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  • 1
    Language: English
    In: Pediatrics, March 2013, Vol.131(3), pp.e789-96
    Description: To evaluate the impact of clinician-targeted computer-generated reminders on compliance with HIV care guidelines in a resource-limited setting. We conducted this randomized, controlled trial in an HIV referral clinic in Kenya caring for HIV-infected and HIV-exposed children (〈14 years of age). For children randomly assigned to the intervention group, printed patient summaries containing computer-generated patient-specific reminders for overdue care recommendations were provided to the clinician at the time of the child's clinic visit. For children in the control group, clinicians received the summaries, but no computer-generated reminders. We compared differences between the intervention and control groups in completion of overdue tasks, including HIV testing, laboratory monitoring, initiating antiretroviral therapy, and making referrals. During the 5-month study period, 1611 patients (49% female, 70% HIV-infected) were eligible to receive at least 1 computer-generated reminder (ie, had an overdue clinical task). We observed a fourfold increase in the completion of overdue clinical tasks when reminders were availed to providers over the course of the study (68% intervention vs 18% control, P 〈 .001). Orders also occurred earlier for the intervention group (77 days, SD 2.4 days) compared with the control group (104 days, SD 1.2 days) (P 〈 .001). Response rates to reminders varied significantly by type of reminder and between clinicians. Clinician-targeted, computer-generated clinical reminders are associated with a significant increase in completion of overdue clinical tasks for HIV-infected and exposed children in a resource-limited setting.
    Keywords: Computers -- Standards ; HIV Infections -- Epidemiology ; Health Resources -- Standards ; Quality of Health Care -- Standards ; Reminder Systems -- Standards
    ISSN: 00314005
    E-ISSN: 1098-4275
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  • 2
    In: Molecular Ecology, May 2013, Vol.22(9), pp.2496-2510
    Description: Although the evolutionary and ecological processes that contribute to plant invasion have been the focus of much research, investigation into the molecular basis of invasion is just beginning. Common ragweed () is an annual weed native to North merica and has been introduced to urope where it has become invasive. Using a custom‐designed imbleen oligoarray, we examined differences in gene expression between five native and six introduced populations of common ragweed in three different environments (control, light stress and nutrient stress), as well as two different time points. We identified candidate genes that may contribute to invasiveness in common ragweed based on differences in expression between native and introduced populations from urope. Specifically, we found 180 genes where range explained a significant proportion of the variation in gene expression and a further 103 genes with a significant range by treatment interaction. Several of these genes are potentially involved in the metabolism of secondary compounds, stress response and the detoxification of xenobiotics. Previously, we found more rapid growth and greater reproductive success in introduced populations, particularly in benign and competitive (light stress) environments, and many of these candidate genes potentially underlie these growth differences. We also found expression differences among populations within each range, reflecting either local adaptation or neutral processes, although no associations with climate or latitude were identified. These data provide a first step in identifying genes that are involved with introduction success in an aggressive annual weed.
    Keywords: Ambrosia Artemisiifolia ; Common Ragweed ; Gene Expression ; Invasion Biology ; Microarray ; Stress
    ISSN: 0962-1083
    E-ISSN: 1365-294X
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  • 3
    In: Nature, 2018
    Description: Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
    Keywords: DNA Methylation ; Tumors ; Standardization ; Data Processing ; Classification ; Methylation ; Brain Cancer ; Bioinformatics ; Cancer ; Generalized Linear Models ; DNA Methylation ; Diagnosis ; Tumors ; Genomes ; Classification ; Central Nervous System ; Central Nervous System ; Diagnosis ; Cancer ; Learning Algorithms ; Diagnostic Software ; Data Processing ; Tumors ; Central Nervous System ; Gene Expression ; Standardization ; Classification ; Cancer ; Classifiers ; Classification ; Clinical Trials ; Deoxyribonucleic Acid–DNA ; Probability ; Diagnostic Systems ; Nervous System ; Methylation ; Data Processing ; Tumors ; Data Processing ; Deoxyribonucleic Acid–DNA ; Deoxyribonucleic Acid–DNA ; World Health Organization;
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 4
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(5), p.e0126211
    Description: Mycobacterial tuberculosis (Mtb) is able to preserve its intrabacterial pH (pHIB) near neutrality in the acidic phagosomes of immunologically activated macrophages and to cause lethal pathology in immunocompetent mice. In contrast, when its ability to maintain pHIB homeostasis is genetically compromised, Mtb dies in acidic phagosomes and is attenuated in the mouse. Compounds that phenocopy the genetic disruption of Mtb's pHIB homeostasis could serve as starting points for drug development in their own right or through identification of their targets. A previously reported screen of a natural product library identified a phloroglucinol, agrimophol, that lowered Mtb's pHIB and killed Mtb at an acidic extrabacterial pH. Inability to identify agrimophol-resistant mutants of Mtb suggested that the compound may have more than one target. Given that polyphenolic compounds may undergo covalent reactions, we attempted an affinity-based method for target identification. The structure-activity relationship of synthetically tractable polyhydroxy diphenylmethane analogs with equivalent bioactivity informed the design of a bioactive agrimophol alkyne. After click-chemistry reaction with azido-biotin and capture on streptavidin, the biotinylated agrimophol analog pulled down the Mtb protein Rv3852, a predicted membrane protein that binds DNA in vitro. A ligand-protein interaction between agrimophol and recombinant Rv3852 was confirmed by isothermal calorimetry (ITC) and led to disruption of Rv3852's DNA binding function. However, genetic deletion of rv3852 in Mtb did not phenocopy the effect of agrimophol on Mtb, perhaps because of redundancy of its function.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 5
    In: Research in Nursing & Health, August 2014, Vol.37(4), pp.302-311
    Description: This study examined whether cognitive distortions (i.e., assimilated and overaccommodated thoughts) and realistic (i.e., accommodated) thoughts assessed from impact statements written 5–10 years after completing cognitive processing therapy (CPT) accurately predicted posttreatment maintenance or decline in treatment gains during the same period.The sample included 50 women diagnosed with posttraumatic stress disorder (PTSD) secondary to rape who participated in a randomized clinical trial of CPT for PTSD. Cognitions were assessed via coding and analyses of participants' written impact statements at three time points: beginning of treatment, end of treatment, and at 5–10 years follow-up. Primary mental health outcomes were symptoms of PTSD (Clinician-Administered PTSD Scale) and depression (Beck Depression Inventory).Changes in trauma-related beliefs between the end of treatment and long-term follow-up were associated with concomitant changes in PTSD and depression symptoms (effect sizes ranging from r = .35–.54). Declines in accommodated thinking and increases in overaccommodated thinking were associated with elevations in symptomatology. Improvement in accommodated thinking and declines in overaccommodated thinking were associated with lower PTSD and depression symptoms during this same time period.Findings provided support for the role of changes in accommodated and overaccommodated thinking being associated with level of PTSD and depression many years after participating in CPT. •Cognitive improvments during cognitive processing therapy were maintained 5-10 years after treatment.•Declines in accommodation and resumption of overaccommodation were associated with increased symptoms following treatment.•Associations between cognition types and symptoms grew stronger during treatment and persisted 5-10 years after treatment.
    Keywords: Female Veterans ; Department Of Veterans Affairs ; Domestic Violence ; Screening ; Counseling ; Qualitative Research
    ISSN: 0160-6891
    ISSN: 00057967
    E-ISSN: 1098-240X
    E-ISSN: 1873622X
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  • 6
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 02 August 2016, Vol.113(31), pp.E4523-30
    Description: The rising incidence of antimicrobial resistance (AMR) makes it imperative to understand the underlying mechanisms. Mycobacterium tuberculosis (Mtb) is the single leading cause of death from a bacterial pathogen and estimated to be the leading cause of death from AMR. A pyrido-benzimidazole, 14, was reported to have potent bactericidal activity against Mtb. Here, we isolated multiple Mtb clones resistant to 14. Each had mutations in the putative DNA-binding and dimerization domains of rv2887, a gene encoding a transcriptional repressor of the MarR family. The mutations in Rv2887 led to markedly increased expression of rv0560c. We characterized Rv0560c as an S-adenosyl-L-methionine-dependent methyltransferase that N-methylates 14, abolishing its mycobactericidal activity. An Mtb strain lacking rv0560c became resistant to 14 by mutating decaprenylphosphoryl-β-d-ribose 2-oxidase (DprE1), an essential enzyme in arabinogalactan synthesis; 14 proved to be a nanomolar inhibitor of DprE1, and methylation of 14 by Rv0560c abrogated this activity. Thus, 14 joins a growing list of DprE1 inhibitors that are potently mycobactericidal. Bacterial methylation of an antibacterial agent, 14, catalyzed by Rv0560c of Mtb, is a previously unreported mechanism of AMR.
    Keywords: Antimicrobial Resistance ; Arabinogalactan Synthesis ; Methyltransferase ; Transcription Factor ; Drug Resistance, Bacterial ; Antitubercular Agents -- Metabolism ; Bacterial Proteins -- Metabolism ; Mycobacterium Tuberculosis -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 7
    Language: English
    In: Heart Rhythm, 2011, Vol.8(11), pp.1788-1795
    Description: Autoimmune diseases are associated with significant morbidity and mortality, afflicting about 5% of the US population. They encompass a wide range of disorders that affect all organs of the human body and have a predilection for women. In the past, autoimmune pathogenesis was not thought to be a major mechanism for cardiovascular disorders, and potential relationships remain understudied. However, accumulating evidence suggests that a number of vascular and cardiac conditions are autoimmune mediated. Recent studies indicate that autoantibodies play an important role in the development of cardiac arrhythmias, including atrial fibrillation, modulation of autonomic influences on heart rate and rhythm, conduction system abnormalities, and ventricular arrhythmias. This article will review the current evidence for the role of autoantibodies in the development of cardiac arrhythmias.
    Keywords: Atrial Fibrillation ; Autoantibodies ; Cardiac Arrhythmias ; Cardiomyopathy ; Complete Heart Block ; Sudden Cardiac Death ; Medicine
    ISSN: 1547-5271
    E-ISSN: 1556-3871
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  • 8
    Language: English
    In: Journal of Substance Use, 03 May 2016, Vol.21(3), pp.263-267
    Description: Ratings of the perceived personality (Five-Factor Model) of an anabolic-androgenic steroid(s) (AAS) user, an erythropoietin (EPO) user, a protein powder user and a nonuser of these ergogenic aids were investigated. The sample of 328 (236 females) non-substance use participants providing the...
    Keywords: Anabolic-Androgenic Steroids ; Doping ; Neuroticism ; Five-Factor Model
    ISSN: 1465-9891
    E-ISSN: 1475-9942
    Source: Taylor & Francis Medical Library
    Source: Taylor & Francis (Taylor & Francis Group)
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  • 9
    Language: English
    In: Home Health Care Services Quarterly, 01 October 2016, Vol.35(3-4), pp.172-181
    Description: Telemedicine holds promise in bridging the gap between homebound patients and high quality health care, but uptake of such technology remains limited. Qualitative interviews conducted with 17 homebound patients found two major barriers to telemedicine. First, participants who lack familiarity...
    Keywords: Community and Home Care ; Engaged Technology ; Home Health Care ; Literacy Technology ; Service Delivery/Utilization ; Technology ; Public Health
    ISSN: 0162-1424
    E-ISSN: 1545-0856
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  • 10
    Language: English
    In: Journal of geriatric cardiology : JGC, September 2011, Vol.8(3), pp.184-94
    Description: Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intracellular Ca(2+) overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhythmics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient's physiology, disease processes, and medication regimen.
    Keywords: Aging ; Antiarrhythmic Drugs ; Cardiac Electrophysiology ; Ion Channels ; Pharmacodynamics ; Pharmacokinetics ; Polypharmacy
    ISSN: 1671-5411
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