The Trail, 1965-04-09

https://soundideas.pugetsound.edu/thetrail_all/4035/thumbnail.jp

Paramedics’ perceptions of the care they provide to people who self-harm: A qualitative study using evolved grounded theory methodology

BACKGROUND:Self-harm (SH) accounts for over 5% of the workload of emergency ambulance services, and therefore Paramedics are often the first health professional in contact with people who SH. The authors of this paper have reported elsewhere the significant gaps in our understandings which exist surrounding this early care interaction, and some of the challenges paramedics and opportunities in paramedic care for people who SH. This study aimed to explore paramedics' perceptions of caring for those who SH using Evolved Grounded Theory Methodology. METHODS:This study took place between 2014-2016 in one UK ambulance service covering a population of three million people. Semi structured interviews were conducted, purposively sampling paramedics until saturation was reached. Interviews were recorded, transcribed verbatim, and coded through open, axial, and selective levels of coding, identifying the Basic Social Process (BSP) and developing a Grounded Theory. A second researcher (SH) independently reviewed early results, which were also member-checked with participants. RESULTS:Eleven paramedics were interviewed. The following six categories emerged: Context; Judgements and values; Isolation and system failure; Managing risk; Competence at the boundary of mental and physical health needs; Professional, legal and ethical tensions. The BSP Decision making in a context of risk was identified. The final Grounded Theory that emerged was one of 'Wicked Complexity of paramedic care for people who SH, which includes usual factors such as tiredness and frequent callers, heightened factors including lack of support and pathways, and factors specific to SH such assessing mental health and suicide risk. CONCLUSIONS:This study builds on a very small body of literature to have explored paramedic care for people who SH and has found that this care interaction provides uniquely complex challenges. The multiple influences within the categories defined in this study need considering conjointly when making improvements to care

Immunophenotyping and Transcriptomic Outcomes in PDX-Derived TNBC Tissue

Cancer tissue functions as an ecosystem of a diverse set of cells that interact in a complex tumor microenvironment (TME). Genomic tools applied to biopsies in bulk fail to account for this tumor heterogeneity while single cell imaging methods limit the number of cells which can be assessed or are very resource intensive. The current study presents methods based on flow cytometric analysis and cell sorting using known cell surface markers (eg, CD184, CD24, CD90) to identify and interrogate distinct groups of cells in triple-negative breast cancer (TNBC) clinical biopsy specimens from patient-derived xenograft (PDX) models. The results demonstrate that flow cytometric analysis allows a relevant subgrouping of cancer tissue and that sorting of these subgroups provides insights on cancer cell populations with unique, reproducible and functionally divergent gene expression profiles. The discovery of a drug resistance signature implies that uncovering the functional interaction between these populations will lead to deeper understanding of cancer progression and drug response. Implications: PDX-derived human breast cancer tissue was investigated at the single cell level and cell subpopulations defined by surface markers were identified which suggest specific roles for distinct cellular compartments within a solid tumor

Atypical Retinal Phenotype in a Patient With Alström Syndrome and Biallelic Novel Pathogenic Variants in ALMS1, Including a de novo Variation

Alström syndrome (ALMS) is a rare autosomal recessive multi-organ syndrome considered to date as a ciliopathy and caused by variations in ALMS1. Phenotypic variability is well-documented, particularly for the systemic disease manifestations; however, early-onset progressive retinal degeneration affecting both cones and rods (cone-rod type) is universal, leading to blindness by the teenage years. Other features include cardiomyopathy, kidney dysfunction, sensorineural deafness, and childhood obesity associated with hyperinsulinemia and type 2 diabetes mellitus. Here, we present an unusual and delayed retinal dystrophy phenotype associated with ALMS in a 14-year-old female, with affected cone function and surprising complete preservation of rod function on serial electroretinograms (ERGs). High-throughput sequencing of the affected proband revealed compound heterozygosity with two novel nonsense variations in the ALMS1 gene, including one variant of de novo inheritance, an unusual finding in autosomal recessive diseases. To confirm the diagnosis in the context of an unusually mild phenotype and identification of novel variations, we demonstrated the biallelic status of the compound heterozygous variations (c.[286C > T];[1211C > G], p.[(Gln96*)];[(Ser404*)]). This unique case extends our knowledge of the phenotypic variability and the pathogenic variation spectrum in ALMS patients

Determination of HBCD, PBDEs and MeO-BDEs in California sea lions (Zalophus californianus) stranded between 1993 and 2003

Author Posting. © Elsevier B.V., 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Pollution Bulletin 52 (2006): 522-531, doi:10.1016/j.marpolbul.2005.09.045.Blubber samples from male California sea lions (Zalphophus californianus) stranded between 1993 and 2003 were analyzed for 27 polybrominated diphenyl ether (PBDE) congeners, three isomers of hexabromocyclododecane (HBCD) and 14 methoxylated polybrominated diphenyl ether (MeO-BDE) congeners. Total PBDEs ranged from 450 ng/g to 4740 ng/g wet mass and total HBCD ranged from <0.3 ng/g to 12 ng/g wet mass. The concentration of HBCD increased from 0.7 ng/g to12.0 ng/g wet mass in sea lion blubber between 1993 and 2003. However, no significant temporal trend was observed for any of the other brominated compounds over this ten year period. Only one of the 14 MeO-BDE congeners was detected in the blubber samples, 6-methoxy- 2,2’,4,4’-tetrabromodiphenyl ether (6-MeO-BDE 47), and concentrations ranged from <0.2 ng/g to 12 ng/g wet mass. A bromo-, chloro- heterocyclic compound, 1,1’-dimethyl-tetrabromo-dichloro-2,2’-bipyrrole (DBP-Br4Cl2), previously reported in marine species along the Pacific coast, was also identified in the sea lion blubber. DBP-Br4Cl2 ranged from 44 ng/g wet mass to 660 ng/g wet mass and was present at concentrations rivaling the dominant PBDE congener, BDE 47 (2,2’,4,4’-tetrabromodiphenyl ether). Concentrations of DBP-Br4Cl2 were positively correlated with 6-MeO-BDE 47 (r= 0.7; p<0.05). Both of these compounds have been identified in marine algae and sponges, and studies suggest they are both produced from natural sources. This study demonstrates that brominated compounds from both anthropogenic and biogenic sources can accumulate to similar levels in marine mammals. In addition, HBCD concentrations appear to be increasing in California sea lion populations, whereas PBDE concentrations, between 1993 and 2003, were highly variable

A novel, highly sensitive and specific biomarker for Niemann-Pick type C1 disease

Background Lysosomal storage disorders (LSDs), are a heterogeneous group of rare disorders caused by defects in genes encoding for proteins involved in the lysosomal degradation of macromolecules. They occur at a frequency of about 1 in 5,000 live births, though recent neonatal screening suggests a higher incidence. New treatment options for LSDs demand a rapid, early diagnosis of LSDs if maximal clinical benefit is to be achieved. Methods Here, we describe a novel, highly specific and sensitive biomarker for Niemann-Pick Type C disease type 1 (NPC1), lyso-sphingomyelin-509. We cross-validate this biomarker with cholestane-3β,5α,6β-triol and relative lysosomal volume. The primary cohort for establishment of the biomarker contained 135 NPC1 patients, 66 NPC1 carriers, 241 patients with other LSDs and 46 healthy controls. Results With a sensitivity of 100.0% and specificity of 91.0% a cut-off of 1.4 ng/ml was established. Comparison with cholestane-3β,5α,6β-triol and relative acidic compartment volume measurements were carried out with a subset of 125 subjects. Both cholestane-3β,5α,6β-triol and lyso-Sphingomyelin-509 were sufficient in establishing the diagnosis of NPC1 and correlated with disease severity. Conclusion In summary, we have established a new biomarker for the diagnosis of NPC1, and further studies will be conducted to assess correlation to disease progress and monitoring treatment

Regulating Clothing Outwork: A Sceptic's View

By applying the strategies of international anti-sweatshop campaigns to the Australian context, recent regulations governing home-based clothing production hold retailers responsible for policing the wages and employment conditions of clothing outworkers who manufacture clothing on their behalf. This paper argues that the new approach oversimplifies the regulatory challenge by assuming (1) that Australian clothing production is organised in a hierarchical ‘buyer-led’ linear structure in which core retail firms have the capacity to control their suppliers’ behaviour; (2) that firms act as unitary moral agents; and (3) that interventions imported from other times and places are applicable to the contemporary Australian context. After considering some alternative regulatory approaches, the paper concludes that the new regulatory strategy effectively privatises responsibility for labour market conditions – a development that cries out for further debate

An acidic microenvironment in Tuberculosis increases extracellular matrix degradation by regulating macrophage inflammatory responses

Mycobacterium tuberculosis (M.tb) infection causes marked tissue inflammation leading to lung destruction and morbidity. The inflammatory extracellular microenvironment is acidic, however the effect of this acidosis on the immune response to M.tb is unknown. Using RNA-seq we show that acidosis produces system level transcriptional change in M.tb infected human macrophages regulating almost 4000 genes. Acidosis specifically upregulated extracellular matrix (ECM) degradation pathways with increased expression of Matrix metalloproteinases (MMPs) which mediate lung destruction in Tuberculosis. Macrophage MMP-1 and -3 secretion was increased by acidosis in a cellular model. Acidosis markedly suppresses several cytokines central to control of M.tb infection including TNF-α and IFN-γ. Murine studies demonstrated expression of known acidosis signaling G-protein coupled receptors OGR-1 and TDAG-8 in Tuberculosis which are shown to mediate the immune effects of decreased pH. Receptors were then demonstrated to be expressed in patients with TB lymphadenitis. Collectively, our findings show that an acidic microenvironment modulates immune function to reduce protective inflammatory responses and increase extracellular matrix degradation in Tuberculosis. Acidosis receptors are therefore potential targets for host directed therapy in patients

The Concept of Medicalisation Reassessed

Medicalisation has been an important concept in sociological discussions of medicine since the term?s adoption by medical sociologists in the early 1970s. Yet arguably it has somewhat fallen out of fashion amongst sociologists, attacked by some, not least because it seems to be too critical of medicine, and modified or replaced by others with concepts deemed more relevant, such as biomedicalisation and pharmaceuticalisation. My aim in this paper is to reassess the concept and consider whether it still has value in exploring certain aspects of the changing role of medicine in present-day society. I start with an archaeology of the concept?s development and the different ways it has been used. This is essential to the main task: examining criticisms of the concept and assessing its value