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"Cook, Daniel"
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The cross-sectional association between state-level public health funding per capita and physical health among adults in the United States
This study examined the association between state-level public health funding per capita and the odds of poor physical health.
Cross-sectional.
Data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS) were used. Participants' self-reported physical health was reported using the CDC Healthy Days Core Module. State-level public health funding per capita was obtained from the State Health Access Data Assistance Center website. Multilevel logistic regression was used to adjust for self-reported individual-level characteristics and state-level characteristics from the 2018 American Community Survey. We also tested whether household income or education attainment moderated any observed associations.
A one SD increase in state-level public health funding per capita was not associated with the odds ≥ 14 days of poor physical health (OR = 0.96, 95% CI: 0.90, 1.01). However, heterogeneity across household income was observed. Greater public health funding per capita was associated with lower predicted probabilities of reporting ≥ 14 days of poor physical health among respondents from low household income backgrounds ( <$35,000 USD) compared to participants with high household incomes (>$75,000 USD). No associations were observed among those with moderate ($35,000 - $70,000 USD) household incomes. A similar finding was observed among participants with less than high school education when compared to participants with post-secondary education.
Greater state-level public health funding per capita appears to have a protective association against reporting ≥ 14 days of poor physical health in individuals with lower household incomes and may be helpful in reducing health inequities. Future research is needed to determine whether this association is causal.
Journal Article
The Cambridge companion to Gulliver's travels
\"Approaching Gulliver's Travels from a variety of critical perspectives, this Cambridge Companion provides students and researchers with a multifaceted understanding of the enduring legacy of one of literature's most profound and provocative works of fiction in the lead-up to the 300th anniversary of its first publication\"-- Provided by publisher.
BOOK
Metastatic triple negative breast cancer adapts its metabolism to destination tissues while retaining key metabolic signatures
Triple negative breast cancer (TNBC) metastases are assumed to exhibit similar functions in different organs as in the original primary tumor. However, studies of metastasis are often limited to a comparison of metastatic tumors with primary tumors of their origin, and little is known about the adaptation to the local environment of the metastatic sites. We therefore used transcriptomic data and metabolic network analyses to investigate whether metastatic tumors adapt their metabolism to the metastatic site and found that metastatic tumors adopt a metabolic signature with some similarity to primary tumors of their destinations. The extent of adaptation, however, varies across different organs, and metastatic tumors retain metabolic signatures associated with TNBC. Our findings suggest that a combination of anti-metastatic approaches and metabolic inhibitors selected specifically for different metastatic sites, rather than solely targeting TNBC primary tumors, may constitute a more effective treatment approach.
Journal Article
Reimagining childhood studies
Reimagining Childhood Studies incites, and provides a forum for, dialogue and debate about the direction and impetus for critical and global approaches to social-cultural studies of children and their childhoods. Set against the backdrop of a quarter century of research and theorising arising out of the \"new\" social studies of childhood, each of the 13 original contributions strives to extend the conceptual reach and relevance of the work being undertaken in the dynamic and expanding field of childhood studies in the 21st century. Internationally renowned contributors engage with contemporary scholarship from both the global north and south to address questions of power, inequity, reflexivity, subjectivities and representation from poststructuralist, posthumanist, postcolonial, feminist, queer studies and political economy perspectives. In so doing, the book provides a deconstructive and reconstructive dialogue, offering a renewed agenda for future scholarship. The book also moves the insights of childhood studies beyond the boundaries of this field, helping to mainstream insights about children's everyday lives from this burgeoning area of study and avoid the dangers of marginalizing both children and scholarship about childhood. This carefully curated collection extends beyond critiques of specified research arenas, traditions, concepts or approaches to serve as a bridge in the transformation of childhood studies at this important juncture in its history.
Book
Natural variation in a single amino acid substitution underlies physiological responses to topoisomerase II poisons
Many chemotherapeutic drugs are differentially effective from one patient to the next. Understanding the causes of this variability is a critical step towards the development of personalized treatments and improvements to existing medications. Here, we investigate sensitivity to a group of anti-neoplastic drugs that target topoisomerase II using the model organism Caenorhabditis elegans. We show that wild strains of C. elegans vary in their sensitivity to these drugs, and we use an unbiased genetic approach to demonstrate that this natural variation is explained by a methionine-to-glutamine substitution in topoisomerase II (TOP-2). The presence of a non-polar methionine at this residue increases hydrophobic interactions between TOP-2 and its poison etoposide, as compared to a polar glutamine. We hypothesize that this stabilizing interaction results in increased genomic instability in strains that contain a methionine residue. The residue affected by this substitution is conserved from yeast to humans and is one of the few differences between the two human topoisomerase II isoforms (methionine in hTOPIIα and glutamine in hTOPIIβ). We go on to show that this amino acid difference between the two human topoisomerase isoforms influences cytotoxicity of topoisomerase II poisons in human cell lines. These results explain why hTOPIIα and hTOPIIβ are differentially affected by various poisons and demonstrate the utility of C. elegans in understanding the genetics of drug responses.
Journal Article
DeepConsensus improves the accuracy of sequences with a gap-aware sequence transformer
Circular consensus sequencing with Pacific Biosciences (PacBio) technology generates long (10–25 kilobases), accurate ‘HiFi’ reads by combining serial observations of a DNA molecule into a consensus sequence. The standard approach to consensus generation, pbccs, uses a hidden Markov model. We introduce DeepConsensus, which uses an alignment-based loss to train a gap-aware transformer–encoder for sequence correction. Compared to pbccs, DeepConsensus reduces read errors by 42%. This increases the yield of PacBio HiFi reads at Q20 by 9%, at Q30 by 27% and at Q40 by 90%. With two SMRT Cells of HG003, reads from DeepConsensus improve hifiasm assembly contiguity (NG50 4.9 megabases (Mb) to 17.2 Mb), increase gene completeness (94% to 97%), reduce the false gene duplication rate (1.1% to 0.5%), improve assembly base accuracy (Q43 to Q45) and reduce variant-calling errors by 24%. DeepConsensus models could be trained to the general problem of analyzing the alignment of other types of sequences, such as unique molecular identifiers or genome assemblies.
Deep learning reduces errors in sequences from PacBio HiFi reads.
Journal Article
استعادة التوازن : استراتيجية للشرق الأوسط برسم الرئيس الجديد
لا شك في أن الرئيس الرابع والأربعين للولايات المتحدة الأميركية سيجد في انتظاره سلسلة من التحديات الحاسمة، المعقدة والمتشابكة في الشرق الأوسط، التي تتطلب إيلاءها اهتماما عاجلا. ذلك أن النموذج الذي اعتمده جورج بدليو بوش القائم على تغيير أنظمة الحكم ونشر الديمقراطية بالقوة لم يعد يتلاءم والظروف المتغيرة التي ستواجه الإدارة الجديدة على الأرجح الحاجة ماسة إذن لأفكار جديدة، وتحليلات غير حزبية، وتوصيات حصيفة. والكتاب الذي بين أيديكم يفي بتلك الحاجة على أفضل وجه. في اتسعادة التوازن، تتضافر جهود الخبراء والمختصين بشؤون الشرق الأوسط من مجلس العلاقات الخارجية ومركز صبان لسياسة الشرق الأوسط بمعهد بروكنغز، لتطرح استراتيجية أميركية جديدة لمنظمة حيوية لكن متفجرة كالشرق الأوسط فبناء على أبحاث ميدانية معنقة، قام هؤلاء الخبراء ببلورة مجموعة من التوصيات السياسية برسم الرئيس الأميركي الجديد وقد قامت بفحصها وتمحيصها ونقدها هيئة من المختصين من كلا الحزبين يتمتعون بخبرة سياسية واسعة ومعرفة غنية بالمنطقة، هذا التمرين في تخطيط السياسات الذي استغرق سنة كاملة هو الأول من نوعه على الإطلاق، الذي يوحد جهود وقدرات العاملين في هاتين المؤسستين المحترمتين بالسياسة الخارجية لتنصب على درس وتحليل واحدة من أخطر وأهم مناطق العالم. وكل فصل من هذا الكتاب يستضيف اثنين أو أكثر من الباحثين في مجلس العلاقات الخارجية ومعهد بروكنغز لمعاينة واستعراض التحديات التي ستواجه الرئيس المقبل.
Book
Discovery of genomic intervals that underlie nematode responses to benzimidazoles
Parasitic nematodes impose a debilitating health and economic burden across much of the world. Nematode resistance to anthelmintic drugs threatens parasite control efforts in both human and veterinary medicine. Despite this threat, the genetic landscape of potential resistance mechanisms to these critical drugs remains largely unexplored. Here, we exploit natural variation in the model nematodes Caenorhabditis elegans and Caenorhabditis briggsae to discover quantitative trait loci (QTL) that control sensitivity to benzimidazoles widely used in human and animal medicine. High-throughput phenotyping of albendazole, fenbendazole, mebendazole, and thiabendazole responses in panels of recombinant lines led to the discovery of over 15 QTL in C. elegans and four QTL in C. briggsae associated with divergent responses to these anthelmintics. Many of these QTL are conserved across benzimidazole derivatives, but others show drug and dose specificity. We used near-isogenic lines to recapitulate and narrow the C. elegans albendazole QTL of largest effect and identified candidate variants correlated with the resistance phenotype. These QTL do not overlap with known benzimidazole target resistance genes from parasitic nematodes and present specific new leads for the discovery of novel mechanisms of nematode benzimidazole resistance. Analyses of orthologous genes reveal conservation of candidate benzimidazole resistance genes in medically important parasitic nematodes. These data provide a basis for extending these approaches to other anthelmintic drug classes and a pathway towards validating new markers for anthelmintic resistance that can be deployed to improve parasite disease control.
Journal Article