221 research outputs found

    Моделі процесів захисту цілісності інформаційних об’єктів з використанням коду умовних лишків. Алгоритм нулізації

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    The models of processes of defense of integrity of information’s holding object with application of code of conditional tailings which provide high probabilities of exposure of violations of integrity and correction of the exposed curvatures are examined

    Additive effects of the dopamine D2 receptor and dopamine transporter genes on the error-related negativity in young children

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    The error-related negativity (ERN) is a negative deflection in the event-related potential that occurs approximately 50ms following the commission of an error at fronto-central electrode sites. Previous models suggest dopamine plays a role in the generation of the ERN. We recorded event-related potentials (ERPs) while 279 children aged 5-7 years completed a simple Go/No-Go task; the ERN was examined in relation to the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes. Results suggest an additive effect of the DRD2 and DAT1 genotype on ERN magnitude such that children with at least one DRD2 A1 allele and children with at least one DAT1 9 allele have an increased (i.e. more negative) ERN. These results provide further support for the involvement of dopamine in the generation of the ERN. © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society

    Modelling the impact and cost-effectiveness of combination prevention amongst HIV serodiscordant couples in Nigeria

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    Objective: To estimate the impact and cost-effectiveness of treatment as prevention (TasP), pre-exposure prophylaxis (PrEP) and condom promotion for serodiscordant couples in Nigeria. / Design: Mathematical and cost modelling. / Methods: A deterministic model of HIV-1 transmission within a cohort of serodiscordant couples and to/from external partners was parameterized using data from Nigeria and other African settings. The impact and cost-effectiveness were estimated for condom promotion, PrEP and/or TasP, compared with a baseline where antiretroviral therapy (ART) was offered according to 2010 national guidelines (CD4+ <350 cells/μl) to all HIV-positive partners. The impact was additionally compared with a baseline of current ART coverage (35% of those with CD4+ <350 cells/μl). Full costs (in US 2012)ofprogrammeintroductionandimplementationwereestimatedfromaproviderperspective./Results:SubstantialbenefitscamefromscalingupARTtoallHIVpositivepartnersaccordingto2010nationalguidelines,withadditionalsmallerbenefitsofprovidingTasP,PrEPorcondompromotion.ComparedwithabaselineofofferingARTtoallHIVpositivepartnersatthe2010nationalguidelines,condompromotionwasthemostcosteffectivestrategy[US2012) of programme introduction and implementation were estimated from a provider perspective. / Results: Substantial benefits came from scaling up ART to all HIV-positive partners according to 2010 national guidelines, with additional smaller benefits of providing TasP, PrEP or condom promotion. Compared with a baseline of offering ART to all HIV-positive partners at the 2010 national guidelines, condom promotion was the most cost-effective strategy [US 1206/disability-adjusted-life-year (DALY)], the next most cost-effective intervention was to additionally give TasP to HIV-positive partners (incremental cost-effectiveness ratio US 1607/DALY),followedbyadditionallygivingPrEPtoHIVnegativepartnersuntiltheirHIVpositivepartnersinitiateART(US1607/DALY), followed by additionally giving PrEP to HIV-negative partners until their HIV-positive partners initiate ART (US 7870/DALY). When impact was measured in terms of infections averted, PrEP with condom promotion prevented double the number of infections as condom promotion alone. / Conclusions: The first priority intervention for serodiscordant couples in Nigeria should be scaled up ART access for HIV-positive partners. Subsequent incremental benefits are greatest with condom promotion and TasP, followed by PrEP

    Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies

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    Abstract View references (47) The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy-proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow-up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24-70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P <.001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010-019631-35). \ua9 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeon

    Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience

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    Background: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft. Methods: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function. Results: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m2. Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases. Conclusions: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients

    Organ transplantation from deceased donors with vaccine-induced thrombosis and thrombocytopenia

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    Vaccine-induced thrombosis and thrombocytopenia (VITT) may follow immunisation with the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2. Autoantibodies to platelet factor 4 (PF4) may mediate VITT through antibody-dependent platelet activation, though the underlying etiology is uncertain. Anti-PF4 antibodies are also seen in heparin-induced thrombocytopenia, though most cases of VITT do not have prior heparin exposure. More than 20 million people in the United Kingdom (UK) have received the ChAdOx1 nCoV-19 vaccine

    Identifying models of HIV care and treatment service delivery in Tanzania, Uganda, and Zambia using cluster analysis and Delphi survey.

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    BACKGROUND: Organization of HIV care and treatment services, including clinic staffing and services, may shape clinical and financial outcomes, yet there has been little attempt to describe different models of HIV care in sub-Saharan Africa (SSA). Information about the relative benefits and drawbacks of different models could inform the scale-up of antiretroviral therapy (ART) and associated services in resource-limited settings (RLS), especially in light of expanded client populations with country adoption of WHO's test and treat recommendation. METHODS: We characterized task-shifting/task-sharing practices in 19 diverse ART clinics in Tanzania, Uganda, and Zambia and used cluster analysis to identify unique models of service provision. We ran descriptive statistics to explore how the clusters varied by environmental factors and programmatic characteristics. Finally, we employed the Delphi Method to make systematic use of expert opinions to ensure that the cluster variables were meaningful in the context of actual task-shifting of ART services in SSA. RESULTS: The cluster analysis identified three task-shifting/task-sharing models. The main differences across models were the availability of medical doctors, the scope of clinical responsibility assigned to nurses, and the use of lay health care workers. Patterns of healthcare staffing in HIV service delivery were associated with different environmental factors (e.g., health facility levels, urban vs. rural settings) and programme characteristics (e.g., community ART distribution or integrated tuberculosis treatment on-site). CONCLUSIONS: Understanding the relative advantages and disadvantages of different models of care can help national programmes adapt to increased client load, select optimal adherence strategies within decentralized models of care, and identify differentiated models of care for clients to meet the growing needs of long-term ART patients who require more complicated treatment management
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