Second Human Case of Cache Valley Virus Disease

We document the second known case of Cache Valley virus disease in a human. Cache Valley virus disease is rarely diagnosed in North America, in part because laboratories rarely test for it. Its true incidence, effect on public health, and full clinical spectrum remain to be determined

The possibility of critical realist randomised controlled trials.

BACKGROUND: Some realists have criticised randomised controlled trials for their inability to explain the causal relations that they identify; to take into account the influence of the social context of the interventions they evaluate; and to account for individual difference. However, among realists, there is controversy over whether it is possible to improve trials by making them realist, or whether realism and the philosophical assumptions underlying trials are incompatible. This paper contributes to the debate in Trials on this issue. The debate thus far has concentrated on the possibility of combining trial methodology with that of realist evaluation. MAIN BODY: We concur with the contention that it is not feasible to combine randomised controlled trial design with the realist evaluation approach. However, we argue that a different variant of realism, critical realism, provides a more appropriate theoretical grounding for realist trials. In contrast to realist evaluation, which regards social mechanisms as an amalgam of social resources and people's reasoning, critical realism insists on their distinction. It does so on the basis of its assertion of the need to distinguish between social structures (in which resources lie) and human agency (which is at least partly guided by reasoning). From this perspective, conceiving of social mechanisms as external to participants can be seen as a valid methodological strategy for supplementing the exclusive concentration of trials on outcomes. While accepting realist evaluation's insistence that causality in open systems involves a configuration of multiple generative mechanisms, we adopt the critical realist interpretation of the experimental method, which sees it as creating artificial closure in order to identify the effects of specific causal mechanisms. If randomised controlled trials can be regarded as epidemiological proxies that substitute probabilistic controls over extraneous factors for closed experiments, their examination of the powers of discrete mechanisms through observation of the variation of outcomes is appropriate. CONCLUSION: While there are still issues to be resolved, critical realist randomised controlled trials are possible and have the potential to overcome some of the difficulties faced by traditional trial designs in accounting for the influence of social context and individual interpretation

Live Imaging at the Onset of Cortical Neurogenesis Reveals Differential Appearance of the Neuronal Phenotype in Apical versus Basal Progenitor Progeny

The neurons of the mammalian brain are generated by progenitors dividing either at the apical surface of the ventricular zone (neuroepithelial and radial glial cells, collectively referred to as apical progenitors) or at its basal side (basal progenitors, also called intermediate progenitors). For apical progenitors, the orientation of the cleavage plane relative to their apical-basal axis is thought to be of critical importance for the fate of the daughter cells. For basal progenitors, the relationship between cell polarity, cleavage plane orientation and the fate of daughter cells is unknown. Here, we have investigated these issues at the very onset of cortical neurogenesis. To directly observe the generation of neurons from apical and basal progenitors, we established a novel transgenic mouse line in which membrane GFP is expressed from the beta-III-tubulin promoter, an early pan-neuronal marker, and crossed this line with a previously described knock-in line in which nuclear GFP is expressed from the Tis21 promoter, a pan-neurogenic progenitor marker. Mitotic Tis21-positive basal progenitors nearly always divided symmetrically, generating two neurons, but, in contrast to symmetrically dividing apical progenitors, lacked apical-basal polarity and showed a nearly randomized cleavage plane orientation. Moreover, the appearance of beta-III-tubulin–driven GFP fluorescence in basal progenitor-derived neurons, in contrast to that in apical progenitor-derived neurons, was so rapid that it suggested the initiation of the neuronal phenotype already in the progenitor. Our observations imply that (i) the loss of apical-basal polarity restricts neuronal progenitors to the symmetric mode of cell division, and that (ii) basal progenitors initiate the expression of neuronal phenotype already before mitosis, in contrast to apical progenitors

Domain formation in DODAB–cholesterol mixed systems monitored via nile red anisotropy

The effect of the cholesterol (Ch) on liposomes composed of the cationic lipid dioctadecyldimethylammonium bromide (DODAB) was assessed by studying both the steady-state and time-resolved fluorescence anisotropy of the dye Nile Red. The information obtained combined with analysis of the steady-state emission and luorescence lifetime of Nile Red (NR) for different cholesterol concentrations (5–50%) elucidated the presence of “condensed complexes” and cholesterol-rich domains in these mixed systems. The steady-state fluorescence spectra were decomposed into the sum of two lognormal emissions, emanating from two different states, and the effect of temperature on the anisotropy decay of Nile Red for different cholesterol concentrations was observed. At room temperature, the time-resolved anisotropy decays are indicative of NR being relatively immobile (manifest by a high r∞ value). At higher temperature, rotational times ca. 1 ns were obtained throughout and a trend in increasing hindrance was seen with increase of Ch content

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Increased indoleamine-2,3-dioxygenase activity is associated with poor clinical outcome in adults hospitalized with influenza in the INSIGHT FLU003Plus study

BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. METHODS: We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. RESULTS: We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21-0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25-43.90). CONCLUSIONS: High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration. CLINICALTRIALSGOV IDENTIFIER: NCT01056185

Financial wellbeing of Asian Americans

The Asian American population in the United States has been increasing. Research on the economic wellbeing of this minority group is far from being adequate. It is generally found that Asian Americans are more highly educated and have more wealth. Although the homeownership rate of this population is lower than the national average rate, the gap is gradually narrowing. Asian Americans are found to have more confidence in their financial future and have better management in their financial lives. In addition, Asian-owned businesses have been an important part of the U.S. economy and, as such, the self-employment status of Asian Americans has stimulated great interest for research. Large differences in financial behaviors exist among different groups in Asian Americans. This chapter serves the purpose to summarize past research on Asian American consumer finances and provide directions for future research.Includes bibliographical references

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high risk, early breast cancer.

BACKGROUND: The randomized, double-blind OlympiA trial compared one year of the oral poly(adenosine diphosphate-ribose) polymerase) inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2 (HER2)-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive-disease-free survival (IDFS) and distant-disease-free survival (DDFS). The olaparib-group had fewer deaths than the placebo-group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. PATIENTS AND METHODS: 1,836 patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy (N)ACT, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone-receptor-positive-cancers. Statistical significance for OS at this IA required P<0.015. RESULTS: With median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib-group relative to the placebo-group (HR, 0.68; 98.5% CI 0.47 to 0.97; P=0.009). Four-year OS was 89.8% in the olaparib-group and 86.4% in the placebo-group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for olaparib-group versus placebo-group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myelogenous leukemia or myelodysplastic syndrome (AML/MDS). CONCLUSION: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals