeneity is common among patients with Parkinson's disease, even among those carriers sharing the same mutation. Our findings add new insight into the preexisting information about α-synuclein p.E46K, improving our understanding about the endophenotypes associated to this mutation and corroborate that missense alterations and multiplications in α-synuclein are uncommon among Brazilian patients with Parkinson's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Insight in psychosis: Metacognitive processes and treatment

OpenAIRE

de Vos, Annerieke

2016-01-01

Insight is impaired in 50- 80% of the patients with schizophrenia. Annerieke de Vos working at GGZ Drenthe and the University Medical Hospital Groningen, aimed to elucidate which processes underlie impaired insight and tried to improve insight in patients by targeting these processes. On September 21st she will defend her thesis entitled: "Insight in psychosis. Metacognitive processes and treatment.". Patients with impaired insight may fail to recognize that things in life are not going well ...

New insights into insight: Neurophysiological correlates of the difference between the intrinsic "aha" and the extrinsic "oh yes" moment.

Science.gov (United States)

Rothmaler, Katrin; Nigbur, Roland; Ivanova, Galina

2017-01-27

Insight refers to a situation in which a problem solver immediately changes his understanding of a problem situation. This representational change can either be triggered by external stimuli, like a hint or the solution itself, or by internal solution attempts. In the present paper, the differences and similarities between these two phenomena, namely "extrinsic" and "intrinsic" insight, are examined. To this end, electroencephalogram (EEG) is recorded while subjects either recognize or generate solutions to German verbal compound remote associate problems (CRA). Based on previous studies, we compare the alpha power prior to insightful solution recognition with the alpha power prior to insightful solution generation. Results show that intrinsic insights are preceded by an increase in alpha power at right parietal electrodes, while extrinsic insights are preceded by a respective decrease. These results can be interpreted in two ways. In consistency with other studies, the increase in alpha power before intrinsic insights can be interpreted as an increased internal focus of attention. Accordingly, the decrease in alpha power before extrinsic insights may be associated with a more externally oriented focus of attention. Alternatively, the increase in alpha power prior to intrinsic insights can be interpreted as an active inhibition of solution-related information, while the alpha power decrease prior to extrinsic insights may reflect its activation. Regardless of the interpretation, the results provide strong evidence that extrinsic and intrinsic insight differ on the behavioral as well as the neurophysiological level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Translational Bioinformatics and Clinical Research (Biomedical) Informatics.

Science.gov (United States)

Sirintrapun, S Joseph; Zehir, Ahmet; Syed, Aijazuddin; Gao, JianJiong; Schultz, Nikolaus; Cheng, Donavan T

2015-06-01

Translational bioinformatics and clinical research (biomedical) informatics are the primary domains related to informatics activities that support translational research. Translational bioinformatics focuses on computational techniques in genetics, molecular biology, and systems biology. Clinical research (biomedical) informatics involves the use of informatics in discovery and management of new knowledge relating to health and disease. This article details 3 projects that are hybrid applications of translational bioinformatics and clinical research (biomedical) informatics: The Cancer Genome Atlas, the cBioPortal for Cancer Genomics, and the Memorial Sloan Kettering Cancer Center clinical variants and results database, all designed to facilitate insights into cancer biology and clinical/therapeutic correlations. Copyright © 2015 Elsevier Inc. All rights reserved.

Insight and satisfaction with life among adolescents with mental disorders: assessing associations with self-stigma and parental insight.

Science.gov (United States)

Gaziel, M; Hasson-Ohayon, I; Morag-Yaffe, M; Schapir, L; Zalsman, G; Shoval, G

2015-02-01

The purpose of the current study was to assess the associations of illness perception-related variables with satisfaction with life (SwL) among adolescents with mental disorders. Insight into mental disorder (SAI-E), Internalized stigma of mental illness (ISMI) and Multidimensional Students' Life Satisfaction Scale (MSLSS) were administrated to 30 adolescent patients. Adapted version for parents of the SAI-E was also administrated to 37 of their parents. Significant positive correlations were found between insight into the illness, self-stigma and parental insight. Insight and self-stigma were significantly negatively related to the total score of SwL and few of its dimensions while parental insight was significantly associated only with the SwL dimensions of school and self. Regression models revealed main negative effects of insight and self-stigma on SwL and no interaction effect. The possible independent contribution of insight and self-stigma to SwL should be addressed in interventions designed for family and adolescents coping with mental illness. Special attention should be given to the possible negative implications that insight possesses. In lack of support of the moderation role of self-stigma, reported in studies among adults with mental illness, future studies should trace other variables in order to further understand the insight paradox among adolescents. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Course of insight in manic episode

Directory of Open Access Journals (Sweden)

A Kumar

2013-01-01

Full Text Available Background: Insight is an important factor associated with non compliance and poor outcome. Poor level of insight has been described as a characteristic in patients with acute bipolar disorder with more unawareness in social consequences with increasing severity in manic episode. Aim: Main aim of study was to see the baseline and longitudinal relationship between dimensions of insight with improvement in psychopathology. Setting and Design: Forty four patients diagnosed with mania, were selected from an inpatient setting at Institute of Mental Health and Hospital, Agra with mean age of 31.07(±9.00 years. They were assessed at base line and were followed up weekly or psychopathology and insight. Materials and Methods: The Young′s mania rating scale for psychopathology and insight was assessed on three dimensions of SUMD. Results: Twenty five patients eventually completed the study. There was a positive correlation with global insight and with psychopathology consistent in longitudinal follow-up (P<0.05, but not correlating for awareness for achieved effect of medication and social consequences. Linear regression showed a positive relationship at the first and second week of assessment of SUMD and YMRS scores (P=0.001; 0.019. Conclusion: Improvement in insight is graded in a manic episode as compared to psychopathology. There is slower improvement in awareness of social consequences of mental disorder. It means that improvement in psychopathology may not necessarily indicate remission and need further supervision to improve insight and hence monitoring.

Urea derivatives on the move: cytokinin-like activity and adventitious rooting enhancement depend on chemical structure.

Science.gov (United States)

Ricci, A; Bertoletti, C

2009-05-01

Urea derivatives are synthetic compounds, some of which have proved to be positive regulators of cell division and differentiation. N-phenyl-N'-(2-chloro-4-pyridyl)urea (forchlorofenuron, CPPU) and N-phenyl-N'-(1,2,3-thiadiazol-5-yl)urea (thidiazuron, TDZ), well known urea cytokinin representatives, are extensively used in in vitro plant morphogenesis studies, as they show cytokinin-like activity often exceeding that of adenine compounds. In recent years, renewed interest in structure-activity relationship studies allowed identification of new urea cytokinins and other urea derivatives that specifically enhance adventitious root formation. In this review, we report the research history of urea derivatives, new insights into their biological activity, and recent progress on their mode of action.

Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

Energy Technology Data Exchange (ETDEWEB)

Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com; Talbert, Dominique R.; Trusk, Patricia B.; Moran, Diarmuid M.; Shell, Scott A.; Bacus, Sarah

2015-05-15

Safety pharmacology studies that evaluate new drug entities for potential cardiac liability remain a critical component of drug development. Current studies have shown that in vitro tests utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) may be beneficial for preclinical risk evaluation. We recently demonstrated that an in vitro multi-parameter test panel assessing overall cardiac health and function could accurately reflect the associated clinical cardiotoxicity of 4 FDA-approved targeted oncology agents using hiPS-CM. The present studies expand upon this initial observation to assess whether this in vitro screen could detect cardiotoxicity across multiple drug classes with known clinical cardiac risks. Thus, 24 drugs were examined for their effect on both structural (viability, reactive oxygen species generation, lipid formation, troponin secretion) and functional (beating activity) endpoints in hiPS-CM. Using this screen, the cardiac-safe drugs showed no effects on any of the tests in our panel. However, 16 of 18 compounds with known clinical cardiac risk showed drug-induced changes in hiPS-CM by at least one method. Moreover, when taking into account the Cmax values, these 16 compounds could be further classified depending on whether the effects were structural, functional, or both. Overall, the most sensitive test assessed cardiac beating using the xCELLigence platform (88.9%) while the structural endpoints provided additional insight into the mechanism of cardiotoxicity for several drugs. These studies show that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. - Highlights: • 24 drugs were tested for cardiac liability using an in vitro multi-parameter screen. • Changes in beating activity were the most sensitive in predicting cardiac risk. • Structural effects add in

The Biodistribution and Immune Suppressive Effects of Breast Cancer-Derived Exosomes.

Science.gov (United States)

Wen, Shu Wen; Sceneay, Jaclyn; Lima, Luize Goncalves; Wong, Christina S F; Becker, Melanie; Krumeich, Sophie; Lobb, Richard J; Castillo, Vanessa; Wong, Ke Ni; Ellis, Sarah; Parker, Belinda S; Möller, Andreas

2016-12-01

Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highly metastatic murine breast cancer cells distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45 + bone marrow-derived cells. Subsequent long-term conditioning of naïve mice with exosomes from highly metastatic breast cancer cells revealed the accumulation of myeloid-derived suppressor cells in the lung and liver. This favorable immune suppressive microenvironment was capable of promoting metastatic colonization in the lung and liver, an effect not observed from exosomes derived from nonmetastatic cells and liposome control vesicles. Furthermore, we determined that breast cancer exosomes directly suppressed T-cell proliferation and inhibited NK cell cytotoxicity, and hence likely suppressed the anticancer immune response in premetastatic organs. Together, our findings provide novel insight into the tissue-specific outcomes of breast cancer-derived exosome accumulation and their contribution to immune suppression and promotion of metastases. Cancer Res; 76(23); 6816-27. ©2016 AACR. ©2016 American Association for Cancer Research.

Clinical presentation of (subclinical) jaundice - The Euricterus project in The Netherlands

NARCIS (Netherlands)

Reisman, Y; Gips, CH; Lavelle, SM; Wilson, JHP

1996-01-01

Background: From a primary clinical database, rue wanted to obtain insight in disease distribution and clinical presentation of adult jaundiced patients in a Western country. Materials and Methods: As part of the Euricterus project, 24 Dutch general and academic hospitals in a period of 2 years

The role of model checking in critiquing based on clinical guidelines

NARCIS (Netherlands)

Groot, Perry; Hommersom, Arjen; Lucas, Peter; Serban, Radu; Ten Teije, Annette; Van Harmelen, Frank

2007-01-01

Medical critiquing systems criticise clinical actions performed by a physician. In order to provide useful feedback, an important task is to find differences between the actual actions and a set of 'ideal' actions as described by a clinical guideline. In case differences exist, insight to which

Insights into implementation of sacubitril/valsartan into clinical practice.

Science.gov (United States)

Martens, Pieter; Beliën, Hanne; Dupont, Matthias; Mullens, Wilfried

2018-06-01

Sacubitril/valsartan significantly reduced heart failure hospitalization and mortality in PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure). However, real-world data from its use are lacking. We retrospectively assessed all baseline and follow-up data of consecutive heart failure patients with reduced ejection fraction receiving therapy with sacubitril/valsartan for Class I recommendation between December 2016 and July 2017. Baseline characteristics and dose titration of sacubitril/valsartan were compared between patients in clinical practice and in PARADIGM-HF. A total of 120 patients (81% male) were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. A total of 20.1% of patients received dose uptitration. Patients were treated with an equipotential dose of renin-angiotensin system blockers before and after uptitration of sacubitril/valsartan (57 ± 29% vs. 53 ± 29% of target dose indicated by European Society of Cardiology guidelines; P = 0.286). However, they received a lower dose of sacubitril/valsartan in comparison with those in the PARADIGM-HF (219 ± 12 vs. 375 ± 75 mg; P sacubitril/valsartan in PARADIGM-HF, patients in clinical practice were older and had a higher serum creatinine, higher New York Heart Association functional classification, and lower left ventricular ejection fraction (all P-value sacubitril/valsartan, New York Heart Association class significantly improved (P sacubitril/valsartan therapy to reduce the risk of heart failure hospitalization and all-cause mortality. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Well-being therapy in depression: New insights into the role of psychological well-being in the clinical process.

Science.gov (United States)

Fava, Giovanni A; Cosci, Fiammetta; Guidi, Jenny; Tomba, Elena

2017-09-01

A specific psychotherapeutic strategy for increasing psychological well-being and resilience, well-being therapy (WBT), has been developed and validated in a number of randomized controlled trials. The findings indicate that flourishing and resilience can be promoted by specific interventions leading to a positive evaluation of one's self, a sense of continued growth and development, the belief that life is purposeful and meaningful, the possession of quality relations with others, the capacity to manage effectively one's life, and a sense of self-determination. The evidence supporting the use of WBT and its specific contribution when it is combined with other psychotherapeutic techniques is still limited. However, the insights gained by the use of WBT may unravel innovative approaches to assessment and treatment of mood and anxiety disorders, to be confirmed by controlled studies, with particular reference to decreasing vulnerability to relapse and modulating psychological well-being and mood. An important characteristic of WBT is self-observation of psychological well-being associated with specific homework. Such perspective is different from interventions that are labeled as positive but are actually distress oriented. Another important feature of WBT is the assumption that imbalances in well-being and distress may vary from one illness to another and from patient to patient. Customary clinical taxonomy and evaluation do not include psychological well-being, which may demarcate major prognostic and therapeutic differences among patients who otherwise seem to be deceptively similar since they share the same diagnosis. © 2017 Wiley Periodicals, Inc.

Understanding Insight in the Context of Q

Science.gov (United States)

Coghlan, David

2012-01-01

In Revans' learning formula, L = P + Q, Q represents "questioning insight", by which Revans means that insight comes out of the process of questioning programmed knowledge (P) in the light of experience. We typically focus on the content of an insight rather than on the act of insight. Drawing primarily on the work of Bernard Lonergan this paper…

Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease

DEFF Research Database (Denmark)

Cooper, Oliver; Seo, Hyemyung; Andrabi, Shaida

2012-01-01

, or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insight into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress...... of reactive oxygen species, mitochondrial respiration, proton leakage, and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial dysfunction in iPSC-derived neural cells from familial PD patients and at-risk individuals could be rescued with coenzyme Q(10), rapamycin...

Elucidation of the binding mechanism of coumarin derivatives with human serum albumin.

Directory of Open Access Journals (Sweden)

Archit Garg

Full Text Available Coumarin is a benzopyrone which is widely used as an anti-coagulant, anti-oxidant, anti-cancer and also to cure arthritis, herpes, asthma and inflammation. Here, we studied the binding of synthesized coumarin derivatives with human serum albumin (HSA at physiological pH 7.2 by using fluorescence spectroscopy, circular dichroism spectroscopy, molecular docking and molecular dynamics simulation studies. By addition of coumarin derivatives to HSA the maximum fluorescence intensity was reduced due to quenching of intrinsic fluorescence upon binding of coumarin derivatives to HSA. The binding constant and free energy were found to be 1.957±0.01×10(5 M(-1, -7.175 Kcal M(-1 for coumarin derivative (CD enamide; 0.837±0.01×10(5 M(-1, -6.685 Kcal M(-1 for coumarin derivative (CD enoate, and 0.606±0.01×10(5 M(-1, -6.49 Kcal M(-1 for coumarin derivative methylprop (CDM enamide. The CD spectroscopy showed that the protein secondary structure was partially unfolded upon binding of coumarin derivatives. Further, the molecular docking studies showed that coumarin derivatives were binding to HSA at sub-domain IB with the hydrophobic interactions and also with hydrogen bond interactions. Additionally, the molecular dynamics simulations studies contributed in understanding the stability of protein-drug complex system in the aqueous solution and the conformational changes in HSA upon binding of coumarin derivatives. This study will provide insights into designing of the new inspired coumarin derivatives as therapeutic agents against many life threatening diseases.

The functions and clinical applications of tumor-derived exosomes

Science.gov (United States)

Shao, Yingkuan; Shen, Yanwei; Chen, Ting; Xu, Fei; Chen, Xuewen; Zheng, Shu

2016-01-01

Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm. They can be secreted by all cell types and transfer information in the form of their contents, which include proteins, lipids and nucleic acids, to other cells throughout the body. They have roles in normal physiological processes as well as in disease development. Here, we review recent findings regarding tumor-derived exosomes, including methods for their extraction and preservation. We also describe the actions of exosomes in tumorigenesis. The exosomal antigen-presenting effect during antitumor immune responses and its suppressive function in immune tolerance are discussed. Finally, we describe the potential application of exosomes to cancer therapy and liquid biopsy. PMID:27517627

Vibrational spectroscopic study of dehydroacetic acid and its cinnamoyl pyrone derivatives

Science.gov (United States)

Billes, Ferenc; Elečková, Lenka; Mikosch, Hans; Andruch, Vasil

2015-07-01

The infrared and Raman spectra of dehydroacetic acid and some of its derivatives were measured. The assignments of the vibrational bands were based on quantum chemical calculations and normal coordinate analysis. The optimized structures, atomic net charges and dipole moments of the investigated molecules were also results of our quantum chemical calculations. The analysis of the last properties made possible a deeper insight into the structure and substituent effect on the investigated molecules. One of them is presented in the graphical abstract.

Clinical evaluation of the Serum CrossLaps One Step ELISA, a new assay measuring the serum concentration of bone-derived degradation products of type I collagen C-telopeptides

DEFF Research Database (Denmark)

Christgau, S; Rosenquist, C; Alexandersen, P

1998-01-01

The Serum CrossLaps One Step ELISA is a sandwich assay using two monoclonal antibodies specific for a beta-aspartate form of the epitope EKAHDGGR derived from the carboxy-terminal telopeptide region of type I collagen alpha1-chain. Our objective was to assess the clinical value of the Serum Cross...

Biomarkers in T cell therapy clinical trials

Directory of Open Access Journals (Sweden)

Kalos Michael

2011-08-01

Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

Bioethics in practice: Addressing ethically sensitive requests in a Dutch fertility clinic

NARCIS (Netherlands)

Gerrits, T.; Reis, R.; Braat, D.D.M.; Kremer, J.A.M.; Hardon, A.P.

2013-01-01

This article provides insight into how ethically sensitive requests for the use of assisted reproductive technologies (ARTs) are dealt within the daily practice of a Dutch fertility clinic. The findings presented are part of an ethnographic study conducted in this clinic from September 2003 until

Monitoring cancer stem cells: insights into clinical oncology

Directory of Open Access Journals (Sweden)

Lin SC

2016-02-01

Full Text Available ShuChen Lin,1,* YingChun Xu,2,* ZhiHua Gan,1 Kun Han,1 HaiYan Hu,3 Yang Yao,3 MingZhu Huang,4 DaLiu Min1 1Department of Oncology, Shanghai Sixth People’s Hospital East Campus, Shanghai Jiao Tong University, 2Department of Oncology, Renji Hospital, Shanghai Jiao Tong University, 3Department of Oncology, The Sixth People’s Hospital, Shanghai Jiao Tong University, 4Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Cancer stem cells (CSCs are a small, characteristically distinctive subset of tumor cells responsible for tumor initiation and progression. Several treatment modalities, such as surgery, glycolytic inhibition, driving CSC proliferation, immunotherapy, and hypofractionated radiotherapy, may have the potential to eradicate CSCs. We propose that monitoring CSCs is important in clinical oncology as CSC populations may reflect true treatment response and assist with managing treatment strategies, such as defining optimal chemotherapy cycles, permitting pretreatment cancer surveillance, conducting a comprehensive treatment plan, modifying radiation treatment, and deploying rechallenge chemotherapy. Then, we describe methods for monitoring CSCs. Keywords: cancer stem cells, glycolytic inhibition, watchful waiting, rechallenge, immunotherapy

Contextualized perceptions of movement as a source of expanded insight: People with multiple sclerosis' experience with physiotherapy.

Science.gov (United States)

Normann, Britt; Sørgaard, Knut W; Salvesen, Rolf; Moe, Siri

2013-01-01

The hospitals' outpatient clinics for people with multiple sclerosis (PwMS) are important in the health care. Research regarding physiotherapy in such clinics is limited. The purpose was to investigate how PwMS perceive movement during single sessions of physiotherapy in a hospital's outpatient clinic, and what do these experiences mean for the patient's insight into their movement disturbances? Qualitative research interviews were performed with a purposive sample of 12 PwMS and supplemented with seven videotaped sessions. Content analysis was performed. The results indicate that contextualized perceptions of movement appear to be an essential source for PwMS to gain expanded insight with regard to their individual movement disturbances regardless of their ambulatory status. The contextualization implies that perceptions of movement are integrated with the physiotherapist's explanations regarding optimizing gait and balance or other activities of daily life. Perceptions of improvement in body part movement and/or functional activities are vital to enhancing their understanding of their individual movement disorders, and they may provide expanded insight regarding future possibilities and limitations involving everyday tasks. The implementation of movements, which transforms the perceived improvement into self-assisted exercises, appeared to be meaningful. Contextualized perceptions of improvements in movement may strengthen the person's sense of ownership and sense of agency and thus promote autonomy and self-encouragement. The findings underpin the importance of contextualized perceptions of movement based on exploration of potential for change, as an integrated part of information and communication in the health care for PwMS. Further investigations are necessary to deepen our knowledge.

Vaccination of metastatic melanoma patients with autologous dendritic cell (DC derived-exosomes: results of thefirst phase I clinical trial

Directory of Open Access Journals (Sweden)

Piperno Sophie

2005-03-01

Full Text Available Abstract Background DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. Patients and methods Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 × 1014 molecules or peptides (10 versus 100 μg/ml were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. Results The GMP process allowed to harvest about 5 × 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. Conclusion The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration.

An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia

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Zhisheng Her

2017-10-01

Full Text Available Abstract Background Xenotransplantation of patient-derived AML (acute myeloid leukemia cells in NOD-scid Il2rγ null (NSG mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. Methods Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically. Results Introduction of primary cells from AML patients resulted in high levels of engraftment in peripheral blood, spleen, and bone marrow (BM of recipient mice. The phenotype of engrafted AML cells remained unaltered during serial transplantation. The mice developed features that are consistent with human AML including spleen enlargement and infiltration of AML cells into multiple organs. Importantly, we demonstrated that although leukemic stem cell activity is enriched and mediated by CD34+CD117+ subpopulation, CD34+CD117− subpopulation can acquire CD34+CD117+ phenotype through de-differentiation. Lastly, we evaluated the therapeutic potential of Sorafenib and Regorafenib in this AML model and found that periphery and spleen AML cells are sensitive to these treatments, whereas BM provides a protective environment to AML. Conclusions Collectively, our improved model is robust, easy-to-construct, and reliable for pre-clinical AML studies.

Disorganization at the stage of schizophrenia clinical outcome: Clinical-biological study.

Science.gov (United States)

Nestsiarovich, A; Obyedkov, V; Kandratsenka, H; Siniauskaya, M; Goloenko, I; Waszkiewicz, N

2017-05-01

According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors. We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality. Neuropsychological tests included Wisconsin Card Sorting Test (WCST), Stroop Color-Word test. Neurophysiological examination included registration of P300 wave of the evoked cognitive auditory potentials. Environmental factors related to patient's education, family, surrounding and nicotine use, as well as subjectively significant traumatic events in childhood and adolescence were assessed. Using PCR we detected SNP of genes related to the systems of neurotransmission (COMT, SLC6A4 and DRD2), inflammatory response (IL6, TNF), cellular detoxification (GSTM1, GSTT1), DNA methylation (MTHFR, DNMT3b, DNMT1). Disorganization is associated with early schizophrenia onset and history of psychosis in family, low level of insight and compliance, high risk of committing delicts, distraction errors in WCST, lengthened P300 latency of evoked cognitive auditory potentials, low-functional alleles of genes MTHFR (rs1801133) and DNMT3b (rs2424913), high level of urbanicity and psychotraumatic events at early age. Severe disorganization at the stage of schizophrenia clinical outcome is associated with the set of specific biological and social-psychological characteristics that indicate its epigenetic nature and maladaptive social significance. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

32 CLINICAL CHARACTERISTICS OF DERMATOPHYTOSIS ...

African Journals Online (AJOL)

Although its clinical course is often considered trivial, this disease frequently becomes refractory and recurrent. Variable prevalence has been reported among healthy school children1,2. Its clinical importance derives from the morbidity caused by its itch-scratch phenomenon, the resultant skin disfiguration, its propensity for.

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.; Bajic, Vladimir B.

2010-01-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil

2010-09-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Derivation of Two New Human Embryonic Stem Cell Lines from Nonviable Human Embryos

Directory of Open Access Journals (Sweden)

Svetlana Gavrilov

2011-01-01

Full Text Available We report the derivation and characterization of two new human embryonic stem cells (hESC lines (CU1 and CU2 from embryos with an irreversible loss of integrated organismic function. In addition, we analyzed retrospective data of morphological progression from embryonic day (ED 5 to ED6 for 2480 embryos not suitable for clinical use to assess grading criteria indicative of loss of viability on ED5. Our analysis indicated that a large proportion of in vitro fertilization (IVF embryos not suitable for clinical use could be used for hESC derivation. Based on these combined findings, we propose that criteria commonly used in IVF clinics to determine optimal embryos for uterine transfer can be employed to predict the potential for hESC derivation from poor quality embryos without the destruction of vital human embryos.

OpenGL Insights

CERN Document Server

Cozzi, Patrick

2012-01-01

Get Real-World Insight from Experienced Professionals in the OpenGL Community With OpenGL, OpenGL ES, and WebGL, real-time rendering is becoming available everywhere, from AAA games to mobile phones to web pages. Assembling contributions from experienced developers, vendors, researchers, and educators, OpenGL Insights presents real-world techniques for intermediate and advanced OpenGL, OpenGL ES, and WebGL developers. Go Beyond the Basics The book thoroughly covers a range of topics, including OpenGL 4.2 and recent extensions. It explains how to optimize for mobile devices, explores the design

Contact allergy to isoeugenol and its derivatives

DEFF Research Database (Denmark)

Tanaka, Susumu; Royds, C; Buckley, Christopher D

2004-01-01

A total of 2261 (808 male, 1453 female) consecutive patients attending contact dermatitis clinics were patch tested to isoeugenol and its derivatives listed in the EU Inventory of Fragrance Ingredients. Positive reactions were found to isoeugenol in 40, transisoeugenol in 40, isoeugenyl acetate...... and 15/16 of those to isoeugenyl phenylacetate but in none of those 6 positive to isoeugenyl methyl ether and in neither of those 2 positive to benzyl isoeugenyl ether. Concomitant contact allergy between isoeugenol and its derivatives may occur through chemical cross-reactivity or local skin metabolism...... of the derivatives. It is more commonly observed with the esters rather than the ethers. Isoeugenyl acetate has been proposed as an alternative to isoeugenol, but there is a high degree of concomitant reactivity with isoeugenol....

Practical Insights from Initial Studies Related to Human Error Analysis Project (HEAP)

International Nuclear Information System (INIS)

Follesoe, Knut; Kaarstad, Magnhild; Droeivoldsmo, Asgeir; Hollnagel, Erik; Kirwan; Barry

1996-01-01

This report presents practical insights made from an analysis of the three initial studies in the Human Error Analysis Project (HEAP), and the first study in the US NRC Staffing Project. These practical insights relate to our understanding of diagnosis in Nuclear Power Plant (NPP) emergency scenarios and, in particular, the factors that influence whether a diagnosis will succeed or fail. The insights reported here focus on three inter-related areas: (1) the diagnostic strategies and styles that have been observed in single operator and team-based studies; (2) the qualitative aspects of the key operator support systems, namely VDU interfaces, alarms, training and procedures, that have affected the outcome of diagnosis; and (3) the overall success rates of diagnosis and the error types that have been observed in the various studies. With respect to diagnosis, certain patterns have emerged from the various studies, depending on whether operators were alone or in teams, and on their familiarity with the process. Some aspects of the interface and alarm systems were found to contribute to diagnostic failures while others supported performance and recovery. Similar results were found for training and experience. Furthermore, the availability of procedures did not preclude the need for some diagnosis. With respect to HRA and PSA, it was possible to record the failure types seen in the studies, and in some cases to give crude estimates of the failure likelihood for certain scenarios. Although these insights are interim in nature, they do show the type of information that can be derived from these studies. More importantly, they clarify aspects of our understanding of diagnosis in NPP emergencies, including implications for risk assessment, operator support systems development, and for research into diagnosis in a broader range of fields than the nuclear power industry. (author)

Delbruck Prize Award: Insights into HIV Dynamics and Cure

Science.gov (United States)

Perelson, Alan S.

A large effort is being made to find a means to cure HIV infection. I will present a dynamical model of a phenomenon called post-treatment control (PTC) or functional cure of HIV-infection in which some patients treated with suppressive antiviral therapy have been taken off of therapy and then spontaneously control HIV infection. The model relies on an immune response and bistability to explain PTC. I will then generalize the model to explicitly include immunotherapy with monoclonal antibodies approved for use in cancer to show that one can induce PTC with a limited number of antibody infusions and compare model predictions with experiments in SIV infected macaques given immunotherapy. Lastly, I will argue that quantitative insights derived from models of HIV infection have and will continue to play an important role in medicine.

Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Clinical and laboratory outcomes.

Science.gov (United States)

Pérez-Merino, E M; Usón-Casaús, J M; Zaragoza-Bayle, C; Duque-Carrasco, J; Mariñas-Pardo, L; Hermida-Prieto, M; Barrera-Chacón, R; Gualtieri, M

2015-12-01

Mesenchymal stem cells (MSCs) have shown immunomodulatory and anti-inflammatory effects in experimental colitis, and promising clinical results have been obtained in humans with Crohn's disease and ulcerative colitis. The aim of this study was to determine the safety and feasibility of adipose tissue-derived MSC (ASC) therapy in dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received one ASC intravascular (IV) infusion (2 × 10(6) cells/kg bodyweight). The outcome measures were clinical response based on percentage reduction of the validated Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) and Canine Chronic Enteropathy Clinical Activity Index (CCECAI), as well as normalisation of C-reactive protein (CRP), albumin, folate and cobalamin serum concentrations at day 42 post-treatment. The Wilcoxon test was used to compare variables before and after treatment. No acute reaction to ASC infusion and no side effects were reported during follow-up in any dog. Six weeks post-treatment, the CIBDAI and CCECAI decreased significantly and albumin, cobalamin and folate concentrations increased substantially. Differences in CRP concentrations pre- and post-treatment were not significant (P = 0.050). Clinical remission (defined by a reduction of initial CIBDAI and CCECAI >75%) occurred in 9/11 dogs at day 42. The two remaining dogs showed a partial response with reduction percentages of 69.2% and 71.4%. In conclusion, a single IV infusion of allogeneic ASCs was well tolerated and appeared to produce clinical benefits in dogs with severe IBD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reaction pathways of model compounds of biomass-derived oxygenates on Fe/Ni bimetallic surfaces

Science.gov (United States)

Yu, Weiting; Chen, Jingguang G.

2015-10-01

Controlling the activity and selectivity of converting biomass-derivatives to fuels and valuable chemicals is critical for the utilization of biomass feedstocks. There are primarily three classes of non-food competing biomass, cellulose, hemicellulose and lignin. In the current work, glycolaldehyde, furfural and acetaldehyde are studied as model compounds of the three classes of biomass-derivatives. Monometallic Ni(111) and monolayer (ML) Fe/Ni(111) bimetallic surfaces are studied for the reaction pathways of the three biomass surrogates. The ML Fe/Ni(111) surface is identified as an efficient surface for the conversion of biomass-derivatives from the combined results of density functional theory (DFT) calculations and temperature programmed desorption (TPD) experiments. A correlation is also established between the optimized adsorption geometry and experimental reaction pathways. These results should provide helpful insights in catalyst design for the upgrading and conversion of biomass.

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database

NARCIS (Netherlands)

Thompson, Bryony A.; Spurdle, Amanda B.; Plazzer, John-Paul; Greenblatt, Marc S.; Akagi, Kiwamu; Al-Mulla, Fahd; Bapat, Bharati; Bernstein, Inge; Capella, Gabriel; den Dunnen, Johan T.; du Sart, Desiree; Fabre, Aurelie; Farrell, Michael P.; Farrington, Susan M.; Frayling, Ian M.; Frebourg, Thierry; Goldgar, David E.; Heinen, Christopher D.; Holinski-Feder, Elke; Kohonen-Corish, Maija; Robinson, Kristina Lagerstedt; Leung, Suet Yi; Martins, Alexandra; Moller, Pal; Morak, Monika; Nystrom, Minna; Peltomaki, Paivi; Pineda, Marta; Qi, Ming; Ramesar, Rajkumar; Rasmussen, Lene Juel; Royer-Pokora, Brigitte; Scott, Rodney J.; Sijmons, Rolf; Tavtigian, Sean V.; Tops, Carli M.; Weber, Thomas; Wijnen, Juul; Woods, Michael O.; Macrae, Finlay; Genuardi, Maurizio

The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and

Hip fracture discrimination by the Achilles Insight QUS imaging device

International Nuclear Information System (INIS)

Damilakis, John; Papadokostakis, George; Perisinakis, Kostas; Maris, Thomas G.; Karantanas, Apostolos H.

2007-01-01

The importance of osteoporosis as a major health problem is well recognized. Its major clinical manifestation is low energy fractures. Considerable effort has been directed towards search of noninvasive methods for assessing osteoporotic fracture risk. The aim of this study was to evaluate the ability of quantitative ultrasound (QUS) variables measured by a new heel QUS imaging device to discriminate between postmenopausal women with and without hip fracture. The subjects included 30 postmenopausal female patients with hip fracture and 30 age-matched healthy women. Measurements were acquired using the Achilles Insight QUS imaging device. Bone mineral density (BMD) measurements were carried out using the Lunar Prodigy DXA scanner. Achilles Insight provides images of the heel bone and measures broadband ultrasound attenuation (BUA) and speed of sound (SOS) values in a circular region of interest. A third QUS variable, the stiffness index (SI) was also determined. The short-term precision for healthy subjects was 2.05%, 0.17% and 1.91% for BUA, SOS and SI, respectively. Corresponding values for patients with fractures were 1.80%, 0.16% and 2.04%. All QUS variables measured using the Achilles Insight were significant discriminators of hip fractures (area under ROC curve = 0.77, 0.74 and 0.77 for BUA, SOS and SI, respectively). BMD measurements of the hip had the greatest discriminatory ability (area under ROC curve = 0.88). Statistically significant differences were found between the area under the ROC curve of BMD and the corresponding curves of the QUS variables (P < 0.05 for each of the three comparisons). QUS variables measured by Achilles Insight can be expected to be useful as indicators of the risk of hip fracture in postmenopausal women

Soil solution phosphorus turnover: derivation, interpretation, and insights from a global compilation of isotope exchange kinetic studies

Science.gov (United States)

Helfenstein, Julian; Jegminat, Jannes; McLaren, Timothy I.; Frossard, Emmanuel

2018-01-01

The exchange rate of inorganic phosphorus (P) between the soil solution and solid phase, also known as soil solution P turnover, is essential for describing the kinetics of bioavailable P. While soil solution P turnover (Km) can be determined by tracing radioisotopes in a soil-solution system, few studies have done so. We believe that this is due to a lack of understanding on how to derive Km from isotopic exchange kinetic (IEK) experiments, a common form of radioisotope dilution study. Here, we provide a derivation of calculating Km using parameters obtained from IEK experiments. We then calculated Km for 217 soils from published IEK experiments in terrestrial ecosystems, and also that of 18 long-term P fertilizer field experiments. Analysis of the global compilation data set revealed a negative relationship between concentrations of soil solution P and Km. Furthermore, Km buffered isotopically exchangeable P in soils with low concentrations of soil solution P. This finding was supported by an analysis of long-term P fertilizer field experiments, which revealed a negative relationship between Km and phosphate-buffering capacity. Our study highlights the importance of calculating Km for understanding the kinetics of P between the soil solid and solution phases where it is bioavailable. We argue that our derivation can also be used to calculate soil solution turnover of other environmentally relevant and strongly sorbing elements that can be traced with radioisotopes, such as zinc, cadmium, nickel, arsenic, and uranium.

Probabilistic safety assessment applications and insights

International Nuclear Information System (INIS)

Hitchler, M.J.; Burns, N.L.; Liparulo, N.J.; Mink, F.J.

1987-01-01

The insights gained through a comparison of seven PRA studies (Italian PUN, Sizewell B, Ringhals 2, Millstone 3, Zion 1 and 2, Oconee 3, and Seabrook) included insights regarding the adequacy of the PRA technology utilized in the studies and the potential areas for improvement and insights regarding the adequacy of plant designs and how PRA has been utilized to enhance the design and operation of nuclear power plants. (orig.)

Formal thought disorder, neuropsychology and insight in schizophrenia.

Science.gov (United States)

Barrera, Alvaro; McKenna, Peter J; Berrios, German E

2009-01-01

Information provided by patients with schizophrenia and their respective carers is used to study the descriptive psychopathology and neuropsychology of formal thought disorder (FTD). Relatively intellectually preserved schizophrenia patients (n = 31) exhibiting from no to severe positive FTD completed a self-report scale of FTD, a scale of insight as well as several tests of executive and semantic function. The patients' carers completed another scale of FTD to assess the patients' speech. FTD as self-reported by patients was significantly associated with the synonyms test performance and severity of the reality distortion dimension. FTD as assessed by a clinician and by the patients' carers was significantly associated with executive test performance and performance in a test of associative semantics. Overall insight was significantly associated with severity of the reality distortion dimension and graded naming test performance, but was not associated with self-reported FTD or severity of FTD as assessed by the clinician or carers. The self-reported experience of FTD has different clinical and neuropsychological correlates from those of FTD as assessed by clinicians and carers. The assessment of FTD by patients and carers used along with the clinician's assessment may further the study of this group of symptoms. 2009 S. Karger AG, Basel.

The therapeutic potential of plant-derived vaccines and antibodies.

Science.gov (United States)

Rodgers, P B; Hamilton, W D; Adair, J R

1999-03-01

The production of recombinant proteins in plants is reviewed with a particular focus on plant-derived vaccines and antibodies for human healthcare. Issues relating to foreign gene expression, such as protein yield, localisation and glycosylation are also considered. Emphasis is placed on reporting progress with preclinical and clinical evaluation of plant-derived vaccines and antibodies. An assessment is made of the likely future direction of research and development in this area.

Induction of discrete apoptotic pathways by bromo-substituted indirubin derivatives in invasive breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Nicolaou, Katerina A. [Department of Biological Sciences, University of Cyprus, Nicosia (Cyprus); Liapis, Vasilis; Evdokiou, Andreas [Department of Surgery, Basil Hetzel Institute, Adelaide University, Adelaide (Australia); Constantinou, Constantina [St. George' s University of London Medical School at the University of Nicosia, Nicosia (Cyprus); Magiatis, Prokopios; Skaltsounis, Alex L. [Faculty of Pharmacy, University of Athens, Athens (Greece); Koumas, Laura; Costeas, Paul A. [Center for Study of Hematological Malignancies, Nicosia (Cyprus); Constantinou, Andreas I., E-mail: andreasc@ucy.ac.cy [Department of Biological Sciences, University of Cyprus, Nicosia (Cyprus)

2012-08-17

Highlights: Black-Right-Pointing-Pointer The effects of 6BIO and 7BIO are evaluated against five breast cancer cell lines. Black-Right-Pointing-Pointer 6BIO induces a caspase dependent apoptotic effect via the intrinsic pathway. Black-Right-Pointing-Pointer 7BIO promotes G{sub 2}/M cells cycle arrest. Black-Right-Pointing-Pointer 7BIO triggers a caspase-8 mediated apoptotic pathway. Black-Right-Pointing-Pointer 7BIO triggers and a caspase independent pathway. -- Abstract: Indirubin derivatives gained interest in recent years for their anticancer and antimetastatic properties. The objective of the present study was to evaluate and compare the anticancer properties of the two novel bromo-substituted derivatives 6-bromoindirubin-3 Prime -oxime (6BIO) and 7-bromoindirubin-3 Prime -oxime (7BIO) in five different breast cancer cell lines. Cell viability assays identified that 6BIO and 7BIO are most effective in preventing the proliferation of the MDA-MB-231-TXSA breast cancer cell line from a total of five breast cancer cell lined examined. In addition it was found that the two compounds induce apoptosis via different mechanisms. 6BIO induces caspase-dependent programmed cell death through the intrinsic (mitochondrial) caspase-9 pathway. 7BIO up-regulates p21 and promotes G{sub 2}/M cell cycle arrest which is subsequently followed by the activation of two different apoptotic pathways: (a) a pathway that involves the upregulation of DR4/DR5 and activation of caspase-8 and (b) a caspase independent pathway. In conclusion, this study provides important insights regarding the molecular pathways leading to cell cycle arrest and apoptosis by two indirubin derivatives that can find clinical applications in targeted cancer therapeutics.

Deploying innovations in wearable technology to gain insight into clinical disorders and their treatment

DEFF Research Database (Denmark)

Parsons, Christine; Jensen, Kasper Løvborg; Linehan, Conor

a smartphone application that can gather and analyse physiological and behavioural data securely. From testing wearable device capacities, we suggest that resting sleeping heart rate may comprise a measurable index of physiological functioning. This measure, together with behavioural indices, such as daily......, but infrequent assessment. Wearable technology can provide new ways to understand physiology beyond the laboratory. In order to harness this potential, we need to develop methods to monitor patients unobtrusively, with minimal patient burden, and due concern for privacy issues. Furthermore, we need to ensure...... rhythmic patterns of activity, may provide new insights into patient functioning. Furthermore, high-frequency recording, over extended periods as available from wearable devices, will provide us with a temporally-sensitive means to investigate treatment effects....

Insight in schizophrenia: involvement of self-reflection networks?

Science.gov (United States)

van der Meer, Lisette; de Vos, Annerieke E; Stiekema, Annemarie P M; Pijnenborg, Gerdina H M; van Tol, Marie-José; Nolen, Willem A; David, Anthony S; Aleman, André

2013-11-01

Impaired insight is a common feature in psychosis and an important predictor of variables such as functional outcome, prognosis, and treatment adherence. A cognitive process that may underlie insight in psychosis is self-reflection, or the conscious evaluation of one's traits and characteristics. The current study aims to investigate the neural correlates of self-reflective processing and its relationship with insight in schizophrenia. Forty-seven schizophrenia patients and 21 healthy controls performed a self-reflection task in a functional magnetic resonance imaging (fMRI) scanner. The tasks comprised a self-reflection, close other-reflection, and a semantic (baseline) condition. Insight scores were obtained with the Schedule of Assessment of Insight Expanded. In addition, cognitive insight scores were obtained (Beck Cognitive Insight Scale [BCIS]). Schizophrenia patients demonstrated less activation in the posterior cingulate cortex in the self- and other-reflection conditions and less activation in the precuneus in the other-reflection condition compared with healthy controls. Better insight was associated with greater response in the inferior frontal gyrus, anterior insula, and inferior parietal lobule during self-reflection. In addition, better cognitive insight was associated with higher activation in ventromedial prefrontal cortex during self-reflection. In the current study, evidence for a relationship between self-reflection and insight in patients with schizophrenia was found in brain areas related to self-reflection, self/other distinction and source attribution. The findings support the rationale for a treatment that is currently under evaluation, which attempts to increase insight by enhancing self-reflection.

Neural activity in relation to clinically derived personality syndromes in depression using a psychodynamic fMRI paradigm

Directory of Open Access Journals (Sweden)

Svenja eTaubner

2013-12-01

Full Text Available Objective: The heterogeneity between patients with depression cannot be captured adequately with existing descriptive systems of diagnosis and neurobiological models of depression. Furthermore, considering the highly individual nature of depression, the application of general stimuli in past research efforts may not capture the essence of the disorder. This study aims to identify subtypes of depression by using empirically-derived personality-syndromes, and to explore neural correlates of the derived personality syndromes.Method: In the present exploratory study an individually tailored and psychodynamically based fMRI paradigm using dysfunctional relationship patterns was presented to 20 chronically depressed patients. Results from the Shedler-Westen-Assessment-Procedure (SWAP-200 were analyzed by Q-factor analysis to identify clinically relevant subgroups of depression and related brain activation.Results: The principle component analysis of SWAP-200 items from all 20 patients lead to a 2-factor solution: Depressive Personality and Emotional-Hostile-Externalizing Personality. Both factors were used in a whole-brain correlational analysis but only the second factor yielded significant positive correlations in four regions: A large cluster in the right orbitofrontal cortex (OFC, the left ventral striatum, a small cluster in the left temporal pole and another small cluster in the right middle frontal gyrus. Discussion: The degree to which patients with depression score high on the factor Emotional-Hostile-Externalizing Personality correlated with relatively higher activity in three key areas involved in emotion processing, evaluation of reward/punishment, negative cognitions, depressive pathology and social knowledge (OFC, ventral striatum, temporal pole. Results may contribute to an alternative description of neural correlates of depression showing differential brain activation dependent on the extent of specific personality syndromes in

Insight in psychosis : Metacognitive processes and treatment

NARCIS (Netherlands)

de Vos, Annerieke

2016-01-01

Insight is impaired in 50- 80% of the patients with schizophrenia. Annerieke de Vos working at GGZ Drenthe and the University Medical Hospital Groningen, aimed to elucidate which processes underlie impaired insight and tried to improve insight in patients by targeting these processes. On September

Cell-assisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells.

Science.gov (United States)

Yoshimura, Kotaro; Sato, Katsujiro; Aoi, Noriyuki; Kurita, Masakazu; Inoue, Keita; Suga, Hirotaka; Eto, Hitomi; Kato, Harunosuke; Hirohi, Toshitsugu; Harii, Kiyonori

2008-09-01

Lipoinjection is a promising treatment, but its efficacy in recontouring facial lipoatrophy remains to be established. The objective was to evaluate the efficacy and adverse effects of lipoinjection and supplementation of adipose-derived stem/stromal cells (ASCs) to adipose grafts. To overcome drawbacks of autologous lipoinjection, we have developed a novel strategy called cell-assisted lipotransfer (CAL). In CAL, stromal vascular fraction containing ASCs was freshly isolated from half of an aspirated fat sample and attached to the other half of aspirated fat sample with the fat acting as a scaffold. This process converts relatively ASC-poor aspirated fat into ASC-rich fat. We performed conventional lipoinjection (non-CAL; n=3) or CAL (n=3) on six patients with facial lipoatrophy due to lupus profundus or Parry-Romberg syndrome. All patients obtained improvement in facial contour, but the CAL group had a better clinical improvement score than did the non-CAL patients, although the difference did not reach statistical significance (p=.11). Adipose necrosis was found in one non-CAL case who took perioperative oral corticosteroids. Our results suggest that CAL is both effective and safe and potentially superior to conventional lipoinjection for facial recontouring. The authors have indicated no significant interest with commercial supporters.

Insights gained through probabilistic risk assessments

International Nuclear Information System (INIS)

Hitchler, M.J.; Burns, N.L.; Liparulo, N.J.; Mink, F.J.

1987-01-01

The insights gained through a comparison of seven probabilistic risk assessments (PRA) studies (Italian PUN, Sizewell B, Ringhals 2, Millstone 3, Zion 1 and 2, Oconee 3, and Seabrook) included insights regarding the adequacy of the PRA technology utilized in the studies and the potential areas for improvement and insights regarding the adequacy of plant designs and how PRA has been utilized to enhance the design and operation of nuclear power plants

Overutilization and underutilization of operating rooms - insights from behavioral health care operations management.

Science.gov (United States)

Fügener, Andreas; Schiffels, Sebastian; Kolisch, Rainer

2017-03-01

The planning of surgery durations is crucial for efficient usage of operating theaters. Both planning too long and too short durations for surgeries lead to undesirable consequences, e.g. idle time, overtime, or rescheduling of surgeries. We define these consequences as operating room inefficiency. The overall objective of planning surgery durations is to minimize expected operating room inefficiency, since surgery durations are stochastic. While most health care studies assume economically rational behavior of decision makers, experimental studies have shown that decision makers often do not act according to economic incentives. Based on insights from health care operations management, medical decision making, behavioral operations management, as well as empirical observations, we derive hypotheses that surgeons' behavior deviates from economically rational behavior. To investigate this, we undertake an experimental study where experienced surgeons are asked to plan surgeries with uncertain durations. We discover systematic deviations from optimal decision making and offer behavioral explanations for the observed biases. Our research provides new insights to tackle a major problem in hospitals, i.e. low operating room utilization going along with staff overtime.

Sleeping beauties in theoretical physics 26 surprising insights

CERN Document Server

Padmanabhan, Thanu

2015-01-01

This book addresses a fascinating set of questions in theoretical physics which will both entertain and enlighten all students, teachers and researchers and other physics aficionados. These range from Newtonian mechanics to quantum field theory and cover several puzzling issues that do not appear in standard textbooks. Some topics cover conceptual conundrums, the solutions to which lead to surprising insights; some correct popular misconceptions in the textbook discussion of certain topics; others illustrate deep connections between apparently unconnected domains of theoretical physics; and a few provide remarkably simple derivations of results which are not often appreciated. The connoisseur of theoretical physics will enjoy a feast of pleasant surprises skilfully prepared by an internationally acclaimed theoretical physicist. Each topic is introduced with proper background discussion and special effort is taken to make the discussion self-contained, clear and comprehensible to anyone with an undergraduate e...

Current insights into hormonal regulation of microspore embryogenesis

Directory of Open Access Journals (Sweden)

Iwona eŻur

2015-06-01

Full Text Available Plant growth regulator (PGR crosstalk and interaction with the plant’s genotype and environmental factors play a crucial role in microspore embryogenesis (ME, controlling microspore-derived embryo differentiation and development as well as haploid/doubled haploid plant regeneration. The complexity of the PGR network which could exist at the level of biosynthesis, distribution, gene expression or signaling pathways, renders the creation of an integrated model of ME-control crosstalk impossible at present. However, the analysis of the published data together with the results received recently with the use of modern analytical techniques brings new insights into hormonal regulation of this process. This review presents a short historical overview of the most important milestones in the recognition of hormonal requirements for effective ME in the most important crop plant species and complements it with new concepts that evolved over the last decade of ME studies.

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

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Clemens Krepler

2017-11-01

Full Text Available Summary: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups. : Krepler et al. have established a collection of melanoma patient-derived xenografts (PDX. Melanoma is a very heterogeneous cancer, and this large collection includes even rare subtypes and genetic aberrations in sufficient numbers. Multiple PDX from therapy-resistant patients are characterized and tested in pre-clinical trials for second line therapies. Keywords: melanoma, patient-derived xenografts, targeted therapy, immune checkpoint blockade, melanoma brain metastasis, in vivo models, BRAF inhibitor resistance, ERK inhibitor, MDM2 inhibitor, PI3K beta inhibitor

Pleuromutilin and its derivatives-the lead compounds for novel antibiotics.

Science.gov (United States)

Tang, Y-Z; Liu, Y-H; Chen, J-X

2012-01-01

Due to the rapid onset of resistance to most antibacterial drugs, research efforts are focusing on new classes of antibacterials with different mechanisms of action from clinically used antibacterials. Pleuromutilin derivatives have received more and more scientific attention for their unique mechanism of action. Two pleuromutilin derivatives, tiamulin and valnemulin have been successfully developed as antibiotics for veterinary use. Retapamulin, another pleuromutilin derivative has been approved for use in humans in April 2007 by Food and Drug Administration (FDA). It has been shown that there is rarely cross-resistance between pleuromutilin derivatives and other antimicrobial agents, and the development of resistance bacterial is still low. This review will demonstrate mechanism of action of pleuromutilin derivatives and reveal the structure-activity relationship (SAR) of pleuromutilin derivatives. Additionally, the pleuromutilin antibacterial derivative agents in the market, such as tiamulin, valnemulin and retapamulin, will be discussed. It is proposed that new antibacterial agents might be developed from pleuromutilin derivatives in the future.

Is Insight Always the Same? A Protocol Analysis of Insight in Compound Remote Associate Problems

Science.gov (United States)

Cranford, Edward A.; Moss, Jarrod

2012-01-01

Compound Remote Associate (CRA) problems have been used to investigate insight problem solving using both behavioral and neuroimaging techniques. However, it is unclear to what extent CRA problems exhibit characteristics of insight such as impasses and restructuring. CRA problem-solving characteristics were examined in a study in which…

99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours; first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives.

Science.gov (United States)

Decristoforo, C; Mather, S J; Cholewinski, W; Donnemiller, E; Riccabona, G; Moncayo, R

2000-09-01

[111In-diethylene triamine penta-acetic acid-D-Phe1]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99mTc-EDDA/HYNIC-TOC were compared with those of 111In-DTPA-octreotide in six cases, and with those of 111In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111In-DTPA-octreotide but faster than that of 111In-DOTA-TOC, while urinary excretion was lower compared with the 111In derivatives. Semi-quantitative region of interest analysis showed that 99mTc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99mTc images. We conclude that 99mTcEDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111In-labelled octreotide derivatives.

99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours: first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives

International Nuclear Information System (INIS)

Decristoforo, C.; Cholewinski, W.; Donnemiller, E.; Riccabona, G.; Moncayo, R.

2000-01-01

[ 111 In-diethylene triamine penta-acetic acid-d-Phe 1 ]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99m Tc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99m Tc-EDDA/HYNIC-TOC were compared with those of 111 In-DTPA-octreotide in six cases, and with those of 111 In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111 In-DTPA-octreotide but faster than that of 111 In-DOTA-TOC, while urinary excretion was lower compared with the 111 In derivatives. Semi-quantitative region of interest analysis showed that 99m Tc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111 In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99m Tc images. We conclude that 99m Tc-EDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111 In-labelled octreotide derivatives. (orig.)

Insight in Schizophrenia: Involvement of Self-Reflection Networks?

Science.gov (United States)

de Vos, Annerieke E.

2013-01-01

Background: Impaired insight is a common feature in psychosis and an important predictor of variables such as functional outcome, prognosis, and treatment adherence. A cognitive process that may underlie insight in psychosis is self-reflection, or the conscious evaluation of one’s traits and characteristics. The current study aims to investigate the neural correlates of self-reflective processing and its relationship with insight in schizophrenia. Methods: Forty-seven schizophrenia patients and 21 healthy controls performed a self-reflection task in a functional magnetic resonance imaging (fMRI) scanner. The tasks comprised a self-reflection, close other-reflection, and a semantic (baseline) condition. Insight scores were obtained with the Schedule of Assessment of Insight Expanded. In addition, cognitive insight scores were obtained (Beck Cognitive Insight Scale [BCIS]). Results: Schizophrenia patients demonstrated less activation in the posterior cingulate cortex in the self- and other-reflection conditions and less activation in the precuneus in the other-reflection condition compared with healthy controls. Better insight was associated with greater response in the inferior frontal gyrus, anterior insula, and inferior parietal lobule during self-reflection. In addition, better cognitive insight was associated with higher activation in ventromedial prefrontal cortex during self-reflection. Conclusion: In the current study, evidence for a relationship between self-reflection and insight in patients with schizophrenia was found in brain areas related to self-reflection, self/other distinction and source attribution. The findings support the rationale for a treatment that is currently under evaluation, which attempts to increase insight by enhancing self-reflection. PMID:23104865

Pleasures of the Mind: What Makes Jokes and Insight Problems Enjoyable

Directory of Open Access Journals (Sweden)

Carla Canestrari

2018-01-01

Full Text Available In this paper, a parallel analysis of the enjoyment derived from humor and insight problem solving is presented with reference to a “general” Theory of the Pleasures of the Mind (TPM (Kubovy, 1999 rather than to “local” theories regarding what makes humor and insight problem solving enjoyable. The similarity of these two cognitive activities has already been discussed in previous literature in terms of the cognitive mechanisms which underpin getting a joke or having an insight experience in a problem solving task. The paper explores whether we can learn something new about the similarities and differences between humor and problem solving by means of an investigation of what makes them pleasurable. In the first part of the paper, the framework for this joint analysis is set. Two descriptive studies are then presented in which the participants were asked to report on their experiences relating to solving visuo-spatial insight problems (Study 1 or understanding cartoons (Study 2 in terms of whether they were enjoyable or otherwise. In both studies, the responses were analyzed with reference to a set of categories inspired by the TPM. The results of Study 1 demonstrate that finding the solution to a problem is associated with a positive evaluation, and the most frequent explanations for this were reported as being Curiosity, Virtuosity and Violation of expectations. The results of Study 2 suggest that understanding a joke (Joy of verification and being surprised by it (Feeling of surprise were two essential conditions: when they were not present, the cartoons were perceived as not enjoyable. However, this was not enough to explain the motivations for the choice of the most enjoyable cartoons. Recognizing a Violation of expectations and experiencing a Diminishment in the cleverness or awareness initially attributed to the characters in the cartoon were the aspects which were most frequently indicated by the participants to explain why they

Clinical course and variability of non-Rasmussen, nonstroke motor and sensory epilepsia partialis continua: a European survey and analysis of 65 cases

DEFF Research Database (Denmark)

Mameniskiene, Ruta; Bast, Thomas; Bentes, Carla

2011-01-01

To gain new insights into the clinical presentation, causes, treatment and prognosis of epilepsia partialis continua (EPC), and to develop hypotheses to be tested in a prospective investigation.......To gain new insights into the clinical presentation, causes, treatment and prognosis of epilepsia partialis continua (EPC), and to develop hypotheses to be tested in a prospective investigation....

Human Performance on Insight Problem Solving: A Review

Science.gov (United States)

Chu, Yun; MacGregor, James N.

2011-01-01

The article provides a review of recent research on insight problem-solving performance. We discuss what insight problems are, the different types of classic and newer insight problems, and how we can classify them. We also explain some of the other aspects that affect insight performance, such as hints, analogs, training, thinking aloud, and…

Cognitive functioning and insight in schizophrenia and in schizoaffective disorder.

Science.gov (United States)

Birindelli, Nadia; Montemagni, Cristiana; Crivelli, Barbara; Bava, Irene; Mancini, Irene; Rocca, Paola

2014-01-01

The aim of this study was to investigate cognitive functioning and insight of illness in two groups of patients during their stable phases, one with schizophrenia and one with schizoaffective disorder. We recruited 104 consecutive outpatients, 64 with schizophrenia, 40 with schizoaffective disorder, in the period between July 2010 and July 2011. They all fulfilled formal Diagnostic and Statistical Manual of Mental disorders (DSM-IV-TR) diagnostic criteria for schizophrenia and schizoaffective disorder. Psychiatric assessment included the Clinical Global Impression Scale-Severity (CGI-S), the Positive and Negative Sindrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Global Assessment of Functioning (GAF). Insight of illness was evaluated using SUMD. Neuropsychological assessment included Winsconsin Card Sorting Test (WCST), California Verbal Learning Test (CVLT), Stroop Test and Trail Making Test (TMT). Differences between the groups were tested using Chi-square test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. All variables significantly different between the two groups of subjects were subsequently analysed using a logistic regression with a backward stepwise procedure using diagnosis (schizophrenia/schizoaffective disorder) as dependent variable. After backward selection of variables, four variables predicted a schizoaffective disorder diagnosis: marital status, a higher number of admission, better attentive functions and awareness of specific signs or symptoms of disease. The prediction model accounted for 55% of the variance of schizoaffective disorder diagnosis. With replication, our findings would allow higher diagnostic accuracy and have an impact on clinical decision making, in light of an amelioration of vocational functioning.

Potential of cancer cell-derived exosomes in clinical application: a review of recent research advances.

Science.gov (United States)

Sun, Yu; Liu, Jing

2014-06-01

Exosomes are 30- to 100-nm, membrane-bound vesicles that are released by most types of cells, including tumor cells. Exosomes contain a great variety of bioactive molecules, including signal peptides, microRNA, lipids, and DNA. In cancer, tumor cells aberrantly secrete large quantities of exosomes to transport paracrine signals or to contribute to tumor-environment interaction at a distance. The goal of this review was to discuss the recent advances on the mechanism of cancer-derived exosomes in tumor regulation. Pertinent articles and abstracts were identified through searches of PubMed for literature published from 1983 to December 2013. Search terms included exosome, tumor, cancer, diagnosis, and therapy. All of the exposed evidence points to communication between cancer cells and their surroundings, either mediated by cancer cell-derived exosomes or by stromal cell-derived exosomes. This communication probably supports tumor proliferation, motility, invasion, angiogenesis, and premetastatic niche preparation. In addition, recent research implies that cancer cell-derived exosomes play a suppressive role in cancer-directed immune response. The biomarkers detected in bodily fluid-derived exosomes imply a potential for exosomes in cancer diagnosis. Also, exosomes could be used as a vehicle to selectively deliver therapeutic nucleic-acid drugs or conventional drugs for tumor therapy. The tolerability and feasibility of cancer exosomes in diagnosis and therapy need to be further evaluated. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Clinical data miner: an electronic case report form system with integrated data preprocessing and machine-learning libraries supporting clinical diagnostic model research.

Science.gov (United States)

Installé, Arnaud Jf; Van den Bosch, Thierry; De Moor, Bart; Timmerman, Dirk

2014-10-20

Using machine-learning techniques, clinical diagnostic model research extracts diagnostic models from patient data. Traditionally, patient data are often collected using electronic Case Report Form (eCRF) systems, while mathematical software is used for analyzing these data using machine-learning techniques. Due to the lack of integration between eCRF systems and mathematical software, extracting diagnostic models is a complex, error-prone process. Moreover, due to the complexity of this process, it is usually only performed once, after a predetermined number of data points have been collected, without insight into the predictive performance of the resulting models. The objective of the study of Clinical Data Miner (CDM) software framework is to offer an eCRF system with integrated data preprocessing and machine-learning libraries, improving efficiency of the clinical diagnostic model research workflow, and to enable optimization of patient inclusion numbers through study performance monitoring. The CDM software framework was developed using a test-driven development (TDD) approach, to ensure high software quality. Architecturally, CDM's design is split over a number of modules, to ensure future extendability. The TDD approach has enabled us to deliver high software quality. CDM's eCRF Web interface is in active use by the studies of the International Endometrial Tumor Analysis consortium, with over 4000 enrolled patients, and more studies planned. Additionally, a derived user interface has been used in six separate interrater agreement studies. CDM's integrated data preprocessing and machine-learning libraries simplify some otherwise manual and error-prone steps in the clinical diagnostic model research workflow. Furthermore, CDM's libraries provide study coordinators with a method to monitor a study's predictive performance as patient inclusions increase. To our knowledge, CDM is the only eCRF system integrating data preprocessing and machine-learning libraries

Reliability of clinical ICD-10 schizophrenia diagnoses

DEFF Research Database (Denmark)

Jakobsen, Klaus D; Frederiksen, Julie N; Hansen, Thomas

2005-01-01

Concern has been expressed as to the reliability of clinical ICD-10 diagnosis of schizophrenia. This study was designed to assess the diagnostic reliability of the clinical ICD-10 diagnosis of schizophrenia in a random sample of Danish in- and outpatients with a history of psychosis. A sample...... value (87%) of ICD-10 schizophrenia and an overall good agreement between clinical and OPCRIT-derived diagnoses (kappa=0.60). An even higher positive predictive value was obtained when diagnoses were amalgamated into a diagnostic entity of schizophrenia-spectrum disorders (98%). Near perfect agreement...... was seen between OPCRIT-derived ICD-10 and DSM-IV diagnoses (kappa=0.87). Thus, this study demonstrates high reliability of the clinical diagnosis of schizophrenia and even more so of the diagnosis of schizophrenia-spectrum disorder....

Quantifying the Qualitative: Measuring the Insight Experience

Science.gov (United States)

Jarman, Matthew S.

2014-01-01

No scales currently exist that measure variability in the insight experience. Two scales were created to measure two factors hypothesized to be key drivers of the insight experience: insight radicality (i.e., perceived deviation between previous and new problem representations) and restructuring experience (i.e., the subjective experience of the…

Synthesis of Gibberellic Acid Derivatives and Their Effects on Plant Growth

Directory of Open Access Journals (Sweden)

Hao Tian

2017-04-01

Full Text Available A series of novel C-3-OH substituted gibberellin derivatives bearing an amide group were designed and synthesized from the natural product gibberellic acid (GA3. Their activities on the plant growth regulation of rice and Arabidopsis were evaluated in vivo. Among these compounds, 10d and 10f exhibited appreciable inhibitory activities on rice (48.6% at 100 μmol/L and Arabidopsis (41.4% at 100 μmol/L, respectively. These results provide new insights into the design and synthesis of potential plant growth regulators.

Medical student resilience and stressful clinical events during clinical training.

Science.gov (United States)

Houpy, Jennifer C; Lee, Wei Wei; Woodruff, James N; Pincavage, Amber T

2017-01-01

Medical students face numerous stressors during their clinical years, including difficult clinical events. Fostering resilience is a promising way to mitigate negative effects of stressors, prevent burnout, and help students thrive after difficult experiences. However, little is known about medical student resilience. To characterize medical student resilience and responses to difficult clinical events during clinical training. Sixty-two third-year (MS3) and 55 fourth-year (MS4) University of Chicago medical students completed surveys in 2016 assessing resilience (Connor Davidson Resilience Scale, CD-RISC 10), symptoms of burnout, need for resilience training, and responses to difficult clinical events. Medical student mean resilience was lower than in a general population sample. Resilience was higher in males, MS4s, those without burnout symptoms, and students who felt able to cope with difficult clinical events. When students experienced difficult events in the clinical setting, the majority identified poor team dynamics among the most stressful, and agreed their wellbeing was affected by difficult clinical events. A majority also would prefer to discuss these events with their team later that day. Students discussed events with peers more than with attendings or residents. Students comfortable discussing stress and burnout with peers had higher resilience. Most students believed resilience training would be helpful and most beneficial during MS3 year. Clinical medical student resilience was lower than in the general population but higher in MS4s and students reporting no burnout. Students had some insight into their resilience and most thought resilience training would be helpful. Students discussed difficult clinical events most often with peers. More curricula promoting medical student resilience are needed.

Exploiting biospectroscopy as a novel screening tool for cervical cancer: towards a framework to validate its accuracy in a routine clinical setting.

LENUS (Irish Health Repository)

Purandare, Nikhil C

2013-11-01

Biospectroscopy is an emerging field that harnesses the platform of physical sciences with computational analysis in order to shed novel insights on biological questions. An area where this approach seems to have potential is in screening or diagnostic clinical settings, where there is an urgent need for new approaches to objectively interrogate large numbers of samples in an objective fashion with acceptable levels of sensitivity and specificity. This review outlines the benefits of biospectroscopy in screening for precancer lesions of the cervix due to its ability to separate different grades of dysplasia. It evaluates the feasibility of introducing this technique into cervical screening programs on the basis of its ability to identify biomarkers of progression within derived spectra (\\'biochemical‑cell fingerprints\\').

Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

Science.gov (United States)

Waight, Jeremy D.; Hu, Qiang; Miller, Austin; Liu, Song; Abrams, Scott I.

2011-01-01

Myeloid-derived suppressor cells (MDSC) are induced under diverse pathologic conditions, including neoplasia, and suppress innate and adaptive immunity. While the mechanisms by which MDSC mediate immunosuppression are well-characterized, details on how they develop remain less understood. This is complicated further by the fact that MDSC comprise multiple myeloid cell types, namely monocytes and granulocytes, reflecting diverse stages of differentiation and the proportion of these subpopulations vary among different neoplastic models. Thus, it is thought that the type and quantities of inflammatory mediators generated during neoplasia dictate the composition of the resultant MDSC response. Although much interest has been devoted to monocytic MDSC biology, a fundamental gap remains in our understanding of the derivation of granulocytic MDSC. In settings of heightened granulocytic MDSC responses, we hypothesized that inappropriate production of G-CSF is a key initiator of granulocytic MDSC accumulation. We observed abundant amounts of G-CSF in vivo, which correlated with robust granulocytic MDSC responses in multiple tumor models. Using G-CSF loss- and gain-of-function approaches, we demonstrated for the first time that: 1) abrogating G-CSF production significantly diminished granulocytic MDSC accumulation and tumor growth; 2) ectopically over-expressing G-CSF in G-CSF-negative tumors significantly augmented granulocytic MDSC accumulation and tumor growth; and 3) treatment of naïve healthy mice with recombinant G-CSF protein elicited granulocytic-like MDSC remarkably similar to those induced under tumor-bearing conditions. Collectively, we demonstrated that tumor-derived G-CSF enhances tumor growth through granulocytic MDSC-dependent mechanisms. These findings provide us with novel insights into MDSC subset development and potentially new biomarkers or targets for cancer therapy. PMID:22110722

INSIGHT AND SELF-STIGMA IN PATIENTS WITH SCHIZOPHRENIA.

Science.gov (United States)

Vidović, Domagoj; Brecić, Petrana; Vilibić, Maja; Jukić, Vlado

2016-03-01

Poor insight and high level of self-stigma are often present among patients with schizophrenia and are related to poorer treatment adherence, poorer social function and rehabilitation, aggressive behavior, higher level of depression, social anxiety, lower quality of life and self-esteem. Reports on a relationship between insight and stigma are controversial. We examined the relationship of the level of insight and self-stigma in a sample of 149 patients with schizophrenia. Insight was measured with the Scale to assess Unawareness of Mental Disorder and self-stigma with the Internalized Stigma of Mental Illness. Results showed 88.6% of the patients to have high or moderate insight, with a mean value of 2.73. General insight showed the highest level (2.58) and insight in positive symptoms the lowest level (2.9). The self-stigma score in general was 2.13, with stereotype endorsement being lowest (1.98). According to study results, 77.1% of patients felt minimal or low self-stigma across all subscales, except for stigma resistance subscale. Statistically significant correlation was found between insight and four subscales of self-stigma, while no correlation was found for the stigma resistance subscale only. These results imply the need of individually tailored antistigma and insight promoting programs for patients with schizophrenia.

Theoretical Aeroacoustics: Compiled Mathematical Derivations of Fereidoun 'Feri' Farassat

Science.gov (United States)

Miller, Steven A. E.

2016-01-01

Dr. Fereidoun 'Feri' Farassat was a theoretical aero-acoustician at the National Aeronautics and Space Administration (NASA) Langley Research Center. This book contains technical derivations, notes, and classes that Dr. Farassat produced during his professional career. The layout of the book has been carefully crafted so that foundational ideas through advanced theories, which altered the technical discipline of aeroacoustics, build upon one another. The book can be used to understand the theories of acoustics and learn one contemporary aeroacoustic prediction approach made popular by Dr. Farassat. Most importantly, this book gives the general reader insight into how one of NASA's best aeroacoustics theoreticians thought, constructed, and solved problems throughout his career.

Augmenting Predictive Modeling Tools with Clinical Insights for Care Coordination Program Design and Implementation.

Science.gov (United States)

Johnson, Tracy L; Brewer, Daniel; Estacio, Raymond; Vlasimsky, Tara; Durfee, Michael J; Thompson, Kathy R; Everhart, Rachel M; Rinehart, Deborath J; Batal, Holly

2015-01-01

The Center for Medicare and Medicaid Innovation (CMMI) awarded Denver Health's (DH) integrated, safety net health care system $19.8 million to implement a "population health" approach into the delivery of primary care. This major practice transformation builds on the Patient Centered Medical Home (PCMH) and Wagner's Chronic Care Model (CCM) to achieve the "Triple Aim": improved health for populations, care to individuals, and lower per capita costs. This paper presents a case study of how DH integrated published predictive models and front-line clinical judgment to implement a clinically actionable, risk stratification of patients. This population segmentation approach was used to deploy enhanced care team staff resources and to tailor care-management services to patient need, especially for patients at high risk of avoidable hospitalization. Developing, implementing, and gaining clinical acceptance of the Health Information Technology (HIT) solution for patient risk stratification was a major grant objective. In addition to describing the Information Technology (IT) solution itself, we focus on the leadership and organizational processes that facilitated its multidisciplinary development and ongoing iterative refinement, including the following: team composition, target population definition, algorithm rule development, performance assessment, and clinical-workflow optimization. We provide examples of how dynamic business intelligence tools facilitated clinical accessibility for program design decisions by enabling real-time data views from a population perspective down to patient-specific variables. We conclude that population segmentation approaches that integrate clinical perspectives with predictive modeling results can better identify high opportunity patients amenable to medical home-based, enhanced care team interventions.

Assessment of Genetics Knowledge and Skills in Medical Students: Insight for a Clinical Neurogenetics Curriculum

Science.gov (United States)

Pearl, Phillip L.; Pettiford, Jennifer M.; Combs, Susan E.; Heffron, Ari; Healton, Sean; Hovaguimian, Alexandra; Macri, Charles J.

2011-01-01

The pace of discovery in biochemistry and genetics and its effect on clinical medicine places new curricular challenges in medical school education. We sought to evaluate students' understanding of neurogenetics and its clinical applications to design a pilot curriculum into the clinical neurology clerkship. We utilized a needs assessment and a…

Chronic alcoholism: insights from neurophysiology.

Science.gov (United States)

Campanella, S; Petit, G; Maurage, P; Kornreich, C; Verbanck, P; Noël, X

2009-01-01

Increasing knowledge of the anatomical structures and cellular processes underlying psychiatric disorders may help bridge the gap between clinical signs and basic physiological processes. Accordingly, considerable insight has been gained in recent years into a common psychiatric condition, i.e., chronic alcoholism. We reviewed various physiological parameters that are altered in chronic alcoholic patients compared to healthy individuals--continuous electroencephalogram, oculomotor measures, cognitive event-related potentials and event-related oscillations--to identify links between these physiological parameters, altered cognitive processes and specific clinical symptoms. Alcoholic patients display: (1) high beta and theta power in the resting electroencephalogram, suggesting hyperarousal of their central nervous system; (2) abnormalities in smooth pursuit eye movements, in saccadic inhibition during antisaccade tasks, and in prepulse inhibition, suggesting disturbed attention modulation and abnormal patterns of prefrontal activation that may stem from the same prefrontal "inhibitory" cortical dysfunction; (3) decreased amplitude for cognitive event-related potentials situated along the continuum of information-processing, suggesting that alcoholism is associated with neurophysiological deficits at the level of the sensory cortex and not only disturbances involving associative cortices and limbic structures; and (4) decreased theta, gamma and delta oscillations, suggesting cognitive disinhibition at a functional level. The heterogeneity of alcoholic disorders in terms of symptomatology, course and outcome is the result of various pathophysiological processes that physiological parameters may help to define. These alterations may be related to precise cognitive processes that could be easily monitored neurophysiologically in order to create more homogeneous subgroups of alcoholic individuals.

Transforming clinical practice guidelines and clinical pathways into fast-and-frugal decision trees to improve clinical care strategies.

Science.gov (United States)

Djulbegovic, Benjamin; Hozo, Iztok; Dale, William

2018-02-27

Contemporary delivery of health care is inappropriate in many ways, largely due to suboptimal Q5 decision-making. A typical approach to improve practitioners' decision-making is to develop evidence-based clinical practice guidelines (CPG) by guidelines panels, who are instructed to use their judgments to derive practice recommendations. However, mechanisms for the formulation of guideline judgments remains a "black-box" operation-a process with defined inputs and outputs but without sufficient knowledge of its internal workings. Increased explicitness and transparency in the process can be achieved by implementing CPG as clinical pathways (CPs) (also known as clinical algorithms or flow-charts). However, clinical recommendations thus derived are typically ad hoc and developed by experts in a theory-free environment. As any recommendation can be right (true positive or negative), or wrong (false positive or negative), the lack of theoretical structure precludes the quantitative assessment of the management strategies recommended by CPGs/CPs. To realize the full potential of CPGs/CPs, they need to be placed on more solid theoretical grounds. We believe this potential can be best realized by converting CPGs/CPs within the heuristic theory of decision-making, often implemented as fast-and-frugal (FFT) decision trees. This is possible because FFT heuristic strategy of decision-making can be linked to signal detection theory, evidence accumulation theory, and a threshold model of decision-making, which, in turn, allows quantitative analysis of the accuracy of clinical management strategies. Fast-and-frugal provides a simple and transparent, yet solid and robust, methodological framework connecting decision science to clinical care, a sorely needed missing link between CPGs/CPs and patient outcomes. We therefore advocate that all guidelines panels express their recommendations as CPs, which in turn should be converted into FFTs to guide clinical care. © 2018 John Wiley

On data processing required to derive mobility patterns from passively-generated mobile phone data

Science.gov (United States)

Wang, Feilong; Chen, Cynthia

2018-01-01

Passively-generated mobile phone data is emerging as a potential data source for transportation research and applications. Despite the large amount of studies based on the mobile phone data, only a few have reported the properties of such data, and documented how they have processed the data. In this paper, we describe two types of common mobile phone data: Call Details Record (CDR) data and sightings data, and propose a data processing framework and the associated algorithms to address two key issues associated with the sightings data: locational uncertainty and oscillation. We show the effectiveness of our proposed methods in addressing these two issues compared to the state of art algorithms in the field. We also demonstrate that without proper processing applied to the data, the statistical regularity of human mobility patterns—a key, significant trait identified for human mobility—is over-estimated. We hope this study will stimulate more studies in examining the properties of such data and developing methods to address them. Though not as glamorous as those directly deriving insights on mobility patterns (such as statistical regularity), understanding properties of such data and developing methods to address them is a fundamental research topic on which important insights are derived on mobility patterns. PMID:29398790

Fibrin related antigens: assay development, clinical and kinetic studies

Energy Technology Data Exchange (ETDEWEB)

Kruskal, J B

1987-08-01

This thesis describes an assay which is able to measure and to determine the proportions of fibrin- and fibrinogen-related antigens (FRA) present in clinical samples. No assay exists at present which is capable of distinguishing between fibrin and fibrinogen degradation products concurrently and in a clinical setting. The assay may be used as a tool with which to gain further insight to pathophysiology of disorders characterized by activation of the coagulation and fibrinolytic pathways. This study provides and analysis of the FRA profiles in patients with disorders characterised by possible enhanced fibrinolytic activity. Studies have been undertaken on patients with acute and chronic liver diseases, on patients with the various syndromes of coronary artery disease and on patients with insulin-dependent diabetes mellitus with and without evidence of microvascular disease. Certain observations made it evident that further studies were required in order to explain previously undocumented fibrinolytic abnormalities in certain patient groups. Data obtained from patients with liver disease provided information compatible with the activation of their fibrinolytic pathways. The initial scope of this study was then extended to further investigate the deranged haemostatic mechanisms in patients with severe liver diseases. Kinetic studies were performed which required the development of specific technology to be able to measure certain previously undertermined parameters. Mathematical models describing the rates of fibrin formation and lysis were developed for human studies. Fibrin-derived D-dimer was radiolabelled and its validity as and intravenous tracer and maker of fibrin degradation established.

Improving insight and non-insight problem solving with brief interventions.

Science.gov (United States)

Wen, Ming-Ching; Butler, Laurie T; Koutstaal, Wilma

2013-02-01

Developing brief training interventions that benefit different forms of problem solving is challenging. In earlier research, Chrysikou (2006) showed that engaging in a task requiring generation of alternative uses of common objects improved subsequent insight problem solving. These benefits were attributed to a form of implicit transfer of processing involving enhanced construction of impromptu, on-the-spot or 'ad hoc' goal-directed categorizations of the problem elements. Following this, it is predicted that the alternative uses exercise should benefit abilities that govern goal-directed behaviour, such as fluid intelligence and executive functions. Similarly, an indirect intervention - self-affirmation (SA) - that has been shown to enhance cognitive and executive performance after self-regulation challenge and when under stereotype threat, may also increase adaptive goal-directed thinking and likewise should bolster problem-solving performance. In Experiment 1, brief single-session interventions, involving either alternative uses generation or SA, significantly enhanced both subsequent insight and visual-spatial fluid reasoning problem solving. In Experiment 2, we replicated the finding of benefits of both alternative uses generation and SA on subsequent insight problem-solving performance, and demonstrated that the underlying mechanism likely involves improved executive functioning. Even brief cognitive- and social-psychological interventions may substantially bolster different types of problem solving and may exert largely similar facilitatory effects on goal-directed behaviours. © 2012 The British Psychological Society.

Molecular characterisation of stromal populations derived from human embryonic stem cells

DEFF Research Database (Denmark)

Harkness, L.; Twine, N. A.; Abu Dawud, R.

2015-01-01

Human bone marrow-derived stromal (skeletal) stem cells (BM-hMSC) are being employed in an increasing number of clinical trials for tissue regeneration. A limiting factor for their clinical use is the inability to obtain sufficient cell numbers. Human embryonic stem cells (hESC) can provide an un...

Molecular-level insights into aging processes of skin elastin

DEFF Research Database (Denmark)

Mora Huertas, Angela C; Schmelzer, Christian E H; Hoehenwarter, Wolfgang

2016-01-01

Skin aging is characterized by different features including wrinkling, atrophy of the dermis and loss of elasticity associated with damage to the extracellular matrix protein elastin. The aim of this study was to investigate the aging process of skin elastin at the molecular level by evaluating...... the influence of intrinsic (chronological aging) and extrinsic factors (sun exposure) on the morphology and susceptibility of elastin towards enzymatic degradation. Elastin was isolated from biopsies derived from sun-protected or sun-exposed skin of differently aged individuals. The morphology of the elastin...... pronounced in sun-exposed tissue. Marker peptides were identified, which showed an age-related increase or decrease in their abundances and provide insights into the progression of the aging process of elastin fibers. Strong age-related cleavage occurs in hydrophobic tropoelastin domains 18, 20, 24 and 26...

Effects of an ascorbic acid-derivative dentifrice in patients with gingivitis: a double-masked, randomized, controlled clinical trial.

Science.gov (United States)

Shimabukuro, Yoshio; Nakayama, Yohei; Ogata, Yorimasa; Tamazawa, Kaoru; Shimauchi, Hidetoshi; Nishida, Tetsuya; Ito, Koichi; Chikazawa, Takashi; Kataoka, Shinsuke; Murakami, Shinya

2015-01-01

Reactive oxygen species might be associated with the onset and progression of gingival inflammation. The aim of this study is to investigate the effect of a dentifrice containing L-ascorbic acid 2-phosphate magnesium salt (APM), a long-acting ascorbic acid derivative with antioxidant properties, on gingival inflammation. The clinical effects of APM were investigated in a multicenter, randomized, parallel-group, controlled clinical trial comprising 300 individuals with gingivitis. Half of the participants were given an APM-containing dentifrice and half were given a control dentifrice. The primary outcome was the gingival index (GI) at 3 months. Secondary outcomes included gingival redness as an indicator of the degree of local gingival inflammation, gingival bleeding as a measure of the gingivitis severity index, and total antioxidant activity of the saliva. Under the intent-to-treat analysis, GI did not significantly differ between the groups (P = 0.12). However, under the per-protocol analysis, GI was significantly lower in the APM group (P = 0.01) than in the control group. In the APM group, gingival redness was significantly lower, and the difference from the baseline gingivitis severity index was significantly greater (P = 0.04 and P = 0.02, respectively). The total antioxidant activity of the saliva was significantly higher in the APM group (P = 0.03). The incidence of adverse events did not significantly differ between the groups (P > 0.15). These findings indicate that the regular application of an APM-containing dentifrice could reduce gingival inflammation.

Design and validation of a consistent and reproducible manufacture process for the production of clinical-grade bone marrow-derived multipotent mesenchymal stromal cells.

Science.gov (United States)

Codinach, Margarita; Blanco, Margarita; Ortega, Isabel; Lloret, Mireia; Reales, Laura; Coca, Maria Isabel; Torrents, Sílvia; Doral, Manel; Oliver-Vila, Irene; Requena-Montero, Miriam; Vives, Joaquim; Garcia-López, Joan

2016-09-01

Multipotent mesenchymal stromal cells (MSC) have achieved a notable prominence in the field of regenerative medicine, despite the lack of common standards in the production processes and suitable quality controls compatible with Good Manufacturing Practice (GMP). Herein we describe the design of a bioprocess for bone marrow (BM)-derived MSC isolation and expansion, its validation and production of 48 consecutive batches for clinical use. BM samples were collected from the iliac crest of patients for autologous therapy. Manufacturing procedures included: (i) isolation of nucleated cells (NC) by automated density-gradient centrifugation and plating; (ii) trypsinization and expansion of secondary cultures; and (iii) harvest and formulation of a suspension containing 40 ± 10 × 10(6) viable cells. Quality controls were defined as: (i) cell count and viability assessment; (ii) immunophenotype; and (iii) sterility tests, Mycoplasma detection, endotoxin test and Gram staining. A 3-week manufacturing bioprocess was first designed and then validated in 3 consecutive mock productions, prior to producing 48 batches of BM-MSC for clinical use. Validation included the assessment of MSC identity and genetic stability. Regarding production, 139.0 ± 17.8 mL of BM containing 2.53 ± 0.92 × 10(9) viable NC were used as starting material, yielding 38.8 ± 5.3 × 10(6) viable cells in the final product. Surface antigen expression was consistent with the expected phenotype for MSC, displaying high levels of CD73, CD90 and CD105, lack of expression of CD31 and CD45 and low levels of HLA-DR. Tests for sterility, Mycoplasma, Gram staining and endotoxin had negative results in all cases. Herein we demonstrated the establishment of a feasible, consistent and reproducible bioprocess for the production of safe BM-derived MSC for clinical use. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Mindfulness and Emotion Regulation: Insights from Neurobiological, Psychological, and Clinical Studies

OpenAIRE

Guendelman, Simón; Medeiros, Sebastián; Rampes, Hagen

2017-01-01

There is increasing interest in the beneficial clinical effects of mindfulness-based interventions (MBIs). Research has demonstrated their efficacy in a wide range of psychological conditions characterized by emotion dysregulation. Neuroimaging studies have evidenced functional and structural changes in a myriad of brain regions mainly involved in attention systems, emotion regulation, and self-referential processing. In this article we review studies on psychological and neurobiological corr...

New Insights Offered by a Computational Model of Deep Brain Stimulation

DEFF Research Database (Denmark)

Modolo, J.; Mosekilde, Erik; Beuter, A.

2007-01-01

Deep brain stimulation (DBS) is a standard neurosurgical procedure used to treat motor symptoms in about 5% of patients with Parkinson's disease (PD). Despite the indisputable success of this procedure, the biological mechanisms underlying the clinical benefits of DBS have not yet been fully...... and exploring the physiological mechanisms which respond to this treatment strategy (i.e., DBS). Finally, we present new insights into the ways this computational model may help to elucidate the dynamic network effects produced in a cerebral structure when DBS is applied. (C) 2007 Elsevier Ltd. All rights...

The association of lifetime insight and cognition in psychosis.

Science.gov (United States)

Sánchez-Torres, Ana M; Zarzuela, Amalia; Peralta, Victor; Cuesta, Manuel J

2015-03-01

Poor insight has been related to poor course in psychosis. However, the role of cognition in insight remains unclear. The aim of this study was to examine the influence of cognition and lifetime psychopathological dimensions on insight in psychosis. We followed up 42 patients with psychotic disorders over 10years. Lifetime psychopathological dimensions and cognitive performance were assessed. Patients were divided into two groups by lifetime patterns of insight and compared with 42 healthy volunteers. Lower IQ and poorer social cognition were associated with higher risks of poorer lifetime insight of feeling ill and global insight respectively. Lifetime negative symptoms were associated with a higher risk of poorer lifetime insight into symptoms. Lifetime lack of insight is independent of cognitive impairment in specific domains, except for social cognition. Higher IQ may contribute to better lifetime awareness of illness, while better ability to manage emotions is involved in lifetime global insight. Copyright © 2014 Elsevier B.V. All rights reserved.

The emergence of trust in clinics of alternative medicine

DEFF Research Database (Denmark)

Pedersen, Inge Kryger; Hansen, Vibeke Holm; Grünenberg, Kristina

2016-01-01

qualitative studies and informing the empirical findings with a sociological concept of trust, this article provides new empirical insights on how trust emerges in Danish clinics of acupuncture, reflexology and homeopathy. The analysis demonstrates how trust is situational and emerges through both clients...

Blindness and Insight in King Lear

Institute of Scientific and Technical Information of China (English)

岳元玉

2008-01-01

This paper intends to explore how William Shakespeare illustrates the theme of blindness and insight in his great tragedy "King Lear".Four characters’ deeds and their fate are used as a case study to examine what blindness is,what insight is,and the relationship between the two.The writer finds that by depicting the characters’ deeds and their fate in a double plot,Shakespeare renders the folly of blindness,the transition from blindness to insight,and the use of reason and thought to understand the truth.

Social media insights for sustainable development and humanitarian action in Indonesia

Science.gov (United States)

Amin, Imaduddin; Pramestri, Zakiya; Hodge, George; Lee, Jong Gun

2018-03-01

Tracking human development and humanitarian action has been enhanced by the growth of social media. Twitter is a data source with potential, when used alongside data from surveys, especially the national census, to understand the situation on the ground and track changes. In Indonesia, a country with one of the highest Twitter penetration rates, we seize this opportunity by using Twitter data to produce more timely insights and to enhance evidence-based decision-making. Despite social media’s limitations, namely representativeness and validity, we are able to show its potential by looking at case studies on five different topics; (a) food and agriculture, (b) public health (c) economic well-being (d) urban resilience and (e) humanitarian action. We observe that the insights gained by using Twitter data were derived not only from the content of posts such as understanding public opinion or sentiment, but also from activities related to it, for instance the location and time-stamp of the post, which furthers our real-time understanding of the situation and user behavior changes. In this paper, we also briefly explain “social listener”, a social media monitoring tool that used by Government of Indonesia to understand citizen opinions in social media related to government priorities.

Derived data storage and exchange workflow for large-scale neuroimaging analyses on the BIRN grid

Directory of Open Access Journals (Sweden)

David B Keator

2009-09-01

Full Text Available Organizing and annotating biomedical data in structured ways has gained much interest and focus in the last 30 years. Driven by decreases in digital storage costs and advances in genetics sequencing, imaging, electronic data collection, and microarray technologies, data is being collected at an alarming rate. The need to store and exchange data in meaningful ways in support of data analysis, hypothesis testing and future collaborative use is pervasive. Because trans-disciplinary projects rely on effective use of data from many domains, there is a genuine interest in informatics community on how best to store and combine this data while maintaining a high level of data quality and. The difficulties in sharing and combining raw data become amplified after post-processing and/or data analysis in which the new dataset of interest is a function of the original data and may have been collected by multiple collaborating sites. Simple meta-data, documenting which subject and version of data were used for a particular analysis, becomes complicated by the heterogeneity of the collecting sites yet is critically important to the interpretation and reuse of derived results. This manuscript will present a case study of using the XML-Based Clinical Experiment Data Exchange (XCEDE schema and the Human Imaging Database (HID in the Biomedical Informatics Research Network’s (BIRN distributed environment to document and exchange derived data. The discussion includes an overview of the data structures used in both the XML and the database representations, insight into the design considerations, and the extensibility of the design to support additional analysis streams.

Hyperons: Insights into baryon structures

International Nuclear Information System (INIS)

Lach, J.

1991-08-01

The baryon octet is composed mainly of hyperons. Modern high energy hyperon beams provide a tool for the study of hyperon static properties and interactions. Experiments with these beams have provided new insights into hyperon rare decays, magnetic moments, and interactions. These experiments provide us with insights into the strong, weak, and electromagnetic structure of the baryons. 65 refs., 45 figs., 5 tabs

An overview of insights gained and lessons learned from U.S. plant-specific PRA studies

International Nuclear Information System (INIS)

Joksimovich, V.

1985-01-01

Probabilistic Risk Assessment (PRA) has been under development for over twenty years, but it has reached the level of widespread use only in the aftermath of the TMI accident. Over thirty PRAs have now been completed in the U.S. PRAs have been in the mainstream of many licensing decisions because the NRC recognizes that they provide independent and comprehensive plant safety audit. Some difficulties have been experienced leading to interpretive and intercomparison studies. Numerous global and plant-specific insights have been derived. A new application termed risk management is clearly emerging. (orig./HP)

Electron-deficient anthraquinone derivatives as cathodic material for lithium ion batteries

Science.gov (United States)

Takeda, Takashi; Taniki, Ryosuke; Masuda, Asuna; Honma, Itaru; Akutagawa, Tomoyuki

2016-10-01

We studied the electronic and structural properties of electron-deficient anthraquinone (AQ) derivatives, Me4N4AQ and TCNAQ, and investigated their charge-discharge properties in lithium ion batteries along with those of AQ. Cyclic voltammogram, X-ray structure analysis and theoretical calculations revealed that these three acceptors have different features, such as different electron-accepting properties with different reduction processes and lithium coordination abilities, and different packing arrangements with different intermolecular interactions. These differences greatly affect the charge-discharge properties of lithium ion batteries that use these compounds as cathode materials. Among these compounds, Me4N4AQ showed a high charge/discharge voltage (2.9-2.5 V) with high cyclability (>65% of the theoretical capacity after 30 cycles; no decrease after 15 cycles). These results provide insight into more in-depth design principles for lithium ion batteries using AQ derivatives as cathodic materials.

Dithiazole thione derivative as competitive NorA efflux pump inhibitor to curtail multi drug resistant clinical isolate of MRSA in a zebrafish infection model.

Science.gov (United States)

Lowrence, Rene Christena; Raman, Thiagarajan; Makala, Himesh V; Ulaganathan, Venkatasubramanian; Subramaniapillai, Selva Ganesan; Kuppuswamy, Ashok Ayyappa; Mani, Anisha; Chittoor Neelakantan, Sundaresan; Nagarajan, Saisubramanian

2016-11-01

Multi drug resistant (MDR) pathogens pose a serious threat to public health since they can easily render most potent drugs ineffective. Efflux pump inhibitors (EPI) can be used to counter the MDR phenotypes arising due to increased efflux. In the present study, a series of dithiazole thione derivatives were synthesized and checked for its antibacterial and efflux pump inhibitory (EPI) activity. Among 10 dithiazole thione derivatives, real-time efflux studies revealed that seven compounds were potent EPIs relative to CCCP. Zebrafish toxicity studies identified four non-toxic putative EPIs. Both DTT3 and DTT9 perturbed membrane potential and DTT6 was haemolytic. Among DTT6 and DTT10, the latter was less toxic as evidenced by histopathology studies. Since DTT10 was non-haemolytic, did not affect the membrane potential, and was least toxic, it was chosen further for in vivo study, wherein DTT10 potentiated effect of ciprofloxacin against clinical strain of MRSA and reduced bacterial burden in muscle and skin tissue of infected zebrafish by ~ 1.7 and 2.5 log fold respectively. Gene expression profiling of major efflux transport proteins by qPCR revealed that clinical isolate of MRSA, in the absence of antibiotic, upregulated NorA, NorB and MepA pump, whereas it downregulates NorC and MgrA relative to wild-type strain of Staphylococcus aureus. In vitro studies with NorA mutant strains and substrate profiling revealed that at higher concentrations DTT10 is likely to function as a competitive inhibitor of NorA efflux protein in S. aureus, whereas at lower concentrations it might inhibit ciprofloxacin efflux through NorB and MepA as implied by docking studies. A novel non-toxic, non-haemolytic dithiazole thione derivative (DTT10) was identified as a potent competitive inhibitor of NorA efflux pump in S. aureus using in silico, in vitro and in vivo studies. This study also underscores the importance of using zebrafish infection model to screen and evaluate putative EPI for

[Insight and psychiatric dangerousness: A review of the literature].

Science.gov (United States)

Bonnet, S; Lacambre, M; Schandrin, A; Capdevielle, D; Courtet, P

2017-04-01

Violence committed by individuals with severe mental illness has become an increasing focus of concern among clinicians, policy makers, and the general public, often as the result of tragic events. Research has shown in the past two decades an increased risk of violence among patients with mental disorder. Nevertheless, of those suffering from mental illness, perpetrators of other directed violence form a minority subgroup. The means by which there is this association between mental illness and violence has remained controversial. Factors such as positive psychotic symptoms, medication non-adherence, alcohol or psychoactive substance abuse and antisocial personality were found to be predictive of violence. Overall, literature provides support to the assertion that violent behavior of mentally ill patients is a heterogeneous phenomenon that is driven by multiple inter-related and independent factors. Furthermore, psychiatrists are often asked to predict an individual's future dangerousness, in a medical or a legal context. In the process of risk assessment of dangerousness, more focus has been placed on dynamic risk factor. In this context, lack of insight has established itself both as a part of violence risk models and as a clinical item in structured approaches to measure dangerousness. However, few studies have tested these associations. The main purpose of this paper is to review the literature concerning the relationship between insight and dangerousness and discuss the contributions of the insight in the assessment of dangerousness in patients with mental illness. We included twenty studies that evaluated the association between insight and variable such as physical or verbal violence, aggressiveness, hostility or sexual aggression. According to the findings of this review, the strength and specific nature of this relationship remain unclear due to considerable methodological and conceptual shortcomings, including heterogeneity in the definition and

Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment.

Science.gov (United States)

Van Dijk, F S; Sillence, D O

2014-06-01

Recently, the genetic heterogeneity in osteogenesis imperfecta (OI), proposed in 1979 by Sillence et al., has been confirmed with molecular genetic studies. At present, 17 genetic causes of OI and closely related disorders have been identified and it is expected that more will follow. Unlike most reviews that have been published in the last decade on the genetic causes and biochemical processes leading to OI, this review focuses on the clinical classification of OI and elaborates on the newly proposed OI classification from 2010, which returned to a descriptive and numerical grouping of five OI syndromic groups. The new OI nomenclature and the pre-and postnatal severity assessment introduced in this review, emphasize the importance of phenotyping in order to diagnose, classify, and assess severity of OI. This will provide patients and their families with insight into the probable course of the disorder and it will allow physicians to evaluate the effect of therapy. A careful clinical description in combination with knowledge of the specific molecular genetic cause is the starting point for development and assessment of therapy in patients with heritable disorders including OI. © 2014 The Authors. American Journal of Medical Genetics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2014 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Amniotic membrane-derived stem cells: immunomodulatory properties and potential clinical application

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Insausti CL

2014-03-01

Full Text Available Carmen L Insausti,1 Miguel Blanquer,1 Ana M García-Hernández,1 Gregorio Castellanos,2 José M Moraleda11Unidad de Trasplante Hematopoyético y Terapia Celular, 2Servicio de Cirugía, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, Campus Mare Nostrum, Universidad de Murcia, El Palmar, Murcia, SpainAbstract: Epithelial and mesenchymal cells isolated from the amniotic membrane (AM possess stem cell characteristics, differentiation potential toward lineages of different germ layers, and immunomodulatory properties. While their expansion and differentiation potential have been well studied and characterized, knowledge about their immunomodulatory properties and the mechanisms involved is still incomplete. These mechanisms have been evaluated on various target cells of the innate and the adaptive system and in animal models of different inflammatory diseases. Some results have evidenced that the immunomodulatory effect of AM-derived cells is dependent on cell-cell contact, but many of them have demonstrated that these properties are mediated through the secretion of suppressive molecules. In this review, we present an update on the described immunomodulatory properties of the derived amniotic cells and some of the proposed involved mechanisms. Furthermore, we describe some assays in animal models of different inflammatory diseases which reveal the potential use of these cells to treat such diseases.Keywords: epithelial cells, mesenchymal cells, cell therapy, immunomodulation

Safety of recombinant human platelet-derived growth factor-BB in Augment® Bone Graft

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Luis A Solchaga

2012-12-01

Full Text Available This article discusses nonclinical and clinical data regarding the safety of recombinant human platelet-derived growth factor-BB as a component of the Augment® Bone Graft (Augment. Augment is a bone graft substitute intended to be used as an alternative to autologous bone graft in the fusion of hindfoot and ankle joints. Nonclinical studies included assessment of the pharmacokinetic profile of intravenously administered recombinant human platelet-derived growth factor-BB in rat and dog, effects of intravenous administration of recombinant human platelet-derived growth factor-BB in a reproductive and development toxicity study in rats, and chronic toxicity and carcinogenicity of Augment in a 12-month implantation model. These studies showed that systemic exposure was brief and clearance was rapid. No signs of toxicity, carcinogenicity, or tumor promotion were observed even with doses far exceeding the maximum clinical dose. Results of clinical trials (605 participants and commercial use of recombinant human platelet-derived growth factor-BB containing products indicate that these products are not associated with increased incidence of adverse events or cancer. The safety data presented provide evidence that recombinant human platelet-derived growth factor-BB is a safe therapeutic when used in combination products as a single administration during surgical procedures for bone repair and fusion. There is no evidence associating use of recombinant human platelet-derived growth factor-BB in Augment with chronic toxicity, carcinogenicity, or tumor promotion.

Energy transitions research: Insights and cautionary tales

International Nuclear Information System (INIS)

Grubler, Arnulf

2012-01-01

This short essay first reviews the pioneers of energy transition research both in terms of data as well as theories. Three major insights that have emerged from this nascent research fields are summarized highlighting the importance of energy end-use and services, the lengthy process of transitions, as well as the patterns that characterize successful scale up of technologies and industries that drive historical energy transitions. The essay concludes with cautionary notes also derived from historical experience. In order to trigger a next energy transition policies and innovation efforts need to be persistent and continuous, aligned, as well as balanced. It is argued that current policy frameworks in place invariably do not meet these criteria and need to change in order to successfully trigger a next energy transition towards sustainability. - Highlights: ► Includes the first literature review of early energy transition research. ► Summarizes three major research findings from the literature. ► Reviews policy implications of recent case studies of energy technology innovation. ► Argues that current policy frameworks are deficient in view of above lessons.

Satellite-derived surface and sub-surface water storage in the Ganges–Brahmaputra River Basin

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Fabrice Papa

2015-09-01

New hydrological insights: Basin-scale monthly SWS variations for the period 2003–2007 show a mean annual amplitude of ∼410 km3, contributing to about 45% of the Gravity Recovery And Climate Experiment (GRACE-derived total water storage variations (TWS. During the drought-like conditions in 2006, we estimate that the SWS deficit over the entire GB basin in July–August–September was about 30% as compared to other years. The SWS variations are then used to decompose the GB GRACE-derived TWS and isolate the variations of SSWS whose mean annual amplitude is estimated to be ∼550 km3. This new dataset of water storage variations represent an unprecedented source of information for hydrological and climate modeling studies of the ISC.

Do behavioural insights matter for competition policy?

OpenAIRE

CIRIOLO Emanuele

2016-01-01

Behavioural insights make use of behavioural economics and psychology to analyse how humans behave when adopting economic decisions. The use of behavioural insights to improve policy-making is becoming increasing popular all over the world. Pensions, taxes, unemployment, energy efficiency, adult education, charitable giving and, of course, competition policy have benefitted from the application of behavioural insights. Emanuele Ciriolo, from the European Commission Joint Research Centre, expl...

Stigma moderates the associations of insight with depressed mood, low self-esteem, and low quality of life in patients with schizophrenia spectrum disorders.

Science.gov (United States)

Staring, A B P; Van der Gaag, M; Van den Berge, M; Duivenvoorden, H J; Mulder, C L

2009-12-01

Good insight into illness in patients with schizophrenia is related not only to medication compliance and high service engagement, but also to depression, low self-esteem, and low quality of life. The detrimental effects of insight pose a problem for treatment. To investigate whether the negative associations of good insight are moderated by perceived stigma. Respondents were 114 patients with schizophrenia spectrum disorders. We used Analyses of Variance (ANOVA) and Structural Equation Modeling (SEM) to test moderation. Good insight was associated with high service engagement and high compliance. Also, good insight was associated with depressed mood, low quality of life, and negative self-esteem. This association was strong when stigma was high and weak when stigma was low. SEM showed that the constrained model performed significantly worse than the unconstrained model, in which detrimental associations of insight were free to vary across stigma groups (chi(2)=19.082; df=3; plow quality of life, and negative self-esteem are moderated by stigma. Patients with good insight who do not perceive much stigmatization seem to be best off across various outcome parameters. Those with poor insight have problems with service engagement and medication compliance. Patients with good insight accompanied by stigmatizing beliefs have the highest risk of experiencing low quality of life, negative self-esteem, and depressed mood. A clinical implication is that when it is attempted to increase insight, perceived stigma should also be addressed.

Clinical follow-up of horses treated with allogeneic equine mesenchymal stem cells derived from umbilical cord blood for different tendon and ligament disorders.

Science.gov (United States)

Van Loon, Vic J F; Scheffer, Carmen J W; Genn, Herman J; Hoogendoorn, Arie C; Greve, Jan W

2014-01-01

Mesenchymal stem cells (MSCs) offer promise as therapeutic aids in the repair of tendon and ligament disorders in sport horses. Equine allogeneic MSCs derived from umbilical cord blood (eUCB-MSCs) can be obtained in a minimally invasive fashion with successful propagation of MSCs. The objective of this study was to determine the applicability and therapeutic effect of eUCB-MSCs on tendinitis of the superficial digital flexor tendon, desmitis of the suspensory ligament, tendinitis of the deep digital flexor tendon, and desmitis of the inferior check ligament in clinical cases. A retrospective clinical study was performed. At two equine clinics, 52 warmblood horses were treated with cultured eUCB-MSCs between 2009 and 2012. About 2-10 × 10(6) cells per lesion were administered. When a lesion was treated twice, the total amount could run up to 20 × 10(6) cells. Pearson's chi-squared test was used to compare the effect of the injured structure on the success rate, as well as the effect of the age of the horse. Based on repeated examinations, 40 horses (77%) returned to work on the same or a higher level based on information provided by the owner. Neither the injured structure nor the age of the horse had a statistically significant influence on the result. Overall, the results of treatment of some tendon and ligament injuries with eUCB-MSCs in clinical cases are promising.

Characteristics of Kodak Insight, an F-speed intraoral film.

Science.gov (United States)

Ludlow, J B; Platin, E; Mol, A

2001-01-01

This study reports film speed, contrast, exposure latitude, resolution, and response to processing solution depletion of Kodak Insight intraoral film. Densitometric curves were generated by using International Standards Organization protocol. Additional curves were generated for Ultra-speed, Ektaspeed Plus, and Insight films developed in progressively depleted processing solutions. Eight observers viewed images of a resolution test tool for maximum resolution assessment. Images of an aluminum step-wedge were reviewed to determine useful exposure latitude. Insight's sensitivity in fresh automatic processor solutions places it in the F-speed group. An average gradient of 1.8 was found with all film types. Insight provided 93% of the useful exposure latitude of Ektaspeed Plus film. Insight maintained contrast in progressively depleted processing solutions. Like Ektaspeed Plus, Insight was able to resolve at least 20 line-pairs per millimeter. Under International Standards Organization conditions, Insight required only 77% of the exposure of Ektaspeed Plus film. Insight film provided stable contrast in depleted processing solutions.

Development of large-scale manufacturing of adipose-derived stromal cells for clinical applications using bioreactors and human platelet lysate.

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Haack-Sørensen, Mandana; Juhl, Morten; Follin, Bjarke; Harary Søndergaard, Rebekka; Kirchhoff, Maria; Kastrup, Jens; Ekblond, Annette

2018-04-17

In vitro expanded adipose-derived stromal cells (ASCs) are a useful resource for tissue regeneration. Translation of small-scale autologous cell production into a large-scale, allogeneic production process for clinical applications necessitates well-chosen raw materials and cell culture platform. We compare the use of clinical-grade human platelet lysate (hPL) and fetal bovine serum (FBS) as growth supplements for ASC expansion in the automated, closed hollow fibre quantum cell expansion system (bioreactor). Stromal vascular fractions were isolated from human subcutaneous abdominal fat. In average, 95 × 10 6 cells were suspended in 10% FBS or 5% hPL medium, and loaded into a bioreactor coated with cryoprecipitate. ASCs (P0) were harvested, and 30 × 10 6 ASCs were reloaded for continued expansion (P1). Feeding rate and time of harvest was guided by metabolic monitoring. Viability, sterility, purity, differentiation capacity, and genomic stability of ASCs P1 were determined. Cultivation of SVF in hPL medium for in average nine days, yielded 546 × 10 6 ASCs compared to 111 × 10 6 ASCs, after 17 days in FBS medium. ASCs P1 yields were in average 605 × 10 6 ASCs (PD [population doublings]: 4.65) after six days in hPL medium, compared to 119 × 10 6 ASCs (PD: 2.45) in FBS medium, after 21 days. ASCs fulfilled ISCT criteria and demonstrated genomic stability and sterility. The use of hPL as a growth supplement for ASCs expansion in the quantum cell expansion system provides an efficient expansion process compared to the use of FBS, while maintaining cell quality appropriate for clinical use. The described process is an obvious choice for manufacturing of large-scale allogeneic ASC products.

Africa Insight

African Journals Online (AJOL)

Africa Insight is a quarterly, peer-reviewed journal of the Africa Institute of South Africa. It is accredited by the South African National Department of Higher Education and Training (DHET) and is indexed in the International Bibliography of Social Science (IBSS). It is a multi-disciplinary journal primarily focusing on African ...

The politics of insight.

Science.gov (United States)

Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

2016-01-01

Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs.

The politics of insight

Science.gov (United States)

Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

2016-01-01

Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs. PMID:26810954

The use of derivatives in Slovenian non-financial firms: is financial risk already well managed?

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Aleš Berk

2006-12-01

Full Text Available Recent research about the financial behaviour of Slovenian firms has documented enterprise risk management as being one of its weakest areas. The goal of this article is to present insights into financial risk management, i.e. into the extent of the use of derivatives in the largest Slovenian firms and the related practices. The resultsare confronted with the same types of characteristics of US and German firms (although being much larger revealed in comparable studies. These firms provide relevant benchmarks for assessing the development gap since they operate in more advanced financial environments and are therefore expected to have much morerefined approaches to the use of derivatives than Slovenian firms. A survey points to the much smaller extent of the use of derivatives by Slovenian firms. There is a substantial gap, especially in the area of risk management policies (e.g. documentation, reporting, counterparty risk, valuation etc..

Biological Actions of Artemisinin: Insights from Medicinal Chemistry Studies

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Jian Li

2010-03-01

Full Text Available Artemisinins have become essential antimalarial drugs for increasingly widespread drug-resistant malaria strains. Although tremendous efforts have been devoted to decipher how this class of molecules works, their exact antimalarial mechanism is still an enigma. Several hypotheses have been proposed to explain their actions, including alkylation of heme by carbon-centered free radicals, interference with proteins such as the sarcoplasmic/endoplasmic calcium ATPase (SERCA, as well as damaging of normal mitochondrial functions. Besides artemisinins, other endoperoxides with various backbones have also been synthesized, some of which showed comparable or even higher antimalarial effects. It is noteworthy that among these artemisinin derivatives, some enantiomers displayed similar in vitro malaria killing efficacy. In this article, the proposed mechanisms of action of artemisinins are reviewed in light of medicinal chemistry findings characterized by efficacy-structure studies, with the hope of gaining more insight into how these potent drugs work.

Fostering new relational experience: clinical process in couple psychotherapy.

Science.gov (United States)

Marmarosh, Cheri L

2014-03-01

One of the most critical goals for couple psychotherapy is to foster a new relational experience in the session where the couple feels safe enough to reveal more vulnerable emotions and to explore their defensive withdrawal, aggressive attacking, or blaming. The lived intimate experience in the session offers the couple an opportunity to gain integrative insight into their feelings, expectations, and behaviors that ultimately hinder intimacy. The clinical processes that are necessary include empathizing with the couple and facilitating safety within the session, looking for opportunities to explore emotions, ruptures, and unconscious motivations that maintain distance in the relationship, and creating a new relational experience in the session that has the potential to engender integrative insight. These clinical processes will be presented with empirical support. Experts from a session will be used to highlight how these processes influence the couple and promote increased intimacy. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Imbalanced target prediction with pattern discovery on clinical data repositories.

Science.gov (United States)

Chan, Tak-Ming; Li, Yuxi; Chiau, Choo-Chiap; Zhu, Jane; Jiang, Jie; Huo, Yong

2017-04-20

Clinical data repositories (CDR) have great potential to improve outcome prediction and risk modeling. However, most clinical studies require careful study design, dedicated data collection efforts, and sophisticated modeling techniques before a hypothesis can be tested. We aim to bridge this gap, so that clinical domain users can perform first-hand prediction on existing repository data without complicated handling, and obtain insightful patterns of imbalanced targets for a formal study before it is conducted. We specifically target for interpretability for domain users where the model can be conveniently explained and applied in clinical practice. We propose an interpretable pattern model which is noise (missing) tolerant for practice data. To address the challenge of imbalanced targets of interest in clinical research, e.g., deaths less than a few percent, the geometric mean of sensitivity and specificity (G-mean) optimization criterion is employed, with which a simple but effective heuristic algorithm is developed. We compared pattern discovery to clinically interpretable methods on two retrospective clinical datasets. They contain 14.9% deaths in 1 year in the thoracic dataset and 9.1% deaths in the cardiac dataset, respectively. In spite of the imbalance challenge shown on other methods, pattern discovery consistently shows competitive cross-validated prediction performance. Compared to logistic regression, Naïve Bayes, and decision tree, pattern discovery achieves statistically significant (p-values repositories with imbalance and noise. The prediction results and interpretable patterns can provide insights in an agile and inexpensive way for the potential formal studies.

Characterization of single cell derived cultures of periosteal progenitor cells to ensure the cell quality for clinical application.

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Stefan Stich

Full Text Available For clinical applications of cells and tissue engineering products it is of importance to characterize the quality of the used cells in detail. Progenitor cells from the periosteum are already routinely applied in the clinics for the regeneration of the maxillary bone. Periosteal cells have, in addition to their potential to differentiate into bone, the ability to develop into cartilage and fat. However, the question arises whether all cells isolated from periosteal biopsies are able to differentiate into all three tissue types, or whether there are subpopulations. For an efficient and approved application in bone or cartilage regeneration the clarification of this question is of interest. Therefore, 83 different clonal cultures of freshly isolated human periosteal cells derived from mastoid periosteum biopsies of 4 donors were generated and growth rates calculated. Differentiation capacities of 51 clonal cultures towards the osteogenic, the chondrogenic, and the adipogenic lineage were investigated. Histological and immunochemical stainings showed that 100% of the clonal cultures differentiated towards the osteogenic lineage, while 94.1% demonstrated chondrogenesis, and 52.9% could be stimulated to adipogenesis. For osteogenesis real-time polymerase chain reaction (PCR of BGLAP and RUNX2 and for adipogenesis of FABP4 and PPARG confirmed the results. Overall, 49% of the cells exhibited a tripotent potential, 45.1% showed a bipotent potential (without adipogenic differentiation, 3.9% bipotent (without chondrogenic differentiation, and 2% possessed a unipotent osteogenic potential. In FACS analyses, no differences in the marker profile of undifferentiated clonal cultures with bi- and tripotent differentiation capacity were found. Genome-wide microarray analysis revealed 52 differentially expressed genes for clonal subpopulations with or without chondrogenic differentiation capacity, among them DCN, NEDD9, TGFBR3, and TSLP. For clinical

New insights into the pathophysiology of post-stroke spasticity

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Sheng eLi

2015-04-01

Full Text Available Spasticity is one of many consequences after stroke. It is characterized by a velocity-dependent increase in resistance during passive stretch, resulting from hyperexcitability of the stretch reflex. The underlying mechanism of the hyperexcitable stretch reflex, however, remains poorly understood. Accumulated experimental evidence has supported supraspinal origins of spasticity, likely from an imbalance between descending inhibitory and facilitatory regulation of spinal stretch reflexes secondary to cortical disinhibition after stroke. The excitability of reticulospinal and vestibulospinal tracts has been assessed in stroke survivors with spasticity using non-invasive indirect measures. There are strong experimental findings that support the reticulospinal hyperexcitability as a prominent underlying mechanism of post-stroke spasticity. This mechanism can at least partly account for clinical features associated with spasticity and provide insightful guidance for clinical assessment and management of spasticity. However, the possible role of VST hyperexcitability can not be ruled out from indirect measures. In vivo measure of individual brainstem nuclei in stroke survivors with spasticity using advanced fMRI techniques in the future is probably able to provide direct evidence of pathogenesis of post-stroke spasticity.

New insights into the pathophysiology of post-stroke spasticity.

Science.gov (United States)

Li, Sheng; Francisco, Gerard E

2015-01-01

Spasticity is one of many consequences after stroke. It is characterized by a velocity-dependent increase in resistance during passive stretch, resulting from hyperexcitability of the stretch reflex. The underlying mechanism of the hyperexcitable stretch reflex, however, remains poorly understood. Accumulated experimental evidence has supported supraspinal origins of spasticity, likely from an imbalance between descending inhibitory and facilitatory regulation of spinal stretch reflexes secondary to cortical disinhibition after stroke. The excitability of reticulospinal (RST) and vestibulospinal tracts (VSTs) has been assessed in stroke survivors with spasticity using non-invasive indirect measures. There are strong experimental findings that support the RST hyperexcitability as a prominent underlying mechanism of post-stroke spasticity. This mechanism can at least partly account for clinical features associated with spasticity and provide insightful guidance for clinical assessment and management of spasticity. However, the possible role of VST hyperexcitability cannot be ruled out from indirect measures. In vivo measure of individual brainstem nuclei in stroke survivors with spasticity using advanced fMRI techniques in the future is probably able to provide direct evidence of pathogenesis of post-stroke spasticity.

Long-term MRI tracking of dual-labeled adipose-derived stem cells homing into mouse carotid artery injury

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Qin JB

2012-10-01

Full Text Available Jin-Bao Qin,1,5,* Kang-An Li,2,* Xiang-Xiang Li,1,5 Qing-Song Xie,3 Jia-Ying Lin,4 Kai-Chuang Ye,1,5 Mi-Er Jiang,1,5 Gui-Xiang Zhang,2 Xin-Wu Lu1,51Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 2Department of Radiology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 3Department of Neurosurgery, Cixi Municipal People's Hospital, Zhejiang Province, China; 4Clinic for Gynecology, Charite-Universitatsmedizin Berlin, Berlin, Germany; 5Vascular Center, Shanghai Jiao Tong University, Shanghai, China*These two authors contributed equally to this workBackground: Stem cell therapy has shown great promise for regenerative repair of injured or diseased tissues. Adipose-derived stem cells (ADSCs have become increasingly attractive candidates for cellular therapy. Magnetic resonance imaging has been proven to be effective in tracking magnetic-labeled cells and evaluating their clinical relevance after cell transplantation. This study investigated the feasibility of imaging green fluorescent protein-expressing ADSCs (GFP-ADSCs labeled with superparamagnetic iron oxide particles, and tracked them in vivo with noninvasive magnetic resonance imaging after cell transplantation in a model of mouse carotid artery injury.Methods: GFP-ADSCs were isolated from the adipose tissues of GFP mice and labeled with superparamagnetic iron oxide particles. Intracellular stability, proliferation, and viability of the labeled cells were evaluated in vitro. Next, the cells were transplanted into a mouse carotid artery injury model. Clinical 3 T magnetic resonance imaging was performed immediately before and 1, 3, 7, 14, 21, and 30 days after cell transplantation. Prussian blue staining and histological analysis were performed 7 and 30 days after transplantation.Results: GFP-ADSCs were found to be efficiently labeled with superparamagnetic iron oxide

Genomics of Systemic Lupus Erythematosus: Insights Gained by Studying Monogenic Young-Onset Systemic Lupus Erythematosus.

Science.gov (United States)

Hiraki, Linda T; Silverman, Earl D

2017-08-01

Systemic lupus erythematosus (SLE) is a systemic, autoimmune, multisystem disease with a heterogeneous clinical phenotype. Genome-wide association studies have identified multiple susceptibility loci, but these explain a fraction of the estimated heritability. This is partly because within the broad spectrum of SLE are monogenic diseases that tend to cluster in patients with young age of onset, and in families. This article highlights insights into the pathogenesis of SLE provided by these monogenic diseases. It examines genetic causes of complement deficiency, abnormal interferon production, and abnormalities of tolerance, resulting in monogenic SLE with overlapping clinical features, autoantibodies, and shared inflammatory pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Anthracycline extravasation: a comprehensive review of experimental and clinical treatments

DEFF Research Database (Denmark)

Langer, S.W.; Sehested, M.; Jensen, P.B.

2009-01-01

, and is the only approved treatment against anthracyline extravasation. It is thus now widely recommended. The present article represents a comprehensive review of, and historical insight to, the experimental and clinical studies of surgical and non-surgical treatments of extravasation during forty years...

Insight and its relationship with stigma in psychiatric patients

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Deepak K Mishra

2009-01-01

Full Text Available Background: The literature on insight has paid insufficient attention to the social experiences that are associated with receiving and endorsing a diagnosis of mental illness. The psychological and behavioral commitments associated with insight extend beyond agreeing with a diagnosis and accepting treatment to include taking on the identity of an individual diagnosed with mental illness. This study sought to examine the relationship between insight and stigma in psychiatric patients. Materials and Methods: Cross-sectional assessment of insight and stigma was done using the system adopted by Kaplan and Sadock in their comprehensive textbook of psychiatry and Felt Stigma Scale in 100 psychiatric patients (40 patients suffering from Bipolar affective disorder, 30 Schizophrenics, 20 Substance dependents and 10 with Obsessive Compulsive disorder. Results: It was found that the level of stigma felt by patients with insight was significantly higher than that felt by patients without insight. Conclusion: Though there is a certain extent of stigma present in patients without insight, as is expected, the level of stigma increases as the patients develop insight.

Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Vainshtein, Jeffrey M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Kabarriti, Rafi; Mehta, Keyur J. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Roy-Chowdhury, Jayanta [Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Department of Genetics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Guha, Chandan, E-mail: cguhamd@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2014-07-15

Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local disease control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the

Base-metal dental casting alloy biocompatibility assessment using a human-derived 3D oral mucosal model

OpenAIRE

MORAN, GARY; MC GINLEY, EMMA LOUISE; FLEMING, GARRY

2012-01-01

PUBLISHED Nickel-chromium (Ni-Cr) alloys used in fixed prosthodontics have been associated with type IV nickel-induced hypersensitivity. We hypothesized the full-thickness human-derived oral mucosa model employed for biocompatibility testing of base-metal dental alloys would provide insights into mechanisms of nickel-induced toxicity. Primary oral keratinocytes and gingival fibroblasts were seeded onto Alloderm? and maintained until full-thickness was achieved prior to Ni-Cr and cobalt-chr...

Unicystic plexiform ameloblastoma: An insight for pediatric dentists

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Yavagal C

2009-03-01

Full Text Available Ameloblastomas have been categorized broadly into three biologic variants: cystic (unicystic, solid, and peripheral. The term plexiform unicystic ameloblastoma refers to a pattern of epithelial proliferation that has been described in cystic lesions of the jaws. Although the histology suggests that cystic ameloblastomas follow a biologically low-grade course, recent evidence suggests that they may often behave clinically as biologically aggressive tumors. This is supported by the high incidence of cortical perforation, tooth resorption, lesion size, bony destruction, and a high rate of recurrence after simple enucleation. This article tries to provide an insight for pediatric dentists regarding this biologically distinct entity. A literature review on the topic has been added along with a case report highlighting the state-of-the-art approach and management of such ameloblastomas, in pediatric patients.

The Potential of GMP-Compliant Platelet Lysate to Induce a Permissive State for Cardiovascular Transdifferentiation in Human Mediastinal Adipose Tissue-Derived Mesenchymal Stem Cells

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Camilla Siciliano

2015-01-01

Full Text Available Human adipose tissue-derived mesenchymal stem cells (ADMSCs are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL, a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs.

The Potential of GMP-Compliant Platelet Lysate to Induce a Permissive State for Cardiovascular Transdifferentiation in Human Mediastinal Adipose Tissue-Derived Mesenchymal Stem Cells

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Bordin, Antonella; Ponti, Donatella; Iudicone, Paola; Rendina, Erino Angelo; Calogero, Antonella; Pierelli, Luca; Ibrahim, Mohsen; De Falco, Elena

2015-01-01

Human adipose tissue-derived mesenchymal stem cells (ADMSCs) are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL), a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs. PMID:26495284

Ferroquine and its derivatives: new generation of antimalarial agents.

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Wani, Waseem A; Jameel, Ehtesham; Baig, Umair; Mumtazuddin, Syed; Hun, Lee Ting

2015-08-28

Malaria has been teasing human populations from a long time. Presently, several classes of antimalarial drugs are available in market, but the issues of toxicity, lower efficacy and the resistance by malarial parasites have decreased their overall therapeutic indices. Thus, the search for new promising antimalarials continues, however, the battle against malaria is far from over. Ferroquine is a derivative of chloroquine with antimalarial properties. It is the most successful of the chloroquine derivatives. Not only ferroquine, but also its derivatives have shown promising potential as antimalarials of clinical interest. Presently, much research is dedicated to the development of ferroquine derivatives as safe alternatives to antimalarial chemotherapy. The present article describes the structural, chemical and biological features of ferroquine. Several classes of ferroquine derivatives including hydroxyferroquines, trioxaferroquines, chloroquine-bridged ferrocenophanes, thiosemicarbazone derivatives, ferrocene dual conjugates, 4-N-substituted derivatives, and others have been discussed. Besides, the mechanism of action of ferroquine has been discussed. A careful observation has been made into pharmacologically significant ferroquine derivatives with better or equal therapeutic effects to that of chloroquine and ferroquine. A brief discussion of the toxicities of ferroquine derivatives has been made. Finally, efforts have been made to discuss the current challenges and future perspectives of ferroquine-based antimalarial drug development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Molecular Insights into the Potential Insecticidal Interaction of β-Dihydroagarofuran Derivatives with the H Subunit of V-ATPase

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Jielu Wei

2017-10-01

Full Text Available Celangulin V (CV, one of dihydroagarofuran sesquiterpene polyesters isolated from Chinese bittersweet (Celastrus angulatus Maxim, is famous natural botanical insecticide. Decades of research suggests that is displays excellent insecticidal activity against some insects, such as Mythimna separata Walker. Recently, it has been validated that the H subunit of V-ATPase is one of the target proteins of the insecticidal dihydroagarofuran sesquiterpene polyesters. As a continuation of the development of new pesticides from these natural products, a series of β-dihydroagarofuran derivatives have been designed and synthesized. The compound JW-3, an insecticidal derivative of CV with a p-fluorobenzyl group, exhibits higher insecticidal activity than CV. In this study, the potential inhibitory effect aused by the interaction of JW-3 with the H subunit of V-ATPase c was verified by confirmatory experiments at the molecular level. Both spectroscopic techniques and isothermal titration calorimetry measurements showed the binding of JW-3 to the subunit H of V-ATPase was specific and spontaneous. In addition, the possible mechanism of action of the compound was discussed. Docking results indicated compound JW-3 could bind well in ‘the interdomain cleft’ of the V-ATPase subunit H by the hydrogen bonding and make conformation of the ligand–protein complex become more stable. All results are the further validations of the hypothesis, that the target protein of insecticidal dihydroagarofuran sesquiterpene polyesters and their β-dihydroagarofuran derivatives is the subunit H of V-ATPase. The results also provide new ideas for developing pesticides acting on V-ATPase of insects.

Behavioral Design Teams: The Next Frontier in Clinical Delivery Innovation?

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Robertson, Ted; Darling, Matthew; Leifer, Jennifer; Footer, Owen; Gordski, Dani

2017-11-01

A deep understanding of human behavior is critical to designing effective health care delivery models, tools, and processes. Currently, however, few mechanisms exist to systematically apply insights about human behavior to improve health outcomes. Behavioral design teams (BDTs) are a successful model for applying behavioral insights within an organization. Already operational within government, this model can be adapted to function in a health care setting. To explore how BDTs could be applied to clinical care delivery and review models for integrating these teams within health care organizations. Interviews with experts in clinical delivery innovation and applied behavioral science, as well as leaders of existing government BDTs. BDTs are most effective when they enjoy top-level executive support, are co-led by a domain expert and behavioral scientist, collaborate closely with key staff and departments, have access to data and IT support, and operate a portfolio of projects. BDTs could be embedded in health care organizations in multiple ways, including in or just below the CEO’s office, within a quality improvement unit, or within an internal innovation center. When running a portfolio, BDTs achieve a greater number and diversity of insights at lower costs. They also become a platform for strategic learning and scaling.

Bridging the gap between the neurocognitive lab and the addiction clinic.

Science.gov (United States)

Franken, Ingmar H A; van de Wetering, Ben J M

2015-05-01

In the past decennium there has been an enormous increase in new insights in cognitive mechanisms of addiction and their neural substrates. These candidate neurocognitive mechanisms, particularly those associated with "drive" and "control" aspects of addiction, are clearly involved in substance use problems but do not yet provide a full explanation. The neurocognitive mechanisms addressed in the present perspective are attentional bias, reward processing (both drive aspects) and error-processing and cognitive control (both control aspects). The time has come to transfer these recent insights more consistently to clinical practice by studying their relevance for diagnosis and treatment in patient samples. The present perspective echoes the development of recent initiatives such as the RDoC system to integrate developments in neuroscience into clinical practice. The aim of this article is to open new vistas for addiction diagnosis and treatment and to discuss why and how these neurocognitive aspects of addictive behavior can be used in clinical practice. In addition, present problematic issues and a future research agenda are provided. Copyright © 2014 Elsevier Ltd. All rights reserved.

Implementing Peer Learning in Clinical Education: A Framework to Address Challenges In the "Real World".

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Tai, Joanna Hong Meng; Canny, Benedict J; Haines, Terry P; Molloy, Elizabeth K

2017-01-01

Phenomenon: Peer learning has many benefits and can assist students in gaining the educational skills required in future years when they become teachers themselves. Peer learning may be particularly useful in clinical learning environments, where students report feeling marginalized, overwhelmed, and unsupported. Educational interventions often fail in the workplace environment, as they are often conceived in the "ideal" rather than the complex, messy real world. This work sought to explore barriers and facilitators to implementing peer learning activities in a clinical curriculum. Previous peer learning research results and a matrix of empirically derived peer learning activities were presented to local clinical education experts to generate discussion around the realities of implementing such activities. Potential barriers and limitations of and strategies for implementing peer learning in clinical education were the focus of the individual interviews. Thematic analysis of the data identified three key considerations for real-world implementation of peer learning: culture, epistemic authority, and the primacy of patient-centered care. Strategies for peer learning implementation were also developed from themes within the data, focusing on developing a culture of safety in which peer learning could be undertaken, engaging both educators and students, and establishing expectations for the use of peer learning. Insights: This study identified considerations and strategies for the implementation of peer learning activities, which took into account both educator and student roles. Reported challenges were reflective of those identified within the literature. The resultant framework may aid others in anticipating implementation challenges. Further work is required to test the framework's application in other contexts and its effect on learner outcomes.

Role of Serum Brain Derived Neurotrophic Factor and Central N-Acetylaspartate for Clinical Response under Antidepressive Pharmacotherapy

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Sarah Nase

2016-02-01

Full Text Available Background: The predictive therapeutic value of brain derived neurotrophic factor (BDNF and its changes associated with the use of specific antidepressants are still unclear. In this study, we examined BDNF as a peripheral and NAA as a central biomarker over the time course of antidepressant treatment to specify both of their roles in the response to the medication and clinical outcome. Methods: We examined serum BDNF (ELISA kit in a sample of 76 (47 female and 29 male depressed patients in a naturalistic setting. BDNF was assessed before medication and subsequently after two, four and six weeks of antidepressant treatment. Additionally, in fifteen patients, N-acetylaspartate (NAA was measured in the anterior cingulate cortex (ACC with magnetic resonance spectroscopy (MRS. Over a time course of six weeks BDNF and NAA were also examined in a group of 41 healthy controls. Results: We found significant lower serum BDNF concentrations in depressed patients compared to the sample of healthy volunteers before and after medication. BDNF and clinical symptoms decreased significantly in the patients over the time course of antidepressant treatment. Serum BDNF levels at baseline predicted the symptom outcome after eight weeks. Specifically, responders and remitters had lower serum BDNF at baseline than the nonresponders and nonremitters. NAA was slightly decreased but not significantly lower in depressed patients when compared with healthy controls. During treatment period, NAA showed a tendency to increase. Limitations: A relative high drop-out rate and possibly, a suboptimal observation period for BDNF. Conclusion: Our data confirm serum BDNF as a biomarker of depression with a possible role in response prediction. However, our findings argue against serum BDNF increase being a prerequisite to depressive symptom reduction.

Implementing human factors in clinical practice

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Timmons, Stephen; Baxendale, Bryn; Buttery, Andrew; Miles, Giulia; Roe, Bridget; Browes, Simon

2015-01-01

Objectives To understand whether aviation-derived human factors training is acceptable and useful to healthcare professionals. To understand whether and how healthcare professionals have been able to implement human factors approaches to patient safety in their own area of clinical practice. Methods Qualitative, longitudinal study using semi-structured interviews and focus groups, of a multiprofessional group of UK NHS staff (from the emergency department and operating theatres) who have received aviation-derived human factors training. Results The human factors training was evaluated positively, and thought to be both acceptable and relevant to practice. However, the staff found it harder to implement what they had learned in their own clinical areas, and this was principally attributed to features of the informal organisational cultures. Conclusions In order to successfully apply human factors approaches in hospital, careful consideration needs to be given to the local context and informal culture of clinical practice. PMID:24631959

The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress.

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Chow, Matthew; Cao, Michelle

2016-01-01

Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep-wake regulation came from narcolepsy-cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep-wake control through complex interactions between monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of sleep-wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders.

Dispositional Insight Scale: Development and Validation of a Tool That Measures Propensity toward Insight in Problem Solving

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Ovington, Linda A.; Saliba, Anthony J.; Goldring, Jeremy

2016-01-01

This article reports the development of a brief self-report measure of dispositional insight problem solving, the Dispositional Insight Scale (DIS). From a representative Australian database, 1,069 adults (536 women and 533 men) completed an online questionnaire. An exploratory and confirmatory factor analysis revealed a 5-item scale, with all…

Franchise Business Model: Theoretical Insights

OpenAIRE

Levickaitė, Rasa; Reimeris, Ramojus

2010-01-01

The article is based on literature review, theoretical insights, and deals with the topic of franchise business model. The objective of the paper is to analyse peculiarities of franchise business model and its developing conditions in Lithuania. The aim of the paper is to make an overview on franchise business model and its environment in Lithuanian business context. The overview is based on international and local theoretical insights. In terms of practical meaning, this article should be re...

Neural activity when people solve verbal problems with insight.

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Mark Jung-Beeman

2004-04-01

Full Text Available People sometimes solve problems with a unique process called insight, accompanied by an "Aha!" experience. It has long been unclear whether different cognitive and neural processes lead to insight versus noninsight solutions, or if solutions differ only in subsequent subjective feeling. Recent behavioral studies indicate distinct patterns of performance and suggest differential hemispheric involvement for insight and noninsight solutions. Subjects solved verbal problems, and after each correct solution indicated whether they solved with or without insight. We observed two objective neural correlates of insight. Functional magnetic resonance imaging (Experiment 1 revealed increased activity in the right hemisphere anterior superior temporal gyrus for insight relative to noninsight solutions. The same region was active during initial solving efforts. Scalp electroencephalogram recordings (Experiment 2 revealed a sudden burst of high-frequency (gamma-band neural activity in the same area beginning 0.3 s prior to insight solutions. This right anterior temporal area is associated with making connections across distantly related information during comprehension. Although all problem solving relies on a largely shared cortical network, the sudden flash of insight occurs when solvers engage distinct neural and cognitive processes that allow them to see connections that previously eluded them.

Insight and suicidality in psychosis: A cross-sectional study.

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Massons, Carmen; Lopez-Morinigo, Javier-David; Pousa, Esther; Ruiz, Ada; Ochoa, Susana; Usall, Judith; Nieto, Lourdes; Cobo, Jesus; David, Anthony S; Dutta, Rina

2017-06-01

We aimed to test whether specific insight dimensions are associated with suicidality in patients with psychotic disorders. 143 patients with schizophrenia spectrum disorders were recruited. Suicidality was assessed by item 8 of the Calgary Depression Scale for Schizophrenia (CDSS). Insight was measured by the Scale of Unawareness of Mental Disorder (SUMD) and the Markova and Berrios Insight Scale. Bivariate analyses and multivariable logistic regression models were conducted. Those subjects aware of having a mental illness and its social consequences had higher scores on suicidality than those with poor insight. Awareness of the need for treatment was not linked with suicidality. The Markova and Berrios Insight scale total score and two specific domains (awareness of "disturbed thinking and loss of control over the situation" and "having a vague feeling that something is wrong") were related to suicidality. However, no insight dimensions survived the multivariable regression model, which found depression and previous suicidal behaviour to predict suicidality. Suicidality in psychosis was linked with some insight dimensions: awareness of mental illness and awareness of social consequences, but not compliance. Depression and previous suicidal behaviour mediated the associations with insight; thus, predicting suicidality. Copyright © 2017. Published by Elsevier B.V.

Clinical Trial of Human Fetal Brain-Derived Neural Stem/Progenitor Cell Transplantation in Patients with Traumatic Cervical Spinal Cord Injury

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Ji Cheol Shin

2015-01-01

Full Text Available In a phase I/IIa open-label and nonrandomized controlled clinical trial, we sought to assess the safety and neurological effects of human neural stem/progenitor cells (hNSPCs transplanted into the injured cord after traumatic cervical spinal cord injury (SCI. Of 19 treated subjects, 17 were sensorimotor complete and 2 were motor complete and sensory incomplete. hNSPCs derived from the fetal telencephalon were grown as neurospheres and transplanted into the cord. In the control group, who did not receive cell implantation but were otherwise closely matched with the transplantation group, 15 patients with traumatic cervical SCI were included. At 1 year after cell transplantation, there was no evidence of cord damage, syrinx or tumor formation, neurological deterioration, and exacerbating neuropathic pain or spasticity. The American Spinal Injury Association Impairment Scale (AIS grade improved in 5 of 19 transplanted patients, 2 (A → C, 1 (A → B, and 2 (B → D, whereas only one patient in the control group showed improvement (A → B. Improvements included increased motor scores, recovery of motor levels, and responses to electrophysiological studies in the transplantation group. Therefore, the transplantation of hNSPCs into cervical SCI is safe and well-tolerated and is of modest neurological benefit up to 1 year after transplants. This trial is registered with Clinical Research Information Service (CRIS, Registration Number: KCT0000879.

Immunomodulatory Effects of Adipose-Derived Stem Cells: Fact or Fiction?

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Angelo A. Leto Barone

2013-01-01

Full Text Available Adipose-derived stromal cells (ASCs are often referred to as adipose-derived stem cells due to their potential to undergo multilineage differentiation. Their promising role in tissue engineering and ability to modulate the immune system are the focus of extensive research. A number of clinical trials using ASCs are currently underway to better understand the role of such cell niche in enhancing or suppressing the immune response. If governable, such immunoregulatory role would find application in several conditions in which an immune response is present (i.e., autoimmune conditions or feared (i.e., solid organ or reconstructive transplantation. Although allogeneic ASCs have been shown to prevent acute GvHD in both preclinical and clinical studies, their potential warrants further investigation. Well-designed and standardized clinical trials are necessary to prove the role of ASCs in the treatment of immune disorders or prevention of tissue rejection. In this paper we analyze the current literature on the role of ASCs in immunomodulation in vitro and in vivo and discuss their potential in regulating the immune system in the context of transplantation.

Graphene derived carbon confined sulfur cathodes for lithium-sulfur batteries: Electrochemical impedance studies

International Nuclear Information System (INIS)

Ganesan, Aswathi; Varzi, Alberto; Passerini, Stefano; Shaijumon, Manikoth M.

2016-01-01

Highlights: • Graphene-derived carbon (GDC) with distinctive porosity characteristics are prepared. • Effect of micro-/mesoporosity of GDC for improved Li-S battery performance is studied. • Impedance studies reveal insights into Li-S redox reactions and capacity fading phenomena. - Abstract: Sulfur nanocomposites are prepared by using graphene derived carbon (GDC), with controlled porosity characteristics, as confining matrix and are studied as efficient cathodes for lithium-sulfur (Li-S) batteries. To understand the effect of micro-/mesoporosity in porous carbon for the effective encapsulation of sulfur and polysulfides towards improved Li-S battery performance, two different GDC samples with controlled porosity characteristics, one with predominantly micropores (GDC-1) and a surface area of 1970 m 2 g −1 and the other with a surface area of 3239 m 2 g −1 , having more or less equal contribution of micro- and mesopores (GDC-2), are used to synthesize nanocomposite sulfur electrodes following melt diffusion process. Electrochemical studies are carried out by using cyclic voltammetry, galvanostatic charge/discharge cycling and electrochemical impedance spectroscopy (EIS). EIS spectra collected at different depth of discharge (DOD) in the first cycle as well as upon cycling give valuable insights into the Li-S redox reactions and capacity fading phenomena in these electrodes. The impedance response of GDC-S electrodes suggests a detrimental effect of the mesopores, where insoluble reaction products can easily accumulate, resulting in the loss of active material leading to capacity fading of Li-S cells.

The Meta-Analysis of Clinical Judgment Project: Fifty-Six Years of Accumulated Research on Clinical Versus Statistical Prediction

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Aegisdottir, Stefania; White, Michael J.; Spengler, Paul M.; Maugherman, Alan S.; Anderson, Linda A.; Cook, Robert S.; Nichols, Cassandra N.; Lampropoulos, Georgios K.; Walker, Blain S.; Cohen, Genna; Rush, Jeffrey D.

2006-01-01

Clinical predictions made by mental health practitioners are compared with those using statistical approaches. Sixty-seven studies were identified from a comprehensive search of 56 years of research; 92 effect sizes were derived from these studies. The overall effect of clinical versus statistical prediction showed a somewhat greater accuracy for…

Spontaneous neural activity in the right superior temporal gyrus and left middle temporal gyrus is associated with insight level in obsessive-compulsive disorder.

Science.gov (United States)

Fan, Jie; Zhong, Mingtian; Gan, Jun; Liu, Wanting; Niu, Chaoyang; Liao, Haiyan; Zhang, Hongchun; Tan, Changlian; Yi, Jinyao; Zhu, Xiongzhao

2017-01-01

Insight into illness is an important issue for psychiatry disorder. Although the existence of a poor insight subtype of obsessive-compulsive disorder (OCD) was recognized in the DSM-IV, and the insight level in OCD was specified further in DSM-V, the neural underpinnings of insight in OCD have been rarely explored. The present study was designed to bridge this research gap by using resting-state functional magnetic resonance imaging (fMRI). Spontaneous neural activity were examined in 19 OCD patients with good insight (OCD-GI), 18 OCD patients with poor insight (OCD-PI), and 25 healthy controls (HC) by analyzing the amplitude of low-frequency fluctuation (ALFF) in the resting state. Pearson correlation analysis was performed between regional ALFFs and insight levels among OCD patients. OCD-GI and OCD-PI demonstrated overlapping and distinct brain alterations. Notably, compared with OCD-GI, tOCD-PI had reduced ALFF in left middle temporal gyrus (MTG) and right superior temporal gyrus (STG), as well as increased ALFF in right middle occipital gyrus. Further analysis revealed that ALFF values for the left MTG and right STG were correlated negatively with insight level in patients with OCD. Relatively small sample size and not all patients were un-medicated are our major limitations. Spontaneous brain activity in left MTG and right STG may be neural underpinnings of insight in OCD. Our results suggest the great role of human temporal brain regions in understanding insight, and further underscore the importance of considering insight presentation in understanding the clinical heterogeneity of OCD. Copyright © 2016 Elsevier B.V. All rights reserved.

World energy insight 2011