An analysis of the subtypes of dengue fever infections in Barbados 2003–2007 by reverse transcriptase polymerase chain reaction

<p>Abstract</p> <p>Background</p> <p>To perform a retrospective analysis of patients with IgM antibodies to dengue fever infection to determine the serotypes present by molecular techniques. A representative sample (~20%/per year) of patients diagnosed with dengue fever infection were selected based on the detection of IgM antibodies in the acute phase serum sample. RNA was extracted from each sample and reverse transcribed. Following this, the amplicons were electrophoresed and serotyped based on band sizes.</p> <p>Results</p> <p>This study consisted of 71 males and 101 females ranging in age from 0 – 50+ yrs giving a total of 172 persons with an average of 34.4 patients per year. Onset averaged 6.9 days ranging from 0–90 days. Common symptoms were as follows: fever (69%), headache (52%), arthralgia (36%), ocular pain (32%), emesis (15%) and lumbar pain (15%). All patients investigated with the exception of one, were infected with DENV-3.</p> <p>Conclusion</p> <p>DENV-3 is currently circulating on the island and not DENV-1 or DENV-2 as in previous years. This has implications for the enhancement of clinical, laboratory and environmental surveillance systems.</p

Galaxy Cluster Pressure Profiles as Determined by Sunyaev Zel'dovich Effect Observations with MUSTANG and Bolocam I: Joint Analysis Technique

We present a technique to constrain galaxy cluster pressure profiles by jointly fitting Sunyaev-Zel'dovich effect (SZE) data obtained with MUSTANG and Bolocam for the clusters Abell 1835 and MACS0647. Bolocam and MUSTANG probe different angular scales and are thus highly complementary. We find that the addition of the high resolution MUSTANG data can improve constraints on pressure profile parameters relative to those derived solely from Bolocam. In Abell 1835 and MACS0647, we find gNFW inner slopes of $\gamma = 0.36_{-0.21}^{+0.33}$ and $\gamma = 0.38_{-0.25}^{+0.20}$, respectively when $\alpha$ and $\beta$ are constrained to 0.86 and 4.67 respectively. The fitted SZE pressure profiles are in good agreement with X-ray derived pressure profiles.Comment: 12 pages, 12 figures. Submitted to Ap

The Agricultural Genome to Phenome Initiative (AG2PI): creating a shared vision across crop and livestock research communities

Predicting phenotype from genotype is a central challenge in biology. By understanding genomic information to predict and improve traits, scientists can address the challenges and opportunities of achieving sustainable genetic improvement of complex, economically important traits in agriculturally relevant species. Converting the enormous, recent technical advances in all areas of genomics and phenomics into sustained and ecologically responsible improvements in food and fuel production is complex. It will require engaging agricultural genome to phenome (G2P) experts, drawing from a broad community, including crop and livestock scientists and essential integrative disciplines (e.g., engineers, economists, data and social scientists). To achieve this vision, the USDA NIFA-funded project inaugurating the Agricultural Genome to Phenome Initiative (AG2PI) is working to: Develop a cohesive vision for agricultural G2P research by identifying research gaps and opportunities; advancing community solutions to these challenges and gaps; and rapidly disseminating findings to the broader community. Towards these ends, this AG2PI project is organizing virtual field days, conferences, training workshops, and awarding seed grants to conceive new insights (details at www.ag2pi.org). Since October 2020, more than 10,000 unique participants from every inhabited continent have engaged in these activities. To illustrate AG2PI’s scope, we present survey results on agricultural G2P research needs and opportunities, highlighting opinions and suggestions for the future. We invite stakeholders interested in this complex but critical effort to help create an optimal, sustainable food supply for society and challenge the community to add to our vision for future accomplishments by a fully actualized AG2PI enterprise

Shear thickening and jamming in densely packed suspensions of different particle shapes

We investigated the effects of particle shape on shear thickening in densely packed suspensions. Rods of different aspect ratios and non-convex hooked rods were fabricated. Viscosity curves and normal stresses were measured using a rheometer for a wide range of packing fractions for each shape. Suspensions of each shape exhibit qualitatively similar Discontinuous Shear Thickening. The logarithmic slope of the stress/shear-rate relation increases dramatically with packing fraction and diverges at a critical packing fraction phi_c which depends on particle shape. The packing fraction dependence of the viscosity curves for different convex shapes can be collapsed when the packing fraction is normalized by phi_c. Intriguingly, viscosity curves for non-convex particles do not collapse on the same set as convex particles, showing strong shear thickening over a wider range of packing fraction. The value of phi_c is found to coincide with the onset of a yield stress at the jamming transition, suggesting the jamming transition also controls shear thickening. The yield stress is found to correspond with trapped air in the suspensions, and the scale of the stress can be attributed to interfacial tension forces which dramatically increase above phi_c due to the geometric constraints of jamming. The relationship between shear and normal stresses is found to be linear in both the shear thickening and jammed regimes, indicating that the shear stresses come from friction. In the limit of zero shear rate, normal stresses pull the rheometer plates together due to the surface tension of the liquid below phi_c, but push the rheometer plates apart due to jamming above phi_c.Comment: 13 pages, 13 figures. published in Physical Review

A multi-centred sequential trial comparing PEGASUS, an intervention to promote shared decision making about breast reconstruction with usual care

Decision making about breast reconstruction (BR) is complex. The Patients’ Expectations and Goals: Assisting Shared Understanding of Surgery (PEGASUS) intervention aims to support shared decision making by helping women and clinicians clarify and discuss their expectations around reconstructive surgery. We conducted a multi-centred sequential trial comparing PEGASUS (n = 52) with usual care (UC) (n = 86) in women considering reconstruction, who completed outcome measures at baseline, and 3, 6 and 12 months post-surgery. The primary outcome was BR-specific quality of life (Breast-Q) 6 months post-intervention. Secondary outcomes were health-related quality of life (EQ-5D-5L), capabilities (ICECAP-A) and decisional regret, compared using t-tests and Cohen's d. Comparative analyses revealed no significant differences between groups in Breast-Q scores at any time point, except for a favourable effect for UC on psychological well-being at 3 months (t = -2.41, p = .019, d= -0.59). Intervention participants reported significantly higher, therefore improved, ICECAP-A (t = -2.13, p = .037, d = -0.45) and EQ VAS (t = -2.28, p = .026, d = -0.49) scores at 12 months compared to UC. Decisional regret was significantly lower in the PEGASUS group compared to the UC group at 6 months (t =2.06, p = .044, d= -0.51), but this was not sustained at 12 months. In conclusion, the PEGASUS intervention offers some benefits to women considering BR. At times, women experienced less decisional regret, improved health-related quality of life and capability well-being. Findings are discussed in the light of fidelity testing and embedding PEGASUS into practice

GSK3β-SCFFBXW7α mediated phosphorylation and ubiquitination of IRF1 are required for its transcription-dependent turnover

IRF1 (Interferon Regulatory Factor-1) is the prototype of the IRF family of DNA binding transcription factors. IRF1 protein expression is regulated by transient up-regulation in response to external stimuli followed by rapid degradation via the ubiquitin-proteasome system. Here we report that DNA bound IRF1 turnover is promoted by GSK3β (Glycogen Synthase Kinase 3β) via phosphorylation of the T181 residue which generates a phosphodegron for the SCF (Skp-Cul-Fbox) ubiquitin E3-ligase receptor protein Fbxw7α (F-box/WD40 7). This regulated turnover is essential for IRF1 activity, as mutation of T181 results in an improperly stabilised protein that accumulates at target promoters but fails to induce RNA-Pol-II elongation and subsequent transcription of target genes. Consequently, the anti-proliferative activity of IRF1 is lost in cell lines expressing T181A mutant. Further, cell lines with dysfunctional Fbxw7 are less sensitive to IRF1 overexpression, suggesting an important co-activator function for this ligase complex. As T181 phosphorylation requires both DNA binding and RNA-Pol-II elongation, we propose that this event acts to clear " spent " molecules of IRF1 from transcriptionally engaged target promoters

Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism

CONTEXT: Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency. OBJECTIVE: To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)]. DESIGN: Open-label extension study; 5-year interim analysis. SETTING: 12 US centers. PATIENTS: Adults (N = 49) with chronic hypoparathyroidism. INTERVENTION(S): rhPTH(1-84) 25 or 50 µg/d initially, with 25-µg adjustments permitted to a 100 µg/d maximum. MAIN OUTCOME MEASURE(S): Safety parameters; composite efficacy outcome was the proportion of patients with ≥50% reduction in oral calcium (or ≤500 mg/d) and calcitriol (or ≤0.25 µg/d) doses, and albumin-corrected serum calcium normalized or maintained compared with baseline, not exceeding upper limit of normal. RESULTS: Forty patients completed 60 months of treatment. Mean albumin-corrected serum calcium levels remained between 8.2 and 8.7 mg/dL. Between baseline and month 60, levels ± SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 ± 236.24 mg/24 hours, 1.0 ± 0.78 mg/dL, and 8.5 ± 8.29 mg2/dL2, respectively. Serum creatinine level and estimated glomerular filtration rate were unchanged. Treatment-emergent adverse events (AEs) were reported in 48 patients (98.0%; hypocalcemia, 36.7%; muscle spasms, 32.7%; paresthesia, 30.6%; sinusitis, 30.6%; nausea, 30.6%) and serious AEs in 13 (26.5%). At month 60, 28 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ∼12 months, and then declined to values that remained above baseline. CONCLUSION: Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters

Galaxy Cluster Pressure Profiles as Determined by Sunyaev Zel’dovich Effect Observations with MUSTANG and Bolocam. II. Joint Analysis of 14 Clusters

We present pressure profiles of galaxy clusters determined from high resolution Sunyaev-Zel'dovich (SZ) effect observations of fourteen clusters, which span the redshift range $0.25 < z < 0.89$. The procedure simultaneously fits spherical cluster models to MUSTANG and Bolocam data. In this analysis, we adopt the generalized NFW parameterization of pressure profiles to produce our models. Our constraints on ensemble-average pressure profile parameters, in this study $\gamma$, $C_{500}$, and $P_0$, are consistent with those in previous studies, but for individual clusters we find discrepancies with the X-ray derived pressure profiles from the ACCEPT2 database. We investigate potential sources of these discrepancies, especially cluster geometry, electron temperature of the intracluster medium, and substructure. We find that the ensemble mean profile for all clusters in our sample is described by the parameters: $[\gamma,C_{500},P_0] = [0.3_{-0.1}^{+0.1}, 1.3_{-0.1}^{+0.1}, 8.6_{-2.4}^{+2.4}]$, for cool core clusters: $[\gamma,C_{500},P_0] = [0.6_{-0.1}^{+0.1}, 0.9_{-0.1}^{+0.1}, 3.6_{-1.5}^{+1.5}]$, and for disturbed clusters: $[\gamma,C_{500},P_0] = [0.0_{-0.0}^{+0.1}, 1.5_{-0.2}^{+0.1},13.8_{-1.6}^{+1.6}]$. Four of the fourteen clusters have clear substructure in our SZ observations, while an additional two clusters exhibit potential substructure.Comment: 22 pages, 9 figures, accepted to Ap

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes