A longitudinal empirical investigation of the pathways model of problem gambling

Background and Aims: The Pathways Model of Problem Gambling suggests the existence of three developmental pathways to problem gambling, each differentiated by a set of predisposing biopsychosocial characteristics: Behaviorally Conditioned (BC), Emotionally Vulnerable (EV), and Biologically Vulnerable (BV) gamblers. This study examined the empirical validity of the Pathways Model among adolescents followed up to early adulthood. Design: A prospectivelongitudinal design was used, thus overcoming limitations of past studies that used concurrent or retrospective designs. Setting: Two samples were used: a) a population sample of French-speaking adolescents (N = 1,033) living in low socio-economic status (SES) neighborhoods from the Greater Region of Montreal (Quebec, Canada), and b) a population sample of adolescents (N = 3,017), representative of French-speaking students in Quebec. Participants: Only participants with at-risk or problem gambling by mid-adolescence or early adulthood were included in the main analysis (n = 180). Analyses: Latent Profile Analyses were conducted to identify the optimal number of profiles, in accordance with participants’ scores on a set of variables prescribed by the Pathways Model and measured during early adolescence: depression, anxiety, impulsivity, hyperactivity, antisocial/aggressive behavior, and drug problems. Findings: A four-profile model fit the data best. Three profiles differed from each other in ways consistent with the Pathways Model (i.e., BC, EV, and BV gamblers). A fourth profile emerged, resembling a combination of EV and BV gamblers. Conclusions: Four profiles of at-risk and problem gamblers were identified. Three of these profiles closely resemble those suggested by the Pathways Model

Young "Dipper" Stars in Upper Sco and ρ\rho Oph Observed by K2

We present ten young ($\lesssim$10 Myr) late-K and M dwarf stars observed in K2 Campaign 2 that host protoplanetary disks and exhibit quasi-periodic or aperiodic dimming events. Their optical light curves show $\sim$10-20 dips in flux over the 80-day observing campaign with durations of $\sim$0.5-2 days and depths of up to $\sim$40%. These stars are all members of the $\rho$ Ophiuchus ($\sim$1 Myr) or Upper Scorpius ($\sim$10 Myr) star-forming regions. To investigate the nature of these "dippers" we obtained: optical and near-infrared spectra to determine stellar properties and identify accretion signatures; adaptive optics imaging to search for close companions that could cause optical variations and/or influence disk evolution; and millimeter-wavelength observations to constrain disk dust and gas masses. The spectra reveal Li I absorption and H$\alpha$ emission consistent with stellar youth (<50 Myr), but also accretion rates spanning those of classical and weak-line T Tauri stars. Infrared excesses are consistent with protoplanetary disks extending to within $\sim$10 stellar radii in most cases; however, the sub-mm observations imply disk masses that are an order of magnitude below those of typical protoplanetary disks. We find a positive correlation between dip depth and WISE-2 excess, which we interpret as evidence that the dipper phenomenon is related to occulting structures in the inner disk, although this is difficult to reconcile with the weakly accreting aperiodic dippers. We consider three mechanisms to explain the dipper phenomenon: inner disk warps near the co-rotation radius related to accretion; vortices at the inner disk edge produced by the Rossby Wave Instability; and clumps of circumstellar material related to planetesimal formation.Comment: Accepted to ApJ, 19 pages, 10 figure

X-ray structure of <i>Fasciola hepatica</i> Sigma class glutathione transferase 1 reveals a disulfide bond to support stability in gastro-intestinal environment

This is the final version. Available on open access from Nature Research via the DOI in this recordData delivery: The structure factors and the refined coordinates of the FhGST-S1 structures have been deposited with the Protein Data Bank and have the access codes 2WB9 and 2WDU.Sigma class GST (Prostaglandin D synthase), FhGST-S1, is present in the excretory–secretory products (ES) of the liver fluke parasite Fasciola hepatica as cargo of extracellular vesicles (EVs) released by the parasite. FhGST-S1 has a well characterised role in the modulation of the immune response; a key fluke intercession that allows for establishment and development within their hosts. We have resolved the three-dimensional structure of FhGST-S1 in complex with its co-factor glutathione, in complex with a glutathione-cysteine adduct, and in a glutathione disulfide complex in order to initiate a research pipeline to mechanistically understand how FhGST-S1 functions within the host environment and to rationally design selective inhibitors. The overall fold of FhGST-S1 shows high structural similarity to other Sigma class GSTs. However, a unique interdomain disulfide bond was found in the FhGST-S1 which could stabilise the structure within the host gastro-intestinal environment. The position of the two domains of the protein with respect to each other is seen to be crucial in the formation of the active site cleft of the enzyme. The interdomain disulfide bond raises the possibility of oxidative regulation of the active site of this GST protein.European Union FP6Biotechnology and Biological Sciences Research Council (BBSRC)NRN WalesUniversity of Exete

In vitro biomarker discovery in the parasitic flatworm Fasciola hepatica for monitoring chemotherapeutic treatment

The parasitic flatworm Fasciola hepatica is a global food security risk. With no vaccines, the sustainability of triclabendazole (TCBZ) is threatened by emerging resistance. F. hepatica excretory/secretory (ES) products can be detected in host faeces and used to estimate TCBZ success and failure. However, there are no faecal based molecular diagnostics dedicated to assessing drug failure or resistance to TCBZ in the field. Utilising in vitro maintenance and sub-proteomic approaches two TCBZ stress ES protein response fingerprints were identified: markers of non-killing and lethal doses. This study provides candidate protein/peptide biomarkers to validate for detection of TCBZ failure and resistance

EPIC 220204960: A Quadruple Star System Containing Two Strongly Interacting Eclipsing Binaries

We present a strongly interacting quadruple system associated with the K2 target EPIC 220204960. The K2 target itself is a Kp = 12.7 magnitude star at Teff ~ 6100 K which we designate as "B-N" (blue northerly image). The host of the quadruple system, however, is a Kp = 17 magnitude star with a composite M-star spectrum, which we designate as "R-S" (red southerly image). With a 3.2" separation and similar radial velocities and photometric distances, 'B-N' is likely physically associated with 'R-S', making this a quintuple system, but that is incidental to our main claim of a strongly interacting quadruple system in 'R-S'. The two binaries in 'R-S' have orbital periods of 13.27 d and 14.41 d, respectively, and each has an inclination angle of >89 degrees. From our analysis of radial velocity measurements, and of the photometric lightcurve, we conclude that all four stars are very similar with masses close to 0.4 Msun. Both of the binaries exhibit significant ETVs where those of the primary and secondary eclipses 'diverge' by 0.05 days over the course of the 80-day observations. Via a systematic set of numerical simulations of quadruple systems consisting of two interacting binaries, we conclude that the outer orbital period is very likely to be between 300 and 500 days. If sufficient time is devoted to RV studies of this faint target, the outer orbit should be measurable within a year.Comment: 20 pages, 18 figures, 7 tables; accepted for publication in MNRA

Intestinal schistosomiasis in Uganda at high altitude (>1400 m): malacological and epidemiological surveys on Mount Elgon and in Fort Portal crater lakes reveal extra preventive chemotherapy needs

Background Intestinal schistosomiasis is of public health importance in Uganda but communities living above 1400 m are not targeted for control as natural transmission is thought unlikely. To assess altitudinal boundaries and at-risk populations, conjoint malacological and epidemiological surveys were undertaken on Mount Elgon (1139 m–3937 m), in Fort Portal crater lakes and in the Rwenzori Mountains (1123 m–4050 m). Methods Seventy freshwater habitats [Mount Elgon (37), Fort Portal crater lakes (23), Rwenzori Mountains (8) and Lake Albert (2)] were inspected for Biomphalaria species. Water temperature, pH and conductivity were recorded. A parasitological examination of 756 schoolchildren [Mount Elgon (300), Fort Portal crater lakes (456)] by faecal microscopy of duplicate Kato-Katz smears from two consecutive stool samples was bolstered by antigen (urine-CCA dipstick) and antibody (SEA-ELISA) diagnostic assays. Results Biomphalaria spp. was found up to 1951 m on Mount Elgon and 1567 m in the Fort Portal crater lakes. Although no snail from Mount Elgon shed cercariae, molecular analysis judged 7.1% of snails sampled at altitudes above 1400 m as having DNA of Schistosoma mansoni; in Fort Portal crater lakes three snails shed schistosome cercariae. Prevalence of intestinal schistosomiasis as measured in schoolchildren by Kato-Katz (Mount Elgon = 5.3% v. Fort Portal crater lakes = 10.7%), CCA urine-dipsticks (18.3% v. 34.4%) and SEA-ELISA (42.3% v. 63.7%) showed negative associations with increasing altitude with some evidence of infection up to 2000 m. Conclusions Contrary to expectations, these surveys clearly show that natural transmission of intestinal schistosomiasis occurs above 1400 m, possibly extending up to 2000 m. Using spatial epidemiological predictions, this now places some extra six million people at-risk, denoting an expansion of preventive chemotherapy needs in Uganda