Diagnostics based on nucleic acid sequence variant profiling: PCR, hybridization, and NGS approaches.

PubMed

Khodakov, Dmitriy; Wang, Chunyan; Zhang, David Yu

2016-10-01

Nucleic acid sequence variations have been implicated in many diseases, and reliable detection and quantitation of DNA/RNA biomarkers can inform effective therapeutic action, enabling precision medicine. Nucleic acid analysis technologies being translated into the clinic can broadly be classified into hybridization, PCR, and sequencing, as well as their combinations. Here we review the molecular mechanisms of popular commercial assays, and their progress in translation into in vitro diagnostics. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

H. pylori and Barrett's Esophagus: Implications for Populations and Practice.

PubMed

Howden, Colin W

2018-06-19

In this edition of the American Journal of Gastroenterology, Wang and colleagues report the results of an analysis of six different case-control studies examining the relationship between Helicobacter pylori (H. pylori) infection and Barrett's esophagus. They present a cogent argument that there is an inverse association between these two that is mediated via GERD. This is broadly consistent with previous reports. While further establishing this inverse association, the findings should not materially influence our routine clinical practice regarding GERD or H. pylori infection.

Recurrent Soft Tissue Abscesses Caused by Legionella cincinnatiensis

PubMed Central

Gubler, Jacques G. H.; Schorr, Mirjam; Gaia, V.; Zbinden, R.; Altwegg, M.

2001-01-01

Recurrent soft tissue abscesses of the jaw, wrist, and arm developed in a 73-year-old housewife with nephrotic syndrome and immunoglobulin A(κ) gammopathy of unknown etiology. Conventional cultures remained negative, despite visible gram-negative rods on microscopy. Broad-spectrum PCR revealed Legionella cincinnatiensis, which was confirmed by isolation of the organism on special Legionella medium. Infections due to Legionella species outside the lungs are rare. L. cincinnatiensis has been implicated in only four cases of clinical infection; these involved the lungs in three patients and the central nervous system in one patient. We conclude that broad-spectrum PCR can be a valuable tool for the evaluation of culture-negative infections with a high probability of bacterial origin and that Legionella might be an underdiagnosed cause of pyogenic soft tissue infection. PMID:11724886

Graduate admissions in clinical neuropsychology: the importance of undergraduate training.

PubMed

Karazsia, Bryan T; Stavnezer, Amy Jo; Reeves, Jonathan W

2013-11-01

Discussions of and recommendations for the training of clinical neuropsychologists exist at the doctoral, internship, and post-doctoral level. With few exceptions, the literature on undergraduate preparations in clinical neuropsychology is sparse and lacks empirical evidence. In the present study, graduate-level faculty and current trainees completed surveys about graduate school preparations. Faculty expectations of minimum and ideal undergraduate training were highest for research methods, statistics, and assessment. Preferences for "goodness of fit" also emerged as important admissions factors. These results offer evidence for desirable undergraduate preparations for advanced study in clinical neuropsychology. Although undergraduate training in psychology is intentionally broad, results from this study suggest that students who desire advanced study in clinical neuropsychology need to tailor their experiences to be competitive in the application process. The findings have implications for prospective graduate students, faculty who train and mentor undergraduates, and faculty who serve on admissions committees.

Ethical implications for clinical practice and future research in "at risk" individuals.

PubMed

Singh, Fiza; Mirzakhanian, Heline; Fusar-Poli, Paolo; de la Fuente-Sandoval, Camilo; Cadenhead, Kristin S

2012-01-01

The last 15 years have witnessed a shift in schizophrenia research with increasing interest in earlier stages of illness with the hope of early intervention and ultimately prevention of psychotic illness. Large-scale longitudinal studies have identified clinical and biological risk factors associated with increased risk of psychotic conversion, which together with symptomatic and demographic risk factors may improve the power of prediction algorithms for psychotic transition. Despite these advances, 45-70% of at risk subjects in most samples do not convert to frank psychosis, but continue to function well below their age matched counterparts. The issue is of utmost importance in light of the upcoming DSM-V and the possible inclusion of the attenuated psychotic symptoms syndrome (APSS) diagnosis, with clinical and ethical implications. Clinical considerations include feasibility of reliably diagnosing the at risk state in non-academic medical centers, variable psychotic conversion rates, a non-uniform definition of conversion and extensive debate about treatment for individuals with an ill-defined outcome. On the ethical side, diagnosing APSS could lead to unnecessary prescribing of antipsychotics with long-term deleterious consequences, slow research by providing a false sense of comfort in the diagnosis, and have psychosocial implications for those who receive a diagnosis. Thus it may be prudent to engage at risk populations early and to use broad-spectrum treatments with low risk benefit ratios to relieve functional impairments, while simultaneously studying all subsets of the at risk population.

Drug-nutrient interactions: a broad view with implications for practice.

PubMed

Boullata, Joseph I; Hudson, Lauren M

2012-04-01

The relevance of drug?nutrient interactions in daily practice continues to grow with the widespread use of medication. Interactions can involve a single nutrient, multiple nutrients, food in general, or nutrition status. Mechanistically, drug?nutrient interactions occur because of altered intestinal transport and metabolism, or systemic distribution, metabolism and excretion, as well as additive or antagonistic effects. Optimal patient care includes identifying, evaluating, and managing these interactions. This task can be supported by a systematic approach for categorizing interactions and rating their clinical significance. This review provides such a broad framework using recent examples, as well as some classic drug?nutrient interactions. Pertinent definitions are presented, as is a suggested approach for clinicians. This important and expanding subject will benefit tremendously from further clinician involvement. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Perspectives on clinical leadership: a qualitative study exploring the views of senior healthcare leaders in the UK

PubMed Central

Mohanna, Kay; Cowpe, Jenny

2014-01-01

Introduction Clinicians are being asked to play a major role leading the NHS. While much is written on about clinical leadership, little research in the medical literature has examined perceptions of the term or mapped the perceived attributes required for success. Objective To capture the views of senior UK healthcare leaders regarding their perception of the term `clinical leadership' and the cultural backdrop in which it is being espoused. Setting UK Healthcare sector Participants Senior UK Healthcare leaders Methods Twenty senior healthcare leaders including a former Health Minister, NHS Executives, NHS Strategic Health Authority, PCT and Acute Trust chief executives and medical directors, Medical Deans and other key actors in the UK medical leadership arena were interviewed between 2010 and 2011 using a semi-structured interview technique. Using grounded theory, themes were identified and subsequently analysed in an attempt to answer the broad questions posed. Main outcome measures Not applicable for a qualitative research project Results A number of themes emerged from this qualitative study. First, there was evidence of changing attitudes among doctors, particularly trainees, towards becoming involved in clinical leadership. However, there was unease over the ambiguity of the term ‘clinical leadership’ and the implications for the future. There was, however, broad agreement as to the perceived attributes and skills required for success in healthcare leadership. Conclusions Clinical leadership is often perceived to be doctor centric and ‘Healthcare Leadership’ may be a more inclusive term. An understanding of the historical medico-political context of the leadership debate is required by all healthcare leaders to fully understand the challenges of changing healthcare culture. Whilst the broad attributes deemed essential for success as a healthcare leaders are not new, significant effort and investment, including a physical Healthcare Academy, are required to best utilise and harmonise the breadth of leadership talent in the NHS. PMID:25013095

Skin-interfaced systems for sweat collection and analytics

PubMed Central

Choi, Jungil; Ghaffari, Roozbeh; Baker, Lindsay B.; Rogers, John A.

2018-01-01

Recent interdisciplinary advances in materials, mechanics, and microsystem designs for biocompatible electronics, soft microfluidics, and electrochemical biosensors establish the foundations for emerging classes of thin, skin-interfaced platforms capable of capturing, storing, and performing quantitative, spatiotemporal measurements of sweat chemistry, instantaneous local sweat rate, and total sweat loss. This review summarizes scientific and technical progress in this area and highlights the implications in real time and ambulatory modes of deployment during physical activities across a broad range of contexts in clinical health, physiology research, fitness/wellness, and athletic performance. PMID:29487915

Reflections on Self-Reflection: Contemplating Flawed Self-Judgments in the Clinic, Classroom, and Office Cubicle.

PubMed

Dunning, David; Heath, Chip; Suls, Jerry M

2018-03-01

We reflect back on our 2004 monograph reviewing the implications of faulty self-judgment for health, education, and the workplace. The review proved popular, no doubt because the importance of accurate self-assessment is best reflected in just how broad the literature is that touches on this topic. We discuss opportunities and challenges to be found in the future study of self-judgment accuracy and error, and suggest that designing interventions aimed at improving self-judgments may prove to be a worthwhile but complex and nuanced task.

Povidone iodine in wound healing: A review of current concepts and practices.

PubMed

Bigliardi, Paul Lorenz; Alsagoff, Syed Abdul Latiff; El-Kafrawi, Hossam Yehia; Pyon, Jai-Kyong; Wa, Chad Tse Cheuk; Villa, Martin Anthony

2017-08-01

Of the many antimicrobial agents available, iodophore-based formulations such as povidone iodine have remained popular after decades of use for antisepsis and wound healing applications due to their favorable efficacy and tolerability. Povidone iodine's broad spectrum of activity, ability to penetrate biofilms, lack of associated resistance, anti-inflammatory properties, low cytotoxicity and good tolerability have been cited as important factors, and no negative effect on wound healing has been observed in clinical practice. Over the past few decades, numerous reports on the use of povidone iodine have been published, however, many of these studies are of differing design, endpoints, and quality. More recent data clearly supports its use in wound healing. Based on data collected through PubMed using specified search criteria based on above topics and clinical experience of the authors, this article will review preclinical and clinical safety and efficacy data on the use of povidone iodine in wound healing and its implications for the control of infection and inflammation, together with the authors' advice for the successful treatment of acute and chronic wounds. Povidone iodine has many characteristics that position it extraordinarily well for wound healing, including its broad antimicrobial spectrum, lack of resistance, efficacy against biofilms, good tolerability and its effect on excessive inflammation. Due to its rapid, potent, broad-spectrum antimicrobial properties, and favorable risk/benefit profile, povidone iodine is expected to remain a highly effective treatment for acute and chronic wounds in the foreseeable future. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Relationship between the broad autism phenotype, social relationships and mental health for mothers of children with autism spectrum disorder.

PubMed

Pruitt, Megan M; Rhoden, Madeline; Ekas, Naomi V

2018-02-01

This study aimed to examine the mechanisms responsible for the association between the broad autism phenotype and depressive symptoms in mothers of a child with autism spectrum disorder. A total of 98 mothers who had a child with autism spectrum disorder between the ages of 2 and 16 years completed assessments of maternal broad autism phenotype, child behavior problems, romantic relationship satisfaction, friend support, family support, and maternal depressive symptoms. Results indicated that only romantic relationship satisfaction was a significant mediator of the relationship between maternal broad autism phenotype social abnormalities and maternal depressive symptoms, where greater broad autism phenotype social abnormalities were associated with lower relationship satisfaction, which in turn was associated with increased depressive symptoms. Child behavior problems were directly related to increased depressive symptoms. Implications regarding maternal mental health outcomes within this population as well as intervention implications are discussed.

What Is the Optimal Target Convective Volume in On-Line Hemodiafiltration Therapy?

PubMed

Canaud, Bernard; Koehler, Katrin; Bowry, Sudhir; Stuard, Stefano

2017-01-01

Conventional diffusion-based dialysis modalities including high-flux hemodialysis are limited in their capacity to effectively remove large uremic toxins and to improve outcomes for end-stage chronic kidney disease (ESKD) patients. By increasing convective solute transport, hemodiafiltration (HDF) enhances solute removal capacity over a broad range of middle- and large-size uremic toxins implicated in the pathophysiology of chronic kidney disease. Furthermore, by offering flexible convection volume, on-line HDF permits customizing the treatment dose to the patient's needs. In addition, convective-based modalities have been shown to improve hemodynamic stability and to reduce patients' inflammation profile - both of which are implicated in CKD morbidity and mortality. Growing clinical evidence indicates that HDF-based modalities provide ESKD patients with a number of clinical and biological benefits, including improved outcomes. Interestingly, it has recently emerged that the clinical benefits associated with HDF are positively associated with the total ultrafiltered volume per session (and per week), namely convective dose. In this chapter, we revisit the concept of convective dose and discuss the threshold value above which an improvement in ESKD patient outcome can be expected. This particular point will be addressed by stratifying the level of efficacy of convective volumes, schematically defined as minimal, optimal, personalized, and maximal. In addition, factors and best clinical practices implicated in the achievement of an optimal convective dose are reviewed. To conclude, we show how HDF differs from standard hemodialysis and why HDF offers a paradigm shift in renal replacement therapy. © 2017 S. Karger AG, Basel.

Assessment Practices of Child Clinicians.

PubMed

Cook, Jonathan R; Hausman, Estee M; Jensen-Doss, Amanda; Hawley, Kristin M

2017-03-01

Assessment is an integral component of treatment. However, prior surveys indicate clinicians may not use standardized assessment strategies. We surveyed 1,510 clinicians and used multivariate analysis of variance to explore group differences in specific measure use. Clinicians used unstandardized measures more frequently than standardized measures, although psychologists used standardized measures more frequently than nonpsychologists. We also used latent profile analysis to classify clinicians based on their overall approach to assessment and examined associations between clinician-level variables and assessment class or profile membership. A four-profile model best fit the data. The largest profile consisted of clinicians who primarily used unstandardized assessments (76.7%), followed by broad-spectrum assessors who regularly use both standardized and unstandardized assessment (11.9%), and two smaller profiles of minimal (6.0%) and selective assessors (5.5%). Compared with broad-spectrum assessors, unstandardized and minimal assessors were less likely to report having adequate standardized measures training. Implications for clinical practice and training are discussed.

Barriers to Considering Ethical and Societal Implications of Research: Perceptions of Life Scientists.

PubMed

McCormick, Jennifer Blair; Boyce, Angie M; Ladd, Jennifer M; Cho, Mildred

2012-01-01

BACKGROUND: As part of an empirical study investigating how life scientists think about ethical and societal implications of their work, and about life science research in general, we sought to elucidate barriers that scientists might face in considering such implications. METHOD: Between 2005 and 2007, we conducted a study consisting of phone interviews, focus groups, and a national survey of life scientists at biomedical research institutions. The study population included graduate students, postdoctoral fellows, faculty, clinical instructors, and research staff. We analyzed data through qualitative and quantitative methods. RESULTS: In analyzing the data, we found that life scientists do, in fact, face barriers to considering ethical and societal implications of research. We categorized these barriers as falling into four broad domains: (1) lack of awareness of ethical and societal implications; (2) lack of relevance of such concerns to their specific research; (3) self-confidence in their ability to resolve such concerns; and (4) aspects of the daily practice of science itself. CONCLUSIONS: Life science researchers experience elements inherent in their training and in the conduct of science as barriers to thinking about ethical and societal implications related to their work. These findings suggest areas in which research ethics educators, bioethicists, and the scientific community can focus their efforts to improve social and ethical accountability in research.

The Broad Challenge to Democratic Leadership: The Other Crisis in Education

ERIC Educational Resources Information Center

Miller, Vachel W.

2012-01-01

This article interrogates the workings of the Broad Superintendents Academy, as a specific illustration of the influence of venture philanthropy in American public education. It introduces the Broad Foundation's agenda for educational leadership training, foregrounding how it frames the problem of leadership and the implications of such training…

Implications of the Vienna Integrated Model of Art Perception for art-based interventions in clinical populations: Comment on "Move me, astonish me... delight my eyes and brain: The Vienna Integrated Model of top-down and bottom-up processes in Art Perception (VIMAP) and corresponding affective, evaluative, and neurophysiological correlates" by Matthew Pelowski et al.

NASA Astrophysics Data System (ADS)

Taruffi, Liila; Koelsch, Stefan

2017-07-01

Pelowski et al. present a holistic framework within which the multiple processes underlying art viewing can be systematically organized [1]. The proposed model integrates a broad range of dynamic mechanisms, which can effectively account for empirical as well as humanistic perspectives on art perception. Particularly challenging is the final section of the article, where the authors draw a correspondence between behavioral and cognitive components and brain structures (as well as networks). Here, we comment on the implications of the Vienna Integrated Model of Art Perception for art therapy in clinical populations, particularly focusing on (1) expanding Pelowski et al.'s considerations of the Default Mode Network (DMN) into discussion of its relevance to mental diseases, and (2) elaborating on empathic resonance in aesthetic contexts and the capacity of art to build up empathic skills.

Personality and psychopathology: mapping the MMPI-2-RF on Cloninger's psychobiological model of personality.

PubMed

van der Heijden, Paul T; Egger, Jos I M; Rossi, Gina M P; van der Veld, William M; Derksen, Jan J L

2013-10-01

This study investigates the relationship between the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) and the Temperament and Character Inventory (TCI) in a combined data set (N = 491) of patients with a broad range of psychiatric disorders (n = 286) as well as alcohol use disorder (n = 205). We examined bivariate correlations between both measures. The MMPI-2-RF scales relate to the TCI dimensions as was hypothesized, and relationships between both measurements were largely similar for psychiatric patients and alcohol-dependent patients. Theoretical and clinical implications are considered.

New directions for feminist therapy based on social constructionism.

PubMed

Finfgeld, D L

2001-06-01

Feminist therapy has made significant contributions in the area of women's mental health care. Of late, however, critics have argued that feminist therapists are neglecting the needs of many women. The unique perspectives of women of color, lower and upper class women, lesbians, and other persons have been ignored. As such, it is proposed that social constructionism offers a metaframework for reinterpreting feminist therapy tenets to better address the needs of a broad range of individuals. Clinical implications are offered along with future directions for research and education. Copyright 2001 by W.B. Saunders Company

Mobile health: the power of wearables, sensors, and apps to transform clinical trials.

PubMed

Munos, Bernard; Baker, Pamela C; Bot, Brian M; Crouthamel, Michelle; de Vries, Glen; Ferguson, Ian; Hixson, John D; Malek, Linda A; Mastrototaro, John J; Misra, Veena; Ozcan, Aydogan; Sacks, Leonard; Wang, Pei

2016-07-01

Mobile technology has become a ubiquitous part of everyday life, and the practical utility of mobile devices for improving human health is only now being realized. Wireless medical sensors, or mobile biosensors, are one such technology that is allowing the accumulation of real-time biometric data that may hold valuable clues for treating even some of the most devastating human diseases. From wearable gadgets to sophisticated implantable medical devices, the information retrieved from mobile technology has the potential to revolutionize how clinical research is conducted and how disease therapies are delivered in the coming years. Encompassing the fields of science and engineering, analytics, health care, business, and government, this report explores the promise that wearable biosensors, along with integrated mobile apps, hold for improving the quality of patient care and clinical outcomes. The discussion focuses on groundbreaking device innovation, data optimization and validation, commercial platform integration, clinical implementation and regulation, and the broad societal implications of using mobile health technologies. © 2016 New York Academy of Sciences.

Clinical and molecular features of Joubert syndrome and related disorders

PubMed Central

Parisi, Melissa A.

2009-01-01

Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least 8 genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium. PMID:19876931

The functions of assessment: implications for selection and development of devices for assessing repertoires in clinical, educational, and other settings.

PubMed Central

Hawkins, R P

1979-01-01

An attempt is made to identify the many different functions that assessment of an individual's repertoire can serve. Implications of these functions for the character of and evidence about assessment devices are suggested. The functions fall into two general groups, those which influence decisions regarding an individual learner, and those which influence policy, program development, and scientific knowledge. The first group of functions is presented in a rough chronological sequence such that they form a "behavioral assessment funnel," beginning with functions involving broad-band assessment to identify likely persons and skill areas, and narrowing to the precise pinpointing, monitoring, and follow-up functions. The contribution of behavior analysis and behavior therapy to assessment methodology in this sequence is identified as well as the areas where more traditionally conceived methods are still useful. The second group of functions and behavioral contributions to it are then discussed. PMID:541308

Health technology adoption and the politics of governance in the UK.

PubMed

Milewa, Timothy

2006-12-01

The manner in which clinical and cost-effectiveness data are used to inform decisions about the funding and availability of drugs, therapies and medical devices is inherently politicised within collectively financed systems of health care. The National Institute for Health and Clinical Excellence (NICE) was established by the British government in 1999 to reach evidence-based decisions on whether selected health technologies should be made available by the National Health Service in England and Wales. But NICE is also required to involve a broad range of interested parties in the decision-making process, provide detailed rationales for its rulings and defend appeals from aggrieved parties. Debates about the emergence of "deliberative" forms of policy governance--based upon participation by a broad range of stakeholders rather than reliance on scientific, bureaucratic or political expertise alone--are thus particularly apposite. This article draws on a study of decision-making within NICE by focusing upon the tenor and orientation of deliberation about the adoption of health technologies. Does such deliberation take place upon a level playing field for different interests? Or do implicit parameters and understandings in the deliberative process tend to privilege some interests by structuring debate and attendant outcomes? Findings suggest that deliberative assumptions and parameters pertaining to fluid and contestable ideas of transparent reasoning and domain competence both reflect and shape relationships of influence and marginality among participants. Broader analytical implications centre on a distinction between "deliberative democracy" and "democratic deliberation". The extent to which this distinction is acknowledged and addressed in policy and practise will have marked implications for the substantive nature of attempts to broaden involvement in decision-making within public sector bodies such as NICE.

Broad-range PCR: past, present, or future of bacteriology?

PubMed

Renvoisé, A; Brossier, F; Sougakoff, W; Jarlier, V; Aubry, A

2013-08-01

PCR targeting the gene encoding 16S ribosomal RNA (commonly named broad-range PCR or 16S PCR) has been used for 20 years as a polyvalent tool to study prokaryotes. Broad-range PCR was first used as a taxonomic tool, then in clinical microbiology. We will describe the use of broad-range PCR in clinical microbiology. The first application was identification of bacterial strains obtained by culture but whose phenotypic or proteomic identification remained difficult or impossible. This changed bacterial taxonomy and allowed discovering many new species. The second application of broad-range PCR in clinical microbiology is the detection of bacterial DNA from clinical samples; we will review the clinical settings in which the technique proved useful (such as endocarditis) and those in which it did not (such as characterization of bacteria in ascites, in cirrhotic patients). This technique allowed identifying the etiological agents for several diseases, such as Whipple disease. This review is a synthesis of data concerning the applications, assets, and drawbacks of broad-range PCR in clinical microbiology. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Emerging Trends in Clinical Research: With Implications for Population Health and Health Policy.

PubMed

Chin-Yee, Benjamin; Subramanian, S V; Verma, Amol A; Laupacis, Andreas; Razak, Fahad

2018-06-01

Policy Points: Significant advances in clinical medicine that have broader societal relevance may be less accessible to population health researchers and policymakers because of increased specialization within fields. We describe important recent clinical advances and discuss their broader societal impact. These advances include more expansive strategies for disease prevention, the rise of precision medicine, applications of human microbiome research, and new and highly successful treatments for hepatitis C infection. These recent developments in clinical research raise important issues surrounding health care costs and equitable resource allocation that necessitate an ongoing dialogue among the fields of clinical medicine, population health, and health policy. Developments in clinical medicine have important implications for population health, and there is a need for interdisciplinary engagement among clinical medicine, the social sciences, and public health research. The aim of this article is to help bridge the divide between these fields by exploring major recent advances in clinical medicine that have important implications for population health. We reviewed the most cited articles published from 2010 to 2015 in 5 high-impact clinical journals and selected 5 randomized controlled trials and 2 related clinical practice guidelines that are broadly relevant to population health and policy. We discuss the following themes: (1) expanding indications for drug therapy and the inherent medicalization of the population as highlighted by studies and clinical guidelines supporting lower blood pressure targets or widespread statin use; (2) the tension in nutritional research between quantifying the impact of isolated nutrients and studying specific foods and dietary patterns, for example, the role of the Mediterranean diet in the primary prevention of cardiovascular disease; (3) the issue of high medication costs and the challenge of providing equitable access raised by the development of new and effective treatments for hepatitis C infection; (4) emerging clinical applications of research on the human microbiome as illustrated by fecal transplant to treat Clostridium difficile infections; and (5) the promise and limitations of precision medicine as demonstrated by the rise of novel targeted therapies in oncology. These developments in clinical science hold promise for improving individual and population health and raise important questions about resource allocation, the role of prevention, and health disparities. © 2018 Milbank Memorial Fund.

DSM-5 pathological personality traits and the personality assessment inventory.

PubMed

Hopwood, Christopher J; Wright, Aidan G C; Krueger, Robert F; Schade, Nick; Markon, Kristian E; Morey, Leslie C

2013-06-01

Section 3 of the DSM-5 will include a pathological personality trait system rooted in the quantitative epistemology of personality and clinical psychology. This system has the potential to enhance the clinical utility of the diagnostic nosology by providing a means for the dimensional assessment of individuals with psychopathology. However, there is limited research on the associations of DSM-5 traits with common mental disorders and related clinical phenomena as measured by currently popular assessment instruments. The purpose of this article was to evaluate the convergence of the DSM-5 trait system with a well-validated broadband clinical instrument, the Personality Assessment Inventory (PAI). Bivariate correlations were examined and factor analytic methods were used to examine the degree to which the DSM-5 traits and PAI capture common variance in personality and mental health. In a student sample (N = 1,001), we found broad convergence between the DSM-5 traits and PAI, which could be organized effectively using five factors. The implications of these findings for using traits to address issues related to diagnostic co-occurrence and heterogeneity in routine clinical assessment are discussed.

Battery-free, wireless sensors for full-body pressure and temperature mapping

PubMed Central

Han, Seungyong; Kim, Jeonghyun; Won, Sang Min; Ma, Yinji; Kang, Daeshik; Xie, Zhaoqian; Lee, Kyu-Tae; Chung, Ha Uk; Banks, Anthony; Min, Seunghwan; Heo, Seung Yun; Davies, Charles R.; Lee, Jung Woo; Lee, Chi-Hwan; Kim, Bong Hoon; Li, Kan; Zhou, Yadong; Wei, Chen; Feng, Xue; Huang, Yonggang; Rogers, John A.

2018-01-01

Thin, soft, skin-like sensors capable of precise, continuous measurements of physiological health have broad potential relevance to clinical health care. Use of sensors distributed over a wide area for full-body, spatiotemporal mapping of physiological processes would be a considerable advance for this field. We introduce materials, device designs, wireless power delivery and communication strategies, and overall system architectures for skin-like, battery-free sensors of temperature and pressure that can be used across the entire body. Combined experimental and theoretical investigations of the sensor operation and the modes for wireless addressing define the key features of these systems. Studies with human subjects in clinical sleep laboratories and in adjustable hospital beds demonstrate functionality of the sensors, with potential implications for monitoring of circadian cycles and mitigating risks for pressure-induced skin ulcers. PMID:29618561

Disease concepts and treatment by tribal healers of an Amazonian forest culture.

PubMed

Herndon, Christopher N; Uiterloo, Melvin; Uremaru, Amasina; Plotkin, Mark J; Emanuels-Smith, Gwendolyn; Jitan, Jeetendra

2009-10-12

The extensive medicinal plant knowledge of Amazonian tribal peoples is widely recognized in the scientific literature and celebrated in popular lore. Despite this broad interest, the ethnomedical systems and knowledge of disease which guide indigenous utilization of botanical diversity for healing remain poorly characterized and understood. No study, to our knowledge, has attempted to directly examine patterns of actual disease recognition and treatment by healers of an Amazonian indigenous culture. The establishment of traditional medicine clinics, operated and directed by elder tribal shamans in two remote Trio villages of the Suriname rainforest, presented a unique investigational opportunity. Quantitative analysis of clinic records from both villages permitted examination of diseases treated over a continuous period of four years. Cross-cultural comparative translations were articulated of recorded disease conditions through ethnographic interviews of elder Trio shamans and a comprehensive atlas of indigenous anatomical nomenclature was developed. 20,337 patient visits within the period 2000 to 2004 were analyzed. 75 disease conditions and 127 anatomical terms are presented. Trio concepts of disease and medical practices are broadly examined within the present and historical state of their culture. The findings of this investigation support the presence of a comprehensive and highly formalized ethnomedical institution within Trio culture with attendant health policy and conservation implications.

Disease concepts and treatment by tribal healers of an Amazonian forest culture

PubMed Central

Herndon, Christopher N; Uiterloo, Melvin; Uremaru, Amasina; Plotkin, Mark J; Emanuels-Smith, Gwendolyn; Jitan, Jeetendra

2009-01-01

Background The extensive medicinal plant knowledge of Amazonian tribal peoples is widely recognized in the scientific literature and celebrated in popular lore. Despite this broad interest, the ethnomedical systems and knowledge of disease which guide indigenous utilization of botanical diversity for healing remain poorly characterized and understood. No study, to our knowledge, has attempted to directly examine patterns of actual disease recognition and treatment by healers of an Amazonian indigenous culture. Methods The establishment of traditional medicine clinics, operated and directed by elder tribal shamans in two remote Trio villages of the Suriname rainforest, presented a unique investigational opportunity. Quantitative analysis of clinic records from both villages permitted examination of diseases treated over a continuous period of four years. Cross-cultural comparative translations were articulated of recorded disease conditions through ethnographic interviews of elder Trio shamans and a comprehensive atlas of indigenous anatomical nomenclature was developed. Results 20,337 patient visits within the period 2000 to 2004 were analyzed. 75 disease conditions and 127 anatomical terms are presented. Trio concepts of disease and medical practices are broadly examined within the present and historical state of their culture. Conclusion The findings of this investigation support the presence of a comprehensive and highly formalized ethnomedical institution within Trio culture with attendant health policy and conservation implications. PMID:19821968

Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus.

PubMed

Evers, Andrea W M; Colloca, Luana; Blease, Charlotte; Annoni, Marco; Atlas, Lauren Y; Benedetti, Fabrizio; Bingel, Ulrike; Büchel, Christian; Carvalho, Claudia; Colagiuri, Ben; Crum, Alia J; Enck, Paul; Gaab, Jens; Geers, Andrew L; Howick, Jeremy; Jensen, Karin B; Kirsch, Irving; Meissner, Karin; Napadow, Vitaly; Peerdeman, Kaya J; Raz, Amir; Rief, Winfried; Vase, Lene; Wager, Tor D; Wampold, Bruce E; Weimer, Katja; Wiech, Katja; Kaptchuk, Ted J; Klinger, Regine; Kelley, John M

2018-06-12

Placebo and nocebo effects occur in clinical or laboratory medical contexts after administration of an inert treatment or as part of active treatments and are due to psychobiological mechanisms such as expectancies of the patient. Placebo and nocebo studies have evolved from predominantly methodological research into a far-reaching interdisciplinary field that is unravelling the neurobiological, behavioural and clinical underpinnings of these phenomena in a broad variety of medical conditions. As a consequence, there is an increasing demand from health professionals to develop expert recommendations about evidence-based and ethical use of placebo and nocebo effects for clinical practice. A survey and interdisciplinary expert meeting by invitation was organized as part of the 1st Society for Interdisciplinary Placebo Studies (SIPS) conference in 2017. Twenty-nine internationally recognized placebo researchers participated. There was consensus that maximizing placebo effects and minimizing nocebo effects should lead to better treatment outcomes with fewer side effects. Experts particularly agreed on the importance of informing patients about placebo and nocebo effects and training health professionals in patient-clinician communication to maximize placebo and minimize nocebo effects. The current paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts. Future research might focus on how to implement these recommendations, including how to optimize conditions for educating patients about placebo and nocebo effects and providing training for the implementation in clinical practice. © 2018 S. Karger AG, Basel.

Febrile neutropenia in cats treated with chemotherapy.

PubMed

Pierro, J; Krick, E; Flory, A; Regan, R; DeRegis, C; Boudreaux, B; Barber, L; Saam, D; Saba, C

2017-06-01

The purpose of this study was to describe the clinical presentation, potential causative agents, treatment and outcome of febrile neutropenia (FN) in chemotherapy-treated cats. Medical records from eight institutions were retrospectively reviewed. A total of 22 FN events in 20 cats were evaluated. Lymphoma was the most common cancer diagnosis; lomustine and vinca alkaloids were the most frequently implicated causative agents. Presenting clinical signs included decreased appetite, lethargy, vomiting and diarrhoea. Median body temperature and absolute neutrophil count at presentation were 104.1 °F; 40 °C (range: 103.1-105.1 °F; 39.5-40.6 °C) and 246 mL -1 (range: 0-1600 mL -1 ), respectively. Median number of days between chemotherapy administration and FN onset was 5 (range: 4-25 days). All but one cat were treated with intravenous fluids and broad spectrum antibiotics. Fevers resolved in all cases and absolute neutrophil counts returned to normal in 19 cats. Clinical presentation of cats with FN appears similar to that of dogs. © 2016 John Wiley & Sons Ltd.

Novel risk predictor for thrombus deposition in abdominal aortic aneurysms

NASA Astrophysics Data System (ADS)

Nestola, M. G. C.; Gizzi, A.; Cherubini, C.; Filippi, S.; Succi, S.

2015-10-01

The identification of the basic mechanisms responsible for cardiovascular diseases stands as one of the most challenging problems in modern medical research including various mechanisms which encompass a broad spectrum of space and time scales. Major implications for clinical practice and pre-emptive medicine rely on the onset and development of intraluminal thrombus in which effective clinical therapies require synthetic risk predictors/indicators capable of informing real-time decision-making protocols. In the present contribution, two novel hemodynamics synthetic indicators, based on a three-band decomposition (TBD) of the shear stress signal, are introduced. Extensive fluid-structure computer simulations of patient-specific scenarios confirm the enhanced risk-prediction capabilities of the TBD indicators. In particular, they permit a quantitative and accurate localization of the most likely thrombus deposition in realistic aortic geometries, where previous indicators would predict healthy operation. The proposed methodology is also shown to provide additional information and discrimination criteria on other factors of major clinical relevance, such as the size of the aneurysm.

Acetabular fractures: anatomic and clinical considerations.

PubMed

Lawrence, David A; Menn, Kirsten; Baumgaertner, Michael; Haims, Andrew H

2013-09-01

Classifying acetabular fractures can be an intimidating topic. However, it is helpful to remember that there are only three basic types of acetabular fractures: column fractures, transverse fractures, and wall fractures. Within this framework, acetabular fractures are classified into two broad categories: elementary or associated fractures. We will review the osseous anatomy of the pelvis and provide systematic approaches for reviewing both radiographs and CT scans to effectively evaluate the acetabulum. Although acetabular fracture classification may seem intimidating, the descriptions and distinctions discussed and shown in this article hopefully make the topic simpler to understand. Approach the task by recalling that there are only three basic types of acetabular fractures: column fractures (coronally oriented on CT images), transverse fractures (sagittally oriented on CT images), and wall fractures (obliquely oriented on CT images). We have provided systematic approaches for reviewing both conventional radiographs and CT scans to effectively assess the acetabulum. The clinical implications of the different fracture patterns have also been reviewed because it is critically important to include pertinent information for our clinical colleagues to provide the most efficient and timely clinical care.

Massive Broad Ligament Cellular Leiomyoma with Cystic Change: A Diagnostic Dilemma.

PubMed

Sharma, Preeti; Zaheer, Sufian; Yadav, Amit Kumar; Mandal, Ashish Kumar

2016-04-01

Leiomyomas are known to arise from uterus, but rarely from broad ligament. Further, cellular leiomyoma of broad ligament is the least common variant reported in literature. The diagnostic dilemma arises when leiomyomas undergo degenerative changes. This poses both clinical and radiological difficulty in differentiating with an ovarian tumour. We present an unusual case of a huge broad ligament mass measuring 29x19x09cm, mimicking an ovarian tumour both clinically and radiologically. Histopathology revealed cellular leiomyoma of broad ligament with cystic and myxoid degeneration hereby being the second case reported in literature. This case is being presented not only because of the rare incidence but also due to its diagnostic confusion with ovarian malignancy on clinical evaluation and radiological findings.

MIPPA: First Broad Changes to Medicare Part D Plan Operations.

PubMed

LeMasurier, Jean D; Edgar, Babette

2009-04-01

In July 2008, as part of broad Medicare reform, Congress passed the first major legislative changes to Medicare Part D since its enactment in 2003-the Medicare Improvements for Patients and Providers Act. This new legislation has significant implications for how Part D plans can market and enroll Medicare beneficiaries. The new legislation also strengthened beneficiary protections, expanded the low-income subsidy provisions originally included in Part D, and expanded Part D coverage. These changes have significant implications for the operation of Part D plans and can affect those involved in benefit design, including specialty pharmacy coverage. This article discusses the major changes that took effect on January 1, 2009, and have immediate implications for Part D plan sponsors, including Medicare Advantage plans and stand-alone prescription drug plans.

MIPPA: First Broad Changes to Medicare Part D Plan Operations

PubMed Central

LeMasurier, Jean D.; Edgar, Babette

2009-01-01

In July 2008, as part of broad Medicare reform, Congress passed the first major legislative changes to Medicare Part D since its enactment in 2003—the Medicare Improvements for Patients and Providers Act. This new legislation has significant implications for how Part D plans can market and enroll Medicare beneficiaries. The new legislation also strengthened beneficiary protections, expanded the low-income subsidy provisions originally included in Part D, and expanded Part D coverage. These changes have significant implications for the operation of Part D plans and can affect those involved in benefit design, including specialty pharmacy coverage. This article discusses the major changes that took effect on January 1, 2009, and have immediate implications for Part D plan sponsors, including Medicare Advantage plans and stand-alone prescription drug plans. PMID:25126279

Advances in the management of PML: focus on natalizumab.

PubMed

Fox, Robert

2011-11-01

Progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection of the central nervous system, occurs mainly in the setting of broad-based and selective immunosuppression. The immunomodulatory agent most often implicated in the development of PML is the monoclonal antibody natalizumab. Management of PML begins with risk stratification. Factors that predict the risk of PML are JC virus (JCV) antibody status, history of chemotherapy use, and cumulative exposure to natalizumab. The risk of natalizumab-related PML increases up to a duration of 36 months of therapy, after which the risk appears to level off. If suspicious for PML, the use of a sensitive JCV polymerase chain reaction assay permits early diagnosis. Immune reconstitution represents the mainstay of treatment for PML. With rapid reversal of immunosuppression followed by immunologic recovery, almost all patients suffer clinical deterioration termed immune reconstitution inflammatory syndrome (IRIS). High-dose corticosteroids are often recommended if a clinical and imaging syndrome resembling IRIS develops after immune restoration.

Legal aspects of clinical ethics committees.

PubMed

Hendrick, J

2001-04-01

In an increasingly litigious society where ritual demands for accountability and "taking responsibility" are now commonplace, it is not surprising that members of clinical ethics committees (CECs) are becoming more aware of their potential legal liability. Yet the vulnerability of committee members to legal action is difficult to assess with any certainty. This is because the CECs which have been set up in the UK are--if the American experience is followed--likely to vary significantly in terms of their functions, procedures, composition, structures and authority. As a consequence it is difficult to generalize about the legal implications. Nevertheless, despite these difficulties this article will outline the broad legal principles governing the potential liability of committee members. It will also consider the relationship between CECs and the courts. It begins, however, with a brief analysis of the relationship between ethics and law in committee deliberations, and in particular of the role of law and legal expertise on CECs.

Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents

PubMed Central

Botkin, Jeffrey R.; Belmont, John W.; Berg, Jonathan S.; Berkman, Benjamin E.; Bombard, Yvonne; Holm, Ingrid A.; Levy, Howard P.; Ormond, Kelly E.; Saal, Howard M.; Spinner, Nancy B.; Wilfond, Benjamin S.; McInerney, Joseph D.

2015-01-01

In 1995, the American Society of Human Genetics (ASHG) and American College of Medical Genetics and Genomics (ACMG) jointly published a statement on genetic testing in children and adolescents. In the past 20 years, much has changed in the field of genetics, including the development of powerful new technologies, new data from genetic research on children and adolescents, and substantial clinical experience. This statement represents current opinion by the ASHG on the ethical, legal, and social issues concerning genetic testing in children. These recommendations are relevant to families, clinicians, and investigators. After a brief review of the 1995 statement and major changes in genetic technologies in recent years, this statement offers points to consider on a broad range of test technologies and their applications in clinical medicine and research. Recommendations are also made for record and communication issues in this domain and for professional education. PMID:26140447

External validity and anchoring heuristics: application of DUNDRUM-1 to secure service gatekeeping in South Wales.

PubMed

Lawrence, Daniel; Davies, Tracey-Lee; Bagshaw, Ruth; Hewlett, Paul; Taylor, Pamela; Watt, Andrew

2018-02-01

Aims and method Structured clinical judgement tools provide scope for the standardisation of forensic service gatekeeping and also allow identification of heuristics in this decision process. The DUNDRUM-1 triage tool was completed retrospectively for 121 first-time referrals to forensic services in South Wales. Fifty were admitted to medium security, 49 to low security and 22 remained in open conditions. DUNDRUM-1 total scores differed appropriately between different levels of security. However, regression revealed heuristic anchoring on the 'legal process' and 'immediacy of risk due to mental disorder' items. Clinical implications Patient placement was broadly aligned with DUNDRUM-1 recommendations. However, not all triage items informed gatekeeping decisions. It remains to be seen whether decisions anchored in this way are effective. Declaration of interest Dr Mark Freestone gave permission for AUC values from Freestone et al. (2015) to be presented here for comparison.

Clinical Perspectives on Lupus Genetics: Advances and Opportunities

PubMed Central

James, Judith A.

2014-01-01

Synopsis In recent years, genome wide association studies have led to an explosion in the identification of regions containing confirmed genetic risk variants within complex human diseases, for example in systemic lupus erythematosus (SLE). Many of these strongest SLE genetic associations can be divided into groups based upon their potential roles in different processes implicated in lupus pathogenesis, including ubiquitination (a process of marking proteins for degradation), DNA degradation, innate immunity, cellular immunity (B cell, T cell, neutrophil, monocytes), lymphocyte development, and antigen presentation. Recent advances have also demonstrated several genetic associations with SLE subphenotypes and subcriteria, such as autoantibody production, lupus nephritis, serositis, and arthritis. Despite the broad range of lupus genetic studies to date, many areas for further exploration remain to move lupus genetic studies toward clinically informative endpoints, such as identifying individuals at the greatest risk of end-organ damage, early mortality or poor response to a specific therapeutic regimen. PMID:25034154

Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

PubMed Central

Bleeker, Jonathan S.; Hogan, William J.

2011-01-01

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera. PMID:22084665

Negotiating identity at the intersection of paediatric and genetic medicine: the parent as facilitator, narrator and patient.

PubMed

Dimond, Rebecca

2014-01-01

This article identifies a significant transformation in the role and identity of parents accompanying their child to clinic. This shift is a product of the intersection between paediatric and genetic medicine, where parents play a critical role in providing information about their child, family and ultimately, about themselves. To provide a context for this matrix, two broad areas of sociological inquiry are highlighted. The first is explanations of the role a parent plays in paediatric medicine and the second is the diagnostic process in paediatric genetics and the implications for parent and child identities. Drawing from an ethnographic study of clinical consultations, attention is paid to the changing role of parenthood and the extended role of patienthood in paediatric genetic medicine. © 2013 The Author. Sociology of Health & Illness © 2013 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.

Implications of the Definition of an Episode of Care Used in the Comprehensive Care for Joint Replacement Model.

PubMed

Ellimoottil, Chad; Ryan, Andrew M; Hou, Hechuan; Dupree, James M; Hallstrom, Brian; Miller, David C

2017-01-01

Under the Comprehensive Care for Joint Replacement (CJR) model, hospitals are held accountable for nearly all Medicare payments that occur during the initial hospitalization until 90 days after hospital discharge (ie, the episode of care). It is not known whether unrelated expenditures resulting from this "broad" definition of an episode of care will affect participating hospitals' average episode-of-care payments. To compare the CJR program's broad definition of an episode of care with a clinically narrow definition of an episode of care. We identified Medicare claims for 23 251 patients in Michigan who were Medicare beneficiaries and who underwent joint replacement during the period from 2011 through 2013 at hospitals located in metropolitan statistical areas. Using specifications from the CJR model and the clinically narrow Hospital Compare payment measure, we constructed episodes of care and calculated 90-day episode payments. We then compared hospitals' average 90-day episode payments using the 2 definitions of an episode of care and fit linear regression models to understand whether payment differences were associated with specific hospital characteristics (average Centers for Medicare & Medicaid Services-hierarchical condition categories risk score, rural hospital status, joint replacement volume, percentage of Medicaid discharges, teaching hospital status, number of beds, percentage of joint replacements performed on African American patients, and median income of the hospital's county). We performed analyses from July 1 through October 1, 2015. The correlation and difference between average 90-day episode payments using the broad definition of an episode of care in the CJR model and the clinically narrow Hospital Compare definition of an episode of care. We identified 23 251 joint replacements (ie, episodes of care). The 90-day episode payments using the broad definition of the CJR model ranged from $17 349 to $29 465 (mean [SD] payment, $22 122 [$2600]). Episode payments were slightly lower (mean payment, $21 670) when the Hospital Compare definition was used. Both methods were strongly correlated (r = 0.99, P < .001). The average payment difference between these 2 types of episodes of care was small (mean [SD], $452 [$177]; range, $73-$1006). In our multivariable analysis, we found that the hospital characteristics examined had a minimal impact or no impact on the payment differential. The average 90-day episode payments determined by both definitions of an episode of care were strongly correlated, and there was a small payment differential for most hospitals. In the context of joint replacement bundled payments, these data suggest that hospital performance will be consistent whether a broad or clinically narrow definition of an episode of care is used.

Attachment and Chronic Pain in Children and Adolescents

PubMed Central

Donnelly, Theresa J.; Jaaniste, Tiina

2016-01-01

Although attachment theory is not new, its theoretical implications for the pediatric chronic pain context have not been thoroughly considered, and the empirical implications and potential clinical applications are worth exploring. The attachment framework broadly focuses on interactions between a child’s developing self-regulatory systems and their caregiver’s responses. These interactions are believed to create a template for how individuals will relate to others in the future, and may help account for normative and pathological patterns of emotions and behavior throughout life. This review outlines relevant aspects of the attachment framework to the pediatric chronic pain context. The theoretical and empirical literature is reviewed regarding the potential role of attachment-based constructs such as vulnerability and maintaining factors of pediatric chronic pain. The nature and targets of attachment-based pediatric interventions are considered, with particular focus on relevance for the pediatric chronic pain context. The potential role of attachment style in the transition from acute to chronic pain is considered, with further research directions outlined. PMID:27792141

Targeting the hallmarks of cancer with therapy-induced endoplasmic reticulum (ER) stress

PubMed Central

Garg, Abhishek D; Maes, Hannelore; van Vliet, Alexander R; Agostinis, Patrizia

2015-01-01

The endoplasmic reticulum (ER) is at the center of a number of vital cellular processes such as cell growth, death, and differentiation, crosstalk with immune or stromal cells, and maintenance of proteostasis or homeostasis, and ER functions have implications for various pathologies including cancer. Recently, a number of major hallmarks of cancer have been delineated that are expected to facilitate the development of anticancer therapies. However, therapeutic induction of ER stress as a strategy to broadly target multiple hallmarks of cancer has been seldom discussed despite the fact that several primary or secondary ER stress-inducing therapies have been found to exhibit positive clinical activity in cancer patients. In the present review we provide a brief historical overview of the major discoveries and milestones in the field of ER stress biology with important implications for anticancer therapy. Furthermore, we comprehensively discuss possible strategies enabling the targeting of multiple hallmarks of cancer with therapy-induced ER stress. PMID:27308392

First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy

PubMed Central

Sen, Malabika; Thomas, Sufi. M.; Kim, Seungwon; Yeh, Joanne I.; Ferris, Robert L.; Johnson, Jonas T.; Duvvuri, Umamaheswar; Lee, Jessica; Sahu, Nivedita; Joyce, Sonali; Freilino, Maria L.; Shi, Haibin; Li, Changyou; Ly, Danith; Rapireddy, Srinivas; Etter, Jonathan P.; Li, Pui-Kai; Wang, Lin; Chiosea, Simion; Seethala, Raja R.; Gooding, William. E.; Chen, Xiaomin; Kaminski, Naftali; Pandit, Kusum; Johnson, Daniel. E.; Grandis, Jennifer R.

2013-01-01

Despite evidence implicating transcription factors, including STAT3, in oncogenesis, these proteins have been regarded as “undruggable”. We developed a decoy targeting STAT3 and performed a phase 0 trial. Expression levels of STAT3 target genes were decreased in the head and neck cancers following injection with the STAT3 decoy compared with tumors receiving saline control. Decoys have not been amenable to systemic administration due to instability. To overcome this barrier, we linked the oligonucleotide strands using hexa-ethyleneglycol spacers. This cyclic STAT3 decoy bound with high affinity to STAT3 protein, reduced cellular viability, and suppressed STAT3 target gene expression in cancer cells. Intravenous injection of the cyclic STAT3 decoy inhibited xenograft growth and downregulated STAT3 target genes in the tumors. These results provide the first demonstration of a successful strategy to inhibit tumor STAT3 signaling via systemic administration of a selective STAT3 inhibitor, thereby paving the way for broad clinical development. PMID:22719020

Are nutrition messages lost in transmission? Assessing the quality and consistency of diabetes guideline recommendations on the delivery of nutrition therapy.

PubMed

Hale, Kelli; Capra, Sandra; Bauer, Judy

2016-12-01

To provide an overview of (1) the consistency of Type 2 Diabetes Clinical Practice Guidelines recommendations on the delivery of nutrition therapy and (2) Clinical Practice Guideline quality. Large international clinical practice guideline repositories, diabetes organisation websites, and electronic databases (Pubmed, Scopus), were searched to identify Clinical Practice Guidelines for adults with type 2 diabetes published 2005 to August 2014. Recommendations on the delivery of nutrition therapy were extracted and inductive content analysis was used to analyse consistency. Two researchers independently assessed guideline quality using the AGREE II tool. Nine topics were identified from the recommendations. Overall the consistency of the recommendations was related to guideline type. Compared with nutrition-specific guidelines, the broad ones had a broader focus and included more patient-focused recommendations. The ten Clinical Practice Guidelines assessed included six broad guidelines and four nutrition specific guidelines. Based on AGREE II analysis, the broad guidelines were higher quality than nutrition-specific ones. Broad Clinical Practice Guidelines were higher quality and included more patient-focused recommendations than nutrition-specific ones. Our findings suggest a need for nutrition-specific guidelines to be modified to include greater patient-focus, or for practitioners delivering nutrition therapy to adopt broad Clinical Practice Guidelines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV.

PubMed

Uher, Rudolf; Payne, Jennifer L; Pavlova, Barbara; Perlis, Roy H

2014-06-01

The changes in diagnostic criteria for major depressive disorder (MDD) from the fourth to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) may appear small but have important consequences for how the diagnosis is used. In DSM-5, MDD is part of the new "Depressive disorders" section, which is separate from "Bipolar disorders", marking a division in what had been known as "Mood disorders". A small wording change has expanded the core mood criterion to include hopelessness, potentially broadening the diagnosis. The replacement of an operationalized bereavement exclusion with a call for clinical judgment in distinguishing normal reactions to significant loss from a disorder in need of clinical attention makes the diagnosis less objective and complicates investigations of the relationship between adversity and depression. A new persistent depressive disorder category is intended to encompass both dysthymia and chronic depression, but its relationship to MDD is ambiguous with conflicting statements on whether the two diagnoses should be concurrent if both sets of criteria are fulfilled. Clarification is also needed on whether MDD can be concurrent with the new broad "other specified bipolar and related disorders". New specifiers of MDD "with anxious distress" and "with mixed features" allow characterization of additional symptoms. The specifier "with perinatal onset" expands on the DSM-IV "postnatal onset" to include onset during pregnancy. We review the changes in MDD definition, provide guidance on their implementation and discuss their implications for clinical practice and research. © 2013 Wiley Periodicals, Inc.

Religion, assessment and the problem of 'normative uncertainty' for mental health student nurses: a critical incident-informed qualitative interview study.

PubMed

Bassett, A M; Baker, C; Cross, S

2015-10-01

There is limited research around how mental health (MH) student nurses interpret and differentiate between people's religious and cultural beliefs and the existence of psychopathological symptomatology and experiences. Here we focus on one cultural issue that arose from research exploring how MH student nurses approach and interpret religion and culture in their practice - that is, the difficulties in determining the clinical significance of the religious beliefs and experiences expressed by the people they care for. While problems with establishing the cultural boundaries of normality in clinical assessments are an important area of debate in cultural psychiatry, it remains a peripheral issue in MH nurse education. An anthropologically informed qualitative research design underpinned 'critical incident' (CI)-focused ethnographic interviews with 36 second and third-year MH nursing field students and seven undergraduate MH branch lecturers. Follow up focus groups were also carried out. Interview transcripts were subject to thematic analysis. Four subthemes were identified under the broad theme of the clinical significance of religious-type expression and experience: (1) identifying the difference between delusions and religious belief; (2) identifying whether an experience was hallucination or religious experience; (3) the clinical implications of such challenges; and (4) applying religion-specific knowledge. There are clinical implications that may result from the difficulties with assessing the clinical significance of religious beliefs and experiences, identified in both our research and within international cultural psychiatry literature and research. Misinterpretation and therefore wrongly assessing someone's experience as pathological is a significant concern. It is suggested that CI analysis could be adapted to help nurses, nursing students and nurse educators recognize the religious dimensions of mental distress, particularly those that then potentially impact upon the accuracy and person centeredness of clinical assessment. Further research is proposed to investigate the clinical assessment and training needs of nurses in the area of religion and mental distress. © 2015 John Wiley & Sons Ltd.

Cancer-Specific Stress and Mood Disturbance: Implications for Symptom Perception, Quality of Life, and Immune Response in Women Shortly after Diagnosis of Breast Cancer

PubMed Central

Kang, Duck-Hee; Park, Na-Jin; McArdle, Traci

2012-01-01

Purpose. To determine the levels of cancer-specific stress and mood disturbance in women shortly after diagnosis of breast cancer and to assess their associations with symptom perception, quality of life, and immune response. Design. Descriptive and correlational. Sample and Setting. One hundred women with newly diagnosed breast cancer were recruited from interdisciplinary breast clinics. Methods. Baseline data were collected using standardized questionnaires and established bioassay prior to the initiation of cancer adjuvant therapy. Blood samples were collected about the same time of day. Results. High cancer-specific stress was significantly correlated with high mood disturbance, which, in turn, was correlated with high symptom perception, poor quality of life, and an immune profile indicating high neutrophils and low lymphocytes. Conclusions. High cancer-specific stress and related mood disturbance show extensive negative relationships with multiple behavioral, clinical, and biological factors. Implications for Nursing. Routine screening for cancer-related stress and mood disturbance should be incorporated into nursing practice for all patients diagnosed with cancer. Given broad negative associations with other biobehavioral factors, early identification of patients at risk and provision and evaluation of stress and mood management programs may have a beneficial effect on subsequent health outcomes over time. PMID:23316388

Characterization of a multi-module tunable EC-QCL system for mid-infrared biofluid spectroscopy for hospital use and personalized diabetes technology

NASA Astrophysics Data System (ADS)

Grafen, M.; Nalpantidis, K.; Ostendorf, A.; Ihrig, D.; Heise, H. M.

2016-03-01

Blood glucose monitoring systems are important point-of-care devices for the hospital and personalised diabetes technology. FTIR-spectrometers have been successfully employed for the development of continuous bed-side monitoring systems in combination with micro-dialysis. For implementation in miniaturised portable systems, external-cavity quantum cascade lasers (EC-QCL) are suited. An ultra-broadly tunable pulsed EC-QCL system, covering a spectral range from 1920 to 780 cm-1, has been characterised with regard to the spectral emission profiles and wavenumber scale accuracy. The measurement of glucose in aqueous solution is presented and problems with signal linearity using Peltier-cooled MCT-detectors are discussed. The use of larger optical sample pathlengths for attenuating the laser power in transmission measurements has recently been suggested and implemented, but implications for broad mid-infrared measurements have now been investigated. The utilization of discrete wavenumber variables as an alternative for sweep-tune measurements has also been studied and sparse multivariate calibration models intended for clinical chemistry applications are described for glucose and lactate.

Dissecting disease entities out of the broad spectrum of bipolar-disorders.

PubMed

Levine, Joseph; Toker, Lilach; Agam, Galila

2018-01-01

The etiopathology of bipolar disorders is yet unraveled and new avenues should be pursued. One such avenue may be based on the assumption that the bipolar broad spectrum includes, among others, an array of rare medical disease entities. Towards this aim we propose a dissecting approach based on a search for rare medical diseases with known etiopathology which also exhibit bipolar disorders symptomatology. We further suggest that the etiopathologic mechanisms underlying such rare medical diseases may also underlie a rare variant of bipolar disorder. Such an assumption may be further reinforced if both the rare medical disease and its bipolar clinical phenotype demonstrate a] a similar mode of inheritance (i.e, autosomal dominant); b] brain involvement; and c] data implicating that the etiopathological mechanisms underlying the rare diseases affect biological processes reported to be associated with bipolar disorders and their treatment. We exemplify our suggested approach by a rare case of autosomal dominant leucodystrophy, a disease entity exhibiting nuclear lamin B1 pathology also presenting bipolar symptomatology. Copyright © 2017 Elsevier B.V. All rights reserved.

The Marriage Checkup: Increasing Access to Marital Health Care

PubMed Central

Morrill, Melinda

2016-01-01

Despite the ongoing prevalence of marital distress, very few couples seek therapy. Researchers and clinicians have increasingly been calling for innovative interventions that can reach a larger number of untreated couples. Based on a motivational marital health model, the Marriage Checkup (MC) was designed to attract couples who are unlikely to seek traditional tertiary therapy. The objective of the MC is to promote marital health for as broad of a population of couples as possible, much like regular physical health checkups. This first paper from the largest MC study to date examines whether the MC engaged previously unreached couples who might benefit from intervention. Interview and survey data suggested that the MC attracted couples across the distress continuum and was perceived by couples as more accessible than traditional therapy. Notably, the MC attracted a substantial number of couples who had not previously participated in marital interventions. The motivational health checkup model appeared to encourage a broad range of couples who might not have otherwise sought relationship services to deliberately take care of their marital health. Clinical implications are discussed. PMID:22145720

Coupled plasma filtration adsorption: rationale, technical development and early clinical experience.

PubMed

Ronco, Claudio; Brendolan, Alessandra; d'Intini, Vincenzo; Ricci, Zaccaria; Wratten, Mary Lou; Bellomo, Rinaldo

2003-01-01

The adjuvant treatment of sepsis remains a major therapeutic challenge. Blood purification is theoretically appealing if the humoral theory of sepsis is accepted as the basis for intervention. In this setting, blood purification would provide a broad-based restoration of humoral homeostasis thereby avoiding both excessive inflammation and counterinflammation. Several techniques of blood purification have been tried or are under active investigation. One of these is the so-called coupled plasma filtration adsorption (CPFA). CPFA is a novel extracorporeal blood purification therapy aimed at nonselectively reducing the circulating levels and activities of both pro- and anti-inflammatory mediators during sepsis and multiorgan failure. In vitro studies have shown CPFA to be effective in binding a broad range of such mediators proving its technical efficacy. Subsequent animal models have shown a beneficial effect on survival in endotoxemia. These studies have provided the necessary technical developments and biologic rationale for initial human studies. Two phase I/IIa clinical studies have now been performed. Both studies have shown that CPFA improves blood pressure and restores immune function in patients with severe sepsis and multiorgan dysfunction. In this article, we will discuss some of the basic principles involved in sorbent technology, and how these may contribute to treatment efficacy, review animal experiments with CPFA and finally discuss the results of recent human studies and their implications. Copyright 2003 S. Karger AG, Basel

The Joint Structure of DSM–IV Axis I and Axis II Disorders

PubMed Central

Røysamb, Espen; Tambs, Kristian; Ørstavik, Ragnhild E.; Torgersen, Svenn; Kendler, Kenneth S.; Neale, Michael C.; Aggen, Steven H.; Reichborn-Kjennerud, Ted

2011-01-01

The Diagnostic and Statistical Manual (4th ed. [DSM–IV]; American Psychiatric Association, 1994) distinction between clinical disorders on Axis I and personality disorders on Axis II has become increasingly controversial. Although substantial comorbidity between axes has been demonstrated, the structure of the liability factors underlying these two groups of disorders is poorly understood. The aim of this study was to determine the latent factor structure of a broad set of common Axis I disorders and all Axis II personality disorders and thereby to identify clusters of disorders and account for comorbidity within and between axes. Data were collected in Norway, through a population-based interview study (N = 2,794 young adult twins). Axis I and Axis II disorders were assessed with the Composite International Diagnostic Interview (CIDI) and the Structured Interview for DSM–IV Personality (SIDP–IV), respectively. Exploratory and confirmatory factor analyses were used to investigate the underlying structure of 25 disorders. A four-factor model fit the data well, suggesting a distinction between clinical and personality disorders as well as a distinction between broad groups of internalizing and externalizing disorders. The location of some disorders was not consistent with the DSM–IV classification; antisocial personality disorder belonged primarily to the Axis I externalizing spectrum, dysthymia appeared as a personality disorder, and borderline personality disorder appeared in an interspectral position. The findings have implications for a meta-structure for the DSM. PMID:21319931

Surgical Pathology of Gastrointestinal Stromal Tumors: Practical Implications of Morphologic and Molecular Heterogeneity for Precision Medicine.

PubMed

Charville, Gregory W; Longacre, Teri A

2017-11-01

Gastrointestinal stromal tumor (GIST), the most common mesenchymal neoplasm of the gastrointestinal tract, exhibits diverse histologic and clinical manifestations. With its putative origin in the gastrointestinal pacemaker cell of Cajal, GIST can arise in association with any portion of the tubular gastrointestinal tract. Morphologically, GISTs are classified as spindled or epithelioid, though each of these subtypes encompasses a broad spectrum of microscopic appearances, many of which mimic other histologic entities. Despite this morphologic ambiguity, the diagnosis of GIST is aided in many cases by immunohistochemical detection of KIT (CD117) or DOG1 expression. The natural history of GIST ranges from that of a tumor cured by surgical resection to that of a locally advanced or even widely metastatic, and ultimately fatal, disease. This clinicopathologic heterogeneity is paralleled by an underlying molecular diversity: the majority of GISTs are associated with spontaneous activating mutations in KIT, PDGFRA, or BRAF, while additional subsets are driven by genetic lesions-often inherited-of NF1 or components of the succinate dehydrogenase enzymatic complex. Specific gene mutations correlate with particular anatomic or morphologic characteristics and, in turn, with distinct clinical behaviors. Therefore, prognostication and treatment are increasingly dictated not only by morphologic clues, but also by accompanying molecular genetic features. In this review, we provide a comprehensive description of the heterogenous molecular underpinnings of GIST, including implications for the practicing pathologist with regard to morphologic identification, immunohistochemical diagnosis, and clinical management.

New Constraints for X-ray Reprocessing Around Supermassive Black Holes: Near and Far with State-of-the-Art Multi-Mission Modeling

NASA Astrophysics Data System (ADS)

Tzanavaris, Panayiotis

Fluorescent Fe K emission from neutral matter in AGN spectracan arise in the accretion disk around the centralsupermassive black hole [SMBH] ("broad" line) and/or in distant matter ("narrow"line). If it is broad, it provides a unique windowto the strong gravity SMBH regime, including information on SMBH spin;if it is narrow, it probesthe distant reprocessor, likely a clumpy torus. We will use broadband X-ray data from four NASA X-ray missionsfor 45 nearby AGNs, and 1. Assess whether any known "broad" relativistic lines can be modeledas "narrow"instead, by means of self-consistent modeling of fluorescence,direct, and scattered continua; 2. Measure absorbing column densities both in and out of the line of sight; 3. Bootstrap measures of intrinsic bolometric AGN luminosity, with X-ray and optical data. This work will provide updated results on a) black hole spin, with implications on AGN jet power and accretion history; b) the census of highly-obscured (Compton thick) vs. Compton thin AGNs, with implications on models of the Cosmic X-ray Background; c) calibrations of Fe K line, X-ray intrinsic continuum, [OIII] and [OIV] luminosities as measures of intrinsc bolometric AGN luminosity, with implications on AGN feedback and galaxy evolution. Key in our approach is a physically based, self-consistent modeling of the narrow line, with finite column density in and out of the line of sight, and the latest relativistic modeling of the broad line.

Cystic mass of the floor of the mouth

PubMed Central

Lucena-Rivero, Elizabeth-Daniela; Brunet-Garcia, Laia; Faubel-Serra, Marta

2018-01-01

Background Epidermoid and dermoid cysts in the oral cavity are relatively uncommon lesions of developmental origin. They often remain asymptomatic for years until they grow enough to interfere with speech, deglutition and less often with breathing which can pose a critical risk to the airway and require immediate surgery. Case description A case of an epidermoid cyst of the floor of the mouth affecting a 37-year-old man is presented; this lesion was surgically enucleated with an intraoral approach. Patient did well postoperatively and there was no evidence of recurrence up to 2 years of follow up. Clinical implications Floor of the mouth is a challenging site for the diagnosis of a broad variety of lesions which the surgeon should be aware. Depending on the anatomical relation to the muscles of the floor of the mouth dermoid cysts are classified as supramylohyoid or inframylohyoid, and they will both have different clinical and radiological features. This article also includes literature review about the etiopathological, clinical, radiological and histological features, the differential diagnosis and its treatment. Key words:Epidermoid cyst, dermoid cyst, floor of mouth. PMID:29721231

The Need to Apply Medical Device Informatics in Developing Standards for Safe Interoperable Medical Systems.

PubMed

Weininger, Sandy; Jaffe, Michael B; Goldman, Julian M

2017-01-01

Medical device and health information technology systems are increasingly interdependent with users demanding increased interoperability. Related safety standards must be developed taking into account these systems' perspective. In this article, we describe the current development of medical device standards and the need for these standards to address medical device informatics. Medical device information should be gathered from a broad range of clinical scenarios to lay the foundation for safe medical device interoperability. Five clinical examples show how medical device informatics principles, if applied in the development of medical device standards, could help facilitate the development of safe interoperable medical device systems. These examples illustrate the clinical implications of the failure to capture important signals and device attributes. We provide recommendations relating to the coordination between historically separate standards development groups, some of which focus on safety and effectiveness and others focus on health informatics. We identify the need for a shared understanding among stakeholders and describe organizational structures to promote cooperation such that device-to-device interactions and related safety information are considered during standards development.

The Need to Apply Medical Device Informatics in Developing Standards for Safe Interoperable Medical Systems

PubMed Central

Weininger, Sandy; Jaffe, Michael B.; Goldman, Julian M

2016-01-01

Medical device and health information technology systems are increasingly interdependent with users demanding increased interoperability. Related safety standards must be developed taking into account this systems perspective. In this article we describe the current development of medical device standards and the need for these standards to address medical device informatics. Medical device information should be gathered from a broad range of clinical scenarios to lay the foundation for safe medical device interoperability. Five clinical examples show how medical device informatics principles, if applied in the development of medical device standards, could help facilitate the development of safe interoperable medical device systems. These examples illustrate the clinical implications of the failure to capture important signals and device attributes. We provide recommendations relating to the coordination between historically separate standards development groups; some which focus on safety and effectiveness, and others that focus on health informatics. We identify the need for a shared understanding among stakeholders and describe organizational structures to promote cooperation such that device-to-device interactions and related safety information are considered during standards development. PMID:27584685

Oncolytic Polio Virotherapy of Cancer

PubMed Central

Brown, Michael C.; Dobrikova, Elena Y.; Dobrikov, Mikhail I.; Walton, Ross W.; Gemberling, Sarah L.; Nair, Smita K.; Desjardins, Annick; Sampson, John H.; Friedman, Henry S.; Friedman, Allan H.; Tyler, Douglas S.; Bigner, Darell D.; Gromeier, Matthias

2014-01-01

Recently, the century-old idea of targeting cancer with viruses (‘oncolytic viruses’) has come of age, with promise documented in early-stage and several late-stage clinical trials in a variety of cancers. While originally prized for their direct tumor cytotoxicity (‘oncolytic virotherapy’), recently, the pro-inflammatory and immunogenic effects of viral tumor infection (‘oncolytic immunotherapy’) have come into focus. Indeed, a capacity for eliciting broad, sustained anti-neoplastic effects stemming from combined direct viral cytotoxicity, innate antiviral activation, stromal pro-inflammatory stimulation and recruitment of adaptive immune effector responses is the greatest asset of oncolytic viruses. However, it also is the source for enormous mechanistic complexity that must be considered for successful clinical translation. Due to fundamentally different relationships with their hosts (malignant or not), diverse replication strategies and distinct modes of tumor cytotoxicity/ killing, oncolytic viruses should not be referred to collectively. These agents must be evaluated based on their individual merits. In this review, we highlight key mechanistic principles of cancer treatment with the polio:rhinovirus chimera PVSRIPO, and their implications for oncolytic immunotherapy in the clinic. PMID:24939611

Joint Estimation of Effective Brain Wave Activation Modes Using EEG/MEG Sensor Arrays and Multimodal MRI Volumes.

PubMed

Galinsky, Vitaly L; Martinez, Antigona; Paulus, Martin P; Frank, Lawrence R

2018-04-13

In this letter, we present a new method for integration of sensor-based multifrequency bands of electroencephalography and magnetoencephalography data sets into a voxel-based structural-temporal magnetic resonance imaging analysis by utilizing the general joint estimation using entropy regularization (JESTER) framework. This allows enhancement of the spatial-temporal localization of brain function and the ability to relate it to morphological features and structural connectivity. This method has broad implications for both basic neuroscience research and clinical neuroscience focused on identifying disease-relevant biomarkers by enhancing the spatial-temporal resolution of the estimates derived from current neuroimaging modalities, thereby providing a better picture of the normal human brain in basic neuroimaging experiments and variations associated with disease states.

The Daniel K. Inouye College of Pharmacy Scripts

PubMed Central

Ciarleglio, Anita E; Ma, Carolyn

2017-01-01

The precision medicine initiative brought forth by President Barack Obama in 2015 is an important step on the journey to truly personalized medicine. A broad knowledge and understanding of the implications of the pharmacogenomic literature will be critical to the achievement of this goal. While a great amount of data has been published in the areas of pharmacogenomics and pharmacogenetics, there are still relatively few instances in which the need for clinical intervention can be stated without doubt, and which are widely accepted and practiced by the medical community. As our knowledge base rapidly expands, issues such as insurance reimbursement for genetic testing and education of the health care workforce will be paramount to achieving the goal of precision medicine for all patients. PMID:28900583

A model linking clinical workforce skill mix planning to health and health care dynamics.

PubMed

Masnick, Keith; McDonnell, Geoff

2010-04-30

In an attempt to devise a simpler computable tool to assist workforce planners in determining what might be an appropriate mix of health service skills, our discussion led us to consider the implications of skill mixing and workforce composition beyond the 'stock and flow' approach of much workforce planning activity. Taking a dynamic systems approach, we were able to address the interactions, delays and feedbacks that influence the balance between the major components of health and health care. We linked clinical workforce requirements to clinical workforce workload, taking into account the requisite facilities, technologies, other material resources and their funding to support clinical care microsystems; gave recognition to productivity and quality issues; took cognisance of policies, governance and power concerns in the establishment and operation of the health care system; and, going back to the individual, gave due attention to personal behaviour and biology within the socio-political family environment. We have produced the broad endogenous systems model of health and health care which will enable human resource planners to operate within real world variables. We are now considering the development of simple, computable national versions of this model.

Resilients, overcontrollers and undercontrollers: A systematic review of the utility of a personality typology method in understanding adult mental health problems.

PubMed

Bohane, Laura; Maguire, Nick; Richardson, Thomas

2017-11-01

The person-centred typological approach to personality makes the distinction between overcontrolled and undercontrolled personality types. This review systematically searched for research on the utility of these personality types in adult mental health. A total of 43 papers were included, which were divided broadly into cross-sectional studies, longitudinal studies and studies with clinical populations. Three personality types have been largely replicated in both normal and clinical populations: resilients, overcontrollers and undercontrollers. These types show utility in predicting long-term functioning and mental health, understanding heterogeneous personalities within clinical subgroups and have implications for treatment. Some disagreement on the number of personality types deemed replicable across samples and differing methodologies do exist, with some finding a dimensional approach to personality to have greater predictive utility. These personality types have been shown to be important in a number of mental health problems such as eating disorders, which may prove helpful in developing new psychological interventions. These studies point to the importance of overcontrolled personality types as well as undercontrolled in mental health. More research is needed with a greater range of clinical populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Psychometric properties of the Dresden Body Image Questionnaire: A multiple-group confirmatory factor analysis across sex and age in a Dutch non-clinical sample

PubMed Central

Scheffers, Mia; van Duijn, Marijtje A. J.; Bosscher, Ruud J.; Wiersma, Durk; Schoevers, Robert A.; van Busschbach, Jooske T.

2017-01-01

Background Body image has implications for psychosocial functioning and quality of life and its disturbance is reported in a broad range of psychiatric disorders. In view of the lack of instruments in Dutch measuring body image as a broad concept, we set out to make an instrument available that reflects the multidimensional character of this construct by including more dimensions than physical appearance. The Dresden Körperbildfragebogen (DBIQ, Dresden Body Image Questionnaire) particularly served this purpose. The DBIQ consists of 35 items and five subscales: body acceptance, sexual fulfillment, physical contact, vitality, and self-aggrandizement. The main objective of the present study was to evaluate the psychometric properties of the Dutch translation of the Dresden Body Image Questionnaire (DBIQ-NL) in a non-clinical sample. Methods The psychometric properties of the DBIQ-NL were examined in a non-clinical sample of 988 respondents aged between 18 and 65. We investigated the subscales' internal consistency and test-retest reliability. In order to establish construct validity we evaluated the association with a related construct, body cathexis, and with indices of self-esteem and psychological wellbeing. The factor structure of the DBIQ-NL was examined via confirmatory factor analysis (CFA). The equivalence of the measurement model across sex and age was evaluated by multiplegroup confirmatory factor analyses. Results Confirmatory factor analyses showed a structure in accordance with the original scale, where model fit was improved significantly by moving one item to another subscale. Multiple group confirmatory factor analysis across sex and age demonstrated partial strong invariance. Internal consistency was good with little overlap between the subscales. Temporal reliability and construct validity were satisfactory. Conclusion Results indicate that the DBIQ-NL is a reliable and valid instrument for non-clinical subjects. This provides a sound basis for further investigation of the DBIQ-NL in a clinical sample. PMID:28746387

Distinctive Features of Schools in Multiple Deprived Communities in South Africa: Implications for Policy and Leadership

ERIC Educational Resources Information Center

Maringe, Felix; Masinire, Alfred; Nkambule, Thabisile

2015-01-01

Multiple deprivation affects a large proportion of schools in South Africa. The past 20 years of democracy have tended to focus on reforming education through curricula revision and a raft of redress-directed interventions, through the application of what we call a broad-brush policy approach. The paper argues that a broad-brush policy application…

Place-Related Identities through Texts: From Interdisciplinary Theory to Research Agenda

ERIC Educational Resources Information Center

Charlton, Emma; Wyse, Dominic; Hodges, Gabrielle Cliff; Nikolajeva, Maria; Pointon, Pam; Taylor, Liz

2011-01-01

The implications of the transdisciplinary spatial turn are attracting growing interest in a broad range of areas related to education. This paper draws on a methodology for interdisciplinary thinking in order to articulate a new theoretical configuration of place-related identity, and its implications for a research agenda. The new configuration…

Strengthening the Superintendent Pipeline and Professional Development Options. Implications from UCEA

ERIC Educational Resources Information Center

McCord, Bob

2009-01-01

The dramatic change over the past 20 years of the demographics, education and career trajectory of superintendents has significant implications for the nation's schools. Since 1923, the State of the American School Superintendency has documented the evolution of superintendents' careers and school district leadership more broadly. The most recent…

Internet Gaming Disorder as a formative construct: Implications for conceptualization and measurement.

PubMed

van Rooij, Antonius J; Van Looy, Jan; Billieux, Joël

2017-07-01

Some people have serious problems controlling their Internet and video game use. The DSM-5 now includes a proposal for 'Internet Gaming Disorder' (IGD) as a condition in need of further study. Various studies aim to validate the proposed diagnostic criteria for IGD and multiple new scales have been introduced that cover the suggested criteria. Using a structured approach, we demonstrate that IGD might be better interpreted as a formative construct, as opposed to the current practice of conceptualizing it as a reflective construct. Incorrectly approaching a formative construct as a reflective one causes serious problems in scale development, including: (i) incorrect reliance on item-to-total scale correlation to exclude items and incorrectly relying on indices of inter-item reliability that do not fit the measurement model (e.g., Cronbach's α); (ii) incorrect interpretation of composite or mean scores that assume all items are equal in contributing value to a sum score; and (iii) biased estimation of model parameters in statistical models. We show that these issues are impacting current validation efforts through two recent examples. A reinterpretation of IGD as a formative construct has broad consequences for current validation efforts and provides opportunities to reanalyze existing data. We discuss three broad implications for current research: (i) composite latent constructs should be defined and used in models; (ii) item exclusion and selection should not rely on item-to-total scale correlations; and (iii) existing definitions of IGD should be enriched further. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

PubMed Central

2015-01-01

Abstract Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid- and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686–729. PMID:25546574

Battery-free, wireless sensors for full-body pressure and temperature mapping.

PubMed

Han, Seungyong; Kim, Jeonghyun; Won, Sang Min; Ma, Yinji; Kang, Daeshik; Xie, Zhaoqian; Lee, Kyu-Tae; Chung, Ha Uk; Banks, Anthony; Min, Seunghwan; Heo, Seung Yun; Davies, Charles R; Lee, Jung Woo; Lee, Chi-Hwan; Kim, Bong Hoon; Li, Kan; Zhou, Yadong; Wei, Chen; Feng, Xue; Huang, Yonggang; Rogers, John A

2018-04-04

Thin, soft, skin-like sensors capable of precise, continuous measurements of physiological health have broad potential relevance to clinical health care. Use of sensors distributed over a wide area for full-body, spatiotemporal mapping of physiological processes would be a considerable advance for this field. We introduce materials, device designs, wireless power delivery and communication strategies, and overall system architectures for skin-like, battery-free sensors of temperature and pressure that can be used across the entire body. Combined experimental and theoretical investigations of the sensor operation and the modes for wireless addressing define the key features of these systems. Studies with human subjects in clinical sleep laboratories and in adjustable hospital beds demonstrate functionality of the sensors, with potential implications for monitoring of circadian cycles and mitigating risks for pressure-induced skin ulcers. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Immoral behaviour following brain damage: A review.

PubMed

Roberts, Stefanie; Henry, Julie D; Molenberghs, Pascal

2018-04-16

Despite the apparent sociability of human kind, immoral behaviour is ever present in society. The term 'immoral behaviour' represents a complex array of conduct, ranging from insensitivity to topics of conversation through to violent assault and murder. To better understand the neuroscience of immoral behaviour, this review investigates two clinical populations that commonly present with changes in moral behaviour - behavioural-variant frontotemporal dementia and acquired brain injuries. Based on evidence from these groups, it is argued that rather than a single underlying cause, immoral behaviour can result from three distinct types of cognitive failure: (1) problems understanding others; (2) difficulties controlling behaviour; or (3) deficits in the capacity to make appropriate emotional contributions. Each of these failures is associated with damage to different brain regions. A more nuanced approach to the neuroscience of immoral behaviour has important implications for our understanding of immoral behaviour in a wide range of clinical groups, as well as human society more broadly. © 2018 The British Psychological Society.

Integrity, standards, and QC-related issues with big data in pre-clinical drug discovery.

PubMed

Brothers, John F; Ung, Matthew; Escalante-Chong, Renan; Ross, Jermaine; Zhang, Jenny; Cha, Yoonjeong; Lysaght, Andrew; Funt, Jason; Kusko, Rebecca

2018-06-01

The tremendous expansion of data analytics and public and private big datasets presents an important opportunity for pre-clinical drug discovery and development. In the field of life sciences, the growth of genetic, genomic, transcriptomic and proteomic data is partly driven by a rapid decline in experimental costs as biotechnology improves throughput, scalability, and speed. Yet far too many researchers tend to underestimate the challenges and consequences involving data integrity and quality standards. Given the effect of data integrity on scientific interpretation, these issues have significant implications during preclinical drug development. We describe standardized approaches for maximizing the utility of publicly available or privately generated biological data and address some of the common pitfalls. We also discuss the increasing interest to integrate and interpret cross-platform data. Principles outlined here should serve as a useful broad guide for existing analytical practices and pipelines and as a tool for developing additional insights into therapeutics using big data. Copyright © 2018 Elsevier Inc. All rights reserved.

The skin as a window to the blood: Cutaneous manifestations of myeloid malignancies.

PubMed

Li, Alvin W; Yin, Emily S; Stahl, Maximilian; Kim, Tae Kon; Panse, Gauri; Zeidan, Amer M; Leventhal, Jonathan S

2017-11-01

Cutaneous manifestations of myeloid malignancies are common and have a broad range of presentations. These skin findings are classified as specific, due to direct infiltration by malignant hematopoietic cells, or non-specific. Early recognition and diagnosis can have significant clinical implications, as skin manifestations may be the first indication of underlying hematologic malignancy, can reflect the immune status and stage of disease, and cutaneous reactions may occur from conventional and targeted agents used to treat myeloid disease. In addition, infections with cutaneous involvement are common in immunocompromised patients with myeloid disease. Given the varying presentations, dermatologic findings associated with myeloid malignancies can pose diagnostic challenges for hematologists and dermatologists. In this clinical review intended for the practicing hematologist/oncologist, we discuss the presentation, diagnosis, treatment, and prognostic value of the most common cutaneous manifestations associated with myeloid malignancies using illustrative macro- and microscopic figures and with a special emphasis on practical considerations. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Specific Role of Childhood Abuse, Parental Bonding, and Family Functioning in Female Adolescents With Borderline Personality Disorder.

PubMed

Infurna, Maria Rita; Brunner, Romuald; Holz, Birger; Parzer, Peter; Giannone, Francesca; Reichl, Corinna; Fischer, Gloria; Resch, Franz; Kaess, Michael

2016-04-01

This study examined a broad variety of adverse childhood experiences in a consecutive sample of female adolescent inpatients with borderline personality disorder (BPD; n = 44) compared with a clinical control (CC; n = 47) group with mixed psychiatric diagnoses. BPD was diagnosed using a structured clinical interview; different dimensions of childhood adversity were assessed using the Childhood Experiences of Care and Abuse Questionnaire, the Parental Bonding Instrument, and the Family Assessment Device. A history of childhood adversity was significantly more common in patients with BPD than in the CC group. Using a multivariate model, sexual abuse (OR = 13.8), general family functioning (OR = 8.9), and low maternal care (OR = 7.6) were specific and independent predictors of adolescent BPD. The results increase our knowledge of the specific role of different dimensions of childhood adversity in adolescent BPD. They have important implications for prevention and early intervention as they highlight the need for specific strategies for involving the family.

Fusion peptides from oncogenic chimeric proteins as putative specific biomarkers of cancer.

PubMed

Conlon, Kevin P; Basrur, Venkatesha; Rolland, Delphine; Wolfe, Thomas; Nesvizhskii, Alexey I; MacCoss, Michael J; Lim, Megan S; Elenitoba-Johnson, Kojo S J

2013-10-01

Chromosomal translocations encoding chimeric fusion proteins constitute one of the most common mechanisms underlying oncogenic transformation in human cancer. Fusion peptides resulting from such oncogenic chimeric fusions, though unique to specific cancer subtypes, are unexplored as cancer biomarkers. Here we show, using an approach termed fusion peptide multiple reaction monitoring mass spectrometry, the direct identification of different cancer-specific fusion peptides arising from protein chimeras that are generated from the juxtaposition of heterologous genes fused by recurrent chromosomal translocations. Using fusion peptide multiple reaction monitoring mass spectrometry in a clinically relevant scenario, we demonstrate the specific, sensitive, and unambiguous detection of a specific diagnostic fusion peptide in clinical samples of anaplastic large cell lymphoma, but not in a diverse array of benign lymph nodes or other forms of primary malignant lymphomas and cancer-derived cell lines. Our studies highlight the utility of fusion peptides as cancer biomarkers and carry broad implications for the use of protein biomarkers in cancer detection and monitoring.

Iraq and Afghanistan Veterans: National Findings from VA Residential Treatment Programs

PubMed Central

Cook, Joan M.; Dinnen, Stephanie; O’Donnell, Casey; Bernardy, Nancy; Rosenheck, Robert; Desai, Rani

2013-01-01

A quality improvement effort was undertaken in Department of Veterans Affairs’ (VA) residential treatment programs for Posttraumatic Stress Disorder (PTSD) across the United States. Qualitative interviews were conducted with over 250 directors, providers, and staff during site visits of 38 programs. The aims of this report are to describe clinical issues and distinctive challenges in working with veterans from Iraq and Afghanistan and approaches to addressing their needs. Providers indicated that the most commonly reported problems were: acute PTSD symptomotology; other complex mental health symptom presentations; broad readjustment problems; and difficulty with time demands of and readiness for intensive treatment. Additional concerns included working with active duty personnel and mixing different eras in therapy. Programmatic solutions address structure (e.g., blended versus era-specific therapy), content (e.g., physical activity), and adaptations (e.g., inclusion of family; shortened length of stay). Clinical implications for VA managers and policy makers as well as non-VA health care systems and individual health care providers are noted. PMID:23458113

Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations

PubMed Central

Gilbert, Jessica R.; Symmonds, Mkael; Hanna, Michael G.; Dolan, Raymond J.; Friston, Karl J.; Moran, Rosalyn J.

2016-01-01

Clinical assessments of brain function rely upon visual inspection of electroencephalographic waveform abnormalities in tandem with functional magnetic resonance imaging. However, no current technology proffers in vivo assessments of activity at synapses, receptors and ion-channels, the basis of neuronal communication. Using dynamic causal modeling we compared electrophysiological responses from two patients with distinct monogenic ion channelopathies and a large cohort of healthy controls to demonstrate the feasibility of assaying synaptic-level channel communication non-invasively. Synaptic channel abnormality was identified in both patients (100% sensitivity) with assay specificity above 89%, furnishing estimates of neurotransmitter and voltage-gated ion throughput of sodium, calcium, chloride and potassium. This performance indicates a potential novel application as an adjunct for clinical assessments in neurological and psychiatric settings. More broadly, these findings indicate that biophysical models of synaptic channels can be estimated non-invasively, having important implications for advancing human neuroimaging to the level of non-invasive ion channel assays. PMID:26342528

Genome medicine: gene therapy for the millennium, 30 September-3 October 2001, Rome, Italy.

PubMed

Gruenert, D C; Novelli, G; Dallapiccola, B; Colosimo, A

2002-06-01

The recent surge of DNA sequence information resulting from the efforts of agencies interested in deciphering the human genetic code has facilitated technological developments that have been critical in the identification of genes associated with numerous disease pathologies. In addition, these efforts have opened the door to the opportunity to develop novel genetic therapies to treat a broad range of inherited disorders. Through a joint effort by the University of Vermont, the University of Rome, Tor Vergata, University of Rome, La Sapienza, and the CSS Mendel Institute, Rome, an international meeting, 'Genome Medicine: Gene Therapy for the Millennium' was organized. This meeting provided a forum for the discussion of scientific and clinical advances stimulated by the explosion of sequence information generated by the Human Genome Project and the implications these advances have for gene therapy. The meeting had six sessions that focused on the functional evaluation of specific genes via biochemical analysis and through animal models, the development of novel therapeutic strategies involving gene targeting, artificial chromsomes, DNA delivery systems and non-embryonic stem cells, and on the ethical and social implications of these advances.

Affective Traits in Schizophrenia and Schizotypy

PubMed Central

Horan, William P.; Blanchard, Jack J.; Clark, Lee Anna; Green, Michael F.

2008-01-01

This article reviews empirical studies of affective traits in individuals with schizophrenia spectrum disorders, population-based investigations of vulnerability to psychosis, and genetic and psychometric high-risk samples. The review focuses on studies that use self-report trait questionnaires to assess Negative Affectivity (NA) and Positive Affectivity (PA), which are conceptualized in contemporary models of personality as broad, temperamentally-based dispositions to experience corresponding emotional states. Individuals with schizophrenia report a pattern of stably elevated NA and low PA throughout the illness course. Among affected individuals, these traits are associated with variability in several clinically important features, including functional outcome, quality of life, and stress reactivity. Furthermore, evidence that elevated NA and low PA (particularly the facet of anhedonia) predict the development of psychosis and are detectable in high-risk samples suggests that these traits play a role in vulnerability to schizophrenia, though they are implicated in other forms of psychopathology as well. Results are discussed in terms of their implications for treatment, etiological models, and future research to advance the study of affective traits in schizophrenia and schizotypy. PMID:18667393

A Hierarchical Multiple-Level Approach to the Assessment of Interpersonal Relatedness and Self-Definition: Implications for Research, Clinical Practice, and DSM Planning.

PubMed

Luyten, Patrick; Blatt, Sidney J

2016-01-01

Extant research suggests there is considerable overlap between so-called 2-polarities models of personality development; that is, models that propose that personality development evolves through a dialectic synergistic interaction between 2 key developmental tasks across the life span-the development of self-definition on the one hand and of relatedness on the other. These models have attracted considerable research attention and play a central role in DSM planning. This article provides a researcher- and clinician-friendly guide to the assessment of these personality theories. We argue that current theoretical models focus on issues of relatedness and self-definition at different hierarchically organized levels of analysis; that is (a) at the level of broad personality features, (b) at the motivational level (i.e., the motivational processes underlying the development of these dimensions), and (c) at the level of underlying internal working models or cognitive affective schemas, and the specific interpersonal features and problems in which they are expressed. Implications for further research and DSM planning are outlined.

Interpersonal relatedness and self-definition in normal and disrupted personality development: retrospect and prospect.

PubMed

Luyten, Patrick; Blatt, Sidney J

2013-04-01

Two-polarities models of personality propose that personality development evolves through a dialectic synergistic interaction between two fundamental developmental psychological processes across the life span-the development of interpersonal relatedness on the one hand and of self-definition on the other. This article offers a broad review of extant research concerning these models, discusses their implications for psychology and psychiatry, and addresses future research perspectives deriving from these models. We first consider the implications of findings in this area for clinical research and practice. This is followed by a discussion of emerging research findings concerning the role of developmental, cross-cultural, evolutionary, and neurobiological factors influencing the development of these two fundamental personality dimensions. Taken together, this body of research suggests that theoretical formulations that focus on interpersonal relatedness and self-definition as central coordinates in personality development and psychopathology provide a comprehensive conceptual paradigm for future research in psychology and psychiatry exploring the interactions among neurobiological, psychological, and sociocultural factors in adaptive and disrupted personality development across the life span.

The Microbiome: a Revolution in Treatment for Rheumatic Diseases?

PubMed

Rosenbaum, James T; Asquith, Mark J

2016-10-01

The microbiome is the term that describes the microbial ecosystem that cohabits an organism such as humans. The microbiome has been implicated in a long list of immune-mediated diseases which include rheumatoid arthritis, ankylosing spondylitis, and even gout. The mechanisms to account for this effect are multiple. The clinical implications from observations on the microbiome and disease are broad. A growing number of microbiota constituents such as Prevotella copri, Porphyromonas gingivalis, and Collinsella have been correlated or causally related to rheumatic disease. The microbiome has a marked effect on the immune system. Our understanding of immune pathways modulated by the microbiota such as the induction of T helper 17 (Th17) cells and secretory immunoglobulin A (IgA) responses to segmented filamentous bacteria continues to expand. In addition to the gut microbiome, bacterial communities of other sites such as the mouth, lung, and skin have also been associated with the pathogenesis of rheumatic diseases. Strategies to alter the microbiome or to alter the immune activation from the microbiome might play a role in the future therapy for rheumatic diseases.

On the Assessment of Paramedic Competence: A Narrative Review with Practice Implications.

PubMed

Tavares, W; Boet, S

2016-02-01

Paramedicine is experiencing significant growth in scope of practice, autonomy, and role in the health care system. Despite clinical governance models, the degree to which paramedicine ultimately can be safe and effective will be dependent on the individuals the profession deems suited to practice. This creates an imperative for those responsible for these decisions to ensure that assessments of paramedic competence are indeed accurate, trustworthy, and defensible. The purpose of this study was to explore and synthesize relevant theoretical foundations and literature informing best practices in performance-based assessment (PBA) of competence, as it might be applied to paramedicine, for design or evaluation of assessment programs. A narrative review methodology was applied to focus intentionally, but broadly, on purpose relevant, theoretically derived research that could inform assessment protocols in paramedicine. Primary and secondary studies from a number of health professions that contributed to and informed best practices related to the assessment of paramedic clinical competence were included and synthesized. Multiple conceptual frameworks, psychometric requirements, and emerging lines of research are forwarded. Seventeen practice implications are derived to promote understanding as well as best practices and evaluation criteria for educators, employers, and/or licensing/certifying bodies when considering the assessment of paramedic competence. The assessment of paramedic competence is a complex process requiring an understanding, appreciation for, and integration of conceptual and psychometric principles. The field of PBA is advancing rapidly with numerous opportunities for research.

A Model of Parental Distress and Factors that Mediate its Link with Parental Monitoring of Youth Diabetes Care, Adherence, and Glycemic Control

PubMed Central

Robinson, Elizabeth M.; Weaver, Patrick; Chen, Rusan; Streisand, Randi; Holmes, Clarissa S.

2016-01-01

Objective Parental monitoring of adolescents’ diabetes self-care is associated with better adherence and glycemic control (A1c). A number of parent-level factors are associated with higher levels of parental monitoring, including lower levels of parental distress (depressive symptoms, stress, anxiety), as well as higher levels of parental self-efficacy for diabetes management and authoritative parenting. Often studied in isolation, these factors may be best considered simultaneously as they are interrelated and are associated with parental monitoring and youth adherence. Methods Structural equation modeling with a cross-sectional sample of 257 parent/youth (aged 11-14) dyads: 1) examined a broad model of parental factors (i.e., parental distress, parental diabetes self-efficacy, authoritative parenting) and 2) assessed their relation to parental monitoring, youth adherence, and A1c. Post-hoc ANOVAs evaluated clinical implications of daily parental monitoring. Results Parental distress was not related directly to parental monitoring. Instead less distress related indirectly to more monitoring via higher parental self-efficacy and more authoritative parenting which in turn related to better adherence and A1c. Higher parental self-efficacy also related directly to better youth adherence and then to better A1c. Clinically, more parental monitoring related to more daily blood glucose checks and to better A1c (8.48% v. 9.17%). Conclusions A broad model of parent-level factors revealed more parental distress was linked only indirectly to less monitoring via lower parental self-efficacy and less authoritative parenting. Behaviorally, more parental monitoring related to better adherence and to clinically better A1c in adolescents. Further study of parent-level factors that relate to parental distress and monitoring of adherence appears warranted. PMID:27513476

Understanding health advocacy in family medicine and psychiatry curricula and practice: A qualitative study

PubMed Central

Andermann, Lisa; Fefergrad, Mark; Fung, Kenneth; Iglar, Karl; Johnson, Andrew; Whitehead, Cynthia

2018-01-01

Background We explored understanding and experiences of health advocacy among psychiatry and family medicine residents and faculty and the implications for clinical care and teaching through the lens of relationship-centred care. Methods This qualitative study was conducted in the psychiatry and family medicine departments at a large urban university. We interviewed 19 faculty members and conducted two focus groups with 18 residents. Semi-structured questions explored the relational meaning of health advocacy, how residents and faculty learned about the role and ethical considerations involved in incorporating advocacy work into clinical practice within a relationship-centred care framework. Results Four themes emerged from the interviews and focus groups: 1) health advocacy as an extension of the relationship to self; 2) health advocacy and professional boundaries in the physician–patient relationship; 3) health advocacy within a team-based approach; and 4) health advocacy and the physician–community/organization relationship. Participants described implications for practice of the challenges of health advocacy, including perceived institutional risks, professional boundaries and the appropriation of patient voice. Conclusions Our study provides insights into the relational complexities of the health advocate role in residency curriculum and clinical practice. All participants described health advocacy as a broad spectrum of actions that are guided by relationships among patients, health care professionals and communities. Our analysis revealed that some challenges that participants identified with a health advocacy role could be addressed by anchoring the role within a specific theoretical framework. This would better enable us to create a culture of advocacy in the training and development of physicians. PMID:29791466

Prescription opioid abuse, pain and addiction: Clinical issues and implications

PubMed Central

LING, WALTER; MOONEY, LARISSA; HILLHOUSE, MAUREEN

2014-01-01

Issues Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. Approach This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial μ agonist buprenorphine in the management of concurrent pain and opioid addiction. Implications Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. Conclusions The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. PMID:21545561

Understanding health advocacy in family medicine and psychiatry curricula and practice: A qualitative study.

PubMed

Soklaridis, Sophie; Bernard, Carrie; Ferguson, Genevieve; Andermann, Lisa; Fefergrad, Mark; Fung, Kenneth; Iglar, Karl; Johnson, Andrew; Paton, Morag; Whitehead, Cynthia

2018-01-01

We explored understanding and experiences of health advocacy among psychiatry and family medicine residents and faculty and the implications for clinical care and teaching through the lens of relationship-centred care. This qualitative study was conducted in the psychiatry and family medicine departments at a large urban university. We interviewed 19 faculty members and conducted two focus groups with 18 residents. Semi-structured questions explored the relational meaning of health advocacy, how residents and faculty learned about the role and ethical considerations involved in incorporating advocacy work into clinical practice within a relationship-centred care framework. Four themes emerged from the interviews and focus groups: 1) health advocacy as an extension of the relationship to self; 2) health advocacy and professional boundaries in the physician-patient relationship; 3) health advocacy within a team-based approach; and 4) health advocacy and the physician-community/organization relationship. Participants described implications for practice of the challenges of health advocacy, including perceived institutional risks, professional boundaries and the appropriation of patient voice. Our study provides insights into the relational complexities of the health advocate role in residency curriculum and clinical practice. All participants described health advocacy as a broad spectrum of actions that are guided by relationships among patients, health care professionals and communities. Our analysis revealed that some challenges that participants identified with a health advocacy role could be addressed by anchoring the role within a specific theoretical framework. This would better enable us to create a culture of advocacy in the training and development of physicians.

Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions.

PubMed

Belmonte, Frances R; Martin, James L; Frescura, Kristin; Damas, Joana; Pereira, Filipe; Tarnopolsky, Mark A; Kaufman, Brett A

2016-04-28

Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error.

Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions

PubMed Central

Belmonte, Frances R.; Martin, James L.; Frescura, Kristin; Damas, Joana; Pereira, Filipe; Tarnopolsky, Mark A.; Kaufman, Brett A.

2016-01-01

Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error. PMID:27122135

Ketogenic diets, mitochondria, and neurological diseases

PubMed Central

Gano, Lindsey B.; Patel, Manisha; Rho, Jong M.

2014-01-01

The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate “classic KD”, as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD. PMID:24847102

Collaboratively charting the gene-to-phenotype network of human congenital heart defects

PubMed Central

2010-01-01

Background How to efficiently integrate the daily practice of molecular biologists, geneticists, and clinicians with the emerging computational strategies from systems biology is still much of an open question. Description We built on the recent advances in Wiki-based technologies to develop a collaborative knowledge base and gene prioritization portal aimed at mapping genes and genomic regions, and untangling their relations with corresponding human phenotypes, congenital heart defects (CHDs). This portal is not only an evolving community repository of current knowledge on the genetic basis of CHDs, but also a collaborative environment for the study of candidate genes potentially implicated in CHDs - in particular by integrating recent strategies for the statistical prioritization of candidate genes. It thus serves and connects the broad community that is facing CHDs, ranging from the pediatric cardiologist and clinical geneticist to the basic investigator of cardiogenesis. Conclusions This study describes the first specialized portal to collaboratively annotate and analyze gene-phenotype networks. Of broad interest to the biological community, we argue that such portals will play a significant role in systems biology studies of numerous complex biological processes. CHDWiki is accessible at http://www.esat.kuleuven.be/~bioiuser/chdwiki PMID:20193066

A History of Social Work in Public Health.

PubMed

Ruth, Betty J; Marshall, Jamie Wyatt

2017-12-01

Social work is a core health profession with origins deeply connected to the development of contemporary public health in the United States. Today, many of the nation's 600 000 social workers practice broadly in public health and in other health settings, drawing on a century of experience in combining clinical, intermediate, and population approaches for greater health impact. Yet, the historic significance of this long-standing interdisciplinary collaboration-and its current implications-remains underexplored in the present era. This article builds on primary and contemporary sources to trace the historic arc of social work in public health, providing examples of successful collaborations. The scope and practices of public health social work practice are explored, and we articulate a rationale for an expanded place for social work in the public health enterprise.

Comparative genomic analysis of three Leishmania species that cause diverse human disease

PubMed Central

Peacock, Christopher S; Seeger, Kathy; Harris, David; Murphy, Lee; Ruiz, Jeronimo C; Quail, Michael A; Peters, Nick; Adlem, Ellen; Tivey, Adrian; Aslett, Martin; Kerhornou, Arnaud; Ivens, Alasdair; Fraser, Audrey; Rajandream, Marie-Adele; Carver, Tim; Norbertczak, Halina; Chillingworth, Tracey; Hance, Zahra; Jagels, Kay; Moule, Sharon; Ormond, Doug; Rutter, Simon; Squares, Rob; Whitehead, Sally; Rabbinowitsch, Ester; Arrowsmith, Claire; White, Brian; Thurston, Scott; Bringaud, Frédéric; Baldauf, Sandra L; Faulconbridge, Adam; Jeffares, Daniel; Depledge, Daniel P; Oyola, Samuel O; Hilley, James D; Brito, Loislene O; Tosi, Luiz R O; Barrell, Barclay; Cruz, Angela K; Mottram, Jeremy C; Smith, Deborah F; Berriman, Matthew

2008-01-01

Leishmania parasites cause a broad spectrum of clinical disease. Here we report the sequencing of the genomes of two species of Leishmania: Leishmania infantum and Leishmania braziliensis. The comparison of these sequences with the published genome of Leishmania major reveals marked conservation of synteny and identifies only ∼200 genes with a differential distribution between the three species. L. braziliensis, contrary to Leishmania species examined so far, possesses components of a putative RNA-mediated interference pathway, telomere-associated transposable elements and spliced leader–associated SLACS retrotransposons. We show that pseudogene formation and gene loss are the principal forces shaping the different genomes. Genes that are differentially distributed between the species encode proteins implicated in host-pathogen interactions and parasite survival in the macrophage. PMID:17572675

Multiple diagnosis in posttraumatic stress disorder. The role of war stressors.

PubMed

Green, B L; Lindy, J D; Grace, M C; Gleser, G C

1989-06-01

Prior studies have shown that posttraumatic stress disorder (PTSD) in Vietnam veterans is associated with various aspects of war stressors and that other diagnoses often co-occur with PTSD in this population. The present report examines the prediction of other diagnoses, in combination with PTSD, from a variety of war stressor experiences in a broad sample of veterans recruited from clinical and nonclinical sources. The results show that PTSD with panic disorder is better explained by war stressors than other diagnostic combinations and that high-risk assignments and exposure to grotesque deaths were more salient than other stressor experiences in accounting for different diagnostic combinations. Implications of the findings for PTSD's placement in the DSM-III-R and for psychological and pharmacological treatments were discussed.

The role of antisense oligonucleotide therapy in patients with familial hypercholesterolemia: risks, benefits, and management recommendations.

PubMed

Agarwala, Anandita; Jones, Peter; Nambi, Vijay

2015-01-01

Antisense oligonucleotide therapy is a promising approach for the treatment of a broad variety of medical conditions. It functions at the cellular level by interfering with RNA function, often leading to degradation of specifically targeted abnormal gene products implicated in the disease process. Mipomersen is a novel antisense oligonucleotide directed at apolipoprotein (apoB)-100, the primary apolipoprotein associated with low-density lipoprotein cholesterol (LDL-C), which has recently been approved for the treatment of familial hypercholesterolemia. A number of clinical studies have demonstrated its efficacy in lowering LDL-C and apoB levels in patients with elevated LDL-C despite maximal medical therapy using conventional lipid-lowering agents. This review outlines the risks and benefits of therapy and provides recommendations on the use of mipomersen.

Neuroethics: a modern context for ethics in neuroscience

PubMed Central

Illes, Judy; Bird, Stephanie J.

2006-01-01

Neuroethics, a recently modernized field at the intersection of bioethics and neuroscience, is founded on centuries of discussion of the ethical issues associated with mind and behavior. Broadly defined, neuroethics is concerned with ethical, legal and social policy implications of neuroscience, and with aspects of neuroscience research itself. Advances in neuroscience increasingly challenge long-held views of the self and the individual's relationship to society. Neuroscience also has led to innovations in clinical medicine that have not only therapeutic but also non-therapeutic dimensions that extend well beyond previously charted boundaries. The exponential increase in cross-disciplinary research, the commercialization of cognitive neuroscience, the impetus for training in ethics, and the increased attention being paid to public understanding of science all illuminate the important role of neuroethics in neuroscience. PMID:16859760

A modular, closed-loop platform for intracranial stimulation in people with neurological disorders.

PubMed

Sarma, Anish A; Crocker, Britni; Cash, Sydney S; Truccolo, Wilson

2016-08-01

Neuromodulation systems based on electrical stimulation can be used to investigate, probe, and potentially treat a range of neurological disorders. The effects of ongoing neural state and dynamics on stimulation response, and of stimulation parameters on neural state, have broad implications for the development of closed-loop neuro-modulation approaches. We describe the development of a modular, low-latency platform for pre-clinical, closed-loop neuromodulation studies with human participants. We illustrate the uses of the platform in a stimulation case study with a person with epilepsy undergoing neuro-monitoring prior to resective surgery. We demonstrate the efficacy of the system by tracking interictal epileptiform discharges in the local field potential to trigger intracranial electrical stimulation, and show that the response to stimulation depends on the neural state.

Effect of fluoroscopic X-ray beam spectrum on air-kerma measurement accuracy: implications for establishing correction coefficients on interventional fluoroscopes with KAP meters.

PubMed

Wunderle, Kevin A; Rakowski, Joseph T; Dong, Frank F

2016-05-08

The first goal of this study was to investigate the accuracy of the displayed reference plane air kerma (Ka,r) or air kerma-area product (Pk,a) over a broad spectrum of X-ray beam qualities on clinically used interventional fluoroscopes incorporating air kerma-area product meters (KAP meters) to measure X-ray output. The second goal was to investigate the accuracy of a correction coefficient (CC) determined at a single beam quality and applied to the measured Ka,r over a broad spectrum of beam qualities. Eleven state-of-the-art interventional fluoroscopes were evaluated, consisting of eight Siemens Artis zee and Artis Q systems and three Philips Allura FD systems. A separate calibrated 60 cc ionization chamber (external chamber) was used to determine the accuracy of the KAP meter over a broad range of clinically used beam qualities. For typical adult beam qualities, applying a single CC deter-mined at 100 kVp with copper (Cu) in the beam resulted in a deviation of < 5% due to beam quality variation. This result indicates that applying a CC determined using The American Association of Physicists in Medicine Task Group 190 protocol or a similar protocol provides very good accuracy as compared to the allowed ± 35% deviation of the KAP meter in this limited beam quality range. For interventional fluoroscopes dedicated to or routinely used to perform pediatric interventions, using a CC established with a low kVp (~ 55-60 kVp) and large amount of Cu filtration (~ 0.6-0.9 mm) may result in greater accuracy as compared to using the 100 kVp values. KAP meter responses indicate that fluoroscope vendors are likely normalizing or otherwise influencing the KAP meter output data. Although this may provide improved accuracy in some instances, there is the potential for large discrete errors to occur, and these errors may be difficult to identify.

Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

PubMed

Mandelker, Diana; Zhang, Liying; Kemel, Yelena; Stadler, Zsofia K; Joseph, Vijai; Zehir, Ahmet; Pradhan, Nisha; Arnold, Angela; Walsh, Michael F; Li, Yirong; Balakrishnan, Anoop R; Syed, Aijazuddin; Prasad, Meera; Nafa, Khedoudja; Carlo, Maria I; Cadoo, Karen A; Sheehan, Meg; Fleischut, Megan H; Salo-Mullen, Erin; Trottier, Magan; Lipkin, Steven M; Lincoln, Anne; Mukherjee, Semanti; Ravichandran, Vignesh; Cambria, Roy; Galle, Jesse; Abida, Wassim; Arcila, Marcia E; Benayed, Ryma; Shah, Ronak; Yu, Kenneth; Bajorin, Dean F; Coleman, Jonathan A; Leach, Steven D; Lowery, Maeve A; Garcia-Aguilar, Julio; Kantoff, Philip W; Sawyers, Charles L; Dickler, Maura N; Saltz, Leonard; Motzer, Robert J; O'Reilly, Eileen M; Scher, Howard I; Baselga, Jose; Klimstra, David S; Solit, David B; Hyman, David M; Berger, Michael F; Ladanyi, Marc; Robson, Mark E; Offit, Kenneth

2017-09-05

Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention. To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines. From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing. Since May 2015, 1040 of these patients with advanced cancer were referred by their oncologists for germline analysis of 76 cancer predisposition genes. Patients with clinically actionable inherited mutations whose genetic test results would not have been predicted by published decision rules were identified. Follow-up for potential clinical implications of mutation detection was through May 2017. Tumor and germline sequencing compared with the predicted yield of targeted germline sequencing based on clinical guidelines. Proportion of clinically actionable germline mutations detected by universal tumor-normal sequencing that would not have been detected by guideline-directed testing. Of 1040 patients, the median age was 58 years (interquartile range, 50.5-66 years), 65.3% were male, and 81.3% had stage IV disease at the time of genomic analysis, with prostate, renal, pancreatic, breast, and colon cancer as the most common diagnoses. Of the 1040 patients, 182 (17.5%; 95% CI, 15.3%-19.9%) had clinically actionable mutations conferring cancer susceptibility, including 149 with moderate- to high-penetrance mutations; 101 patients tested (9.7%; 95% CI, 8.1%-11.7%) would not have had these mutations detected using clinical guidelines, including 65 with moderate- to high-penetrance mutations. Frequency of inherited mutations was related to case mix, stage, and founder mutations. Germline findings led to discussion or initiation of change to targeted therapy in 38 patients tested (3.7%) and predictive testing in the families of 13 individuals (1.3%), including 6 for whom genetic evaluation would not have been initiated by guideline-based testing. In this referral population with selected advanced cancers, universal sequencing of a broad panel of cancer-related genes in paired germline and tumor DNA samples was associated with increased detection of individuals with potentially clinically significant heritable mutations over the predicted yield of targeted germline testing based on current clinical guidelines. Knowledge of these additional mutations can help guide therapeutic and preventive interventions, but whether all of these interventions would improve outcomes for patients with cancer or their family members requires further study. clinicaltrials.gov Identifier: NCT01775072.

Gene Technology: Also a Gender Issue. Views of Dutch Informed Women on Genetic Screening and Gene Therapy.

ERIC Educational Resources Information Center

van Berkel, Dymphie; Klinge, Ineke

1997-01-01

The views of Dutch women on the implications of the analysis of the human genome were studied by questionnaire and interview. Although a serious lack of knowledge about the topic was found, interviews produced a broad range of problematic issues. Attention to gender implications of gene technology is needed. (Author/EMK)

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan.

PubMed

Teede, H; Deeks, A; Moran, L

2010-06-30

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS.

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan

PubMed Central

2010-01-01

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS. PMID:20591140

Targeting disease through novel pathways of apoptosis and autophagy.

PubMed

Maiese, Kenneth; Chong, Zhao Zhong; Shang, Yan Chen; Wang, Shaohui

2012-12-01

Apoptosis and autophagy impact cell death in multiple systems of the body. Development of new therapeutic strategies that target these processes must address their complex role during developmental cell growth as well as during the modulation of toxic cellular environments. Novel signaling pathways involving Wnt1-inducible signaling pathway protein 1 (WISP1), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), β-catenin and mammalian target of rapamycin (mTOR) govern apoptotic and autophagic pathways during oxidant stress that affect the course of a broad spectrum of disease entities including Alzheimer's disease, Parkinson's disease, myocardial injury, skeletal system trauma, immune system dysfunction and cancer progression. Implications of potential biological and clinical outcome for these signaling pathways are presented. The CCN family member WISP1 and its intimate relationship with canonical and non-canonical wingless signaling pathways of PI3K, Akt1, β-catenin and mTOR offer an exciting approach for governing the pathways of apoptosis and autophagy especially in clinical disorders that are currently without effective treatments. Future studies that can elucidate the intricate role of these cytoprotective pathways during apoptosis and autophagy can further the successful translation and development of these cellular targets into robust and safe clinical therapeutic strategies.

Structure of Work as Purposeful Activity

ERIC Educational Resources Information Center

Quey, Richard L.

1971-01-01

Work is purposeful activity linking the present to the future through manipulation of objects, symbols, and experience and possessing broad implications for education, vocational guidance and human work satisfaction. (Author)

Consequences of hot gas in the broad line region of active galactic nuclei

NASA Technical Reports Server (NTRS)

Kallman, T.; Mushotzky, R.

1985-01-01

Models for hot gas in the broad line region of active galactic nuclei are discussed. The results of the two phase equilibrium models for confinement of broad line clouds by Compton heated gas are used to show that high luminosity quasars are expected to show Fe XXVI L alpha line absorption which will be observed with spectrometers such as those planned for the future X-ray spectroscopy experiments. Two phase equilibrium models also predict that the gas in the broad line clouds and the confining medium may be Compton thick. It is shown that the combined effects of Comptonization and photoabsorption can suppress both the broad emission lines and X-rays in the Einstein and HEAO-1 energy bands. The observed properties of such Compton thick active galaxies are expected to be similar to those of Seyfert 2 nuclei. The implications for polarization and variability are also discussed.

Leiomyoma of broad ligament mimicking ovarian malignancy- report of a unique case.

PubMed

Mallick, D; Saha, M; Chakrabarti, S; Chakraborty, J

2014-01-01

Tumors of the broad ligament are uncommon. Leiomyoma, which is the commonest female genital neoplasm, is also the most common solid tumor of the broad ligament. Leiomyomas affect 30% of all women of reproductive age but the incidence of broad-ligament leiomyoma is <1%. These benign tumors are usually asymptomatic. A case is being described where a 52 year old presented with gradual abdominal swelling which was clinically and radiologically diagnosed as ovarian malignancy. On abdominal and bimanual palpation a soft cystic mass was noted in the right pelvic region. CA 125 was mildly raised. CEA, CA 19.9 levels were within normal limit. The radiological diagnosis was ovarian cyst with possibility of malignant changes. Staging laparotomy and histopathological examination of the resected specimen revealed a right sided broad ligament leiomyoma with cystic changes. The degenerative changes in the leiomyoma lead to the clinical and radiological diagnostic confusion. Thus, though uncommon, broad ligament leiomyoma should be considered during evaluation of adnexal masses for optimal patient management. The above description of leiomyoma in the broad ligament is a highly unique case and thus deserves appropriate attention.

Evaluation of DNA extraction methods and their clinical application for direct detection of causative bacteria in continuous ambulatory peritoneal dialysis culture fluids from patients with peritonitis by using broad-range PCR.

PubMed

Kim, Si Hyun; Jeong, Haeng Soon; Kim, Yeong Hoon; Song, Sae Am; Lee, Ja Young; Oh, Seung Hwan; Kim, Hye Ran; Lee, Jeong Nyeo; Kho, Weon-Gyu; Shin, Jeong Hwan

2012-03-01

The aims of this study were to compare several DNA extraction methods and 16S rDNA primers and to evaluate the clinical utility of broad-range PCR in continuous ambulatory peritoneal dialysis (CAPD) culture fluids. Six type strains were used as model organisms in dilutions from 10(8) to 10(0) colony-forming units (CFU)/mL for the evaluation of 5 DNA extraction methods and 5 PCR primer pairs. Broad-range PCR was applied to 100 CAPD culture fluids, and the results were compared with conventional culture results. There were some differences between the various DNA extraction methods and primer sets with regard to the detection limits. The InstaGene Matrix (Bio-Rad Laboratories, USA) and Exgene Clinic SV kits (GeneAll Biotechnology Co. Ltd, Korea) seem to have higher sensitivities than the others. The results of broad-range PCR were concordant with the results from culture in 97% of all cases (97/100). Two culture-positive cases that were broad-range PCR-negative were identified as Candida albicans, and 1 PCR-positive but culture-negative sample was identified as Bacillus circulans by sequencing. Two samples among 54 broad-range PCR-positive products could not be sequenced. There were differences in the analytical sensitivity of various DNA extraction methods and primers for broad-range PCR. The broad-range PCR assay can be used to detect bacterial pathogens in CAPD culture fluid as a supplement to culture methods.

The Uses (and Misuses) of Collaborative Distance Education Technologies Implications for the Debate on Transience in Technology: Implications for the Debate on Transience in Technology

ERIC Educational Resources Information Center

Chang, YunJeong; Hannafin, Michael J.

2015-01-01

Collaborative learning technologies (tools that are used for facilitating or mediating collaborative learning) have been widely incorporated in distance education as well as broadly adopted in higher education. While a range of collaborative technologies has been incorporated, their implementation has often failed to align with well-established…

Cognitive neuroscience of social emotions and implications for psychopathology: examining embarrassment, guilt, envy, and schadenfreude.

PubMed

Jankowski, Kathryn F; Takahashi, Hidehiko

2014-05-01

Social emotions are affective states elicited during social interactions and integral for promoting socially appropriate behaviors and discouraging socially inappropriate ones. Social emotion-processing deficits significantly impair interpersonal relationships, and play distinct roles in the manifestation and maintenance of clinical symptomatology. Elucidating the neural correlates of discrete social emotions can serve as a window to better understanding and treating neuropsychiatric disorders. Moral cognition and social emotion-processing broadly recruit a fronto-temporo-subcortical network, supporting empathy, perspective-taking, self-processing, and reward-processing. The present review specifically examines the neural correlates of embarrassment, guilt, envy, and schadenfreude. Embarrassment and guilt are self-conscious emotions, evoked during negative evaluation following norm violations and supported by a fronto-temporo-posterior network. Embarrassment is evoked by social transgressions and recruits greater anterior temporal regions, representing conceptual social knowledge. Guilt is evoked by moral transgressions and recruits greater prefrontal regions, representing perspective-taking and behavioral change demands. Envy and schadenfreude are fortune-of-other emotions, evoked during social comparison and supported by a prefronto-striatal network. Envy represents displeasure in others' fortunes, and recruits increased dorsal anterior cingulate cortex, representing cognitive dissonance, and decreased reward-related striatal regions. Schadenfreude represents pleasure in others' misfortunes, and recruits reduced empathy-related insular regions and increased reward-related striatal regions. Implications for psychopathology and treatment design are discussed. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Therapeutic Potential of Matrix Metalloproteinase Inhibition in Breast Cancer

PubMed Central

Raeeszadeh‐Sarmazdeh, Maryam; Radisky, Derek C.

2017-01-01

ABSTRACT Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that cleave nearly all components of the extracellular matrix as well as many other soluble and cell‐associated proteins. MMPs have been implicated in normal physiological processes, including development, and in the acquisition and progression of the malignant phenotype. Disappointing results from a series of clinical trials testing small molecule, broad spectrum MMP inhibitors as cancer therapeutics led to a re‐evaluation of how MMPs function in the tumor microenvironment, and ongoing research continues to reveal that these proteins play complex roles in cancer development and progression. It is now clear that effective targeting of MMPs for therapeutic benefit will require selective inhibition of specific MMPs. Here, we provide an overview of the MMP family and its biological regulators, the tissue inhibitors of metalloproteinases (TIMPs). We then summarize recent research from model systems that elucidate how specific MMPs drive the malignant phenotype of breast cancer cells, including acquisition of cancer stem cell features and induction of the epithelial–mesenchymal transition, and we also outline clinical studies that implicate specific MMPs in breast cancer outcomes. We conclude by discussing ongoing strategies for development of inhibitors with therapeutic potential that are capable of selectively targeting the MMPs most responsible for tumor promotion, with special consideration of the potential of biologics including antibodies and engineered proteins based on the TIMP scaffold. J. Cell. Biochem. 118: 3531–3548, 2017. © 2017 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc. PMID:28585723

New advances in stem cell research: practical implications for regenerative medicine.

PubMed

Ratajczak, Mariusz Z; Jadczyk, Tomasz; Pędziwiatr, Daniel; Wojakowski, Wojciech

2014-01-01

Regenerative medicine is searching for stem cells that can be safely and efficiently employed for regeneration of damaged solid organs (e.g., the heart, brain, or liver). Ideal for this purpose would be pluripotent stem cells, which, according to their definition, have broad potential to differentiate into all types of adult cells. For almost 20 years, there have been unsuccessful attempts to harness controversial embryonic stem cells (ESCs) isolated from embryos. Induced pluripotent stem cells (iPSCs), generated by genetic modification of adult somatic cells, are a more promising source. However, both iPSC and ESCs are associated with a risk of teratoma formation. At the same time, various types of more‑differentiated adult stem and progenitor cells derived from the bone marrow, umbilical cord blood, mobilized peripheral blood, or fat tissue are being employed in clinical trials to regenerate damaged solid organs. However, for most of these cells, there is a lack of convincing documentation for successful regeneration of the treated organs. Beneficial effects of those cells might be explained by paracrine effects of growth factors, cytokines, chemokines, bioactive lipids, and extracellular microvesicles, which are released from the cells and have trophic, antiapoptotic, and angiopoietic effects. Nevertheless, there is evidence that adult tissues harbor a promising population of very rare dormant stem cells with broad differentiation potential. In this review, we will discuss various potential sources of stem cells for regenerative medicine and the mechanisms that explain some of their beneficial effects as well as highlight the results of the first clinical trials.  

Genetically mediated Nf1 loss in mice promotes diverse radiation-induced tumors modeling second malignant neoplasms

PubMed Central

Choi, Grace; Huang, Brian; Pinarbasi, Emile; Braunstein, Steve E.; Horvai, Andrew E.; Kogan, Scott; Bhatia, Smita; Faddegon, Bruce; Nakamura, Jean L.

2013-01-01

Second malignant neoplasms (SMNs) are therapy-induced malignancies and a growing problem in cancer survivors, particularly survivors of childhood cancers. The lack of experimental models of SMNs has limited understanding of their pathogenesis. It is currently not possible to predict or prevent this devastating late complication. Individuals with Neurofibromatosis I (NF1) are at increased risk of developing therapy-induced cancers for unclear reasons. To model SMNs, we replicated clinical radiotherapy and delivered fractionated abdominal irradiation to Nf1+/− and wildtype mice. Similar to irradiated cancer survivors, irradiated wildtype and Nf1+/− mice developed diverse in-field malignancies. In Nf1+/− mice, fractionated irradiation promoted both classical NF1-associated malignancies and malignancies unassociated with the NF1 syndrome but typical of SMNs. Nf1 heterozygosity potentiated the mutagenic effects of irradiation, as evidenced by the significantly reduced survival after irradiation and tumor development that was often characterized by synchronous primary tumors. Interestingly, diverse radiation-induced tumors arising in wildtype and Nf1+/− mice shared a genetic signature characterized by monoallelic loss of Nf1 and the adjacent Trp53 allele. These findings implicate Nf1 loss as mediating tumorigenesis in a broad range of cell types and organs extending beyond the classical NF1 tumor histologies. Examining clinical SMN samples, we found LOH of NF1 in SMNs from non-NF1 patients. Nf1 heterozygosity confers broad susceptibility to genotoxin-induced tumorigenesis and this paradigm serves as an experimental platform for future studies of SMNs. PMID:23071067

The Daniel K. Inouye College of Pharmacy Scripts: Precision Medicine Through the Use of Pharmacogenomics: Current Status and Barriers to Implementation.

PubMed

Ciarleglio, Anita E; Ma, Carolyn

2017-09-01

The precision medicine initiative brought forth by President Barack Obama in 2015 is an important step on the journey to truly personalized medicine. A broad knowledge and understanding of the implications of the pharmacogenomic literature will be critical to the achievement of this goal. While a great amount of data has been published in the areas of pharmacogenomics and pharmacogenetics, there are still relatively few instances in which the need for clinical intervention can be stated without doubt, and which are widely accepted and practiced by the medical community. As our knowledge base rapidly expands, issues such as insurance reimbursement for genetic testing and education of the health care workforce will be paramount to achieving the goal of precision medicine for all patients.

Translating Population Difference: The Use and Re-Use of Genetic Ancestry in Brazilian Cancer Genetics

PubMed Central

Gibbon, Sahra

2016-01-01

ABSTRACT In the past ten years, there has been an expansion of scientific interest in population genetics linked to both understanding histories of human migration and the way that population difference and diversity may account for and/or be implicated in health and disease. In this article, I examine how particular aspects of a globalizing research agenda related to population differences and genetic ancestry are taken up in locally variant ways in the nascent field of Brazilian cancer genetics. Drawing on a broad range of ethnographic data from clinical and nonclinical contexts in the south of Brazil, I examine the ambiguities that attention to genetic ancestry generates, so revealing the disjunctured and diverse ways a global research agenda increasingly orientated to questions of population difference and genetic ancestry is being used and reused. PMID:26452039

The relationship between internalized stigma, negative symptoms and social functioning in schizophrenia: the mediating role of self-efficacy.

PubMed

Hill, Kimberley; Startup, Mike

2013-04-30

The broad aim of the present study was to gain a greater understanding of the processes that contribute to negative symptoms and social functioning in schizophrenia. More specifically, a theoretical model was proposed predicting that self-efficacy would mediate the relationship between internalized stigma and both negative symptoms and social functioning in schizophrenia. Initial analyses revealed that all variables were correlated. Specifically, internalized stigma was strongly correlated with negative symptoms, social functioning and self-efficacy. Furthermore, self-efficacy was strongly related to negative symptoms and moderately associated with social functioning. Further analyses however did not support the mediational role of self-efficacy. The theoretical and clinical implications of the findings, together with recommendations for future research, are outlined. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

PubMed Central

2014-01-01

Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). Methods We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p<1·66 × 10−8. Findings We included 8696 cases and 26 157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71 × 10−10), implicating SCN1A, and at 4p15.1 (p=5·44 × 10−9), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99 × 10−9), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. Interpretation This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the ultimate aim of assisting in disease classification and prognosis. The data suggest that specific loci can act pleiotropically raising risk for epilepsy broadly, or can have effects limited to a specific epilepsy subtype. Future genetic analyses might benefit from both lumping (ie, grouping of epilepsy types together) or splitting (ie, analysis of specific clinical subtypes). Funding International League Against Epilepsy and multiple governmental and philanthropic agencies. PMID:25087078

Features of ciguatera fish poisoning cases in Hong Kong 2004-2007.

PubMed

Wong, Chun-Kwan; Hung, Patricia; Lee, Kellie L H; Mok, Tina; Chung, Thomas; Kam, Kai-Man

2008-12-01

To review the clinical features and laboratory investigations of ciguatera patients in Hong Kong between 2004 and 2007 in order to show the timely sampling of implicated fish from ciguatera victims and application of validated mouse bioassay for confirming suspected clinical cases of ciguatera. Diagnosis of the ciguatera victims was based on history of coral fish consumption and clinical presentations stated in official guidelines for clinical diagnosis of ciguatera fish poisoning in Hong Kong. Food remnants of coral fish samples were collected swiftly from ciguatera victims between 2004 and 2007 for ciguatoxins (CTXs) analysis. Major clinical symptoms in ciguatera patients included gastrointestinal and neurological effects including limb numbness and diarrhoea, which developed at 0.5 to 15 hours after consumption of fish. In most cases, neurological symptoms were more common than gastrointestinal symptoms. A broad range of attack rate (10%-100%) was observed in each ciguatera outbreak. Validated mouse bioassay on ether extracts of the food remnant samples confirmed that all were CTXs-positive (<0.5 - 4.3 MU/20 mg ether extract) and directly linked to the corresponding ciguatera cases. Consistency between clinical and laboratory analysis for ciguatera poisoning illustrates the application of laboratory mouse bioassay in a timely fashion for confirming ciguatera poisoning cases and implementing effective public health measures. With further improvement in laboratory techniques, features of ciguatera fish poisoning cases can be better defined. Further studies are needed to determine the risk of each class of CTXs (Pacific-, Indian- and Caribbean-CTXs) in Hong Kong.

Critical connections: Communication for the future

NASA Astrophysics Data System (ADS)

1990-01-01

A broad context for evaluating the impacts of new communication technologies is provided. The implications of new communication technologies for business, politics, culture, and individuals, and possible strategies and options for congressional consideration are suggested.

Implications of the concept of minimal risk in research on informed choice in clinical practice

PubMed Central

Wada, Kyoko; Nisker, Jeff

2015-01-01

The concept of a minimal risk threshold in research, beneath which exception to informed consent and ethics review processes may occur, has been codified for over 30 years in many national research regulations and by the Council for International Organizations of Medical Sciences. Although minimal risk in research constitutes one of the criteria for allowing waiver of informed consent or modification to the consent process and a large body of literature exists, discussion of a minimal risk threshold in clinical practice has not occurred. One reason for lack of discussion may be that implicit consent is accepted for a wide range of routine clinical practices. Extending the role of minimal risk in research to clinical practice might assist clinicians in identifying circumstances for which implicit consent is indeed sufficient and circumstances in which it is not. Further, concepts from minimal risk in research might assist clinicians regarding when information provision in health promotion is required. We begin by reviewing concepts in both minimal risk in research and informed choice in clinical practice. We then explore how a clinical minimal risk concept may clarify recommendations for information provision in clinical practice and support the patient's informed choice regarding therapeutic and diagnostic procedures and also health promotion. Given that clinical practice involves a broad scope of health information, professional practice guidelines on information provision based on the application of the minimal risk threshold in research could be developed to guide clinicians in what information must be provided to their patients. PMID:26108215

Fanconi Anemia: A DNA repair disorder characterized by accelerated decline of the hematopoietic stem cell compartment and other features of aging.

PubMed

Brosh, Robert M; Bellani, Marina; Liu, Yie; Seidman, Michael M

2017-01-01

Fanconi Anemia (FA) is a rare autosomal genetic disorder characterized by progressive bone marrow failure (BMF), endocrine dysfunction, cancer, and other clinical features commonly associated with normal aging. The anemia stems directly from an accelerated decline of the hematopoietic stem cell compartment. Although FA is a complex heterogeneous disease linked to mutations in 19 currently identified genes, there has been much progress in understanding the molecular pathology involved. FA is broadly considered a DNA repair disorder and the FA gene products, together with other DNA repair factors, have been implicated in interstrand cross-link (ICL) repair. However, in addition to the defective DNA damage response, altered epigenetic regulation, and telomere defects, FA is also marked by elevated levels of inflammatory mediators in circulation, a hallmark of faster decline in not only other hereditary aging disorders but also normal aging. In this review, we offer a perspective of FA as a monogenic accelerated aging disorder, citing the latest evidence for its multi-factorial deficiencies underlying its unique clinical and cellular features. Published by Elsevier B.V.

Genome-wide CpG island methylation and intergenic demethylation propensities vary among different tumor sites.

PubMed

Lee, Seung-Tae; Wiemels, Joseph L

2016-02-18

The epigenetic landscape of cancer includes both focal hypermethylation and broader hypomethylation in a genome-wide manner. By means of a comprehensive genomic analysis on 6637 tissues of 21 tumor types, we here show that the degrees of overall methylation in CpG island (CGI) and demethylation in intergenic regions, defined as 'backbone', largely vary among different tumors. Depending on tumor type, both CGI methylation and backbone demethylation are often associated with clinical, epidemiological and biological features such as age, sex, smoking history, anatomic location, histological type and grade, stage, molecular subtype and biological pathways. We found connections between CGI methylation and hypermutability, microsatellite instability, IDH1 mutation, 19p gain and polycomb features, and backbone demethylation with chromosomal instability, NSD1 and TP53 mutations, 5q and 19p loss and long repressive domains. These broad epigenetic patterns add a new dimension to our understanding of tumor biology and its clinical implications. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Environmental Determinants of Chronic Disease and Medical Approaches: Recognition, Avoidance, Supportive Therapy, and Detoxification

PubMed Central

Sears, Margaret E.; Genuis, Stephen J.

2012-01-01

The World Health Organization warns that chronic, noncommunicable diseases are rapidly becoming epidemic worldwide. Escalating rates of neurocognitive, metabolic, autoimmune and cardiovascular diseases cannot be ascribed only to genetics, lifestyle, and nutrition; early life and ongoing exposures, and bioaccumulated toxicants may also cause chronic disease. Contributors to ill health are summarized from multiple perspectives—biological effects of classes of toxicants, mechanisms of toxicity, and a synthesis of toxic contributors to major diseases. Healthcare practitioners have wide-ranging roles in addressing environmental factors in policy and public health and clinical practice. Public health initiatives include risk recognition and chemical assessment then exposure reduction, remediation, monitoring, and avoidance. The complex web of disease and environmental contributors is amenable to some straightforward clinical approaches addressing multiple toxicants. Widely applicable strategies include nutrition and supplements to counter toxic effects and to support metabolism; as well as exercise and sweating, and possibly medication to enhance excretion. Addressing environmental health and contributors to chronic disease has broad implications for society, with large potential benefits from improved health and productivity. PMID:22315626

Understanding fear of cancer recurrence in terms of damage to 'everyday health competence'.

PubMed

Horlick-Jones, Tom

2011-09-01

Advances in clinical treatments are resulting in cancer patients living longer, but with the threat of the disease returning at some later date. Anxiety associated with this fear of recurrence, which seems widespread among patients, can lead to an enhanced bodily awareness and a pronounced tendency to interpret mundane sensations as symptoms of pathology. Relatively little sociological work has been done to systematically document, understand, and find ways of addressing, this syndrome and its impact on the quality of patients' lives. It is argued that this syndrome is best understood not in cognitive terms, as a form of irrationality, but rather as resulting from damage to certain aspects of social competence, namely one's 'everyday health competence'. In investigating this issue, the author draws upon his personal experience of breast cancer diagnosis, surgery and adjuvant therapy; and on a broadly phenomenological approach to examining the relationship between bodily sensations and practical reasoning about experience. The implications for clinical practice are considered briefly. © 2011 The Author. Sociology of Health & Illness © 2011 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

Immunomodulatory effects of histone deacetylase inhibitors.

PubMed

Licciardi, P V; Ververis, K; Tang, M L; El-Osta, A; Karagiannis, T C

2013-05-01

Histone deacetylase inhibitors (HDACi) have emerged as a new generation of anticancer therapeutics. The classical broad-spectrum HDACi typically alter the cell cycle distribution and induce cell death, apoptosis and differentiation in malignant and transformed cells. This provides the basis for the clinical potential of HDACi in cancer therapy. Currently two compounds, suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza™) and depsipeptide (Romidepsin, Istodax™) have been approved for by the US Food and Drug Administration for the treatment of refractory cutaneous T-cell lymphoma. Apart from clinical application in oncology, HDACi have also been investigated as potential therapeutics for various pathologies including those of the central nervous system (such as Huntington's disease and multiple sclerosis), cardiac conditions (particularly hypertrophy), arthritis and malaria. Further, evidence is accumulating for potent immunomodulatory effects of classical HDACi which is the focus of this review. We review the antiinflammatory effects of HDACi and in particular findings implicating regulation of the innate and adaptive immune systems by HDAC enzymes. The recent findings highlighting the immunomodulatory function of HDAC11 which relates to balancing immune activation versus tolerance are also discussed.

Propionibacterium acnes bacteriophages display limited genetic diversity and broad killing activity against bacterial skin isolates.

PubMed

Marinelli, Laura J; Fitz-Gibbon, Sorel; Hayes, Clarmyra; Bowman, Charles; Inkeles, Megan; Loncaric, Anya; Russell, Daniel A; Jacobs-Sera, Deborah; Cokus, Shawn; Pellegrini, Matteo; Kim, Jenny; Miller, Jeff F; Hatfull, Graham F; Modlin, Robert L

2012-01-01

Investigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne. Propionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne.

Cultural Aspects of Astrobiology: A Preliminary Reconnaissance at

NASA Astrophysics Data System (ADS)

Dick, Steven

NASA's Astrobiology Roadmap, developed in 1998 by an interdisciplinary team of more than 150 individuals, recognizes ten science goals, 17 more specific science objectives, and four broad principles for the Astrobiology Program. Among the four operating principles, which emphasize multidisciplinarity, planetary stewardship and public outreach, is one that also recognizes broad societal interest for the implications of astrobiology, especially its extraterrestrial life component. Although several meetings ahve been convened in the past decade to discuss the implications of extraterrestrial intelligence, including NASA's own CASETI workshops in 1991-1992, none have surveyed the broader implications of astrobiology as now defined at NASA. In this paper we survey these societal questions raised by astrobiology, and then focus on those related to extraterrestrial life, and in particular how they might differ from SETI concerns already discussed. As we enter the new millennium, the necessity for interdisciplinary studies is increasingly recognized in academia, industry and government. Astrobiology provides an unprecedented opportunity to encourage the unity of knowledge, as recently proposed in E. O. Wilson's book Consilience: The Unity of Knowledge. It is incumbent on scientists to support research on the implications of their work, in particular large government-funded scientific projects. The deep insights such study may yield has been amply demonstrated by the Human Genome Project, among others.

Broad- versus Narrow-Spectrum Oral Antibiotic Transition and Outcomes in Health Care-associated Pneumonia.

PubMed

Buckel, Whitney R; Stenehjem, Edward; Sorensen, Jeff; Dean, Nathan; Webb, Brandon

2017-02-01

Guidelines recommend a switch from intravenous to oral antibiotics once patients who are hospitalized with pneumonia achieve clinical stability. However, little evidence guides the selection of an oral antibiotic for patients with health care-associated pneumonia, especially where no microbiological diagnosis is made. To compare outcomes between patients who were transitioned to broad- versus narrow-spectrum oral antibiotics after initially receiving broad-spectrum intravenous antibiotic coverage. We performed a secondary analysis of an existing database of adults with community-onset pneumonia admitted to seven Utah hospitals. We identified 220 inpatients with microbiology-negative health care-associated pneumonia from 2010 to 2012. After excluding inpatient deaths and treatment failures, 173 patients remained in which broad-spectrum intravenous antibiotics were transitioned to an oral regimen. We classified oral regimens as broad-spectrum (fluoroquinolone) versus narrow-spectrum (usually a β-lactam). We compared demographic and clinical characteristics between groups. Using a multivariable regression model, we adjusted outcomes by severity (electronically calculated CURB-65), comorbidity (Charlson Index), time to clinical stability, and length of intravenous therapy. Age, severity, comorbidity, length of intravenous therapy, and clinical response were similar between the two groups. Observed 30-day readmission (11.9 vs. 21.4%; P = 0.26) and 30-day all-cause mortality (2.3 vs. 5.3%; P = 0.68) were also similar between the narrow and broad oral antibiotic groups. In multivariable analysis, we found no statistically significant differences for adjusted odds of 30-day readmission (adjusted odds ratio, 0.56; 95% confidence interval, 0.06-5.2; P = 0.61) or 30-day all-cause mortality (adjusted odds ratio, 0.55; 95% confidence interval, 0.19-1.6; P = 0.26) between narrow and broad oral antibiotic groups. On the basis of analysis of a limited number of patients observed retrospectively, our findings suggest that it may be safe to switch from broad-spectrum intravenous antibiotic coverage to a narrow-spectrum oral antibiotic once clinical stability is achieved for hospitalized patients with health care-associated pneumonia when no microbiological diagnosis is made. A larger retrospective study with propensity matching or regression-adjusted test of equivalence or ideally a prospective comparative effectiveness study will be necessary to confirm our observations.

Broad absorption-line time variability in the QSO CSO 203

NASA Technical Reports Server (NTRS)

Barlow, Thomas A.; Junkkarinen, Vesa T.; Burbidge, E. M.; Weymann, Ray J.; Morris, Simon L.; Korista, Kirk T.

1992-01-01

We present spectroscopy of the BALQSO CSO 203 during four epochs over a 17-month time span. These data show three distinct levels in the broad absorption lines (BALs) of Si IV 1397A and C IV 1549A. We also note possible variations in the N V 1240A and Al III 1857A absorption troughs. A broad-band monitoring effort during this period shows that the continuum level remained constant to within 10 percent. We argue that the triggering mechanism for the absorption-line changes is most likely synchronous with the continuum source photons; however, no correlation with the central source has yet been found. The observed variations are consistent with changes in the ionization level in the broad absorption-line region (BALR). We discuss possible mechanisms for these changes and the implications for the structure of the BALR.

Policy implications of emerging vehicle and infrastructure technology.

DOT National Transportation Integrated Search

2014-08-01

This report considers a broad range of emerging transportation technologies that have potential : for enhancing travel on and operations of the Texas transportation system. It provides an : overview of technology classifications and assesses the poli...

Hypersensitivity linked to exposure of broad bean protein(s) in allergic patients and BALB/c mice.

PubMed

Kumar, Dinesh; Kumar, Sandeep; Verma, Alok K; Sharma, Akanksha; Tripathi, Anurag; Chaudhari, Bhushan P; Kant, Surya; Das, Mukul; Jain, Swatantra K; Dwivedi, Premendra D

2014-01-01

Broad bean (Vicia faba L.), a common vegetable, belongs to the family Fabaceae and is consumed worldwide. Limited studies have been done on allergenicity of broad beans. The aim of this study was to determine if broad bean proteins have the ability to elicit allergic responses due to the presence of clinically relevant allergenic proteins. Simulated gastric fluid (SGF) assay and immunoglobulin E (IgE) immunoblotting were carried out to identify pepsin-resistant and IgE-binding proteins. The allergenicity of broad beans was assessed in allergic patients, BALB/c mice, splenocytes, and RBL-2H3 cells. Eight broad bean proteins of approximate molecular weight 70, 60, 48, 32, 23, 19, 15, and 10 kDa that remained undigested in SGF, showed IgE-binding capacity as well. Of 127 allergic patients studied, broad bean allergy was evident in 16 (12%). Mice sensitized with broad bean showed increased levels of histamine, total and specific IgE, and severe signs of systemic anaphylaxis compared with controls. Enhanced levels of histamine, prostaglandin D2, cysteinyl leukotriene, and β-hexosaminidase release were observed in the primed RBL-2H3 cells following broad bean exposure. The levels of interleukin IL-4, IL-5, IL-13 and regulated on activation, normal T-cell expressed and secreted were found enhanced in broad bean-treated splenocytes culture supernatant compared with controls. This study inferred that broad bean proteins have the ability to elicit allergic responses due to the presence of clinically relevant allergenic proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

REGIONAL CARDIAC BLOOD FLOW WITH AIR PARTICLE EXPOSURE

EPA Science Inventory

This proposal offers the unique application of novel techniques to improve understanding of the mechanisms whereby ambient particulate exerts deleterious influences on the heart and circulation. Enhanced ischemia has broad implications for cardiac morbidity and mor...

A model of parental distress and factors that mediate its link with parental monitoring of youth diabetes care, adherence, and glycemic control.

PubMed

Robinson, Elizabeth M; Weaver, Patrick; Chen, Rusan; Streisand, Randi; Holmes, Clarissa S

2016-12-01

Parental monitoring of adolescents' diabetes self-care is associated with better adherence and glycemic control (A1c). A number of parent-level factors are associated with higher levels of parental monitoring, including lower levels of parental distress (depressive symptoms, stress, anxiety), as well as higher levels of parental self-efficacy for diabetes management and authoritative parenting. Often studied in isolation, these factors may be best considered simultaneously as they are interrelated and are associated with parental monitoring and youth adherence. Structural equation modeling with a cross-sectional sample of 257 parent/youth (aged 11-14) dyads: (a) examined a broad model of parental factors (i.e., parental distress, parental diabetes self-efficacy, authoritative parenting), and (b) assessed their relation to parental monitoring, youth adherence, and A1c. Post hoc analyses of variance (ANOVAs) evaluated clinical implications of daily parental monitoring. Parental distress was not related directly to parental monitoring. Instead less distress related indirectly to more monitoring via higher parental self-efficacy and more authoritative parenting which, in turn, related to better adherence and A1c. Higher parental self-efficacy also related directly to better youth adherence and then to better A1c. Clinically, more parental monitoring related to more daily blood glucose checks and to better A1c (8.48% vs. 9.17%). A broad model of parent-level factors revealed more parental distress was linked only indirectly to less monitoring via lower parental self-efficacy and less authoritative parenting. Behaviorally, more parental monitoring related to better adherence and to clinically better A1c in adolescents. Further study of parent-level factors that relate to parental distress and monitoring of adherence appears warranted. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A State-of-the-Science Overview of Randomized Controlled Trials Evaluating Acute Management of Moderate-to-Severe Traumatic Brain Injury

PubMed Central

Synnot, Anneliese; Maas, Andrew I.; Menon, David K.; Cooper, D. James; Rosenfeld, Jeffrey V.; Gruen, Russell L.

2016-01-01

Abstract Moderate-to-severe traumatic brain injury (TBI) remains a major global challenge, with rising incidence, unchanging mortality and lifelong impairments. State-of-the-science reviews are important for research planning and clinical decision support. This review aimed to identify randomized controlled trials (RCTs) evaluating interventions for acute management of moderate/severe TBI, synthesize key RCT characteristics and findings, and determine their implications on clinical practice and future research. RCTs were identified through comprehensive database and other searches. Key characteristics, outcomes, risk of bias, and analysis approach were extracted. Data were narratively synthesized, with a focus on robust (multi-center, low risk of bias, n > 100) RCTs, and three-dimensional graphical figures also were used to explore relationships between RCT characteristics and findings. A total of 207 RCTs were identified. The 191 completed RCTs enrolled 35,340 participants (median, 66). Most (72%) were single center and enrolled less than 100 participants (69%). There were 26 robust RCTs across 18 different interventions. For 74% of 392 comparisons across all included RCTs, there was no significant difference between groups. Positive findings were broadly distributed with respect to RCT characteristics. Less than one-third of RCTs demonstrated low risk of bias for random sequence generation or allocation concealment, less than one-quarter used covariate adjustment, and only 7% employed an ordinal analysis approach. Considerable investment of resources in producing 191 completed RCTs for acute TBI management has resulted in very little translatable evidence. This may result from broad distribution of research effort, small samples, preponderance of single-center RCTs, and methodological shortcomings. More sophisticated RCT design, large multi-center RCTs in priority areas, increased focus on pre-clinical research, and alternatives to RCTs, such as comparative effectiveness research and precision medicine, are needed to fully realize the potential of acute TBI research to benefit patients. PMID:26711675

CYP21A2 mutation update: Comprehensive analysis of databases and published genetic variants.

PubMed

Simonetti, Leandro; Bruque, Carlos D; Fernández, Cecilia S; Benavides-Mori, Belén; Delea, Marisol; Kolomenski, Jorge E; Espeche, Lucía D; Buzzalino, Noemí D; Nadra, Alejandro D; Dain, Liliana

2018-01-01

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of adrenal steroidogenesis. Disorders in steroid 21-hydroxylation account for over 95% of patients with CAH. Clinically, the 21-hydroxylase deficiency has been classified in a broad spectrum of clinical forms, ranging from severe or classical, to mild late onset or non-classical. Known allelic variants in the disease causing CYP21A2 gene are spread among different sources. Until recently, most variants reported have been identified in the clinical setting, which presumably bias described variants to pathogenic ones, as those found in the CYPAlleles database. Nevertheless, a large number of variants are being described in massive genome projects, many of which are found in dbSNP, but lack functional implications and/or their phenotypic effect. In this work, we gathered a total of 1,340 GVs in the CYP21A2 gene, from which 899 variants were unique and 230 have an effect on human health, and compiled all this information in an integrated database. We also connected CYP21A2 sequence information to phenotypic effects for all available mutations, including double mutants in cis. Data compiled in the present work could help physicians in the genetic counseling of families affected with 21-hydroxylase deficiency. © 2017 Wiley Periodicals, Inc.

Steroids induce acetylcholine receptors on cultured human muscle: Implications for myasthenia gravis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaplan, I.; Blakely, B.T.; Pavlath, G.K.

1990-10-01

Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immunemore » system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.« less

Antiseptics and Disinfectants: Activity, Action, and Resistance

PubMed Central

McDonnell, Gerald; Russell, A. Denver

1999-01-01

Antiseptics and disinfectants are extensively used in hospitals and other health care settings for a variety of topical and hard-surface applications. A wide variety of active chemical agents (biocides) are found in these products, many of which have been used for hundreds of years, including alcohols, phenols, iodine, and chlorine. Most of these active agents demonstrate broad-spectrum antimicrobial activity; however, little is known about the mode of action of these agents in comparison to antibiotics. This review considers what is known about the mode of action and spectrum of activity of antiseptics and disinfectants. The widespread use of these products has prompted some speculation on the development of microbial resistance, in particular whether antibiotic resistance is induced by antiseptics or disinfectants. Known mechanisms of microbial resistance (both intrinsic and acquired) to biocides are reviewed, with emphasis on the clinical implications of these reports. PMID:9880479

Epigenetics and child abuse: Modern-day Darwinism--The miraculous ability of the human genome to adapt, and then adapt again.

PubMed

Gershon, Naomi B; High, Pamela C

2015-12-01

It has long been recognized that early adversity can have life-long consequences, and the extent to which this is true is gaining increasing attention. A growing body of literature implicates Adverse Childhood Experiences, including physical, sexual, and emotional abuse, in a broad range of negative health consequences including adult psychopathology, cardiovascular, and immune disease. Increasing evidence from animal, clinical, and epidemiological studies highlight the critical role of epigenetic programing, such as DNA methylation and histone modification, in altering gene expression, brain structure and function, and ultimately life-course trajectories. This review outlines our developing insight into the interplay between our human biology and our changing environment, and explores the growing evidence base for how interventions may prevent and ameliorate damage inflicted by toxic stress in early life. © 2015 Wiley Periodicals, Inc.

Comparative modelling of human β tubulin isotypes and implications for drug binding

NASA Astrophysics Data System (ADS)

Torin Huzil, J.; Ludueña, Richard F.; Tuszynski, Jack

2006-02-01

The protein tubulin is a target for several anti-mitotic drugs, which affect microtubule dynamics, ultimately leading to cell cycle arrest and apoptosis. Many of these drugs, including the taxanes and Vinca alkaloids, are currently used clinically in the treatment of several types of cancer. Another tubulin binding drug, colchicine, although too toxic to be used as a chemotherapeutic agent, is commonly used for the treatment of gout. The main disadvantage that all of these drugs share is that they bind tubulin indiscriminately, leading to the death of both cancerous and healthy cells. However, the broad cellular distribution of several tubulin isotypes provides a platform upon which to construct novel chemotherapeutic drugs that could differentiate between different cell types, reducing the undesirable side effects associated with current chemotherapeutic treatments. Here, we report an analysis of ten human β tubulin isotypes and discuss differences within each of the previously characterized paclitaxel, colchicine and vinblastine binding sites.

Soluble NKG2D ligands: prevalence, release, and functional impact.

PubMed

Salih, Helmut Rainer; Holdenrieder, Stefan; Steinle, Alexander

2008-05-01

Natural Killer (NK) cells are capable to recognize and eliminate malignant cells. Anti-tumor responses of NK cells are promoted by the tumor-associated expression of cell stress-inducible ligands of the activating NK receptor NKG2D. Current evidence suggests that established tumors subvert NKG2D-mediated tumor immunosurveillance by releasing NKG2D ligands (NKG2DL). Release of NKG2DL has been observed in a broad variety of human tumor entities and is thought to interfere with NKG2D-mediated tumor immunity in several ways. Further, levels of soluble NKG2DL (sNKG2DL) were also found to be elevated under various non-malignant conditions, although the functional implications remain largely unclear. Here we review and discuss the available data on the prevalence, release, functional impact, and potential clinical value of sNKG2DL.

Nanomedicine concepts in the general medical curriculum: initiating a discussion

PubMed Central

Sweeney, Aldrin E

2015-01-01

Various applications of nanoscale science to the field of medicine have resulted in the ongoing development of the subfield of nanomedicine. Within the past several years, there has been a concurrent proliferation of academic journals, textbooks, and other professional literature addressing fundamental basic science research and seminal clinical developments in nanomedicine. Additionally, there is now broad consensus among medical researchers and practitioners that along with personalized medicine and regenerative medicine, nanomedicine is likely to revolutionize our definitions of what constitutes human disease and its treatment. In light of these developments, incorporation of key nanomedicine concepts into the general medical curriculum ought to be considered. Here, I offer for consideration five key nanomedicine concepts, along with suggestions regarding the manner in which they might be incorporated effectively into the general medical curriculum. Related curricular issues and implications for medical education also are presented. PMID:26677322

Pharmacologic overview of Withania somnifera, the Indian Ginseng.

PubMed

Dar, Nawab John; Hamid, Abid; Ahmad, Muzamil

2015-12-01

Withania somnifera, also called 'Indian ginseng', is an important medicinal plant of the Indian subcontinent. It is widely used, singly or in combination, with other herbs against many ailments in Indian Systems of Medicine since time immemorial. Withania somnifera contains a spectrum of diverse phytochemicals enabling it to have a broad range of biological implications. In preclinical studies, it has shown anti-microbial, anti-inflammatory, anti-tumor, anti-stress, neuroprotective, cardioprotective, and anti-diabetic properties. Additionally, it has demonstrated the ability to reduce reactive oxygen species, modulate mitochondrial function, regulate apoptosis, and reduce inflammation and enhance endothelial function. In view of these pharmacologic properties, W. somnifera is a potential drug candidate to treat various clinical conditions, particularly related to the nervous system. In this review, we summarize the pharmacologic characteristics and discuss the mechanisms of action and potential therapeutic applications of the plant and its active constituents.

Definition and measurement of guilt: Implications for clinical research and practice.

PubMed

Tilghman-Osborne, Carlos; Cole, David A; Felton, Julia W

2010-07-01

Research on the relation of guilt to psychopathology is highly inconsistent. Some studies suggest that guilt contributes to psychopathology; others suggest that guilt serves a protective role. This review of 23 theory-based definitions of guilt and 25 measures of guilt suggests that a lack of conceptual clarity may be to blame. Measures of guilt do not correspond well to the definitions from which they derive. Many definitions and measures reflect the intrusion of extraneous constructs that could confound guilt research. Furthermore, definitions and measures of guilt change with developmental level. Nevertheless, two broad conceptualizations of guilt emerge. Central to both is a focus on one's action or inactions involving real or imagined moral transgressions. Distinguishing the two conceptualizations is whether or not guilt is inherently adaptive construct, generating remorse, augmenting a sense of responsibility, and motivating reparation. Recommendations for the definition and measurement of guilt are discussed. 2010 Elsevier Ltd. All rights reserved.

Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design.

PubMed

Mease, Kirsten M; Kimzey, Amy L; Lansita, Janice A

2017-06-01

The observation of an infusion reaction (IR) in a nonclinical study can cause concern among investigators and regulators in the development of biotherapeutics. Biomarkers can be informative to determine whether the reactions are immune-mediated or test-article related and if there is a potential risk to human subjects. IRs encompass a broad range of adverse events with a variety of triggers; the focus of this paper is IRs due to cytokine release syndrome or immune complex formation and the associated biomarkers. Such reactions generally do not preclude clinical development or marketing approval, because it is widely accepted that immune-mediated reactions in nonclinical species are not predictive of human outcomes. Several US approved products (from 2004 to 2016) have documented IRs in nonclinical species. This review article discusses recent examples, the biomarkers evaluated, and implications for study design and conduct.

Child and adolescent psychopathology: spiritual and religious perspectives.

PubMed

Mabe, P Alex; Josephson, Allan M

2004-01-01

This article addresses the relationship between children's religious beliefs and spiritual practices and the presence of psychopathology. Study of this subject represents a formidable task due to the complexity and diversity of the constructs involved, heterogeneity in religious beliefs and practices, and the difficulty in discriminating between the independent effects of religion and culture. Nevertheless, broad links between child psychopathology and spiritual/religious beliefs and practices are proposed. On the whole, the available empiric data suggest that religion is primarily health promoting in direct, positive benefits for children and in indirect, positive effects through parent and family functioning, although there are isolated exceptions. When spirituality and religious beliefs/practices are associated with negative mental health outcomes in children or their families, evidence points to "poorness-of-fit," based on an interaction between the child's psychopathology and aspects and religious beliefs/practice. Clinical implications of the findings and proposels are outlined.

Cross-Cultural Studies of Personality Traits and their Relevance to Psychiatry

PubMed Central

Terracciano, Antonio; McCrae, Robert R.

2009-01-01

Aims This article provides a brief review of recent cross-cultural research on personality traits at both individual and culture levels, highlighting the relevance of recent findings for psychiatry. Method In most cultures around the world, personality traits can be clearly summarized by the five broad dimensions of the Five-Factor Model (FFM), which makes it feasible to compare cultures on personality and psychopathology. Results Maturational patterns and sex differences in personality traits generally show cultural invariance, which generates the hypothesis that age of onset, clinical evolution, and sex differences in the prevalence of psychiatric disorders might follow similar universal patterns. The average personality profiles from 51 cultures show meaningful geographical distributions and associations with culture-level variables, but are clearly unrelated to national character stereotypes. Conclusions Aggregate personality scores can potentially be related to epidemiological data on psychiatric disorders, and dimensional personality models have implications for psychiatric diagnosis and treatment around the world. PMID:17128620

Stress Increases Peripheral Axon Growth and Regeneration through Glucocorticoid Receptor-Dependent Transcriptional Programs

PubMed Central

Alexander, Jessica K.; Madalena, Kathryn M.; Motti, Dario; Quach, Tam; Zha, Alicia; Webster Marketon, Jeanette

2017-01-01

Abstract Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain, but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal GC receptor (Nr3c1, also known as GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (M. musculus). In response to stress or GCs, adult DRG neurite growth increases through mechanisms involving GR-dependent gene transcription. In vivo, prior exposure to an acute systemic stress increases peripheral nerve regeneration. These data have broad clinical implications and highlight the importance of stress and GCs as novel behavioral and circulating modifiers of neuronal plasticity. PMID:28828403

Definition and measurement of guilt: Implications for clinical research and practice

PubMed Central

Tilghman-Osborne, Carlos; Cole, David A.; Felton, Julia W.

2014-01-01

Research on the relation of guilt to psychopathology is highly inconsistent. Some studies suggest that guilt contributes to psychopathology; others suggest that guilt serves a protective role. This review of 23 theory-based definitions of guilt and 25 measures of guilt suggests that a lack of conceptual clarity may be to blame. Measures of guilt do not correspond well to the definitions from which they derive. Many definitions and measures reflect the intrusion of extraneous constructs that could confound guilt research. Furthermore, definitions and measures of guilt change with developmental level. Nevertheless, two broad conceptualizations of guilt emerge. Central to both is a focus on one’s action or inactions involving real or imagined moral transgressions. Distinguishing the two conceptualizations is whether or not guilt is inherently adaptive construct, generating remorse, augmenting a sense of responsibility, and motivating reparation. Recommendations for the definition and measurement of guilt are discussed. PMID:20451312

Noonan syndrome.

PubMed

Bhambhani, Vikas; Muenke, Maximilian

2014-01-01

Noonan syndrome is a common genetic disorder that causes multiple congenital abnormalities and a large number of potential health conditions. Most affected individuals have characteristic facial features that evolve with age; a broad, webbed neck; increased bleeding tendency; and a high incidence of congenital heart disease, failure to thrive, short stature, feeding difficulties, sternal deformity, renal malformation, pubertal delay, cryptorchidism, developmental or behavioral problems, vision problems, hearing loss, and lymphedema. Familial recurrence is consistent with an autosomal dominant mode of inheritance, but most cases are due to de novo mutations. Diagnosis can be made on the basis of clinical features, but may be missed in mildly affected patients. Molecular genetic testing can confirm diagnosis in 70% of cases and has important implications for genetic counseling and management. Most patients with Noonan syndrome are intellectually normal as adults, but some may require multidisciplinary evaluation and regular follow-up care. Age-based Noonan syndrome-specific growth charts and treatment guidelines are available.

Commentary: Understanding the impact of domestic violence on children, recognizing strengths, and promoting resilience: reflections on Harold and Sellers (2018).

PubMed

Osofsky, Joy D

2018-04-01

Violence and abuse in families occurs frequently with significant impact on children of all ages. However, this type of interpersonal violence is often the least disclosed or discussed. Therefore, the Harold and Sellers paper is important to bring attention to the broad range of both behavioral and neuroscience research in this area and the clinical implications for children and adolescents including risk for later psychopathology. The commentary also expands an understanding of the impact and outcomes for very young children exposed to domestic violence. The authors provide a thorough description of the many prevention and intervention programs and approaches to help children exposed to domestic violence. In conclusion, it is essential to recognize that even at times of adversity for children and families, such as when domestic violence occurs, it is important to recognize strengths and support resilience. © 2018 Association for Child and Adolescent Mental Health.

Orchestration of intestinal homeostasis and tolerance by group 3 innate lymphoid cells.

PubMed

Penny, Hugo A; Hodge, Suzanne H; Hepworth, Matthew R

2018-05-08

The gastrointestinal tract is the primary site of exposure to a multitude of microbial, environmental, and dietary challenges. As a result, immune responses in the intestine need to be tightly regulated in order to prevent inappropriate inflammatory responses to exogenous stimuli. Intestinal homeostasis and tolerance are mediated through a multitude of immune mechanisms that act to reinforce barrier integrity, maintain the segregation and balance of commensal microbes, and ensure tissue health and regeneration. Here, we discuss the role of group 3 innate lymphoid cells (ILC3) as key regulators of intestinal health and highlight how increasing evidence implicates dysregulation of this innate immune cell population in the onset or progression of a broad range of clinically relevant pathologies. Finally, we discuss how the next generation of immunotherapeutics may be utilized to target ILC3 in disease and restore gastrointestinal tolerance and tissue health.

Magnesium deficiency: What is our status

USDA-ARS?s Scientific Manuscript database

Low magnesium intake has been implicated in a broad range of cardiometabolic conditions, including diabetes, hypertension, and cardiovascular disease. Dietary magnesium and total body magnesium status have a widely-used but imperfect biomarker in serum magnesium. Despite serum magnesium’s limitation...

Activity of pradofloxacin against Porphyromonas and Prevotella spp. Implicated in periodontal disease in dogs: susceptibility test data from a European multicenter study.

PubMed

Stephan, Bernd; Greife, Heinrich A; Pridmore, Andrew; Silley, Peter

2008-06-01

Collaborating veterinarians from five European countries collected subgingival bacterial samples from dogs exhibiting clinical periodontal disease. Sterile endodontic paper points were used for collection of the samples, which were transported to a central laboratory for susceptibility testing. Anaerobic bacteria were isolated and Porphyromonas and Prevotella isolates identified to the species level; susceptibility to pradofloxacin and metronidazole was determined using the CLSI agar dilution methodology. A total of 630 isolates, 310 of Porphyromonas spp. and 320 of Prevotella spp., were isolated. Pradofloxacin MIC data for all isolates were in the range of < or =0.016 to 1 microg/ml, the overall MIC(50) was 0.062, and the overall MIC(90) was 0.25 microg/ml. There were no differences in activity against Porphyromonas and Prevotella isolates or in the pradofloxacin susceptibility distributions from the different European countries. All isolates were within the wild-type distribution and were fully susceptible to pradofloxacin. Metronidazole was also highly active against these strains: 316 of 320 Prevotella strains (98.8%) and 309 of 310 Porphyromonas strains (99.7%) were susceptible (MICs of < or =8 microg/ml). However, three Prevotella strains had intermediate metronidazole susceptibility (MICs of 16 microg/ml), while one Prevotella and one Porphyromonas strain were metronidazole resistant (MICs of 128 and 256 microg/ml, respectively). Pradofloxacin, a novel broad-spectrum fluoroquinolone, demonstrates a high degree of antianaerobic activity against strains isolated from clinical cases of periodontal disease and shows activity against metronidazole-resistant isolates. The broad-spectrum activity of pradofloxacin makes it a suitable candidate for the treatment of periodontal disease in dogs.

Activity of Pradofloxacin against Porphyromonas and Prevotella spp. Implicated in Periodontal Disease in Dogs: Susceptibility Test Data from a European Multicenter Study▿

PubMed Central

Stephan, Bernd; Greife, Heinrich A.; Pridmore, Andrew; Silley, Peter

2008-01-01

Collaborating veterinarians from five European countries collected subgingival bacterial samples from dogs exhibiting clinical periodontal disease. Sterile endodontic paper points were used for collection of the samples, which were transported to a central laboratory for susceptibility testing. Anaerobic bacteria were isolated and Porphyromonas and Prevotella isolates identified to the species level; susceptibility to pradofloxacin and metronidazole was determined using the CLSI agar dilution methodology. A total of 630 isolates, 310 of Porphyromonas spp. and 320 of Prevotella spp., were isolated. Pradofloxacin MIC data for all isolates were in the range of ≤0.016 to 1 μg/ml, the overall MIC50 was 0.062, and the overall MIC90 was 0.25 μg/ml. There were no differences in activity against Porphyromonas and Prevotella isolates or in the pradofloxacin susceptibility distributions from the different European countries. All isolates were within the wild-type distribution and were fully susceptible to pradofloxacin. Metronidazole was also highly active against these strains: 316 of 320 Prevotella strains (98.8%) and 309 of 310 Porphyromonas strains (99.7%) were susceptible (MICs of ≤8 μg/ml). However, three Prevotella strains had intermediate metronidazole susceptibility (MICs of 16 μg/ml), while one Prevotella and one Porphyromonas strain were metronidazole resistant (MICs of 128 and 256 μg/ml, respectively). Pradofloxacin, a novel broad-spectrum fluoroquinolone, demonstrates a high degree of antianaerobic activity against strains isolated from clinical cases of periodontal disease and shows activity against metronidazole-resistant isolates. The broad-spectrum activity of pradofloxacin makes it a suitable candidate for the treatment of periodontal disease in dogs. PMID:18411326

Defining the relationship between COPD and CVD: what are the implications for clinical practice?

PubMed Central

Morgan, Ann D; Zakeri, Rosita; Quint, Jennifer K

2018-01-01

Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD). CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality. The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself. Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade. But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population. The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors. In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence. We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD. While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years. Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective. PMID:29355081

Development of a large urban longitudinal HIV clinical cohort using a web-based platform to merge electronically and manually abstracted data from disparate medical record systems: technical challenges and innovative solutions

PubMed Central

Hays, Harlen; Castel, Amanda D; Subramanian, Thilakavathy; Happ, Lindsey Powers; Jaurretche, Maria; Binkley, Jeff; Kalmin, Mariah M; Wood, Kathy; Hart, Rachel

2016-01-01

Objective Electronic medical records (EMRs) are being increasingly utilized to conduct clinical and epidemiologic research in numerous fields. To monitor and improve care of HIV-infected patients in Washington, DC, one of the most severely affected urban areas in the United States, we developed a city-wide database across 13 clinical sites using electronic data abstraction and manual data entry from EMRs. Materials and Methods To develop this unique longitudinal cohort, a web-based electronic data capture system (Discovere®) was used. An Agile software development methodology was implemented across multiple EMR platforms. Clinical informatics staff worked with information technology specialists from each site to abstract data electronically from each respective site’s EMR through an extract, transform, and load process. Results Since enrollment began in 2011, more than 7000 patients have been enrolled, with longitudinal clinical data available on all patients. Data sets are produced for scientific analyses on a quarterly basis, and benchmarking reports are generated semi-annually enabling each site to compare their participants’ clinical status, treatments, and outcomes to the aggregated summaries from all other sites. Discussion Numerous technical challenges were identified and innovative solutions developed to ensure the successful implementation of the DC Cohort. Central to the success of this project was the broad collaboration established between government, academia, clinics, community, information technology staff, and the patients themselves. Conclusions Our experiences may have practical implications for researchers who seek to merge data from diverse clinical databases, and are applicable to the study of health-related issues beyond HIV. PMID:26721732

Nicotinamide Suppresses the DNA Damage Sensitivity of Saccharomyces cerevisiae Independently of Sirtuin Deacetylases.

PubMed

Rössl, Anthony; Bentley-DeSousa, Amanda; Tseng, Yi-Chieh; Nwosu, Christine; Downey, Michael

2016-10-01

Nicotinamide is both a reaction product and an inhibitor of the conserved sirtuin family of deacetylases, which have been implicated in a broad range of cellular functions in eukaryotes from yeast to humans. Phenotypes observed following treatment with nicotinamide are most often assumed to stem from inhibition of one or more of these enzymes. Here, we used this small molecule to inhibit multiple sirtuins at once during treatment with DNA damaging agents in the Saccharomyces cerevisiae model system. Since sirtuins have been previously implicated in the DNA damage response, we were surprised to observe that nicotinamide actually increased the survival of yeast cells exposed to the DNA damage agent MMS. Remarkably, we found that enhanced resistance to MMS in the presence of nicotinamide was independent of all five yeast sirtuins. Enhanced resistance was also independent of the nicotinamide salvage pathway, which uses nicotinamide as a substrate to generate NAD+, and of a DNA damage-induced increase in the salvage enzyme Pnc1 Our data suggest a novel and unexpected function for nicotinamide that has broad implications for its use in the study of sirtuin biology across model systems. Copyright © 2016 by the Genetics Society of America.

Nicotinamide Suppresses the DNA Damage Sensitivity of Saccharomyces cerevisiae Independently of Sirtuin Deacetylases

PubMed Central

Rössl, Anthony; Bentley-DeSousa, Amanda; Tseng, Yi-Chieh; Nwosu, Christine; Downey, Michael

2016-01-01

Nicotinamide is both a reaction product and an inhibitor of the conserved sirtuin family of deacetylases, which have been implicated in a broad range of cellular functions in eukaryotes from yeast to humans. Phenotypes observed following treatment with nicotinamide are most often assumed to stem from inhibition of one or more of these enzymes. Here, we used this small molecule to inhibit multiple sirtuins at once during treatment with DNA damaging agents in the Saccharomyces cerevisiae model system. Since sirtuins have been previously implicated in the DNA damage response, we were surprised to observe that nicotinamide actually increased the survival of yeast cells exposed to the DNA damage agent MMS. Remarkably, we found that enhanced resistance to MMS in the presence of nicotinamide was independent of all five yeast sirtuins. Enhanced resistance was also independent of the nicotinamide salvage pathway, which uses nicotinamide as a substrate to generate NAD+, and of a DNA damage-induced increase in the salvage enzyme Pnc1. Our data suggest a novel and unexpected function for nicotinamide that has broad implications for its use in the study of sirtuin biology across model systems. PMID:27527516

Tricyclic GyrB/ParE (TriBE) Inhibitors: A New Class of Broad-Spectrum Dual-Targeting Antibacterial Agents

PubMed Central

Tari, Leslie W.; Li, Xiaoming; Trzoss, Michael; Bensen, Daniel C.; Chen, Zhiyong; Lam, Thanh; Zhang, Junhu; Lee, Suk Joong; Hough, Grayson; Phillipson, Doug; Akers-Rodriguez, Suzanne; Cunningham, Mark L.; Kwan, Bryan P.; Nelson, Kirk J.; Castellano, Amanda; Locke, Jeff B.; Brown-Driver, Vickie; Murphy, Timothy M.; Ong, Voon S.; Pillar, Chris M.; Shinabarger, Dean L.; Nix, Jay; Lightstone, Felice C.; Wong, Sergio E.; Nguyen, Toan B.; Shaw, Karen J.; Finn, John

2013-01-01

Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highly conserved ATP-binding subunits of DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD), we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models. PMID:24386374

No Compton Reflection In a Chandra/RXTE Observation of Mkn 509: Implications for the Fe-K Line Emission From Accreting X-Ray Sources

NASA Technical Reports Server (NTRS)

Yaqoob, Tahir; Padmanabhan, Urmila; Kraemer, Steven B.; Crenshaw, D. Michael; Mckernan, Barry; George, Ian M.; Turner, T. Jane; White, Nicholas E. (Technical Monitor)

2002-01-01

We report the results of simultaneous Chandra and RXTE observations of the Seyfert 1 galaxy Mkn 509. We deconvolve the broad and narrow Fe-K emission-line components for which we measure rest-frame equivalent widths of 119+/-18 eV and 57+/-13 eV respectively. The broad line has a FWHM of 57,600((sup 14,400)(sub -21,000)) km/s and the narrow line is unresolved, with an upper limit on the FWHM of 4,940 km/s. Both components must originate in cool matter since we measure rest-frame center energies of 6.36((sup +0.13)(sub -0.12)) keV and 6.42+/-0.01 keV for the broad and narrow line respectively. This rules out He-like and H-like Fe for the origin of both the broad and narrow lines. If, as is widely accepted, the broad Fe-K line originates in Thomson-thick matter (such as an accretion disk), then one expects to observe spectral curvature above approximately 10 keV, (commensurate with the observed broad line), characteristic of the Compton-reflection continuum. However our data sets very stringent limits on deviations of the observed continuum from a power law. Light travel-time delays cannot be invoked to explain anomalies in the relative strengths of the broad Ferry line and Compton-reflection continuum since they are supposed to originate in the same physical location. We are forced to conclude that both the broad and narrow Fe-K lines had to originate in Thomson-thin matter during our observation. This result, for a single observation of just one source, means that our understanding of Fe K line emission and Compton reflection from accreting X-ray sources in general needs to be re-examined. For example, if an irradiated accretion disk existed in Mkn 509 at the time of the observations, the lack of spectral curvature above approximately 10 keV suggests two possibilities. Either the disk was Thomson-thick and highly ionized, having negligible Fe-K line emission and photoelectric absorption or the disk was Thomson-thin producing some or all of the broad Fe-K line emission. In the former case, the broad Fe-K line had to have produced in a Thomson-thin region elsewhere. In both cases the predicted spectral curvature above approximately 10 keV is negligible. An additional implication of our results is that any putative obscuring torus in the system, required by unification models of active galaxies, must also be Thomson-thin. The same applies to the optical broad line region (BLR) if it has a substantial covering factor.

Improving clinical trials in the critically ill.

PubMed

Angus, Derek C; Mira, Jean-Paul; Vincent, Jean-Louis

2010-02-01

To propose ways in which clinical trials in intensive care can be improved. An international roundtable conference was convened focused on improvement in three broad areas: translation of new knowledge from bench to bedside; design and conduct of clinical trials; and clinical trial infrastructure and environment. The roundtable recommendations were: improvement in clinical trials is a multistep process from better preclinical studies to better clinical trial methodology; new technologies should be used to improve models of critical illness; diseasomes and theragnostics will aid inpatient population selection and more appropriate targeting of interventions; broader study end points should include morbidity as well as mortality; more multicenter studies should be conducted by national and international networks or clinical trials groups; and better collaboration is needed with the industry. There was broad agreement among the roundtable participants regarding a number of explicit opportunities for the improvement of clinical trials in critical care.

Broad-Spectrum Molecular Detection of Fungal Nucleic Acids by PCR-Based Amplification Techniques.

PubMed

Czurda, Stefan; Lion, Thomas

2017-01-01

Over the past decade, the incidence of life-threatening invasive fungal infections has dramatically increased. Infections caused by hitherto rare and emerging fungal pathogens are associated with significant morbidity and mortality among immunocompromised patients. These observations render the coverage of a broad range of clinically relevant fungal pathogens highly important. The so-called panfungal or, perhaps more correctly, broad-range nucleic acid amplification techniques do not only facilitate sensitive detection of all clinically relevant fungal species but are also rapid and can be applied to analyses of any patient specimens. They have therefore become valuable diagnostic tools for sensitive screening of patients at risk of invasive fungal infections. This chapter summarizes the currently available molecular technologies employed in testing of a wide range of fungal pathogens, and provides a detailed workflow for patient screening by broad-spectrum nucleic acid amplification techniques.

THE ANXIETY SPECTRUM AND THE REFLEX PHYSIOLOGY OF DEFENSE: FROM CIRCUMSCRIBED FEAR TO BROAD DISTRESS

PubMed Central

McTeague, Lisa M.; Lang, Peter J.

2013-01-01

Guided by the diagnostic nosology, anxiety patients are expected to show defensive hyperarousal during affective challenge, irrespective of the principal phenotype. In the current study, patients representing the whole spectrum of anxiety disorders (i.e., specific phobia, social phobia, panic disorder with or without agoraphobia, obsessive-compulsive disorder, generalized anxiety disorder (GAD), posttraumatic stress disorder(PTSD)), and healthy community control participants, completed an imagery-based fear elicitation paradigm paralleling conventional intervention techniques. Participants imagined threatening and neutral narratives as physiological responses were recorded. Clear evidence emerged for exaggerated reactivity to clinically relevant imagery—most pronounced in startle reflex responding. However, defensive propensity varied across principal anxiety disorders. Disorders characterized by focal fear and impairment (e.g., specific phobia) showed robust fear potentiation. Conversely, for disorders of long-enduring, pervasive apprehension and avoidance with broad anxiety and depression comorbidity (e.g., PTSD secondary to cumulative trauma, GAD), startle responses were paradoxically diminished to all aversive contents. Patients whose expressed symptom profiles were intermediate between focal fearfulness and broad anxious-misery in both severity and chronicity exhibited a still heightened but more generalized physiological propensity to respond defensively. Importantly, this defensive physiological gradient—the inverse of self-reported distress—was evident not only between but also within disorders. These results highlight that fear circuitry could be dysregulated in chronic, pervasive anxiety, and preliminary functional neuroimaging findings suggest that deficient amygdala recruitment could underlie attenuated reflex responding. In summary, adaptive defensive engagement during imagery may be compromised by long-term dysphoria and stress—a phenomenon with implications for prognosis and treatment planning. Depression and Anxiety 29:264–281, 2012. PMID:22511362

Understanding Women: Implications for Personality Theory and Research

ERIC Educational Resources Information Center

Carlson, Rae

1972-01-01

Addressing the neglect of work on feminine psychology, this paper proposes three research issues: duality in human nature, typology and qualitative patterning, and biological bases of personality. Such research would end the broad impoverishment of contemporary work in personality. (Author/JM)

Technological Strategies and National Purpose

ERIC Educational Resources Information Center

Gilpin, Robert

1970-01-01

Discusses the international and domestic implications of technological growth. Defines three basic national strategies: a broad front approach, scientific and technological specialization and importation. Analyzes the strategies followed by form countries - France, the United States, Sweden, and Japan- to illustrate the alternatives and the…

At, with and beyond risk: expectations of living with the possibility of future dementia.

PubMed

Milne, Richard; Diaz, Ana; Badger, Shirlene; Bunnik, Eline; Fauria, Karine; Wells, Katie

2018-04-16

Biomedical research aimed at the development of therapies for chronic and late-onset conditions increasingly concentrates on the early treatment of symptom-less disease. This broad trend is evidenced in prominent shifts in contemporary dementia research. Revised diagnostic criteria and new approaches to clinical trials propose a focus on earlier stages of disease and prompt concerns about the implications of communicating test results associated with the risk of developing dementia when no effective treatments are available. This article examines expectations of the implications of learning test results related to dementia risk, based on focus group research conducted in the UK and Spain. It points to the extended social and temporal aspects of the dementia risk experience. Three key dimensions of this risk experience are elaborated: living 'at risk', represented in efforts to reduce risk and plan for the future; 'with risk', through vigilance towards cognitive health and earlier or prolonged contact with healthcare services; and finally, 'beyond risk' through a cessation of the self in its current social, legal and financial form. A virtual abstract of this paper can be viewed at: https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA. © 2018 Foundation for the Sociology of Health & Illness.

FLARE-LIKE VARIABILITY OF THE Mg II {lambda}2800 EMISSION LINE IN THE {gamma}-RAY BLAZAR 3C 454.3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leon-Tavares, J.; Chavushyan, V.; Patino-Alvarez, V.

2013-02-01

We report the detection of a statistically significant flare-like event in the Mg II {lambda}2800 emission line of 3C 454.3 during the outburst of autumn 2010. The highest levels of emission line flux recorded over the monitoring period (2008-2011) coincide with a superluminal jet component traversing through the radio core. This finding crucially links the broad emission line fluctuations to the non-thermal continuum emission produced by relativistically moving material in the jet and hence to the presence of broad-line region clouds surrounding the radio core. If the radio core were located at several parsecs from the central black hole, thenmore » our results would suggest the presence of broad-line region material outside the inner parsec where the canonical broad-line region is envisaged to be located. We briefly discuss the implications of broad emission line material ionized by non-thermal continuum in the context of virial black hole mass estimates and gamma-ray production mechanisms.« less

Factors associated with self-reported health: implications for screening level community-based health and environmental studies

EPA Science Inventory

BACKGROUND: Advocates for environmental justice, local, state, and national public health officials, exposure scientists, need broad-based heath indices to identify vulnerable communities. Longitudinal studies show that perception of current health status predicts subsequent mort...

Is there an Asian idiom of distress? Somatic symptoms in female Japanese and Korean students.

PubMed

Saint Arnault, Denise; Kim, Oksoo

2008-02-01

The term 'idiom of distress' is used to describe culturally specific experiences of suffering. Most of these studies have been conducted with small groups, making comparison of symptom profiles difficult. Female undergraduate and graduate students in Japan (n = 50) and Korea (n = 61) completed the Beck Depression Inventory (BDI) and 7-day daily reports of their experiences of 46 somatic symptoms. Between-culture comparisons revealed that BDI scores did not differ; however, the Korean women had significantly higher somatic distress means than the Japanese women. Despite the higher Korean distress mean, regression analysis showed that somatic distress explained 30% of the variance of BDI score for the Japanese but only 22% of the variance for the Koreans. Within-culture comparisons showed that both high-BDI Japanese and Koreans had 19 somatic distress symptoms with significantly higher means than their low-BDI counterparts; 11 somatic symptoms were shared by the two groups. Multidimensional scaling matrices were used to compare symptom proximities and revealed cultural differences. The problems with using broad racial categories in clinical research, the clinical significance of these findings, and the implications for psychiatric nursing assessment and practice are discussed.

The enigma of nonarteritic anterior ischemic optic neuropathy: an update for the comprehensive ophthalmologist.

PubMed

Gaier, Eric D; Torun, Nurhan

2016-11-01

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute optic nerve injury, and frequently presents to comprehensive ophthalmologists. We review the typical and atypical clinical features and current literature on various treatment modalities for NAION. The epidemiology and clinical presentation of this disease can be variable, making a definitive diagnosis difficult in many cases. In addition, the differential diagnoses for this disorder, although comprising much less prevalent entities, are quite broad and can have substantial systemic implications if these alternatives go unrecognized. NAION has many systemic associations and comorbidities that deserve inquiry when the diagnosis is made. There are currently no widely accepted, evidence-based treatments for NAION. All recommendations made to patients to reduce their risk of sequential eye involvement, including avoidance of potential nocturnal hypotension, erectile dysfunction medication, and treatment of obstructive sleep apnea, have theoretical bases. NAION is a common cause of acute vision loss in adult and older patients, and thus, comprehensive ophthalmologists need to be able to diagnose and appropriately manage this disorder. We anticipate fruitful results from current and future trials aimed at neuroprotection in the affected eye and prevention of sequential eye involvement.

Is there an Asian idiom of distress? Somatic Symptoms in Female Japanese and Korean Students

PubMed Central

Arnault, Denise Saint; Kim, Oksoo

2007-01-01

The term “idiom of distress” is used to describe culturally-specific experiences of suffering. Most of these studies have been conducted with small groups, making comparison of symptom profiles difficult. Female undergraduate and graduate students in Japan (N=50) and Korea (N=61) completed Beck Depression Inventory (BDI) and seven-day dairy reports of their experiences of 46 somatic symptoms. Between-culture comparisons revealed that BDI scores did not differ; however, Korean women had significantly higher somatic distress means than the Japanese women. Despite the higher Korean distress mean, regression analysis showed that somatic distress explained 30% of the variance of BDI score for the Japanese, but only 22% of the variance for the Koreans. Within-culture comparisons showed that both the High BDI Japanese and Koreans had 19 somatic distress symptoms with significantly higher means than their Low BDI counterparts; eleven somatic symptoms were shared by the two groups. Multidimensional Scaling matrices were used to compare symptom proximities and revealed cultural differences. The problems with using broad racial categories in clinical research, the clinical significance of these findings, and implications for psychiatric nursing assessment and practice are discussed. PMID:18207054

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer

PubMed Central

Carethers, John M; Stoffel, Elena M

2015-01-01

Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management. PMID:26309352

Psychological Flexibility as a Buffer against Caregiver Distress in Families with Psychosis.

PubMed

Jansen, Jens E; Haahr, Ulrik H; Lyse, Hanne-Grethe; Pedersen, Marlene B; Trauelsen, Anne M; Simonsen, Erik

2017-01-01

Background: Research has shown that caregivers of persons with psychosis play an invaluable role in recovery, but unfortunately, often report high levels of distress. While cognitive models of caregiver distress have been well-supported, there is still limited knowledge of the psychological factors involved. Recent advances in cognitive behavioral therapy seem to converge on the importance of acceptance- and mindfulness based processes. Aim: To examine the impact of psychological flexibility on caregiver distress in the early phases of psychosis, while controlling for known predictors of caregiver distress. Method: Within a cross-sectional design, 101 caregivers of 38 persons with first-episode psychosis in a clinical epidemiological sample completed a series of self-report measures. Results: A linear mixed model analysis found that, after controlling for caregiver socio-demographic factors, service user symptoms, drug use and global functioning, psychological flexibility was a significant predictor of caregiver distress. Conclusion: Greater level of psychological flexibility in caregivers, seems to be related to lower levels of caregiver distress. This finding corresponds to studies within a broad range of emotional disorders. There may be important clinical implications in terms of facilitating the process of acceptance through interventions from the 'third-wave' or contextual cognitive behavioral therapies.

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.

PubMed

Carethers, John M; Stoffel, Elena M

2015-08-21

Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.

Loss of Cytoplasmic CDK1 Predicts Poor Survival in Human Lung Cancer and Confers Chemotherapeutic Resistance

PubMed Central

Zhang, Chunyu; Elkahloun, Abdel G.; Robertson, Matthew; Gills, Joell J.; Tsurutani, Junji; Shih, Joanna H.; Fukuoka, Junya; Hollander, M. Christine; Harris, Curtis C.; Travis, William D.; Jen, Jin; Dennis, Phillip A.

2011-01-01

The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer. We profiled gene expression signatures during lung epithelial cell immortalization and transformation, and showed that genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes were validated by immunoblotting and 4 genes were further evaluated in non-small cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor tissues, its loss from the cytoplasm unexpectedly predicted poor survival and conferred resistance to chemotherapy in multiple cell lines, especially microtubule-directed agents. An analysis of expression of CDK1 and CDK1-associated genes in the NCI60 cell line database confirmed the broad association of these genes with chemotherapeutic responsiveness. These results have implications for personalizing lung cancer therapy and highlight the potential of combined approaches for biomarker discovery. PMID:21887332

Considering virtue: public health and clinical ethics.

PubMed

Meagher, Karen M

2011-10-01

As bioethicists increasingly turn their attention to the profession of public health, many candidate frameworks have been proposed, often with an eye toward articulating the values and foundational concepts that distinguish this practice from curative clinical medicine. First, I will argue that while these suggestions for a distinct ethics of public health are promising, they arise from problems within contemporary bioethics that must be taken into account. Without such cognizance of the impetus for public health ethics, we risk developing a set of ethical resources meant exclusively for public health professionals, thereby neglecting implications for curative medical ethics and the practice of bioethics more broadly. Second, I will present reasons for thinking some of the critiques of dominant contemporary bioethics can be met by a virtue ethics approach. I present a virtue ethics response to criticisms that concern (1) increased rigor in bioethics discourse; (2) the ability of normative theory to accommodate context; and (3) explicit attention to the nature of ethical conflict. I conclude that a virtue ethics approach is a viable avenue for further inquiry, one that leads us away from developing ethics of public health in a vacuum and has the potential for overcoming certain pitfalls of contemporary bioethics discourse. © 2011 Blackwell Publishing Ltd.

Necroptosis in Acute Kidney Injury.

PubMed

Anders, Hans-Joachim

2018-05-31

Regulated necrosis is an expanding research field with important implications for acute kidney injury (AKI). A focused review of the evolving evidence for necroptosis in AKI, one of several forms of regulated necrosis defines the known and unknown. A literature search was performed in PUBMED and ScienceDirect between January 1957 and April 2018 using the following keywords: "acute kidney injury," "necrosis," "necroptosis," "necroinflammation." The necroptosis signaling cascade involves a number of proteins including receptor-interacting protein-1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) as well as the MLKL regulator RGMb. The existing experimental evidence in AKI based on mice with genetic deletions of these proteins, more or less specific inhibitory compounds, and diverse experimental AKI models is reviewed. There is broad consistency suggesting a role for necroptosis in AKI, but some studies report divergent evidence potentially relating to the specific model used and the time point of analysis. Mlkl-deficient mice are currently the most specific and reliable experimental tool to study necroptosis in vivo (in kidney disease). The clinical potential of necroptosis inhibition in AKI is to be evaluated, but conceptual problems in AKI definitions and in complex clinical scenarios remain a concern. © 2018 S. Karger AG, Basel.

Noncardiac Vascular Toxicities of Vascular Endothelial Growth Factor Inhibitors in Advanced Cancer: A Review

PubMed Central

Bowen, Joanne; Gibson, Rachel; Tan, Thean; Okera, Meena; Stringer, Andrea

2011-01-01

Summary. The introduction of molecularly targeted anticancer therapies has brought the promise of longer survival times for select patients with cancers previously considered untreatable. However, it has also brought new toxicities that require understanding and management, sometimes for long periods of time. Vascular endothelial growth factor inhibitors are associated with a broad range of adverse effects, with vascular toxicity being particularly serious. This review focuses on the current understanding of the pathophysiology and mechanisms of macrovascular toxicities (hypertension, hemorrhage, and thromboembolism), their incidence and severity, the current clinical management, and implications in the advanced cancer setting. Movement of these agents into the early disease setting will alter the impact of these toxicities. Search Strategy and Selection Criteria. Information for this review was collected by searching PubMed/Medline and American Society of Clinical Oncology abstract databases. The medical subject heading terms used included toxicity, hypertension, thromboembolism, hemorrhage, intestinal perforation, risk factors, pharmacokinetics, and metabolism, combined with free text search terms including, but not limited to, VEGF inhibitor*, bevacizumab, sunitinib, and sorafenib. Articles published in English before March 2010 were included, in addition to information from case reports and pharmaceutical agent package inserts. PMID:21441297

Dimensions of Emotion Dysregulation in Anorexia Nervosa and Bulimia Nervosa: A Conceptual Review of the Empirical Literature

PubMed Central

Lavender, Jason M.; Wonderlich, Stephen A.; Engel, Scott G.; Gordon, Kathryn H.; Kaye, Walter H.; Mitchell, James E.

2015-01-01

Several existing conceptual models and psychological interventions address or emphasize the role of emotion dysregulation in eating disorders. The current article uses Gratz and Roemer’s (2004) multidimensional model of emotion regulation and dysregulation as a clinically relevant framework to review the extant literature on emotion dysregulation in anorexia nervosa (AN) and bulimia nervosa (BN). Specifically, the dimensions reviewed include: (1) the flexible use of adaptive and situationally appropriate strategies to modulate the duration and/or intensity of emotional responses, (2) the ability to successfully inhibit impulsive behavior and maintain goal-directed behavior in the context of emotional distress, (3) awareness, clarity, and acceptance of emotional states, and (4) the willingness to experience emotional distress in the pursuit of meaningful activities. The current review suggests that both AN and BN are characterized by broad emotion regulation deficits, with difficulties in emotion regulation across the four dimensions found to characterize both AN and BN, although a small number of more specific difficulties may distinguish the two disorders. The review concludes with a discussion of the clinical implications of the findings, as well as a summary of limitations of the existing empirical literature and suggestions for future research. PMID:26112760

Sensorineural Deafness, Distinctive Facial Features and Abnormal Cranial Bones

PubMed Central

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R.; Matsushita, Mark; Raskind, Wendy H.

2008-01-01

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. PMID:18553554

The interpersonal context of client motivational language in cognitive-behavioral therapy.

PubMed

Sijercic, Iris; Button, Melissa L; Westra, Henny A; Hara, Kimberley M

2016-03-01

Previous research has found that client motivational language (especially arguments against change or counterchange talk; CCT) in early therapy sessions is a reliable predictor of therapy process and outcomes across a broad range of treatments including cognitive-behavioral therapy (CBT). Existing studies have considered the general occurrence of CCT, but the present study differentiated 2 types of CCT in early CBT sessions for 37 clients with generalized anxiety disorder: (a) statements that are uttered to express ambivalence regarding change versus (b) statements that are intended to oppose the therapist or therapy. Two process coding systems were used to accomplish this differentiation. Findings indicated that a higher number of CCT statements that occurred in the presence of resistance (opposition to the therapist or therapy) were a substantive and consistent predictor of lower homework compliance and poorer outcomes, up to 1 year posttreatment. Moreover, when both types of CCT were considered together, only opposition CCT was related to outcomes, and ambivalent CCT was not significantly predictive of proximal and distal outcomes. These findings suggest that the interpersonal context in which CCT statements occur may be critically important to their predictive capacity. More broadly, the findings of this study have implications for the future study of client motivational language and underscore the clinical importance of detecting opposition CCT. (c) 2016 APA, all rights reserved).

Tricyclic GyrB/ParE (TriBE) Inhibitors. A new class of broad-spectrum dual-targeting antibacterial agents

DOE PAGES

Tari, Leslie W.; Li, Xiaoming; Trzoss, Michael; ...

2013-12-26

Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. Growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highlymore » conserved ATP-binding subunits of DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD), we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Moreover, lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models.« less

Tricyclic GyrB/ParE (TriBE) Inhibitors. A new class of broad-spectrum dual-targeting antibacterial agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tari, Leslie W.; Li, Xiaoming; Trzoss, Michael

Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. Growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highlymore » conserved ATP-binding subunits of DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD), we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Moreover, lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models.« less

A cross-sectional analysis of pharmaceutical industry-funded events for health professionals in Australia

PubMed Central

Fabbri, Alice; Grundy, Quinn; Mintzes, Barbara; Swandari, Swestika; Moynihan, Ray; Walkom, Emily; Bero, Lisa A

2017-01-01

Objectives To analyse patterns and characteristics of pharmaceutical industry sponsorship of events for Australian health professionals and to understand the implications of recent changes in transparency provisions that no longer require reporting of payments for food and beverages. Design Cross-sectional analysis. Participants and setting 301 publicly available company transparency reports downloaded from the website of Medicines Australia, the pharmaceutical industry trade association, covering the period from October 2011 to September 2015. Results Forty-two companies sponsored 116 845 events for health professionals, on average 608 per week with 30 attendees per event. Events typically included a broad range of health professionals: 82.0% included medical doctors, including specialists and primary care doctors, and 38.3% trainees. Oncology, surgery and endocrinology were the most frequent clinical areas of focus. Most events (64.2%) were held in a clinical setting. The median cost per event was $A263 (IQR $A153–1195) and over 90% included food and beverages. Conclusions Over this 4-year period, industry-sponsored events were widespread and pharmaceutical companies maintained a high frequency of contact with health professionals. Most events were held in clinical settings, suggesting a pervasive commercial presence in everyday clinical practice. Food and beverages, known to be associated with changes to prescribing practice, were almost always provided. New Australian transparency provisions explicitly exclude meals from the reporting requirements; thus, a large proportion of potentially influential payments from pharmaceutical companies to health professionals will disappear from public view. PMID:28667226

Discovery of BMS-955176, a Second Generation HIV-1 Maturation Inhibitor with Broad Spectrum Antiviral Activity.

PubMed

Regueiro-Ren, Alicia; Liu, Zheng; Chen, Yan; Sin, Ny; Sit, Sing-Yuen; Swidorski, Jacob J; Chen, Jie; Venables, Brian L; Zhu, Juliang; Nowicka-Sans, Beata; Protack, Tricia; Lin, Zeyu; Terry, Brian; Samanta, Himadri; Zhang, Sharon; Li, Zhufang; Beno, Brett R; Huang, Xiaohua S; Rahematpura, Sandhya; Parker, Dawn D; Haskell, Roy; Jenkins, Susan; Santone, Kenneth S; Cockett, Mark I; Krystal, Mark; Meanwell, Nicholas A; Hanumegowda, Umesh; Dicker, Ira B

2016-06-09

HIV-1 maturation inhibition (MI) has been clinically validated as an approach to the control of HIV-1 infection. However, identifying an MI with both broad polymorphic spectrum coverage and good oral exposure has been challenging. Herein, we describe the design, synthesis, and preclinical characterization of a potent, orally active, second generation HIV-1 MI, BMS-955176 (2), which is currently in Phase IIb clinical trials as part of a combination antiretroviral regimen.

Spiritual Wellness for Clients with HIV/AIDS: Review of Counseling Issues.

ERIC Educational Resources Information Center

Holt, Jennifer L.; Houg, Bonnie L.; Romano, John L.

1999-01-01

Reviews the salient literature concerning the relationship between HIV/AIDS clients' counseling and spiritual issues. Three broad themes are used: terminal illness issues, religious disenfranchisement, and multicultural spiritual and religious issues. Practical recommendations for counselors and research implications are included. (Author/GCP)

Profiles of Discourse Recognition

ERIC Educational Resources Information Center

Singer, Murray

2013-01-01

A discourse recognition theory derived from more general memory formulations would be broad in its psychological implications. This study compared discourse recognition with some established profiles of item recognition. Participants read 10 stories either once or twice each. They then rated their confidence in recognizing explicit, paraphrased,…

Genetic Counseling as an Educational Process.

ERIC Educational Resources Information Center

Eddy, James M.; St. Pierre, Richard

Historically genetic counseling programs have not included strong educational components or sound educational foundations. This paper deals with some of the drawbacks of current genetic counseling programs and the implications for education in the genetic counseling process. The author adopts a broad definition of genetic counseling which…

The persistent sampling bias in developmental psychology: A call to action.

PubMed

Nielsen, Mark; Haun, Daniel; Kärtner, Joscha; Legare, Cristine H

2017-10-01

Psychology must confront the bias in its broad literature toward the study of participants developing in environments unrepresentative of the vast majority of the world's population. Here, we focus on the implications of addressing this challenge, highlight the need to address overreliance on a narrow participant pool, and emphasize the value and necessity of conducting research with diverse populations. We show that high-impact-factor developmental journals are heavily skewed toward publishing articles with data from WEIRD (Western, educated, industrialized, rich, and democratic) populations. Most critically, despite calls for change and supposed widespread awareness of this problem, there is a habitual dependence on convenience sampling and little evidence that the discipline is making any meaningful movement toward drawing from diverse samples. Failure to confront the possibility that culturally specific findings are being misattributed as universal traits has broad implications for the construction of scientifically defensible theories and for the reliable public dissemination of study findings. Copyright © 2017 Elsevier Inc. All rights reserved.

"In this scenario, I do this, for these reasons": narrative, genre and ethical reasoning in the clinic.

PubMed

Jordens, Christopher F C; Little, Miles

2004-05-01

Narrative analysis has been applied by health researchers to investigate (among other things) clinical reasoning, clinical ethics and human identity. The term 'narrative' is often used as a broad category that covers a variety of spoken genres, however, and it thereby lacks delicacy as an analytic tool. We introduce genre theory, which enables us to differentiate more clearly between story genres and other spoken genres. We then apply the theory to ten narrative-style interviews with clinicians involved in the treatment and management of colorectal cancer in Sydney, Australia. We characterise the narrative-style interview as a macro-genre, and draw attention to the occurrence of spoken genres other than stories. We focus our analysis on a policy genre that occurred naturally and frequently in the spoken discourse of the informants, but which has not been described before in either the literature of social linguistics or the health and medical literature. We analyse two examples of this genre in detail in order to characterise its main semantic features, and differentiate it from story genres. We then discuss the genre with reference to Aristotelian interpretations of ethical reasoning in the clinic. We conclude that the policy genre is both the unfolding of practical wisdom in speech, and the appropriate choice of genre where a display of ethical identity is called for. Finally, we discuss the implications of our findings for ongoing research, for ethics education, for bioethical theory, and for communication between some of the different stakeholder groups in clinical medicine.

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

PubMed Central

Campos-Parra, Alma D.; Cuamani Mitznahuatl, Gerardo; Pedroza-Torres, Abraham; Vázquez Romo, Rafael; Porras Reyes, Fany Iris; López-Urrutia, Eduardo; Pérez-Plasencia, Carlos

2017-01-01

Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC. PMID:28574440

Psychosis prediction and clinical utility in familial high-risk studies: Selective review, synthesis, and implications for early detection and intervention

PubMed Central

Shah, Jai L.; Tandon, Neeraj; Keshavan, Matcheri S.

2016-01-01

Aim Accurate prediction of which individuals will go on to develop psychosis would assist early intervention and prevention paradigms. We sought to review investigations of prospective psychosis prediction based on markers and variables examined in longitudinal familial high-risk (FHR) studies. Methods We performed literature searches in MedLine, PubMed and PsycINFO for articles assessing performance characteristics of predictive clinical tests in FHR studies of psychosis. Studies were included if they reported one or more predictive variables in subjects at FHR for psychosis. We complemented this search strategy with references drawn from articles, reviews, book chapters and monographs. Results Across generations of familial high-risk projects, predictive studies have investigated behavioral, cognitive, psychometric, clinical, neuroimaging, and other markers. Recent analyses have incorporated multivariate and multi-domain approaches to risk ascertainment, although with still generally modest results. Conclusions While a broad range of risk factors has been identified, no individual marker or combination of markers can at this time enable accurate prospective prediction of emerging psychosis for individuals at FHR. We outline the complex and multi-level nature of psychotic illness, the myriad of factors influencing its development, and methodological hurdles to accurate and reliable prediction. Prospects and challenges for future generations of FHR studies are discussed in the context of early detection and intervention strategies. PMID:23693118

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications.

PubMed

Campos-Parra, Alma D; Mitznahuatl, Gerardo Cuamani; Pedroza-Torres, Abraham; Romo, Rafael Vázquez; Reyes, Fany Iris Porras; López-Urrutia, Eduardo; Pérez-Plasencia, Carlos

2017-06-02

Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC.

Why Ineffective Psychotherapies Appear to Work: A Taxonomy of Causes of Spurious Therapeutic Effectiveness.

PubMed

Lilienfeld, Scott O; Ritschel, Lorie A; Lynn, Steven Jay; Cautin, Robin L; Latzman, Robert D

2014-07-01

The past 40 years have generated numerous insights regarding errors in human reasoning. Arguably, clinical practice is the domain of applied psychology in which acknowledging and mitigating these errors is most crucial. We address one such set of errors here, namely, the tendency of some psychologists and other mental health professionals to assume that they can rely on informal clinical observations to infer whether treatments are effective. We delineate four broad, underlying cognitive impediments to accurately evaluating improvement in psychotherapy-naive realism, confirmation bias, illusory causation, and the illusion of control. We then describe 26 causes of spurious therapeutic effectiveness (CSTEs), organized into a taxonomy of three overarching categories: (a) the perception of client change in its actual absence, (b) misinterpretations of actual client change stemming from extratherapeutic factors, and (c) misinterpretations of actual client change stemming from nonspecific treatment factors. These inferential errors can lead clinicians, clients, and researchers to misperceive useless or even harmful psychotherapies as effective. We (a) examine how methodological safeguards help to control for different CSTEs, (b) delineate fruitful directions for research on CSTEs, and (c) consider the implications of CSTEs for everyday clinical practice. An enhanced appreciation of the inferential problems posed by CSTEs may narrow the science-practice gap and foster a heightened appreciation of the need for the methodological safeguards afforded by evidence-based practice. © The Author(s) 2014.

Assessment of large copy number variants in patients with apparently isolated congenital left-sided cardiac lesions reveals clinically relevant genomic events.

PubMed

Hanchard, Neil A; Umana, Luis A; D'Alessandro, Lisa; Azamian, Mahshid; Poopola, Mojisola; Morris, Shaine A; Fernbach, Susan; Lalani, Seema R; Towbin, Jeffrey A; Zender, Gloria A; Fitzgerald-Butt, Sara; Garg, Vidu; Bowman, Jessica; Zapata, Gladys; Hernandez, Patricia; Arrington, Cammon B; Furthner, Dieter; Prakash, Siddharth K; Bowles, Neil E; McBride, Kim L; Belmont, John W

2017-08-01

Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data were used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families. CNVs were molecularly confirmed and the medical records of individual carriers reviewed. The gene content of novel CNVs was then compared with public CNV data from CHD patients. Large CNVs (>1 MB) were observed in 33 probands (∼3%). Six of these were de novo and 14 were not observed in the only available parent sample. Associated cardiac phenotypes spanned a broad spectrum without clear predilection. Candidate CNVs were largely non-recurrent, associated with heterozygous loss of copy number, and overlapped known CHD genomic regions. Novel CNV regions were enriched for cardiac development genes, including seven that have not been previously associated with human CHD. CNV analysis can be a clinically useful and molecularly informative tool in LSLs without obvious extra-cardiac defects, and may identify a clinically relevant genomic disorder in a small but important proportion of these individuals. © 2017 Wiley Periodicals, Inc.

Training in neurology.

PubMed

Aminoff, Michael J

2008-05-13

The training of clinical neurologists is undergoing profound change. Increasing subspecialization within neurology, the widening separation of clinical neurology from other branches of internal medicine, limitations of exposure to training in internal medicine, mandated restrictions in working hours, and attempts to shorten the training period are likely to have adverse effects on the next generation of clinical neurologists. Despite the need for a broad base in general medicine, discussed here, the exposure of neurology trainees to general medical disorders is diminishing. An emphasis on an algorithmic approach to patient management rather than on educating residents to use their reasoning faculties when applying new techniques and knowledge to clinical practice may adversely affect patient care. Neurologists require broad-based training in neurology, internal medicine, and psychiatry, to ensure excellence in clinical practice. It is time to question again whether they are receiving the training that they need.

Competitive exclusion over broad spatial extents is a slow process: Evidence and implications for species distribution modeling

USGS Publications Warehouse

Yackulic, Charles B.

2016-01-01

There is considerable debate about the role of competition in shaping species distributions over broad spatial extents. This debate has practical implications because predicting changes in species' geographic ranges in response to ongoing environmental change would be simpler if competition could be ignored. While this debate has been the subject of many reviews, recent literature has not addressed the rates of relevant processes. This omission is surprising in that ecologists hypothesized decades ago that regional competitive exclusion is a slow process. The goal of this review is to reassess the debate under the hypothesis that competitive exclusion over broad spatial extents is a slow process.Available evidence, including simulations presented for the first time here, suggests that competitive exclusion over broad spatial extents occurs slowly over temporal extents of many decades to millennia. Ecologists arguing against an important role for competition frequently study modern patterns and/or range dynamics over periods of decades, while much of the evidence for competition shaping geographic ranges at broad spatial extents comes from paleoecological studies over time scales of centuries or longer. If competition is slow, as evidence suggests, the geographic distributions of some, perhaps many species, would continue to change over time scales of decades to millennia, even if environmental conditions did not continue to change. If the distributions of competing species are at equilibrium it is possible to predict species distributions based on observed species–environment relationships. However, disequilibrium is widespread as a result of competition and many other processes. Studies whose goal is accurate predictions over intermediate time scales (decades to centuries) should focus on factors associated with range expansion (colonization) and loss (local extinction), as opposed to current patterns. In general, understanding of modern range dynamics would be enhanced by considering the rates of relevant processes.

Strain diversity plays no major role in the varying efficacy of rotavirus vaccines: an overview.

PubMed

Velasquez, Daniel E; Parashar, Umesh D; Jiang, Baoming

2014-12-01

While a monovalent Rotarix® [RV1] and a pentavalent RotaTeq® [RV5] have been extensively tested and found generally safe and equally efficacious in clinical trials, the question still lingers about the evolving diversity of circulating rotavirus strains over time and their relationship with protective immunity induced by rotavirus vaccines. We reviewed data from clinical trials and observational studies that assessed the efficacy or field effectiveness of rotavirus vaccines against different rotavirus strains worldwide. RV1 provided broad clinical efficacy and field effectiveness against severe diarrhea due to all major circulating strains, including the homotypic G1P[8] and the fully heterotypic G2P[4] strains. Similarly, RV5 provided broad efficacy and effectiveness against RV5 and non-RV5 strains throughout different locations. Rotavirus vaccination provides broad heterotypic protection; however continuing surveillance is needed to track the change of circulating strains and monitor the effectiveness and safety of vaccines. Published by Elsevier B.V.

Effect of Shufeng Jiedu capsules as a broad-spectrum antibacterial.

PubMed

Bao, Yanyan; Gao, Yingjie; Cui, Xiaolan

2016-02-01

This study sought to investigate the broad-spectrum antibacterial action of an alternative medicine, Shufeng Jiedu capsules (SFJDC). Antibacterial testing was performed to determine whether SFJDC had broad-spectrum antibacterial action in vitro, and testing was performed to verify whether SFJDC prevented death due to a Streptococcus or Staphylococcus aureus infection in mice. Results of antibacterial testing suggested that SFJDC are a broad-spectrum antibacterial and that SFJDC are superior to Lianhua Qingwen capsules as a broad-spectrum antibacterial. Results of testing revealed that SFJDC lowered the mortality rate, it reduced mortality, it increased average survival time, and it increased the lifespan of mice dying due to a Staphylococcus aureus or Streptococcus infection. Thus, SFJDC could become a complement to broad-spectrum antimicrobials in clinical settings.

Mechanically robust and transparent N-halamine grafted PVA-co-PE films with renewable antimicrobial activity

USDA-ARS?s Scientific Manuscript database

Antimicrobial polymeric films that are both mechanically robust and function renewable would have broad technological implications for areas ranging from medical safety and bioengineering to foods industry; however, creating such materials has proven extremely challenging. Here, a novel strategy is ...

An integrated science-based methodology to assess potential risks and implications of engineered nanomaterials

EPA Science Inventory

There is an urgent need for broad and integrated studies that address the risks of engineered nanomaterials (ENMs) along the different endpoints of the society, environment, and economy (SEE) complex adaptive system. This article presents an integrated science-based methodology ...

Organisational Learning and Leadership: On Metaphor, Meaning Making, Liminality and Intercultural Communication

ERIC Educational Resources Information Center

Patterson, Jean A.

2009-01-01

This article discusses sensemaking as a broad framework for understanding organisational learning and its implications for leadership in a global context. Organisational metaphors, the concept of liminality and understanding organisations as interpretation systems are presented as possibilities for enhancing intercultural communication within…

Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.

PubMed

Lowery, Maeve A; Wong, Winston; Jordan, Emmet J; Lee, Jonathan W; Kemel, Yelena; Vijai, Joseph; Mandelker, Diana; Zehir, Ahmet; Capanu, Marinela; Salo-Mullen, Erin; Arnold, Angela G; Yu, Kenneth H; Varghese, Anna M; Kelsen, David P; Brenner, Robin; Kaufmann, Erica; Ravichandran, Vignesh; Mukherjee, Semanti; Berger, Michael F; Hyman, David M; Klimstra, David S; Abou-Alfa, Ghassan K; Tjan, Catherine; Covington, Christina; Maynard, Hannah; Allen, Peter J; Askan, Gokce; Leach, Steven D; Iacobuzio-Donahue, Christine A; Robson, Mark E; Offit, Kenneth; Stadler, Zsofia K; O'Reilly, Eileen M

2018-02-28

Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410-468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an "identified" manner in 356 (57.9%) patients and in an "anonymized" manner in 259 (42.1%) patients, using an institutional review board-approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

Dawn of ocular gene therapy: implications for molecular diagnosis in retinal disease

PubMed Central

Jacques, ZANEVELD; Feng, WANG; Xia, WANG; Rui, CHEN

2013-01-01

Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for rare genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients’ genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation(s) underlying disease. In this review, we discuss the application of Next Generation Sequencing (NGS) to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases: Leber’s Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt’s disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinformatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine. PMID:23393028

Improvement of a predictive model in ovarian cancer patients submitted to platinum-based chemotherapy: implications of a GST activity profile.

PubMed

Pereira, Deolinda; Assis, Joana; Gomes, Mónica; Nogueira, Augusto; Medeiros, Rui

2016-05-01

The success of chemotherapy in ovarian cancer (OC) is directly associated with the broad variability in platinum response, with implications in patients survival. This heterogeneous response might result from inter-individual variations in the platinum-detoxification pathway due to the expression of glutathione-S-transferase (GST) enzymes. We hypothesized that GSTM1 and GSTT1 polymorphisms might have an impact as prognostic and predictive determinants for OC. We conducted a hospital-based study in a cohort of OC patients submitted to platinum-based chemotherapy. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. GSTM1-null genotype patients presented a significantly longer 5-year survival and an improved time to progression when compared with GSTM1-wt genotype patients (log-rank test, P = 0.001 and P = 0.013, respectively). Multivariate Cox regression analysis indicates that the inclusion of genetic information regarding GSTM1 polymorphism increased the predictive ability of risk of death after OC platinum-based chemotherapy (c-index from 0.712 to 0.833). Namely, residual disease (HR, 4.90; P = 0.016) and GSTM1-wt genotype emerged as more important predictors of risk of death (HR, 2.29; P = 0.039; P = 0.036 after bootstrap). No similar effect on survival was observed regarding GSTT1 polymorphism, and there were no statistically significant differences between GSTM1 and GSTT1 genotypes and the assessed patients' clinical-pathological characteristics. GSTM1 polymorphism seems to have an impact in OC prognosis as it predicts a better response to platinum-based chemotherapy and hence an improved survival. The characterization of the GSTM1 genetic profile might be a useful molecular tool and a putative genetic marker for OC clinical outcome.

Comparison between pathogen directed antibiotic treatment and empirical broad spectrum antibiotic treatment in patients with community acquired pneumonia: a prospective randomised study

PubMed Central

van der Eerden, M M; Vlaspolder, F; de Graaff, C S; Groot, T; Bronsveld, W; Jansen, H; Boersma, W

2005-01-01

Background: There is much controversy about the ideal approach to the management of community acquired pneumonia (CAP). Recommendations differ from a pathogen directed approach to an empirical strategy with broad spectrum antibiotics. Methods: In a prospective randomised open study performed between 1998 and 2000, a pathogen directed treatment (PDT) approach was compared with an empirical broad spectrum antibiotic treatment (EAT) strategy according to the ATS guidelines of 1993 in 262 hospitalised patients with CAP. Clinical efficacy was primarily determined by the length of hospital stay (LOS). Secondary outcome parameters for clinical efficacy were assessment of therapeutic failure on antibiotics, 30 day mortality, duration of antibiotic treatment, resolution of fever, side effects, and quality of life. Results: Three hundred and three patients were enrolled in the study; 41 were excluded, leaving 262 with results available for analysis. No significant differences were found between the two treatment groups in LOS, 30 day mortality, clinical failure, or resolution of fever. Side effects, although they did not have a significant influence on the outcome parameters, occurred more frequently in patients in the EAT group than in those in the PDT group (60% v 17%, 95% CI –0.5 to –0.3; p<0.001). Conclusions: An EAT strategy with broad spectrum antibiotics for the management of hospitalised patients with CAP has comparable clinical efficacy to a PDT approach. PMID:16061709

Advancing beyond AP Courses

ERIC Educational Resources Information Center

Hammond, Bruce G.

2009-01-01

A quiet revolution is picking up steam in the nation's private secondary schools, with broad implications for college admissions and for teaching and learning on both sides of the transition from high school to college. About 50 of the nation's leading college-preparatory schools have opted out of the College Board's Advanced Placement (AP)…

Examining Intercultural Competency through Social Exchange Theory

ERIC Educational Resources Information Center

Pillay, Soma; James, Reynold

2015-01-01

Intercultural competency (ICC) has been an extensively researched area within the past decade, given the broad consensus that this trait constitutes one of the key competencies of the 21st century manager. However, somewhat under-explored are aspects including the implications and effects that pedagogies such as blended learning have on the…

Perspectives on the Social Psychology of Creativity

ERIC Educational Resources Information Center

Amabile, Teresa M.; Pillemer, Julianna

2012-01-01

Scholars began serious study into the social psychology of creativity about 25 years after the field of creativity research had taken root. Over the past 35 years, examination of social and environmental influences on creativity has become increasingly vigorous, with broad implications for the psychology of human performance, and with applications…

Individual Differences in Online Spoken Word Recognition: Implications for SLI

ERIC Educational Resources Information Center

McMurray, Bob; Samelson, Vicki M.; Lee, Sung Hee; Tomblin, J. Bruce

2010-01-01

Thirty years of research has uncovered the broad principles that characterize spoken word processing across listeners. However, there have been few systematic investigations of individual differences. Such an investigation could help refine models of word recognition by indicating which processing parameters are likely to vary, and could also have…

The Hydrologic Implications Of Unique Urban Soil Horizon Sequencing On The Functions Of Passive Green Infrastructure

EPA Science Inventory

Green infrastructure represents a broad set of site- to landscape-scale practices that can be flexibly implemented to increase sewershed retention capacity, and can thereby improve on the management of water quantity and quality. Although much green infrastructure presents as for...

Results from Federal Emissions Tests on Alternative Fuel Vehicles and Their Implications for the Environment and Public Health

DOT National Transportation Integrated Search

1996-06-17

The FHWA is charged with meeting the Nation's need for the safe, efficient, and environmentally sound transport of people and goods. This ambitious goal can be broadly divided into efforts toward the dissemination of innovative technology, safer high...

Effects of silvicultural treatments on forest birds in the Rocky Mountains: implications and management recommendations

Treesearch

Richard L. Hutto; Sallie J. Hejl; Charles R. Preston; Deborah M. Finch

1993-01-01

The short-term effects of timber harvesting practices on landbird species vary widely among species. Thus, the maintenance of populations of all species will require a long-term management strategy that involves maintenance of a variety of habitats over a broad landscape.

Collaborative Counseling: A Conceptual Framework and Approach for Counselors of Adults in Life Transitions.

ERIC Educational Resources Information Center

Avis, Joan P.

1987-01-01

Proposes collaborative counseling as a comprehensive definition of adult counseling. Presents rationale for definition based on broad implications for counselors of adult development and life transitions literature. Discusses three perspectives as a conceptual framework for defining the phenomenology of the counselor of adults. Outlines elements…

Excellence in Public Relations: Lesson from Larry Speakes.

ERIC Educational Resources Information Center

Detweiler, John S.

Former presidential press secretary Larry Speakes' confession that he manufactured a quote for President Reagan at the November 1987 summit in Geneva, Switzerland, created a firestorm which cost Speakes dearly, raised serious problems about the ethics of public relations practitioners, and contained broad implications for the profession. A study…

Implications of gender differences for human health risk assessment and toxicology

EPA Science Inventory

This paper from The Human Health working group of SGOMSEC 16 examines a broad range of issues on gender effects in toxicology. Gender differences in toxicology begin at the gamete and embryo stage, continuing through development and maturation and into old age. Sex influences exp...

Religious Communities, Immigration, and Social Cohesion in Rural Areas: Evidence from England

ERIC Educational Resources Information Center

Andrews, Rhys

2011-01-01

Religious communities are important sources of bridging and bonding social capital that have varying implications for perceptions of social cohesion in rural areas. In particular, as well as cultivating cohesiveness more broadly, the bridging social capital associated within mainline religious communities may represent an especially important…

The Philippine System of Education: Some Implications to Agricultural Education.

ERIC Educational Resources Information Center

Mancebo, Samuel T.

The Philippine educational system views education as a human development resource conversion process that can maximize the realization of the national developmental goals. Students comprise the principal input of this manpower resource conversion process. The output is individuals who can find useful and productive employment. Two broad strategies…

Equity, the Arts, and Urban Education: A Review

ERIC Educational Resources Information Center

Kraehe, Amelia M.; Acuff, Joni B.; Travis, Sarah

2016-01-01

This review examines empirical studies of educational equity in and through the arts with broad implications for urban education. It extends the literature by (a) describing the interrelated spaces of urban education and the arts, (b) integrating knowledge of arts education across formal and informal learning environments, and (c) examining the…

Housing is positively associated with invasive exotic plant species richness in New England, USA

Treesearch

Gregorio I. Gavier-Pizarro; Volker C. Radeloff; Susan I. Stewart; Cynthia D. Huebner; Nicholas S. Keuler

2010-01-01

Understanding the factors related to invasive exotic species distributions at broad spatial scales has important theoretical and management implications, because biological invasions are detrimental to many ecosystem functions and processes. Housing development facilitates invasions by disturbing land cover, introducing nonnative landscaping plants, and facilitating...

Construction of Trust Judgments within Cooperative Dyads

ERIC Educational Resources Information Center

Evin, Agathe; Sève, Carole; Saury, Jacques

2014-01-01

Introduction: One of the aims of physical education (PE) is to develop social skills such as cooperation, teamwork, and mutual helping among students. Cooperation is a broad research topic, implicating several disciplines in the human sciences (e.g. psychology, sociology, linguistics, philosophy). It is also an important topic in various domains…

Variables Affecting Readiness to Benefit from Career Interventions

ERIC Educational Resources Information Center

Sampson, James P., Jr.; McClain, Mary-Catherine; Musch, Elisabeth; Reardon, Robert C.

2013-01-01

This article identifies and briefly describes the broad range of variables that may influence clients' readiness to benefit from career interventions. The article also discusses consequences of low readiness for effective use of career interventions and addresses implications for practice as well as for future research. Variables contributing to…

Cognition and Instruction: Recent Theories of Human Competence and How It Is Acquired.

ERIC Educational Resources Information Center

Resnick, Lauren B.

This paper outlines the current state of knowledge about how intellectual competence is acquired. Implications resulting from recent changes in the psychology of learning and development are beginning to revitalize the science of learning and instruction. Four broad topics illustrate the links between instructional experiments, fundamental…

Boys' Changing Voices in the First Century of MENC Journals

ERIC Educational Resources Information Center

Freer, Patrick K.

2008-01-01

Since 1914, "The Music Educators Journal" (MEJ, initially the "Music Supervisors' Bulletin" and then "Music Supervisors' Journal") has served the music education profession by providing a platform for the broad dissemination of philosophy, practice-based techniques, research implications, and reports of the efforts of MENC: The National…

The Challenging Australian Policy Context for University Engagement

ERIC Educational Resources Information Center

Barker, Karen

2015-01-01

Despite the current broad agreement amongst Australian universities that engagement is now a core activity, the implications of that commitment are yet to be fully realised. The difficulties many universities face in articulating engagement as a strategic priority begin with the conceptual and definitional issues around the third mission and its…

Genetic Essentialism, Neuroessentialism, and Stigma: Commentary on Dar-Nimrod and Heine (2011)

ERIC Educational Resources Information Center

Haslam, Nick

2011-01-01

Dar-Nimrod and Heine (2011) presented a masterfully broad review of the implications of genetic essentialism for understandings of human diversity. This commentary clarifies the reasons that essentialist thinking has problematic social consequences and links genetic forms of essentialism to those invoking neural essences. The mounting evidence…

Space-Derived Transparency: Players, Policies, Implications, and Synergies

DTIC Science & Technology

2001-06-01

69 William J. Broad, �Spy Photos of Korea Missile Site Brings Dispute,� The New York Times, 11 January 2000. 70 Ibid. 71 Tabassum Zakaria...of international Associations: on-line, Internet, 31 March 2001, available from http://www.uia.org/ Zakaria, Tabassum . �US Group Puts N. Korea

Freedom of Education and Common Civic Values

ERIC Educational Resources Information Center

Karsten, Sjoerd

2006-01-01

A critical issue facing European school systems and one with broad social implications is how to accommodate the different demands of a growing number of non-Western immigrants, particularly Muslims. "Historically, faith-based schools have provided a route for immigrants, refugees and minorities...to gain a foothold in their new country, yet…

Freehand Sketching as a Catalyst for Developing Concept Driven Competencies

ERIC Educational Resources Information Center

Lane, Diarmaid; Seery, Niall

2011-01-01

At a time when concept driven competencies are perceived to be critical in redefining effective technological education, the introduction of Design and Communication Graphics at senior cycle in Irish high schools has broad implications. Students now have the potential to explore applied geometries, integrated with conceptual thinking in addition…

Human Cognitive Limitations. Broad, Consistent, Clinical Application of Physiological Principles Will Require Decision Support.

PubMed

Morris, Alan H

2018-02-01

Our education system seems to fail to enable clinicians to broadly understand core physiological principles. The emphasis on reductionist science, including "omics" branches of research, has likely contributed to this decrease in understanding. Consequently, clinicians cannot be expected to consistently make clinical decisions linked to best physiological evidence. This is a large-scale problem with multiple determinants, within an even larger clinical decision problem: the failure of clinicians to consistently link their decisions to best evidence. Clinicians, like all human decision-makers, suffer from significant cognitive limitations. Detailed context-sensitive computer protocols can generate personalized medicine instructions that are well matched to individual patient needs over time and can partially resolve this problem.

The relationship between voice climate and patients’ experience of timely care in primary care clinics

PubMed Central

Nembhard, Ingrid M.; Yuan, Christina T.; Shabanova, Veronika; Cleary, Paul D.

2017-01-01

Background Aspects of the patient care experience, despite being central to quality care, are often problematic. In particular, patients frequently report problems with timeliness of care. As yet, research offers little insight on setting characteristics that contribute to patients’ experience of timely care. Purpose The aims of this study were to assess the relationship between organizational climate and patients’ reports of timely care in primary care clinics and to broadly examine the link between staff’s work environment and patient care experiences. We test hypotheses about the relationship between voice climate—staff feeling safe to speak up about issues—and reported timeliness of care, consistency in reported voice climate across professions, and how climate differences for various professions relate to timely care. Methodology We conducted a cross-sectional study of employees (n = 1,121) and patients (n = 8,164) affiliated with 37 clinics participating in a statewide reporting initiative. Employees were surveyed about clinics’ voice climate, and patients were surveyed about the timeliness of care. Hypotheses were tested using analysis of variance and generalized estimating equations. Findings Clinical and administrative staff (e.g., nurses and office assistants) reported clinics’ climates to be significantly less supportive of voice than did clinical leaders (e.g., physicians). The greater the difference in reported support for voice between professional groups, the less patients reported experiencing timely care in three respects: obtaining an appointment, seeing the doctor within 15 minutes of appointment time, and receiving test results. In clinics where staff reported climates supportive of voice, patients indicated receiving more timely care. Clinical leaders’ reports of voice climate had no relationship to reported timeliness of care. Practical Implications Our findings suggest the importance of clinics developing a strong climate for voice, particularly for clinical and administrative staff, to support better service quality for patients. PMID:24589927

Rib stress fractures in pregnancy: a case report and review of literature.

PubMed

Pouwels, S; Dabekausen, Y A

2017-01-01

Thoracic pain in pregnancy has a broad differential diagnosis. The authors report a young pregnant woman with acute pain in the thoracic region due to a rib fracture after a coughing flare. Physicians must be aware of the broad differential diagnosis (and its clinical consequences) of thoracic pain in pregnancy. Radiographic imaging is not necessary if the clinical signs are obvious. If there is no suspicion for underlying pathology other (expensive) diagnostic tests lose their value. Treatment consists of adequate analgesia and no firther measures need to be taken.

Practice-Based Research Network Infrastructure Design for Institutional Review Board Risk Assessment and Generalizability of Clinical Results.

PubMed

Curro, Frederick; Thompson, Van P; Naftolin, Frederick; Grill, Ashley; Vena, Don; Terracio, Louis; Hashimoto, Mariko; Buchholz, Matthew; McKinstry, Andrea; Cannon, Diane; Alfano, Vincent; Gooden, Thalia; Vernillo, Anthony; Czeisler, Elan

2013-01-01

Data from clinical studies generated by Practice Based Research Networks should be generalizable to the profession. For nationally representative data a broad recruitment of practitioners may pose added risks to IRB's. Infrastructure must assure data integrity while minimizing risk to assure that the clinical results are generalizable. The PEARL Network is an interdisciplinary dental/medical PBRN conducting a broad range of clinical studies. The infrastructure is designed to support the principles of Good Clinical Practice (GCP) and create a data audit trail to ensure data integrity for generalizability. As the PBRN concept becomes of greater interest, membership may expand beyond the local community, and the issue of geography versus risk management becomes of concern to the IRB. The PEARL Network describes how it resolves many of the issues related to recruiting on a National basis while maintaining study compliance to ensure patient safety and minimize risk to the IRB.

The context, influences and challenges for undergraduate nurse clinical education: Continuing the dialogue.

PubMed

Forber, Jan; DiGiacomo, Michelle; Davidson, Patricia; Carter, Bernie; Jackson, Debra

2015-11-01

Approaches to clinical education are highly diverse and becoming increasingly complex to sustain in complex milieu To identify the influences and challenges of providing nurse clinical education in the undergraduate setting and to illustrate emerging solutions. A discursive exploration into the broad and varied body of evidence including peer reviewed and grey literature. Internationally, enabling undergraduate clinical learning opportunities faces a range of challenges. These can be illustrated under two broad themes: (1) legacies from the past and the inherent features of nurse education and (2) challenges of the present, including, population changes, workforce changes, and the disconnection between the health and education sectors. Responses to these challenges are triggering the emergence of novel approaches, such as collaborative models. Ongoing challenges in providing accessible, effective and quality clinical learning experiences are apparent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lesions of the Broad Ligament: A Review.

PubMed

Heller, Debra S

2015-01-01

The differential diagnosis of lesions arising in the broad ligament is quite large. Many of these lesions can be clinically interpreted before surgery as adnexal or uterine neoplasms. Although some lesions are similar to those arising in other müllerian sites, there are unique lesions as well. The lesions are uncommon and may prove challenging to clinicians. The purpose was to review the scope of lesions affecting the broad ligament. A literature review was conducted. A Medline search was performed using the terms broad ligament, mesosalpinx, and mesovarium. A review of the scope of broad ligament lesions is presented to assist in developing a differential diagnosis if a patient with such a lesion is encountered. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

The effects of familiarity on thought--action fusion.

PubMed

Berman, Noah C; Wheaton, Michael G; Fabricant, Laura E; Jacobson, Spenser R; Abramowitz, Jonathan S

2011-10-01

The present study examined whether beliefs about the importance of thoughts (i.e., thought--action fusion; TAF) are related to the target subject of the negative thought. One hundred and seven undergraduate students were randomly assigned to imagine either a beloved relative or a stranger being diagnosed with cancer and provided in vivo ratings of anxiety, likelihood, moral wrongness, urge to neutralize, and how upsetting the event would be if it occurred. Results indicated that thinking of a relative being diagnosed with cancer provoked more distress, urges to neutralize, and higher estimates of likelihood, as well greater use of mental neutralizing behaviors, compared to thinking of a stranger. Contrary to our prediction, the groups did not differ in their ratings of the moral wrongness. These findings broadly support the assertion that the more personally significant a negative intrusive thought, the more it will provoke distress and urges to neutralize. Results are discussed in terms of the cognitive model of obsessions and clinical implications are addressed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Where we are today: prioritizing women's health services and health policy. A report by the Women's Health Expert Panel of the American Academy of Nursing.

PubMed

Berg, Judith A; Taylor, Diana; Woods, Nancy Fugate

2013-01-01

There has been a recent resurgence of interest in women's health as evidenced by several federal and international policy-shaping reports that will impact women's health services. These reports include the 2010 Affordable Care Act, the formation of the National Prevention Council and Strategy, the 2011 IOM report on clinical preventives services for women, and the World Health Organization strategic plan for 2010-2015. In this paper, we summarize and discuss these reports and discuss implications of enacting the suggested health policies. We highlight policy strategies and recommendations that will extend national and global recommendations to improve women's health and wellness across the lifespan and emphasize the urgent need for preventive services. We conclude this paper by detailing our broad recommendations for putting prevention into practice illustrated by specific recommendations related to unintended pregnancy prevention and management. Copyright © 2013 Elsevier Inc. All rights reserved.

Hypocretin-1 deficiency in a girl with ROHHAD syndrome.

PubMed

Dhondt, Karlien; Verloo, Patrick; Verhelst, Hélène; Van Coster, Rudy; Overeem, Sebastiaan

2013-09-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare and complex pediatric syndrome, essentially caused by dysfunction of 3 vital systems regulating endocrine, respiratory, and autonomic nervous system functioning. The clinical spectrum of ROHHAD is broad, but sleep/wake disorders have received relatively little attention so far, although the central hypothalamic dysfunction would make the occurrence of sleep symptoms likely. In this case report, we expand the phenotype of ROHHAD with a number of striking sleep symptoms that together can be classified as a secondary form of narcolepsy. We present a 7-year-old girl with ROHHAD who displayed the classic features of narcolepsy with cataplexy: excessive daytime sleepiness with daytime naps, visual hallucinations, and partial cataplexy reflected in intermittent loss of facial muscle tone. Nocturnal polysomnography revealed sleep fragmentation and a sleep-onset REM period characteristic for narcolepsy. The diagnosis was confirmed by showing an absence of hypocretin-1 in the cerebrospinal fluid. We discuss potential pathophysiological implications as well as symptomatic treatment options.

Evaluation of the Psychometric Properties of the Asian Adolescent Depression Scale and Construction of a Short Form: An Item Response Theory Analysis.

PubMed

Lo, Barbara Chuen Yee; Zhao, Yue; Kwok, Alice Wai Yee; Chan, Wai; Chan, Calais Kin Yuen

2017-07-01

The present study applied item response theory to examine the psychometric properties of the Asian Adolescent Depression Scale and to construct a short form among 1,084 teenagers recruited from secondary schools in Hong Kong. Findings suggested that some items of the full form reflected higher levels of severity and were more discriminating than others, and the Asian Adolescent Depression Scale was useful in measuring a broad range of depressive severity in community youths. Differential item functioning emerged in several items where females reported higher depressive severity than males. In the short form construction, preliminary validation suggested that, relative to the 20-item full form, our derived short form offered significantly greater diagnostic performance and stronger discriminatory ability in differentiating depressed and nondepressed groups, and simultaneously maintained adequate measurement precision with a reduced response burden in assessing depression in the Asian adolescents. Cultural variance in depressive symptomatology and clinical implications are discussed.

Developmental psychopathology: Attention Deficit Hyperactivity Disorder (ADHD).

PubMed

Schmidt, Sören; Petermann, Franz

2009-09-17

Attention Deficit/Hyperactivity Disorder (ADHD), formerly regarded as a typical childhood disorder, is now known as a developmental disorder persisting over the lifespan. Starting in preschool-age, symptoms vary depending on the age group affected. According to the variability of ADHD-symptoms and the heterogeneity of comorbid psychiatric disorders, a broad review of recent studies was performed. These findings were summarized in a developmental psychopathological model, documenting relevant facts on a timeline. Based on a genetic disposition and a neuropsychological deregulation, there is evidence for factors which persist across the lifespan, change age-dependently, or show validity in a specific developmental phase. Qualitative changes can be found for children in preschool-age and adults. These differences have implications for clinical practice as they can be used for prevention, diagnostic proceedings, and therapeutic intervention as well as for planning future studies. The present article is a translated and modified version of the German article "Entwicklungspsychopathologie der ADHS", published in Zeitschrift für Psychiatrie, Psychologie und Psychotherapie, 56, 2008, S. 265-274.

Seizures presenting as incessant laughter: a case of gelastic epilepsy.

PubMed

Holmes, Christina M; Goldman, Mitchell J

2012-12-01

Gelastic seizures are defined as seizure activity manifesting as laughter inappropriate to the situation, with supporting evidence on electroencephalogram or magnetic resonance imaging. Gelastic seizures are most commonly reported in patients with hypothalamic hamartomas causing precocious puberty. The differential diagnosis of incessant laughter is important to recognize in the Emergency Department, as some conditions warrant immediate treatment and others require further diagnostic work-up with implications for the entire family. The background and pathophysiology of gelastic epilepsy will be discussed. The case of a previously healthy girl with acute onset of incessant laughter is reported. This patient was diagnosed with a clinical case of gelastic seizures. This case illustrates the importance of recognizing this form of seizures for accurate treatment and follow-up. This case report illustrates the importance of a broad differential for a patient presenting emergently with uncontrollable laughter. Gelastic epilepsy is relatively rare but requires further work-up and often may require chronic therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Determinants of turnover among low wage earners in long term care: the role of manager-employee relationships.

PubMed

Matthews, Michael; Carsten, Melissa K; Ayers, Douglas J; Menachemi, Nir

2018-02-27

The demand for Long-Term Care (LTC) is steadily increasing as Baby Boomers age and enter retirement. High turnover rates among employees in LTC creates challenges for supervisors and administrators, and can negatively impact quality of care. This study examines manager-subordinate relationship quality using Leader-Member Exchange Theory (LMX) as an antecedent to turnover among low-wage earners in the LTC environment. Survey data measuring LMX, job satisfaction, and demographic information was collected at time 1, and turnover data was collected 18 months later at time 2. The results reveal that all four LMX dimensions were rated significantly different among subordinates who left versus those who stayed, however, only the LMX dimension of supervisor loyalty was a significant predictor of turnover among low wage earners. Our study adds a more nuanced view of the reasons low-wage employees turnover, and presents implications for clinical managers and LTC organizations more broadly. Copyright © 2017 Elsevier Inc. All rights reserved.

Suicidality in Bipolar Disorder: The Role of Emotion-Triggered Impulsivity

PubMed Central

Johnson, Sheri L.; Carver, Charles S.; Tharp, Jordan A.

2018-01-01

A growing body of research suggests that impulsive responses to emotion more robustly predict suicidality than do other forms of impulsivity. This issue has not yet been examined within bipolar disorder, however. Participants diagnosed with bipolar I disorder (n = 133) and control participants (n = 110) diagnosed with no mood or psychotic disorder completed self-report measures of emotion-triggered impulsivity (Negative and Positive Urgency Scales) and interviews concerning lifetime suicidality. Analyses examined the effects of emotion-triggered impulsivity alone and in combination with gender, age of onset, depression severity, comorbid anxiety, comorbid substance use, and medication. A history of suicide ideation and attempts, as well as self-harm, were significantly more common in the bipolar disorder group compared with the control group. Impulsive responses to positive emotions related to suicide ideation, attempts, and self-harm within the bipolar group. Findings extend research on the importance of emotion-triggered impulsivity to a broad range of key outcomes within bipolar disorder. The discussion focuses on limitations and potential clinical implications. PMID:27406282

Cannabinoids as therapeutic agents in cancer: current status and future implications

PubMed Central

Ganju, Ramesh K.

2014-01-01

The pharmacological importance of cannabinoids has been in study for several years. Cannabinoids comprise of (a) the active compounds of the Cannabis sativa plant, (b) endogenous as well as (c) synthetic cannabinoids. Though cannabinoids are clinically used for anti-palliative effects, recent studies open a promising possibility as anti-cancer agents. They have been shown to possess anti-proliferative and anti-angiogenic effects in vitro as well as in vivo in different cancer models. Cannabinoids regulate key cell signaling pathways that are involved in cell survival, invasion, angiogenesis, metastasis, etc. There is more focus on CB1 and CB2, the two cannabinoid receptors which are activated by most of the cannabinoids. In this review article, we will focus on a broad range of cannabinoids, their receptor dependent and receptor independent functional roles against various cancer types with respect to growth, metastasis, energy metabolism, immune environment, stemness and future perspectives in exploring new possible therapeutic opportunities. PMID:25115386

Genetic secrets: Protecting privacy and confidentiality in the genetic era

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothstein, M.A.

1998-07-01

Few developments are likely to affect human beings more profoundly in the long run than the discoveries resulting from advances in modern genetics. Although the developments in genetic technology promise to provide many additional benefits, their application to genetic screening poses ethical, social, and legal questions, many of which are rooted in issues of privacy and confidentiality. The ethical, practical, and legal ramifications of these and related questions are explored in depth. The broad range of topics includes: the privacy and confidentiality of genetic information; the challenges to privacy and confidentiality that may be projected to result from the emergingmore » genetic technologies; the role of informed consent in protecting the confidentiality of genetic information in the clinical setting; the potential uses of genetic information by third parties; the implications of changes in the health care delivery system for privacy and confidentiality; relevant national and international developments in public policies, professional standards, and laws; recommendations; and the identification of research needs.« less

Genetic secrets: Protecting privacy and confidentiality in the genetic era. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothstein, M.A.

1998-09-01

Few developments are likely to affect human beings more profoundly in the long run than the discoveries resulting from advances in modern genetics. Although the developments in genetic technology promise to provide many additional benefits, their application to genetic screening poses ethical, social, and legal questions, many of which are rooted in issues of privacy and confidentiality. The ethical, practical, and legal ramifications of these and related questions are explored in depth. The broad range of topics includes: the privacy and confidentiality of genetic information; the challenges to privacy and confidentiality that may be projected to result from the emergingmore » genetic technologies; the role of informed consent in protecting the confidentiality of genetic information in the clinical setting; the potential uses of genetic information by third parties; the implications of changes in the health care delivery system for privacy and confidentiality; relevant national and international developments in public policies, professional standards, and laws; recommendations; and the identification of research needs.« less

Costing behavioral interventions: a practical guide to enhance translation.

PubMed

Ritzwoller, Debra P; Sukhanova, Anna; Gaglio, Bridget; Glasgow, Russell E

2009-04-01

Cost and cost effectiveness of behavioral interventions are critical parts of dissemination and implementation into non-academic settings. Due to the lack of indicative data and policy makers' increasing demands for both program effectiveness and efficiency, cost analyses can serve as valuable tools in the evaluation process. To stimulate and promote broader use of practical techniques that can be used to efficiently estimate the implementation costs of behavioral interventions, we propose a set of analytic steps that can be employed across a broad range of interventions. Intervention costs must be distinguished from research, development, and recruitment costs. The inclusion of sensitivity analyses is recommended to understand the implications of implementation of the intervention into different settings using different intervention resources. To illustrate these procedures, we use data from a smoking reduction practical clinical trial to describe the techniques and methods used to estimate and evaluate the costs associated with the intervention. Estimated intervention costs per participant were $419, with a range of $276 to $703, depending on the number of participants.

Receptor for Advanced Glycation End Products and Its Involvement in Inflammatory Diseases

PubMed Central

Talib, Herni; Tie, Tung Hing; Nordin, Norshariza

2013-01-01

The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF-κB as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions. PMID:24102034

Updating the OMERACT filter: implications of filter 2.0 to select outcome instruments through assessment of "truth": content, face, and construct validity.

PubMed

Tugwell, Peter; Boers, Maarten; D'Agostino, Maria-Antonietta; Beaton, Dorcas; Boonen, Annelies; Bingham, Clifton O; Choy, Ernest; Conaghan, Philip G; Dougados, Maxime; Duarte, Catia; Furst, Daniel E; Guillemin, Francis; Gossec, Laure; Heiberg, Turid; van der Heijde, Désirée M; Hewlett, Sarah; Kirwan, John R; Kvien, Tore K; Landewé, Robert B; Mease, Philip J; Østergaard, Mikkel; Simon, Lee; Singh, Jasvinder A; Strand, Vibeke; Wells, George

2014-05-01

The Outcome Measures in Rheumatology (OMERACT) Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The "Truth" section of the OMERACT Filter requires that criteria be met to demonstrate that the outcome instrument meets the criteria for content, face, and construct validity. Discussion groups critically reviewed a variety of ways in which case studies of current OMERACT Working Groups complied with the Truth component of the Filter and what issues remained to be resolved. The case studies showed that there is broad agreement on criteria for meeting the Truth criteria through demonstration of content, face, and construct validity; however, several issues were identified that the Filter Working Group will need to address. These issues will require resolution to reach consensus on how Truth will be assessed for the proposed Filter 2.0 framework, for instruments to be endorsed by OMERACT.

"From that moment on my life changed": turning points in the healing process for men recovering from child sexual abuse.

PubMed

Easton, Scott D; Leone-Sheehan, Danielle M; Sophis, Ellen J; Willis, Danny G

2015-01-01

Recent research indicates that child sexual abuse often undermines the health of boys and men across the lifespan. However, some male survivors experience a turning point marking a positive change in their health trajectories and healing process. Although frequently discussed in reference to physical health problems or addictions, very little is known about turning points with respect to child sexual abuse for men. The purpose of this secondary qualitative analysis was to describe the different types of turning points experienced by male survivors who completed the 2010 Health and Well-Being Survey (N = 250). Using conventional content analysis, researchers identified seven types of turning points that were classified into three broad categories: influential relationships (professional and group support, personal relationships), insights and new meanings (cognitive realizations, necessity to change, spiritual transformation), and action-oriented communication (disclosure of CSA, pursuit of justice). Implications for clinical practice and future research are discussed.

Balance within the Neurexin Trans-Synaptic Connexus Stabilizes Behavioral Control

PubMed Central

Clarke, Raymond A.; Eapen, Valsamma

2014-01-01

Autism spectrum disorder (ASD) is characterized by a broad spectrum of behavioral deficits of unknown etiology. ASD associated mutations implicate numerous neurological pathways including a common association with the neurexin trans-synaptic connexus (NTSC) which regulates neuronal cell-adhesion, neuronal circuitry, and neurotransmission. Comparable DNA lesions affecting the NTSC, however, associate with a diversity of behavioral deficits within and without the autism spectrum including a very strong association with Tourette syndrome. The NTSC is comprised of numerous post-synaptic ligands competing for trans-synaptic connection with one of the many different neurexin receptors yet no apparent association exists between specific NTSC molecules/complexes and specific behavioral deficits. Together these findings indicate a fundamental role for NTSC-balance in stabilizing pre-behavioral control. Further molecular and clinical characterization and stratification of ASD and TS on the basis of NTSC status will help elucidate the molecular basis of behavior – and define how the NTSC functions in combination with other molecular determinates to strengthen behavioral control and specify behavioral deficits. PMID:24578685

Epidemic cholera in Latin America, 1991-1993: implications of case definitions used for public health surveillance.

PubMed

Koo, D; Traverso, H; Libel, M; Drasbek, C; Tauxe, R; Brandling-Bennett, D

1996-06-01

This report presents the various cholera case definitions used by the affected countries of Latin America, shows the numbers of cholera cases and deaths attributable to cholera (as reported by Latin American countries to PAHO through 1993), and describes some regional trends in cholera incidence. The information about how cholera cases were defined was obtained from an October 1993 PAHO questionnaire. In all, 948429 cholera cases were reported to PAHO by affected Latin American countries from January 1991 through December 1993, the highest annual incidences being registered in Peru (1991 and 1992) and Guatemala (1993). The case-fatality rate over the three-year period, and also in 1993, was 0.8%. A general downward trend in the incidence of cholera was observed in most South American countries, while the incidence increased in most Central American countries. A good deal of variation was noted in the definitions used for reporting cholera cases, hospitalized cholera cases, and cholera-attributable deaths. Because of these variations, broad intercountry comparisons (including disease burden calculations and care quality assessments based on case-fatality rates) are difficult to make, and even reported trends within a single country need to be evaluated with care. The situation is likely to be complicated in the future by the arrival of V. cholerae O139 in Latin America, creating a need to distinguish between it and the prevailing O1 strain. For purposes of simplicity, wide acceptance, and broad dissemination of case data, the following definitions are recommended: Confirmed case of O1 cholera: laboratory-confirmed infection with toxigenic V. cholerae O1 in any person who has diarrhea. Confirmed case of O139 cholera: laboratory-confirmed infection with toxigenic V. cholerae O139 in any person who has diarrhea. Clinical case of cholera: acute watery diarrhea in a person over 5 years old who is seeking treatment. Death attributable to cholera: death within one week of the onset of diarrhea in a person with confirmed or clinically defined cholera. Hospitalized patient with cholera:a person who has confirmed or clinically defined cholera and who remains at least 12 hours in a health care facility for treatment of the disease.

A review of the clinical implications of bisphosphonates in dentistry.

PubMed

Borromeo, G L; Tsao, C E; Darby, I B; Ebeling, P R

2011-03-01

Bisphosphonates are drugs that suppress bone turnover and are commonly prescribed to prevent skeletal related events in malignancy and for benign bone diseases such as osteoporosis. Bisphosphonate associated jaw osteonecrosis (ONJ) is a potentially debilitating, yet poorly understood condition. A literature review was undertaken to review the dental clinical implications of bisphosphonates. The present paper briefly describes the postulated pathophysiology of ONJ and conditions with similar clinical presentations. The implications of bisphosphonates for implantology, periodontology, orthodontics and endodontics are reviewed. Whilst bisphosphonates have potential positive applications in some clinical settings, periodontology particularly, further clinical research is limited by the risk of ONJ. Prevention and management are reviewed, including guidelines for reducing cumulative intravenous bisphosphonate dose, cessation of bisphosphonates prior to invasive dental treatment or after ONJ development, and the use of serum beta-CTX-1 in assessing risk. In the context of substantial uncertainty, the implications of bisphosphonate use in the dental clinical setting are still being determined. © 2010 Australian Dental Association.

The practice of clinical neuropsychology in Australia.

PubMed

Ponsford, Jennie

2016-11-01

This paper describes the development and practice of clinical neuropsychology in Australia. Clinical Neuropsychology has shown rapid growth in Australia over the past three decades. Comprehensive and specialized training programs are producing high quality graduates who are employed in a broad range of settings or private practice. Australia now has a substantial number of clinical neuropsychologists with specialist training. Whilst the majority of Australian clinical neuropsychologists still undertake assessment predominantly, there are growing opportunities for clinical neuropsychologists in rehabilitation and in a broad range of research contexts. Cultural issues relating to the assessment of Indigenous Australians and immigrants from many countries present significant challenges. Some major contributions have been made in the realms of test development and validation across various age groups. Australian clinical neuropsychologists are also contributing significantly to research in the fields of traumatic brain injury, aging and dementias, epilepsy, memory assessment, rehabilitation, substance abuse, and other psychiatric disorders. Expansion of roles of clinical neuropsychologists, in domains such as rehabilitation and research is seen as essential to underpin continuing growth of employment opportunities for the profession.

Antigenicity and Immunogenicity in HIV-1 Antibody-Based Vaccine Design

PubMed Central

Kong, Leopold; Sattentau, Quentin J

2012-01-01

Neutralizing antibodies can protect from infection by immunodeficiency viruses. However, the induction by active vaccination of antibodies that can potently neutralize a broad range of circulating virus strains is a goal not yet achieved, despite more than 2 decades of research. Here we review progress made in the field, from early empirical studies to today’s rational structure-based vaccine antigen design. We discuss the existence of broadly neutralizing antibodies, their implications for epitope discovery and recent progress made in antigen design. Finally, we consider the relationship between antigenicity and immunogenicity for B cell recognition and antibody production, a major hurdle for rational vaccine design to overcome. PMID:23227445

Ambulatory surgery centers--current business and legal issues.

PubMed

Becker, S; Biala, M

2000-01-01

This article explores a handful of critical trends that have broad implications for ambulatory surgery centers and health care entities as a whole. As of the year 2000, the health care delivery system is experiencing broad changes and reconstruction in a variety of manners. One of the largest changes revolves around the accelerating movement of patient care from inpatient models to outpatient models, and the commensurate investment and development in outpatient systems and outpatient bricks and mortar. This metamorphosis is particularly evident as it relates to freestanding ambulatory surgery centers. This change in health care delivery will prove to have severe economic impacts on many of the nation's hospital systems.

The evolutionary biology of musical rhythm: was Darwin wrong?

PubMed

Patel, Aniruddh D

2014-03-01

In The Descent of Man, Darwin speculated that our capacity for musical rhythm reflects basic aspects of brain function broadly shared among animals. Although this remains an appealing idea, it is being challenged by modern cross-species research. This research hints that our capacity to synchronize to a beat, i.e., to move in time with a perceived pulse in a manner that is predictive and flexible across a broad range of tempi, may be shared by only a few other species. Is this really the case? If so, it would have important implications for our understanding of the evolution of human musicality.

The Evolutionary Biology of Musical Rhythm: Was Darwin Wrong?

PubMed Central

Patel, Aniruddh D.

2014-01-01

In The Descent of Man, Darwin speculated that our capacity for musical rhythm reflects basic aspects of brain function broadly shared among animals. Although this remains an appealing idea, it is being challenged by modern cross-species research. This research hints that our capacity to synchronize to a beat, i.e., to move in time with a perceived pulse in a manner that is predictive and flexible across a broad range of tempi, may be shared by only a few other species. Is this really the case? If so, it would have important implications for our understanding of the evolution of human musicality. PMID:24667562

Differentiating among singular and comorbid obsessive-compulsive disorder and social phobia symptomology.

PubMed

Rudy, Brittany M; May, Anna C; Whiting, Sara E; Davis, Thompson E; Jenkins, Whitney S; Reuther, Erin T

2014-01-01

Social phobia is a frequent co-occurring diagnosis with obsessive-compulsive disorder (OCD); however, co-occurring OCD in those with social phobia is less common. Genetic, environmental, and cognitive traits are common risk factors for anxiety disorders broadly. It is plausible that shared variables related to OCD and/or social phobia could provide insight into the co-occurrence of these two disorders. The current study explored differences in fear of negative evaluation (FNE) and perfectionism among four groups: those with (1) elevated social phobia symptoms, (2) elevated OCD symptoms, (3) elevated symptoms of OCD and social phobia, and those who were (4) asymptomatic as a control group. A non-clinical sample of 196 participants completed several online questionnaires about social phobia and OCD symptomology. Results identified three cognitive variables (i.e., FNE, total perfectionism, and concern over mistakes) as differential variables in comorbid symptom presentation of OCD and social phobia. A fourth variable (i.e., doubts about actions) was identified as a potential dual risk factor, and four subsequent variables (i.e., parental criticism, personal standards, parental expectations, and organization) were not implicated in differential symptom presentation. Given the different rates of OCD and social phobia co-occurrence, identification of differentiating variables could aid in better understanding of potential risk factors, which may enhance preventative and therapeutic techniques. Study implications, limitations, and future recommendations are discussed.

Autophagy promotes escape from phosphatidylinositol 3-kinase inhibition in estrogen receptor-positive breast cancer.

PubMed

Yang, Wei; Hosford, Sarah R; Traphagen, Nicole A; Shee, Kevin; Demidenko, Eugene; Liu, Stephanie; Miller, Todd W

2018-03-01

Hyperactivation of the PI3K pathway has been implicated in resistance to antiestrogen therapies in estrogen receptor α (ER)-positive breast cancer, prompting the development of therapeutic strategies to inhibit this pathway. Autophagy has tumor-promoting and -suppressing roles and has been broadly implicated in resistance to anticancer therapies, including antiestrogens. Chloroquine (CQ) is an antimalarial and amebicidal drug that inhibits autophagy in mammalian cells and human tumors. Herein, we observed that CQ inhibited proliferation and autophagy in ER + breast cancer cells. PI3K inhibition with GDC-0941 (pictilisib) induced autophagy. Inhibition of autophagy using CQ or RNA interference potentiated PI3K inhibitor-induced apoptosis. Combined inhibition of PI3K and autophagy effectively induced mitochondrial membrane depolarization, which required the BH3-only proapoptotic proteins Bim and PUMA. Treatment with GDC-0941, CQ, or the combination, significantly suppressed the growth of ER + breast cancer xenografts in mice. In an antiestrogen-resistant xenograft model, GDC-0941 synergized with CQ to provide partial, but durable, tumor regression. These findings warrant clinical evaluation of therapeutic strategies to target ER, PI3K, and autophagy for the treatment of ER + breast cancer.-Yang, W., Hosford, S. R., Traphagen, N. A., Shee, K., Demidenko, E., Liu, S., Miller, T. W. Autophagy promotes escape from phosphatidylinositol 3-kinase inhibition in estrogen receptor-positive breast cancer.

SCA17 repeat expansion: mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications.

PubMed

Chen, Chiung-Mei; Lee, Li-Ching; Soong, Bing-Wen; Fung, Hon-Chung; Hsu, Wen-Chuin; Lin, Pei-Ying; Huang, Hui-Ju; Chen, Fen-Lin; Lin, Cheng-Yueh; Lee-Chen, Guey-Jen; Wu, Yih-Ru

2010-03-01

Spinocerebellar ataxia type 17 (SCA17) involves the expression of a CAG/CAA expansion mutation in the gene encoding TATA-box binding protein (TBP), a general transcription initiation factor. The spectrum of SCA17 clinical presentation is broad. We screened for triplet expansion in the TBP gene in Taiwanese Parkinson's disease (PD), Alzheimer's disease (AD) and atypical parkinsonism and investigated the functional implication of expanded alleles using lymphoblastoid cells as a model. A total of 6 mildly expanded alleles (44-46) were identified in patients group. The frequency of the individuals carrying expanded alleles in PD (3/602 [0.5%]), AD (2/245 [0.8%]) and atypical parkinsonism (1/44 [2.3%]) is not significant as compared to that in the control subjects (0/644 [0.0%]). In lymphoblastoid cells, HSPA5, HSPA8 and HSPB1 expression levels in cells with expanded TBP were significantly lower than that of the control cells. Although not significantly, the levels of PARK7 protein isoforms 6.1 and 6.4 are notably increased in SCA17 lymphoblastoid cells. Treatment of TBH (tert-butyl hydroperoxide) significantly increases cell death in the cells with mildly expanded TBP. Our findings expand the spectrum of SCA17 phenotype and may contribute to our understanding of the disease. Copyright 2009 Elsevier B.V. All rights reserved.

Frontal plane comparison between drop jump and vertical jump: implications for the assessment of ACL risk of injury.

PubMed

Cesar, Guilherme M; Tomasevicz, Curtis L; Burnfield, Judith M

2016-11-01

The potential to use the vertical jump (VJ) to assess both athletic performance and risk of anterior cruciate ligament (ACL) injury could have widespread clinical implications since VJ is broadly used in high school, university, and professional sport settings. Although drop jump (DJ) and VJ observationally exhibit similar lower extremity mechanics, the extent to which VJ can also be used as screening tool for ACL injury risk has not been assessed. This study evaluated whether individuals exhibit similar knee joint frontal plane kinematic and kinetic patterns when performing VJs compared with DJs. Twenty-eight female collegiate athletes performed DJs and VJs. Paired t-tests indicated that peak knee valgus angles did not differ significantly between tasks (p = 0.419); however, peak knee internal adductor moments were significantly larger during the DJ vs. VJ (p < 0.001). Pearson correlations between the DJ and VJ revealed strong correlations for knee valgus angles (r = 0.93, p < 0.001) and for internal knee adductor moments (r = 0.82, p < 0.001). Our results provide grounds for investigating whether frontal plane knee mechanics during VJ can predict ACL injuries and thus can be used as an effective tool for the assessment of risk of ACL injury in female athletes.

Age of onset and course of major depressive disorder: associations with psychosocial functioning outcomes in adulthood.

PubMed

Wilson, S; Hicks, B M; Foster, K T; McGue, M; Iacono, W G

2015-02-01

Major depressive disorder (MDD) that onsets by adolescence is associated with various deficits in psychosocial functioning. However, adolescent-onset MDD often follows a recurrent course that may drive its associated impairment. To tease apart these two clinical features, we examined the relative associations of age of onset (adolescent versus adult) and course (recurrent versus single episodes) of MDD with a broad range of psychosocial functioning outcomes assessed in early adulthood. Participants comprised a large, population-based sample of male and female twins from the Minnesota Twin Family Study (MTFS; n = 1252) assessed prospectively from ages 17 to 29 years. A recurrent course of MDD predicted impairment in several psychosocial domains in adulthood, regardless of whether the onset was in adolescence or adulthood. By contrast, adolescent-onset MDD showed less evidence of impairment in adulthood after accounting for recurrence. Individuals with both an adolescent onset and recurrent episodes of MDD represented a particularly severe group with pervasive psychosocial impairment in adulthood. The negative implications of adolescent-onset MDD for psychosocial functioning in adulthood seem to be due primarily to its frequently recurrent course, rather than its early onset, per se. The results highlight the importance of considering both age of onset and course for understanding MDD and its implications for functioning, and also in guiding targeted intervention efforts.

The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.

PubMed

West, Christina E; Renz, Harald; Jenmalm, Maria C; Kozyrskyj, Anita L; Allen, Katrina J; Vuillermin, Peter; Prescott, Susan L

2015-01-01

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Unravelling the myotonic dystrophy type 1 clinical spectrum: A systematic registry-based study with implications for disease classification.

PubMed

De Antonio, M; Dogan, C; Hamroun, D; Mati, M; Zerrouki, S; Eymard, B; Katsahian, S; Bassez, G

2016-10-01

The broad clinical spectrum of myotonic dystrophy type 1 (DM1) creates particular challenges for both medical care and design of clinical trials. Clinical onset spans a continuum from birth to late adulthood, with symptoms that are highly variable in both severity and nature of the affected organ systems. In the literature, this complex phenotype is divided into three grades (mild, classic, and severe) and four or five main clinical categories (congenital, infantile/juvenile, adult-onset and late-onset forms), according to symptom severity and age of onset, respectively. However, these classifications are still under discussion with no consensus thus far. While some specific clinical features have been primarily reported in some forms of the disease, there are no clear distinctions. As a consequence, no modifications in the management of healthcare or the design of clinical studies have been proposed based on the clinical form of DM1. The present study has used the DM-Scope registry to assess, in a large cohort of DM1 patients, the robustness of a classification divided into five clinical forms. Our main aim was to describe the disease spectrum and investigate features of each clinical form. The five subtypes were compared by distribution of CTG expansion size, and the occurrence and onset of the main symptoms of DM1. Analyses validated the relevance of a five-grade model for DM1 classification. Patients were classified as: congenital (n=93, 4.5%); infantile (n=303, 14.8%); juvenile (n=628, 30.7%); adult (n=694, 34.0%); and late-onset (n=326, 15.9%). Our data show that the assumption of a continuum from congenital to the late-onset form is valid, and also highlights disease features specific to individual clinical forms of DM1 in terms of symptom occurrence and chronology throughout the disease course. These results support the use of the five-grade model for disease classification, and the distinct clinical profiles suggest that age of onset and clinical form may be key criteria in the design of clinical trials when considering DM1 health management and research. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Preschoolers’ Emotion Knowledge and the Differential Effects of Harsh Punishment

PubMed Central

Berzenski, Sara R.; Yates, Tuppett M.

2013-01-01

This study examined the influence of caregiver-reported harsh physical and verbal punishment on children’s behavioral and self-system adjustment. Children’s emotion knowledge was evaluated as a heretofore unrecognized moderator of these relations. Two hundred fifty preschool age children (50% female; Mage=49.06 months) from diverse backgrounds (50% Hispanic, 18% African American, 10.4% Caucasian, 21.6% Multiracial/Other) were assessed through teacher, caregiver, self, and observer report in the domains of harsh punishment (Parent Child Conflict Tactics Scale), conduct problems (Teacher Report Form, California Child Q-Sort), self concept (Self Description Questionnaire for Preschoolers, California Child Q-Sort), and emotion knowledge (Kuschè Emotion Inventory). Emotion knowledge moderated the relation between harsh punishment and child adjustment. Harsh physical punishment was associated with conduct problems for children with higher emotion knowledge, especially for boys. Harsh verbal punishment was associated with self concept deficits among children with higher emotion knowledge, especially for girls. These relations were also specifically applicable to non-Hispanic children. These results highlight the importance of investigating hypothesis driven interactive effects and the specificity of experience to understand the psychosocial sequelae of parenting practices broadly, and to clarify the mixed evidence in the punishment literature specifically. Clinical implications point to the salience of emotion processes in parent-child disciplinary interventions for understanding the prevalence and pattern of child behavioral adjustment and self concept, as well as more broadly to the role of individual differences in children’s responses to adversity and subsequent therapeutic needs. PMID:23750528

Research on the cognitively impaired: lessons and warnings from the emergency research debate.

PubMed

Karlawish, J H; Sachs, G A

1997-04-01

To demonstrate that the recent events in emergency research have broad implications for the conduct of human subjects research with the cognitively impaired. This essay illustrates the similarities between the two kinds of research and suggests how understanding these similarities might help to resolve issues in human subjects research on the cognitively impaired. A review of pertinent journal articles, books, regulations, and court cases. The emergency research controversy resulted in large part because of conflicting interpretations of arguably inadequate research regulations. The proposed Food and Drug Administration (FDA) regulations include advance informed consent, a broad role for family in approving a subject's participation, replacement of a threshold of permissible risk, called minimal risk, with a more sensible balancing of risks and benefits, and a role for the community in research approval. The current state of research on the cognitively impaired suggests that many of the same problems exist now that existed in emergency research before the FDA issued its proposed regulations. The ongoing case of T.D. et al. vs N.Y. State Office of Mental Health suggest that unless steps are taken similar to those taken in emergency research, much of clinical research on the cognitively impaired could cease. Representatives of the government, medicine, and the public must recognize the unresolved issues and inadequate regulations relating to research on the cognitively impaired. The proposed FDA regulations for emergency research may provide guidance for a settlement of these issues.

Hemispheric differentiation and category width.

PubMed

Huang, M S

1979-12-01

This study concerns the relationship between a cognitive style dimension, category width, and hemispheric differentiation. When lists of word pairs were presented simultaneously in a dichotic listening task to broad and narrow categorisers (all female, right-handed), both groups of subjects recalled more words presented to the right ear than those presented to the left ear; indicating left hemisphere's superiority in verbal processing. Both broad and narrow categorisers recalled a similar number of words in the right ear (left hemisphere), but the former recalled significantly more words in the left ear than did the latter. This finding is interpreted as meaning that narrow categorisers rely predominantly on the left hemisphere in verbal processing, and that in comparison with narrow categories, there is greater right hemispheric involvement in processing in the case of broad categorisers. The implication of this finding in terms of the differential processing strategies adopted by the two groups of individuals is discussed.

Clinical and economic impact of an antibiotics stewardship programme in a regional hospital in Hong Kong.

PubMed

Ng, C K; Wu, T C; Chan, W M J; Leung, Y S W; Li, C K P; Tsang, D N C; Leung, G M

2008-10-01

Inappropriate use of antibiotics is one of the important factors attributing to emergence of drug-resistant pathogens. Infection with multidrug-resistant pathogens adversely affects quality of medical care. Queen Elizabeth Hospital, an 1800-bed acute service hospital in Hong Kong. Antibiotics are commonly prescribed for treating acute infections. Reduce inappropriate prescription of broad-spectrum antibiotics and overall antibiotic prescription through implementation of a multidisciplinary antibiotics stewardship programme (ASP). A multidisciplinary programme involving policy and guideline formulation, education and feedback, monthly antibiotic consumption and cost monitoring, antimicrobial susceptibility pattern reporting and concurrent feedbacks for commonly prescribed broad-spectrum antibiotics was implemented in 2004. Predefined logistics to prescribe "restricted" antibiotics were formulated and implemented with collaborative efforts from clinical and non-clinical departments. The programme was supported by management at department and hospital levels. Broad-spectrum antibiotics were prescribed inappropriately in 28.9% (n = 192) clinical scenarios. The ASP reduced the restricted and total antibiotic consumption as well as the antibiotics-related costs. Predefined clinical outcomes were not adversely affected. Economic analysis suggested that the extra human cost in running ASP could be offset by savings from antibiotic expenditure. It is cost-effective to implement a multidisciplinary ASP in acute service hospitals as the programme reduces antibiotic consumption and results in overall cost savings. The quality of medical care is not jeopardized as the important clinical outcomes are not adversely affected. The generalisability and sustainability of ASPs in other clinical contexts warrant further studies to ensure the continuous success of this programme.

B-cell depletion in SLE: clinical and trial experience with rituximab and ocrelizumab and implications for study design.

PubMed

Reddy, Venkat; Jayne, David; Close, David; Isenberg, David

2013-01-01

B cells are believed to be central to the disease process in systemic lupus erythematosus (SLE), making them a target for new therapeutic intervention. In recent years there have been many publications regarding the experience in SLE of B-cell depletion utilising rituximab, an anti-CD20 mAb that temporarily depletes B cells,reporting promising results in uncontrolled open studies and in routine clinical use. However, the two large randomised controlled trials in extra-renal lupus (EXPLORER study) and lupus nephritis (LUNAR study) failed to achieve their primary endpoints. Based on the clinical experience with rituximab this failure was somewhat unexpected and raised a number of questions and concerns, not only into the true level of benefit of B-cell depletion in a broad population but also how to test the true level of effectiveness of an investigational agent as we seek to improve the design of therapeutic trials in SLE. A better understanding of what went wrong in these trials is essential to elucidate the underlying reasons for the disparate observations noted in open studies and controlled trials. In this review, we focus on various factors that may affect the ability to accurately and confidently establish the level of treatment effect of the investigational agent, in this case rituximab, in the tw studies and explore hurdles faced in the randomised controlled trials investigating the efficacy of ocrelizumab, the humanised anti-CD20 mAb, in SLE. Further, based on the lessons learned from the clinical trials, we make suggestions that could be implemented in future clinical trial design to overcome the hurdles faced.

Cytologic diagnosis: expression of probability by clinical pathologists.

PubMed

Christopher, Mary M; Hotz, Christine S

2004-01-01

Clinical pathologists use descriptive terms or modifiers to express the probability or likelihood of a cytologic diagnosis. Words are imprecise in meaning, however, and may be used and interpreted differently by pathologists and clinicians. The goals of this study were to 1) assess the frequency of use of 18 modifiers, 2) determine the probability of a positive diagnosis implied by the modifiers, 3) identify preferred modifiers for different levels of probability, 4) ascertain the importance of factors that affect expression of diagnostic certainty, and 5) evaluate differences based on gender, employment, and experience. We surveyed 202 clinical pathologists who were board-certified by the American College of Veterinary Pathologists (Clinical Pathology). Surveys were distributed in October 2001 and returned by e-mail, fax, or surface mail over a 2-month period. Results were analyzed by parametric and nonparametric tests. Survey response rate was 47.5% (n = 96) and primarily included clinical pathologists at veterinary schools (n = 58) and diagnostic laboratories (n = 31). Eleven of 18 terms were used "often" or "sometimes" by >/= 50% of respondents. Broad variability was found in the probability assigned to each term, especially those with median values of 75 to 90%. Preferred modifiers for 7 numerical probabilities ranging from 0 to 100% included 68 unique terms; however, a set of 10 terms was used by >/= 50% of respondents. Cellularity and quality of the sample, experience of the pathologist, and implications of the diagnosis were the most important factors affecting the expression of probability. Because of wide discrepancy in the implied likelihood of a diagnosis using words, defined terminology and controlled vocabulary may be useful in improving communication and the quality of data in cytology reporting.

Therapist Adherence in Brief Strategic Family Therapy for Adolescent Drug Abusers

PubMed Central

Robbins, Michael S.; Feaster, Daniel J.; Horigian, Viviana E.; Puccinelli, Marc J.; Henderson, Craig; Szapocznik, José

2012-01-01

Objective Therapist adherence has been shown to predict clinical outcomes in family therapy. In prior studies, adherence has been represented broadly by core principles and a consistent family (vs. individual) focus. To date, these studies have not captured the range of clinical skills that are represented in complex family-based approaches or examined how variations in these skills predict different clinically relevant outcomes over the course of treatment. In this study, the authors examined the reliability and validity of an observational adherence measure and the relationship between adherence and outcome in a sample of drug-using adolescents who received brief strategic family therapy within a multisite effectiveness study. Method Participants were 480 adolescents (age 12–17) and their family members, who were randomized to the Brief Strategic Family Therapist treatment condition (J. Szapocznik, U. Hervis, & S. Schwartz, 2003) or treatment as usual. The adolescents were mostly male (377 vs. 103 female) and Hispanic (213), whereas 148 were White, and 110 were Black. Therapists were also randomly assigned to treatment condition within agencies. Results Results supported the proposed factor structure of the adherence measure, providing evidence that it is possible to capture and discriminate between distinct dimensions of family therapy. Analyses demonstrated that the mean levels of the factors varied over time in theoretically and clinically relevant ways and that therapist adherence was associated with engagement and retention in treatment, improvements in family functioning, and reductions in adolescent drug use. Conclusions Clinical implications and future research directions are discussed, including the relevance of these findings on training therapists and studies focusing on mechanisms of action in family therapy. PMID:21261433

Measurement of DSM-5 section II personality disorder constructs using the MMPI-2-RF in clinical and forensic samples.

PubMed

Anderson, Jaime L; Sellbom, Martin; Pymont, Carly; Smid, Wineke; De Saeger, Hilde; Kamphuis, Jan H

2015-09-01

In the current study, we evaluated the associations between the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) scale scores and the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) Section II personality disorder (PD) criterion counts in inpatient and forensic psychiatric samples from The Netherlands using structured clinical interviews to operationalize PDs. The inpatient psychiatric sample included 190 male and female patients and the forensic sample included 162 male psychiatric patients. We conducted correlation and count regression analyses to evaluate the utility of relevant MMPI-2-RF scales in predicting PD criterion count scores. Generally, results from these analyses emerged as conceptually expected and provided evidence that MMPI-2-RF scales can be useful in assessing PDs. At the zero-order level, most hypothesized associations between Section II disorders and MMPI-2-RF scales were supported. Similarly, in the regression analyses, a unique set of predictors emerged for each PD that was generally in line with conceptual expectations. Additionally, the results provided general evidence that PDs can be captured by dimensional psychopathology constructs, which has implications for both DSM-5 Section III specifically and the personality psychopathology literature more broadly. (c) 2015 APA, all rights reserved.

An alternate pathophysiologic paradigm of sepsis and septic shock

PubMed Central

Kumar, Anand

2014-01-01

The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. PMID:24184742

Cutaneous Papillomaviruses and Non-melanoma Skin Cancer: Causal Agents or Innocent Bystanders?

PubMed

Hasche, Daniel; Vinzón, Sabrina E; Rösl, Frank

2018-01-01

There is still controversy in the scientific field about whether certain types of cutaneous human papillomaviruses (HPVs) are causally involved in the development of non-melanoma skin cancer (NMSC). Deciphering the etiological role of cutaneous HPVs requires - besides tissue culture systems - appropriate preclinical models to match the obtained results with clinical data from affected patients. Clear scientific evidence about the etiology and underlying mechanisms involved in NMSC development is fundamental to provide reasonable arguments for public health institutions to classify at least certain cutaneous HPVs as group 1 carcinogens. This in turn would have implications on fundraising institutions and health care decision makers to force - similarly as for anogenital cancer - the implementation of a broad vaccination program against "high-risk" cutaneous HPVs to prevent NMSC as the most frequent cancer worldwide. Precise knowledge of the multi-step progression from normal cells to cancer is a prerequisite to understand the functional and clinical impact of cofactors that affect the individual outcome and the personalized treatment of a disease. This overview summarizes not only recent arguments that favor the acceptance of a viral etiology in NMSC development but also reflects aspects of causality in medicine, the use of empirically meaningful model systems and strategies for prevention.

The failure of formal rights and equality in the clinic: a critique of bioethics.

PubMed

Atkins, Chloe G K

2005-01-01

For communities which espouse egalitarian principles, the hierarchical nature of care-giving relationships poses an extraordinary challenge. Patients' accounts of their illnesses and of their medical care capture the latent tension which exists between notional, political equality and the need for dependency on care from others. I believe that the power imbalance in doctor-patient relationships has broad implications for liberal democracies. Professional and care-giving relationships almost always consist of an imbalance of knowledge and expertise which no template of egalitarian moralism can suppress. When we seek help or guidance from authority figures, we are at a disadvantage politically even though we may be equal citizens theoretically and legally. Hierarchic relationships persist within democracies. Moreover, they tend to exist within a realm of privacy which is only partially visible from the social realm. In the end, traditional notions of liberal autonomy and egalitarianism do not properly describe or monitor these interactions. Liberal rhetoric (i.e., terms such as equality, rights, consent, etc.) pervades much of bioethical literature and interventions but, this very language tends to mask the persistence of structural hierarchies in the clinic. The doctor-patient relationship forces democratic communities to confront the problem of continuing hierarchic power relations and challenges liberalism to revise its understanding of individual autonomies.

[The concept of quality of life in medicine: its history and current relevance].

PubMed

Bullinger, Monika

2014-01-01

This paper attempts to review 40 years of quality-of-life research. The increasing recognition of the topic is obvious from the number of publications and its representation in academic discussions. Despite a rather weak theoretical foundation, methods of quality-of-life assessment have been developed successfully. Both the number and the quality of assessment tools have increased over the years so that there is now a broad spectrum of instruments for adults and children available, which is used from epidemiological studies to health services research, and especially in quality assurance and comparative benchmarking. Assessment is still underrepresented in clinical trials, which is why only few meta-analyses and reviews are available. Also, implementation of results in recommendations for treatment and in guidelines has just started. Implications for clinical practice also relate to the patient orientation in the physician-patient communication. A future perspective is the widespread use of available instruments, provided that relevant information is gained, which depends on the study design as well as the interpretation and dissemination of results. Consequences for the healthcare systems are expected if improvements in quality of life can be attributed to benefits of treatment and surrounding services. Copyright © 2014. Published by Elsevier GmbH.

Cutaneous Papillomaviruses and Non-melanoma Skin Cancer: Causal Agents or Innocent Bystanders?

PubMed Central

Hasche, Daniel; Vinzón, Sabrina E.; Rösl, Frank

2018-01-01

There is still controversy in the scientific field about whether certain types of cutaneous human papillomaviruses (HPVs) are causally involved in the development of non-melanoma skin cancer (NMSC). Deciphering the etiological role of cutaneous HPVs requires – besides tissue culture systems – appropriate preclinical models to match the obtained results with clinical data from affected patients. Clear scientific evidence about the etiology and underlying mechanisms involved in NMSC development is fundamental to provide reasonable arguments for public health institutions to classify at least certain cutaneous HPVs as group 1 carcinogens. This in turn would have implications on fundraising institutions and health care decision makers to force – similarly as for anogenital cancer – the implementation of a broad vaccination program against “high-risk” cutaneous HPVs to prevent NMSC as the most frequent cancer worldwide. Precise knowledge of the multi-step progression from normal cells to cancer is a prerequisite to understand the functional and clinical impact of cofactors that affect the individual outcome and the personalized treatment of a disease. This overview summarizes not only recent arguments that favor the acceptance of a viral etiology in NMSC development but also reflects aspects of causality in medicine, the use of empirically meaningful model systems and strategies for prevention. PMID:29770129

Psychosocial correlates of fatigue in multiple sclerosis.

PubMed

Schwartz, C E; Coulthard-Morris, L; Zeng, Q

1996-02-01

To explore: (1) the interrelation among the neuropsychological, psychological, and psychosocial factors and fatigue as measured by the Multidimensional Assessment of Fatigue scale, and (2) the impact of fatigue on role performance. Clinical interview with neuropsychological testing and cross-sectional study by mail. Multiple sclerosis (MS) clinic registry of a large Boston teaching hospital. 139 MS patients representing a broad range of disability. The Multidimensional Assessment of Fatigue (MAF) scale, the Extended Disability Status Scale, the Sickness Impact Profile, Rao cognitive battery, the Trailmaking Test, depression, anxiety, and social activity limitations subscales from the Arthritis Impact Measurement Scales, and the Ryff Happiness Scale. Stepwise multiple regression analyses revealed that having a low sense of environmental mastery was the best psychosocial predictor of both global fatigue and fatigue-related distress, after adjusting for sociodemographic and medical factors. Further, people who reported being more depressed tended to report more severe fatigue. Neuropsychological performance was not associated with fatigue. Fatigue was found to limit social, work, and overall role performance, but not physical role performance. People who feel that they can choose or create environments suitable to their psychic or physical conditions report less global fatigue and less fatigue-related distress, and fatigue can have an important impact on role performance. The implications of these findings for designing fatigue management interventions are discussed.

Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?

PubMed

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R; Matsushita, Mark; Raskind, Wendy H

2008-07-15

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. 2008 Wiley-Liss, Inc.

Guiding Neuronal Growth in Tissues with Light

DTIC Science & Technology

2010-02-27

and structural properties of their surroundings in addition to the biochemical properties. Furthermore, three-dimensional biopolymer matrices provide...Properties of Biopolymer Networks Biopolymer networks exhibit unique nonlinear rheological behavior that differs dramatically from most synthetic...and presumably other biopolymers , is not well defined in variable gap geometries. These findings have broad implications for the interpretation of

Counterfeit Social Capital and Mexican-American Underachievement

ERIC Educational Resources Information Center

Ream, Robert K.

2003-01-01

A critical issue facing U.S. schools and one with broad social implication is the persistent disparity in educational achievement between racial/ethnic groups. The achievement gap may be particularly pronounced for Mexican-Americans who constitute the vast majority of U.S. Latinos and are among the most educationally at risk of all Latino…

China-U.S. Relations: Current Issues and Implications for U.S. Policy

DTIC Science & Technology

2007-11-09

publicized recalls of PRC imported products including fish, tires, toothpaste , and toys. Two of these — Menu Foods pet food recall and Mattel’s...assistance to rogue states and other international bad actors. CRS-6 10 Statement by State Department spokesman Sean McCormack, March 8, 2007. 11 Broad

Visualization of Plasticity in Fear-Evoked Calcium Signals in Midbrain Dopamine Neurons

ERIC Educational Resources Information Center

Gore, Bryan B.; Soden, Marta E.; Zweifel, Larry S.

2014-01-01

Dopamine is broadly implicated in fear-related processes, yet we know very little about signaling dynamics in these neurons during active fear conditioning. We describe the direct imaging of calcium signals of dopamine neurons during Pavlovian fear conditioning using fiber-optic confocal microscopy coupled with the genetically encoded calcium…

Looking within and beyond the Geometry Curriculum: Connecting Spatial Reasoning to Mathematics Learning

ERIC Educational Resources Information Center

Mulligan, Joanne

2015-01-01

This commentary adopts a broad perspective in considering the contributions of papers from cross- and interdisciplinary fields of mathematics education, psychology, child development and neuroscience. The discussion aims to complement the commentary by Dindyal, focused on background research on geometry and implications for pedagogy and curricula.…

[Microbial secondary metabolites as potential reserve of pharmaceuticals].

PubMed

Orlova, T I; Bulgakova, V G; Polin, A N

2014-01-01

The major characteristics of new bioactive microbial secondary metabolites are summarized in the review. A wide range of new molecular targets are implicated in discovery of new nonantibiotic compounds with some other pharmacological activities (noninfectious diseases). Microorganisms represent fascinating resources due to their production of novel products with broad spectra of bioactivities.

Why Adults Participate in Education: Some Implications for Program Development of Research on Motivational Orientations.

ERIC Educational Resources Information Center

Darkenwald, Gordon G.

While recent research on why adults participate in continuing education programs does not provide educational planners with any easy prescriptions for programing success, it does suggest some broad directions for more effective program development, particularly in relation to needs assessment, the promotional aspect of marketing, and the design…

The Future of the Web, Intelligent Devices, and Education.

ERIC Educational Resources Information Center

Strauss, Howard

1999-01-01

Examines past trends in hardware, software, networking, and education, in an attempt to determine where they are going and what their broad implications might be. Speculates on what will replace the World Wide Web. Describes new applications and telematons along with a new paradigm for education called SMILE (Software-Managed Instruction,…

Development of Youth Digital Citizenship Scale and Implication for Educational Setting

ERIC Educational Resources Information Center

Kim, Minjeong; Choi, Dongyeon

2018-01-01

Digital citizens need comprehensive knowledge and technological accessibility to the internet and digital world and teachers have a responsibility to lead them to become digital citizens. However, existing Digital Citizenship Scales contain too broad ranges and do not precisely focus on the target students, so teachers do not have clear criteria…

What Are the Implications of Neuroscience for Musical Education?

ERIC Educational Resources Information Center

Stewart, Lauren; Williamon, Aaron

2008-01-01

Background: In this paper, we consider music education in a broad sense-not merely pertaining to the development of exceptional levels of artistry in talented performers, but also to notions of musical listening and appreciation enjoyed by the casual listener. Purpose: This review cannot be exhaustive, but aims to illustrate what we already know…

Disability, Stigma and Otherness: Perspectives of Parents and Teachers

ERIC Educational Resources Information Center

Lalvani, Priya

2015-01-01

This qualitative study explored the perspectives of parents and teachers in the US with regard to the meaning and implications of disability in the context of schoolling, and of raising a child with a disability. The findings revealed broad conceptual differences in the perspectives of these two groups. Teachers' beliefs were generally consistent…

Considering Life Cycle during Design: A Longitudinal Study of Engineering Undergraduates. Research Brief

ERIC Educational Resources Information Center

Yasuhara, Ken; Morozov, Andrew; Kilgore, Deborah; Atman, Cynthia; Loucks-Jaret, Christine

2009-01-01

In this age of global warming and diminishing fossil fuel stores, society is becoming increasingly aware that seemingly small decisions can have surprisingly far-reaching implications on the environment and future generations. Accordingly, today's engineers must approach design problems with a holistic, broad view of the impacts,…

Development and Validation of the Delaying Gratification Inventory

ERIC Educational Resources Information Center

Hoerger, Michael; Quirk, Stuart W.; Weed, Nathan C.

2011-01-01

Deficits in gratification delay are associated with a broad range of public health problems, such as obesity, risky sexual behavior, and substance abuse. However, 6 decades of research on the construct has progressed less quickly than might be hoped, largely because of measurement issues. Although past research has implicated 5 domains of delay…

Theoretical Constructs of Well-Being and Their Implications for Education

ERIC Educational Resources Information Center

Thorburn, Malcolm

2015-01-01

In the broad area of moral philosophy, critiques of well-being values have notably increased since the 1980's. Often underpinning analysis are contrasting theories of well-being, e.g. subjective constructs that value highly reflections on personal experiences and individual fulfillment, and objective theories that emphasise more through specific…

Writing Essentials | Center for Cancer Research

Cancer.gov

To effectively communicate research results, the manuscript should be carefully structured to tell a compelling story. As a rule, the introduction should bring the reader from a broad understanding of the topic to the specific question being addressed. In contrast, the discussion should transition the reader from the specific results to their broader implications.

Methods of Identification of Students with Learning Disabilities in Reading: Perceptions of Administrators in Illinois and Implications for School Psychologists

ERIC Educational Resources Information Center

Hopper, Christy L.

2014-01-01

School psychologists' training provides a variety of skills from which its practitioners may draw, including consultation, intervention, counseling, staff development, and assessment. Despite these broad skills, school psychologists' primary roles involve assessment and assessment-related tasks, generally as related to eligibility determination…

Implications of Small Samples for Generalization: Adjustments and Rules of Thumb

ERIC Educational Resources Information Center

Tipton, Elizabeth; Hallberg, Kelly; Hedges, Larry V.; Chan, Wendy

2015-01-01

Policy-makers are frequently interested in understanding how effective a particular intervention may be for a specific (and often broad) population. In many fields, particularly education and social welfare, the ideal form of these evaluations is a large-scale randomized experiment. Recent research has highlighted that sites in these large-scale…

Education in Emergencies: The Gender Implications. Advocacy Brief

ERIC Educational Resources Information Center

Kirk, Jackie

2006-01-01

"Education in emergencies" refers to a broad range of education activities, both formal and non-formal, which are life saving and sustaining. They are critical for children, youth and their families in times of crisis. Programmes for emergency education are often designed according to a specific environmental context and sometimes as temporary…

Family-Centered Early Intervention for Communication Disorders: Prevention and Treatment. Excellence in Practice Series.

ERIC Educational Resources Information Center

Donahue-Kilburg, Gail

This book is designed to provide a broad range of information on family structure and function in an increasingly multicultural society, family system characteristics and the implications for intervention, communication development in the family context, the nature and delivery of family centered-services, specific requirements of Public Law…

Recreation and the Environment as Cultural Dimensions in Contemporary American Society

Treesearch

H. Ken Cordell; Carter J. Betz; Gary T. Green

2002-01-01

This paper broadly explores changing outdoor recreation demands, environmental opinions and demographics in the United States. With this country's population predicted to more than double by the end of this century, it is imperative that we understand these trends and their implications for better managing our natural envimnment and providing opportunities for...

Education for Future-Oriented Citizenship: Implications for the Education of Twenty-First Century Competencies

ERIC Educational Resources Information Center

Lee, Wing On

2012-01-01

Globalization and the knowledge economy have opened up worldwide agendas for national development. Following this is the emphasis on the social dimension, otherwise known as social capital. Much of social capital includes "soft skills" and "twenty-first century skills", which broadly cover critical, creative and inventive…

Implicit and Explicit Learning Mechanisms Meet in Monkey Prefrontal Cortex.

PubMed

Chafee, Matthew V; Crowe, David A

2017-10-11

In this issue, Loonis et al. (2017) provide the first description of unique synchrony patterns differentiating implicit and explicit forms of learning in monkey prefrontal networks. Their results have broad implications for how prefrontal networks integrate the two learning mechanisms to control behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Feed intake of gilts following intracerebroventicular injection of the novel hypothalamic RFamide (RFa) neuropeptide, 26RFa

USDA-ARS?s Scientific Manuscript database

RFamide (RFa) peptides have been implicated in a broad spectrum of biological processes including energy expenditure and feed intake. 26RFa is a recently discovered hypothalamic neuropeptide that altered the release of pituitary hormones and stimulated feed intake via a NPY-specific mechanism in rat...

Nuclear genetic variation across the range of ponderosa pine (Pinus ponderosa): Phylogeographic, taxonomic and conservation implications

Treesearch

Kevin M. Potter; Valerie D. Hipkins; Mary F. Mahalovich; Robert E. Means

2015-01-01

Ponderosa pine (Pinus ponderosa) is among the most broadly distributed conifer species of western North America, where it possesses considerable ecological, esthetic, and commercial value. It exhibits complicated patterns of morphological and genetic variation, suggesting that it may be in the process of differentiating into distinct regional...

Secondary Mathematics Coaching: The Components of Effective Mathematics Coaching and Implications

ERIC Educational Resources Information Center

Bengo, Priscilla

2016-01-01

Mathematics coaching, which can be defined broadly as job-embedded learning for mathematics teachers with someone who can help, is being used in Canada to improve teaching practice and increase student achievement. Mathematics coaching research is quite new with little written on the components of effective coaching. The paper attempts to…

Restoration planning on the Okanogan-Wenatchee national forest: prescriptions for resilient landscapes

Treesearch

Keith Reynolds; Paul Hessburg; Joan O’Callaghan

2014-01-01

Human settlement and land management have radically altered the composition and structure of eastern Washington forests. Restoring high-functioning landscapes and habitat patterns have broad implications for the future sustainability of native species, ecosystem services, and ecosystem processes. Many land managers and scientists have turned their attention to whole...

Teenage Pregnancy: A Theoretical Analysis of a Social Problem.

ERIC Educational Resources Information Center

Davis, Richard A.

1989-01-01

Broadly outlines scope of the problem of teenage pregnancy, some of its more obvious causes, and some of the long-term implications of not truly understanding the nature of the problem. Concludes with theoretical critique of social disorganizational, social definitional, and social organizational approaches to the problem of teenage pregnancy.…

Advancing beyond AP Courses

ERIC Educational Resources Information Center

Hammond, Bruce G.

2008-01-01

According to this author, a quiet revolution is picking up steam in the nation's private secondary schools, with broad implications for college admissions and for teaching and learning on both sides of the transition from high school to college. About 50 of the nation's leading college-preparatory schools have opted out of the College Board's…

Key Lessons Learned from Moffitt's Molecular Tumor Board: The Clinical Genomics Action Committee Experience.

PubMed

Knepper, Todd C; Bell, Gillian C; Hicks, J Kevin; Padron, Eric; Teer, Jamie K; Vo, Teresa T; Gillis, Nancy K; Mason, Neil T; McLeod, Howard L; Walko, Christine M

2017-02-01

The increasing practicality of genomic sequencing technology has led to its incorporation into routine clinical practice. Successful identification and targeting of driver genomic alterations that provide proliferative and survival advantages to tumor cells have led to approval and ongoing development of several targeted cancer therapies. Within many major cancer centers, molecular tumor boards are constituted to shepherd precision medicine into clinical practice. In July 2014, the Clinical Genomics Action Committee (CGAC) was established as the molecular tumor board companion to the Personalized Medicine Clinical Service (PMCS) at Moffitt Cancer Center in Tampa, Florida. The processes and outcomes of the program were assessed in order to help others move into the practice of precision medicine. Through the establishment and initial 1,400 patients of the PMCS and its associated molecular tumor board at a major cancer center, five practical lessons of broad applicability have been learned: transdisciplinary engagement, the use of the molecular report as an aid to clinical management, clinical actionability, getting therapeutic options to patients, and financial considerations. Value to patients includes access to cutting-edge practice merged with individualized preferences in treatment and care. Genomic-driven cancer medicine is increasingly becoming a part of routine clinical practice. For successful implementation of precision cancer medicine, strategically organized molecular tumor boards are critical to provide objective evidence-based translation of observed molecular alterations into patient-centered clinical action. Molecular tumor board implementation models along with clinical and economic outcomes will define future treatment standards. The Oncologist 2017;22:144-151 Implications for Practice: It is clear that the increasing practicality of genetic tumor sequencing technology has led to its incorporation as part of routine clinical practice. Subsequently, many cancer centers are seeking to develop a personalized medicine services and/or molecular tumor board to shepherd precision medicine into clinical practice. This article discusses the key lessons learned through the establishment and development of a molecular tumor board and personalized medicine clinical service. This article highlights practical issues and can serve as an important guide to other centers as they conceive and develop their own personalized medicine services and molecular tumor boards. © AlphaMed Press 2017.

Key Lessons Learned from Moffitt's Molecular Tumor Board: The Clinical Genomics Action Committee Experience

PubMed Central

Knepper, Todd C.; Bell, Gillian C.; Hicks, J. Kevin; Padron, Eric; Teer, Jamie K.; Vo, Teresa T.; Gillis, Nancy K.; Mason, Neil T.; Walko, Christine M.

2017-01-01

Abstract Background. The increasing practicality of genomic sequencing technology has led to its incorporation into routine clinical practice. Successful identification and targeting of driver genomic alterations that provide proliferative and survival advantages to tumor cells have led to approval and ongoing development of several targeted cancer therapies. Within many major cancer centers, molecular tumor boards are constituted to shepherd precision medicine into clinical practice. Materials and Methods. In July 2014, the Clinical Genomics Action Committee (CGAC) was established as the molecular tumor board companion to the Personalized Medicine Clinical Service (PMCS) at Moffitt Cancer Center in Tampa, Florida. The processes and outcomes of the program were assessed in order to help others move into the practice of precision medicine. Results. Through the establishment and initial 1,400 patients of the PMCS and its associated molecular tumor board at a major cancer center, five practical lessons of broad applicability have been learned: transdisciplinary engagement, the use of the molecular report as an aid to clinical management, clinical actionability, getting therapeutic options to patients, and financial considerations. Value to patients includes access to cutting‐edge practice merged with individualized preferences in treatment and care. Conclusions. Genomic‐driven cancer medicine is increasingly becoming a part of routine clinical practice. For successful implementation of precision cancer medicine, strategically organized molecular tumor boards are critical to provide objective evidence‐based translation of observed molecular alterations into patient‐centered clinical action. Molecular tumor board implementation models along with clinical and economic outcomes will define future treatment standards. Implications for Practice. It is clear that the increasing practicality of genetic tumor sequencing technology has led to its incorporation as part of routine clinical practice. Subsequently, many cancer centers are seeking to develop a personalized medicine services and/or molecular tumor board to shepherd precision medicine into clinical practice. This article discusses the key lessons learned through the establishment and development of a molecular tumor board and personalized medicine clinical service. This article highlights practical issues and can serve as an important guide to other centers as they conceive and develop their own personalized medicine services and molecular tumor boards. PMID:28179575

Approaches to veterinary education--tracking versus a final year broad clinical experience. Part one: effects on career outcome.

PubMed

Klosterman, E S; Kass, P H; Walsh, D A

2009-08-01

This is the first of two papers that provide extensive data and analysis on the two major approaches to clinical veterinary education, which either provide students with experience of a broad range of species (often defined as omni/general clinical competence), or just a few species (sometimes just one), usually termed 'tracking'. Together the two papers provide a detailed analysis of these two approaches for the first time. The responsibilities of veterinary medicine and veterinary education are rapidly increasing throughoutthe globe. It is critical for all in veterinary education to reassess the approaches that have been used, and evaluate on a school-by-school basis which may best meet its expanding and ever-deepening responsibilities.

The Impact of Data Fragmentation on High-Throughput Clinical Phenotyping

ERIC Educational Resources Information Center

Wei, Weiqi

2012-01-01

Subject selection is essential and has become the rate-limiting step for harvesting knowledge to advance healthcare through clinical research. Present manual approaches inhibit researchers from conducting deep and broad studies and drawing confident conclusions. High-throughput clinical phenotyping (HTCP), a recently proposed approach, leverages…

Progressive Climate Change on Titan: Implications for Habitability

NASA Technical Reports Server (NTRS)

Moore, J. M.; A. D. Howard

2014-01-01

Titan's landscape is profoundly shaped by its atmosphere and comparable in magnitude perhaps with only the Earth and Mars amongst the worlds of the Solar System. Like the Earth, climate dictates the intensity and relative roles of fluvial and aeolian activity from place to place and over geologic time. Thus Titan's landscape is the record of climate change. We have investigated three broad classes of Titan climate evolution hypotheses (Steady State, Progressive, and Cyclic), regulated by the role, sources, and availability of methane. We favor the Progressive hypotheses, which we will outline here, then discuss their implication for habitability.

Neuroimaging in Posttraumatic Stress Disorder and Other Stress-related Disorders

PubMed Central

Bremner, J. Douglas

2009-01-01

Synopsis Traumatic stress has a broad range of effects on the brain. Brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Studies in patients with posttraumatic stress disorder (PTSD) and other psychiatric disorders related to stress have replicated findings in animal studies by finding alterations in these brain areas. Brain regions implicated in PTSD also play an important role in memory function, highlighting the important interplay between memory and the traumatic stress response. Abnormalities in these brain areas are hypothesized to underlie symptoms of PTSD and other stress-related psychiatric disorders. PMID:17983968

Objective assessment of attention in delirium: a narrative review.

PubMed

Tieges, Zoë; Brown, Laura J E; MacLullich, Alasdair M J

2014-12-01

Inattention is a core feature of delirium, and valid assessment of attention is central to diagnosis. Methods of measuring attention in delirium can be divided into two broad categories: (i) objective neuropsychological testing; and (ii) subjective grading of behaviour during interview and clinical examination. Here, we review and critically evaluate studies of objective neuropsychological testing of attention in delirium. We examine the implications of these studies for delirium detection and monitoring in clinical practice and research, and how these studies inform understanding of the nature of attentional deficits in delirium. Searches of MEDLINE and ISI Web of Knowledge databases were performed to identify studies in which objective tests of attention had been administered to patients with delirium, who had been diagnosed using DSM or ICD criteria. Sixteen publications were identified. The attention tests administered in these studies were grouped into the following categories: measures of attention span, vigilance tests, other pen-and-paper tests (e.g. Trail Making Test) and computerised tests of speeded reaction, vigilance and sustained attention. Patients with delirium showed deficits on all tasks, although most tasks were not considered pure measures of attention. Five papers provided data on differential diagnosis from dementia. Cancellation tests, spatial span tests and computerised tests of sustained attention discriminated delirium from dementia. Five studies presented reliability or validity statistics. The existing evidence base on objective assessment of attention in delirium is small. Objective testing of attention is underdeveloped but shows considerable promise in clinical practice and research. Copyright © 2014 John Wiley & Sons, Ltd.

Clinical methods of cryopreservation for donor lymphocyte infusions vary in their ability to preserve functional T-cell subpopulations.

PubMed

Worsham, D Nicole; Reems, Jo-Anna; Szczepiorkowski, Zbigniew M; McKenna, David H; Leemhuis, Thomas; Mathew, Aby J; Cancelas, Jose A

2017-06-01

Cryopreserved donor lymphocyte infusion (DLI) products are manufactured and administered to treat relapse after allogeneic hematopoietic stem cell transplantation. Reported clinical responses to DLIs vary broadly, even within the same group of patients. While there is an implicit recognition of the fact that different manufacturing protocols may have specific effects on different cell types, cryopreservation protocols are frequently derived from our experience in the cryopreservation of stem cell products and do not account for the heterogeneous functional nature of DLI T-cell populations. Here, we report the results of a prospective, multicenter trial on the effect of four different cryopreservation solutions that were used to freeze DLIs compared to control DLIs that were refrigerated overnight. Cryopreserved postthawed and refrigerated specimens were analyzed side by side for their T-cell subpopulation content and viability, as well as T-cell proliferation, cytokine secretion, and cytotoxic activities. This study indicates that "homemade" 10% dimethyl sulfoxide (DMSO) results in reduced viability of different CD4+ T-cell populations, including T-helper, T-cytotoxic, and T-regulatory populations, and a decrease in their proliferative and cytotoxic response to immunologically relevant stimuli, while the use of solutions containing 5% DMSO with intracellular-like cryoprotectant stabilizers maintains T-cell function at levels similar to refrigerated control samples. This study has important implications in determining the best cryoprotectant solution for specific clinical applications in allogeneic immunotherapy. © 2017 AABB.

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

PubMed

Oyarzún, Patricio; Kobe, Bostjan

2016-03-03

Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

Chikungunya Arthritis: Implications of Acute and Chronic Inflammation Mechanisms on Disease Management.

PubMed

Zaid, Ali; Gérardin, Patrick; Taylor, Adam; Mostafavi, Helen; Malvy, Denis; Mahalingam, Suresh

2018-04-01

In the past decade, arboviruses-arthropod-borne viruses-have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus, an arbovirus that belongs to the alphavirus genus, is a reemerging arthritogenic virus that has caused explosive outbreaks since 2006, notably on Réunion Island, and more recently in the Caribbean, South America, India, and Southeast Asia. The severity of arthritic disease caused by chikungunya virus has prompted public health authorities in affected countries to develop specific guidelines to tackle this pathogen. Chikungunya virus disease manifests first as an acute stage of severe joint inflammation and febrile illness, which later progresses to a chronic stage, during which patients may experience debilitating and persisting articular pain for extended periods. This review aims to provide a broad perspective on current knowledge of chikungunya virus pathogenesis by identifying key clinical and experimental studies that have contributed to our understanding of chikungunya virus to date. In addition, the review explores the practical aspects of treatment and management of both acute and chronic chikungunya virus based on clinical experience during chikungunya virus outbreaks. Finally, recent findings on potential therapeutic solutions-from antiviral agents to immunomodulators-are reviewed to provide both viral immunologists and clinical rheumatologists with a balanced perspective on the nature of a reemerging arboviral disease of significant public health concern, and insight into future therapeutic approaches to better address the treatment and management of chikungunya virus. © 2017, American College of Rheumatology.

Expression of Eukaryotic Initiation Factor 5A and Hypusine Forming Enzymes in Glioblastoma Patient Samples: Implications for New Targeted Therapies

PubMed Central

Preukschas, Michael; Hagel, Christian; Schulte, Alexander; Weber, Kristoffer; Lamszus, Katrin; Sievert, Henning; Pällmann, Nora; Bokemeyer, Carsten; Hauber, Joachim; Braig, Melanie; Balabanov, Stefan

2012-01-01

Glioblastomas are highly aggressive brain tumors of adults with poor clinical outcome. Despite a broad range of new and more specific treatment strategies, therapy of glioblastomas remains challenging and tumors relapse in all cases. Recent work demonstrated that the posttranslational hypusine modification of the eukaryotic initiation factor 5A (eIF-5A) is a crucial regulator of cell proliferation, differentiation and an important factor in tumor formation, progression and maintenance. Here we report that eIF-5A as well as the hypusine-forming enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) are highly overexpressed in glioblastoma patient samples. Importantly, targeting eIF-5A and its hypusine modification with GC7, a specific DHS-inhibitor, showed a strong antiproliferative effect in glioblastoma cell lines in vitro, while normal human astrocytes were not affected. Furthermore, we identified p53 dependent premature senescence, a permanent cell cycle arrest, as the primary outcome in U87-MG cells after treatment with GC7. Strikingly, combined treatment with clinically relevant alkylating agents and GC7 had an additive antiproliferative effect in glioblastoma cell lines. In addition, stable knockdown of eIF-5A and DHS by short hairpin RNA (shRNA) could mimic the antiproliferative effects of GC7. These findings suggest that pharmacological inhibition of eIF-5A may represent a novel concept to treat glioblastomas and may help to substantially improve the clinical course of this tumor entity. PMID:22927971

Technical and Practical Issues in the Structure and Clinical Invariance of the Wechsler Scales: A Rejoinder to Commentaries

ERIC Educational Resources Information Center

Weiss, Lawrence G.; Keith, Timothy Z.; Zhu, Jianjun; Chen, Hsinyi

2013-01-01

This discussion article addresses issues related to expansion of the Wechsler model from four to five factors; multiple broad CHC abilities measured by the Arithmetic subtest; advantages and disadvantages of including complex tasks requiring integration of multiple broad abilities when measuring intelligence; limitations of factor analysis, which…

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

PubMed Central

Lise, Stefano; Broxholme, John; Cazier, Jean-Baptiste; Rimmer, Andy; Kanapin, Alexander; Lunter, Gerton; Fiddy, Simon; Allan, Chris; Aricescu, A. Radu; Attar, Moustafa; Babbs, Christian; Becq, Jennifer; Beeson, David; Bento, Celeste; Bignell, Patricia; Blair, Edward; Buckle, Veronica J; Bull, Katherine; Cais, Ondrej; Cario, Holger; Chapel, Helen; Copley, Richard R; Cornall, Richard; Craft, Jude; Dahan, Karin; Davenport, Emma E; Dendrou, Calliope; Devuyst, Olivier; Fenwick, Aimée L; Flint, Jonathan; Fugger, Lars; Gilbert, Rodney D; Goriely, Anne; Green, Angie; Greger, Ingo H.; Grocock, Russell; Gruszczyk, Anja V; Hastings, Robert; Hatton, Edouard; Higgs, Doug; Hill, Adrian; Holmes, Chris; Howard, Malcolm; Hughes, Linda; Humburg, Peter; Johnson, David; Karpe, Fredrik; Kingsbury, Zoya; Kini, Usha; Knight, Julian C; Krohn, Jonathan; Lamble, Sarah; Langman, Craig; Lonie, Lorne; Luck, Joshua; McCarthy, Davis; McGowan, Simon J; McMullin, Mary Frances; Miller, Kerry A; Murray, Lisa; Németh, Andrea H; Nesbit, M Andrew; Nutt, David; Ormondroyd, Elizabeth; Oturai, Annette Bang; Pagnamenta, Alistair; Patel, Smita Y; Percy, Melanie; Petousi, Nayia; Piazza, Paolo; Piret, Sian E; Polanco-Echeverry, Guadalupe; Popitsch, Niko; Powrie, Fiona; Pugh, Chris; Quek, Lynn; Robbins, Peter A; Robson, Kathryn; Russo, Alexandra; Sahgal, Natasha; van Schouwenburg, Pauline A; Schuh, Anna; Silverman, Earl; Simmons, Alison; Sørensen, Per Soelberg; Sweeney, Elizabeth; Taylor, John; Thakker, Rajesh V; Tomlinson, Ian; Trebes, Amy; Twigg, Stephen RF; Uhlig, Holm H; Vyas, Paresh; Vyse, Tim; Wall, Steven A; Watkins, Hugh; Whyte, Michael P; Witty, Lorna; Wright, Ben; Yau, Chris; Buck, David; Humphray, Sean; Ratcliffe, Peter J; Bell, John I; Wilkie, Andrew OM; Bentley, David; Donnelly, Peter; McVean, Gilean

2015-01-01

To assess factors influencing the success of whole genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases across a broad spectrum of disorders in whom prior screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritisation. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease causing variants in 21% of cases, rising to 34% (23/68) for Mendelian disorders and 57% (8/14) in trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, though only four were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis, but also highlight many outstanding challenges. PMID:25985138

Influence of clinical outcome and outcome period definitions on estimates of absolute clinical and economic benefits of influenza vaccination in community dwelling elderly persons.

PubMed

Nichol, K L; Nordin, J; Mullooly, J

2006-03-06

Studies assessing the clinical and economic benefits of vaccination in the elderly have used different clinical outcomes (e.g. hospitalizations for pneumonia or influenza versus hospitalizations for respiratory and cardiovascular causes) and different outcome periods (e.g. peak versus total influenza season) on which to base estimates of clinical effectiveness and cost effectiveness. We explored the implications of these varying approaches by comparing two health economic analysis models of influenza vaccination of community-dwelling elderly persons. We developed computerized models using clinical data from 3 large US HMOs for the 1998-1999 and 1999-2000 influenza seasons. The primary health economic model used a broad definition of clinical events and outcome period and included hospitalizations for all respiratory and cardiovascular events that occurred during the entire influenza season. The alternative model used more restrictive definitions and included pneumonia or influenza hospitalizations occurring during the peak influenza season. The results of Monte Carlo simulation showed that, with the more inclusive primary model, influenza vaccination resulted in net medical care cost savings due to fewer respiratory or cardiovascular hospitalizations of Dollars 71/person vaccinated (5th-95th percentile Dollars 32-118) and net savings of Dollars 809/year of life saved (5th-95th percentile Dollars 331-1450). In contrast, the alternate model found costs of Dollars 3.50/person vaccinated (5th-95th percentile Dollars -11 to 5) and net costs of Dollars 91/year of life saved (5th-95th percentile Dollars -309 to 126). Our findings confirm that influenza vaccination of the elderly is most likely cost saving and supports policies and programs that advocate routine immunization of all persons 65 and older. They also highlight how different outcome definitions can influence the results of health economic analyses.

A Deep Learning Method to Automatically Identify Reports of Scientifically Rigorous Clinical Research from the Biomedical Literature: Comparative Analytic Study.

PubMed

Del Fiol, Guilherme; Michelson, Matthew; Iorio, Alfonso; Cotoi, Chris; Haynes, R Brian

2018-06-25

A major barrier to the practice of evidence-based medicine is efficiently finding scientifically sound studies on a given clinical topic. To investigate a deep learning approach to retrieve scientifically sound treatment studies from the biomedical literature. We trained a Convolutional Neural Network using a noisy dataset of 403,216 PubMed citations with title and abstract as features. The deep learning model was compared with state-of-the-art search filters, such as PubMed's Clinical Query Broad treatment filter, McMaster's textword search strategy (no Medical Subject Heading, MeSH, terms), and Clinical Query Balanced treatment filter. A previously annotated dataset (Clinical Hedges) was used as the gold standard. The deep learning model obtained significantly lower recall than the Clinical Queries Broad treatment filter (96.9% vs 98.4%; P<.001); and equivalent recall to McMaster's textword search (96.9% vs 97.1%; P=.57) and Clinical Queries Balanced filter (96.9% vs 97.0%; P=.63). Deep learning obtained significantly higher precision than the Clinical Queries Broad filter (34.6% vs 22.4%; P<.001) and McMaster's textword search (34.6% vs 11.8%; P<.001), but was significantly lower than the Clinical Queries Balanced filter (34.6% vs 40.9%; P<.001). Deep learning performed well compared to state-of-the-art search filters, especially when citations were not indexed. Unlike previous machine learning approaches, the proposed deep learning model does not require feature engineering, or time-sensitive or proprietary features, such as MeSH terms and bibliometrics. Deep learning is a promising approach to identifying reports of scientifically rigorous clinical research. Further work is needed to optimize the deep learning model and to assess generalizability to other areas, such as diagnosis, etiology, and prognosis. ©Guilherme Del Fiol, Matthew Michelson, Alfonso Iorio, Chris Cotoi, R Brian Haynes. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 25.06.2018.

Effects of Clinical Pathways for Common Outpatient Infections on Antibiotic Prescribing

PubMed Central

Jenkins, Timothy C.; Irwin, Amy; Coombs, Letoynia; DeAlleaume, Lauren; Ross, Stephen E.; Rozwadowski, Jeanne; Webster, Brian; Dickinson, L. Miriam; Sabel, Allison L.; MacKenzie, Thomas D.; West, David R.; Price, Connie S.

2013-01-01

Background Antibiotic overuse in the primary care setting is common. Our objective was to evaluate the effect of a clinical pathway-based intervention on antibiotic use. Methods Eight primary care clinics were randomized to receive clinical pathways for upper respiratory infection, acute bronchitis, acute rhinosinusitis, pharyngitis, acute otitis media, urinary tract infection, skin infections, and pneumonia and patient education materials (study group) versus no intervention (control group). Generalized linear mixed effects models were used to assess trends in antibiotic prescriptions for non-pneumonia acute respiratory infections and broad-spectrum antibiotic use for all eight conditions during a 2-year baseline and 1-year intervention period. Results In the study group, antibiotic prescriptions for non-pneumonia acute respiratory infections decreased from 42.7% of cases at baseline to 37.9% during the intervention period (11.2% relative reduction) (p <.0001) and from 39.8% to 38.7%, respectively, in the control group (2.8% relative reduction) (p=0.25). Overall use of broad-spectrum antibiotics in the study group decreased from 26.4% to 22.6% of cases, respectively, (14.4% relative reduction) (p <.0001) and from 20.0% to 19.4%, respectively, in the control group (3.0% relative reduction) (p=0.35). There were significant differences in the trends of prescriptions for acute respiratory infections (p<.0001) and broad-spectrum antibiotic use (p=0.001) between the study and control groups during the intervention period, with greater declines in the study group. Conclusions This intervention was associated with declining antibiotic prescriptions for non-pneumonia acute respiratory infections and use of broad-spectrum antibiotics over the first year. Evaluation of the impact over a longer study period is warranted. PMID:23507206

Social Worker Identity: A Profession in Context.

PubMed

Forenza, Brad; Eckert, Caitlin

2018-01-01

Social work is a broad field encompassing micro, mezzo, and macro areas of practice. Consequently, the field lacks a unifying professional identity due to the expansiveness of the profession. Professional identity is conceptualized as an extension of social identity, vis-à-vis the embodiment of three qualities: connectedness, expansiveness, and effectiveness. This study used 12 in-depth, individual interviews with practicing social workers to explore these qualities. Findings from interviews reveal six primary themes and 21 subthemes pertaining to social worker identity. Themes and subthemes are organized according to three broad families (social work in context, professional trajectories, and external influences). Implications for policy, practice, and future research are presented. © 2017 National Association of Social Workers.

&LDQUO;EFFECTS OF SURFACE OXIDES ON THE BEHAVIOR OF CARBON NANOTUBES AND THEIR INFLUENCE ON THE MOBILITY OF CONTAMINANTS IN AQUATIC ENVIRONMENTS&RDQUO;

EPA Science Inventory

By identifying conditions where CNTs could influence the transport of organic or inorganic contaminants, the proposed studies will have far reaching and broad implications for the health and safety risks associated with CNTs. Moreover, the experimental database generated in th...

Some Implications of Expertise Research for Educational Assessment

ERIC Educational Resources Information Center

Mislevy, Robert J.

2010-01-01

An educational assessment embodies an argument from a handful of observations of what students say, do or make in a handful of particular circumstances, to what they know or can do in what kinds of situations more broadly. This article discusses ways in which research into the nature and development of expertise can help assessment designers…

The Role of Teacher Emotions in Change: Experiences, Patterns and Implications for Professional Development

ERIC Educational Resources Information Center

Saunders, Rebecca

2013-01-01

Research literature in the field of teacher emotions and change broadly accepts that behaviour and cognition are inseparable from perception and emotion. Despite this, educational reform efforts tend to focus predominantly on changing individual behaviours and beliefs and largely neglect or at best pay token attention to the emotional dimensions…

Who Guards the Guardians? National Implications of Accreditation at City College of San Francisco

ERIC Educational Resources Information Center

Barber, Bob; McNair, Delores E.

2017-01-01

Purpose: This article addresses the broad context of community college accreditation which surrounds a controversy involving one of the largest community colleges in the United States, City College of San Francisco (CCSF), and its regional accrediting agency, the Accrediting Commission for Community and Junior Colleges (ACCJC). Its purposes are to…

Implications of Harmonizing the Future of the Federal Depository Library Program within E-Government Principles and Policies

ERIC Educational Resources Information Center

Shuler, John A.; Jaeger, Paul T.; Bertot, John Carlo

2010-01-01

For more than 150 years, the United States Government Printing Office (GPO), along with its Federal Depository Library Program (FDLP), has supported an informed citizenry and democracy by ensuring access and preservation to a broad swath of federal government information. This collaborative national public information program between local…

Argumentation Tasks in Secondary English Language Arts, History, and Science: Variations in Instructional Focus and Inquiry Space

ERIC Educational Resources Information Center

Litman, Cindy; Greenleaf, Cynthia

2018-01-01

This study drew on observations of 40 secondary English language arts, history, and science lessons to describe variation in opportunities for students to engage in argumentation and possible implications for student engagement and learning. The authors focused their analysis on two broad dimensions of argumentation tasks: (1) "Instructional…

China-U.S. Relations: Current Issues and Implications for U.S. Policy

DTIC Science & Technology

2007-12-21

products including fish, tires, toothpaste , and toys. Two of these — Menu Foods pet food recall and Mattel’s voluntary recall of over 18 million toys...international bad actors. CRS-6 10 Statement by State Department spokesman Sean McCormack, March 8, 2007. 11 Broad, William J., “Orbiting junk, once a

Prebiotic and probiotic approaches to improving food safety on the farm and their implications on human health

USDA-ARS?s Scientific Manuscript database

Human health is a broad category that encompasses the entirety of the food production system. Livestock production practices have important impacts on human health because livestock are not only a primary food source, but also can be the source of pathogenic bacteria that may enter the food chain i...

Teachers' and Students' Perceptions of Students' Problem-Solving Difficulties in Physics: Implications for Remediation

ERIC Educational Resources Information Center

Ogunleye, Ayodele O.

2009-01-01

In recent times, science education researchers have identified a lot of instruments for evaluating conceptual understanding as well as students' attitudes and beliefs about physics; unfortunately however, there are no broad based evaluation instruments in the field of problem-solving in physics. This missing tool is an indication of the complexity…

Tree seedling response to LED spectra: Implications for forest restoration

Treesearch

Antonio Montagnoli; R. Kasten Dumroese; Mattia Terzaghi; Jeremiah R. Pinto; Nicoletta Fulgaro; Gabriella Stefania Scippa; Donato Chiatante

2018-01-01

We found that different spectra, provided by light-emitting diodes or a fluorescent lamp, caused different photomorphological responses depending on tree seedling type (coniferous or broad-leaved), species, seedling development stage, and seedling fraction (shoot or root). For two conifers (Picea abies and Pinus sylvestris) soon after germination (≤40 days), more...

Critical Pathways to School Readiness: Implications for First 5 Ventura County Strategic Planning, Funding and Evaluation

ERIC Educational Resources Information Center

Thompson, Lisa; Tullis, Ericka; Franke, Todd; Halfon, Neal

2005-01-01

The UCLA Center for Healthier Children, Families and Communities (CHCFC) has developed the School Readiness Critical Pathways (SRCPs) as an evidence-based conceptual model that links related outcomes and strategies. This helps to organize an array of broad and diffuse evidence regarding the strategies that produce school readiness outcomes for…

A Literature Review of Computers and Pedagogy for Journalism and Mass Communication Education.

ERIC Educational Resources Information Center

Hoag, Anne M.; Bhattacharya, Sandhya; Helsel, Jeffrey; Hu, Yifeng; Lee, Sangki; Kim, Jinhee; Kim, Sunghae; Michael, Patty Wharton; Park, Chongdae; Sager, Sheila S.; Seo, Sangho; Stark, Craig; Yeo, Benjamin

2003-01-01

Notes that a growing body of scholarship on computers and pedagogy encompasses a broad range of topics. Focuses on research judged to have implications within journalism and mass communication education. Discusses literature which considers computer use in course design and teaching, student attributes in a digital learning context, the role of…

Critical Pedagogy Enacted in the Gay-Straight Alliance: New Possibilities for a Third Space in Teacher Development

ERIC Educational Resources Information Center

Mayo, J. B., Jr.

2013-01-01

Critical pedagogy, combined with partnerships with adults at school, enabled the Gay-Straight Alliance (GSA) advisor to create the foundation for reflective, activist-oriented learning at one Midwestern high school. Underreported in current literature, the use of critical pedagogy in school clubs and/or organizations has broad implications for…

Summary Report: State-of-the-Science Workshop on Chemically-Induced Mouse Lung Tumors: Applications to Human Health Assessments

EPA Science Inventory

The EPA hosted a two-day, state-of-the-science workshop which covered a broad range of evidence from human, animal, and in vitro studies with a focus on specific chemicals (ethylbenzene, naphthalene, and styrene) that cause lung tumors in mice and are implicated in a proposed spe...

Isosinglet approximation for nonelastic reactions

NASA Technical Reports Server (NTRS)

Wilson, J. W.

1972-01-01

Group theoretic relations are derived between different combinations of projectile and secondary particles which appear to have a broad range of application in spacecraft shielding or radiation damage studies. These relations are used to reduce the experimental effort required to obtain nuclear reaction data for transport calculations. Implications for theoretical modeling are also noted, especially for heavy-heavy reactions.

Rural Oriented R&D Projects Supported by ETA/USDL: A Review and Synthesis. Papers in Employment and Training Studies.

ERIC Educational Resources Information Center

Leonardson, Gene S.; Nelson, David M.

Seventy-one 1963-75 Research & Development (R&D) reports were reviewed for purposes of providing a rural R&D synthesis useful to Comprehensive Employment and Training Act (CETA) planners and identifying labor market analysis techniques/implications successful rural programmatic initiations, data gaps, and broad policy issues. Conclusions and…

Using Dialogue to Engage Agricultural Audiences in Cooperative Learning about Climate Change: A Strategy with Broad Implications

ERIC Educational Resources Information Center

Doll, Julie E.; Eschbach, Cheryl L.; DeDecker, James

2018-01-01

Dialogue with stakeholders has been recognized as an effective educational strategy for addressing complex topics such as climate change. We report here on the Carbon, Energy, and Climate fishbowl discussion series developed by Michigan State University Extension to assist the state's agricultural community in understanding and adapting to the…

Environmental Quality, the Third Annual Report of the Council on Environmental Quality.

ERIC Educational Resources Information Center

Council on Environmental Quality, Washington, DC.

The state of the environment and efforts to improve it are reported upon in this Third Annual Report of the Council on Environmental Quality. Broad in scope, the report covers federal and state activities during the past year, the development of environmental indices, and legal implications of the National Environmental Policy Act. The chapter on…

Pre-Service Teachers' Attitudes towards Overseas Professional Experience: Implications for Professional Practice

ERIC Educational Resources Information Center

Chinnappan, Mohan; McKenzie, Barbra; Fitzsimmons, Phil

2013-01-01

Reforms in Australia about the education of future teachers has placed a high degree of emphasis on the development of knowledge and skills that are necessary for practitioners who will ply their trade in culturally rich and diverse classrooms (Ramsey, 2000). There is now a broad consensus from key stakeholders (Australian Institute for Teaching…

Verb Selection and Past-Tense Morphology: Crystal's Criteria Revisited

ERIC Educational Resources Information Center

Weiler, Brian

2013-01-01

Research findings concerning verb-level influences on past-tense morphology carry implications for the careful selection of treatment targets. Using 6 of the broad criteria for "good verbs to choose" proposed by D. Crystal (1985) more than 25 years ago as a framework, this article summarizes some of the more recent research with a nod…

How Low Can Conventional Generators Go? | News | NREL

Science.gov Websites

, lead author of the study. "So this paper is a deep dive into one of the many things we need to assumptions, the study is mainly targeted toward the grid modeling community-but the topic has broad policy implications for renewable deployment. According to the study authors, if minimum generation levels are

The Massive Open Online Course Movement, xMOOCs, and Faculty Labor

ERIC Educational Resources Information Center

Rhoads, Robert A.; Camacho, Maria Sayil; Toven-Lindsey, Brit; Lozano, Jennifer Berdan

2015-01-01

Using critical discourse analysis, the authors examine a broad range of texts to make sense of the rise of the MOOC movement and implications for faculty work. Drawing on Braverman's labor process theory and critiques of neoliberalism, the authors highlight the role of xMOOCs in particular, focusing on challenges to faculty labor. They organize…

How to Improve Your Impact Factor: Questioning the Quantification of Academic Quality

ERIC Educational Resources Information Center

Smeyers, Paul; Burbules, Nicholas C.

2011-01-01

A broad-scale quantification of the measure of quality for scholarship is under way. This trend has fundamental implications for the future of academic publishing and employment. In this essay we want to raise questions about these burgeoning practices, particularly how they affect philosophy of education and similar sub-disciplines. First,…

The cingulum: A unique structure of some Dolichopodidae

Treesearch

Justin Runyon

2008-01-01

The cingulum is a U-shaped structure of unknown function which arises between abdominal sterna 4 and 5 and terminates in a pair of variously modified flag-like appendages. This structure is well developed only in males of the genus Scellus. Richard Hurley discovered that Hydatostega have a much reduced cingulum, a finding that had broad implications for elucidating...

Living the Good (Work) Life: Implications of General Values for Work Values

ERIC Educational Resources Information Center

Carlstrom, Aaron H.

2011-01-01

Advances in the understanding of general values from personality and social psychology apply to work values. In this paper, I introduce the concepts of values, value priorities, motivational goals, value types, and personal value systems used to clarify work values. I also introduce the terms basic and broad value and work value types. Second, I…

Education and the Transformation of Markets and Technology in the Textile Industry. Technical Paper No. 2.

ERIC Educational Resources Information Center

Bailey, Thomas

This report on the textile industry focuses on the training and education of production-level textile workers--from unskilled factory hands to first-level supervisors. It is part of a larger study of the educational implications of broad economic changes, particularly the spread of microelectronic technologies, growing national and international…

Using Rasch Measurement to Score, Evaluate, and Improve Examinations in an Anatomy Course

ERIC Educational Resources Information Center

Royal, Kenneth D.; Gilliland, Kurt O.; Kernick, Edward T.

2014-01-01

Any examination that involves moderate to high stakes implications for examinees should be psychometrically sound and legally defensible. Currently, there are two broad and competing families of test theories that are used to score examination data. The majority of instructors outside the high-stakes testing arena rely on classical test theory…

The Future of the Web, Intelligent Devices, and Education

ERIC Educational Resources Information Center

Strauss, Howard

2007-01-01

In this article, the author looks to the past for trends in hardware, software, networking, and education and attempt to extrapolate where they are going and what their broad implications might be. However, there are many different ways that trends can be interpreted, and it is easy to pick trends that support one's thesis and ignore ones that…

A broad range assay for rapid detection and etiologic characterization of bacterial meningitis: performance testing in samples from sub-Sahara.

PubMed

Won, Helen; Yang, Samuel; Gaydos, Charlotte; Hardick, Justin; Ramachandran, Padmini; Hsieh, Yu-Hsiang; Kecojevic, Alexander; Njanpop-Lafourcade, Berthe-Marie; Mueller, Judith E; Tameklo, Tsidi Agbeko; Badziklou, Kossi; Gessner, Bradford D; Rothman, Richard E

2012-09-01

This study aimed to conduct a pilot evaluation of broad-based multiprobe polymerase chain reaction (PCR) in clinical cerebrospinal fluid (CSF) samples compared to local conventional PCR/culture methods used for bacterial meningitis surveillance. A previously described PCR consisting of initial broad-based detection of Eubacteriales by a universal probe, followed by Gram typing, and pathogen-specific probes was designed targeting variable regions of the 16S rRNA gene. The diagnostic performance of the 16S rRNA assay in "127 CSF samples was evaluated in samples from patients from Togo, Africa, by comparison to conventional PCR/culture methods. Our probes detected Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Uniprobe sensitivity and specificity versus conventional PCR were 100% and 54.6%, respectively. Sensitivity and specificity of uniprobe versus culture methods were 96.5% and 52.5%, respectively. Gram-typing probes correctly typed 98.8% (82/83) and pathogen-specific probes identified 96.4% (80/83) of the positives. This broad-based PCR algorithm successfully detected and provided species level information for multiple bacterial meningitis agents in clinical samples. Copyright © 2012 Elsevier Inc. All rights reserved.

A broad range assay for rapid detection and etiologic characterization of bacterial meningitis: performance testing in samples from sub-Sahara☆, ☆☆,★

PubMed Central

Won, Helen; Yang, Samuel; Gaydos, Charlotte; Hardick, Justin; Ramachandran, Padmini; Hsieh, Yu-Hsiang; Kecojevic, Alexander; Njanpop-Lafourcade, Berthe-Marie; Mueller, Judith E.; Tameklo, Tsidi Agbeko; Badziklou, Kossi; Gessner, Bradford D.; Rothman, Richard E.

2012-01-01

This study aimed to conduct a pilot evaluation of broad-based multiprobe polymerase chain reaction (PCR) in clinical cerebrospinal fluid (CSF) samples compared to local conventional PCR/culture methods used for bacterial meningitis surveillance. A previously described PCR consisting of initial broad-based detection of Eubacteriales by a universal probe, followed by Gram typing, and pathogen-specific probes was designed targeting variable regions of the 16S rRNA gene. The diagnostic performance of the 16S rRNA assay in “”127 CSF samples was evaluated in samples from patients from Togo, Africa, by comparison to conventional PCR/culture methods. Our probes detected Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Uniprobe sensitivity and specificity versus conventional PCR were 100% and 54.6%, respectively. Sensitivity and specificity of uniprobe versus culture methods were 96.5% and 52.5%, respectively. Gram-typing probes correctly typed 98.8% (82/83) and pathogen-specific probes identified 96.4% (80/83) of the positives. This broad-based PCR algorithm successfully detected and provided species level information for multiple bacterial meningitis agents in clinical samples. PMID:22809694

Rivastigmine for Alzheimer's disease: Canadian interpretation of intermediate outcome measures and cost implications.

PubMed

Baladi, J F; Bailey, P A; Black, S; Bouchard, R W; Farcnik, K D; Gauthier, S; Kertesz, A; Mohr, E; Robillard, A

2000-12-01

Clinical studies have shown that patients with Alzheimer's disease (AD) who are treated with rivastigmine have statistically significantly better scores on 5 scales used to assess AD than control patients receiving placebo. However, the clinical meaning and cost implications of these differences are not clear. The purpose of this study was to assess the clinical meaning and cost implications of statistically significant results obtained in clinical trials of rivastigmine for the treatment of AD. Potential cost implications for the health care system, caregivers, and society are considered. Data on clinical effects of rivastigmine were obtained from published North American and European clinical studies of patients with mild to moderately severe AD receiving rivastigmine 6 to 12 mg/d (n = 828) or placebo (n = 647). Differences in scores on the Alzheimer's Disease Assessment Scale-Cognitive Function, Clinician's Interview-Based Impression of Change with both clinical and caregiver information considered, Progressive Deterioration Scale, Mini-Mental State Examination (MMSE), and Global Deterioration Scale were assessed. A convenience panel of 9 Canadian specialists experienced in the treatment of AD provided their opinions on the clinical importance of the trial results. Chart review was performed to identify specific behaviors that improved, and cost implications of improvements were assessed. The panel determined that statistically significant differences in scores on all scales except the MMSE were likely associated with functional or cognitive differences that were clinically relevant for patients, reflecting stabilization that would have beneficial consequences for caregivers and health care resource use. Subsequent chart review showed that improvement on specific scale items confirmed the physician panel's opinion. Analysis of possible cost implications to society indicated that medication expenditures would be offset largely by delays in the need for paid home care and institutionalization, positive effects on caregiver health, and less time lost from work for the caregiver. From the perspective of a Canadian specialist panel, rivastigmine treatment for AD produces clinically relevant effects for patients that are beneficial to caregivers. These effects suggest decreased use of caregiver resources and delays in the need for institutionalization, both of which reduce societal costs.

Diagnosis of Meningococcal Meningitis by Broad-Range Bacterial PCR with Cerebrospinal Fluid

PubMed Central

Kotilainen, Pirkko; Jalava, Jari; Meurman, Olli; Lehtonen, Olli-Pekka; Rintala, Esa; Seppälä, Olli-Pekka; Eerola, Erkki; Nikkari, Simo

1998-01-01

We used broad-range bacterial PCR combined with DNA sequencing to examine prospectively cerebrospinal fluid (CSF) samples from patients with suspected meningitis. Fifty-six CSF samples from 46 patients were studied during the year 1995. Genes coding for bacterial 16S and/or 23S rRNA genes could be amplified from the CSF samples from five patients with a clinical picture consistent with acute bacterial meningitis. For these patients, the sequenced PCR product shared 98.3 to 100% homology with the Neisseria meningitidis sequence. For one patient, the diagnosis was initially made by PCR alone. Of the remaining 51 CSF samples, for 50 (98.0%) samples the negative PCR findings were in accordance with the negative findings by bacterial culture and Gram staining, as well as with the eventual clinical diagnosis for the patient. However, the PCR test failed to detect the bacterial rRNA gene in one CSF sample, the culture of which yielded Listeria monocytogenes. These results invite new research efforts to be focused on the application of PCR with broad-range bacterial primers to improve the etiologic diagnosis of bacterial meningitis. In a clinical setting, Gram staining and bacterial culture still remain the cornerstones of diagnosis. PMID:9665992

In Vitro Neutralisation of Rotavirus Infection by Two Broadly Specific Recombinant Monovalent Llama-Derived Antibody Fragments

PubMed Central

Aladin, Farah; Einerhand, Alexandra W. C.; Bouma, Janneke; Bezemer, Sandra; Hermans, Pim; Wolvers, Danielle; Bellamy, Kate; Frenken, Leon G. J.; Gray, Jim; Iturriza-Gómara, Miren

2012-01-01

Rotavirus is the main cause of viral gastroenteritis in young children. Therefore, the development of inexpensive antiviral products for the prevention and/or treatment of rotavirus disease remains a priority. Previously we have shown that a recombinant monovalent antibody fragment (referred to as Anti-Rotavirus Proteins or ARP1) derived from a heavy chain antibody of a llama immunised with rotavirus was able to neutralise rotavirus infection in a mouse model system. In the present work we investigated the specificity and neutralising activity of two llama antibody fragments, ARP1 and ARP3, against 13 cell culture adapted rotavirus strains of diverse genotypes. In addition, immunocapture electron microscopy (IEM) was performed to determine binding of ARP1 to clinical isolates and cell culture adapted strains. ARP1 and ARP3 were able to neutralise a broad variety of rotavirus serotypes/genotypes in vitro, and in addition, IEM showed specific binding to a variety of cell adapted strains as well as strains from clinical specimens. These results indicated that these molecules could potentially be used as immunoprophylactic and/or immunotherapeutic products for the prevention and/or treatment of infection of a broad range of clinically relevant rotavirus strains. PMID:22403728

Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor suppressor genes

PubMed Central

Chen, Kaifu; Chen, Zhong; Wu, Dayong; Zhang, Lili; Lin, Xueqiu; Su, Jianzhong; Rodriguez, Benjamin; Xi, Yuanxin; Xia, Zheng; Chen, Xi; Shi, Xiaobing; Wang, Qianben; Li, Wei

2016-01-01

Tumor suppressors are mostly defined by inactivating mutations in tumors, yet little is known about their epigenetic features in normal cells. Through integrative analysis of 1,134 genome-wide epigenetic profiles, mutations from >8,200 tumor-normal pairs, and our experimental data from clinical samples, we discovered broad H3K4me3 (wider than 4 kb) as the first epigenetic signature for tumor suppressors in normal cells. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity together leading to exceptionally high gene expression, and is distinct from other broad epigenetic features, such as super-enhancers. Broad H3K4me3 conserved across normal cells may represent pan-cancer tumor suppressors, such as P53 and PTEN, whereas cell-type-specific broad H3K4me3 may indicate cell-identity genes and cell-type-specific tumor suppressors. Furthermore, widespread shortening of broad H3K4me3 in cancers is associated with repression of tumor suppressors. Together, the broad H3K4me3 epigenetic signature provides mutation-independent information for the discovery and characterization of novel tumor suppressors. PMID:26301496

A Systematic Review of Strategies to Prevent Cisplatin‐Induced Nephrotoxicity

PubMed Central

Crona, Daniel J.; Faso, Aimee; Nishijima, Tomohiro F.; McGraw, Kathleen A.; Galsky, Matthew D.

2017-01-01

Abstract Introduction. Cisplatin, a platinum‐based antineoplastic agent, is the cornerstone for the treatment of many malignancies. Nephrotoxicity is the primary dose‐limiting toxicity, and various hydration regimens and supplementation strategies are used to prevent cisplatin‐induced kidney injury. However, evidence‐based recommendations on specific hydration regimens are limited. A systematic review was performed to evaluate clinical studies that have examined hydration and supplementation strategies to prevent cisplatin‐induced nephrotoxicity. Materials and Methods. PubMed and Excerpta Medica databases were searched from 1966 through October 2015 for clinical trials and other studies focused on hydration regimens to prevent nephrotoxicity in cancer patients treated with cisplatin. The University of Oxford Centre for Evidence‐Based Medicine criteria were used to grade level of evidence. Results. Among the 1,407 identified studies, 24 were included in this systematic review. All studies differed on type, volume, and duration of hydration. Among the 24 studies, 5 evaluated short‐duration hydration, 4 evaluated low‐volume hydration, 4 investigated magnesium supplementation, and 7 reviewed forced diuresis with hydration. Short‐duration and lower‐volume hydration regimens are effective in preventing cisplatin‐induced nephrotoxicity. Magnesium supplementation may have a role as a nephroprotectant, and forced diuresis may be appropriate in some patients receiving cisplatin. Conclusion. Hydration is essential for all patients to prevent cisplatin‐induced nephrotoxicity. Specifically, short‐duration, low‐volume, outpatient hydration with magnesium supplementation and mannitol forced diuresis (in select patients) represent best practice principles for the safe use of cisplatin. The Oncologist 2017;22:609–619 Implications for Practice. The findings contained within this systematic review show that (a) hydration is essential for all patients to prevent cisplatin‐induced nephrotoxicity, (b) short‐duration, low‐volume, outpatient hydration regimens appear to be safe and feasible, even in patients receiving intermediate‐ to high‐dose cisplatin, (c) magnesium supplementation (8–16 milliequivalents) may limit cisplatin‐induced nephrotoxicity, and (d) mannitol may be considered for high‐dose cisplatin and/or patients with preexisting hypertension. These findings have broad implications for clinical practice and represent best practice principles for the prevention of cisplatin‐induced nephrotoxicity. PMID:28438887

Poisoning in goats by the monofluoracetate-containing plant Palicourea aeneofusca (Rubiaceae)

USDA-ARS?s Scientific Manuscript database

The epidemiological, clinical and pathological aspects of a spontaneous outbreak of Palicourea aeneofusca poisoning in goats are reported. The main clinical signs were motor incoordination, generalized muscle tremors, broad-based posture, tachypnea, tachycardia, vocalization and respiratory distress...

A cost analysis of a broad-spectrum antibiotic therapy in the empirical treatment of health care-associated infections in cirrhotic patients

PubMed Central

Lucidi, Cristina; Di Gregorio, Vincenza; Ceccarelli, Giancarlo; Venditti, Mario; Riggio, Oliviero; Merli, Manuela

2017-01-01

Background Early diagnosis and appropriate treatment of infections in cirrhosis are crucial. As new guidelines in this context, particularly for health care-associated (HCA) infections, would be needed, we performed a trial documenting whether an empirical broad-spectrum antibiotic therapy is more effective than the standard one for these infections. Because of the higher daily cost of broad-spectrum than standard antibiotics, we performed a cost analysis to compare: 1) total drug costs, 2) profitability of hospital admissions. Methods This retrospective observational analysis was performed on patients enrolled in the trial NCT01820026, in which consecutive cirrhotic patients with HCA infections were randomly assigned to a standard vs a broad-spectrum treatment. Antibiotic daily doses, days of treatment, length of hospital stay, and DRG (diagnosis-related group) were recorded from the clinical trial medical records. The profitability of hospitalizations was calculated considering DRG tariffs divided by length of hospital stay. Results We considered 84 patients (42 for each group). The standard therapy allowed to obtain a first-line treatment cost lower than in the broad-spectrum therapy. Anyway, the latter, being related to a lower failure rate (19% vs 57.1%), resulted in cost saving in terms of cumulative antibiotic costs (first- and second-line treatments). The mean cost saving per patient for the broad-spectrum arm was €44.18 (−37.6%), with a total cost saving of about €2,000. Compared to standard group, we observed a statistically significant reduction in hospital stay from 17.8 to 11.8 days (p<0.002) for patients treated with broad-spectrum antibiotics. The distribution of DRG tariffs was similar in the two groups. According to DRG, the shorter length of hospital stay of the broad-spectrum group involved a higher mean profitable daily cost than standard group (€345.61 vs €252.23; +37%). Conclusion Our study supports the idea that the use of a broad-spectrum empirical treatment for HCA infections in cirrhosis would be cost-saving and that hospitals need to be aware of the clinical and economic consequences of a wrong antibiotic treatment in this setting. PMID:28721080

A cost analysis of a broad-spectrum antibiotic therapy in the empirical treatment of health care-associated infections in cirrhotic patients.

PubMed

Lucidi, Cristina; Di Gregorio, Vincenza; Ceccarelli, Giancarlo; Venditti, Mario; Riggio, Oliviero; Merli, Manuela

2017-01-01

Early diagnosis and appropriate treatment of infections in cirrhosis are crucial. As new guidelines in this context, particularly for health care-associated (HCA) infections, would be needed, we performed a trial documenting whether an empirical broad-spectrum antibiotic therapy is more effective than the standard one for these infections. Because of the higher daily cost of broad-spectrum than standard antibiotics, we performed a cost analysis to compare: 1) total drug costs, 2) profitability of hospital admissions. This retrospective observational analysis was performed on patients enrolled in the trial NCT01820026, in which consecutive cirrhotic patients with HCA infections were randomly assigned to a standard vs a broad-spectrum treatment. Antibiotic daily doses, days of treatment, length of hospital stay, and DRG (diagnosis-related group) were recorded from the clinical trial medical records. The profitability of hospitalizations was calculated considering DRG tariffs divided by length of hospital stay. We considered 84 patients (42 for each group). The standard therapy allowed to obtain a first-line treatment cost lower than in the broad-spectrum therapy. Anyway, the latter, being related to a lower failure rate (19% vs 57.1%), resulted in cost saving in terms of cumulative antibiotic costs (first- and second-line treatments). The mean cost saving per patient for the broad-spectrum arm was €44.18 (-37.6%), with a total cost saving of about €2,000. Compared to standard group, we observed a statistically significant reduction in hospital stay from 17.8 to 11.8 days ( p <0.002) for patients treated with broad-spectrum antibiotics. The distribution of DRG tariffs was similar in the two groups. According to DRG, the shorter length of hospital stay of the broad-spectrum group involved a higher mean profitable daily cost than standard group (€345.61 vs €252.23; +37%). Our study supports the idea that the use of a broad-spectrum empirical treatment for HCA infections in cirrhosis would be cost-saving and that hospitals need to be aware of the clinical and economic consequences of a wrong antibiotic treatment in this setting.

The majority legal status of women in southern Africa: implications for women and families.

PubMed

Van Hook, M P; Ngwenya, B N

1996-01-01

The introduction to this article, which provides an overview of the legal status of women in southern Africa, notes that the legal majority status of women is an important social policy issue with broad implications for the socioeconomic welfare of women and their families. The dual legal system (general law and customary law) which arose from colonization is a complicating factor in the legal life of women in the region. The colonial legal system legitimized the subordination of women, and during the colonial period the customary system was reinvented to the detriment of women by male African leaders working in collusion with colonial authorities. The next section of this article presents a brief description of the legal standing of women in terms of majority/minority status, marriage arrangements, and right to own immovable property in the states of Botswana, Lesotho, South Africa, Swaziland, Zambia, and Zimbabwe. The implications of the majority/minority status of women are then explored through consideration of the economic effects of majority rights, of family relationships, and of efforts to change the legal system (by changing the content and implementation of laws and by empowering women to take advantage of their rights). The barriers that impede women from asserting their rights point to the need for removal of broad-based economic, educational, and cultural constraints. Granting majority rights is an important step toward the goals of eliminating poverty and ending the marginalization of women.

Evaluation of Novel Broad-Range Real-Time PCR Assay for Rapid Detection of Human Pathogenic Fungi in Various Clinical Specimens▿

PubMed Central

Vollmer, Tanja; Störmer, Melanie; Kleesiek, Knut; Dreier, Jens

2008-01-01

In the present study, a novel broad-range real-time PCR was developed for the rapid detection of human pathogenic fungi. The assay targets a part of the 28S large-subunit ribosomal RNA (rDNA) gene. We investigated its application for the most important human pathogenic fungal genera, including Aspergillus, Candida, Cryptococcus, Mucor, Penicillium, Pichia, Microsporum, Trichophyton, and Scopulariopsis. Species were identified in PCR-positive reactions by direct DNA sequencing. A noncompetitive internal control was applied to prevent false-negative results due to PCR inhibition. The minimum detection limit for the PCR was determined to be one 28S rDNA copy per PCR, and the 95% detection limit was calculated to 15 copies per PCR. To assess the clinical applicability of the PCR method, intensive-care patients with artificial respiration and patients with infective endocarditis were investigated. For this purpose, 76 tracheal secretion samples and 70 heart valve tissues were analyzed in parallel by real-time PCR and cultivation. No discrepancies in results were observed between PCR analysis and cultivation methods. Furthermore, the application of the PCR method was investigated for other clinical specimens, including cervical swabs, nail and horny skin scrapings, and serum, blood, and urine samples. The combination of a broad-range real-time PCR and direct sequencing facilitates rapid screening for fungal infection in various clinical specimens. PMID:18385440

Evaluation of novel broad-range real-time PCR assay for rapid detection of human pathogenic fungi in various clinical specimens.

PubMed

Vollmer, Tanja; Störmer, Melanie; Kleesiek, Knut; Dreier, Jens

2008-06-01

In the present study, a novel broad-range real-time PCR was developed for the rapid detection of human pathogenic fungi. The assay targets a part of the 28S large-subunit ribosomal RNA (rDNA) gene. We investigated its application for the most important human pathogenic fungal genera, including Aspergillus, Candida, Cryptococcus, Mucor, Penicillium, Pichia, Microsporum, Trichophyton, and Scopulariopsis. Species were identified in PCR-positive reactions by direct DNA sequencing. A noncompetitive internal control was applied to prevent false-negative results due to PCR inhibition. The minimum detection limit for the PCR was determined to be one 28S rDNA copy per PCR, and the 95% detection limit was calculated to 15 copies per PCR. To assess the clinical applicability of the PCR method, intensive-care patients with artificial respiration and patients with infective endocarditis were investigated. For this purpose, 76 tracheal secretion samples and 70 heart valve tissues were analyzed in parallel by real-time PCR and cultivation. No discrepancies in results were observed between PCR analysis and cultivation methods. Furthermore, the application of the PCR method was investigated for other clinical specimens, including cervical swabs, nail and horny skin scrapings, and serum, blood, and urine samples. The combination of a broad-range real-time PCR and direct sequencing facilitates rapid screening for fungal infection in various clinical specimens.

Broad Halpha Wing Formation in the Planetary Nebula IC 4997.

PubMed

Lee; Hyung

2000-02-10

The young and compact planetary nebula IC 4997 is known to exhibit very broad wings with a width exceeding 5000 km s-1 around Halpha. We propose that the broad wings are formed through Rayleigh-Raman scattering that involves atomic hydrogen, by which Lybeta photons with a velocity width of a few 102 km s-1 are converted to optical photons and fill the Halpha broad wing region. The conversion efficiency reaches 0.6 near the line center, where the scattering optical depth is much larger than 1, and rapidly decreases in the far wings. Assuming that close to the central star there exists an unresolved inner compact core of high density, nH approximately 109-1010 cm-3, we use the photoionization code "CLOUDY" to show that sufficient Lybeta photons for scattering are produced. Using a top-hat-incident profile for the Lybeta flux and a scattering region with a H i column density NHi=2x1020 cm-2 and a substantial covering factor, we perform a profile-fitting analysis in order to obtain a satisfactory fit to the observed flux. We briefly discuss the astrophysical implications of the Rayleigh-Raman processes in planetary nebulae and other emission objects.

Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.

PubMed

Jing, Lijun; Su, Li; Ring, Brian Z

2014-01-01

The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and employed.

Developing a tool to measure pharmacoeconomic outcomes of post-surgical pain management interventions.

PubMed

Keller, Deborah S; Smalarz, Amy; Haas, Eric M

2016-01-01

Financial pressures have limited the ability of providers to use medication that may improve clinical outcomes and patient satisfaction. New interventions are often fraught with resistance from individual cost centers. A value realization tool (VRT) is essential for separate cost centers to communicate and comprehend the overall financial and clinical implications of post-surgical pain management medication interventions (PSMI). The goal was to describe development of a VRT. An evaluation of common in-patient PSMI approaches, impacts, and costs was performed. A multidisciplinary task force guided development of the VRT to ensure appropriate representation and relevance to clinical practice. The main outcome was an Excel-based tool that communicates the overall cost/benefit of PSMI for the post-operative patient encounter. The VRT aggregated input data on costs, clinical impact, and nursing burden of PSMI assessment and monitoring into two high-level outcome reports: Overall Cost Impact and Nurse & Patient Impact. Costs included PSMI specific medication, equipment, professional placement, labor, overall/opioid-related adverse events, re-admissions, and length of stay. Nursing impact included level of practice interference, job satisfaction, and patient care metrics. Patient impact included pain scores, opioid use, PACU time, and satisfaction. Reference data was provided for individual institutions that may not collect all variables included in the VRT. The VRT is a valuable way for administrators to assess PSMI cost/benefits and for individual cost centers to see the overall value of individual interventions. The user-friendly, decision-support tool allows the end-user to use built-in referenced or personalized outcome data, increasing relevance to their institutions. This broad picture could facilitate communication across cost centers and evidence-based decisions for appropriate use and impacts of PSMI.

A novel mutation in the PAX3 gene causes Waardenburg syndrome type I in an Iranian family.

PubMed

Jalilian, Nazanin; Tabatabaiefar, Mohammad Amin; Farhadi, Mohammad; Bahrami, Tayyeb; Noori-Daloii, Mohammad Reza

2015-10-01

Sensorineural hearing impairment (HI) is one of the most frequent congenital defects, with a prevalence of 1 in 500 among neonates. Although there are over 400 syndromes involving HI, most cases of HI are nonsyndromic (70%), 20% of which follow autosomal dominant mode of inheritance. Waardenburg syndrome (WS) ranks first among autosomal dominant syndromic forms of HI. WS is characterized by sensorineural hearing impairment, pigmentation abnormalities of hair and skin and hypoplastic blue eyes or heterochromia iridis. WS is subdivided into four major types, WS1-WS4. WS1 is diagnosed by the presence of dystopia canthorum and PAX3 is the only gene involved. This study aims to determine the pathogenic mutation in a large Iranian pedigree affected with WS1 in order to further confirm the clinical diagnosis. In the present study, a family segregating HI was ascertained in a genetic counseling center. Upon clinical inspection, white forelock, dystopia canthorum, broad high nasal root and synophrys, characteristic of WS1 were evident. In order to clarify the genetic etiology and confirm the clinical data, primers were designed to amplify exons and exon-intron boundaries of the responsible gene, PAX3 with 10 exons, followed by the Sanger DNA sequencing method. Genetic analysis of PAX3 revealed a novel mutation in PAX3 (c.1024_1040 del AGCACGATTCCTTCCAA). Our data provide genotype-phenotype correlation for the mutation in PAX3 and WS1 in the studied family, with implications for genetic counseling, which necessitates detailed clinical inspection of HI patients to distinguish syndromic HI from the more common non-syndromic cases. Our results reveal the value of phenotype-directed genetic analysis and could further expand the spectrum of PAX3 mutations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Design of virus-based nanomaterials for medicine, biotechnology, and energy

PubMed Central

Wen, Amy M.; Steinmetz, Nicole F.

2016-01-01

Virus-based nanomaterials are versatile materials that naturally self-assemble and have relevance for a broad range of applications including medicine, biotechnology, and energy. This review provides an overview of recent developments in “chemical virology.” Viruses, as materials, provide unique nanoscale scaffolds that have relevance in chemical biology and nanotechnology, with diverse areas of applications. Some fundamental advantages of viruses, compared to synthetically programmed materials, include the highly precise spatial arrangement of their subunits into a diverse array of shapes and sizes and many available avenues for easy and reproducible modification. Here, we will first survey the broad distribution of viruses and various methods for producing virus-based nanoparticles, as well as engineering principles used to impart new functionalities. We will then examine the broad range of applications and implications of virus-based materials, focusing on the medical, biotechnology, and energy sectors. We anticipate that this field will continue to evolve and grow, with exciting new possibilities stemming from advancements in the rational design of virus-based nanomaterials. PMID:27152673

The shared and specific relationships between exposure to potentially traumatic events and transdiagnostic dimensions of psychopathology.

PubMed

Sunderland, Matthew; Carragher, Natacha; Chapman, Cath; Mills, Katherine; Teesson, Maree; Lockwood, Emma; Forbes, David; Slade, Tim

2016-03-01

The experience of traumatic events has been linked to the development of psychopathology. Changing perspectives on psychopathology have resulted in the hypothesis that broad dimensional constructs account for the majority of variance across putatively distinct disorders. As such, traumatic events may be associated with several disorders due to their relationship with these broad dimensions rather than any direct disorder-specific relationship. The current study used data from 8871 Australians to test this hypothesis. Two broad dimensions accounted for the majority of relationships between traumatic events and mental and substance use disorders. Direct relationships remained between post-traumatic stress disorder and six categories of traumatic events in the total population and between drug dependence and accidents/disasters for males only. These results have strong implications for how psychopathology is conceptualized and offer some evidence that traumatic events are associated with an increased likelihood of experiencing psychopathology in general. Copyright © 2016 Elsevier Ltd. All rights reserved.

New Funding Opportunity Announcements (FOAs): Reissuance of Clinical Proteomic Tumor Analysis Consortium (CPTAC) | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute is soliciting applications for the reissuance of its Clinical Proteomic Tumor Analysis Consortium (CPTAC) program.   CPTAC will support broad efforts focused on several cancer types to explore further the complexities of cancer proteomes and their connections to abnormalities in cancer genomes.

Minireview: Signal Bias, Allosterism, and Polymorphic Variation at the GLP-1R: Implications for Drug Discovery

PubMed Central

Koole, Cassandra; Savage, Emilia E.; Christopoulos, Arthur; Miller, Laurence J.

2013-01-01

The glucagon-like peptide-1 receptor (GLP-1R) controls the physiological responses to the incretin hormone glucagon-like peptide-1 and is a major therapeutic target for the treatment of type 2 diabetes, owing to the broad range of effects that are mediated upon its activation. These include the promotion of glucose-dependent insulin secretion, increased insulin biosynthesis, preservation of β-cell mass, improved peripheral insulin action, and promotion of weight loss. Regulation of GLP-1R function is complex, with multiple endogenous and exogenous peptides that interact with the receptor that result in the activation of numerous downstream signaling cascades. The current understanding of GLP-1R signaling and regulation is limited, with the desired spectrum of signaling required for the ideal therapeutic outcome still to be determined. In addition, there are several single-nucleotide polymorphisms (used in this review as defining a natural change of single nucleotide in the receptor sequence; clinically, this is viewed as a single-nucleotide polymorphism only if the frequency of the mutation occurs in 1% or more of the population) distributed within the coding sequence of the receptor protein that have the potential to produce differential responses for distinct ligands. In this review, we discuss the current understanding of GLP-1R function, in particular highlighting recent advances in the field on ligand-directed signal bias, allosteric modulation, and probe dependence and the implications of these behaviors for drug discovery and development. PMID:23864649

Provider and consumer perspectives of community mental health services: Implications for consumer-driven care.

PubMed

Kelly, Erin L; Davis, Lisa; Mendon, Sapna; Kiger, Holly; Murch, Lezlie; Pancake, Laura; Giambone, Leslie; Brekke, John S

2018-05-03

Public mental health services in the community are broad and continue to expand to address the multiple issues faced by those with serious mental illnesses. However, few studies examine and contrast how helpful consumers and providers find the spectrum of services. The present study examines the services at community mental health service clinics (CMHCs) from the perspectives of providers and consumers. There were 351 consumers and 147 providers from 15 CMHCs who rated and ranked the helpfulness of 24 types of common services. All of the agencies were participating in a Practice-Based Research Network (PBRN). Social support was the highest rated service by both types of respondents, and the creation of a welcoming environment was the highest ranked service by both. There were also areas of disagreement. Consumers identified traditional mental health services (individual therapy and medication services) as being most helpful to them whereas providers selected longer-term services that promote self-reliance (e.g., securing housing, and promoting self-sufficiency) as the most helpful. Understanding how consumers and providers perceive the range of CMHC services provided in usual care is important to develop new targets for intervention. A welcoming milieu and providing social support appear important to both, but significant differences exist between these groups regarding other aspects of services. This holds implications for the design and implementation of consumer-driven services. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Pristine Inner Experience and Descriptive Experience Sampling: Implications for Psychology

PubMed Central

Lapping-Carr, Leiszle R.; Heavey, Christopher L.

2017-01-01

Pristine inner experience is that which is directly present in awareness before it is distorted by attempts at observation or interpretation. Many psychological methods, including most introspective methods, attempt to measure some aspect of pristine inner experience (thoughts, feelings, mental imagery, sensations, etc.). We believe, however, that these methods produce unspecifiable combinations of pristine inner experience, beliefs about the self, beliefs about what inner experience should be like, inaccurate recollections, miscommunications, and other confounding influences. We argue that descriptive experience sampling (DES) can produce high fidelity descriptions of pristine inner experience. These descriptions are used to create idiographic profiles, carefully crafted, in-depth characterizations of the pristine inner experience of individuals. We believe these profiles, because they are built from moments apprehended via a method that confronts the challenges inherent in examining inner experience, are uniquely valuable in advancing the science of inner experience and psychology broadly. For example, DES observations raise important questions about the veracity of results gathered via questionnaires and other introspective methods, like casual introspection. DES findings also provide high fidelity phenomenological data that can be useful for those developing psychological theories, such as theories of emotional processing. Additionally, DES procedures may allow clinicians and clients to practice valuable skills, like bracketing presuppositions and attending to internal experiences. This paper will describe difficulties inherent in the study of pristine inner experience and discuss implications of high fidelity descriptions of pristine inner experience for psychological research, theory development, and clinical practice. PMID:29312047

Civil society perspectives on negative biomedical HIV prevention trial results and implications for future trials.

PubMed

Essack, Zaynab; Koen, Jennifer; Slack, Catherine; Lindegger, Graham; Newman, Peter A

2012-01-01

Community engagement is crucial to ongoing development and testing of sorely needed new biomedical HIV prevention technologies. Yet, negative trial results raise significant challenges for community engagement in HIV prevention trials, including the early termination of the Cellulose Sulfate microbicide trial and two Phase IIb HIV vaccine trials (STEP and Phambili). The present study aimed to explore the perspectives and experiences of civil society organization (CSO) representatives regarding negative HIV prevention trial results and perceived implications for future trials. We conducted in-depth interviews with 14 respondents from a broad range of South African and international CSOs, and analyzed data using thematic analysis. CSO representatives reported disappointment in response to negative trial results, but acknowledged such outcomes as inherent to clinical research. Respondents indicated that in theory negative trial results seem likely to impact on willingness to participate in future trials, but that in practice people in South Africa have continued to volunteer. Negative trial results were described as having contributed to improving ethical standards, and to a re-evaluation of the scientific agenda. Such negative results were identified as potentially impacting on funding for trials and engagement activities. Our findings indicate that trial closures may be used constructively to support opportunities for reflection and renewed vigilance in strategies for stakeholder engagement, communicating trial outcomes, and building research literacy among communities; however, these strategies require sustained resources for community engagement and capacity-building.

Targeting Promoter-Associated Noncoding RNA In Vivo.

PubMed

Civenni, Gianluca

2017-01-01

There are many classes of noncoding RNAs (ncRNAs), with wide-ranging functionalities (e.g., RNA editing, mediation of mRNA splicing, ribosomal function). MicroRNAs (miRNAs) and long ncRNAs (lncRNAs) are implicated in a wide variety of cellular processes, including the regulation of gene expression. Incorrect expression or mutation of lncRNAs has been reported to be associated with several disease conditions, such a malignant transformation in humans. Importantly, pivotal players in tumorigenesis and cancer progression, such as c-Myc, may be regulated by lncRNA at promoter level. The function of lncRNA can be reduced with antisense oligonucleotides that sequester or degrade mature lncRNAs. In alternative, lncRNA transcription can be blocked by small interference RNA (RNAi), which had acquired, recently, broad interested in clinical applications. In vivo-jetPEI™ is a linear polyethylenimine mediating nucleic acid (DNA, shRNA, siRNA, oligonucelotides) delivery with high efficiency. Different in vivo delivery routes have been validated: intravenous (IV), intraperitoneal (IP), intratumoral, subcutaneous, topical, and intrathecal. High levels of nucleic acid delivery are achieved into a broad range of tissues, such as lung, salivary glands, heart, spleen, liver, and prostate upon systemic administration. In addition, in vivo-jetPEI™ is also an efficient carrier for local gene and siRNA delivery such as intratumoral or topical application on the skin. After systemic injection, siRNA can be detected and the levels can be validated in target tissues by qRT-PCR. Targeting promoter-associated lncRNAs with siRNAs (small interfering RNAs) in vivo is becoming an exciting breakthrough for the treatment of human disease.

Informed consent in direct-to-consumer personal genome testing: the outline of a model between specific and generic consent.

PubMed

Bunnik, Eline M; Janssens, A Cecile J W; Schermer, Maartje H N

2014-09-01

Broad genome-wide testing is increasingly finding its way to the public through the online direct-to-consumer marketing of so-called personal genome tests. Personal genome tests estimate genetic susceptibilities to multiple diseases and other phenotypic traits simultaneously. Providers commonly make use of Terms of Service agreements rather than informed consent procedures. However, to protect consumers from the potential physical, psychological and social harms associated with personal genome testing and to promote autonomous decision-making with regard to the testing offer, we argue that current practices of information provision are insufficient and that there is a place--and a need--for informed consent in personal genome testing, also when it is offered commercially. The increasing quantity, complexity and diversity of most testing offers, however, pose challenges for information provision and informed consent. Both specific and generic models for informed consent fail to meet its moral aims when applied to personal genome testing. Consumers should be enabled to know the limitations, risks and implications of personal genome testing and should be given control over the genetic information they do or do not wish to obtain. We present the outline of a new model for informed consent which can meet both the norm of providing sufficient information and the norm of providing understandable information. The model can be used for personal genome testing, but will also be applicable to other, future forms of broad genetic testing or screening in commercial and clinical settings. © 2012 John Wiley & Sons Ltd.

A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models.

PubMed

Zhao, Genshi; Li, Wei-Ying; Chen, Daohong; Henry, James R; Li, Hong-Yu; Chen, Zhaogen; Zia-Ebrahimi, Mohammad; Bloem, Laura; Zhai, Yan; Huss, Karen; Peng, Sheng-Bin; McCann, Denis J

2011-11-01

The fibroblast growth factor receptors (FGFR) are tyrosine kinases that are present in many types of endothelial and tumor cells and play an important role in tumor cell growth, survival, and migration as well as in maintaining tumor angiogenesis. Overexpression of FGFRs or aberrant regulation of their activities has been implicated in many forms of human malignancies. Therefore, targeting FGFRs represents an attractive strategy for development of cancer treatment options by simultaneously inhibiting tumor cell growth, survival, and migration as well as tumor angiogenesis. Here, we describe a potent, selective, small-molecule FGFR inhibitor, (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol, designated as LY2874455. This molecule is active against all 4 FGFRs, with a similar potency in biochemical assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship. LY2874455 also exhibits a 6- to 9-fold in vitro and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice. Furthermore, LY2874455 did not show VEGF receptor 2-mediated toxicities such as hypertension at efficacious doses. Currently, this molecule is being evaluated for its potential use in the clinic.

Men's use of positive strategies for preventing and managing depression: A qualitative investigation.

PubMed

Fogarty, Andrea S; Proudfoot, Judy; Whittle, Erin L; Player, Michael J; Christensen, Helen; Hadzi-Pavlovic, Dusan; Wilhelm, Kay

2015-12-01

One in eight men experience depression and men account for 75% of suicides. Previous research has focused on men's reluctance to seek help and use of unhelpful coping strategies. Thematic analysis was used on transcripts from 21 focus groups and 24 in-depth interviews focused on positive strategies men use to prevent and manage depression. In total, 168 men were recruited and the majority (63%) reported no current depression. Four major themes were identified, where men: (1) used a broad variety of positive strategies and made clear distinctions between prevention and management, (2) used strategies that were "typically masculine", as well as challenged expectations of manliness, (3) felt powerless in the face of suicide, and (4) had accumulated wisdom they felt was beneficial for others. Men specifically advised others to talk about problems. Prevention relied upon regular routines for "balance", while management relied upon "having a plan". The majority of the men were aged over 55 years and highly educated. Younger men or those without tertiary education may favour different strategies. In contrast to using only unhelpful strategies, the men used a broad range of positive strategies and adapted their use depending on mood, symptom or problem severity. Use of positive strategies was sophisticated, nuanced, and often underlined by a guiding philosophy. Rather than simply reacting to problems, men actively engaged in preventing the development of depressed moods, and made conscious choices about when or how to take action. Clinical and public health implications are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies.

PubMed

Boscarino, Joseph A

2004-12-01

Research indicates that exposure to traumatic stressors and psychological trauma is widespread. The association of such exposures with posttraumatic stress disorder (PTSD) and other mental health conditions is well known. However, epidemiologic research increasingly suggests that exposure to these events is related to increased health care utilization, adverse health outcomes, the onset of specific diseases, and premature death. To date, studies have linked traumatic stress exposures and PTSD to such conditions as cardiovascular disease, diabetes, gastrointestinal disease, fibromyalgia, chronic fatigue syndrome, musculoskeletal disorders, and other diseases. Evidence linking cardiovascular disease and exposure to psychological trauma is particularly strong and has been found consistently across different populations and stressor events. In addition, clinical studies have suggested the biological pathways through which stressor-induced diseases may be pathologically expressed. In particular, recent studies have implicated the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) stress axes as key in this pathogenic process, although genetic and behavioral/psychological risk factors cannot be ruled out. Recent findings, indicating that victims of PTSD have higher circulating T-cell lymphocytes and lower cortisol levels, are intriguing and suggest that chronic sufferers of PTSD may be at risk for autoimmune diseases. To test this hypothesis, we assessed the association between chronic PTSD in a national sample of 2,490 Vietnam veterans and the prevalence of common autoimmune diseases, including rheumatoid arthritis, psoriasis, insulin-dependent diabetes, and thyroid disease. Our analyses suggest that chronic PTSD, particularly comorbid PTSD or complex PTSD, is associated with all of these conditions. In addition, veterans with comorbid PTSD were more likely to have clinically higher T-cell counts, hyperreactive immune responses on standardized delayed cutaneous hypersensitivity tests, clinically higher immunoglobulin-M levels, and clinically lower dehydroepiandrosterone levels. The latter clinical evidence confirms the presence of biological markers consistent with a broad range of inflammatory disorders, including both cardiovascular and autoimmune diseases.

Organizational characteristics of HIV/syphilis testing services for men who have sex with men in South China: a social entrepreneurship analysis and implications for creating sustainable service models.

PubMed

Tucker, Joseph D; Muessig, Kathryn E; Cui, Rosa; Bien, Cedric H; Lo, Elaine J; Lee, Ramon; Wang, Kaidi; Han, Larry; Liu, Feng-Ying; Yang, Li-Gang; Yang, Bin; Larson, Heidi; Peeling, Rosanna W

2014-11-25

UNAIDS has called for greater HIV/syphilis testing worldwide just as local HIV/syphilis testing programs are cut or altered. New models are needed to make HIV/syphilis testing services sustainable while retaining their essential public health function. Social entrepreneurship, using business principles to promote a social cause, provides a framework to pilot programs that sustainably expand testing. Drawing on fieldwork in two South Chinese cities, we examined organizational and financial characteristics of current HIV/syphilis testing systems for men who have sex with men (MSM) in addition to new pilot programs focused on revenue-generation for sustainability. We undertook a qualitative study to explore organizational and financial characteristics of HIV/syphilis testing for MSM. Data were collected from men who have sex with men and policy stakeholders in Guangzhou and Hong Kong. Framework analysis was used to identify themes and then code the data. Our qualitative research study included MSM and policy stakeholders (n = 84). HIV/syphilis testing services were implemented at a wide range of organizations which we grouped broadly as independent community-based organizations (CBOs), independent clinics, and hybrid CBO-clinic sites. From an organizational perspective, hybrid CBO-clinic sites offered the inclusive environment of an MSM CBO linked to the technical capacity and trained staff of a clinic. From a financial perspective, stakeholders expressed concern about the sustainability and effectiveness of sexual health services reliant on external funding. We identified four hybrid CBO-clinic organizations that launched pilot testing programs in order to generate revenue while expanding HIV testing. Many MSM CBOs are searching for new organizational models to account for decreased external support. Hybrid CBO-clinic organizations create a strong foundation to increase HIV/syphilis testing using social entrepreneurship models in China.

Clinical knowledge governance: the international perspective.

PubMed

Garde, Sebastian

2013-01-01

As a basis for semantic interoperability, ideally, a Clinical Knowledge Resource for a clinical concept should be defined formally and defined once in a way that all clinical professions and all countries can agree on. Clinical Knowledge Governance is required to create high-quality, reusable Clinical Knowledge Resources and achieve this aim. Traditionally, this is a time-consuming and cumbersome process, relying heavily on face-to-face meetings and being able to get sufficient input from clinicians. However, in a national or even international space, it is required to streamline the processes involved in creating Clinical Knowledge Resources. For this, a Web 2.0 tool that supports online collaboration of clinicians during their creation and publishing of Clinical Knowledge Resources has been developed. This tool is named the Clinical Knowledge Manager (CKM) and supports the development, review and publication of Clinical Knowledge Resources. Also, post-publication activities such as adding terminology bindings, translating the Clinical Knowledge Resource into another language and republishing it are supported. The acceptance of Clinical Knowledge Resources depends on their quality and being able to determine their quality, for example it is important to know that a broad umber of reviewers from various clinical disciplines have been involved in the development of the Clinical Knowledge Resource. We are still far from realizing the vision of a global repository of a great number of reusable, high-quality Clinical Knowledge Resources, which can provide the basis for broad semantic interoperability between systems. However progress towards this aim is being made around the world.

The response to selection for broad male response to female sex pheromone and its implications for divergence in close-range mating behavior in the European corn borer moth, Ostrinia nubilalis.

PubMed

Droney, David C; Musto, Callie J; Mancuso, Katie; Roelofs, Wendell L; Linn, Charles E

2012-12-01

Coordinated sexual communication systems, seen in many species of moths, are hypothesized to be under strong stabilizing natural selection. Stabilized communication systems should be resistant to change, but there are examples of species/populations that show great diversification. A possible solution is that it is directional sexual selection on variation in male response that drives evolution. We tested a component of this model by asking whether 'rare' males (ca. 5 % of all males in a population) of the European corn borer moth (ECB), Ostrinia nubilalis, that respond to the sex pheromones of both ECB and a different Ostrinia species (O. furnacalis, the Asian corn borer, ACB), might play an important role in diversification. We specifically tested, via artificial selection, whether this broad male response has an evolvable genetic component. We increased the frequency of broad male response from 5 to 70 % in 19 generations, showing that broad-responding males could be important for the evolution of novel communication systems in ECB. We did not find a broader range of mating acceptance of broad males by females of the base population, however, suggesting that broad response would be unlikely to increase in frequency without the involvement of other factors. However, we found that ECB selection-line females accepted a broader range of courting males, including those of ACB, than did females of the base population. Thus, a genetic correlation exists between broad, long-range response to female sex pheromone and the breadth of female acceptance of males at close range. These results are discussed in the context of evolution of novel communication systems in Ostrinia.

The Problem with Overly Broad Definitions of Bullying: Implications for the Schoolhouse, the Statehouse, and the Ivory Tower

ERIC Educational Resources Information Center

Cascardi, Michele; Brown, Cathy; Iannarone, Melinda; Cardona, Norma

2014-01-01

Within the past few decades, scholars, lawmakers, and educators have increased attention to a specific type of aggressive behavior known as bullying. While bullying is like peer aggression and harassment, in that they all pertain to negative aggressive actions, there are important distinctions among these three forms of behavior. The key features…

Legal Aspects of Oral History Collections. A Report to the Oral History Committee of the Medical Library Association.

ERIC Educational Resources Information Center

Wright, A. J.

Legal implications of oral history research and collection can be divided into four broad areas of concern, including copyright, restriction of access, libel, and contracts. This document presents highlights from various authorities in each of these areas. Peterson notes that interviewers and interviewees hold the copyright to their own words; a…

Touching the Future: Building Skills for Life and Work. Australian Education Review No. 55

ERIC Educational Resources Information Center

Wyn, Johanna

2009-01-01

Australian Education Review (AER) 55 explores the goals of Australian education and of how schools should prepare young people for work and life. Section 1 provides an overview, discussing the nature of broad social and economic changes over the last 20 years, and their implications for the goals of Australian education systems today and for the…

Disturbance and climate change in United States/Mexico borderland plant communities: a state-of-the-knowledge review

Treesearch

Guy R. McPherson; Jake F. Weltzin

2000-01-01

This review evaluates the effects and importance of disturbance and climate change on plant community dynamics in the United States/Mexico borderlands region. Our primary focus is on knowledge of physiognomic-level change in grasslands and woodlands of southeastern Arizona and southwestern New Mexico. Changes in vegetation physiognomy have broad implications for...

Forest products cluster development in central Arizona—implications for landscape-scale forest restoration

Treesearch

David Nicholls

2014-01-01

Since 2004, close to 50,000 ac of hazardous fuels have been mechanically treated in east-central Arizona as part of the USDA Forest Service's first 10-year stewardship project on national forest lands. The need for coordinated wood products and biomass utilization in Arizona is likely to increase as broad-scale restoration treatments across Arizona's national...

DEVELOPMENT OF A THEORY OF EDUCATION FROM PSYCHOLOGICAL AND OTHER BASIC RESEARCH FINDINGS.

ERIC Educational Resources Information Center

TAYLOR, CALVIN W.; AND OTHERS

A BROAD EXPLORATORY AND THEORETICAL STUDY WAS CONDUCTED TO DETERMINE IN A FUNDAMENTAL SENSE THE IMPLICATIONS AND IMPACT WHICH NEW RESEARCH IN THE BASIC BEHAVIORAL SCIENCE FIELDS HAD ON EDUCATIONAL PRACTICE AND THEORY. THE TOTAL TASK WAS TO BUILD A NEW EDUCATIONAL THEORY USING SAMPLINGS FROM ALL BEHAVIORAL RESEARCH AND TO INVESTIGATE WAYS TO REDUCE…

Impact of Job Design Problems and Lack of Support. Draft Version. Working Paper #6.

ERIC Educational Resources Information Center

Gersten, Russell; And Others

This paper presents implications of the path analysis procedures used to interpret data from a study of urban special education teachers' perceptions of working conditions. The analysis looked at a broad range of factors that could affect teacher plans to leave the field. An overall finding emerging from the analysis was that the same fundamental…

Controls on valley width in mountainous landscapes: the role of landsliding and implications for salmonid habitat

Treesearch

C. May; J. Roering; L.S. Eaton; K.M. Burnett

2013-01-01

A fundamental yet unresolved question in fluvial geomorphology is what controls the width of valleys in mountainous terrain. Establishing a predictive relation for valley floor width is critical for realizing links between aquatic ecology and geomorphology because the most productive riverine habitats often occur in low-gradient streams with broad floodplains. Working...

The Impact of Private Sector Competition on Public Schooling in Kuwait: Some Socio-Educational Implications

ERIC Educational Resources Information Center

Al-Shehab, Ali Jasem

2010-01-01

With the diminishing model of the welfare state, public education in Kuwait is facing the challenges of the competition of private schools, while the private sector has always struggled against the monopolistic power of the public schools that educate a broad spectrum of K-12 students. This article presents estimates of the effect of private…

Digital Distribution of Academic Journals and Its Impact on Scholarly Communication: Looking Back after 20 Years

ERIC Educational Resources Information Center

Solomon, David J.

2013-01-01

It has been approximately 20 years since distributing scholarly journals digitally became feasible. This article discusses the broad implications of the transition to digital distributed scholarship from a historical perspective and focuses on the development of open access (OA) and the various models for funding OA in the context of the roles…

Distribution of salmon-habitat potential relative to landscape characteristics and implications for conservation.

Treesearch

K.M. Burnett; G.H. Reeves; D.J. Miller; S. Clarke; K. Vance-Borland; K. Christiansen

2007-01-01

The geographic distribution of stream reaches with potential to support high-quality habitat for salmonids has bearing on the actual status of habitats and populations over broad spatial extents. As part of the Coastal Landscape Analysis and Modeling Study, we examined how salmon-habitat potential was distributed relative to current and future (+100 years) landscape...

Synchrotron-based X-ray fluorescence microscopy enables multiscale spatial visualization of ions involved in fungal lignocellulose deconstruction

Treesearch

Grant T. Kirker; Samuel Zelinka; Sophie-Charlotte Gleber; David Vine; Lydia Finney; Si Chen; Young Pyo Hong; Omar Uyarte; Stefan Vogt; Jody Jellison; Barry Goodell; Joseph E. Jakes

2017-01-01

The role of ions in the fungal decay process of lignocellulose biomaterials, and more broadly fungal metabolism, has implications for diverse research disciplines ranging from plant pathology and forest ecology, to carbon sequestration. Despite the importance of ions in fungal decay mechanisms, the spatial distribution and quantification of ions in lignocellulosic cell...

New Directions in Developmental Emotion Regulation Research across the Life Span: Introduction to the Special Section

ERIC Educational Resources Information Center

Zimmermann, Peter; Thompson, Ross A.

2014-01-01

Research on the development of emotion regulation has become a prominent topic in developmental science covering a broad age range from infancy to old age because of its theoretical importance and practical implications. This introductory essay of this special section includes reflections on some of the conceptual themes of this research field and…

Policy and Ideologies in Schooling and Early Years Education in England: Implications for and Impacts on Leadership, Management and Equality

ERIC Educational Resources Information Center

Robertson, Leena Helavaara; Hill, Dave

2014-01-01

In this article we begin by discussing "ideology" as a theoretical construct, and the interconnections between policy and ideology in the education system in England. We analyse the main principles of education policies that can be broadly defined from Left to Right, according to the following ideologies: Marxism/Socialism/Radical…

Threat bias, not negativity bias, underpins differences in political ideology.

PubMed

Lilienfeld, Scott O; Latzman, Robert D

2014-06-01

Although disparities in political ideology are rooted partly in dispositional differences, Hibbing et al.'s analysis paints with an overly broad brush. Research on the personality correlates of liberal-conservative differences points not to global differences in negativity bias, but to differences in threat bias, probably emanating from differences in fearfulness. This distinction bears implications for etiological research and persuasion efforts.

A Content Analysis of Choral Students' Participation Perceptions: Implications for Lifelong Learning

ERIC Educational Resources Information Center

Rohwer, Debbie; Rohwer, Mark

2009-01-01

The purpose of this study was to describe students' perceptions of their high school choral experience. The participants in the study were 57 choral musicians attending a north Texas high school. Each participant was asked to complete a broad writing task: to write a letter to the incoming varsity choir members in order to help the musicians to…

Population growth rate of dry bulb mite, Aceria tulipae (Keifer) (Acariformes: Eriophyidae) on agriculturally important plants and implications on taxonomic status

USDA-ARS?s Scientific Manuscript database

Dry bulb mite (DBM), Aceria tulipae, is an economically important mite with a worldwide distribution and a broad host range. As a generalist, it is the most important eriophyoid mite attacking bulbous plants such as garlic, onion, and tulip. To date, DBM has been recorded on host plants belonging to...

Social Justice Issues and Music Education in the Post 9/11 United States

ERIC Educational Resources Information Center

Wagoner, Cynthia L.

2015-01-01

The purpose of this paper is two-fold: first, to examine the impact of historical sociopolitical events on music education, particularly post 9/11 with the intent of establishing a context for social justice issues; and second, how we might examine the broad implications to further music education research focusing on social justice. Issues of…

Components of spatial and temporal soil variation at Canyonlands National Park: Implications for P dynamics and cheatgrass (Bromus tectorum) performance

Treesearch

Mark Miller; Jayne Belnap; Susan Beatty; Bruce Webb

2001-01-01

From January 1997 through October 1998, research was conducted at Canyonlands National Park to investigate soil traits responsible for distinct spatial patterns of cheatgrass (Bromus tectorum) occurrence. Field experiments were conducted at sites representing a broad range of soil conditions and cheatgrass abundances. Standard physicochemical soil measures in...

Nanomaterial Case Study: A Comparison of Multiwalled Carbon Nanotube and Decabromodiphenyl Ether Flame-Retardant Coatings Applied to Upholstery Textiles (External Review Draft)

EPA Science Inventory

The draft document is intended to be used as part of a process to identify what is known and, more importantly, what is not yet known that could be of value in assessing the broad implications of specific nanomaterials. Like previous case studies (see History/ Chronology below), ...

Professional and Personal Factors Associated with Gerontological Practice: Implications for Training and Education

ERIC Educational Resources Information Center

Black, Kathy

2011-01-01

Professional practice with older adults is performed in a variety of settings and across a broad range of areas. Planning for care throughout the end of life represents an increasingly important aspect of work with older adults as a result of the nation's aging demographic and concomitant health care needs. Community-based geriatric case managers…

"I Expect to Be Engaged as an Equal": Collegiality Expectations of Full-Time, Non-Tenure-Track Faculty Members

ERIC Educational Resources Information Center

Alleman, Nathan F.; Haviland, Don

2017-01-01

Nationally, non-tenure-track faculty (NTTF) represent the new majority. Efforts to move the full-time NTTF role from expendable labor to sustainable professional position have led to improvements in policy and working conditions at many institutions. Still, the profession broadly has just begun to grapple with the implications of this shifting…

Pedagogy of the Rural: Implications of Size on Conceptualisations of Rural

ERIC Educational Resources Information Center

Walker-Gibbs, Bernadette; Ludecke, Michelle; Kline, Jodie

2015-01-01

This paper proposes a concept of Pedagogy of the Rural that draws together current rural education theory and practice to illustrate the complexities of rural space and place often overlooked in teacher education more broadly. We firstly examine notions of size, and then we explore how this impacts on the ways in which teachers in rural locations…

Contextual Influences on Inquiries into Effective Teaching and Their Implications for Improving Student Learning

ERIC Educational Resources Information Center

Bryk, Anthony S.; Harding, Heather; Greenberg, Sharon

2012-01-01

In this article, Anthony Bryk, Heather Harding, and Sharon Greenberg report on a roundtable jointly sponsored by Teach For America and the Carnegie Foundation for the Advancement of Teaching. The authors brought together a group of scholars and practitioners with a broad range of perspectives and asked them to explore several questions related to…

Hospitals, finance, and health system reform in Britain and the United States, c. 1910-1950: historical revisionism and cross-national comparison.

PubMed

Gorsky, Martin

2012-06-01

Comparative histories of health system development have been variously influenced by the theoretical approaches of historical institutionalism, political pluralism, and labor mobilization. Britain and the United States have figured significantly in this literature because of their very different trajectories. This article explores the implications of recent research on hospital history in the two countries for existing historiographies, particularly the coming of the National Health Service in Britain. It argues that the two hospital systems initially developed in broadly similar ways, despite the very different outcomes in the 1940s. Thus, applying the conceptual tools used to explain the U.S. trajectory can deepen appreciation of events in Britain. Attention focuses particularly on working-class hospital contributory schemes and their implications for finance, governance, and participation; these are then compared with Blue Cross and U.S. hospital prepayment. While acknowledging the importance of path dependence in shaping attitudes of British bureaucrats toward these schemes, analysis emphasizes their failure in pressure group politics, in contrast to the United States. In both countries labor was also crucial, in the United States sustaining employment-based prepayment and in Britain broadly supporting system reform.

NuSTAR Reveals Relativistic Reflection But No Ultra-Fast Outflow in the Quasar Pg∼1211+143

NASA Astrophysics Data System (ADS)

Zoghbi, A.; Miller, J. M.; Walton, D. J.; Harrison, F. A.; Fabian, A. C.; Reynolds, C. S.; Boggs, S. E.; Christensen, F. E.; Craig, W.; Hailey, C. J.; Stern, D.; Zhang, W. W.

2015-01-01

We report on four epochs of observations of the quasar PG 1211+143 using NuSTAR. The net exposure time is 300 ks. Prior work on this source found suggestive evidence of an ultra-fast outflow (UFO) in the Fe K band with a velocity of approximately 0.1c. The putative flow would carry away a high-mass flux and kinetic power, with broad implications for feedback and black hole--galaxy co-evolution. NuSTAR detects PG 1211+143 out to 30 keV, meaning that the continuum is well-defined both through and above the Fe K band. A characteristic relativistic disk reflection spectrum is clearly revealed via a broad Fe K emission line and Compton back-scattering curvature. The data offer only weak constraints on the spin of the black hole. A careful search for UFOs shows no significant absorption feature above 90% confidence. The limits are particularly tight when relativistic reflection is included. We discuss the statistics and the implications of these results in terms of connections between accretion onto quasars, Seyferts, and stellar-mass black holes, and feedback into their host environments.

New Evidence on the Green House Model of Nursing Home Care: Synthesis of Findings and Implications for Policy, Practice, and Research.

PubMed

Zimmerman, Sheryl; Bowers, Barbara J; Cohen, Lauren W; Grabowski, David C; Horn, Susan D; Kemper, Peter

2016-02-01

To synthesize new findings from the THRIVE Research Collaborative (The Research Initiative Valuing Eldercare) related to the Green House (GH) model of nursing home care and broadly consider their implications. Interviews and observations conducted in GH and comparison homes, Minimum Data Set (MDS) assessments, Medicare data, and Online Survey, Certification and Reporting data. Critical integration and interpretation of findings based on primary data collected 2011-2014 in 28 GH homes (from 16 organizations), and 15 comparison nursing home units (from 8 organizations); and secondary data derived from 2005 to 2010 for 72 GH homes (from 15 organizations) and 223 comparison homes. Implementation of the GH model is inconsistent, sometimes differing from design. Among residents of GH homes, adoption lowers hospital readmissions, three MDS measures of poor quality, and Part A/hospice Medicare expenditures. Some evidence suggests the model is associated with lower direct care staff turnover. Recommendations relate to assessing fidelity, monitoring quality, capitalizing opportunities to improve care, incorporating evidence-based practices, including primary care providers, supporting high-performance workforce practices, aligning Medicare financial incentives, promoting equity, informing broad culture change, and conducting future research. © Health Research and Educational Trust.

Application of a Sensemaking Approach to Ethics Training in the Physical Sciences and Engineering

NASA Astrophysics Data System (ADS)

Kligyte, Vykinta; Marcy, Richard T.; Waples, Ethan P.; Sevier, Sydney T.; Godfrey, Elaine S.; Mumford, Michael D.; Hougen, Dean F.

2008-06-01

Integrity is a critical determinant of the effectiveness of research organizations in terms of producing high quality research and educating the new generation of scientists. A number of responsible conduct of research (RCR) training programs have been developed to address this growing organizational concern. However, in spite of a significant body of research in ethics training, it is still unknown which approach has the highest potential to enhance researchers' integrity. One of the approaches showing some promise in improving researchers' integrity has focused on the development of ethical decision-making skills. The current effort proposes a novel curriculum that focuses on broad metacognitive reasoning strategies researchers use when making sense of day-to-day social and professional practices that have ethical implications for the physical sciences and engineering. This sensemaking training has been implemented in a professional sample of scientists conducting research in electrical engineering, atmospheric and computer sciences at a large multi-cultural, multi-disciplinary, and multi-university research center. A pre-post design was used to assess training effectiveness using scenario-based ethical decision-making measures. The training resulted in enhanced ethical decision-making of researchers in relation to four ethical conduct areas, namely data management, study conduct, professional practices, and business practices. In addition, sensemaking training led to researchers' preference for decisions involving the application of the broad metacognitive reasoning strategies. Individual trainee and training characteristics were used to explain the study findings. Broad implications of the findings for ethics training development, implementation, and evaluation in the sciences are discussed.

Application of a sensemaking approach to ethics training in the physical sciences and engineering.

PubMed

Kligyte, Vykinta; Marcy, Richard T; Waples, Ethan P; Sevier, Sydney T; Godfrey, Elaine S; Mumford, Michael D; Hougen, Dean F

2008-06-01

Integrity is a critical determinant of the effectiveness of research organizations in terms of producing high quality research and educating the new generation of scientists. A number of responsible conduct of research (RCR) training programs have been developed to address this growing organizational concern. However, in spite of a significant body of research in ethics training, it is still unknown which approach has the highest potential to enhance researchers' integrity. One of the approaches showing some promise in improving researchers' integrity has focused on the development of ethical decision-making skills. The current effort proposes a novel curriculum that focuses on broad metacognitive reasoning strategies researchers use when making sense of day-to-day social and professional practices that have ethical implications for the physical sciences and engineering. This sensemaking training has been implemented in a professional sample of scientists conducting research in electrical engineering, atmospheric and computer sciences at a large multi-cultural, multi-disciplinary, and multi-university research center. A pre-post design was used to assess training effectiveness using scenario-based ethical decision-making measures. The training resulted in enhanced ethical decision-making of researchers in relation to four ethical conduct areas, namely data management, study conduct, professional practices, and business practices. In addition, sensemaking training led to researchers' preference for decisions involving the application of the broad metacognitive reasoning strategies. Individual trainee and training characteristics were used to explain the study findings. Broad implications of the findings for ethics training development, implementation, and evaluation in the sciences are discussed.

Real-Time in Vivo Detection of H2O2 Using Hyperpolarized 13C-Thiourea.

PubMed

Wibowo, Arif; Park, Jae Mo; Liu, Shie-Chau; Khosla, Chaitan; Spielman, Daniel M

2017-07-21

Reactive oxygen species (ROS) are essential cellular metabolites widely implicated in many diseases including cancer, inflammation, and cardiovascular and neurodegenerative disorders. Yet, ROS signaling remains poorly understood, and their measurements are a challenge due to high reactivity and instability. Here, we report the development of 13 C-thiourea as a probe to detect and measure H 2 O 2 dynamics with high sensitivity and spatiotemporal resolution using hyperpolarized 13 C magnetic resonance spectroscopic imaging. In particular, we show 13 C-thiourea to be highly polarizable and to possess a long spin-lattice relaxation time (T 1 ), which enables real-time monitoring of ROS-mediated transformation. We also demonstrate that 13 C-thiourea reacts readily with H 2 O 2 to give chemically distinguishable products in vitro and validate their detection in vivo in a mouse liver. This study suggests that 13 C-thiourea is a promising agent for noninvasive detection of H 2 O 2 in vivo. More broadly, our findings outline a viable clinical application for H 2 O 2 detection in patients with a range of diseases.

Interoception, contemplative practice, and health

PubMed Central

Farb, Norman; Daubenmier, Jennifer; Price, Cynthia J.; Gard, Tim; Kerr, Catherine; Dunn, Barnaby D.; Klein, Anne Carolyn; Paulus, Martin P.; Mehling, Wolf E.

2015-01-01

Interoception can be broadly defined as the sense of signals originating within the body. As such, interoception is critical for our sense of embodiment, motivation, and well-being. And yet, despite its importance, interoception remains poorly understood within modern science. This paper reviews interdisciplinary perspectives on interoception, with the goal of presenting a unified perspective from diverse fields such as neuroscience, clinical practice, and contemplative studies. It is hoped that this integrative effort will advance our understanding of how interoception determines well-being, and identify the central challenges to such understanding. To this end, we introduce an expanded taxonomy of interoceptive processes, arguing that many of these processes can be understood through an emerging predictive coding model for mind–body integration. The model, which describes the tension between expected and felt body sensation, parallels contemplative theories, and implicates interoception in a variety of affective and psychosomatic disorders. We conclude that maladaptive construal of bodily sensations may lie at the heart of many contemporary maladies, and that contemplative practices may attenuate these interpretative biases, restoring a person’s sense of presence and agency in the world. PMID:26106345

Developmental psychopathology: Attention Deficit Hyperactivity Disorder (ADHD)

PubMed Central

Schmidt, Sören; Petermann, Franz

2009-01-01

Background Attention Deficit/Hyperactivity Disorder (ADHD), formerly regarded as a typical childhood disorder, is now known as a developmental disorder persisting over the lifespan. Starting in preschool-age, symptoms vary depending on the age group affected. Method According to the variability of ADHD-symptoms and the heterogeneity of comorbid psychiatric disorders, a broad review of recent studies was performed. These findings were summarized in a developmental psychopathological model, documenting relevant facts on a timeline. Results Based on a genetic disposition and a neuropsychological deregulation, there is evidence for factors which persist across the lifespan, change age-dependently, or show validity in a specific developmental phase. Qualitative changes can be found for children in preschool-age and adults. Conclusion These differences have implications for clinical practice as they can be used for prevention, diagnostic proceedings, and therapeutic intervention as well as for planning future studies. The present article is a translated and modified version of the German article "Entwicklungspsychopathologie der ADHS", published in Zeitschrift für Psychiatrie, Psychologie und Psychotherapie, 56, 2008, S. 265-274. PMID:19761584

The "Arnold Schwarzenegger Effect": is strength of the "victim" related to misinterpretations of harm intrusions?

PubMed

Berman, Noah C; Wheaton, Michael G; Abramowitz, Jonathan S

2012-12-01

The present study used an in vivo paradigm to examine whether the victim's vulnerability in a harm-related intrusion affects beliefs about the importance of thoughts (i.e., Thought Action Fusion; TAF). Sixty-six undergraduate students at a large university were randomly assigned to imagine either a vulnerable (e.g., elderly man) or able-bodied individual (e.g., strong youthful male) they know getting into a car accident and provided in vivo ratings of anxiety, guilt, likelihood, moral wrongness, and urges to neutralize. Results indicated that thinking of car accident involving a vulnerable, compared to an able-bodied person, provoked more distress (anxiety and guilt), stronger feelings of moral wrongness, greater urges to cancel the effects of thinking such thoughts, and higher estimates of the likelihood that the collision would occur. The findings of our study broadly support Rachman's (1998) assertion that more significance and importance is attached to negative thoughts about vulnerable or helpless people. Current findings are discussed in terms of the cognitive-behavioral model of obsessions and clinical implications are addressed. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Gender Comparison of Motivations for Physical Dating Violence Among College Students

PubMed Central

Elmquist, JoAnna; Wolford-Clevenger, Caitlin; Zapor, Heather; Febres, Jeniimarie; Shorey, Ryan C.; Hamel, John; Stuart, Gregory L.

2015-01-01

There are limited empirical investigations that directly compare men and women’s motivations, or reasons, for perpetrating physical dating violence (DV). In an attempt to further understand whether men and women have similar or different motives for physical DV, the purpose of the current study was to conduct a gender comparison motives in a sample of male (n = 163) and female (n = 319) college students. Motivations for physical DV were classified according to seven broad categories proposed by Langhinrichsen-Rohling and colleagues (2012): (a) power/control, (b) self-defense, (c) expression of negative emotion (e.g., anger), (d) communication difficulties, (e) retaliation, (f) jealousy, and (g) other (e.g., because it was sexually arousing, the influence of alcohol, the influence of drugs). The prevalence of physical violence perpetration in the overall sample was 29.4%. Results indicated that communication difficulties and self-defense were among the most frequently endorsed motive categories for both male and female perpetrated dating violence. In addition, results demonstrated gender similarity in all of the examined motive categories. Research and clinical implications are discussed. PMID:25392388

Introduction to the Special Section on Teaching, Training, and Supervision in Personality and Psychological Assessment.

PubMed

Smith, Justin D

2017-01-01

This special section contains empirical and conceptual articles pertaining to the broad topic of teaching, training, and supervision of assessment. Despite some evidence of a decline in recent decades, assessment remains a defining practice of professional psychologists in many subfields, including clinical, counseling, school, and neuropsychology, that consumes a consequential proportion of their time. To restore assessment to its rightful place of prominence, a clear agenda needs to be developed for advancing teaching and training methods, increasing instruction to state-of-the-art methods, and defining aims that could be elucidated through empirical inquiry. The 7 articles in this special section provide a developmental perspective of these issues that collectively provide practical tools for instructors and begin to set the stage for a research agenda in this somewhat neglected area of study that is vital to the identity of professional psychology. Additionally, 2 comments are provided by distinguished figures in the field concerning the implications of the articles in the special section to health services psychology and the competencies-based movement in applied psychology.

Using an introduction website to start a family: implications for users and health practitioners.

PubMed

Harper, Joyce; Jackson, Emily; Spoelstra-Witjens, Laura; Reisel, Dan

2017-06-01

Donor insemination treatment offered in licensed clinics protects the donor, recipient and offspring both medically and legally. The Internet has opened up novel, unregulated ways of donating sperm through 'introduction websites' and social media forums. Broadly, three categories of women use introduction websites: those who want to have a child with no further involvement of the donor; those who wish to know the identity of the donor from the start; and those who intend to electively co-parent, that is, to bring up the child together with the donor/father. Donors may choose to donate through introduction websites for altruistic reasons and/or in order to have greater involvement with the child. There are some donors who are motivated by the prospect of a sexual encounter, advertising their preference for 'natural insemination' - i.e. via sexual intercourse or partial intercourse. When people make their own arrangements online, they may do so in the absence of clear, accurate information. This article, sets out some of the issues that recipients and donors ought to consider before embarking on unregulated sperm donation.

Quality of care and economic considerations of active surveillance of men with prostate cancer

PubMed Central

2018-01-01

The current health care climate mandates the delivery of high-value care for patients considering active surveillance for newly-diagnosed prostate cancer. Value is defined by increasing benefits (e.g., quality) for acceptable costs. This review discusses quality of care considerations for men contemplating active surveillance, and highlights cost implications at the patient, health-system, and societal level related to pursuit of non-interventional management of men diagnosed with localized prostate cancer. In general, most quality measures are focused on prostate cancer care in general, rather that active surveillance patients specifically. However, most prostate cancer quality measures are pertinent to men seeking close observation of their prostate tumors with active surveillance. These include accurate documentation of clinical stage, informed discussion of all treatment options, and appropriate use of imaging for less-aggressive prostate cancer. Furthermore, interventions that may help improve the quality of care for active surveillance patients are reviewed (e.g., quality collaboratives, judicious antibiotic use, etc.). Finally, the potential economic impact and benefits of broad acceptance of active surveillance strategies are highlighted. PMID:29732278

Quality of care and economic considerations of active surveillance of men with prostate cancer.

PubMed

Filson, Christopher P

2018-04-01

The current health care climate mandates the delivery of high-value care for patients considering active surveillance for newly-diagnosed prostate cancer. Value is defined by increasing benefits (e.g., quality) for acceptable costs. This review discusses quality of care considerations for men contemplating active surveillance, and highlights cost implications at the patient, health-system, and societal level related to pursuit of non-interventional management of men diagnosed with localized prostate cancer. In general, most quality measures are focused on prostate cancer care in general, rather that active surveillance patients specifically. However, most prostate cancer quality measures are pertinent to men seeking close observation of their prostate tumors with active surveillance. These include accurate documentation of clinical stage, informed discussion of all treatment options, and appropriate use of imaging for less-aggressive prostate cancer. Furthermore, interventions that may help improve the quality of care for active surveillance patients are reviewed (e.g., quality collaboratives, judicious antibiotic use, etc.). Finally, the potential economic impact and benefits of broad acceptance of active surveillance strategies are highlighted.

The evidence for and against different modes of tumour cell extravasation in the lung: diapedesis, capillary destruction, necroptosis, and endothelialization.

PubMed

Paku, Sándor; Laszlo, Viktoria; Dezso, Katalin; Nagy, Peter; Hoda, Mir Alireza; Klepetko, Walter; Renyi-Vamos, Ferenc; Timar, Jozsef; Reynolds, Andrew R; Dome, Balazs

2017-03-01

The development of lung metastasis is a significant negative prognostic factor for cancer patients. The extravasation phase of lung metastasis involves interactions of tumour cells with the pulmonary endothelium. These interactions may have broad biological and medical significance, with potential clinical implications ranging from the discovery of lung metastasis biomarkers to the identification of targets for intervention in preventing lung metastases. Because of the potential significance, the mechanisms of tumour cell extravasation require cautious, systematic studies. Here, we discuss the literature pertaining to the proposed mechanisms of extravasation and critically compare a recently proposed mechanism (tumour cell-induced endothelial necroptosis) with the already described extravasation mechanisms in the lung. We also provide novel data that may help to explain the underlying physiological basis for endothelialization as a mechanism of tumour cell extravasation in the lung. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A Critical Role of Zinc Importer AdcABC in Group A Streptococcus-Host Interactions During Infection and Its Implications for Vaccine Development.

PubMed

Makthal, Nishanth; Nguyen, Kimberly; Do, Hackwon; Gavagan, Maire; Chandrangsu, Pete; Helmann, John D; Olsen, Randall J; Kumaraswami, Muthiah

2017-07-01

Bacterial pathogens must overcome host immune mechanisms to acquire micronutrients for successful replication and infection. Streptococcus pyogenes, also known as group A streptococcus (GAS), is a human pathogen that causes a variety of clinical manifestations, and disease prevention is hampered by lack of a human GAS vaccine. Herein, we report that the mammalian host recruits calprotectin (CP) to GAS infection sites and retards bacterial growth by zinc limitation. However, a GAS-encoded zinc importer and a nuanced zinc sensor aid bacterial defense against CP-mediated growth inhibition and contribute to GAS virulence. Immunization of mice with the extracellular component of the zinc importer confers protection against systemic GAS challenge. Together, we identified a key early stage host-GAS interaction and translated that knowledge into a novel vaccine strategy against GAS infection. Furthermore, we provided evidence that a similar struggle for zinc may occur during other streptococcal infections, which raises the possibility of a broad-spectrum prophylactic strategy against multiple streptococcal pathogens. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Implications of the Hierarchical Structure of Psychopathology for Psychiatric Neuroimaging.

PubMed

Zald, David H; Lahey, Benjamin B

2017-05-01

Research into the neurobiological substrates of psychopathology has been impeded by heterogeneity within diagnostic categories, comorbidity among mental disorders, and the presence of symptoms that transcend diagnostic categories. Solutions to these issues increasingly focus neurobiological research on isolated or narrow groupings of symptoms or functional constructs rather than categorical diagnoses. Here we argue for a more integrative approach that also incorporates the broad hierarchical structure of psychopathological symptoms and their etiological mechanisms. This approach places clinical neuroscience research in the context of a hierarchy of empirically defined factors of symptoms such as internalizing disorders, externalizing disorders, and the general factor of psychopathology. Application of this hierarchical approach has the potential to reveal neural substrates that nonspecifically contribute to multiple forms of psychopathology and their comorbidity, and in doing so, facilitate the study of mechanisms that are specific to single dimensions and subsets of symptoms. Neurobiological research on the hierarchy of dimensions of psychopathology is only just beginning to emerge, but has the potential to radically alter our understanding of the neurobiology of abnormal behavior.

Pathophysiology of diverticular disease.

PubMed

Schieffer, Kathleen M; Kline, Bryan P; Yochum, Gregory S; Koltun, Walter A

2018-06-07

Inflammation of diverticula, or outpouchings of the colonic mucosa and submucosa through the muscularis layer, leads to diverticulitis. The development of diverticular disease, encompassing both diverticulosis and diverticulitis, is a result of genetic predisposition, lifestyle, and environmental factors, including the microbiome. Areas covered: Previous reports implicated genetic predisposition, environmental factors, and colonic dysmotility in diverticular disease. Recent studies have associated specific host immune responses and the microbiome as contributors to diverticulitis. To review pertinent literature describing pathophysiological factors associated with diverticulosis or diverticulitis, we searched the PubMed database (March 2018) for articles considering the role of colonic architecture, genetic predisposition, environment, colonic motility, immune response, and the microbiome. Expert commentary: In the recent years, research into the molecular underpinnings of diverticular disease has enhanced our understanding of diverticular disease pathogenesis. Although acute uncomplicated diverticulitis is treated with broad spectrum antibiotics, evaluation of the microbiome has been limited and requires further comprehensive studies. Evidence suggests that a deregulation of the host immune response is associated with both diverticulosis and diverticulitis. Further examining these pathways may reveal proteins that can be therapeutic targets or aid in identifying biological determinants of clinical or surgical decision making.

A Gender Comparison of Motivations for Physical Dating Violence Among College Students.

PubMed

Elmquist, JoAnna; Wolford-Clevenger, Caitlin; Zapor, Heather; Febres, Jeniimarie; Shorey, Ryan C; Hamel, John; Stuart, Gregory L

2016-01-01

There are limited empirical investigations that directly compare men and women's motivations, or reasons, for perpetrating physical dating violence (DV). In an attempt to further understand whether men and women have similar or different motives for physical DV, the purpose of the current study was to conduct a gender comparison of motives in a sample of male (n = 163) and female (n = 319) college students. Motivations for physical DV were classified according to seven broad categories proposed by Langhinrichsen-Rohling and colleagues: (a) power/control, (b) self-defense, (c) expression of negative emotion (e.g., anger), (d) communication difficulties, (e) retaliation, (f) jealousy, and (g) other (e.g., because it was sexually arousing, the influence of alcohol, the influence of drugs). The prevalence of physical violence perpetration in the overall sample was 29.4%. Results indicated that communication difficulties and self-defense were among the most frequently endorsed motive categories for both male and female perpetrated DV. In addition, results demonstrated gender similarity in all of the examined motive categories. Research and clinical implications are discussed. © The Author(s) 2014.

Suicidality in Bipolar Disorder: The Role of Emotion-Triggered Impulsivity.

PubMed

Johnson, Sheri L; Carver, Charles S; Tharp, Jordan A

2017-04-01

A growing body of research suggests that impulsive responses to emotion more robustly predict suicidality than do other forms of impulsivity. This issue has not yet been examined within bipolar disorder, however. Participants diagnosed with bipolar I disorder (n = 133) and control participants (n = 110) diagnosed with no mood or psychotic disorder completed self-report measures of emotion-triggered impulsivity (Negative and Positive Urgency Scales) and interviews concerning lifetime suicidality. Analyses examined the effects of emotion-triggered impulsivity alone and in combination with gender, age of onset, depression severity, comorbid anxiety, comorbid substance use, and medication. A history of suicide ideation and attempts, as well as self-harm, were significantly more common in the bipolar disorder group compared with the control group. Impulsive responses to positive emotions related to suicide ideation, attempts, and self-harm within the bipolar group. Findings extend research on the importance of emotion-triggered impulsivity to a broad range of key outcomes within bipolar disorder. The discussion focuses on limitations and potential clinical implications. © 2016 The American Association of Suicidology.

Eosinophils from Physiology to Disease: A Comprehensive Review

PubMed Central

Yacoub, Mona-Rita; Ripa, Marco; Mannina, Daniele; Cariddi, Adriana; Saporiti, Nicoletta; Ciceri, Fabio; Castagna, Antonella; Dagna, Lorenzo

2018-01-01

Despite being the second least represented granulocyte subpopulation in the circulating blood, eosinophils are receiving a growing interest from the scientific community, due to their complex pathophysiological role in a broad range of local and systemic inflammatory diseases as well as in cancer and thrombosis. Eosinophils are crucial for the control of parasitic infections, but increasing evidence suggests that they are also involved in vital defensive tasks against bacterial and viral pathogens including HIV. On the other side of the coin, eosinophil potential to provide a strong defensive response against invading microbes through the release of a large array of compounds can prove toxic to the host tissues and dysregulate haemostasis. Increasing knowledge of eosinophil biological behaviour is leading to major changes in established paradigms for the classification and diagnosis of several allergic and autoimmune diseases and has paved the way to a “golden age” of eosinophil-targeted agents. In this review, we provide a comprehensive update on the pathophysiological role of eosinophils in host defence, inflammation, and cancer and discuss potential clinical implications in light of recent therapeutic advances. PMID:29619379

A Developmental Neuroscience of Borderline Pathology: Emotion Dysregulation and Social Baseline Theory

PubMed Central

Hughes, Amy E.; Crowell, Sheila E.; Uyeji, Lauren; Coan, James A.

2011-01-01

Theoretical and empirical research has linked poor emotion regulation abilities with dysfunctional frontolimbic circuitry. Consistent with this, research on borderline personality disorder (BPD) finds that frontolimbic dysfunction is a predominant neural substrate underlying the disorder. Emotion regulation is profoundly compromised in BPD. However, BPD is also associated with broad impairment across multiple domains, including impulse control, interpersonal relationships, and cognitive functioning. To date, BPD research has focused largely on single areas of dysfunction, failing to account for overlap at either the biological or behavioral levels of analysis. We examine the literature on frontolimbic dysfunction in BPD within the context of Coan’s social baseline theory. Social baseline theory proposes that healthy human functioning is dependent upon adequate social support and that, at baseline, biological systems are adapted to operate interdependently rather than independently. The social baseline perspective is particularly useful for understanding borderline personality development because the impulsive and emotionally dysregulated behaviors common among those with BPD occur almost invariably within an interpersonal context. We discuss clinical and research implications of this work. PMID:21845379

Healthcare service quality: towards a broad definition.

PubMed

Mosadeghrad, Ali Mohammad

2013-01-01

The main purpose of this study is to define healthcare quality to encompass healthcare stakeholder needs and expectations because healthcare quality has varying definitions for clients, professionals, managers, policy makers and payers. This study represents an exploratory effort to understand healthcare quality in an Iranian context. In-depth individual and focus group interviews were conducted with key healthcare stakeholders. Quality healthcare is defined as "consistently delighting the patient by providing efficacious, effective and efficient healthcare services according to the latest clinical guidelines and standards, which meet the patient's needs and satisfies providers". Healthcare quality definitions common to all stakeholders involve offering effective care that contributes to the patient well-being and satisfaction. This study helps us to understand quality healthcare, highlighting its complex nature, which has direct implications for healthcare providers who are encouraged to regularly monitor healthcare quality using the attributes identified in this study. Accordingly, they can initiate continuous quality improvement programmes to maintain high patient-satisfaction levels. This is the first time a comprehensive healthcare quality definition has been developed using various healthcare stakeholder perceptions and expectations.

A plea for the development of an universally accepted modular tooth wear evaluation system.

PubMed

Wetselaar, P; Faris, A; Lobbezoo, F

2016-11-03

Tooth wear is considered an increasing oral health problem. Due to its multifactorial nature, recognizing and diagnosing of tooth wear is difficult but nevertheless important. Over the years, a wide variety of evaluation systems has been developed, yet none of them is universally accepted. This has implications for both research and clinical practice. This paper describes an in-depth analysis of four commonly used tooth wear evaluation systems, namely, the Eccles index, the Tooth Wear Index, the Lussi index, and the Basic Erosive Wear Examination. Comparing those systems revealed that despite several similarities, they differ considerably from each other. Notably, all four systems have their specific advantages and disadvantages. However, neither one of them meets all necessary characteristics of a hypothetical, broadly applicable tooth wear evaluation system. In fact, it is not realistic that a single system qualifies for all purposes (for example, diagnosing or monitoring individual patients, performing epidemiological studies, etc.). As a potentially feasible solution for this issue, the development of an evaluation system is recommended that consists of multiple, coherent modules, which cover different purposes.

A selective review of selective attention research from the past century.

PubMed

Driver, Jon

2001-02-01

Research on attention is concerned with selective processing of incoming sensory information. To some extent, our awareness of the world depends on what we choose to attend, not merely on the stimulation entering our senses. British psychologists have made substantial contributions to this topic in the past century. Celebrated examples include Donald Broadbent's filter theory of attention, which set the agenda for most subsequent work; and Anne Treisman's revisions of this account, and her later feature-integration theory. More recent contributions include Alan Allport's prescient emphasis on the relevance of neuroscience data, and John Duncan's integration of such data with psychological theory. An idiosyncratic but roughly chronological review of developments is presented, some practical and clinical implications are briefly sketched, and future directions suggested. One of the biggest changes in the field has been the increasing interplay between psychology and neuroscience, which promises much for the future. A related change has been the realization that selection attention is best thought of as a broad topic, encompassing a range of selective issues, rather than as a single explanatory process.

Effects of Sad and Happy Music on Mind-Wandering and the Default Mode Network.

PubMed

Taruffi, Liila; Pehrs, Corinna; Skouras, Stavros; Koelsch, Stefan

2017-10-31

Music is a ubiquitous phenomenon in human cultures, mostly due to its power to evoke and regulate emotions. However, effects of music evoking different emotional experiences such as sadness and happiness on cognition, and in particular on self-generated thought, are unknown. Here we use probe-caught thought sampling and functional magnetic resonance imaging (fMRI) to investigate the influence of sad and happy music on mind-wandering and its underlying neuronal mechanisms. In three experiments we found that sad music, compared with happy music, is associated with stronger mind-wandering (Experiments 1A and 1B) and greater centrality of the nodes of the Default Mode Network (DMN) (Experiment 2). Thus, our results demonstrate that, when listening to sad vs. happy music, people withdraw their attention inwards and engage in spontaneous, self-referential cognitive processes. Importantly, our results also underscore that DMN activity can be modulated as a function of sad and happy music. These findings call for a systematic investigation of the relation between music and thought, having broad implications for the use of music in education and clinical settings.

Implications of the Hierarchical Structure of Psychopathology for Psychiatric Neuroimaging

PubMed Central

Zald, David H.; Lahey, Benjamin B.

2017-01-01

Research into the neurobiological substrates of psychopathology has been impeded by heterogeneity within diagnostic categories, comorbidity among mental disorders, and the presence of symptoms that transcend diagnostic categories. Solutions to these issues increasingly focus neurobiological research on isolated or narrow groupings of symptoms or functional constructs rather than categorical diagnoses. Here we argue for a more integrative approach that also incorporates the broad hierarchical structure of psychopathological symptoms and their etiological mechanisms. This approach places clinical neuroscience research in the context of a hierarchy of empirically defined factors of symptoms such as internalizing disorders, externalizing disorders, and the general factor of psychopathology. Application of this hierarchical approach has the potential to reveal neural substrates that nonspecifically contribute to multiple forms of psychopathology and their comorbidity, and in doing so, facilitate the study of mechanisms that are specific to single dimensions and subsets of symptoms. Neurobiological research on the hierarchy of dimensions of psychopathology is only just beginning to emerge, but has the potential to radically alter our understanding of the neurobiology of abnormal behavior. PMID:28713866

Two-dimensional quasineutral description of particles and fields above discrete auroral arcs

NASA Technical Reports Server (NTRS)

Newman, A. L.; Chiu, Y. T.; Cornwall, J. M.

1985-01-01

Stationary hot and cool particle distributions in the auroral magnetosphere are modelled using adiabatic assumptions of particle motion in the presence of broad-scale electrostatic potential structure. The study has identified geometrical restrictions on the type of broadscale potential structure which can be supported by a multispecies plasma having specified sources and energies. Without energization of cool thermal ionospheric electrons, a substantial parallel potential drop cannot be supported down to altitudes of 2000 km or less. Observed upward-directed field-aligned currents must be closed by return currents along field lines which support little net potential drop. In such regions the plasma density appears significantly enhanced. Model details agree well with recent broad-scale implications of satellite observations.

Environmental protection: applying the precautionary principle and proactive regulation to biotechnology.

PubMed

Richmond, Robert H

2008-08-01

Biotechnology is a broad field encompassing diverse disciplines from agriculture to zoology. Advances in research are occurring at a rapid pace, and applications that have broad implications socially, economically, ecologically and politically are emerging. Along with notable benefits, environmental consequences that affect core quality-of-life issues for present and future generations are materializing. The precautionary principle should be applied to biotechnology research, activities and products, and a strengthened, enforceable and proactive regulatory framework is needed. The environmental impacts of agriculture, aquaculture, genetically modified organisms (GMOs) and even pharmaceuticals are raising public concerns and demonstrate the need for guidance from a variety of social, economic and scientific disciplines to insure the benefits of biotechnology are enjoyed without unacceptable and irreversible environmental costs.

Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections.

PubMed

Gerber, Jeffrey S; Ross, Rachael K; Bryan, Matthew; Localio, A Russell; Szymczak, Julia E; Wasserman, Richard; Barkman, Darlene; Odeniyi, Folasade; Conaboy, Kathryn; Bell, Louis; Zaoutis, Theoklis E; Fiks, Alexander G

2017-12-19

Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment. To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children. A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts. Broad-spectrum antibiotics vs narrow-spectrum antibiotics. In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events. Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868 (35%) were prescribed broad-spectrum antibiotics. Broad-spectrum antibiotics were associated with a slightly worse child quality of life (score of 90.2 for broad-spectrum antibiotics vs 91.5 for narrow-spectrum antibiotics; score difference for full matched analysis, -1.4% [95% CI, -2.4% to -0.4%]) but not with other patient-centered outcomes. Broad-spectrum treatment was associated with a higher risk of adverse events documented by the clinician (3.7% for broad-spectrum antibiotics vs 2.7% for narrow-spectrum antibiotics; risk difference for full matched analysis, 1.1% [95% CI, 0.4% to 1.8%]) and reported by the patient (35.6% for broad-spectrum antibiotics vs 25.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 12.2% [95% CI, 7.3% to 17.2%]). Among children with acute respiratory tract infections, broad-spectrum antibiotics were not associated with better clinical or patient-centered outcomes compared with narrow-spectrum antibiotics, and were associated with higher rates of adverse events. These data support the use of narrow-spectrum antibiotics for most children with acute respiratory tract infections.

Basic Visual Processes and Learning Disability.

ERIC Educational Resources Information Center

Leisman, Gerald

Representatives of a variety of disciplines concerned with either clinical or research problems in vision and learning disabilities present reviews and reports of relevant research and clinical approaches. Contributions are organized into four broad sections: basic processes, specific disorders, diagnosis of visually based problems in learning,…

Clinical validation of a nanodiamond-embedded thermoplastic biomaterial

PubMed Central

Lee, Dong-Keun; Kee, Theodore; Liang, Zhangrui; Hsiou, Desiree; Miya, Darron; Wu, Brian; Osawa, Eiji; Chow, Edward Kai-Hua; Kang, Mo K.; Ho, Dean

2017-01-01

Detonation nanodiamonds (NDs) are promising drug delivery and imaging agents due to their uniquely faceted surfaces with diverse chemical groups, electrostatic properties, and biocompatibility. Based on the potential to harness ND properties to clinically address a broad range of disease indications, this work reports the in-human administration of NDs through the development of ND-embedded gutta percha (NDGP), a thermoplastic biomaterial that addresses reinfection and bone loss following root canal therapy (RCT). RCT served as the first clinical indication for NDs since the procedure sites involved nearby circulation, localized administration, and image-guided treatment progress monitoring, which are analogous to many clinical indications. This randomized, single-blind interventional treatment study evaluated NDGP equivalence with unmodified GP. This progress report assessed one control-arm and three treatment-arm patients. At 3-mo and 6-mo follow-up appointments, no adverse events were observed, and lesion healing was confirmed in the NDGP-treated patients. Therefore, this study is a foundation for the continued clinical translation of NDs and other nanomaterials for a broad spectrum of applications. PMID:29078364

'Holding the line': a qualitative study of the role of evidence in early phase decision-making in the reconfiguration of stroke services in London.

PubMed

Fraser, Alec; Baeza, Juan I; Boaz, Annette

2017-06-09

Health service reconfigurations are of international interest but remain poorly understood. This article focuses on the use of evidence by senior managerial decision-makers involved in the reconfiguration of stroke services in London 2008-2012. Recent work comparing stroke service reconfiguration in London and Manchester emphasises the ability of senior managerial decision-makers in London to 'hold the line' in the crucial early phases of the stroke reconfiguration programme. In this article, we explore in detail how these decision-makers 'held the line' and ask what the broader power implications of doing so are for the interaction between evidence, health policy and system redesign. The research combined semi-structured interviews (n = 20) and documentary analysis of historically relevant policy papers and contemporary stroke reconfiguration documentation published by NHS London and other interested parties (n = 125). We applied a critical interpretive and reflexive approach to the analysis of the data. We identified two forms of power which senior managerial decision-makers drew upon in order to 'hold the line'. Firstly, discursive power, which through an emphasis on evidence, better patient outcomes, professional support and clinical credibility alongside a tightly managed consultation process, helped to set an agenda that was broadly receptive to the overall decision to change stroke services in the capital in a radical way. Secondly, once the essential parameters of the decision to change services had been agreed, senior managerial decision-makers 'held the line' through hierarchical New Public Management style power to minimise the traditional pressures to de-radicalise the reconfiguration through 'top down' decision-making. We problematise the concept of 'holding the line' and explore the power implications of such managerial approaches in the early phases of health service reconfiguration. We highlight the importance of evidence for senior managerial decision-makers in agenda setting and the limitations of clinical research findings in guiding politically sensitive policy decisions which impact upon regional healthcare systems.

Preservation of blood glucose homeostasis in slow-senescing somatotrophism-deficient mice subjected to intermittent fasting begun at middle or old age.

PubMed

Arum, Oge; Saleh, Jamal K; Boparai, Ravneet K; Kopchick, John J; Khardori, Romesh K; Bartke, Andrzej

2014-06-01

Poor blood glucose homeostatic regulation is common, consequential, and costly for older and elderly populations, resulting in pleiotrophically adverse clinical outcomes. Somatotrophic signaling deficiency and dietary restriction have each been shown to delay the rate of senescence, resulting in salubrious phenotypes such as increased survivorship. Using two growth hormone (GH) signaling-related, slow-aging mouse mutants we tested, via longitudinal analyses, whether genetic perturbations that increase survivorship also improve blood glucose homeostatic regulation in senescing mammals. Furthermore, we institute a dietary restriction paradigm that also decelerates aging, an intermittent fasting (IF) feeding schedule, as either a short-term or a sustained intervention beginning at either middle or old age, and assess its effects on blood glucose control. We find that either of the two genetic alterations in GH signaling ameliorates fasting hyperglycemia; additionally, both longevity-inducing somatotrophic mutations improve insulin sensitivity into old age. Strikingly, we observe major and broad improvements in blood glucose homeostatic control by IF: IF improves ad libitum-fed hyperglycemia, glucose tolerance, and insulin sensitivity, and reduces hepatic gluconeogenesis, in aging mutant and normal mice. These results on correction of aging-resultant blood glucose dysregulation have potentially important clinical and public health implications for our ever-graying global population, and are consistent with the Longevity Dividend concept.

Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

PubMed Central

Diamanti-Kandarakis, Evanthia; Bourguignon, Jean-Pierre; Giudice, Linda C.; Hauser, Russ; Prins, Gail S.; Soto, Ana M.; Zoeller, R. Thomas; Gore, Andrea C.

2009-01-01

There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness. PMID:19502515

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications.

PubMed

Kraehenmann, Rainer

2017-01-01

A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or 'classical' psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,Ndimethyltryptamine), and ayahuasca - a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams, and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Research literature related to psychedelics and dreaming is reviewed, and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelicassisted therapy will be provided. Common features between psychedelic states and night dreams include perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body. Differences between these two states are related to differential perceptual input from the environment, clarity of consciousness and meta-cognitive abilities. Therefore, psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness. The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications

PubMed Central

Kraehenmann, Rainer

2017-01-01

Background: A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics such as the prototypical psychedelic drug lysergic acid diethylamide (LSD) psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Methods: Research literature related to psychedelics and dreaming is reviewed and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelic-assisted therapy will be provided. Results: Common features between psychedelic states and night dreams include perception mental imagery emotion activation fear memory extinction and sense of self and body. Differences between these two states are related to differential perceptual input from the environment clarity of consciousness and meta-cognitive abilities. Therefore psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness Conclusion: The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. PMID:28625125

Evaluation of a Booster Intervention Three Years after Acute Treatment for Early-Onset Disruptive Behavior Disorders

PubMed Central

Lindhiem, Oliver; Hart, Jonathan; Bukstein, Oscar G.

2013-01-01

This study examines the impact of a brief booster treatment administered three years after the delivery of an acute treatment in a group (N = 118) of clinically referred boys and girls (ages 6 to 11) originally diagnosed with Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD). At the conclusion of the acute treatment and three-year follow-up period (i.e., study month 42), the sample was re-randomized into Booster treatment or Enhanced Usual Care and then assessed at four later timepoints (i.e., post-booster, and 6-, 12- and 24-month booster follow-up). Booster treatment was directed towards addressing individualized problems and some unique developmental issues of adolescence based on the same original protocol content and treatment setting, whereas the no-booster condition involved providing clinical recommendations based on the assessment and an outside referral for services. HLM analyses identified no significant group differences and few time effects across child, parent, and teacher reports on a broad range of child functioning and impairment outcomes. Analyses examining the role of putative moderators or mediators (e.g., severity of externalizing behavior, dose of treatment) were likewise non-significant. We discuss the nature and implications of these novel findings regarding the role and timing of booster treatment to address the continuity of DBD over time. PMID:23494526

Topoisomerase II Inhibitors and Poisons, and the Influence of Cell Cycle Checkpoints.

PubMed

D Arcy, Nicholas; Gabrielli, Brian

2017-01-01

Interactions between the decatenation checkpoint and Topoisomerase II (TopoII) are vital for maintaining integrity of the genome. Agents that target this enzyme have been in clinical use in cancer therapy for over 30 years with great success. The types of compounds that have been developed to target TopoII are broadly divided into poisons and catalytic inhibitors. The TopoII poisons are in clinical use as anti-cancer therapies, although in common to most chemotherapeutic agents, they display considerable normal tissue toxicity. Inhibition of the TopoIIb isoform has been implicated in this cytotoxicity. Response to TopoII active agents is determined by several factors, but cell cycle checkpoints play a large role in sensitivity and resistance. The G2/M phase checkpoints are of particular importance in considering the effectiveness of these drugs and are reviewed in this article. Functionality of the ATM dependent decatenation checkpoint may represent a new avenue for selective cancer therapy. Here we review the function of TopoII, the anti-cancer mechanisms and limitations of current catalytic inhibitors and poisons, and their influence on cell cycle checkpoints. We will also assess potential new mechanisms for targeting this enzyme to limit normal tissue toxicity, and how the cell cycle checkpoint triggered by these drugs may provide an alternative and possibly better target for novel therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A broad scope knowledge based model for optimization of VMAT in esophageal cancer: validation and assessment of plan quality among different treatment centers.

PubMed

Fogliata, Antonella; Nicolini, Giorgia; Clivio, Alessandro; Vanetti, Eugenio; Laksar, Sarbani; Tozzi, Angelo; Scorsetti, Marta; Cozzi, Luca

2015-10-31

To evaluate the performance of a broad scope model-based optimisation process for volumetric modulated arc therapy applied to esophageal cancer. A set of 70 previously treated patients in two different institutions, were selected to train a model for the prediction of dose-volume constraints. The model was built with a broad-scope purpose, aiming to be effective for different dose prescriptions and tumour localisations. It was validated on three groups of patients from the same institution and from another clinic not providing patients for the training phase. Comparison of the automated plans was done against reference cases given by the clinically accepted plans. Quantitative improvements (statistically significant for the majority of the analysed dose-volume parameters) were observed between the benchmark and the test plans. Of 624 dose-volume objectives assessed for plan evaluation, in 21 cases (3.3 %) the reference plans failed to respect the constraints while the model-based plans succeeded. Only in 3 cases (<0.5 %) the reference plans passed the criteria while the model-based failed. In 5.3 % of the cases both groups of plans failed and in the remaining cases both passed the tests. Plans were optimised using a broad scope knowledge-based model to determine the dose-volume constraints. The results showed dosimetric improvements when compared to the benchmark data. Particularly the plans optimised for patients from the third centre, not participating to the training, resulted in superior quality. The data suggests that the new engine is reliable and could encourage its application to clinical practice.

[From scabies room to modern specialty department. 90 years Ludwigshaven Dermatology Clinic].

PubMed

Voigtländer, V; Boslet, W; Tully, G

2000-12-01

The dermatology clinic Ludwigshafen was founded in 1910. Dr. Siegfried Fuss was head of the clinic for almost 40 years. The clinic's history reflects the rapid industrial growth of the city, the destruction of two world wars and the progress of dermatology during this century. Today, the clinic is an academic teaching hospital affiliated with the University of Mainz with 45 beds and offers a broad spectrum of modern dematological diagnostic procedures and therapies.

Clinical implications of contemporary gender theory.

PubMed

Kulish, Nancy

2010-04-01

The current intellectual scene in psychoanalysis is marked by vigorous theoretical controversies about gender. The ideas being debated have important implications for clinical work, which have not been thoroughly explicated or integrated into common practice. These implications include the following: gender can accrue idiosyncratic meanings; gender identity is considered fluid and rigidity of gender identity deemed problematic; gender-related conflicts are typically described as divergent; analysis of superego conflicts related to gender becomes particularly important; and, finally, gender-related biases are seen as inevitable and must be taken into account in the clinical situation. A detailed clinical example illustrates the application of these ideas. While the more dramatic cases related to gender have been more frequent subjects of study, conflicts about gender are everyday occurrences for our patients and deserve further attention.

A regional interdependence model of musculoskeletal dysfunction: research, mechanisms, and clinical implications

PubMed Central

Sueki, Derrick G; Cleland, Joshua A; Wainner, Robert S

2013-01-01

The term ‘regional interdependence’ or RI has recently been introduced into the vernacular of physical therapy and rehabilitation literature as a clinical model of musculoskeletal assessment and intervention. The underlying premise of this model is that seemingly unrelated impairments in remote anatomical regions of the body may contribute to and be associated with a patient’s primary report of symptoms. The clinical implication of this premise is that interventions directed at one region of the body will often have effects at remote and seeming unrelated areas. The formalized concept of RI is relatively new and was originally derived in an inductive manner from a variety of earlier publications and clinical observations. However, recent literature has provided additional support to the concept. The primary purpose of this article will be to further refine the operational definition for the concept of RI, examine supporting literature, discuss possible clinically relevant mechanisms, and conclude with a discussion of the implications of these findings on clinical practice and research. PMID:24421619

Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes.

PubMed

Chen, Kaifu; Chen, Zhong; Wu, Dayong; Zhang, Lili; Lin, Xueqiu; Su, Jianzhong; Rodriguez, Benjamin; Xi, Yuanxin; Xia, Zheng; Chen, Xi; Shi, Xiaobing; Wang, Qianben; Li, Wei

2015-10-01

Tumor suppressors are mostly defined by inactivating mutations in tumors, yet little is known about their epigenetic features in normal cells. Through integrative analysis of 1,134 genome-wide epigenetic profiles, mutations from >8,200 tumor-normal pairs and our experimental data from clinical samples, we discovered broad peaks for trimethylation of histone H3 at lysine 4 (H3K4me3; wider than 4 kb) as the first epigenetic signature for tumor suppressors in normal cells. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity, which together lead to exceptionally high gene expression, and is distinct from other broad epigenetic features, such as super-enhancers. Genes with broad H3K4me3 peaks conserved across normal cells may represent pan-cancer tumor suppressors, such as TP53 and PTEN, whereas genes with cell type-specific broad H3K4me3 peaks may represent cell identity genes and cell type-specific tumor suppressors. Furthermore, widespread shortening of broad H3K4me3 peaks in cancers is associated with repression of tumor suppressors. Thus, the broad H3K4me3 epigenetic signature provides mutation-independent information for the discovery and characterization of new tumor suppressors.

New therapeutic options for respiratory tract infections.

PubMed

Bassetti, Matteo; Righi, Elda; Carnelutti, Alessia

2016-04-01

The progressive increase of respiratory tract infections caused by multidrug-resistant organisms (MDROs) has been associated with delays in the prescription of an adequate antibiotic treatment and increased mortality, representing a major concern in both community and hospital settings. When infections because of methicillin-resistant Staphylococcus aureus (MRSA) are suspected, vancomycin still represents the first choice, although its efficacy has been recently questioned in favor of new drugs, reported to provide better clinical outcomes. Moreover, few therapeutic options are currently available for the treatment of severe infections caused by Multidrug-resistant (MDR) Gram-negative pathogens, which are frequently resistant to all the available β-lactams, including carbapenems. We have reviewed the therapeutic options for the treatment of respiratory tract infections that have recently become available with promising implications for clinical practice, including ceftaroline, ceftrobiprole, tedizolid, telavancin, delafloxacin, eravacycline, and new β-lactams/β-lactamase inhibitors. A number of new antimicrobials with activity against MDROs have been recently approved for the treatment of respiratory tract infections, and other agents are under investigation. Recent developments, with a specific focus on the possible advantages of new drugs for the management of respiratory tract infections caused by MDROs in everyday clinical practice are discussed. Newly approved and investigational drugs for the treatment of respiratory tract infections are expected to offer many advantages for the management of patients with suspected or confirmed infections caused by MDROs. Most promising features among new compounds include the broad spectrum of activity against both MRSA and MDR Gram-negative bacteria, a limited risk of antimicrobial resistance, the availability of oral formulations, and a promising safety profile.

Prescription opioid abuse, pain and addiction: clinical issues and implications.

PubMed

Ling, Walter; Mooney, Larissa; Hillhouse, Maureen

2011-05-01

Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial µ agonist buprenorphine in the management of concurrent pain and opioid addiction. Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. © 2011 Australasian Professional Society on Alcohol and other Drugs.

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila

PubMed Central

Lugtenberg, Dorien; Reijnders, Margot R F; Fenckova, Michaela; Bijlsma, Emilia K; Bernier, Raphael; van Bon, Bregje W M; Smeets, Eric; Vulto-van Silfhout, Anneke T; Bosch, Danielle; Eichler, Evan E; Mefford, Heather C; Carvill, Gemma L; Bongers, Ernie M H F; Schuurs-Hoeijmakers, Janneke HM; Ruivenkamp, Claudia A; Santen, Gijs W E; van den Maagdenberg, Arn M J M; Peeters-Scholte, Cacha M P C D; Kuenen, Sabine; Verstreken, Patrik; Pfundt, Rolph; Yntema, Helger G; de Vries, Petra F; Veltman, Joris A; Hoischen, Alexander; Gilissen, Christian; de Vries, Bert B A; Schenck, Annette; Kleefstra, Tjitske; Vissers, Lisenka E L M

2016-01-01

Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification. PMID:26757981

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila.

PubMed

Lugtenberg, Dorien; Reijnders, Margot R F; Fenckova, Michaela; Bijlsma, Emilia K; Bernier, Raphael; van Bon, Bregje W M; Smeets, Eric; Vulto-van Silfhout, Anneke T; Bosch, Danielle; Eichler, Evan E; Mefford, Heather C; Carvill, Gemma L; Bongers, Ernie M H F; Schuurs-Hoeijmakers, Janneke Hm; Ruivenkamp, Claudia A; Santen, Gijs W E; van den Maagdenberg, Arn M J M; Peeters-Scholte, Cacha M P C D; Kuenen, Sabine; Verstreken, Patrik; Pfundt, Rolph; Yntema, Helger G; de Vries, Petra F; Veltman, Joris A; Hoischen, Alexander; Gilissen, Christian; de Vries, Bert B A; Schenck, Annette; Kleefstra, Tjitske; Vissers, Lisenka E L M

2016-08-01

Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification.

Policies for patient access to clinical data via PHRs: current state and recommendations.

PubMed

Collins, Sarah A; Vawdrey, David K; Kukafka, Rita; Kuperman, Gilad J

2011-12-01

Healthcare delivery organizations are increasingly using online personal health records (PHRs) to provide patients with direct access to their clinical information; however, there may be a lack of consistency in the data made available. We aimed to understand the general use and functionality of PHRs and the organizational policies and decision-making structures for making data available to patients. A cross-sectional survey was administered by telephone structured interview to 21 organizations to determine the types of data made available to patients through PHRs and the presence of explicit governance for PHR data release. Organizations were identified based on a review of the literature, PHR experts, and snowball sampling. Organizations that did not provide patients with electronic access to their data via a PHR were excluded. Interviews were conducted with 17 organizations for a response rate of 81%. Half of the organizations had explicit governance in the form of a written policy that outlined the data types made available to patients. Overall, 88% of the organizations used a committee structure for the decision-making process and included senior management and information services. All organizations sought input from clinicians. Discussion There was considerable variability in the types of clinical data and the time frame for releasing these data to patients. Variability in data release policies may have implications for PHR use and adoption. Future policy activities, such as requirement specification for the latter stages of Meaningful Use, should be leveraged as an opportunity to encourage standardization of functionality and broad deployment of PHRs.

Monoclonal Antibodies to Hyphal Exoantigens Derived from the Opportunistic Pathogen Aspergillus terreus

EPA Science Inventory

Aspergillus terreus has been difficult to identify in cases of aspergillosis, and clinical identification has been restricted to the broad identification of aspergillosis lesions in affected organs or the detection of fungal carbohydrates. As a result, there is a clinical need to...

Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies.

PubMed

Zhang, Zhiqing; Li, Shaowei; Gu, Ying; Xia, Ningshao

2016-11-18

Human immunodeficiency virus type 1 (HIV-1) infection causes acquired immune deficiency syndrome (AIDS), a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART) but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env protein and the reciprocal broadly neutralizing antibodies, and discuss the ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy as well as antibody combinations, bispecific antibodies, and methods that improve therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs) with latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate these broadly neutralizing and inhibitory antibodies offer the advantage of decreasing virus load and clearing infected cells, which is a promising prospect in HIV-1 prevention and treatment.

A postmenopausal woman with sciatica from broad ligament leiomyoma: a case report.

PubMed

Tsai, Ya-Chu May

2016-10-31

Unilateral lower abdominal pain and/or sciatic nerve pain is a common presentation in the elderly population. The prevalence of broad ligament leiomyoma is <1 % with the prevalence declining after the menopause and it is rare for broad ligament leiomyomas to be clinically significant. Thus, we highlight a case of symptomatic broad ligament leiomyoma in a postmenopausal woman whose symptoms improved after definitive treatment. A 62-year-old postmenopausal Macedonian woman was referred to our gynecological department with unexplained pain in her left leg and left iliac fossa region on walking. There was minimal relief with increasing analgesia use prescribed by the family physician. Investigations revealed an ipsilateral adnexal mass and subsequent treatment with laparoscopic broad ligament myomectomy helped to alleviate her symptoms. Our case highlights the importance of staying mindful of alternate diagnoses when presented with a common presentation of iliac fossa pain and pain in the leg. Although broad ligament leiomyomas are benign tumors, the uncommon symptomatic presentation led us to report and focus some attention on this type of tumor.

Inhibiting cancer cell hallmark features through nuclear export inhibition.

PubMed

Sun, Qingxiang; Chen, Xueqin; Zhou, Qiao; Burstein, Ezra; Yang, Shengyong; Jia, Da

2016-01-01

Treating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical application. Nuclear export factor chromosomal region maintenance 1 (CRM1; Xpo1 and exportin-1) controls cellular localization and function of numerous proteins that are critical for the development of many cancer hallmarks. The diverse actions of CRM1 are likely to explain the broad ranging anti-cancer potency of CRM1 inhibitors observed in pre-clinical studies and/or clinical trials (phase I-III) on both advanced-stage solid and hematological tumors. In this review, we compare and contrast the mechanisms of action of different CRM1 inhibitors, and discuss the potential benefit of unexplored non-covalent CRM1 inhibitors. This emerging field has uncovered that nuclear export inhibition is well poised as an attractive target towards low-toxicity broad-spectrum potent anti-cancer therapy.

Validation of Sensititre Dry-Form Broth Microdilution Panels for Susceptibility Testing of Ceftazidime-Avibactam, a Broad-Spectrum-β-Lactamase Inhibitor Combination.

PubMed

Jones, Ronald N; Holliday, Nicole M; Krause, Kevin M

2015-08-01

Ceftazidime-avibactam is a broad-spectrum-β-lactamase inhibitor combination in late-stage clinical development for the treatment of serious infections. In preparation for clinical microbiology laboratory use, a validation experiment was initiated to evaluate a commercial broth microdilution product (Sensititre dried MIC susceptibility system) compared to reference panels using 525 recent clinical isolates. Among 11 pathogen groups, all had Sensititre MIC/reference MIC ratios predominantly at 1 (47.5% to 97.5%), and automated and manual endpoint results did not differ. Enterobacteriaceae MIC comparisons showed a modest skewing of Sensititre MIC results toward an elevated MIC (33.9%), but the essential agreement was 98.9% with 100.0% reproducibility. In conclusion, Sensititre panels produced accurate ceftazidime-avibactam MIC results, allowing quality MIC guidance for therapy following regulatory approvals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Validation of Sensititre Dry-Form Broth Microdilution Panels for Susceptibility Testing of Ceftazidime-Avibactam, a Broad-Spectrum-β-Lactamase Inhibitor Combination

PubMed Central

Holliday, Nicole M.; Krause, Kevin M.

2015-01-01

Ceftazidime-avibactam is a broad-spectrum-β-lactamase inhibitor combination in late-stage clinical development for the treatment of serious infections. In preparation for clinical microbiology laboratory use, a validation experiment was initiated to evaluate a commercial broth microdilution product (Sensititre dried MIC susceptibility system) compared to reference panels using 525 recent clinical isolates. Among 11 pathogen groups, all had Sensititre MIC/reference MIC ratios predominantly at 1 (47.5% to 97.5%), and automated and manual endpoint results did not differ. Enterobacteriaceae MIC comparisons showed a modest skewing of Sensititre MIC results toward an elevated MIC (33.9%), but the essential agreement was 98.9% with 100.0% reproducibility. In conclusion, Sensititre panels produced accurate ceftazidime-avibactam MIC results, allowing quality MIC guidance for therapy following regulatory approvals. PMID:26014937

Red Scare in the Red State: The Attack on Mexican-American Studies in Arizona and Opportunities for Building National Solidarity

ERIC Educational Resources Information Center

Fernandez, Anita; Hammer, Zoe

2012-01-01

The attack on ethnic studies in Tucson is a local struggle with broad implications. This essay poses that Arizona is a testing ground for neoliberal laws, policies and practices, including HB2281, an anti-Latin@ law banning ethnic studies courses in public schools. Given that many such political "experiments" have been successfully…

Mobilization and Defense Management Technical Reports Series. The Impact of OSHA (Occupational Safety and Health Administration) and EPA (Environmental Protection Agency) on Defense Industry and the Implications for Mobilization.

DTIC Science & Technology

1983-05-01

mat of the voluntary standards thean in existence (JASI and NVA standards, for wcmmle). fwue affected the broad spectrum of Nm rican industry. As OBIA ...have been funded. As OMA matured, programs, standards, and inspections were significantly improved and gained industry aeptance. OBIA has deleted many

The "Living with Dysarthria" Group: Implementation and Feasibility of a Group Intervention for People with Dysarthria Following Stroke and Family Members

ERIC Educational Resources Information Center

Mackenzie, Catherine; Paton, Gillian; Kelly, Shona; Brady, Marian; Muir, Margaret

2012-01-01

Background: The broad life implications of acquired dysarthria are recognized, but they have received little attention in stroke management. Reports of group therapy, which may be a suitable approach to intervention, are not available for stroke-related dysarthria. Aims: To examine the operational feasibility of and response to a new eight-session…

A Rejoinder to Commentaries on "Integrated Reporting: A Review of Developments and Their Implications for the Accounting Curriculum"

ERIC Educational Resources Information Center

Owen, Gareth

2013-01-01

In this rejoinder, Gareth Owen thanks both Dr. Kamp-Roelands and Dr. Correa Ruiz for their views and for putting forward many interesting and thought-provoking arguments concerning his paper (Owen, 2013). It is noted that both commentators broadly welcome the aims of this paper. They express approval of its review of the development of integrated…

GANEing traction: The broad applicability of NE hotspots to diverse cognitive and arousal phenomena

PubMed Central

Mather, Mara; Clewett, David; Sakaki, Michiko; Harley, Carolyn W.

2018-01-01

The GANE (glutamate amplifies noradrenergic effects) model proposes that local glutamate–norepinephrine interactions enable “winner-take-more” effects in perception and memory under arousal. A diverse range of commentaries addressed both the nature of this “hot spot” feedback mechanism and its implications in a variety of psychological domains, inspiring exciting avenues for future research. PMID:28355836

The Perceptions of Autism Spectrum Disorder Students and Their Parents: Implications for Principal Decision Making Regarding School Inclusivity

ERIC Educational Resources Information Center

Meskell, Kathrin Ann

2017-01-01

Autism is a complex biobgical disorder that usually lasts throughout a person's life (CDC, 2015). Persons with autism often find themselves cut off from the world around them. People with autism may exhibit a broad and diverse range of characteristics so doctors now think of autism as a spectrum disorder. Research studies reported that principals…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Weitao

This Special Topic Issue on the Advances in Density Functional Theory, published as a celebration of the fifty years of density functional theory, contains a retrospective article, a perspective article, and a collection of original research articles that showcase recent theoretical advances in the field. It provides a timely discussion reflecting a cross section of our understanding, and the theoretical and computational developments, which have significant implications in broad areas of sciences and engineering.

Health Manpower Credentialing: Legal Implications of Institutional Licensure. Health Manpower Policy Discussion Paper Series No.: C3.

ERIC Educational Resources Information Center

Crane, Stephen

The objective of this analysis is to outline in broad fashion the current trends and issues in the licensure of health manpower and to contrast two proposed alternative systems of credentialing that focus on licensure of health care institutions instead of individual health care providers. The argument of the analysis is that the current system of…

Very Broad [O III] λλ4959, 5007 Emission from the NGC 4472 Globular Cluster RZ 2109 and Implications for the Mass of Its Black Hole X-Ray Source

NASA Astrophysics Data System (ADS)

Zepf, Stephen E.; Stern, Daniel; Maccarone, Thomas J.; Kundu, Arunav; Kamionkowski, Marc; Rhode, Katherine L.; Salzer, John J.; Ciardullo, Robin; Gronwall, Caryl

2008-08-01

We present Keck LRIS spectroscopy of the black hole-hosting globular cluster RZ 2109 in the Virgo elliptical galaxy NGC 4472. We find that this object has extraordinarily broad [O III] λ5007 and [O III] λ4959 emission lines, with velocity widths of approximately 2000 km s-1. This result has significant implications for the nature of this accreting black hole system and the mass of the globular cluster black hole. We show that the broad [O III] λ5007 emission must arise from material driven at high velocity from the black hole system. This is because the volume available near the black hole is too small by many orders of magnitude to have enough [O III]-emitting atoms to account for the observed L([O III] λ5007) at high velocities, even if this volume is filled with oxygen at the critical density for [O III] λ5007. The Balmer emission is also weak, indicating the observed [O III] is not due to shocks. We therefore conclude that the [O III] λλ4959, 5007 is produced by photoionization of material driven across the cluster. The only known way to drive significant material at high velocity is for a system accreting mass near or above its Eddington limit, which indicates a stellar-mass black hole. Since it is dynamically implausible to form an accreting stellar-mass black hole system in a globular cluster with an intermediate-mass black hole (IMBH), it appears this massive globular cluster does not have an IMBH. We discuss further tests of this conclusion, and its implications for the MBH - Mstellar and MBH - σ relations. Based on observations made at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

Is Ureaplasma spp. the leading causative agent of acute chorioamnionitis in women with preterm birth?

PubMed

Kikhney, J; von Schöning, D; Steding, I; Schulze, J; Petrich, A; Hiergeist, A; Reischl, U; Moter, A; Thomas, A

2017-02-01

Aim of this study was to detect microorganisms in fetal membranes and placental tissue in preterm chorioamnionitis by combining fluorescence in situ hybridization (FISH) with broad range PCR. The combination of the two molecular techniques enables identification and localization of the microorganisms within the tissue, confirming their clinical relevance. In a prospective cohort study, we compared 31 women with preterm premature rupture of membranes or preterm labour and preterm delivery by caesarean section with a control group of 26 women undergoing elective caesarean section at term. Fetal membranes and placental tissue were analysed by FISH and broad range 16S rRNA-gene PCR and sequencing. For 20 women in the preterm group, caesarean section was performed because of a clinical diagnosis of chorioamnionitis. Microorganisms were detected in the tissues by both molecular techniques in 11 out of 20 women. Among those, Ureaplasma spp. was most abundant, with five cases that remained culture-negative and would have been missed by routine diagnostic procedures. Other infections were caused by Staphylococcus aureus, Streptococcus mitis or Escherichia coli. FISH and PCR were negative for all women without suspected chorioamnionitis and for the control group. Combination of FISH with broad-range PCR and sequencing permitted unambiguous identification of the causative microorganisms in chorioamnionitis. The high prevalence of Ureaplasma spp. should lead to a re-evaluation of its clinical significance and possible therapeutic consequences. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

“Listening” and “talking” to neurons: Implications of immune activation for pain control and increasing the efficacy of opioids

PubMed Central

Watkins, Linda R.; Hutchinson, Mark R.; Milligan, Erin D.; Maier, Steven F.

2008-01-01

It is recently become clear that activated immune cells and immune-like glial cells can dramatically alter neuronal function. By increasing neuronal excitability, these non-neuronal cells are now implicated in the creation and maintenance of pathological pain, such as occurs in response to peripheral nerve injury. Such effects are exerted at multiple sites along the pain pathway, including at peripheral nerves, dorsal root ganglia, and spinal cord. In addition, activated glial cells are now recognized as disrupting the pain suppressive effects of opioid drugs and contributing to opioid tolerance and opioid dependence/withdrawal. While this review focuses on regulation of pain and opioid actions, such immune-neuronal interactions are broad in their implications. Such changes in neuronal function would be expected to occur wherever immune-derived substances come in close contact with neurons. PMID:17706291

Implications of prospective payment under DRGs for hospital marketing.

PubMed

Folland, S; Ziegenfuss, J T; Chao, P

1988-12-01

The authors analyze the hospital marketing implications of Medicare's prospective payment system under DRGs. They take an appropriately broad view of marketing and consider related impacts on culture, structure, and management, in addition to the traditional marketing mix. The article serves to present in one place the ideas and discussions on the subject from a wide and disparate literature. The aim throughout is to identify those marketing responses warranting recommendation. The recommendations are assembled in a concluding section. Though many of the ideas are not new, they have yet to be widely adopted by hospitals. Hence they represent untapped marketing opportunities attributable to the advent of the DRG system. The authors conclude with suggestions for future research.

Types of Cancer Research

Cancer.gov

An infographic from the National Cancer Institute (NCI) describing the four broad categories of cancer research: basic research, clinical research, population-based research, and translational research.

Assessment of Pediatric Dysphagia and Feeding Disorders: Clinical and Instrumental Approaches

ERIC Educational Resources Information Center

Arvedson, Joan C.

2008-01-01

Assessment of infants and children with dysphagia (swallowing problems) and feeding disorders involves significantly more considerations than a clinical observation of a feeding. In addition to the status of feeding in the child, considerations include health status, broad environment, parent-child interactions, and parental concerns.…

Alternative Methods by Which Basic Science Pharmacy Faculty Can Relate to Clinical Practice.

ERIC Educational Resources Information Center

Kabat, Hugh F.; And Others

1982-01-01

A panel of pharmacy faculty ranked a broad inventory of basic pharmaceutical science topics in terms of their applicability to clinical pharmacy practice. The panel concluded that basic pharmaceutical sciences are essentially applications of foundation areas in biological, physical, and social sciences. (Author/MLW)