Substance Use Disorders, Violence, Mental Health, and HIV: Differentiating a Syndemic Factor by Gender and Sexuality

This paper measures syndemic substance use disorder, violence, and mental health and compares the syndemic among HIV-infected heterosexual men, heterosexual women, and men who have sex with men (MSM). Data were from a sample of high needs substance-using, HIV-infected people in South Florida between 2010 and 2012 (n = 481). We used confirmatory factor analysis to measure a syndemic latent variable and applied measurement invariance models to identify group differences in the data structure of syndemic co-morbidities among heterosexual men, heterosexual women, and MSM. We found that variables used to measure the syndemic fit each sub-group, supporting that substance use disorder, violence, and mental health coincide in HIV-infected individuals. Heterosexual men and MSM demonstrated similar syndemic latent variable factor loadings, but significantly different item intercepts, indicating that heterosexual men had larger mean values on substance use disorder, anxiety, and depression than MSM. Heterosexual men and heterosexual women demonstrated significantly different syndemic variable factor loadings, indicating that anxiety and depression contribute more (and substance use contributes less) to the syndemic in heterosexual men compared to heterosexual women. MSM and heterosexual women demonstrated similar syndemic latent variable factor loadings and intercepts, but had significantly different factor residual variances indicating more variance in violent victimization and depression for MSM and more variance in stress for heterosexual women than what is captured by the observed syndemic indicators. Furthermore, heterosexual women had a larger syndemic factor mean than MSM, indicating that the syndemic burden is greater among heterosexual women than MSM. Our findings support that measurement invariance can elucidate differences in the syndemic to tailor interventions to sub-group needs

A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification

Background:Approximately 5%-10% of gastric cancers have a fibroblast growth factor receptor-2 (FGFR2) gene amplification. AZD4547 is a selective FGFR-1, 2, 3 tyrosine kinase inhibitor with potent preclinical activity in FGFR2 amplified gastric adenocarcinoma SNU16 and SGC083 xenograft models. The randomized phase II SHINE study (NCT01457846) investigated whether AZD4547 improves clinical outcome versus paclitaxel as second-line treatment in patients with advanced gastric adenocarcinoma displaying FGFR2 polysomy or gene amplification detected by fluorescence in situ hybridization. Patients and methods:Patients were randomized 3:2 (FGFR2 gene amplification) or 1:1 (FGFR2 polysomy) to AZD4547 or paclitaxel. Patients received AZD4547 80 mg twice daily, orally, on a 2 weeks on/1 week off schedule of a 21-day cycle or intravenous paclitaxel 80 mg/m2 administered weekly on days 1, 8, and 15 of a 28-day cycle. The primary end point was progression-free survival (PFS). Safety outcomes were assessed and an exploratory biomarker analysis was undertaken. Results:Of 71 patients randomized (AZD4547 n = 41, paclitaxel n = 30), 67 received study treatment (AZD4547 n = 40, paclitaxel n = 27). Among all randomized patients, median PFS was 1.8 months with AZD4547 and 3.5 months with paclitaxel (one-sided P = 0.9581); median follow-up duration for PFS was 1.77 and 2.12 months, respectively. The incidence of adverse events was similar in both treatment arms. Exploratory biomarker analyses revealed marked intratumor heterogeneity of FGFR2 amplification and poor concordance between amplification/polysomy and FGFR2 mRNA expression. Conclusions:AZD4547 did not significantly improve PFS versus paclitaxel in gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2 amplification/polysomy and FGFR2 expression indicates the need for alternative predictive biomarker testing. AZD4547 was generally well tolerated

The surprising Far-UV spectrum of the polar BY Camelopardalis

We report on the first far-UV observations of the asynchronous polar BY Cam made by the Far-Ultraviolet Spectroscopic Explorer (FUSE). The source is known to exhibit the most extreme NV/CIV emission resonance line ratio observed among polars. The FUSE observations reveal a OVI resonance line weaker than in the prototype of polars, AM Her, with the absence of a detectable narrow component. The OVI broad line is detected with an equivalent width of the same order as in AM Her, the blueward doublet component is clearly present but the redward component is strongly affected by H2 absorption. The presence of a strong NIII line and weak CIII lines also confirms the peculiar CNO line flux. We compare the resonance CNO line intensities with the predictions of the CLOUDY plasma code coupled to a geometrical model of the accretion column. Varying the temperature and/or intensity of the ionising spectrum is unable to reproduce the observed broad line ratios. A solution is obtained by significantly altering the element abundances with a strong depletion of C, overabundance of N and a weak underabundance of O. This confirms previous suggestions of non-solar abundances which may result from redistribution in the accreted material following nova outbursts and/or the secondary nuclear evolution. A very significant H2 absorption is observed in front of the source, a possible indication for either the existence of a dense interstellar cloud or of circumstellar material.Comment: 6 pages, 4 Postscript figures, accepted by Astronomy and Astrophysics, uses aa.st

Optical Excitations and Field Enhancement in Short Graphene Nanoribbons

The optical excitations of elongated graphene nanoflakes of finite length are investigated theoretically through quantum chemistry semi-empirical approaches. The spectra and the resulting dipole fields are analyzed, accounting in full atomistic details for quantum confinement effects, which are crucial in the nanoscale regime. We find that the optical spectra of these nanostructures are dominated at low energy by excitations with strong intensity, comprised of characteristic coherent combinations of a few single-particle transitions with comparable weight. They give rise to stationary collective oscillations of the photoexcited carrier density extending throughout the flake, and to a strong dipole and field enhancement. This behavior is robust with respect to width and length variations, thus ensuring tunability in a large frequency range. The implications for nanoantennas and other nanoplasmonic applications are discussed for realistic geometries

Human Wavelength Discrimination of Monochromatic Light Explained by Optimal Wavelength Decoding of Light of Unknown Intensity

We show that human ability to discriminate the wavelength of monochromatic light can be understood as maximum likelihood decoding of the cone absorptions, with a signal processing efficiency that is independent of the wavelength. This work is built on the framework of ideal observer analysis of visual discrimination used in many previous works. A distinctive aspect of our work is that we highlight a perceptual confound that observers should confuse a change in input light wavelength with a change in input intensity. Hence a simple ideal observer model which assumes that an observer has a full knowledge of input intensity should over-estimate human ability in discriminating wavelengths of two inputs of unequal intensity. This confound also makes it difficult to consistently measure human ability in wavelength discrimination by asking observers to distinguish two input colors while matching their brightness. We argue that the best experimental method for reliable measurement of discrimination thresholds is the one of Pokorny and Smith, in which observers only need to distinguish two inputs, regardless of whether they differ in hue or brightness. We mathematically formulate wavelength discrimination under this wavelength-intensity confound and show a good agreement between our theoretical prediction and the behavioral data. Our analysis explains why the discrimination threshold varies with the input wavelength, and shows how sensitively the threshold depends on the relative densities of the three types of cones in the retina (and in particular predict discriminations in dichromats). Our mathematical formulation and solution can be applied to general problems of sensory discrimination when there is a perceptual confound from other sensory feature dimensions

ARCTIC: Durvalumab + tremelimumab and durvalumab monotherapy vs SoC in ≥ 3L advanced NSCLC treatment

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Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case-control study.

In malaria endemic areas anaemia is a usually silent condition that nevertheless places a considerable burden on health services. Cases of severe anaemia often require hospitalization and blood transfusions. The objective of this study was to assess risk factors for admission with anaemia to facilitate the design of anaemia control programmes. We conducted a prospective case-control study of children aged 2-59 months admitted to a district hospital in southern Tanzania. There were 216 cases of severe anaemia [packed cell volume (PCV) < 25%] and 234 age-matched controls (PCV > or = 25%). Most cases [55.6% (n = 120)] were < 1 year of age. Anaemia was significantly associated with the educational level of parents, type of accommodation, health-seeking behaviour, the child's nutritional status and recent and current medical history. Of these, the single most important factor was Plasmodium falciparum parasitaemia [OR 4.3, 95% confidence interval (CI) 2.9-6.5, P < 0.001]. Multivariate analysis showed that increased recent health expenditure [OR 2.2 (95% CI 1.3-3.9), P = 0.005], malnutrition [OR 2.4 (95%CI 1.3-4.3), P < 0.001], living > 10 km from the hospital [OR 3.0 (95% CI 1.9-4.9), P < 0.001], a history of previous blood transfusion [OR 3.8 (95% CI 1.7-9.1), P < 0.001] and P. falciparum parasitaemia [OR 9.5 (95% CI 4.3-21.3), P < 0.001] were independently related to risk of being admitted with anaemia. These findings are considered in terms of the pathophysiological pathway leading to anaemia. The concentration of anaemia in infants and problems of access to health services and adequate case management underline the need for targeted preventive strategies for anaemia control

Species specific anaesthetics for fish anaesthesia and euthanasia.

There is a need to ensure that the care and welfare for fish maintained in the laboratory are to the highest standards. This extends to the use of anaesthetics for both scientific study, humane killing and euthanasia at end of life. An anaesthetic should not induce negative behaviours and fish should not seek to avoid the anaesthetic. Surprisingly little information is available to facilitate a humane choice of anaesthetic agent for fish despite over 100 years of use and the millions of fish currently held in thousands of laboratories worldwide. Using a chemotaxic choice chamber we found different species specific behavioural responses among four closely related fish species commonly held in the laboratory, exposed to three widely used anaesthetic agents. As previously found for zebrafish (Danio rerio), the use of MS-222 and benzocaine also appears to induce avoidance behaviours in medaka (Oryzias latipes); but etomidate could provide an alternative choice. Carp (Cyprinus carpio), although closely related to zebrafish showed avoidance behaviours to etomidate, but not benzocaine or MS-222; and rainbow trout (Oncorhynchus mykiss) showed no avoidance to the three agents tested. We were unable to ascertain avoidance responses in fathead minnows (Pimephales promelas) and suggest different test paradigms are required for that species