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First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
An essential strategy to increase coverage of psychosocial treatments globally is task shifting to non-medical counsellors, but evidence on its effectiveness is still scarce. This study evaluates the effectiveness of lay psychosocial counselling among persons with psychological distress in a primary health care setting in rural Nepal.
A parallel randomized controlled trial in Dang, rural Nepal (NCT03544450). Persons aged 16 and older attending primary care and with a General Health Questionnaire (GHQ-12) score of 6 or more were randomized (1:1) to receive either non-medical psychosocial counselling (PSY) or enhanced usual care (EUC). PSY was provided by lay persons with a 6-month training and consisted of 5-weekly counselling sessions of 35–60 min with a culturally adapted solution-focused approach. EUC was provided by trained primary health workers. Participants were followed up at 1 (T1) and 6 months (T2). The primary outcome, response to treatment, was the reduction of minimum 50% in the Beck Depression Inventory (BDI) score.
A total of 141 participants, predominantly socially disadvantaged women, were randomized to receive PSY and 146 to EUC. In the PSY, 123 participants and 134 in the EUC were analysed. In PSY, 101 participants (81.4%) had a response compared with 57 participants (42.5%) in EUC [percentage difference 39.4% (95% CI 28.4–50.4)]. The difference in BDI scores at T2 between PSY and EUC was −7.43 (95% CI −9.71 to −5.14).
Non-medical (lay) psychosocial counselling appears effective in reducing depressive symptoms, and its inclusion in mental health care should be considered in low-resource settings.
Background: SMA1 is a neurodegenerative disease caused by bi-allelic survival motor neuron 1 gene (SMN1) deletion/mutation. In the phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA1 patients. We report preliminary data of STR1VE, a pivotal study (NCT03306277) evaluating efficacy and safety of a one-time intravenous AVXS-101 infusion. Methods: STR1VE is a phase 3, multicenter, open-label, single-arm study in SMA1 patients aged <6 months (bi-allelic SMN1 loss, 2xSMN2). Primary outcomes: independent sitting for ≥30 seconds (18 months) and survival (14 months). Secondary outcomes: ability to thrive and ventilatory support (18 months). Exploratory outcomes: CHOP-INTEND and Bayley Scales of Infant and Toddler Development scores. Results: Enrollment is complete with 22 patients dosed. Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support, and all exclusively fed by mouth. Mean baseline CHOP-INTEND score was 32.6 (17.0–52.0), which increased 6.9 (-4.0–16.0, n=20), 10.4 (2.0–18.0, n=12), and 11.6 (-3.0–23.0, n=9) points at 1, 2, and 3 months; updates provided at congress. Conclusions: Preliminary data from STR1VE show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.
The new species Lenonchium zanjanense sp. n. is described from a natural habitat of Zanjan province, Iran, including line, light microscopy and scanning electron microscopy illustrations and a molecular (18S, 28S) study. It is characterized by its 3.50–4.51 mm long body, rounded lip region, continuous and 13.5–15.5 µm broad, odontostyle 21–24 µm long, neck 362–490 µm long, double guiding ring, pharyngeal expansion 190–285 µm long, female genital system didelphic–amphidelphic, uterus simple and 185–320 µm long or 3.4–5.9 times the corresponding body diameter, vulva nearly equatorial (V = 45–53), tail conical-elongated to filiform (90–165 µm, c = 23–43, c′ = 2.4–5.3) with three or four mucro-like projections at the tip, spicules 58–64 µm long and 16–21 contiguous ventromedian supplements ending at the level of the anterior end of the spicules. The taxonomy of the genus is updated, with an emended diagnosis, list of species, key to their identification and a compendium of their main morphometrics. Lenonchium asterocaudatum is regarded as identical and a junior synonym of L. denticaudatum. New insights into the phylogeny of the group are also provided, and the classification of Lenonchium within Nordiidae is seriously questioned.
This work reports by the first time a method to control the geometry of Ga2O3 films nanocrystallites at 350 °C. The formation of controlled shaped nano-crystallites of γ-Ga2O3 from amorphous Ga2O3 films grown by RF-Sputtering at room temperature driven by nano-layers of group IB metals (Cu, Ag or Au) is studied. The reported results can be explained by the role of subsurface metal nano-layers and the non-equilibrium nature of the sputtering processes. To study the effects on the surface structure and their optical properties arrays of amorphous-Ga2O3/IB-metal/amorphous-Ga2O3 were annealed in dry N2 atmosphere at 350 °C by 50, 100 and 150 min. The experimental results can be explained by the evolution of the amorphous character of the films amorphous films towards the nanocrystalline γ-Ga2O3 phase driven by the metal nano-layer seed nature. As the annealing time was increased the transition from amorphous-Ga2O3 to the nanocrystalline γ-Ga2O3 phase was detected by X-ray diffraction analysis. The transition to the nanocrystalline γ-Ga2O3 is demonstrated by the formation of octahedral, triangle and ball shape nanocrystallites with sizes of ∼5 to 50 nm according to FE-SEM analysis. The influence of the metal nano-layer is clearly seen by the shift of the plasmon frequency resonance produced by the Ga2O3/IB-metal/Ga2O3 arrays in the region from 400 to 600 nm caused by the modification of the interface Ga2O3/IB-metal produced by the applied annealing stages.
Jakobshavn Isbræ, a tidewater glacier that produces some of Greenland's largest icebergs and highest speeds, reached record-high flow rates in 2012 (Joughin and others, 2014). We use terrestrial radar interferometric observations from August 2012 to characterize the events that led to record-high flow. We find that the highest speeds occurred in response to a small calving retreat, while several larger calving events produced negligible changes in glacier speed. This non-linear response to calving events suggests the terminus was close to flotation and therefore highly sensitive to terminus position. Our observations indicate that a glacier's response to calving is a consequence of two competing feedbacks: (1) an increase in strain rates that leads to dynamic thinning and faster flow, thereby promoting destabilization, and (2) an increase in flow rates that advects thick ice toward the terminus and promotes restabilization. The competition between these feedbacks depends on temporal and spatial variations in the glacier's proximity to flotation. This study highlights the importance of dynamic thinning and advective processes on tidewater glacier stability, and further suggests the latter may be limiting the current retreat due to the thick ice that occupies Jakobshavn Isbræ’s retrograde bed.
Using multilevel models, we examined mother-, father-, and child-reported (N = 1,336 families) externalizing behavior problem trajectories from age 7 to 14 in nine countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States). The intercept and slope of children's externalizing behavior trajectories varied both across individuals within culture and across cultures, and the variance was larger at the individual level than at the culture level. Mothers’ and children's endorsement of aggression as well as mothers’ authoritarian attitudes predicted higher age 8 intercepts of child externalizing behaviors. Furthermore, prediction from individual-level endorsement of aggression and authoritarian attitudes to more child externalizing behaviors was augmented by prediction from cultural-level endorsement of aggression and authoritarian attitudes, respectively. Cultures in which father-reported endorsement of aggression was higher and both mother- and father-reported authoritarian attitudes were higher also reported more child externalizing behavior problems at age 8. Among fathers, greater attributions regarding uncontrollable success in caregiving situations were associated with steeper declines in externalizing over time. Understanding cultural-level as well as individual-level correlates of children's externalizing behavior offers potential insights into prevention and intervention efforts that can be more effectively targeted at individual children and parents as well as targeted at changing cultural norms that increase the risk of children's and adolescents’ externalizing behavior.
Current standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Most tumors recur within a year from diagnosis and median survival for recurrent GBM (rGBM) is 3-9 months. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance, exhibited by most GBM patients. VAL-083 is a DNA-targeting agent with a mechanism-of-action that is independent of MGMT. VAL-083 overcomes temozolomide-resistance in GBM cell-lines, cancer stem cells, and in vivo models. VAL-083 readily crosses the blood-brain barrier and accumulates in brain-tumor tissue. We recently completed a VAL-083 dose-escalation trial in temozolomide- and bevacizumab-refractory rGBM and determined that 40mg/m2/day given intravenously on days 1,2,3 of a 21-day cycle is generally well-tolerated. This dosing regimen was selected for subsequent GBM trials, including an ongoing single-arm, biomarker-driven Phase 2 trial (N=48) in temolozomide-refractory, bevacizumab-naïve rGBM , MGMT-unmethylated (Clinicaltrials.gov:NCT02717962). The primary objective of this study is to determine if VAL-083 improves OS compared to a historical control of 7.15 months for MGMT-unmethylated rGBM patients treated with lomustine (EORTC26101). In addition, another single-arm, biomarker-driven, Phase 2 study (N=25) of VAL-083 in combination with radiotherapy in newly diagnosed GBM, MGMT-unmethylated is ongoing (Clinicaltrials.gov:NCT03050736). This trial aims to determine a dose for further study of VAL-083 in combination with radiotherapy and explore if VAL-083 improves PFS and OS compared to historical results in newly diagnosed GBM. Enrollment and safety data updates will be provided at the meeting. The results of these studies, if successful, may support VAL-083 as part of a new chemotherapeutic treatment paradigm for GBM.
The present study examines the influence of language proficiency and language combination on bilingual lexical access using category fluency in 109 healthy speakers. Participants completed a category fluency task in each of their languages in three main categories (animals, clothing, and food), each with two subcategories, as well as a language use questionnaire assessing their proficiency. Five language combinations were examined (Hindi–English, Kannada–English, Mandarin–English, Spanish–English, and Turkish–English). Multivariate analyses of variance revealed that the average number of correct items named in the category fluency task across the three main categories varied across the different groups only in English and not the other language. Further, results showed that language exposure composite (extracted from the questionnaire using a principal component analysis) significantly affected the average number of items named across the three main categories. Overall, these results demonstrate the effects of particular language combinations on bilingual lexical access and provide important insights into the role of proficiency on access.
Here we evaluated the effect of fermented milk supplemented with whey protein (approximately 80 % protein), probiotic (Bifidobacterium animalis subsp. lactis BB12) and pomegranate juice (Punica granatum L.) on the physical performance, intestinal motility and villi structure, inflammatory markers and intestinal microbiota of rats under high-intensity acute exercise. In all, twenty-four Wistar rats were separated into groups: control (Ctrl), supplemented (Supp), exercised (Exe) and exercised and supplemented (Exe+Supp). Rats in the Supp groups received fermented milk during 6 weeks by oral administration. At the end of the supplementation period, the Exe groups were submitted to high-intensity acute exercise on a treadmill. We found that intense acute exercise caused changes in the intestinal villi interspace, changes in the proportion of Lactobacillus species and an increase in Clostridium species, as well as a decrease in intestinal motility. Supplementation increased intestinal motility, and maintained the intestinal villi interspace and the natural microbiota proportions of the exercised rats. Physical performance was not improved by fermented milk supplementation. We conclude that the fermented milk containing whey protein, B. animalis (BB12) and pomegranate juice can re-establish intestinal microbiota and protect the animals from the undesirable effects of intense acute exercise.
Milk fat composition can be modulated by the inclusion of lipid supplements in ruminant diets. An interaction between the lipid supplement and the forage to concentrate ratio or the type of forage in the rations may affect milk fat composition. However, little is known about the effects of the starch-to-non-forage NDF ratio in the concentrate and lipid supplementation of goat diets. The aim of this work was to determine the role of dietary carbohydrates in goats rations supplemented with linseed oil on animal performance and milk fatty acid (FA) profile. A total of 16 dairy goats were allocated to two simultaneous experiments (two treatments each), in a crossover design with four animals per treatment and two experimental periods of 25 days. In both experiments alfalfa hay was the sole forage and the forage to concentrate ratio (33:67) remained constant. The concentrate in experiment 1 consisted of barley, maize and soybean meal (concentrate rich in starch), whereas it included soybean hulls replacing 25% of barley and 25% maize in experiment 2 (concentrate rich in NDF). As a result, the starch-to-non-forage NDF ratio was 3.1 in experiment 1 and it decreased to 0.8 in experiment 2. Both concentrates were administered either alone or in combination with 30 g/day of linseed oil. Animal performance parameters were not affected by experimental treatments. In contrast, major changes were observed in milk FA profile due to lipid supplementation and the type of concentrate. Linseed oil significantly raised vaccenic and rumenic acids as well as α-linolenic acid and its biohydrogenation intermediates while decreased medium-chain saturated FA (12:0 to 16:0) in milk fat. Milk fat contents of odd and branched-chain FA and trans-10 18:1 responded differently to linseed oil supplementation according to the concentrate fed.
Using data from 1,177 families in eight countries (Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States), we tested a conceptual model of direct effects of childhood family adversity on subsequent externalizing behaviors as well as indirect effects through psychological mediators. When children were 9 years old, mothers and fathers reported on financial difficulties and their use of corporal punishment, and children reported perceptions of their parents’ rejection. When children were 10 years old, they completed a computerized battery of tasks assessing reward sensitivity and impulse control and responded to questions about hypothetical social provocations to assess their hostile attributions and proclivity for aggressive responding. When children were 12 years old, they reported on their externalizing behavior. Multigroup structural equation models revealed that across all eight countries, childhood family adversity had direct effects on externalizing behaviors 3 years later, and childhood family adversity had indirect effects on externalizing behavior through psychological mediators. The findings suggest ways in which family-level adversity poses risk for children's subsequent development of problems at psychological and behavioral levels, situated within diverse cultural contexts.
We examine repeat surface altimetry and radio echo observations of two supraglacial lakes in the percolation zone of the Greenland ice sheet to investigate the changes in firn conditions leading to lake formation and implications for meltwater storage within firn. Both lakes formed in 2011, when an anomalously high melt season was followed by low winter accumulation, resulting in reduced infiltration and storage in the near surface. The lakes expanded during the 2012 record melt season and retained liquid meltwater through the following winter. The lakes then contracted, with one lake slowly draining and refreezing and another rapidly draining to the subsurface. The lack of observable change in firn conditions surrounding the lakes indicates increased run-off in the near surface firn, likely along low-permeability ice layers formed during the previous melt seasons. This implies a reduced ability of the firn to absorb increased meltwater.
Our results are based on SWP 3215, a 120 min large aperture exposure. The electron density derived from N IV), Si III) and C III) ratios are log Ne < 4.3, 5.0 and 3.5. The measured resonance line ratio 1239/1243 of N V is 1.2 ± 0.1 and 1549/1551 of C IV is 1.9 ± 0.2. Both ratios are expected to be 2.0. Furthermore, it had already been reported that the C IV and N V resonance lines are fainter than predicted from models by factors from ~ 4 to ~ 6 (Torres-Peimbert et al., 1980, The First Two Years of IUE, NASA CP-2171, 641). Internal dust cannot account for any significant deviation from 2 for the resonance doublet ratio of N V (Hummer and Kunasz, 1980, Ap. J., 236, 609). However, the anomalous ratio of N V could be explained by a generally distributed hot ionized medium compatible with the C IV absorption found in approximately the same direction by Cowie et al. (1981, Ap. J., 248, 528).
The central star of NGC 2346 is a well known binary with an A-type primary and a hot companion (Méndez and Niemela 1981). The star went through a series of periodic light variations which ceased in 1986 and were interpreted as an eclipse of a dust cloud passing in front of the binary system (e.g. Méndez et al. 1982, Costero et al. 1986). Recently, light variations reappeared with shallower minima compared to the previous eclipse (e.g. Kohoutek et al. 1992).
The physical conditions and chemical abundances were determined for M2-29 and BB-1 from optical spectrophotometric data and from available IUE material (Table 1). M2-29 has the lowest O/H ratio in PNe and it belongs to the Ar and S rich type IV PN group while BB-1 is very C, N, and Ne rich being Ar and S poor. Comparing with all known PNe of type IV it is found that C/N/O/Ne/Ar do not vary in lockstep, but C, N, O and Ne appear enriched in Ar poor objects (Table 2). C and N are expected to be enriched by the central star, however the anomalous O/Ne/Ar behavior is not understood unless O and Ne are also enriched by the progenitor star. The paper in full will appear in P.A.S.P. 1991.
We carried out spectroscopic observations of N67 (in the SMC), and N66, N97 and N102 (in the LMC) with the 4-m telescope of CTIO. The wavelength range is λλ 3500–7400. From these we obtained physical conditions and chemical abundances of these objects.
Optical and UV spectrophotometric data are analyzed for the central stars of the known Population II planetary nebulae. From this, we derive visual magnitudes, spectral classification, color temperatures, luminosities and masses of the objects. It is found that all the stars show absorption type spectrum and most of them have normal H and He photospheric abundances, the only possible exceptions are M 2–29 and GJJC-1 which seem to be H-deficient stars.
We present low dispersion UV and optical spectrophotometry of the central star of the PN ES0166–21. The stellar spectrum, from 1200 to 6600 Å, is a featureless continuum. The energy distribution is consistent with a black body of 120, 000 ± 20, 000K. The observed visual magnitude is 18.1.