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The Synthesis of Multi-Functionalized 1,3-Oxazin-4-ones from Donor-Acceptor Cyclopropanes. - The Journal of organic chemistry
A series of electronically diverse imines were found to readily react with various donor-acceptor cyclopropyl acid chlorides, with complete chemoselectivity, to form 1,3-oxazin-4-ones in moderate yields (25-48% over 2 steps). Select oxazinones underwent a base induced rearrangement to afford the corresponding cycloheptene-fused oxazinones in good yields (up to 70%).
An avian-only Filippov model incorporating culling of both susceptible and infected birds in combating avian influenza. - Journal of mathematical biology
Depopulation of birds has always been an effective method not only to control the transmission of avian influenza in bird populations but also to eliminate influenza viruses. We introduce a Filippov avian-only model with culling of susceptible and/or infected birds. For each susceptible threshold level [Formula: see text], we derive the phase portrait for the dynamical system as we vary the infected threshold level [Formula: see text], focusing on the existence of endemic states; the endemic states are represented by real equilibria, pseudoequilibria and pseudo-attractors. We show generically that all solutions of this model will approach one of the endemic states. Our results suggest that the spread of avian influenza in bird populations is tolerable if the trajectories converge to the equilibrium point that lies in the region below the threshold level [Formula: see text] or if they converge to one of the pseudoequilibria or a pseudo-attractor on the surface of discontinuity. However, we have to cull birds whenever the solution of this model converges to an equilibrium point that lies in the region above the threshold level [Formula: see text] in order to control the outbreak. Hence a good threshold policy is required to combat bird flu successfully and to prevent overkilling birds.
Updates on the genetics and the clinical impacts on phaeochromocytoma and paraganglioma in the new era. - Critical reviews in oncology/hematology
Genetic mutations of phaeochromocytoma (PCC) and paraganglioma (PGL) are mainly classified into two major clusters. Cluster 1 mutations are involved with the pseudo hypoxic pathway and comprised of PHD2, VHL, SDHx, IDH, HIF2A, MDH2 and FH mutated PCC/PGL. Cluster 2 mutations are associated with abnormal activation of kinase signalling pathways and included mutations of RET, NF1, KIF1BÎ², MAX and TMEM127. In addition, VHL, SDHx (cluster 1 genes) and RET, NF1 (cluster 2 genes) germline mutations are involved in the neuronal precursor cell pathway in the pathogeneses of PCC/PGL. Also, GDNF, H-ras, K-ras, GNAS, CDKN2A (p16), p53, BAP1, BRCA1&2, ATRX and KMT2D mutations have roles in the development of PCC/PGLs. Overall, known genetic mutations account for the pathogenesis of approximately 60% of PCC/PGLs. Genetic mutations, pathological parameters and biochemical markers are used for better prediction of the outcome of patients with this group of tumours. Immunohistochemistry and gene sequencing can ensure a more effective detection, prediction of malignant potential and treatment of PCC/PCLs.Copyright Â© 2016 Elsevier Ireland Ltd. All rights reserved.
A questionnaire identifying four key components of patient satisfaction with physician communication. - Patient education and counseling
To improve efficiency and retain the 4 factors of a reliable, valid interview satisfaction questionnaire (ISQ).105 residents conducted 301 patient-centered interviews with 10 simulated patients (SP). SPs portrayed three scenarios for each resident and completed the ISQ and the Communication Assessment Tool (CAT) after each. A confirmatory factor analysis (CFA) of the ISQ and CAT determined which items had >0.5 factor loadings and <0.1 error, criteria for retaining items in a shortened scale.After the CFA, 13 items were deleted resulting in a 12-item scale (RMSE=0.06) that confirmed the initial 4 factor structure of satisfaction with: open-endedness, empathy, confidence in the resident, and general. Scale reliability of each factor was high (Cronbach's alpha ranged from .74 to .93). Demonstrating concurrent validity, all four factors of the ISQ correlated highly with the one-factor CAT (r>.7, p<.001), and the second order unidimensional ISQ scale also correlated highly with the CAT (r=.83, p<.001).The ISQ is an efficient, reliable, and valid instrument that uniquely deconstructs satisfaction with the patient-physician interaction into 4 key components.The 4 components provide a means for better understanding poor satisfaction results.Copyright Â© 2016 Elsevier Ireland Ltd. All rights reserved.
What Predicts an Advanced-Stage Diagnosis of Breast Cancer? Sorting out the Influence of Method of Detection, Access to Care and Biological Factors. - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Multiple studies have yielded important findings regarding the determinants of an advanced-stage diagnosis of breast cancer. We seek to advance this line of inquiry through a broadened conceptual framework and accompanying statistical modeling strategy that recognize the dual importance of access-to-care and biological factors on stage.The CDC-sponsored Breast and Prostate Cancer Data Quality and Patterns of Care Study yielded a 7-state, cancer registry-derived population-based sample of 9,142 women diagnosed with a first primary in situ or invasive breast cancer in 2004. The likelihood of advanced-stage cancer (AJCC IIIB, IIIIC, or IV) was investigated through multivariable regression modeling, with base-case analyses using the method of instrumental variables (IV) to detect and correct for possible selection bias. The robustness of base-case findings were examined through extensive sensitivity analyses.Advanced-stage disease was negatively associated with detection by mammography (p<0.001) and age<50 (p<0.001), and positively related to black race (p=0.066), not being privately insured [Medicaid (p=0.012), Medicare (p=0.036), uninsured (p=0.069)], being single (p=0.058), BMI>40 (p<0.001), a HER2 Type tumor (p<0.001), and tumor grade not well differentiated (p<0.001). This IV model detected and adjusted for significant selection effects associated with method of detection (p=0.017). Sensitivity analyses generally supported these base-case results.Through our comprehensive modeling strategy and multiple sensitivity analyses, we provide new estimates of the magnitude and robustness of the determinants of advanced-stage breast cancer.Statistical approaches frequently used to address observational data biases in treatment-outcome studies can be applied similarly in analyses of the determinants of stage-at-diagnosis.Copyright Â© 2016, American Association for Cancer Research.
Eye movement disorders are an early manifestation of CACNA1A mutations in children. - Developmental medicine and child neurology
The alpha-1 isoform of the calcium channel gene is expressed abundantly in neuronal tissue, especially within the cerebellum. Mutations in this gene may manifest with hemiplegic migraine, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) in adults. There are reports of children with CACAN1A mutations presenting with paroxysmal tonic upgaze, abnormal saccades and congenital nystagmus as well as severe forms of hemiplegic migraine. The aim of this study was to review the clinical presentation and subsequent course of all children with a CACNA1A mutation who presented to a tertiary children's hospital.We reviewed retrospectively nine children with a proven CACNA1A mutation who presented to the Children's Hospital at Westmead between 2005-2015. The initial and subsequent clinical presentation, radiological features and molecular genetic profile of each child was reviewed.Nine children presented to out institute over a 10 year period; six were female and three male. The median age of presentation was 1.2 years. Eye movement disorders were the presenting feature in eight children. Three of these children later presented with severe hemiplegic migraine episodes often requiring ICU care. Affected children also had developmental delay and developed classical hemiplegic migraine, episodic ataxia and seizures. Calcium channel blockers were used with some efficacy in preventing severe HM episodes.Eye movement disorders are an early manifestation of CACNA1A mutations in children. Improved recognition of the CACNA1A phenotype in childhood is important for early diagnosis, counselling and appropriate emergency management. There is some early evidence that calcium channel blockers may be an effective prophylactic agent for the severe hemiplegic migraine episodes.Â© 2016 Mac Keith Press.
Trimethylamine-The Extracorporeal Envoy. - Chemical senses
One of the most widespread and efficient mechanisms that has evolved to enable communication between discrete and spatially separate living organisms is the use of specific chemical messengers. The organoleptic properties of certain molecules, even at concentrations that do not necessarily evoke a conscious response, have been exploited to transmit information across relatively large distances. The trimethylated derivative of ammonia is one such molecule that is ideally suited to this function and several species are known to respond to its presence. This review uniquely collects together and integrates widely dispersed data to show that trimethylamine also may serve a communicatory role in man, with its influence extending outside of the body.Â© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: email@example.com.
Cancer screening in the United States, 2016: A review of current American Cancer Society guidelines and current issues in cancer screening. - CA: a cancer journal for clinicians
Answer questions and earn CME/CNE Each year the American Cancer Society (ACS) publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, we summarize current ACS cancer screening guidelines, including the update of the breast cancer screening guideline, discuss quality issues in colorectal cancer screening and new developments in lung cancer screening, and provide the latest data on utilization of cancer screening from the National Health Interview Survey. CA Cancer J Clin 2016. Â© 2016 American Cancer Society.Â© 2016 American Cancer Society.
CYP450 genotype and pharmacogenetic association studies: a critical appraisal. - Pharmacogenomics
Despite strong pharmacological support, association studies using genotype-predicted phenotype as a variable have yielded conflicting or inconclusive evidence to promote personalized pharmacotherapy. Unless the patient is a genotypic poor metabolizer, imputation of patient's metabolic capacity (or metabolic phenotype), a major factor in drug exposure-related clinical response, is a complex and highly challenging task because of limited number of alleles interrogated, population-specific differences in allele frequencies, allele-specific substrate-selectivity and importantly, phenoconversion mediated by co-medications and inflammatory co-morbidities that modulate the functional activity of drug metabolizing enzymes. Furthermore, metabolic phenotype and clinical outcomes are not binary functions; there is large intragenotypic and intraindividual variability. Therefore, the ability of association studies to identify relationships between genotype and clinical outcomes can be greatly enhanced by determining phenotype measures of study participants and/or by therapeutic drug monitoring to correlate drug concentrations with genotype and actual metabolic phenotype. To facilitate improved analysis and reporting of association studies, we propose acronyms with the prefixes 'g' (genotype-predicted phenotype) and 'm' (measured metabolic phenotype) to better describe this important variable of the study subjects. Inclusion of actually measured metabolic phenotype, and when appropriate therapeutic drug monitoring, promises to reveal relationships that may not be detected by using genotype alone as the variable.
High prevalence of raised lipoprotein(a) in patients with refractory angina. - Global cardiology science & practice
Angina that is refractory to conventional medical therapy and revascularisation, remains challenging to manage and poses significant burden to patients. Elevated lipoprotein(a) [Lp(a)] has emerged as an important independent cardiovascular risk factor and predictor of adverse outcomes in atherosclerotic disease. The prevalence of raised Lp(a) amongst patients with refractory angina has not yet been defined.To establish the prevalence of raised [Lp(a)] >500Â mg/L in patients with refractory angina.We conducted an epidemiological screening pilot study in 75 patients with refractory angina from a UK tertiary cardiac centre. We determined the proportion of the cohort with raised Lp(a) >500Â mg/L using an isoform-insensitive method. In addition, a full fasting lipid profile (including: LDL cholesterol, HDL cholesterol, total cholesterol to HDL ratio and triglycerides) was obtained. Patients were also asked about the presence of conventional cardiovascular risk factors.Our study demonstrated that 60% of the 75 patients with refractory angina had raised Lp(a) levels of >500Â mg/L. The median and inter-quartile range of Lp(a) values were 771Â mg/L (162Â mg/L,1260Â mg/L) respectively.This high prevalence of raised Lp(a) detected in our cohort with refractory angina may suggest a causal role. Further research is necessary to confirm this association and prospective studies are needed to explore the potential therapeutic benefit of Lp(a) reduction in patients with refractory angina.
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416 Division St South Charleston, WV 25309
4619 Kanawha Ave., Sw
4605 Maccorkle Ave Sw
Charleston, WV 25309
4607 Maccorkle Ave Ste 400
4619 Kanawha Ave Sw
4501 Maccorkle Ave Sw Suite 301
1109 Jefferson Rd
S Charleston, WV 25309