72 research outputs found

    The Constructions of Risk by Mental Health Professionals Working in a Low and Medium Secure Forensic Service

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    This study adopts a Foucauldian Discourse Analysis (FDA) on the subject of how mental health professionals working in low and medium secure forensic services construct the meaning of risk. A critical review of the literature illustrates the emergence of the concept of risk and the diversity in which it is constructed including the proliferation of risk assessment tools in an attempt to quantify the phenomenon. In contrast, the aim of this study was to focus on the meaning of the concept by exploring how ten mental health professionals make sense of and construct risk while adopting an epistemological position of critical realism with social constructionism. Such an approach enabled an exploration of broader social and contextual factors influencing the constructed nature of the concept and the implications for their clinical practice. Three interconnecting discursive sites were formed in the analysis of this research. These were termed: ‘Constructing the system as an inhibitor to meaningful information about patients and risk’, ‘The construction of risk to professionals through surveillance and accountability’ and ‘The construction of risk in relation to responsibility and as something that can be transferred’. Implications for clinical practice suggested by the analysis included the role of supervision and reflexivity, the short-term toleration of immediate risk by services, the role of forensic service policy in relation to the recovery agenda, and the suggestion of counter-inquiries alongside the current practice of homicide inquiries

    Cold shock response of Salmonella enterica serovar typhimurium; the involvement of the CspA paralogues

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    Salmonella enterica sv. typhimurium is a major food-borne pathogen, in part because of its ability to persist and multiply at low temperatures. Adaptation to refrigerated temperatures involves induction of a multigenic cold shock response (CSR); where gene expression is co-ordinately modified, to express cold shock proteins (CSPs). Characterisation of CspA, the major cold shock protein, instigated the identification of other CspA paralogues; which are highly conserved and widespread across species. Six CspA paralogues have previously been identified in S. typhimurium and a csp null strain, lacking all CspA paralogues made. This strain is unable to grow following cold shock, demonstrating that the CspA paralogues play an essential role during low temperature adaptation. The individual CspA paralogues exhibit distinct expression profiles; including expression of CspC and CspE at optimal temperature and CspA and CspB following cold shock. This work investigates the transcriptional changes of S. typhimurium during cold shock and the role of the CspA paralogues under both optimal and cold shock conditions. Using a bacteriophage Mu transposon library (Francis and Gallagher, 1993) this study identifies 7 novel cold induced targets and analyses their native expression levels in SL1344 and the csp null strain during cold shock. This revealed that the regulation of 5 discrete loci including tRNApro2, cpxP and 3 uncharacterised ORFS are mediated by CspA paralogues. In addition, the transcriptional profiles of a highly conserved and essential set of genes encoding known cold shock proteins, NusA, IF2, RbfA, PNPase and CsdA have been characterised. Comparative Northern analysis of SL1344 and the csp null strain has identified a role for CspA paralogues in mediating low temperature induction of three of these genes, through transcription anti-termination. Taken together these results demonstrate that during adaptation to low temperature CspA paralogues regulate expression of genes involved in the translational machinery and metabolic biosynthetic pathways: possibly through a number of transcriptional and post transcriptional processing events. Furthermore this study provides in vivo evidence of the RNA binding activity of the S. typhimurium CspA paralogues. Using fusion proteins, the RNA targets of CspE at 37°C and CspA at 10°C were isolated and analysed. This work identifies 17 direct binding targets for CspE and these indicate that CspE performs a role at optimal growth temperature in regulating components of metabolic (coaA and plsX), translational (EF-Tu, EF-G and IF3) and virulence associated (hha) pathways. Functional redundancy between CspE and CspA was suggested as both paralogues bound 16s rRNA. In light of these findings, the functions of CspA & CspE at optimal and low temperature are discussed. Overall this study has revealed novel information about low temperature adaptation of S. typhimurium, expanding our knowledge of the complexity and importance of the CSR in bacterial pathogens. In addition this work enhances our comprehension of the roles of the CspA paralogues at both optimal and low temperature

    Solid-state interconversions: Unique 100% reversible transformations between the ground and metastable states in single-crystals of a series of nickel( II) nitro complexes

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    The solid-state, low-temperature linkage isomerism in a series of five square planar group 10 phosphino nitro complexes have been investigated by a combination of photocrystallographic experiments, Raman spectroscopy and computer modelling. The factors influencing the reversible solid-state interconversion between the nitro and nitrito structural isomers have also been investigated, providing insight into the dynamics of this process. The cis-[Ni(dcpe)(NO2)2] (1) and cis-[Ni(dppe)(NO2)2] (2) complexes show reversible 100 % interconversion between the η1-NO2 nitro isomer and the η1-ONO nitrito form when single-crystals are irradiated with 400 nm light at 100 K. Variable temperature photocrystallographic studies for these complexes established that the metastable nitrito isomer reverted to the ground-state nitro isomer at temperatures above 180 K. By comparison, the related trans complex [Ni(PCy3)2(NO2)2] (3) showed 82 % conversion under the same experimental conditions at 100 K. The level of conversion to the metastable nitrito isomers is further reduced when the nickel centre is replaced by palladium or platinum. Prolonged irradiation of the trans-[Pd(PCy3)2(NO2)2] (4) and trans-[Pt(PCy3)2(NO2)2] (5) with 400 nm light gives reversible conversions of 44 and 27 %, respectively, consistent with the slower kinetics associated with the heavier members of group 10. The mechanism of the interconversion has been investigated by theoretical calculations based on the model complex [Ni(dmpe)Cl(NO2)]

    Barriers to participation in mental health research: are there specific gender, ethnicity and age related barriers?

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    <p>Abstract</p> <p>Background</p> <p>It is well established that the incidence, prevalence and presentation of mental disorders differ by gender, ethnicity and age, and there is evidence that there is also differential representation in mental health research by these characteristics. The aim of this paper is to a) review the current literature on the nature of barriers to participation in mental health research, with particular reference to gender, age and ethnicity; b) review the evidence on the effectiveness of strategies used to overcome these barriers.</p> <p>Method</p> <p>Studies published up to December 2008 were identified using MEDLINE, PsycINFO and EMBASE using relevant mesh headings and keywords.</p> <p>Results</p> <p>Forty-nine papers were identified. There was evidence of a wide range of barriers including transportation difficulties, distrust and suspicion of researchers, and the stigma attached to mental illness. Strategies to overcome these barriers included the use of bilingual staff, assistance with travel, avoiding the use of stigmatising language in marketing material and a focus on education about the disorder under investigation. There were very few evaluations of such strategies, but there was evidence that ethnically matching recruiters to potential participants did not improve recruitment rates. Educational strategies were helpful and increased recruitment.</p> <p>Conclusion</p> <p>Mental health researchers should consider including caregivers in recruitment procedures where possible, provide clear descriptions of study aims and describe the representativeness of their sample when reporting study results. Studies that systematically investigate strategies to overcome barriers to recruitment are needed.</p

    What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

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    Stilbenes are naturally occurring phytoalexins that generally exist as their more stable E isomers. The most well known natural stilbene is resveratrol (Res), firstly isolated in 1939 from roots of Veratrum grandiflorum (white hellebore) (1) and since then found in various edible plants, notably in Vitis vinifera L. (Vitaceae) (2). The therapeutic potential of Res covers a wide range of diseases, and multiple beneficial effects on human health such as antioxidant, anti-inflammatory and anti-cancer activities have been suggested based on several in vitro and animal studies (3). In particular, Res has been reported to be an inhibitor of carcinogenesis at multiple stages via its ability to inhibit cyclooxygenase, and is an anticancer agent with a role in antiangiogenesis (4). Moreover, both in vitro and in vivo studies showed that Res induces cell cycle arrest and apoptosis in tumor cells (4). However, clinical studies in humans evidenced that Res is rapidly absorbed after oral intake, and that the low level observed in the blood stream is caused by a fast conversion into metabolites that are readily excreted from the body (5). Thus, considerable efforts have gone in the design and synthesis of Res analogues with enhanced metabolic stability. Considering that reduced Res (dihydro- resveratrol, D-Res) conjugates may account for as much as 50% of an oral Res dose (5), and that D-Res has a strong proliferative effect on hormone-sensitive cancer cell lines such as breast cancer cell line MCF7 (6), we recently devoted our synthetic efforts to the preparation of trans-restricted analogues of Res in which the E carbon-carbon double bond is embedded into an imidazole nucleus. To keep the trans geometry, the two aryl rings were linked to the heteroaromatic core in a 1,3 fashion. Based on this design, we successfully prepared a variety of 1,4-, 2,4- and 2,5-diaryl substituted imidazoles including Res analogues 1, 2 and 3, respectively, by procedures that involve transition metal-catalyzed Suzuki-Miyaura cross-coupling reactions and highly selective N-H or C-H direct arylation reactions as key synthetic steps. The anticancer activity of compounds 1–3 was evaluated against the 60 human cancer cell lines panel of the National Cancer Institute (NCI, USA). The obtained results, that will be showed and discussed along with the protocols developed for the preparation of imidazoles 1–3, confirmed that a structural optimization of Res may provide analogues with improved potency in inhibiting the growth of human cancer cell lines in vitro when compared to their natural lead. (1) Takaoka,M.J.Chem.Soc.Jpn.1939,60,1090-1100. (2) Langcake, P.; Pryce, R. J. Physiological. Plant Patology 1976, 9, 77-86. (3) Vang, O.; et al. PLoS ONE 2011, 6, e19881. doi:10.1371/journal.pone.0019881 (4) Kraft, T. E.; et al. Critical Reviews in Food Science and Nutrition 2009, 49, 782-799. (5) Walle, T. Ann. N.Y. Acad. Sci. 2011, 1215, 9-15. doi: 10.1111/j.1749-6632.2010.05842.x (6) Gakh,A.A.;etal.Bioorg.Med.Chem.Lett.2010,20,6149-6151

    Plant regrowth as a driver of recent enhancement of terrestrial CO2 uptake

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    The increasing strength of land CO2 uptake in the 2000s has been attributed to a stimulating effect of rising atmospheric CO2 on photosynthesis (CO2 fertilization). Using terrestrial biosphere models, we show that enhanced CO2 uptake is induced not only by CO2 fertilization but also an increasing uptake by plant regrowth (accounting for 0.33 ± 0.10 Pg C/year increase of CO2 uptake in the 2000s compared with the 1960s–1990s) with its effect most pronounced in eastern North America, southern‐eastern Europe, and southeastern temperate Eurasia. Our analysis indicates that ecosystems in North America and Europe have established the current productive state through regrowth since the 1960s, and those in temperate Eurasia are still in a stage from regrowth following active afforestation in the 1980s–1990s. As the strength of model representation of CO2 fertilization is still in debate, plant regrowth might have a greater potential to sequester carbon than indicated by this study

    Adding Spice to the Porridge: The development of a synthetic cannabinoid market in an English prison.

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    In 2014, the annual report of the Her Majesty's Chief Inspector of Prisons (HMIP) for England and Wales raised concerns regarding New Psychoactive Substance (NPS) use in custody, specifically the consumption of synthetic cannabinoids. To date, however, the use of these substances in prison populations, and the markets that have emerged to facilitate it, have been under-researched.Our research was conducted in an English adult male prison using multi-method techniques. These included: in-depth interviews and focus groups with prison staff and prisoners; observations of prisoner-led focus groups, workshops and restorative justice circles involving discussion of synthetic cannabinoid use and markets; and analysis of routinely collected prison data measuring drug seizures, incidents of violence and incidents of self-harm.The findings highlight: (1) the scale and nature of synthetic cannabinoid markets in a custodial setting and the motivations for establishing them; (2) the nature and motivations for synthetic cannabinoids use in prison; and (3) the impact synthetic cannabinoid markets in this setting have upon prisoners, the prison system and the wider criminal justice system. The policy implications of the stated motivations for use and reported problems are discussed in relation to both prison and community settings, and the recently implemented Psychoactive Substance Act (2016).The paper concludes that the rise in synthetic cannabinoid use in custody and the size of the drug market are posing significant challenges to the management of offenders; including healthcare, appropriate detection techniques, license recall and sanctions for both use and supply. We argue that the primary motivation for consumption in this setting is the avoidance of drug use detection, and that this is likely to supersede other motivations for consumption in the future. We propose a revision of the use of mandatory drug tests (MDTs) both in prisons and in the management of offenders in the community

    Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

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    OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

    Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

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    The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

    A blueprint for an inclusive, global deep-sea Ocean Decade field programme

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    The ocean plays a crucial role in the functioning of the Earth System and in the provision of vital goods and services. The United Nations (UN) declared 2021–2030 as the UN Decade of Ocean Science for Sustainable Development. The Roadmap for the Ocean Decade aims to achieve six critical societal outcomes (SOs) by 2030, through the pursuit of four objectives (Os). It specifically recognizes the scarcity of biological data for deep-sea biomes, and challenges the global scientific community to conduct research to advance understanding of deep-sea ecosystems to inform sustainable management. In this paper, we map four key scientific questions identified by the academic community to the Ocean Decade SOs: (i) What is the diversity of life in the deep ocean? (ii) How are populations and habitats connected? (iii) What is the role of living organisms in ecosystem function and service provision? and (iv) How do species, communities, and ecosystems respond to disturbance? We then consider the design of a global-scale program to address these questions by reviewing key drivers of ecological pattern and process. We recommend using the following criteria to stratify a global survey design: biogeographic region, depth, horizontal distance, substrate type, high and low climate hazard, fished/unfished, near/far from sources of pollution, licensed/protected from industry activities. We consider both spatial and temporal surveys, and emphasize new biological data collection that prioritizes southern and polar latitudes, deeper (&gt; 2000 m) depths, and midwater environments. We provide guidance on observational, experimental, and monitoring needs for different benthic and pelagic ecosystems. We then review recent efforts to standardize biological data and specimen collection and archiving, making “sampling design to knowledge application” recommendations in the context of a new global program. We also review and comment on needs, and recommend actions, to develop capacity in deep-sea research; and the role of inclusivity - from accessing indigenous and local knowledge to the sharing of technologies - as part of such a global program. We discuss the concept of a new global deep-sea biological research program ‘Challenger 150,’ highlighting what it could deliver for the Ocean Decade and UN Sustainable Development Goal 14
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