Uneven progress in reducing exposure to violence at home for New Zealand adolescents 2001–2012: a nationally representative cross‐sectional survey series

Objective: To explore trends, and identify risk factors, that may explain changes in adolescent exposure to family violence over time.Methods: Data for this study was drawn from the Youth 2000 series of cross‐sectional surveys, carried out with New Zealand high school students in 2001, 2007 and 2012. Latent class analysis was used to understand different patterns of exposure to multiple risks for witnessing violence at home among adolescents.Results: Across all time periods, there was no change in witnessing emotional violence and a slight decline in witnessing physical violence at home. However, significant differences were noted between 2001 and 2007, and 2007 and 2012, in the proportion of adolescents who reported witnessing emotional and physical violence. Four latent classes were identified in the study sample; these were characterised by respondents' ethnicity, concerns about family relationships, food security and alcohol consumption. For two groups (characterised by food security, positive relationships and lower exposure to physical violence), there was a reduction in the proportion of respondents who witnessed physical violence but an increase in the proportion who witnessed emotional violence between 2001 and 2012. For the two groups characterised by poorer food security and higher exposure to physical violence, there were no changes in witnessing of physical violence in the home.Implications for public health: In addition to strategies directly aimed at violence, policies are needed to address key predictors of violence exposure such as social disparities, financial stress and alcohol use. These social determinants of health cannot be ignored

The health and well-being of transgender high school students: results from the New Zealand adolescent health survey (Youth’12).

Purpose To report the prevalence of students according to four gender groups (i.e., those who reported being non-transgender, transgender, or not sure about their gender, and those who did not understand the transgender question), and to describe their health and well-being. Methods Logistic regressions were used to examine the associations between gender groups and selected outcomes in a nationally representative high school health and well-being survey, undertaken in 2012. Results Of the students (n = 8,166), 94.7% reported being non-transgender, 1.2% reported being transgender, 2.5% reported being not sure about their gender, and 1.7% did not understand the question. Students who reported being transgender or not sure about their gender or did not understand the question had compromised health and well-being relative to their nontransgender peers; in particular, for transgender students perceiving that a parent cared about them (odds ratio [OR], .3; 95% confidence interval[CI], .2 -.4), depressive symptoms (OR, 5.7; 95% CI, 3.6-9.2), suicide attempts (OR, 5.0; 95% CI, 2.9-8.8), and school bullying (OR, 4.5; 95% CI, 2.4-8.2). Conclusions This is the first nationally representative survey to report the health and well-being of students who report being transgender. We found that transgender students and those reporting not being sure are a numerically small but important group. Transgender students are diverse and are represented across demographic variables, including their sexual attractions. Transgender youth face considerable health and well-being disparities. It is important to address the challenging environments these students face and to increase access to responsive services for transgender youth

Unobscured Type 2 AGNs

Type 2 AGNs with intrinsically weak broad emission lines (BELs) would be exceptions to the unified model. After examining a number of proposed candidates critically, we find that the sample is contaminated significantly by objects with BELs of strengths indicating that they actually contain intermediate-type AGNs, plus a few Compton-thick sources as revealed by extremely low ratios of X-ray to nuclear IR luminosities. We develop quantitative metrics that show two (NGC 3147 and NGC 4594) of the remaining candidates to have BELs 2-3 orders of magnitude weaker than those of typical type-1 AGNs. Several more galaxies remain as candidates to have anomalously weak BELs, but this status cannot be confirmed with the existing information. Although the parent sample is poorly defined, the two confirmed objects are well under 1% of its total number of members, showing that the absence of a BEL is possible, but very uncommon in AGN. We evaluate these two objects in detail using multi-wavelength measurements. They have little X-ray extinction with N_H < 10^21 cm^{-2}. Their IR spectra show strong silicate emission (NGC 4594) or weak aromatic features on a generally power law continuum with a suggestion of silicates in emission (NGC 3147). No polarized BEL is detected in NGC 3147. These results indicate that the two unobscured type-2 objects have circumnuclear tori that are approximately face-on. Combined with their X-ray and optical/UV properties, this behavior implies that we have an unobscured view of the nuclei and thus that they have intrinsically weak BELs. We compare their properties with those of the other less-extreme candidates. We then compare the distributions of bolometric luminosities and accretion rates of these objects with theoretical models that predict weak BELs.Comment: Accepted for publication in ApJ, 17 pages, 13 figure

Facilitated Practice-based Research Report: Working together in Safeguarding Children and Vulnerable Adults

The purpose of the report is to share findings from a small-scale exploratory research study, conducted by a group of practitioners who participated in a Facilitated Practice-based Research project. The aim of the research was to understand how partner professional e.g. from health, mental health, education, police, housing, charities etc. perceive and experience safeguarding when working with social workers. A qualitative survey was distributed across the Northeast region with all partner professionals invited to participate, who had experience of working with any Local Authority in the NESWA partnership. Each survey consisted of five open-ended questions giving participants the opportunity to explain their responses, and a total of 67 responses were received – of these 33 worked with adults and 34 with children

N-acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double blind randomised placebo controlled trial targeting negative symptoms

BACKGROUND: Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40-60&nbsp;% of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered \u27clozapine resistant\u27. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ. METHODS: This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2&nbsp;g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes. DISCUSSION: This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a \u27go to\u27 adjunct in patients that are only partly responsive to clozapine.<br /

PaLM: Scaling Language Modeling with Pathways

Large language models have been shown to achieve remarkable performance across a variety of natural language tasks using few-shot learning, which drastically reduces the number of task-specific training examples needed to adapt the model to a particular application. To further our understanding of the impact of scale on few-shot learning, we trained a 540-billion parameter, densely activated, Transformer language model, which we call Pathways Language Model PaLM. We trained PaLM on 6144 TPU v4 chips using Pathways, a new ML system which enables highly efficient training across multiple TPU Pods. We demonstrate continued benefits of scaling by achieving state-of-the-art few-shot learning results on hundreds of language understanding and generation benchmarks. On a number of these tasks, PaLM 540B achieves breakthrough performance, outperforming the finetuned state-of-the-art on a suite of multi-step reasoning tasks, and outperforming average human performance on the recently released BIG-bench benchmark. A significant number of BIG-bench tasks showed discontinuous improvements from model scale, meaning that performance steeply increased as we scaled to our largest model. PaLM also has strong capabilities in multilingual tasks and source code generation, which we demonstrate on a wide array of benchmarks. We additionally provide a comprehensive analysis on bias and toxicity, and study the extent of training data memorization with respect to model scale. Finally, we discuss the ethical considerations related to large language models and discuss potential mitigation strategies

Efflux in Fungi: La Pièce de Résistance

Pathogens must be able to overcome both host defenses and antimicrobial treatment in order to successfully infect and maintain colonization of the host. One way fungi accomplish this feat and overcome intercellular toxin accumulation is efflux pumps, in particular ATP-binding cassette transporters and transporters of the major facilitator superfamily. Members of these two superfamilies remove many toxic compounds by coupling transport with ATP hydrolysis or a proton gradient, respectively. Fungal genomes encode a plethora of members of these families of transporters compared to other organisms. In this review we discuss the role these two fungal superfamilies of transporters play in virulence and resistance to antifungal agents. These efflux transporters are responsible not only for export of compounds involved in pathogenesis such as secondary metabolites, but also export of host-derived antimicrobial compounds. In addition, we examine the current knowledge of these transporters in resistance of pathogens to clinically relevant antifungal agents

KrasP34R and KrasT58I mutations induce distinct RASopathy phenotypes in mice.

Somatic KRAS mutations are highly prevalent in many cancers. In addition, a distinct spectrum of germline KRAS mutations causes developmental disorders called RASopathies. The mutant proteins encoded by these germline KRAS mutations are less biochemically and functionally activated than those in cancer. We generated mice harboring conditional KrasLSL-P34Rand KrasLSL-T58I knock-in alleles and characterized the consequences of each mutation in vivo. Embryonic expression of KrasT58I resulted in craniofacial abnormalities reminiscent of those seen in RASopathy disorders, and these mice exhibited hyperplastic growth of multiple organs, modest alterations in cardiac valvulogenesis, myocardial hypertrophy, and myeloproliferation. By contrast, embryonic KrasP34R expression resulted in early perinatal lethality from respiratory failure due to defective lung sacculation, which was associated with aberrant ERK activity in lung epithelial cells. Somatic Mx1-Cre-mediated activation in the hematopoietic compartment showed that KrasP34R and KrasT58I expression had distinct signaling effects, despite causing a similar spectrum of hematologic diseases. These potentially novel strains are robust models for investigating the consequences of expressing endogenous levels of hyperactive K-Ras in different developing and adult tissues, for comparing how oncogenic and germline K-Ras proteins perturb signaling networks and cell fate decisions, and for performing preclinical therapeutic trials

Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines

Background: EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. Methods: Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. Results: Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. Conclusion: This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination with EGF, on human colon cancer cell lines. The EGFR inhibitors have a weaker effect in the presence of EGF that binds EGFR. Cetuximab treatment showed an expression pattern that inversely correlates with EGF treatment. We found interesting cytomorphological features closely relating to gene expression profile. Both drugs have an effect on differentiation towards cellular death