585 research outputs found

    Is the digital forensic tool user interface broken?

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    The NPCC (2020, p.5) states that: Digital forensic (DF) science - examining digital evidence to support investigations and prosecutions - was once niche but is now very much mainstream. Over 90% of all crime is recognised as having a digital element, and society's accelerating use of technology means the critical role DF science plays will only grow. They identify three core challenges: 1. the sheer volume of data and devices leading to backlogs and delays in investigations; 2. the complexity of digital examinations including the variety of devices available, use of encryption, the number of data formats used, and the increasing use of cloud storage; and  3. the need to maintain the legitimacy of the police in the digital landscape given 1 and 2 and law enforcement's need to work in new ways to deal with these issues. (ibid.) Given the volume of data and complexity of the examinations this research interviewed 12 DF practitioners in an attempt to understand how the user interface of DF tools may exacerbate these issues, and what their suggestions may be to mitigate these. This work explores the responses, provides an initial analysis, and provides suggestions for how these findings may feed into the next generation of DF tools

    LTA application of a long trailing wire high speed/low weight reeling system

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    The successful development of a unique yet simple reeling system for handling long trailing tensile members at high speeds is described. This high speed when combined with the system simplicity, low weight and effective motive power consumption make this reeling system particularly attractive to LTA planners and designers for numerous LTA missions

    From Words to Action: Comparing the Disparities Between National Drug Policy and Local Implementation in Tijuana, Mexico and Vancouver, Canada

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    In 2009, Mexico passed a national drug policy reform decriminalizing the possession of small amounts of certain drugs for personal use with the aim of diverting drug-dependent individuals from prison and towards addiction treatment. However, the public health approach codified by the reform has not yet led to a meaningful change in local police practices nor contributed to the meaningful scale-up of harm reduction and addiction treatment services in many Mexican cities. Specifically, in Tijuana, Baja California, there continues to be a variety of local level barriers – including arbitrary police behaviours – that hinder the ability of people who inject drugs (PWID) from accessing vital harm reduction services. This has implications for the growing HIV epidemic in Mexico’s northern border region, given that access to harm reduction interventions has been shown to effectively reduce the risk of HIV infection among PWID. In contrast to the largely enforcement-based local response seen in Tijuana, the municipal Four Pillars approach implemented in Vancouver, Canada in 2001 was passed as a public-health oriented response to the rising prevalence of HIV/AIDS among PWID in the Downtown Eastside of Vancouver. Centered on the balancing of four approaches – harm reduction, treatment, prevention and enforcement – the Four Pillars approach in Vancouver has led to a well-resourced local harm reduction and addiction treatment system. This local emphasis on harm reduction contrasts with the Canadian Conservative federal government’s opposition to harm reduction approaches. However, police-public health partnerships along with strong political support have led to the substantial scale up of harm reduction services as well as the reduction of HIV/AIDS among PWID in Vancouver, unlike what has been observed in Tijuana. This commentary therefore aims to assess the discrepancies between federal policy and local responses to drug-related harms in order to fully understand the impact and implications of national drug policies in shaping local response to drug related harms among populations of PWID. Through a comparison of the drug policy landscape in two cities linked by a large North American drug trafficking route - Tijuana, Mexico and Vancouver, Canada, - this commentary suggests that drug policy reform in and of itself will have little impact at the local level unless it is appropriately resourced and meaningfully supported by key stakeholders

    Genes for extracellular matrix-degrading metalloproteinases and their inhibitor, TIMP, are expressed during early mammalian development

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    Extracellular matrix (ECM) remodeling accompanies cell migration, cell-cell interactions, embryo expansion, uterine implantation, and tissue invasion during mammalian embryogenesis. We have found that mouse embryos secrete functional ECM-degrading metalloproteinases, including collagenase and stromelysin, that are inhibitable by the tissue inhibitor of metalloproteinases (TIMP) and that are regulated during peri-implantation development and endoderm differentiation. mRNA transcripts for collagenase, stromelysin, and TIMP were detected as maternal transcripts in the unfertilized egg, were present at the zygote and cleavage stages, and increased at the blastocyst stage and with endoderm differentiation. These data suggest that metalloproteinases function in cell-ECM interactions during growth, development, and implantation of mammalian embryos

    The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter

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    Extracellular matrix-degrading matrix metalloproteinases (MMPs) are invariably upregulated in epithelial cancers and are key agonists in angiogenesis, invasion and metastasis. Yet most MMPs are secreted not by the cancer cells themselves, but by stromal cells within and around the tumor mass. Because the stromal environment can influence tumor formation, and because MMPs can alter this environment, MMPs may also contribute to the initial stages of cancer development. Several recent studies in MMP-overexpressing and MMP-deficient mice support this possibility, but have required carcinogens or pre-existing oncogenic mutations to initiate tumorigenesis. Here we review the spontaneous development of premalignant and malignant lesions in the mammary glands of transgenic mice that express an autoactivating form of MMP-3/stromelysin-1 under the control of the whey acidic protein gene promoter. These changes were absent in nontransgenic littermates and were quenched by co-expression of a human tissue inhibitor of metalloproteinases-1 (TIMP-1) transgene. Thus by altering the cellular microenvironment, stromelysin-1 can act as a natural tumor promoter and enhance cancer susceptibility

    Site-specific inductive and inhibitory activities of MMP-2 and MMP-3 orchestrate mammary gland branching morphogenesis

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    During puberty, mouse mammary epithelial ducts invade the stromal mammary fat pad in a wave of branching morphogenesis to form a complex ductal tree. Using pharmacologic and genetic approaches, we find that mammary gland branching morphogenesis requires transient matrix metalloproteinase (MMP) activity for invasion and branch point selection. MMP-2, but not MMP-9, facilitates terminal end bud invasion by inhibiting epithelial cell apoptosis at the start of puberty. Unexpectedly, MMP-2 also represses precocious lateral branching during mid-puberty. In contrast, MMP-3 induces secondary and tertiary lateral branching of ducts during mid-puberty and early pregnancy. Nevertheless, the mammary gland is able to develop lactational competence in MMP mutant mice. Thus, specific MMPs refine the mammary branching pattern by distinct mechanisms during mammary gland branching morphogenesis

    Securing Safe Supply During COVID-19 and Beyond: Scoping Review and Knowledge Mobilization

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    Background Safe supply is defined as the legal and regulated provision of drugs with mind and/or body altering properties that have been typically accessible only through the illegal drug market. In response to the coronavirus disease 2019 (COVID-19) pandemic and related social/physical distancing measures, efforts have been made to scale up and increase access to safe supply programs in an effort to reduce overdose and other drug- and drug policy-related risks. However, it remains unclear whether these efforts taken thus far have meaningfully mitigated the barriers to safe supply experienced by People Who Use Drugs (PWUD), both during and beyond the context of COVID-19. We thus undertook a scoping review to identify key concepts, strategies and gaps in evidence with respect to the provision of safe supply during pandemics and other emergencies. Methods We conducted three searches across Scopus, Medline, Embase, CINAHL, and The Cochrane Central Register of Controlled Trials (CENTRAL) for peer-reviewed and grey literature articles to understand barriers/facilitators to both accessing and prescribing legal, pharmaceutical-grade drugs, including opioids, benzodiazepines, and/or stimulants during public health emergencies from January 1 2002 to June 30 2020. We also included opioid agonist therapies (OAT) during emergency conditions. All potential sources underwent title/abstract screening and duplicate full- text review to determine eligibility for inclusion. Three reviewers extracted characteristics and barriers/facilitators to accessing or prescribing drugs for each study, and these were then inductively analyzed to identify common themes. Key stakeholders (PWUD, prescribers, and policymakers/regulators) informed the search strategy and validated findings and interpretations. Input from PWUD and prescribers was gathered through Advisory Committee meetings and one-on-one consultations, respectively. Results We screened 9,839 references and included 169 studies (135 peer-reviewed articles and 36 grey literature reports). From 119 articles, we identified 35 themes related to barriers/facilitators to prescribing safe supply or OAT. Few studies (n=24) focused on emergency or pandemic contexts. Among the most frequently reported barriers were restrictive laws or policies (n= 33; 28%). The most frequently cited facilitator was temporary legal or regulatory exemptions (n= 16; 13%). Further stakeholder consultation identified barriers/facilitators to safe supply absent in the reviewed literature: PWUD reported barriers including lack of access to desired substances, concerns about child apprehension, and a lack of cultural competency within safe supply/OAT programs; prescribers reported barriers including regional differences in service delivery, colleague support, and a lack of, or disagreement between, clinical guidance documents. Conclusion We identified multiple barriers and facilitators to accessing and/or prescribing safe supply or OAT. With few peer-reviewed studies on safe supply models, particularly in the context of emergencies, input from PWUD and other stakeholders offered crucial insights not reflected in the existing literature. To address the overdose epidemic stemming from the criminalization of an unregulated drug supply, prescribers, regulators, and public health authorities should focus on scaling up, and then evaluating, diverse safe supply frameworks that address the facilitators and barriers we have identified

    Adherence to Tuberculosis Therapy among Patients Receiving Home-Based Directly Observed Treatment: Evidence from the United Republic of Tanzania.

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    \ud \ud Non-adherence to tuberculosis (TB) treatment is the leading contributor to the selection of drug-resistant strains of Mycobacterium tuberculosis and subsequent treatment failure. Tanzania introduced a TB Patient Centred Treatment (PCT) approach which gives new TB patients the choice between home-based treatment supervised by a treatment supporter of their own choice, and health facility-based treatment observed by a medical professional. The aim of this study was to assess the extent and determinants of adherence to anti-TB therapy in patients opting for home-based treatment under the novel PCT approach. In this cross-sectional study, the primary outcome was the percentage of patients adherent to TB therapy as detected by the presence of isoniazid in urine (IsoScreen assay). The primary analysis followed a non-inferiority approach in which adherence could not be lower than 75%. Logistic regression was used to examine the influence of potentially predictive factors. A total of 651 new TB patients were included. Of these, 645 (99.1%) provided urine for testing and 617 patients (95.7%; 90%CI 94.3-96.9) showed a positive result. This result was statistically non-inferior to the postulated adherence level of 75% (p<0.001). Adherence to TB therapy under home-based Directly Observed Treatment can be ensured in programmatic settings. A reliable supply of medication and the careful selection of treatment supporters, who preferably live very close to the patient, are crucial success factors. Finally, we recommend a cohort study to assess the rate of adherence throughout the full course of TB treatment
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