The Star

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Constructions, reconstructions and deconstructions of ‘family’ amongst people who live apart together (LATs)

This article explores how people who live apart from their partners in Britain describe and understand ‘family’. It investigates whether, and how far, non-cohabiting partners, friends, ‘blood’ and legal ties are seen as ‘family’, and how practices of care and support, and feelings of closeness are related to these constructions. It suggests that people in LAT relationships creatively draw and re-draw the boundaries of family belonging in ways that involve emotionally subjective understandings of family life, and that also refer to normative constructions of what ‘family’ ought to be, as well as to practical recognitions of lived family ‘realities’. This often involves handling uncertainties about what constitutes ‘family’

Co-operation in Drug Treatment Services: Views of Offenders on Court Orders in Scotland

Accessing client perspectives about cooperation in substance misuse treatment offers important information to enhance services and improve drop-out rates. This article reports upon qualitative data from a localized study of service needs of offenders in Scotland who were undertaking community-based court orders. The views of 27 men and 2 women on their current and recent treatment offers rich insights into factors influencing their cooperation in treatment. In contradiction to the voluntaristic ideology of treatment services, their voices identify the criminal justice system as offering strong support in the completion of treatment programmes

High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (θsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/θ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

Cardiac Targeting Peptide, a Novel Cardiac Vector: Studies in Bio-Distribution, Imaging Application, and Mechanism of Transduction

Our previous work identified a 12-amino acid peptide that targets the heart, termed cardiac targeting peptide (CTP). We now quantitatively assess the bio-distribution of CTP, show a clinical application with the imaging of the murine heart, and study its mechanisms of transduction. Bio-distribution studies of cyanine5.5-N-Hydroxysuccinimide (Cy5.5) labeled CTP were undertaken in wild-type mice. Cardiac targeting peptide was labeled with Technetium 99m (99mTc) using the chelator hydrazino-nicotinamide (HYNIC), and imaging performed using micro-single photon emission computerized tomography/computerized tomography (SPECT/CT). Human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMCs) were incubated with dual-labeled CTP, and imaged using confocal microscopy. TriCEPs technology was utilized to study the mechanism of transduction. Bio-distribution studies showed peak uptake of CTP at 15 min. 99mTc-HYNIC-CTP showed heart-specific uptake. Robust transduction of beating human iPSC-derived CMCs was seen. TriCEPs experiments revealed five candidate binding partners for CTP, with Kcnh5 being felt to be the most likely candidate as it showed a trend towards being competed out by siRNA knockdown. Transduction efficiency was enhanced by increasing extracellular potassium concentration, and with Quinidine, a Kcnh5 inhibitor, that blocks the channel in an open position. We demonstrate that CTP transduces the normal heart as early as 15 min. 99mTc-HYNIC-CTP targets the normal murine heart with substantially improved targeting compared with 99mTc Sestamibi. Cardiac targeting peptide’s transduction ability is not species limited and has human applicability. Cardiac targeting peptide appears to utilize Kcnh5 to gain cell entry, a phenomenon that is affected by pre-treatment with Quinidine and changes in potassium levels

Materialities and imaginaries of home: geographies of British returnees in later life

This article explores home materialities and home imaginaries in later life, to provide insight into the dialectical relation between the spatial processes of ageing and migration. The article draws on empirical research with British return migrants in older age. The analysis purposively selects four participants from among a wider sample of interviewees to highlight some of the diversity among British returnees and their varied experiences of remaking home upon return. The article explores both the privilege and vulnerabilities of all British returnees as the meaning of home transforms in later life

Exome Sequencing in Suspected Monogenic Dyslipidemias

Abstract BACKGROUND: -Exome sequencing is a promising tool for gene mapping in Mendelian disorders. We utilized this technique in an attempt to identify novel genes underlying monogenic dyslipidemias. METHODS AND RESULTS: -We performed exome sequencing on 213 selected family members from 41 kindreds with suspected Mendelian inheritance of extreme levels of low-density lipoprotein (LDL) cholesterol (after candidate gene sequencing excluded known genetic causes for high LDL cholesterol families) or high-density lipoprotein (HDL) cholesterol. We used standard analytic approaches to identify candidate variants and also assigned a polygenic score to each individual in order to account for their burden of common genetic variants known to influence lipid levels. In nine families, we identified likely pathogenic variants in known lipid genes (ABCA1, APOB, APOE, LDLR, LIPA, and PCSK9); however, we were unable to identify obvious genetic etiologies in the remaining 32 families despite follow-up analyses. We identified three factors that limited novel gene discovery: (1) imperfect sequencing coverage across the exome hid potentially causal variants; (2) large numbers of shared rare alleles within families obfuscated causal variant identification; and (3) individuals from 15% of families carried a significant burden of common lipid-related alleles, suggesting complex inheritance can masquerade as monogenic disease. CONCLUSIONS: -We identified the genetic basis of disease in nine of 41 families; however, none of these represented novel gene discoveries. Our results highlight the promise and limitations of exome sequencing as a discovery technique in suspected monogenic dyslipidemias. Considering the confounders identified may inform the design of future exome sequencing studies

Welfare conditionality in lived experience : aggregating qualitative longitudinal research

Punitive welfare conditionality, combining tough sanctions with minimal self-directed support, is a defining feature of contemporary UK working age social security provision. This approach has been justified by policy makers on the basis that it will increase the numbers in paid employment, and thereby offering savings for the public purse that are also beneficial for individuals who are expected to be healthier and better off financially as a result. In this article, we aggregate two qualitative longitudinal studies (Welfare Conditionality, 2014-17; and Lived Experience, 2011-16) that document lived experiences of claiming benefits and using back-to-work support services. In both studies and over time, we find, contrary to policy expectations, that coercion, including sanctions, was usually experienced as unnecessary and harmful and that poverty was prevalent, both in and out of work, tended to worsen and pushed many close to destitution. Conditionality governed encounters with employment services and, perversely, appeared to impede, rather than support, transitions into employment for participants in both studies. In this way, we propose Combined Study Qualitative Longitudinal Research as a new methodological approach for investigating if ‘shared typical’ aspects of lived experiences of welfare conditionality can be identified

Clearance kinetics and matrix binding partners of the receptor for advanced glycation end products

Elucidating the sites and mechanisms of sRAGE action in the healthy state is vital to better understand the biological importance of the receptor for advanced glycation end products (RAGE). Previous studies in animal models of disease have demonstrated that exogenous sRAGE has an anti-inflammatory effect, which has been reasoned to arise from sequestration of pro-inflammatory ligands away from membrane-bound RAGE isoforms. We show here that sRAGE exhibits in vitro binding with high affinity and reversibly to extracellular matrix components collagen I, collagen IV, and laminin. Soluble RAGE administered intratracheally, intravenously, or intraperitoneally, does not distribute in a specific fashion to any healthy mouse tissue, suggesting against the existence of accessible sRAGE sinks and receptors in the healthy mouse. Intratracheal administration is the only effective means of delivering exogenous sRAGE to the lung, the organ in which RAGE is most highly expressed; clearance of sRAGE from lung does not differ appreciably from that of albumin. Copyright: © 2014 Milutinovic et al