Geothermal Investigations At Manley Hot Springs, Alaska

Thesis (M.S.) University of Alaska Fairbanks, 198

High Educational Aspirations Among Pregnant Adolescents Are Related to Pregnancy Unwantedness and Subsequent Parenting Stress and Inadequacy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106966/1/jomf12103.pd

Associations between Age, Years in Post, Years in the Profession and Personal Experience of Mental Health Problems in UK Mental Health Nurses

Nurses' mental health is of paramount importance, both in terms of patient safety and the sustainability of the workforce. Age, years in the profession, in post and personal experience or exposure to mental health problems are relevant to the mental health nursing workforce crisis in the United Kingdom. This study aimed to determine the relationship between age, years in the profession and post and self-reported experience of mental health problems using an online cross-sectional survey of 225 UK mental health nurses. Number of years in post was inversely correlated with overall experience of mental health problems, particularly living with someone else with mental health problems. Those with experience of living with someone with mental health problems had significantly fewer years of professional experience than those without. This article discusses possible explanations for this phenomenon and makes the case for future research on the topic

Effect of Differential N-linked and O-linked Mannosylation on Recognition of Fungal Antigens by Dendritic Cells

BACKGROUND. An experimental approach for improving vaccine efficacy involves targeting antigens to mannose receptors (MRs) on dendritic cells (DCs) and other professional antigen presenting cells. Previously, we demonstrated that mannosylated Pichia pastoris-derived recombinant proteins exhibited increased immunogenicity compared to proteins lacking mannosylation. In order to gain insight into the mechanisms responsible for this observation, the present study examined the cellular uptake of the mannosylated and deglycosylated recombinant proteins. METHODOLOGY/PRINCIPAL FINDINGS. Utilizing transfected cell lines, roles for the macrophage mannose receptor (MMR, CD206) and DC-SIGN (CD209) in the recognition of the mannosylated, but not deglycosylated, antigens were demonstrated. The uptake of mannosylated antigens into murine bone marrow-derived DCs (BMDCs) was inhibited by yeast mannans (YMs), suggesting a mannose-specific C-type lectin receptor-dependent process, while the uptake of deglycosylated antigens remained unaffected. In particular, antigens with both N-linked and extensive O-linked mannosylation showed the highest binding and uptake by BMDCs. Finally, confocal microscopy studies revealed that both mannosylated and deglycosylated P. pastoris-derived recombinant proteins localized in MHC class II+ compartments within BMDCs. CONCLUSIONS/SIGNIFICANCE. Taken together with our previous results, these data suggest that increased uptake by mannose-specific C-type lectin receptors is the major mechanism responsible for the enhanced antigenicity seen with mannosylated proteins. These findings have important implications for vaccine design and contribute to our understanding of how glycosylation affects the immune response to eukaryotic pathogens.National Institutes of Health (RO1 AI25780, RO1 AI37532

Clinical supervision for clinical psychology students in Uganda: an initial qualitative exploration

Background Burn out in clinical psychologists working in low income countries has been reported. Clinical supervisory structures do not yet exist in Uganda. A way to decrease levels of burn out and increase quality of care for people with mental illness is through clinical supervision. The aim of this study was to explore the initial experiences of supervision for clinical psychology students in Uganda to ascertain whether or not clinical supervision is culturally appropriate, and what aspects of supervision had been helpful and unhelpful. Methods A qualitative design with thematic analysis was utilized. A focus group was held with 12 second year clinical psychology students to ask their experiences of receiving supervision. Results Data analysis created five themes. Firstly, the negative emotions that resulted from the training processed were discussed, and how supervision helped and did not help the students to manage these. Secondly, the students voiced that supervision helped them to learn through observational experiences, co-therapist roles and parallel processes within the supervisory relationship. Thirdly, supervision had taught the clinical psychology students their role as a clinical psychology student, how to act within the Ugandan mental health system and skills to conduct therapy. Fourthly, suggestions for the future of supervision were given, with the students requesting for it to start earlier in the training, for supervisors who can meet with the students on a regular basis to be selected and for the training the students receive at university to match the skills required on their placements, with a request for more practical techniques rather than theory. The final theme related to left over miscellaneous data, such as the students agreeing with each other. Conclusions The students stated that supervision was helpful overall, implying that clinical supervision is culturally appropriate for clinical psychology students in Uganda. Suggestions for future supervision were given. In order to decrease high levels of staff burn out in the mental health systems in Uganda, supervisory structures with an emphasis on self care need to be established

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis