Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of platelet autoantibodies on the course of the disease and clinical response of patients with idiopathic thrombocytopenic purpura

In this study, we evaluated the response to treatment of 409 idiopathic thrombocytopenic purpura (ITP) patients who were tested for the presence of platelet‐associated autoantibodies by direct‐platelet immunofluorescence test (PIFT) and for the presence of plasma antibodies directed against the GPIIb/IIIa, GPIb and GPIa/IIa by monoclonal antibody immobilization of platelet antigens (MAIPA). In patients with platelet autoantibodies in comparison with patients without antibodies more frequently were observed the chronic form of disease (83.5%vs. 68.5%) and severe symptoms of haemorrhage diathesis (17.3%vs. 6.9%). Evaluation of the treatment response (to corticosteroids, immunosuppressive drugs and splenectomy) referred to patients with complete response, e.g. complete remission defined as platelet count of >100 × 109/l for at least 2 years. The percentage of complete response in the whole population of ITP patients, both with and without autoantibodies regardless of the method of treatment, was similar (about 54%). However, the presence of platelet autoantibodies had effect on patients treated with corticosteroids: complete response approximately 71% (36/51) of patients with autoantibodies and in 60% (72/120) of patients without antibodies, as well as in patients treated with immunosuppressive drugs (cyclophosphamide, azathioprine, vincristin and vinblastin); complete response approximately 51% (11/21) of patients with autoantibodies and in 34.8% (6/17) of patients without autoantibodies. The presence of autoantibodies had no effect on the response of splenectomy patients.
Multiple access channels (Ph.D. Thesis abstr.)

The standard performance measures of information theory, including the channel capacity C, the rate-distortion function R(D), and the reliability-rate function E(R), are developed from a new and unifying point of view. New such measures are also introduced. The approach originates in a treatment of the simple hypothesis-testing problem by use of the discrimination, a function of two probability distributions q1 and q2 def ined by
Fluid lavage of open wounds (FLOW): a multicenter, blinded, factorial pilot trial comparing alternative irrigating solutions and pressures in patients with open fractures.

BACKGROUND Open fractures are an important source of morbidity and are associated with delayed union, nonunion, and infection. Preventing infection through meticulous irrigation and debridement is an important goal in management, and different lavage fluids and irrigation techniques (e.g., high- or low-pressure lavage) have been described for this purpose. However, there are a limited number of randomized trials comparing irrigating solutions or irrigating technique. We compared the use of castile soap versus normal saline and high- versus low-pressure pulsatile lavage on the rates of reoperations and complications in patients with open fracture wounds. METHODS We conducted a multicenter, blinded, randomized 2 × 2 factorial pilot trial of 111 patients in whom an open fracture wound was treated with either castile soap solution or normal saline and either high- or low-pressure pulsatile lavage. The primary composite outcome of reoperation, measured at 12 months after initial operative procedure, included infection, wound healing problems, and nonunion. Planned reoperations were not included. Secondary outcomes included all infection, all wound healing problems, and nonunion as well as functional outcomes scores (EuroQol-5 dimensions and short form-12). RESULTS Eighty-nine patients completed the 1-year follow-up. Among all patients, 13 (23%) in the castile soap group and 13 (24%) in the saline group had a primary outcome event (hazard ratio, 0.91, 95% confidence interval: 0.42-2.00, p = 0.52). Sixteen patients (28%) in the high-pressure group and 10 patients (19%) in the low-pressure group had a primary outcome event (hazard ratio 0.55, 95% confidence interval: 0.24-1.27, p = 0.17). Functional outcome scores showed no significant differences at any time point between groups. CONCLUSION The fluid lavage of open wounds pilot randomized controlled trial demonstrated the possibility that the use of low pressure may decrease the reoperation rate for infection, wound healing problems, or nonunion. We have demonstrated the desirability and feasibility of a definitive trial examining the effects of alternative irrigation approaches.
A Double-blind, Randomised Comparative Trial of Amisulpride Versus Olanzapine in the Treatment of Schizophrenia: Short-term Results at Two Months

Summary Objective: To compare the efficacy and safety of the atypical antipsychotics amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia. Design and setting: A multinational, double-blind randomised clinical trial. Patients and treatment:Three hundred and seventy-seven patients with predominantly positive symptomatology were treated for six months with either amisulpride (200-800 mg/d) or olanzapine (5-20 mg/d). Main outcome measures: Short-term results were analysed after two months of treatment. The primary efficacy measure was the change of score on the Brief Psychiatric Rating Scale (BPRS). Other measures of efficacy and safety were also evaluated. Results: Psychotic symptoms, as measured on the BPRS score, improved with both treatments, amisulpride being equivalent to olanzapine. All BPRS factor scores, as well as depressive symptoms, improved to a similar extent with both treatments. Less than five per cent of patients withdrew for adverse events, and there was no evidence for the emergence of extrapyramidal symptoms with either treatment. Statistically significant greater weight gain (2.7 ± 3.9 kg) was observed during the study in the olanzapine group, compared with the amisulpride group (0.9 ± 3.2 kg, p < 0.0001). Conclusions: Amisulpride and olanzapine show equivalent efficacy at 2 months in the treatment of acute psychotic exacerbations of schizophrenia. Amisulpride offers a significant advantage in preserving body weight.
Anti-viral protection conferred by recombinant adenylate cyclase toxins from Bordetella pertussis carrying a CD8+ T cell epitope from lymphocytic choriomeningitis virus.

The elucidation of the mechanisms of antigen presentation by major histocompatibility complex class I molecules has stimulated the search for nonreplicative vectors that could deliver CD8+ T cell epitopes to the cytosol of antigen-presenting cells to trigger the activation of specific cytotoxic T lymphocytes (CTLs) in vivo. In the present study, we investigated the potential ability of an invasive adenylate cyclase toxin from Bordetella pertussis, carrying a CD8+ T cell epitope from the nucleoprotein of lymphocytic choriomeningitis virus (LCMV), to stimulate protective anti-viral immunity. Mice immunized with this recombinant toxin developed strong CTL responses against LCMV-infected target cells. Moreover, these mice were protected against an intracerebral challenge with a virulent strain of LCMV that killed all nonimmunized mice within 7 days. This protection was abolished after in vivo elimination of CD8+ T cells. A mutant toxin devoid of adenylate cyclase activity (i.e., cAMP synthesizing activity) was constructed by insertion of a dipeptide into the catalytic site of the molecule. This genetically detoxified invasive toxin carrying the LCMV epitope stimulated a strong CTL response against both peptide-coated and virus-infected target cells, and mice immunized with this molecule were fully protected against a lethal intracerebral LCMV challenge. To our knowledge, this study represents the first demonstration that a genetically detoxified bacterial toxin carrying a viral CTL epitope can stimulate efficient protective immunity.
Prediction of long-term outcomes of HIV-infected patients developing non-AIDS events using a multistate approach

Objetives Outcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013. Design Prospective multicenter cohort study. Methods Using a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced (“NAE development”); from alive and NAE-experienced to death (“Death after NAE”); and from alive and NAE-free to death (“Death without NAE”). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition “Death after NAE”. Results 8,789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval [CI], 26.80–30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition “Death after NAE” was 12.1 (95%CI, 4.90–29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45–6.57) for intermediate-severity; and 9.85 (5.45–17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11–3.84), age>50 years (1.78, 1.08–2.94), hepatitis C-coinfection (2.52, 1.38–4.61), lower CD4 cell count at cohort entry (HR 2.49; 95%CI 1.20–5.14 for CD4 cell count below 200 and HR 2.16; 95%CI 1.01–4.66 for CD4 cell count between 200–350, both compared to CD4 cell count higher than 500) and concomitant CD4<200 cells/mL (2.22, 1.42–3.44) were associated with death after NAE. CD4 count and HIV-1 RNA at engagement, previous AIDS and hepatitis C-coinfection predicted mortality in NAE-free persons. Conclusion NAEs, including low-severity events, increase prominently the risk for mortality in PLWH. Prognostic factors differ between NAE-experienced and NAE-free persons. These findings should be taken into account in the clinical management of PLWH developing NAEs and may permit more targeted prevention efforts.
Early Phase Limited Sampling Strategy Characterizing Tacrolimus and Mycophenolic Acid Pharmacokinetics Adapted to the Maintenance Phase of Renal Transplant Patients

The aim of this study was to examine whether a limited sampling strategy (LSS) to allow the simultaneous estimation of the area under the concentration-time curves (AUCs) of tacrolimus and mycophenolic acid (MPA) calculated in the early stage after renal transplantation could be applied to maintenance phase pharmacokinetics. Seventy Japanese patients were enrolled. One year after transplantation, samples were collected just before and 1, 2, 3, 4, 6, 9, and 12 hours after tacrolimus and mycophenolate mofetil administration at 9:00 am and at 9:00 pm. The prediction formulas on day 28 (tacrolimus AUC0-12 = 7.04·C0h + 1.71·C2h + 3.23·C4h + 15.19 and 2.25·C2h + 1.92·C4h + 7.27·C9h + 6.61, and MPA AUC0-12 = 0.26·C0h + 2.06·C2h + 3.82·C4h + 20.38 and 1.77·C2h + 2.34·C4h + 4.76·C9h + 15.94) were applied to pharmacokinetic data obtained at 1 year. Three error indices [percent mean prediction error (ME), % mean absolute error, and percent root mean squared prediction error (RMSE)] were used to evaluate the predictive bias, accuracy, and precision. The predicted AUC0-12 of tacrolimus and MPA at 3 time points, C2h-C4h-C9h, showed higher correlation with the measured AUC0-12 of tacrolimus and MPA (r2 = 0.817 and 0.789, respectively) in comparison with those at C0h-C2h-C4h. The values for the prediction formulas for tacrolimus AUC at 1 year using the C2h-C4h-C9h combination yielded less than 5% for %ME and 15% for %RMSE. The %ME and %RMSE values of the prediction formulas for tacrolimus AUC using the C0h-C2h-C4h combination were 6.3% and 15.9%, respectively. The %ME and %RMSE values of the prediction formulas for MPA AUC at 1 year using the C0h-C2h-C4h combination were 5.9% and 25.8%, respectively, and those for the C2h-C4h-C9h combination were 4.9% and 21.2%, respectively. AUC6-12/AUC0-12 of MPA 1 year after transplantation was significantly lower than 28 days after transplantation. An LSS using C2h-C4h-C9h seems to be applicable for predicting the AUC of tacrolimus and MPA at either posttransplantation stage. The enterohepatic circulation of MPA was significantly reduced 1 year after transplantation. Therefore, 1 year after transplantation, the estimation of the AUC0-12 of MPA for the C0h-C2h-C4h equations was imprecise. It is important that the LSS includes C9h because it contains information on the secondary plasma peak of MPA.
Using mathematical modelling to estimate the impact of periodic presumptive treatment on the transmission of sexually transmitted infections and HIV among female sex workers

Background In settings with poor sexually transmitted infection (STI) control in high-risk groups, periodic presumptive treatment (PPT) can quickly reduce the prevalence of genital ulcers, Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). However, few studies have assessed the impact on HIV. Mathematical modelling is used to quantify the likely HIV impact of different PPT interventions. Methods A mathematical model was developed to project the impact of PPT on STI/HIV transmission amongst a homogeneous population of female sex workers (FSWs) and their clients. Using data from Johannesburg, the impact of PPT interventions with different coverages and PPT frequencies was estimated. A sensitivity analysis explored how the projections were affected by different model parameters or if the intervention was undertaken elsewhere. Results Substantial decreases in NG/CT prevalence are achieved among FSWs receiving PPT. Although less impact is achieved among all FSWs, large decreases in NG/CT prevalence (>50%) are possible with >30% coverage and supplying PPT every month. Higher PPT frequencies achieve little additional impact, whereas improving coverage increases impact until NG/CT becomes negligible. The impact on HIV incidence is smaller, longer to achieve, and depends heavily on the assumed NG/CT cofactors, whether they are additive, the assumed STI/HIV transmission probabilities and STI durations. Greater HIV impact can be achieved in settings with lower sexual activity (except at high coverage), less STI treatment or high prevalences of Haemophilus ducreyi. Conclusions Despite the model's assumption of homogeneous risk behaviour probably resulting in optimistic projections, and uncertainty in STI cofactors and transmission probabilities, projections suggest PPT interventions with sufficient coverage (≥40%) and follow-up (≥2 years) could noticeably decrease the HIV incidence (>20%) among FSW populations with inadequate STI treatment.
A New Late Middle Cambrian Paleomagnetic Pole for the Ellsworth Mountains, Antarctica

A paleomagnetic study of the late Middle to possibly early Late Cambrian Liberty Hills Formation in the Ellsworth Mountains, Antarctica, reveals a stable magnetization with positive fold and reversal tests. The paleopole is based on 16 sites from volcanic and sedimentary rocks and lies at lat 7.3°N and long 326.3°E ( \documentclass{aastex} \usepackage{amsbsy} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{bm} \usepackage{mathrsfs} \usepackage{pifont} \usepackage{stmaryrd} \usepackage{textcomp} \usepackage{portland,xspace} \usepackage{amsmath,amsxtra} \usepackage[OT2,OT1]{fontenc} \newcommand\cyr{ \renewcommand\rmdefault{wncyr} \renewcommand\sfdefault{wncyss} \renewcommand\encodingdefault{OT2} \normalfont \selectfont} \DeclareTextFontCommand{\textcyr}{\cyr} \pagestyle{empty} \DeclareMathSizes{10}{9}{7}{6} \begin{document} \landscape $$\mathrm{A}\,_{95}=6.0^{\circ }$$ \end{document} ). The new paleomagnetic data support the view that the Ellsworth Mountains are part of a microplate—the Ellsworth‐Whitmore Mountains crustal block—that rotated independently of the main Gondwana continental blocks during breakup. The Liberty Hills pole differs from both previous poles recovered from Cambrian rocks in the Ellsworth Mountains and from the available Gondwana reference pole data. Our pole indicates a more northerly prebreakup position for the Ellsworth Mountains than previously suggested, contradicting the overwhelming geologic evidence for a prebreakup position close to southern Africa. The reasons for this are uncertain, but we suggest that problems with the Gondwana apparent polar wander path may be important. More well constrained, early Paleozoic paleomagnetic data are required from the Ellsworth Mountains and the Gondwana continents if the data are to constrain further the Middle‐Late Cambrian location of the Ellsworth‐Whitmore Mountains block.
Successful nodulation of Casuarina by Frankia in axenic conditions

Aims: In order to depict the fine interactions that lead to nodulation, absolute microbiological control of the symbiotic partners is required, i.e. the ability to obtain in vitro axenic nodulation, a condition that has never been fulfilled with the Casuarina–Frankia symbiosis. The effects of culture conditions on plant growth and nodule formation by Casuarina cunninghamiana were investigated.
Evaluating the Efficacy of Closed-Loop Glucose Regulation via Control-Variability Grid Analysis

Background: Advancements in subcutaneous continuous glucose monitoring and subcutaneous insulin delivery are stimulating the development of a minimally invasive artificial pancreas that facilitates optimal glycemic regulation in diabetes. The key component of such a system is the blood glucose controller for which different design strategies have been investigated in the literature. In order to evaluate and compare the efficacy of the various algorithms, several performance indices have been proposed. Methods: A new tool—control-variability grid analysis (CVGA)—for measuring the quality of closed-loop glucose control on a group of subjects is introduced. It is a method for visualization of the extreme glucose excursions caused by a control algorithm in a group of subjects, with each subject presented by one data point for any given observation period. A numeric assessment of the overall level of glucose regulation in the population is given by the summary outcome of the CVGA. Results: It has been shown that CVGA has multiple uses: Comparison of different patients over a given time period, of the same patient over different time periods, of different control laws, and of different tuning of the same controller on the same population. Conclusions: Control-variability grid analysis provides a summary of the quality of glycemic regulation for a population of subjects and is complementary to measures such as area under the curve or low/high blood glucose indices, which characterize a single glucose trajectory for a single subject.
Interaction of Bunyamwera Orthobunyavirus NSs Protein with Mediator Protein MED8: a Mechanism for Inhibiting the Interferon Response

ABSTRACT The NSs protein of Bunyamwera virus (Bunyaviridae) is an antiapoptotic interferon antagonist involved in silencing host protein expression by interfering with mRNA synthesis. Here, we show that the ability to inhibit both host transcription and the interferon response is linked to interaction of NSs with the MED8 component of Mediator, a protein complex necessary for mRNA production. The interacting domain on NSs was mapped to the C-terminal region, which contains amino acids conserved among orthobunyavirus NSs proteins. A recombinant virus in which the interacting domain in NSs was deleted had strongly reduced ability to inhibit host protein expression and was unable to inhibit the interferon response. This study provides further information on the mechanisms by which bunyavirus nonstructural proteins are involved in pathogenesis.
Factors affecting platelet yield and their impact on the platelet increment of patients receiving single donor PLT transfusion

The aim of this study was to analyze the impact of various donor and machine parameters on PLT yield in 127 PLT apheresis procedures, to optimize PLT yield achieving clinical and economic advantages. One hundred and twenty‐seven apheresis procedures were analyzed. Age, gender, volume processed, Hb, and PLT precounts were included as donor predicting variables. AC infusion rate, processing time, and plasma volume collected with PLTs were assessed as machine parameters. We evaluated the post‐transfusion effectiveness in 23 patients with thrombocytopenia, studying the effect of PLT dose, ABO group, and PLT storage time. Females gave higher yields, compared to males, P < 0.01. PLT yield correlated positively with PLT precount (r = 0.512), and TBV (r = 0.404), and negatively with donor preapheresis Hb (r = −0.306). Processing time and AC infusion rate had a positive impact on PLT yield. Post‐apheresis decrease in PLT count was 53.6 ± 26.3 × 1011. Donors with Hb ≥ 12 g/dl, donated safely. Most of the complications were citrate related (13.4% of all procedures). PLT increments in transfused patients correlated positively with the number of units transfused (r = 0.41), and negatively with PLT storage days (r = −0.342). PLT increments in patients receiving ABO‐compatible PLTs were 75% higher, compared to the increments in patients receiving incompatible PLTs. PLT count and volume processed were the main predictors of PLT yield. Increasing the processing time, the AC infusion rate, or the volume of plasma obtained with PLTs can increase PLT yields. High PLT dose, short storage time, as well as ABO compatibility should be considered during PLT transfusion. J. Clin. Apheresis, 2007 © 2007 Wiley‐Liss, Inc.
Smokers’ attitudes and support for e-cigarette policies and regulation in the USA

Background In April 2014, the Food and Drug Administration (FDA) proposed a rule to extend its tobacco regulatory authority to e-cigarettes, which have been unregulated and growing in use since their 2006–2007 US introduction. The FDA will issue a final rule based on comments and data received from researchers, tobacco companies and the public. We aimed to present data about current smokers’ awareness of and attitudes towards potential e-cigarette regulation and various policies in the USA. Methods We conducted a cross-sectional online e-cigarette focused survey of 519 adult current smokers in April 2014, before the FDA's proposed rule was announced. Participants were recruited from a private research panel (GFK's Knowledge Networks) designed to be representative of the US population. Results The majority of respondents (62.5%) did not know that e-cigarettes are unregulated by the FDA but agreed that e-cigarettes should be regulated by the FDA for safety and quality (83.5%), carry warning labels about their potential risks (86.6%) and have the same legal age of sale as other tobacco (87.7%). Support was similarly high among current e-cigarette users. Support was substantial though lower overall for policies to restrict e-cigarette indoor use (41.2%), flavouring (44.3%) and advertising (55.5%), and was negatively associated with current e-cigarette use. Conclusions Support for many e-cigarette regulatory policies is strong among smokers, including for policies that the FDA has recently proposed and potential future regulations. States considering indoor e-cigarette restrictions should know that a substantial number of current smokers support such regulations.