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OBJECTIVES/GOALS: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatologic disease childhood and a cause of pain and potential disability. JIA has a strong genetic component and no known cure. The goal of this study is to evaluate allele-dependent effects of a novel JIA risk variant at 1q24.3. METHODS/STUDY POPULATION: JIA patients meeting criteria for the two most common disease subtypes (oligoarticular and RF neg polyarthritis) were genotyped using the Immunochip, an Illumina array with dense coverage of the HLA region and 186 other loci previously reported in autoimmune diseases. Phase I association findings (Hinks, 2013) and Phase II analysis (unpublished) of an expanded cohort (4,271 JIA and 14,390 controls) identified new risk loci, including rs78037977 at 1q24.3. We prioritized rs78037977 and predicted possible impacted mechanisms based on Bayesian predictions of attributable risk, the surrounding chromatin landscape, and transcription factor binding data. A luciferase reporter assay was used to assess allele-dependent enhancer activity. RESULTS/ANTICIPATED RESULTS: rs78037977 is located between FASLG and TNFSF18 at chromosome 1q24.3 is associated with JIA (p = 6.3x10−09), and explains 94% of the posterior probability at this locus; no other SNPs in linkage disequilibrium (r2>0.6). The chromatin landscape around rs78037977 contains H3K4Me1 and H3K27Ac marks, which are indicative of enhancer activity. Further, >160 transcription factors have chromatin immunoprecipitation followed by sequencing (ChIP-seq) peaks overlapping rs78037977 in various cellular contexts. In luciferase reporter assays, the region around rs78037977 containing the reference A allele had ~2-fold increased enhancer activity compared to the non-reference allele. DISCUSSION/SIGNIFICANCE OF IMPACT: This work provides in vitro evidence to support allele-dependent enhancer activity of a novel JIA-risk variant at 1q24.3. Our ongoing work investigates the effect of the DNA-containing region of rs78037977 on gene expression and differential transcription factor binding at rs78037977.
We describe an algorithm that can fit the properties of the dwarf galaxy progenitor of a tidal stream, given the properties of that stream. We show that under ideal conditions (the Milky Way potential, the orbit of the dwarf galaxy progenitor, and the functional form of the dwarf galaxy progenitor are known exactly), the density and angular width of stars along the stream can be used to constrain the mass and radial profile of both the stellar and dark matter components of the progenitor dwarf galaxy that was ripped apart to create the stream. Our provisional fit for the parameters of the dwarf galaxy progenitor of the Orphan Stream indicates that it is less massive and has fewer stars than previous works have indicated.
While much research has focused on crop damage following foliar exposure to auxin herbicides, reports documenting the risk posed by exposure via root uptake of irrigation water are lacking. Herbicide residues circulated in tailwater recovery systems may pose threats of cross-crop impacts to nonresistant cultivars with known sensitivity to auxins. An auxin-susceptible soybean [Glycine max (L.) Merr.] cultivar was grown in a controlled growth chamber environment and exposed to dicamba dissolved in irrigation water applied to the soil surface, simulating furrow irrigation. Five herbicide treatment concentrations, ranging from 0.05 to 5.0 mg L−1 and encompassing estimated field doses of 3.1 to 310g ha−1, were applied to the soil of potted soybean plants at V3/V4 or R1 growth stages. Plant injury (0% to 100%), dry mass, height, number of pods, and number of pod-bearing nodes were measured. Kruskal-Wallis and logistic regression analyses were performed to determine treatment differences and examine dose effects. Yield losses were projected using (1) 14 d after treatment plant injury assessments based on injury–yield relationships described for foliar exposures and (2) pod counts. Dicamba concentration was the main significant factor affecting all growth response metrics, and growth stage was a significant explanatory variable only for the height response metric. A nonlinear response to dicamba dose was observed, with the threshold response dose required to affect 50% of plants being three times greater for 40% crop injury compared with 20% injury. Yield projections derived from plant response to root uptake compared with foliar exposure indicate that soybean may express both magnitude of injury and specific symptomology differently when exposure occurs via root uptake. Drift exposure–based models may be incompatible to predict soybean yield loss when injury results from irrigation. Data are needed to develop correlations for predicting yield losses based on field-scale exposure to dicamba in irrigation water, as well as assessment of real-world concentrations of herbicide residues in tailwater recovery systems.
Mental health services in the UK National Health Service have evolved to include primary-care generalist, secondary-care generalist and secondary-care specialist services. We argue that there continues to be an important role for the secondary-care generalists as they minimise interfaces, can live with diagnostic uncertainty and support continuity of care. The lack of commissioning and clinical boundaries in secondary-care generalist services can undermine their feasibility, leading to difficulties recruiting and retaining staff. There is a risk of a polo-mint service, where the specialist services on the edge are well resourced, but the secondary-care generalist services taking the greatest burden struggle to recruit and retain clinicians. We need to establish equity in resources and expectations between generalist and specialist mental health services.
Over the past 30 years, the number of US doctoral anthropology graduates has increased by about 70%, but there has not been a corresponding increase in the availability of new faculty positions. Consequently, doctoral degree-holding archaeologists face more competition than ever before when applying for faculty positions. Here we examine where US and Canadian anthropological archaeology faculty originate and where they ultimately end up teaching. Using data derived from the 2014–2015 AnthroGuide, we rank doctoral programs whose graduates in archaeology have been most successful in the academic job market; identify long-term and ongoing trends in doctoral programs; and discuss gender division in academic archaeology in the US and Canada. We conclude that success in obtaining a faculty position upon graduation is predicated in large part on where one attends graduate school.
Leibovich et al.'s theory neither accounts for the deep connections between whole numbers and other classes of number nor provides a potential mechanism for mapping continuous magnitudes to symbolic numbers. We argue that focusing on non-symbolic ratio processing abilities can furnish a more expansive account of numerical cognition that remedies these shortcomings.
To discern changes in body mass index (BMI) in patients on long-term antidepressant treatment in a general practice population and establish BMI changes in patients with and without a diagnosis of diabetes. We used a retrospective observational method and identified patients on four antidepressants of interest. We excluded those who did not have start and current BMI readings within the past 3 years and noted whether or not patients had a diagnosis of diabetes.
Long-term treatment with citalopram, fluoxetine, mirtazapine and sertraline was associated with increased BMI in two-thirds of patients. There was reduction in BMI in patients with diabetes and an increase in BMI for patients who did not have diabetes.
Awareness of environmental factors and their impact on individuals is important. Medication is not the only cause of abnormal metabolic effects. Overall monitoring of physical health is important in all groups of patients.
Early intervention for psychosis (EIP) is a model of service delivery that aims to support young people with first-episode psychosis by providing the best available treatments, supporting recovery and preventing relapse. In this editorial, we review the evidence for EIP, how the model has developed since its inclusion in the NHS policy implementation guideline for mental health in 2001, challenges and areas of ongoing debate, and future development.
The concept of an ‘at-risk mental state’ for psychosis arose from previous work attempting to identify a putative psychosis prodrome. In this article we summarise the current criteria used to identify ‘at-risk’ individuals, such as the ultra-high-risk (UHR) criteria, and the further identification of important clinical risk factors or biomarkers to improve prediction of who might develop a psychotic disorder. We also discuss important ethical issues in classifying and treating at-risk individuals, current treatment trials in this area and what treatment current services can offer.
Outpatient hemodialysis bloodstream infection rates, now used for performance measurement and were significantly higher for manual compared with automated surveillance (P<.001), largely owing to the absence of blood culture data in the dialysis electronic health record. Improvement in data sharing between hospitals and outpatient dialysis centers is necessary.
Infect. Control Hosp. Epidemiol. 2016;37(4):472–474
In imbibing seeds, resumption of metabolism leads to the unavoidable release of volatile by-products that are perceived as cues by rodent seed predators. The crypsis hypothesis proposes that the primary function of a water-impermeable, hard seed coat is to reduce rodent seed predation by rendering seeds olfactorily cryptic. In an opinion paper, Jayasuriya et al. (2015) find the crypsis hypothesis unscientific and ‘not consistent with Darwin's theory of evolution by natural selection’. It is unfortunate that Jayasuriya et al. (2015) did not appreciate that the crypsis hypothesis offers an alternative explanation for the evolution of water-impermeable seeds: released seed volatiles are cues used by rodents to locate seeds, and variation in seed-coat permeability leading to differences in seed volatile release represents the variable under selection. Furthermore, the sealing of water-impermeable seed coats imposes a cost of increased generation time and, therefore, dormancy-release mechanisms are expected to subsequently evolve in response to local environmental conditions. We also disagree with most other claims by Jayasuriya et al. (2015), who failed to appreciate how species with dimorphic seeds – one morph with permeable and the other with impermeable seed coats – benefit from rodent caching behaviour and population dynamics. We welcome this opportunity to clarify and elaborate on key features and the evolution of water-impermeable seed coats according to the crypsis hypothesis.