940 research outputs found

    Practitioner perspectives on dealing with victimhood and offending in UK ‘county lines’ drug supply investigations

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    This paper examines the investigative challenges associated with the ‘County Lines’ drug supply phenomenon from the perspective of police practitioners. Two areas are identified and explored: the presence and role of autonomy, coercion, and exploitation, and the legal and procedural issues. The police response appears confounded by non-specific legislation, unintended implications of the statutory defence, problems with the National Referral Mechanism (NRM), safeguarding deficiencies, incomplete statutory guardianship, and limited recognition of neurodevelopment and neurodivergence among those involved. The research is relevant to law and public policy and will be of interest to investigators and criminal justice system professionals

    Cyclopalladated metallomesogens

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    This thesis describes the synthesis and characterisation of novel cyclopalladated metallomesogens from four principal N-functionalised mesogenic ligands:(i) 4-alkyloxy-N- (4' -alkyloxybiphenyl)benzylidene, (H) terephthalylidene-bis-4-N-4' -alkyloxybenzylidene, (iii) bis( 4-alkoxybenzylidene-l ,4-phenylenediamine and (iv) 3, 6 bis- (alkyloxyphenyl)pyridazine). The ligands have been studied to determine their liquid crystalline behaviour and the phase behaviour is reported for the terephthalylidene-bis-4-N-4' -alkyloxybenzylidene series and for the 3, 6 bis-(alkyloxyphenyl)pyridazine series since no comprehensive study of either system has been reported in the literature. The co-ordination chemistry of these ligands is reported. The regiospecificity of the cyclopalladation reaction for the terephthalylidene-bis-4-N-4' -alkyloxybenzylidene and 3, 6 bis(alkyloxyphenyl)pyridazine series has been established and the influence of the primary cyc1opalladationstep on secondary cyclopalladationhas been examined. The co-ligands acetylacetonate, undecane-5,7 -dione, pentandecane-7,9-dione, nonadecane- 9,1O-dione, 2,2,6,6 tetra-methyl-heptane-3,5-dione and cyclopentadienylide have been employed to enable elaboration of the geometry of the organopalladium complexes giving diversity to the structure and physical properties of these materials

    Uterine Endoplasmic Reticulum Stress and Its Unfolded Protein Response May Regulate Caspase 3 Activation in the Pregnant Mouse Uterus

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    We have previously proposed that uterine caspase-3 may modulate uterine contractility in a gestationally regulated fashion. The objective of this study was to determine the mechanism by which uterine caspase-3 is activated and consequently controlled in the pregnant uterus across gestation. Utilizing the mouse uterus as our gestational model we examined the intrinsic and extrinsic apoptotic signaling pathways and the endoplasmic reticulum stress response as potential activators of uterine caspase-3 at the transcriptional and translational level. Our study revealed robust activation of the uterine myocyte endoplasmic reticulum stress response and its adaptive unfolded protein response during pregnancy coinciding respectively with increased uterine caspase-3 activity and its withdrawal to term. In contrast the intrinsic and extrinsic apoptotic signaling pathways remained inactive across gestation. We speculate that physiological stimuli experienced by the pregnant uterus likely potentiates the uterine myocyte endoplasmic reticulum stress response resulting in elevated caspase-3 activation, which is isolated to the pregnant mouse myometrium. However as term approaches, activation of an elevated adaptive unfolded protein response acts to limit the endoplasmic reticulum stress response inhibiting caspase-3 resulting in its decline towards term. We speculate that these events have the capacity to regulate gestational length in a caspase-3 dependent manne

    The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

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    PURPOSE: The aim of this study was to evaluate a candidate haemostat (WoundStat™), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model. MATERIALS AND METHODS: An area of approximately 3 cm2 was dermatomed from the dorsal ear skin to a nominal depth of 100 µm. A discrete droplet of 14C-GD (300 µg kg-1) was applied directly onto the surface of the damaged skin at the centre of the dosing site. Animals assigned to the treatment group were given a 2 g application of WoundStat™ 30 s after GD challenge. The decontamination efficacy of WoundStat™ against GD was measured by the direct quantification of the distribution of 14C-GD, as well as routine determination of whole blood cholinesterase and physiological measurements. RESULTS: WoundStat™ sequestered approximately 70% of the applied 14C-GD. Internal radiolabel recovery from treated animals was approximately 1% of the initially applied dose. Whole blood cholinesterase levels decreased to less than 10% of the original value by 15 min post WoundStat™ treatment and gradually decreased until the onset of apnoea or until euthanasia. All treated animals showed signs of GD intoxication that could be grouped into early (mastication, fasciculations and tremor), intermediate (miosis, salivation and nasal secretions) and late onset (lacrimation, body spasm and apnoea) effects. Two of the six WoundStat™ treated animals survived the study duration. CONCLUSIONS: The current study has shown that the use of WoundStat™ as a decontaminant on damaged pig ear skin was unable to fully protect against GD toxicity. Importantly, the findings indicate that the use of WoundStat™ in GD contaminated wounds would not exacerbate GD toxicity. These data suggest that absorbent haemostatic products may offer some limited functionality as wound decontaminants.Peer reviewedFinal Accepted Versio

    Caesarean section and risk of unexplained stillbirth in subsequent pregnancy

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    Background Caesarean section is associated with an increased risk of disorders of placentation in subsequent pregnancies, but effects on the rate of antepartum stillbirth are unknown. We aimed to establish whether previous caesarean delivery is associated with an increased risk of antepartum stillbirth. Methods We linked pregnancy discharge data from the Scottish Morbidity Record (1980–98) and the Scottish Stillbirth and Infant Death Enquiry (1985–98). We estimated the relative risk of antepartum stillbirth in second pregnancies using time-to-event analyses. Findings For 120 633 singleton second births, there were 68 antepartum stillbirths in 17 754 women previously delivered by caesarean section (2–39 per 10 000 women per week) and 244 in 102879 women previously delivered vaginally (1·44; p<0·001). Risk of unexplained stillbirth associated with previous caesarean delivery differed significantly with gestational age (p=0·04); the excess risk was apparent from 34 weeks (hazard ratio 2·23 [95% Cl 1·48–3·36]). Risk was not attenuated by adjustment for maternal characteristics or outcome of the first pregnancy (2·74 [1·74–4·30]). The absolute risk of unexplained stillbirth at or after 39 weeks' gestation was 1·1 per 1000 women who had had a previous caesarean section and 0·5 per 1000 in those who had not. The difference was due mostly to an excess of unexplained stillbirths among women previously delivered by caesarean section. Interpretation Delivery by caesarean section in the first pregnancy could increase the risk of unexplained stillbirth in the second. In women with one previous caesarean delivery, the risk of unexplained antepartum stillbirth at or after 39 weeks' gestation is about double the risk of stillbirth or neonatal death from intrapartum uterine rupture

    Steroid receptor coactivator 2 is required for female fertility and mammary morphogenesis: insights from the mouse, relevance to the human

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    Although the importance of the progesterone receptor (PR) to female reproductive and mammary gland biology is firmly established, the coregulators selectively co-opted by PR in these systems have not been clearly delineated. A selective gene-knockout approach applied to the mouse, which abrogates gene function only in cell types that express PR, recently disclosed steroid receptor coactivator 2 (SRC-2, also known as TIF-2 or GRIP-1) to be an indispensable coregulator for uterine and mammary gland responses that require progesterone. Uterine cells positive for PR (but devoid of SRC-2) were found to be incapable of facilitating embryo implantation, a necessary first step toward the establishment of the materno-fetal interface. Importantly, such an implantation defect is not exhibited by knockouts for SRC-1 or SRC-3, underscoring the unique coregulator importance of SRC-2 in peri-implantation biology. Moreover, despite normal levels of PR, SRC-1 and SRC-3, progesterone-dependent branching morphogenesis and alveologenesis fails to occur in the murine mammary gland in the absence of SRC-2, thereby establishing a critical coregulator role for SRC-2 in signaling cascades that mediate progesterone-induced mammary epithelial proliferation. Finally, the recent detection of SRC-2 in the human endometrium and breast suggests that this coregulator may represent a new clinical target for the future management of female reproductive health and/or breast cancer

    Using Social Media to Promote STEM Education: Matching College Students with Role Models

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    STEM (Science, Technology, Engineering, and Mathematics) fields have become increasingly central to U.S. economic competitiveness and growth. The shortage in the STEM workforce has brought promoting STEM education upfront. The rapid growth of social media usage provides a unique opportunity to predict users' real-life identities and interests from online texts and photos. In this paper, we propose an innovative approach by leveraging social media to promote STEM education: matching Twitter college student users with diverse LinkedIn STEM professionals using a ranking algorithm based on the similarities of their demographics and interests. We share the belief that increasing STEM presence in the form of introducing career role models who share similar interests and demographics will inspire students to develop interests in STEM related fields and emulate their models. Our evaluation on 2,000 real college students demonstrated the accuracy of our ranking algorithm. We also design a novel implementation that recommends matched role models to the students.Comment: 16 pages, 8 figures, accepted by ECML/PKDD 2016, Industrial Trac
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