125 research outputs found
The School Library Can Do More to Counteract Homophobia
This paper discusses the pervasiveness of homophobia in our culture and its impact on lesbian, gay, bisexual, transgender, and questioning (LGBTQ) teenagers. It argues that teacher-librarians can support LGBTQ teens by collecting and promoting young adult literature that portrays positive, realistic images of the LGBTQ community. It presents the findings of two studies - one that examined the library collections in North Carolina high schools for the inclusion of LGBTQ-themed titles and one that investigated the content of ten journals that are frequently read by teacher-librarians for articles about LGBTQ issues and collection development published since 2006. Results revealed that high school teacher-librarians are under-collecting LGBTQ-themed titles. Although 5.9 percent of American high school students identify as gay, lesbian, or bisexual, LGBTQ-themed collections in school libraries are minimal. Additionally, LGBTQ issues are rarely addressed in the scholarly journals. The paper concludes with recommendations to assist teacher-librarians in supporting LGBTQ students
Factors Associated with the Prescribing of Olanzapine, Quetiapine, and Risperidone in Patients with Bipolar and Related Affective Disorders
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90038/1/phco.31.8.806.pd
Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients
On September 14–15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed
Eighteen year weight trajectories and metabolic markers of diabetes in modernising China: which timescale is most relevant? Reply to Vistisen D and Færch K [letter]
Aims/HypothesisAlthough obesity is a major risk factor for diabetes, little is known about weight gain trajectories across adulthood, and whether they are differentially associated with metabolic markers of diabetes.MethodsWe used fasting blood samples and longitudinal weight data for 5,436 adults (5,734 observations, aged 18–66years) from the China Health and Nutrition Survey (1991–2009). Using latent class trajectory analysis, we identified different weight gain trajectories in six age and sex strata, and used multivariable general linear mixed effects models to assess elevated metabolic markers of diabetes (fasting glucose, HbA1c, HOMA-IR, insulin) across weight trajectory classes. Models were fitted within age and sex strata, and controlled for baseline weight (or baseline weight by weight trajectory interaction terms), height, and smoking habit, with random intercepts to control for community-level correlations.ResultsCompared with weight gain, classes with weight maintenance, weight loss, or a switch from weight gain to loss had lower values for metabolic markers of diabetes. These associations were stronger among younger women (aged 18–29 and 30–39years) and men (18–29years) than in older (40–66years) men and women. An exception was HOMA-IR, which showed class differences across all ages (at least p < 0.004).ConclusionTrajectory analysis identified heterogeneity in adult weight gain associated with diabetes-related metabolic markers, independent of baseline weight. Our findings suggest that variation in metabolic markers of diabetes across patterns of weight gain is masked by a homogeneous classification of weight gain.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-014-3284-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users
Mapping genetic variations to three- dimensional protein structures to enhance variant interpretation: a proposed framework
The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods
Altered Immune Responses in Rhesus Macaques Co-Infected with SIV and Plasmodium cynomolgi: An Animal Model for Coincident AIDS and Relapsing Malaria
BACKGROUND:Dual epidemics of the malaria parasite Plasmodium and HIV-1 in sub-Saharan Africa and Asia present a significant risk for co-infection in these overlapping endemic regions. Recent studies of HIV/Plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid CD4+ T cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. Here, we describe a novel rhesus macaque model for co-infection that supports and expands upon findings in human co-infection studies and can be used to identify interactions between these two pathogens. METHODOLOGY/PRINCIPAL FINDINGS:Five rhesus macaques were infected with P. cynomolgi and, following three parasite relapses, with SIV. Compared to macaques infected with SIV alone, co-infected animals had, as a group, decreased survival time and more rapid declines in markers for SIV progression, including peripheral CD4+ T cells and CD4+/CD8+ T cell ratios. The naĂŻve CD4+ T cell pool of the co-infected animals was depleted more rapidly than animals infected with SIV alone. The co-infected animals also failed to generate proliferative responses to parasitemia by CD4+ and CD8+ T cells as well as B cells while also having a less robust anti-parasite and altered anti-SIV antibody response. CONCLUSIONS/SIGNIFICANCE:These data suggest that infection with both SIV and Plasmodium enhances SIV-induced disease progression and impairs the anti-Plasmodium immune response. These data support findings in HIV/Plasmodium co-infection studies. This animal model can be used to further define impacts of lentivirus and Plasmodium co-infection and guide public health and therapeutic interventions
Development and validation of a targeted gene sequencing panel for application to disparate cancers
Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy
Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?
The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients
Legionella pneumophila Secretes a Mitochondrial Carrier Protein during Infection
The Mitochondrial Carrier Family (MCF) is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner membrane in eukaryotes. MCF proteins are characterized by six transmembrane segments that assemble to form a highly-selective channel for metabolite transport. We discovered a novel MCF member, termed Legionella nucleotide carrier Protein (LncP), encoded in the genome of Legionella pneumophila, the causative agent of Legionnaire's disease. LncP was secreted via the bacterial Dot/Icm type IV secretion system into macrophages and assembled in the mitochondrial inner membrane. In a yeast cellular system, LncP induced a dominant-negative phenotype that was rescued by deleting an endogenous ATP carrier. Substrate transport studies on purified LncP reconstituted in liposomes revealed that it catalyzes unidirectional transport and exchange of ATP transport across membranes, thereby supporting a role for LncP as an ATP transporter. A hidden Markov model revealed further MCF proteins in the intracellular pathogens, Legionella longbeachae and Neorickettsia sennetsu, thereby challenging the notion that MCF proteins exist exclusively in eukaryotic organisms
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