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(E)-5-[3-Cyano-2-(dicyanomethylene)-1-oxaspiro[4.5]dec-3-en-4-yl]-3-(1-methyl-1,4-dihydropyridin-4-ylidene)pent-4-en-1-yl 3,5-bis(benzyloxy)benzoate
Graeme J. Gainsford,David J. Clarke,Andrew J. Kay
Acta Crystallographica Section E , 2013, DOI: 10.1107/s1600536812050532
Abstract: In the title compound, C45H40N4O5, the cyclohexane entity on the (3-cyano-2,5-dihydrofuran-2-ylidene)propanedinitrile group, which replaces the usual dimethyl substituents, has not perturbed the delocalization geometry significantly. Weak intermolecular interactions, viz. C—H...N(cyano), C—H...O(ether), C—H...π and π–π [between the aromatic rings with the shortest centroid–centroid distance of 3.603 (3) ], consolidate the crystal packing, which exhibits voids of 57 3.
In vivo MRI Characterization of Progressive Cardiac Dysfunction in the mdx Mouse Model of Muscular Dystrophy
Daniel J. Stuckey, Carolyn A. Carr, Patrizia Camelliti, Damian J. Tyler, Kay E. Davies, Kieran Clarke
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0028569
Abstract: Aims The mdx mouse has proven to be useful in understanding the cardiomyopathy that frequently occurs in muscular dystrophy patients. Here we employed a comprehensive array of clinically relevant in vivo MRI techniques to identify early markers of cardiac dysfunction and follow disease progression in the hearts of mdx mice. Methods and Results Serial measurements of cardiac morphology and function were made in the same group of mdx mice and controls (housed in a non-SPF facility) using MRI at 1, 3, 6, 9 and 12 months after birth. Left ventricular (LV) and right ventricular (RV) systolic and diastolic function, response to dobutamine stress and myocardial fibrosis were assessed. RV dysfunction preceded LV dysfunction, with RV end systolic volumes increased and RV ejection fractions reduced at 3 months of age. LV ejection fractions were reduced at 12 months, compared with controls. An abnormal response to dobutamine stress was identified in the RV of mdx mice as early as 1 month. Late-gadolinium-enhanced MRI identified increased levels of myocardial fibrosis in 6, 9 and 12-month-old mdx mice, the extent of fibrosis correlating with the degree of cardiac remodeling and hypertrophy. Conclusions MRI could identify cardiac abnormalities in the RV of mdx mice as young as 1 month, and detected myocardial fibrosis at 6 months. We believe these to be the earliest MRI measurements of cardiac function reported for any mice, and the first use of late-gadolinium-enhancement in a mouse model of congenital cardiomyopathy. These techniques offer a sensitive and clinically relevant in vivo method for assessment of cardiomyopathy caused by muscular dystrophy and other diseases.
Osteoporosis: A Disease of Men  [PDF]
Anu Garg, Samantha Kay
Health (Health) , 2018, DOI: 10.4236/health.2018.101005
Abstract: Objective: The goal of this study was to evaluate osteoporosis screening practices in male patients aged 70 and older. Methods: A survey-based study was carried out over six months at an academic primary care institution in the Midwest. Results: Seventy-nine male patients and fifteen primary care physicians were surveyed. Less than 10% of males recalled being screened for osteoporosis. Two-thirds of physicians reported regularly screening males for osteoporosis. Conclusion: Elderly male patients are overwhelmingly under-screened and undertreated for osteoporosis.
The Internet of Things and Next-generation Public Health Information Systems  [PDF]
Robert Steele, Andrew Clarke
Communications and Network (CN) , 2013, DOI: 10.4236/cn.2013.53B1002
Abstract: The Internet of things has particularly novel implications in the area of public health. This is due to (1) The rapid and widespread adoption of powerful contemporary Smartphone’s; (2) The increasing availability and use of health and fitness sensors, wearable sensor patches, smart watches, wireless-enabled digital tattoos and ambient sensors; and (3) The nature of public health to implicitly involve connectivity with and the acquisition of data in relation to large numbers of individuals up to population scale. Of particular relevance in relation to the Internet of Things (IoT) and public health is the need for privacy and anonymity of users. It should be noted that IoT capabilities are not inconsistent with maintaining privacy, due to the focus of public health on aggregate data not individual data and broad public health interventions. In addition, public health information systems utilizing IoT capabilities can be constructed to specifically ensure privacy, security and anonymity, as has been developed and evaluated in this work. In this paper we describe the particular characteristics of the IoT that can play a role in enabling emerging public health capabilities; we describe a privacy-preserving IoT-based public health information system architecture; and provide a privacy evaluation.
Prediction in several conventional contexts
Bertrand Clarke,Jennifer Clarke
Statistics Surveys , 2012,
Abstract: We review predictive techniques from several traditional branches of statistics. Starting with prediction based on the normal model and on the empirical distribution function, we proceed to techniques for various forms of regression and classification. Then, we turn to time series, longitudinal data, and survival analysis. Our focus throughout is on the mechanics of prediction more than on the properties of predictors.
Difficult-to-Treat-Depression and GPs’ Role: Perceptions of Psychiatry Registrars  [PDF]
Kay M. Jones, Leon Piterman
Open Journal of Psychiatry (OJPsych) , 2014, DOI: 10.4236/ojpsych.2014.44037
Abstract: Introduction: For patients, GPs are the most accessible medical resource in the community and are the gatekeepers to other community resources including psychiatrists. Qualifying as a psychiatrist in Australia involves completing a five-year training program that includes rotations in hospitals and community settings. The aims of this research were to 1) explore psychiatry registrars’ perceptions of difficult-to-treat-depression (DTTD) and 2) what they thought about the GPs’ role in this regard. Methods: A semi-structured interview schedule comprising six questions was used; 10 psychiatry registrars (6 females, 4 males) participated in a one-and-half-hour focus group. All were in their final year of training and undertaking a training post in a public hospital in Melbourne, Australia. Data were analysed using the Framework Method. Findings: Similar to GPs and GP trainees, psychiatry registrars’ perceptions and understanding of DTTD varied. While acknowledging limited experience in diagnosis and management, issues important to them included the utility of labels such as DTTD; patients distressed because of another diagnosis, substance abuse and/or life problems, the importance of accurate histories and notes, cost and limited availability of services particularly in the private sector, prescribing regimens, referring to allied health professionals, and suggesting/prescribing non pharmacological and/or complementary treatment. Also what was of concern was communication, both between health professionals and between health professionals and patients. Consensus was that treating depression in general practice is one of the hardest things for GPs to manage but there was value in using mental health plans. Discussion and Conclusion: While this cohort was small in number with limited experience, this study is the first to contribute to the literature that provides some insight into psychiatry registrars’ experiences and perceptions of DTTD. Outcomes may have implications for thepsychiatry training program and GPs who diagnose and manage patients with mental health problems.
Difficult-to-Treat-Depression and GPs’ Role: Perceptions of Psychologists  [PDF]
Kay M. Jones, Leon Piterman
Open Journal of Psychiatry (OJPsych) , 2015, DOI: 10.4236/ojpsych.2015.51005
Abstract: Introduction: Since the Australian Government introduced the “Better Access to Mental Health Services” program in 2006, psychiatrists, psychologists and general practitioners (GPs) have become increasingly involved in service provision for people seeking help with mental health problems. The aim of this research was to a) explore psychologists’ perceptions of difficult to treat depression (DTTD) and b) explore what they thought about the GPs’ role in managing these patient given that most patients are referred to psychologist by GPs. Methods: A previously developed semi-structured interview schedule comprising six questions was used. Seven psychologists participated in a focus group held in Melbourne. Data were analysed using the framework method. Findings, including Discussion: While psychologists understood the term DTTD it was suggested that using different terms may limit understanding between health professionals. Rather than diagnosing, psychologists were more likely to conduct further assessment contextually to confirm GPs’ diagnosis. Communication with GPs was important, particularly when managing “long-term” and suicidal patients. Management included cognitive and behavioural interventions and referring to other mental health services, psychiatrists and/or other allied health professionals. Referral to psychiatrists could be difficult because of limited availability and for some patients, prohibitive costs. Although psychologists discussed non-pharmacological and/or complementary treatment options with patients, they were more likely to rely on GPs to discuss/prescribe these options. Conclusion: While generalisability may be limited, this study is the first to document some understanding of psychologists perceptions of DTTD and the importance of GPs and other health professionals’ role in managing this patient cohort.
Interprofessional Communication and Relationships in the Management of “Difficult to Treat” Depression: Perceptions of the Role of General Practitioners  [PDF]
Kay M. Jones, Leon Piterman
Open Journal of Psychiatry (OJPsych) , 2015, DOI: 10.4236/ojpsych.2015.53029
Abstract: Background: Team based care is an essential ingredient of chronic disease management including chronic mental illness. Effective health care teams include members who have defined, yet intersecting roles, where mutual respect characterises professional interaction and the patient’s well-being is central. The aim was to explore the perception of psychologists, psychiatry registrars and psychiatrists with respect to GPs’ role in managing difficult-to-treat-depression (DTTD). Methods: A previously developed semi-structured interview schedule comprising six questions was used. Thirty-two health professionals participated. Data were analysed using the Framework method. Findings: Four main themes emerged: 1) The team approach was important, particularly to ensure information accuracy and/or when responding to patient needs and pressures; 2) Referrals, usually generated by GPs can be a vehicle for other health professionals to provide advice to the GP; 3) Availability and accessibility often depended on health professionals work location and knowing how to navigate the system; 4) Limited availability of government funding impacts on patients’ accessibility to health professionals. Discussion: Interprofessional relationships were described as paramount. Appropriate and timely referrals are integral to patient management, regardless of challenges. Ongoing challenges include program funding, workforce numbers and costs to patients. Improvement to mental health care access was noted, even for patients among relatively disadvantaged groups and those receiving Medicare Benefits Schedule-subsidised services. Conclusion: Despite adequate GP/specialist communication, the delivery of optimal team based care to patients with difficult-to-treat depression is compromised by lack of access to specialised services and inadequate funding.
Pathobiochemical Changes in Diabetic Skeletal Muscle as Revealed by Mass-Spectrometry-Based Proteomics
Kay Ohlendieck
Journal of Nutrition and Metabolism , 2012, DOI: 10.1155/2012/893876
Abstract: Insulin resistance in skeletal muscle tissues and diabetes-related muscle weakness are serious pathophysiological problems of increasing medical importance. In order to determine global changes in the protein complement of contractile tissues due to diabetes mellitus, mass-spectrometry-based proteomics has been applied to the investigation of diabetic muscle. This review summarizes the findings from recent proteomic surveys of muscle preparations from patients and established animal models of type 2 diabetes. The potential impact of novel biomarkers of diabetes, such as metabolic enzymes and molecular chaperones, is critically examined. Disease-specific signature molecules may be useful for increasing our understanding of the molecular and cellular mechanisms of insulin resistance and possibly identify new therapeutic options that counteract diabetic abnormalities in peripheral organ systems. Importantly, the biomedical establishment of biomarkers promises to accelerate the development of improved diagnostic procedures for characterizing individual stages of diabetic disease progression, including the early detection of prediabetic complications.
Biosimilars: a regulatory perspective from America
Jonathan Kay
Arthritis Research & Therapy , 2011, DOI: 10.1186/ar3310
Abstract: Over the past decade, the availability of targeted biological therapies has revolutionized the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis and holds promise to expand treatment options for patients with systemic lupus erythematosus or other systemic autoimmune diseases. However, the significant cost of these medications creates a major barrier that limits universal access to these effective therapeutic agents. Whereas generic equivalents are commercially available for many small-molecule medications, such lower-cost alternatives to targeted biological therapies are not yet available in the US or the European Union.Biopharmaceuticals are medications, predominantly proteins, that are manufactured using live organisms. These include blood and plasma products, non-recombinant proteins purified from their natural sources, recombinant proteins and monoclonal antibodies produced in cell culture, vaccines, and cultured cellular and tissue products [1]. 'Follow-on' protein products are those 'manufactured using biotechnology or derived from natural sources that are intended to be sufficiently similar to a' biopharmaceutical 'product or products' already approved by a regulatory agency [2]. These are called biosimilars and also have been referred to as biogenerics or biocomparables. A biosimilar product is defined in Section 351 of the Public Health Service (PHS) Act (42 USC § 262) as one which is 'highly similar to the reference product notwithstanding minor differences in clinically inactive components' and for which there are 'no clinically meaningful differences between the bio-logical product and the reference product in terms of safety, purity and potency of the product' [1]. The term 'biogeneric' is now obsolete because, unlike small-molecule generic drugs, a biosimilar is never identical to its reference product.A biosimilar etanercept, manufactured in China by CP Guojian Pharmaceutical Co., Ltd. (Shanghai), is already being mark
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