Muon-spin relaxation investigation of magnetic bistability in a crystalline organic radical compound

We present the results of a muon-spin relaxation ($\mu^{+}$SR) investigation of the crystalline organic radical compound 4-(2-benzimidazolyl)-1,2,3,5-dithiadiazolyl (HbimDTDA), in which we demonstrate the hysteretic magnetic switching of the system that takes place at $T = 274 \pm 11\,\mathrm{K}$ caused by a structural phase transition. Muon-site analysis using electronic structure calculations suggests a range of candidate muon stopping sites. The sites are numerous and similar in energy but, significantly, differ between the two structural phases of the material. Despite the difference in the sites, the muon remains a faithful probe of the transition, revealing a dynamically-fluctuating magnetically disordered state in the low-temperature structural phase. In contrast, in the high temperature phase the relaxation is caused by static nuclear moments, with rapid electronic dynamics being motionally narrowed from the muon spectra

A Cross-Sectional Survey of Potential Factors, Motivations, and Barriers Influencing Research Participation and Retention among People Who Use Drugs in the Rural USA

BACKGROUND: Despite high morbidity and mortality among people who use drugs (PWUD) in rural America, most research is conducted within urban areas. Our objective was to describe influencing factors, motivations, and barriers to research participation and retention among rural PWUD. METHODS: We recruited 255 eligible participants from community outreach and community-based, epidemiologic research cohorts from April to July 2019 to participate in a cross-sectional survey. Eligible participants reported opioid or injection drug use to get high within 30 days and resided in high-needs rural counties in Oregon, Kentucky, and Ohio. We aggregated response rankings to identify salient influences, motivations, and barriers. We estimated prevalence ratios to assess for gender, preferred drug use, and geographic differences using log-binomial models. RESULTS: Most participants were male (55%) and preferred methamphetamine (36%) over heroin (35%). Participants reported confidentiality, amount of financial compensation, and time required as primary influential factors for research participation. Primary motivations for participation include financial compensation, free HIV/HCV testing, and contribution to research. Changed or false participant contact information and transportation are principal barriers to retention. Respondents who prefer methamphetamines over heroin reported being influenced by the purpose and use of their information (PR = 1.12; 95% CI: 1.00, 1.26). Females and Oregonians (versus Appalachians) reported knowing and wanting to help the research team as participation motivation (PR = 1.57; 95% CI: 1.09, 2.26 and PR = 2.12; 95% CI: 1.51, 2.99). CONCLUSIONS: Beyond financial compensation, researchers should emphasize confidentiality, offer testing and linkage with care, use several contact methods, aid transportation, and accommodate demographic differences to improve research participation and retention among rural PWUD

Clustering and Alignment of Polymorphic Sequences for HLA-DRB1 Genotyping

Located on Chromosome 6p21, classical human leukocyte antigen genes are highly polymorphic. HLA alleles associate with a variety of phenotypes, such as narcolepsy, autoimmunity, as well as immunologic response to infectious disease. Moreover, high resolution genotyping of these loci is critical to achieving long-term survival of allogeneic transplants. Development of methods to obtain high resolution analysis of HLA genotypes will lead to improved understanding of how select alleles contribute to human health and disease risk. Genomic DNAs were obtained from a cohort of n = 383 subjects recruited as part of an Ulcerative Colitis study and analyzed for HLA-DRB1. HLA genotypes were determined using sequence specific oligonucleotide probes and by next-generation sequencing using the Roche/454 GSFLX instrument. The Clustering and Alignment of Polymorphic Sequences (CAPSeq) software application was developed to analyze next-generation sequencing data. The application generates HLA sequence specific 6-digit genotype information from next-generation sequencing data using MUMmer to align sequences and the R package diffusionMap to classify sequences into their respective allelic groups. The incorporation of Bootstrap Aggregating, Bagging to aid in sorting of sequences into allele classes resulted in improved genotyping accuracy. Using Bagging iterations equal to 60, the genotyping results obtained using CAPSeq when compared with sequence specific oligonucleotide probe characterized 4-digit genotypes exhibited high rates of concordance, matching at 759 out of 766 (99.1%) alleles. © 2013 Ringquist et al

Addressing ethical challenges in HIV prevention research with people who inject drugs

Despite recent advances in HIV prevention and treatment, high HIV incidence persists among people who inject drugs (PWID). Difficult legal and political environments and lack of services for PWID likely contribute to high HIV incidence. Some advocates question whether any HIV prevention research is ethically justified in settings where healthcare system fails to provide basic services to PWID and where implementation of research findings is fraught with political barriers. Ethical challenges in research with PWID include concern about whether research evidence will be translated into practice; concerns that research might exacerbate background risks; and ethical challenges regarding the standard of HIV prevention in research. While these questions arise in other research settings, for research with PWID, these questions are especially controversial. This paper analyses four ethical questions in determining whether research could be ethically acceptable: (1) Can researchers ensure that research does not add to the burden of social harms and poor health experienced by PWID? (2) Should research be conducted in settings where it is uncertain whether research findings will be translated into practice? (3) When best practices in prevention and care are not locally available, what standard of care and prevention is ethically appropriate? (4) Does the conduct of research in settings with oppressive policies constitute complicity? We outline specific criteria to address these four ethical challenges. We also urge researchers to join the call to action for policy change to provide proven safe and effective HIV prevention and harm reduction interventions for PWID around the world

Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity

Background: The term ‘self-harm’ encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as ‘Alternative’ (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as ‘Jocks’ are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group ‘bonding’) functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.<p></p> Methods: An anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).<p></p> Results: An “Alternative” identity was directly (r ≈ 0.3) and a “Jock” identity inversely (r ≈ -0.1) correlated with self-harm. “Alternative” teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4–8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.<p></p> Conclusions: About half of ‘Alternative’ adolescents’ self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. ‘To feel more a part of a group’

Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

A community-based intervention (Young SMILES) to improve the health-related quality of life of children and young people of parents with serious mental illness: randomised feasibility protocol

Children and young people of parents with mental illness (COPMI) are at risk of poor mental, physical and emotional health, which can persist into adulthood. They also experience poorer social outcomes and wellbeing as well as poorer quality of life than their peers with ‘healthy’ parents. The needs of COPMI are likely to be significant; however, their prevalence is unknown, although estimates suggest over 60% of adults with a serious mental illness have children. Many receive little or no support and remain ‘hidden’, stigmatised or do not regard themselves as ‘in need’. Recent UK policies have identified supporting COPMI as a key priority, but this alone is insufficient and healthrelated quality of life has been neglected as an outcome

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD