Objective—To evaluate the prevalence of suicide risk factors, attitudes toward mental illness, and practice-related stressors among US veterinarians. Design—Cross-sectional survey. Sample—11,627 US ...veterinarians. Procedures—Between July 1 and October 20, 2014, a Web-based questionnaire was made available through the Veterinary Information Network (VIN), VIN News Service, JAVMA News, and email messages to US veterinarians sent by a veterinary medical association, agriculture or livestock department, or health department of each state (except Maine) and Puerto Rico. Results—Of 11,627 respondents, 3,628 (31%) were male. Modal age category was 30 to 39 years, and modal range for years practicing veterinary medicine was 10 to 19 years. There were 7,460 (64%) respondents who primarily practiced small animal medicine, and 4,224 (36%) who were practice owners. There were 1,077 (9%) respondents with current serious psychological distress. Since leaving veterinary school, 3,655 (31%) respondents experienced depressive episodes, 1,952 (17%) experienced suicidal ideation, and 157 (1%) attempted suicide. Currently, 2,228 (19%) respondents were receiving treatment for a mental health condition. Only 3,250 of 10,220 (32%) respondents somewhat or strongly agreed that people are sympathetic toward persons with mental illness. The most commonly reported practice-related stressor was demands of practice. Conclusions and Clinical Relevance—In this survey, approximately 1 in 11 veterinarians had serious psychological distress and 1 in 6 experienced suicidal ideation since leaving veterinary school. Implementing measures to help veterinarians cope with practice-related stressors and reducing barriers veterinarians face in seeking mental health treatment might reduce the risk for suicide among veterinarians.
Molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. Here we used high-resolution proteomics analysis of ...immunoglobulin (referred to as Ig-seq) coupled with high-throughput sequencing of transcripts encoding B cell receptors (BCR-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influenza vaccine. The serum repertoire comprised between 40 and 147 clonotypes that were specific to each of the three monovalent components of the trivalent influenza vaccine, with boosted pre-existing clonotypes accounting for ∼60% of the response. An unexpectedly high fraction of serum antibodies recognized both the H1 and H3 monovalent vaccines. Recombinant versions of these H1 + H3 cross-reactive antibodies showed broad binding to hemagglutinins (HAs) from previously circulating virus strains; several of these antibodies, which were prevalent in the serum of multiple donors, recognized the same conserved epitope in the HA head domain. Although the HA-head-specific H1 + H3 antibodies did not show neutralization activity in vitro, they protected mice against infection with the H1N1 and H3N2 virus strains when administered before or after challenge. Collectively, our data reveal unanticipated insights regarding the serological response to influenza vaccination and raise questions about the added benefits of using a quadrivalent vaccine instead of a trivalent vaccine.
Electrocorticography (ECoG) is becoming more prevalent due to improvements in fabrication and recording technology as well as its ease of implantation compared to intracortical electrophysiology, ...larger cortical coverage, and potential advantages for use in long term chronic implantation. Given the flexibility in the design of ECoG grids, which is only increasing, it remains an open question what geometry of the electrodes is optimal for an application. Conductive polymer, PEDOT:PSS, coated microelectrodes have an advantage that they can be made very small without losing low impedance. This makes them suitable for evaluating the required granularity of ECoG recording in humans and experimental animals. We used two-dimensional (2D) micro-ECoG grids to record intra-operatively in humans and during acute implantations in mouse with separation distance between neighboring electrodes (i.e., pitch) of 0.4 mm and 0.2/0.25 mm respectively. To assess the spatial properties of the signals, we used the average correlation between electrodes as a function of the pitch. In agreement with prior studies, we find a strong frequency dependence in the spatial scale of correlation. By applying independent component analysis (ICA), we find that the spatial pattern of correlation is largely due to contributions from multiple spatially extended, time-locked sources present at any given time. Our analysis indicates the presence of spatially structured activity down to the sub-millimeter spatial scale in ECoG despite the effects of volume conduction, justifying the use of dense micro-ECoG grids.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Imaging genomics is a new field of investigation that seeks to gain insights into the impact of human genetic variation on the structure, chemistry, and function of neural systems in health ...and disease. Because publications in this field have increased over the past decade, increasing concerns have been raised about false-positive results entering the literature. Here, we provide an overview of the field of imaging genomic and genetic approaches and discuss factors related to research design and analysis that can enhance the informativeness and replicability of these studies. We conclude that imaging genetic studies can provide important insights into the role of human genetic variation on neural systems and circuits, both in the context of normal quantitative variation and in relation to neuropsychiatric disease. We also argue that demonstrating genetic association to imaging-derived traits is subject to the same constraints as any other genetic study, including stringent type I error control. Adequately powered studies are necessary; however, there are currently limited data available to allow precise estimates of effect sizes for candidate gene studies. Independent replication is necessary before a result can be considered definitive, and for studies with small sample sizes it is necessary before publication. Increased transparency of methods and enhanced data sharing will further enhance replicability.
To achieve the very high oncoprotein levels required to drive the malignant state cancer cells utilise the ubiquitin proteasome system to upregulate transcription factor levels. Here our analyses ...identify ALYREF, expressed from the most common genetic copy number variation in neuroblastoma, chromosome 17q21-ter gain as a key regulator of MYCN protein turnover. We show strong co-operativity between ALYREF and MYCN from transgenic models of neuroblastoma in vitro and in vivo. The two proteins form a nuclear coactivator complex which stimulates transcription of the ubiquitin specific peptidase 3, USP3. We show that increased USP3 levels reduce K-48- and K-63-linked ubiquitination of MYCN, thus driving up MYCN protein stability. In the MYCN-ALYREF-USP3 signal, ALYREF is required for MYCN effects on the malignant phenotype and that of USP3 on MYCN stability. This data defines a MYCN oncoprotein dependency state which provides a rationale for future pharmacological studies.
The prenatal origins of cancer Marshall, Glenn M; Carter, Daniel R; Cheung, Belamy B ...
Nature reviews. Cancer,
04/2014, Letnik:
14, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The concept that some childhood malignancies arise from postnatally persistent embryonal cells has a long history. Recent research has strengthened the links between driver mutations and embryonal ...and early postnatal development. This evidence, coupled with much greater detail on the cell of origin and the initial steps in embryonal cancer initiation, has identified important therapeutic targets and provided renewed interest in strategies for the early detection and prevention of childhood cancer.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The North American Spine Society's (NASS) Evidence Based Clinical Guideline for the Diagnosis and Treatment of Low Back Pain features evidence-based recommendations for diagnosing and treating adult ...patients with nonspecific low back pain. The guideline is intended to reflect contemporary treatment concepts for nonspecific low back pain as reflected in the highest quality clinical literature available on this subject as of February 2016.
The purpose of the guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for adult patients with nonspecific low back pain. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition.
This is a guideline summary review.
This guideline is the product of the Low Back Pain Work Group of NASS’ Evidence-Based Clinical Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members utilized NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members participated in webcasts and in-person recommendation meetings to update and formulate evidence-based recommendations and incorporate expert opinion when necessary. The draft guideline was submitted to an internal and external peer review process and ultimately approved by the NASS Board of Directors.
Eighty-two clinical questions were addressed, and the answers are summarized in this article. The respective recommendations were graded according to the levels of evidence of the supporting literature.
The evidence-based clinical guideline has been created using techniques of evidence-based medicine and best available evidence to aid practitioners in the diagnosis and treatment of adult patients with nonspecific low back pain. The entire guideline document, including the evidentiary tables, literature search parameters, literature attrition flowchart, suggestions for future research, and all of the references, is available electronically on the NASS website at https://www.spine.org/ResearchClinicalCare/QualityImprovement/ClinicalGuidelines.aspx
Micro-Abstract The management of patients with oligometastatic non–small-cell lung cancer (NSCLC) is controversial. The findings of this metaanalysis of 757 oligometastatic NSCLC patients treated ...with ablative treatments to all sites of disease suggest that the timing of metastatic disease (synchronous vs. metachronous) and intrathoracic nodal status are key determinants of long-term survival. A risk classification scheme is proposed to guide clinical decision-making.
Changes in gene regulation and expression govern orderly transitions from hematopoietic stem cells to terminally differentiated blood cell types. These transitions are disrupted during leukemic ...transformation, but knowledge of the gene regulatory changes underpinning this process is elusive. We hypothesized that identifying core gene regulatory networks in healthy hematopoietic and leukemic cells could provide insights into network alterations that perturb cell state transitions. A heptad of transcription factors (LYL1, TAL1, LMO2, FLI1, ERG, GATA2, and RUNX1) bind key hematopoietic genes in human CD34+ hematopoietic stem and progenitor cells (HSPCs) and have prognostic significance in acute myeloid leukemia (AML). These factors also form a densely interconnected circuit by binding combinatorially at their own, and each other's, regulatory elements. However, their mutual regulation during normal hematopoiesis and in AML cells, and how perturbation of their expression levels influences cell fate decisions remains unclear. In this study, we integrated bulk and single-cell data and found that the fully connected heptad circuit identified in healthy HSPCs persists, with only minor alterations in AML, and that chromatin accessibility at key heptad regulatory elements was predictive of cell identity in both healthy progenitors and leukemic cells. The heptad factors GATA2, TAL1, and ERG formed an integrated subcircuit that regulates stem cell-to-erythroid transition in both healthy and leukemic cells. Components of this triad could be manipulated to facilitate erythroid transition providing a proof of concept that such regulatory circuits can be harnessed to promote specific cell-type transitions and overcome dysregulated hematopoiesis.
•Chromatin accessibility patterns at key heptad regulatory elements can predict cell identity in healthy progenitors and leukemic cells.•A subcircuit comprising GATA2, TAL1, and ERG regulates the stem cell to erythroid transition in both healthy and leukemic cells.
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Black carbon (BC) from biomass and fossil fuel combustion alters chemical and physical properties of the atmosphere and snow albedo, yet little is known about its emission or deposition histories. ...Measurements of BC, vanillic acid, and non-sea-salt sulfur in ice cores indicate that sources and concentrations of BC in Greenland precipitation varied greatly since 1788 as a result of boreal forest fires and industrial activities. Beginning about 1850, industrial emissions resulted in a sevenfold increase in ice-core BC concentrations, with most change occurring in winter. BC concentrations after about 1951 were lower but increasing. At its maximum from 1906 to 1910, estimated surface climate forcing in early summer from BC in Arctic snow was about 3 watts per square meter, which is eight times the typical preindustrial forcing value.
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