Exploring Pathways into and out of Amphetamine Type Stimulant use at Critical Turning Points: A Qualitative Interview Study

Amphetamine Type Stimulants (ATS) are increasingly used drugs globally. There is limited evidence about what shapes ATS use at critical turning points located within drug using pathways. Using turning point theory, as part of a life course approach, the ATTUNE study aimed to understand which social, economic and individual factors shape pathways into and out of ATS use. Qualitative, semi-structured interviews (n=70) were undertaken with individuals who had used ATS, or who had been exposed to them at least once in their lifetime. Our findings show that turning points for initiation were linked to pleasure, curiosity, boredom and declining mental health; increased use was linked to positive effects experienced at initiation and multiple life-stressors, often leading to more intense use. Decreased use was prompted by pivotal events (e.g. imprisonment) and sustained through continued wellbeing, day-to-day structure, and non-using social networks. We argue that the heterogeneity of these individuals challenges stereotypes of stimulant use allied to nightclubs and ‘hedonism’. Further, even at critical turning points for recovery, the use of services for problematic ATS consumption was low because users prioritised their alcohol or opioid use when seeking help. There is a need to develop service provision, training, and better outreach to individuals who need support at critical turning points

What is the impact of structural and cultural factors and interventions within educational settings on promoting positive mental health and preventing poor mental health: a systematic review

Mental health (MH) difficulties are on the increase among children and young people (CYP). Evidence has shown that educational settings contain both risk and protective factors for MH. This review investigated which structural and cultural factors and interventions within educational settings promote positive MH and prevent poor MH in 4-18 year olds. Searches were conducted in PsychINFO, Embase, ERIC, ASSIA and British Education Index, and reference lists from key studies and relevant systematic reviews were hand-searched. Intervention, cohort, and qualitative studies were included. Of the 62 included papers, 36 examined cultural factors (30 social/relational and six value-related) while 12 studies examined structural factors (eight organisational and four physical) and 14 studies examined multiple factors. There was strong evidence for the impact of positive classroom management techniques, access to physical activity, and peer mentoring on student MH. Studies examining the impact of positive school culture, teacher training in MH and parent involvement in school MH activities also found predominantly positive results for student MH, albeit the evidence was of lower quality or from a low number of studies. Few studies explicitly examined the impact of interventions on MH inequalities; those that did indicated limited if any reduction to inequalities. A very small number of studies suggested that interventions targeting those at risk of poor MH due to socioeconomic factors could successfully improve wellbeing and reduce depression, anxiety and behavioural problems. Studies exploring the effect of management and leadership strategies within schools, policies, and aspects of the physical environment other than green space were scarce or absent in the literature. This review highlights the need to consider the ways in which educational settings are organised, the culture that is created and the physical space in order to improve the MH of CYP

Implications of direct-to-consumer whole-exome sequencing in South Africa

This editorial examines a number of vitally important ethical, legal and scientific concerns that have to be addressed to ensure proper and ethical implementation of direct-to-consumer whole-exome sequencing in South Africa. Individuals taking part in this endeavour must be fully informed of the positive and negative sequelae

High prevalence and diversity of species D adenoviruses (HAdV-D) in human populations of four Sub-Saharan countries

Abstract. Background: Human adenoviruses of species D (HAdV-D) can be associated with acute respiratory illness, epidemic ker

What is the impact of structural and cultural factors and interventions within educational settings on promoting positive mental health and preventing poor mental health: a systematic review.

Mental health (MH) difficulties are on the increase among children and young people (CYP). Evidence has shown that educational settings contain both risk and protective factors for MH. This review investigated which structural and cultural factors and interventions within educational settings promote positive MH and prevent poor MH in 4-18 year olds. Searches were conducted in PsychINFO, Embase, ERIC, ASSIA and British Education Index, and reference lists from key studies and relevant systematic reviews were hand-searched. Intervention, cohort, and qualitative studies were included. Of the 62 included papers, 36 examined cultural factors (30 social/relational and six value-related) while 12 studies examined structural factors (eight organisational and four physical) and 14 studies examined multiple factors. There was strong evidence for the impact of positive classroom management techniques, access to physical activity, and peer mentoring on student MH. Studies examining the impact of positive school culture, teacher training in MH and parent involvement in school MH activities also found predominantly positive results for student MH, albeit the evidence was of lower quality or from a low number of studies. Few studies explicitly examined the impact of interventions on MH inequalities; those that did indicated limited if any reduction to inequalities. A very small number of studies suggested that interventions targeting those at risk of poor MH due to socioeconomic factors could successfully improve wellbeing and reduce depression, anxiety and behavioural problems. Studies exploring the effect of management and leadership strategies within schools, policies, and aspects of the physical environment other than green space were scarce or absent in the literature. This review highlights the need to consider the ways in which educational settings are organised, the culture that is created and the physical space in order to improve the MH of CYP

Structural and biochemical insights into the function and evolution of sulfoquinovosidases

An estimated 10 billion tonnes of sulfoquinovose (SQ) are produced and degraded each year. Prokaryotic sulfoglycolytic pathways catabolize sulfoquinovose (SQ) liberated from plant sulfolipid, or its delipidated form α-d-sulfoquinovosyl glycerol (SQGro), through the action of a sulfoquinovosidase (SQase), but little is known about the capacity of SQ glycosides to support growth. Structural studies of the first reported SQase (Escherichia coli YihQ) have identified three conserved residues that are essential for substrate recognition, but crossover mutations exploring active-site residues of predicted SQases from other organisms have yielded inactive mutants casting doubt on bioinformatic functional assignment. Here, we show that SQGro can support the growth of E. coli on par with d-glucose, and that the E. coli SQase prefers the naturally occurring diastereomer of SQGro. A predicted, but divergent, SQase from Agrobacterium tumefaciens proved to have highly specific activity toward SQ glycosides, and structural, mutagenic, and bioinformatic analyses revealed the molecular coevolution of catalytically important amino acid pairs directly involved in substrate recognition, as well as structurally important pairs distal to the active site. Understanding the defining features of SQases empowers bioinformatic approaches for mapping sulfur metabolism in diverse microbial communities and sheds light on this poorly understood arm of the biosulfur cycle

Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas

Background: Borderline resectable pancreatic cancers infiltrate into adjacent vascular structures to an extent that makes an R0 resection unlikely when pancreatectomy is performed de novo. In a pilot study, Alliance for Clinical Trials in Oncology Trial A021101, the median survival of patients who received chemotherapy and radiation prior to anticipated pancreatectomy was 22 months, and 64% of operations achieved an R0 resection. However, the individual contributions of preoperative chemotherapy and radiation therapy to therapeutic outcome remain poorly defined. Methods: In Alliance for Clinical Oncology Trial A021501, a recently activated randomized phase II trial, patients (N = 134) with a CT or MRI showing a biopsy-confirmed pancreatic ductal adenocarcinoma that meets centrally-reviewed anatomic criteria for borderline resectable disease will be randomized to receive either 8 cycles of modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 over 2 days for 4 cycles) or to 7 cycles of modified FOLFIRINOX followed by stereotactic body radiation therapy (33–40 Gy in 5 fractions). Patients without evidence of disease progression following preoperative therapy will undergo pancreatectomy and will subsequently receive 4 cycles of postoperative modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, bolus 5-fluorouracil 400 mg/m2, and infusional 5-fluorouracil 2400 mg/m2 over 2 days for 4 cycles). The primary endpoint is the 18-month overall survival rate of patients enrolled into each of the two treatment arms. An interim analysis of the R0 resection rate within each arm will be conducted to assess treatment futility after accrual of 30 patients. Secondary endpoints include rates of margin-negative resection and event-free survival. The primary analysis will compare the 18-month overall survival rate of each arm to a historical control rate of 50%. The trial is activated nationwide and eligible to be opened for accrual at any National Clinical Trials Network cooperative group member site. Discussion This study will help define standard preoperative treatment regimens for borderline resectable pancreatic cancer and position the superior arm for further evaluation in future phase III trials. Trial registration ClinicalTrials.gov: NCT02839343, registered July 14, 2016. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3441-z) contains supplementary material, which is available to authorized users

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure