tbuckley/cabot-search huggingface dataset:
Rapid Evolution of Genomic Acp Complement in the melanogaster Subgroup of Drosophila
Authors: David J. Begun, Heather A. Lindfors
Journal: Molecular Biology and Evolution (2005)

Unusual properties of molecular evolution in reproduction-related Drosophila genes, including atypically rapid rates of protein evolution, support the idea that natural selection plays an important role in divergence of reproductive function in Drosophila. We used subtractive hybridization to investigate another potential side of evolution of the male reproductive transcriptome. We carried out a screen for genes with much greater transcript abundance in Drosophila simulans reproductive tracts than in Drosophila melanogaster reproductive tracts. Such genes could be present in both species but diverged dramatically in transcript abundance or could be present in D. simulans but absent from D. melanogaster. Here we report data from melanogaster subgroup species for three previously unknown accessory gland protein genes (Acps) identified in this screen. We found multiple Acps that were present in some lineages yet absent from other closely related melanogaster subgroup lineages, representing several losses of genes. An Acp that may have been lost in D. melanogaster and Drosophila erecta is segregating a null allele in Drosophila yakuba, yet shows evidence of adaptive protein evolution in contrasts of polymorphism and divergence within and between D. yakuba and its close relative, Drosophila teissieri. These data suggest that turnover of Acps occurs rapidly in Drosophila, consistent with rapid evolution of seminal fluid function.
Healthy Competition — The Why and How of “Public-Plan Choice”
Authors: Jacob S. Hacker
Journal: New England Journal of Medicine (2009)

The debate over health care reform has increasingly centered on the issue of “public-plan choice” — whether Americans younger than 65 who lack employment-based coverage should have the choice of enrolling in a new public health insurance plan that competes with regulated private plans. The idea — largely ignored in 2008 when it was endorsed by then-presidential-candidate Barack Obama — has come to dominate an increasingly polarized national debate.This polarization is unfortunate, because public-plan choice can be made to work in a way that is effective, enduring, and acceptable to key stakeholders. Far from radical or unprecedented, it is . . .
Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder
Authors: Kristiina Tammimies, Christian R. Marshall, Susan Walker, Gaganjot Kaur, Bhooma Thiruvahindrapuram, Anath C. Lionel, Ryan K. C. Yuen, Mohammed Uddin, Wendy Roberts, Rosanna Weksberg, Marc Woodbury-Smith, Lonnie Zwaigenbaum, Evdokia Anagnostou, Zhuozhi Wang, John Wei, Jennifer L. Howe, Matthew J. Gazzellone, Lynette Lau, Wilson W. L. Sung, Kathy Whitten, Cathy Vardy, Victoria Crosbie, Brian Tsang, Lia D’Abate, Winnie W. L. Tong, Sandra Luscombe, Tyna Doyle, Melissa T. Carter, Peter Szatmari, Susan Stuckless, Daniele Merico, Dimitri J. Stavropoulos, Stephen W. Scherer, Bridget A. Fernandez
Journal: JAMA (2015)

The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study.To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic.The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6).All probands underwent CMA, with WES performed for 95 proband-parent trios.The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups.Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text].Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.
The Veterans Affairs Implantable Insulin Pump Study: Effect on cardiovascular risk factors
Authors: William C Duckworth, Christopher D Saudek, Anita Giobbie-Hurder, William G Henderson, Robert R Henry, David E Kelley, Steven V Edelman, Franklin J Zieve, Robert A Adler, James W Anderson, Robert J Anderson, Bruce P Hamilton, Thomas W Donner, M Sue Kirkman, Nancy A Morgan
Journal: Diabetes Care (1998)

OBJECTIVE To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbAlc levels of ≥8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required antihypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI &amp;lt;33 and for diastolic blood pressure in patients with BMI &amp;gt;34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS IIP therapy in insulinrequiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels
Exercise training does not alter acetylcholine-induced responses in isolated pulmonary artery from rat
Authors: Y Mitani, J Maruyama, K Maruyama, M Sakurai
Journal: European Respiratory Journal (1999)

In chronic exercise-trained animals, acetylcholine (ACh)-stimulated endothelial nitric oxide (NO) release is enhanced in the systemic circulation. The purpose of the present study was to determine whether chronic exercise training also enhances NO-mediated relaxation in rat pulmonary artery. Sprague-Dawley rats were randomly divided into groups of exercise-trained and sedentary control rats. The exercise-trained rats ran on a motor-driven treadmill at 30 m x min(-1) up a 15 degree incline 10-60 min x day(-1), 5 days per week for 10 weeks, and had less body weight, lower serum total cholesterol and triglyceride levels than sedentary rats. Contraction induced by potassium chloride and prostaglandin (PG)F2alpha were similar between isolated conduit pulmonary arterial rings from sedentary and exercise-trained rats. There were no differences between PGF2alpha-precontracted rings from sedentary and exercise trained rats in both ACh and sodium nitroprusside-induced relaxations. The NO synthase inhibitor, nitro-L-arginine, suppressed ACh-induced relaxation in both sedentary and exercise-trained rats. These results suggested chronic exercise training did not alter the acetylcholine-induced endothelial NO production and release and the sensitivity of vascular smooth muscle cell to NO in isolated conduit pulmonary artery of rat.
P25 Sensitivity of the Xpert<sup>®</sup>MTB/RIF assay in bronchoalveolar lavage samples in a North West London Hospital: a useful adjunct to current diagnostic modalities
Authors: CL Ross, M Anwar, M Wickremasinghe, G Cooke, M Rebec, E Fahy, A Jepson, OM Kon
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> The Gene Xpert<sup>®</sup> MTB/RIF test has been validated in sputum samples, facilitating rapid mycobacterium tuberculosis (MTB) diagnosis with improved sensitivity compared to smear alone. Its utility in bronchoalveolar lavage (BAL) samples, in a low prevalence setting, is unclear. Our objective was to examine the sensitivity of the Xpert<sup>®</sup> test in BAL samples and evaluate its use as a rapid diagnostic test in non-productive or smear negative patients undergoing bronchoscopy. <h3>Methods</h3> We conducted a retrospective analysis of all culture-proven MTB samples acquired by BAL between 01.08.2009 and 01.06.2013, which were also sent for the Xpert<sup>®</sup> test, n = 38. We assessed the proportion of Xpert<sup>®</sup> MTB positive samples and compared these results with smear status and time to culture positivity. <h3>Results</h3> 26/38 of the culture-proven cases sent for analysis were MTB Xpert<sup>®</sup> positive, giving a sensitivity (if culture is taken as the 9gold standard9) of 68%. 17/38 samples were smear positive. Of the 21 smear negative/culture positive samples, 43% were MTB Xpert<sup>®</sup> positive. All smear positive cases were Xpert<sup>®</sup> positive. The Xpert<sup>®</sup> positive samples had a lower mean time to positivity: 11.2 days vs. 17.2 days for Xpert<sup>®</sup> negative samples. There was one case of rifampicin resistance correctly identified by Gene Xpert®, giving a lead time of 28 days vs. culture sensitivity. Incidentally 4 additional Xpert<sup>®</sup> positive samples were identified which were BAL culture negative, all in patients with clinically likely MTB, one of whom went on to culture MTB from sputum, and one of whom had necrotising granulomas on subsequent endobronchial ultrasound-guided transbronchial needle aspiration. <h3>Conclusions</h3> To our knowledge this is the largest series reported of MTB culture positive BAL samples analysed using the Xpert<sup>®</sup> MTB/RIF assay. This data supports the use of Xpert<sup>®</sup> in the diagnosis of pulmonary MTB in BAL fluid, with a sensitivity of 68% when compared to MTB culture, adding additional value to simple smear and early detection of rifampicin resistance. In fact, the true sensitivity may well be higher given the cases detected exclusively by Xpert®.
Matrilineal inheritance: New theory and analysis
Authors: John Hartung
Journal: Behavioral and Brain Sciences (1985)

Abstract In most cultures, extramarital sex is highly restricted for women. In most of those cultures, men transfer wealth to their own sons (patrilineal inheritance). In some cultures extramarital sex is not highly restricted for women, and in most of those cultures, men transfer wealth to their sisters' sons (matrilineal inheritance). Inheritance to sisters' sons ensures a man's biological relatedness to his heirs, and matrilineal inheritance has been posited as a male accommodation to cuckoldry—a paternity strategy—at least since the 15th century. However, longitudinal analysis of the cumulative effect of female extramarital sex indicates that matrilineal inheritance is most advantageous for women and would be more accurately considered a grandmaternity strategy. That is, if the probability that men's putative children are their biological children (ρ = probability of paternity) is less than 1, the probabilistic degree of relatedness between a female and her matrilineal heirs is higher than her corresponding relatedness to her patrilineal heirs. The same holds true for men only if ρ is very low (&lt; 0.46). The upshot is that for moderate levels of female extramarital sex, matrilineal inheritance, relative to patrilineal inheritance, is highly advantageous for women and disadvantageous for men. Consideration of female variance in reproductive success beyond the first generation, and of a man's network of obligation to the inclusive fitness of his relatives, suggests that although the establishment of matrilineal inheritance may require extremely high levels of female extramarital sex, once established, it is likely to be maintained at levels of ρ that reasonably characterize many societies in the ethnographic record. New analysis of previously published data shows a strong association between matrilineal inheritance and moderate to low probability of paternity, and an even stronger relationship between patrilineal inheritance and high probability of paternity.
GALACTOSYLATION OF IgG ASSOCIATED OLIGOSACCHARIDES
Authors: D.A. Isenberg, J.S. Axford, P.M. Lydyard, F.C. Hay, G.W. Rook, I.M. Roitt, N. Sumar, R.B. Parekh, R.A. Dwek, T.W. Rademacher
Journal: The Lancet (1988)
Use of insulin pump therapy at nighttime only for children 7-10 years of age with type 1 diabetes.
Authors: F R Kaufman, M Halvorson, C Kim, P Pitukcheewanont
Journal: Diabetes Care (2000)

OBJECTIVE: Because of age-related developmental and cognitive issues, children &amp;lt;10 years of age may not be able to wear an insulin pump safely when they are not under direct parental supervision. The purpose of this study was to determine if insulin pump therapy at nighttime only, when children are at home, could improve fasting and nighttime blood glucose levels without adverse effects. RESEARCH DESIGN AND METHODS: The study cohort consisted of 10 children aged 7-10 years. A randomized crossover design was used to compare nighttime-only pump usage from dinner and throughout the night, combined with a prebreakfast injection of intermediate-acting NPH and rapid-acting lispro insulin, with 3 insulin injections per day. Comparisons were made among mean blood glucose values and percentage of blood glucose levels within the target range (70-150 mg/dl) before meals, at bedtime, and at 3:00 A.M.; serum fructosamine levels; and scores on measures of adherence and fear of hypoglycemia. RESULTS: Compared with baseline levels, the use of the pump resulted in a significant decrease in the mean average (P &amp;lt; 0.001), breakfast (P &amp;lt; 0.0001), and 3:00 A.M. (P &amp;lt; 0.003) blood glucose levels. There was a decrease in the percentage of blood glucose values less than the target range (P &amp;lt; 0.01) and in fructosamine (P &amp;lt; 0.01) values and an increase in the percentage of blood glucose levels within the target range (P &amp;lt; 0.03). CONCLUSIONS: Nighttime-only insulin pump therapy may be a viable alternative that young children can use to improve glycemia when they are not capable of independently managing an insulin pump.
Skin fragility and hypohidrotic ectodermal dysplasia resulting from ablation of plakophilin 1
Authors: None McGRATH, None HOEGER, None CHRISTIANO, None McMILLAN, None MELLERIO, None ASHTON, None DOPPING-HEPENSTAL, None LAKE, None LEIGH, None HARPER, None EADY
Journal: British Journal of Dermatology (1999)

We report a 2-year-old boy with an unusual autosomal recessively inherited skin disease comprising trauma-induced skin fragility and congenital ectodermal dysplasia affecting hair, nails and sweat glands. Skin biopsy showed widening of intercellular spaces between keratinocytes and ultrastructural findings of small, poorly formed desmosomes with reduced connections to the keratin filament cytoskeleton. Immunohistochemical analysis revealed a complete absence of staining for the accessory desmosomal plaque protein plakophilin 1 (PKP1; band 6 protein). The affected individual was a compound heterozygote for null mutations on both alleles of the PKP1 gene. Both mutations occurred within the amino terminus of PKP1, the domain which normally binds the cytoskeletal keratin filament network to the cell membrane. Apart from its localization within desmosomal plaques, PKP1 may also be present within the cytoplasm and nucleus and has putative roles in signal transduction and regulation of gene activity. The clinicopathological observations in this patient demonstrate the relevance of PKP1 to desmosome formation, cutaneous cell–cell adhesion and epidermal development and demonstrate the specific manifestations of human functional knockout mutations in this gene.
First-Line Erlotinib Followed by Second-Line Cisplatin-Gemcitabine Chemotherapy in Advanced Non–Small-Cell Lung Cancer: The TORCH Randomized Trial
Authors: Cesare Gridelli, Fortunato Ciardiello, Ciro Gallo, Ronald Feld, Charles Butts, Vittorio Gebbia, Paolo Maione, Floriana Morgillo, Giovenzio Genestreti, Adolfo Favaretto, Natasha Leighl, Rafal Wierzbicki, Saverio Cinieri, Yasmin Alam, Salvatore Siena, Giampaolo Tortora, Raffaella Felletti, Ferdinando Riccardi, Gianfranco Mancuso, Antonio Rossi, Flavia Cantile, Ming-Sound Tsao, Mauro Saieg, Gilda da Cunha Santos, Maria Carmela Piccirillo, Massimo Di Maio, Alessandro Morabito, Francesco Perrone
Journal: Journal of Clinical Oncology (2012)

Erlotinib prolonged survival of unselected patients with advanced non-small-cell lung cancer (NSCLC) who were not eligible for further chemotherapy, and two phase II studies suggested it might be an alternative to first-line chemotherapy. A randomized phase III trial was designed to test whether first-line erlotinib followed at progression by cisplatin-gemcitabine was not inferior in terms of survival to the standard inverse sequence.Patients with stage IIIB (with pleural effusion or supraclavicular nodes) to IV NSCLC and performance status of 0 to 1 were eligible. With a 95% CI upper limit of 1.25 for the hazard ratio (HR) for death, 80% power, a one-sided α = .025, and two interim analyses, a sample size of 900 patients was planned.At the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study. Seven hundred sixty patients (median age, 62 years; range, 27 to 81 years) had been randomly assigned. Baseline characteristics were balanced between study arms. As of June 1, 2011, median follow-up was 24.3 months, and 536 deaths were recorded (263 in the standard treatment arm and 273 in the experimental arm). Median survival was 11.6 months (95% CI, 10.2 to 13.3 months) in the standard arm and 8.7 months (95% CI, 7.4 to 10.5 months) in the experimental arm. Adjusted HR of death in the experimental arm was 1.24 (95% CI, 1.04 to 1.47). There was no heterogeneity across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation.In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib.
Concurrent hydralazine administration prevents nitroglycerin-induced hemodynamic tolerance in experimental heart failure.
Authors: J A Bauer, H L Fung
Journal: Circulation (1991)

BACKGROUND Organic nitrates such as nitroglycerin and isosorbide dinitrate are useful in the treatment of congestive heart failure (CHF), but tolerance develops rapidly during continuous administration. Because combination therapy of nitrate and hydralazine has been shown to provide both short- and long-term benefit but nitrate alone produces hemodynamic tolerance, we questioned whether hydralazine can preserve the favorable preload effects of nitroglycerin. METHODS AND RESULTS Using an in vivo model of nitroglycerin tolerance in the CHF rat, we examined the effects of hydralazine bolus dosing during continuous nitroglycerin infusion. Continuous infusion of nitroglycerin alone (10 micrograms/min) produced initial reductions in left ventricular end-diastolic pressure of 40-50%, which returned to baseline by 8 hours (tolerance development). Coadministration of hydralazine (2 x 0.1 mg) maintained the effects of nitroglycerin infusion on left ventricular end-diastolic pressure (45% reduction at 10 hours). This hydralazine dose alone reduced left ventricular peak systolic pressure by approximately 12 +/- 3% but had no effect on left ventricular end-diastolic pressure. Hydralazine dosing did not affect steady-state plasma concentrations of nitroglycerin or metabolites, and hydralazine was unable to prevent nitroglycerin tolerance induced in vitro. CONCLUSIONS The beneficial interaction of hydralazine on the preload effects of nitroglycerin may explain the long-term clinical efficacy of hydralazine/nitrate combination in CHF. Our results also suggest that the mechanism of in vivo nitrate tolerance in CHF may be systemic rather than vascular in origin.
The Psychopathology and Treatment of Bipolar Disorder
Authors: David J. Miklowitz, Sheri L. Johnson
Journal: Annual Review of Clinical Psychology (2005)

In this chapter we review research on the diagnosis, course, etiology, and pharmacological and psychosocial treatment of bipolar disorder (BD). BD is a highly recurrent and severe illness, with high rates of suicidality and functional impairment. The disorder is heritable and appears to share susceptibility genes with schizophrenia. It is characterized by dysregulation in the dopamine and serotonin systems and by pathology in the brain systems involved in regulating emotion. Psychosocial stressors, notably life events and familial expressed emotion, significantly influence the course of the illness in the context of these vulnerabilities. Findings of randomized clinical trials indicate that psychosocial interventions enhance long-term outcomes when added to pharmacotherapy. Much remains to be clarified about the interactive contributions of genetic, neurobiological, and psychosocial factors to the course of the disorder, and the moderators and mediators of treatment effects.
Perfluorochemical Emulsion Oxygen Transport Fluids: A Clinical Review
Authors: K K Tremper, S T Anderson
Journal: Annual Review of Medicine (1985)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More