329 research outputs found

    Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors

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    BACKGROUND: Renal dysfunction often occurs in liver transplant (LT) recipients receiving calcineurin inhibitor (CNI)-based immunosuppressive regimens, increasing morbidity and mortality rates. Replacement of CNIs by mTOR inhibitor-based immunosuppressive protocols may prevent renal impairment in LT recipients. MATERIAL AND METHODS: Outcomes in patients who underwent LT between 1996 and 2010 at our center and who were switched from CNI-based to mTOR inhibitor-based immunosuppression were retrospectively analyzed. Renal course, hyperlipidemia, and graft rejection were assessed in patients maintained on this CNI-free regimen for at least 24 months. RESULTS: Of the 85 patients switched from CNI-based to mTOR inhibitor-based, CNI-free immunosuppression, 78 met the inclusion criteria. Within the first 6 weeks after switching, the covariable adjusted estimated glomerular filtration rate (eGFR) increased 5.6 mL/min [95% confidence interval 2.6–8.7 mL/min, p<0.001], but there were no further statistically noticeable changes in eGFR. Concentrations of cholesterol and triglycerides increased statistically, noticeable within the first 12 months after drug conversion. Histologically proven graft rejection was observed in 4 patients (5.1%) after conversion. CONCLUSIONS: Conversion from CNI-based to CNI-free, mTOR inhibitor-based immunosuppression after LT is safe and can result in significant renal recovery. CNI-free, mTOR inhibitor-based immunosuppression is a potential option for patients with contraindications for CNIs and for LT recipients with rapid reduction in kidney function due to CNIs

    From solgel prepared porous silica to monolithic porous Mg2Si/MgO composite materials

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    Mg2Si is apart from its conductivity properties expected to be a promising candidate for thermoelectric applications due to its low toxicity, low costs, and the high abundance of its precursor chemicals. Through the addition of a homogeneous distribution of nanoparticles (e.g. MgO) and by reducing the size of Mg2Si to the nanometer regime, it is possible to decrease the thermal conductivity by increasing phonon-interface scattering and, as a result, improve the thermoelectric properties. However, classical approaches do not allow for the synthesis of nanocomposites from Mg2Si and MgO. In this work, a straightforward route is presented towards homogeneously mixed Mg2Si/MgO via a two-step magnesiothermic reduction process starting from solgel derived hierarchically organized porous silica. Monolithic materials composed of Mg2Si and MgO in variable molar ratios are built up from a macroporous network of Mg2Si with homogeneously distributed MgO particles exhibiting a crystallite size in the range of 2437nm.(VLID)286459

    A historically controlled, single-arm, multi-centre, prospective trial to evaluate the safety and efficacy of MonoMax® suture material for abdominal wall closure after primary midline laparotomy. ISSAAC-Trial [NCT005725079]

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    <p>Abstract</p> <p>Background</p> <p>Several randomized controlled trials have compared different suture materials and techniques for abdominal wall closure with respect to the incidence of incisional hernias after midline laparotomy and shown that it remains, irrespective of the methods used, considerably high, ranging from 9% to 20%. The development of improved suture materials which would reduce postoperative complications may help to lower its frequency.</p> <p>Design</p> <p>This is a historically controlled, single-arm, multi-centre, prospective trial to evaluate the safety of MonoMax<sup>® </sup>suture material for abdominal wall closure in 150 patients with primary elective midline incisions. INSECT patients who underwent abdominal closure using Monoplus<sup>® </sup>and PDS<sup>® </sup>will serve as historical control group. The incidences of wound infections and of burst abdomen are defined as composite primary endpoints. Secondary endpoints are the frequency of incisional hernias within one year after operation and safety. To ensure adequate comparability in surgical performance and recruitment, the 4 largest centres of the INSECT-Trial will participate. After hospital discharge, the investigators will examine the enrolled patients again at 30 days and at 12 ± 1 months after surgery.</p> <p>Conclusion</p> <p>This historically controlled, single-arm, multi-centre, prospective ISSAAC trial aims to assess whether the use of an ultra-long-lasting absorbable monofilament suture material is safe and efficient.</p> <p>Trial registration</p> <p>NCT005725079</p

    Заява Спілки Археологів України щодо проекту Закону України “Про відродження унікального Символу православ’я — церкви Богородиці (Десятинної) в місті Києві” (№ 9196)

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    The Milankovitch theory of climate change is widely accepted, but the registration of the climate changes in the stratigraphic record and their use in building high-resolution astronomically tuned timescales has been disputed due to the complex and fragmentary nature of the stratigraphic record. However, results of time series analysis and consistency with independent magnetobiostratigraphic and/or radio-isotopic age models show that Milankovitch cycles are recorded not only in deep marine and lacustrine successions, but also in ice cores and speleothems, and in eolian and fluvial successions. Integrated stratigraphic studies further provide evidence for continuous sedimentation at Milankovitch time scales (10^4 years up to 10^6 years). This combined approach also shows that strict application of statistical confidence limits in spectral analysis to verify astronomical forcing in climate proxy records is not fully justified and may lead to false negatives. This is in contrast to recent claims that failure to apply strict statistical standards can lead to false positives in the search for periodic signals. Finally, and contrary to the argument that changes in insolation are too small to effect significant climate change, seasonal insolation variations resulting from orbital extremes can be significant (20% and more) and, as shown by climate modelling, generate large climate changes that can be expected to leave a marked imprint in the stratigraphic record. The tuning of long and continuous cyclic successions now underlies the standard geological time scale for much of the Cenozoic and also for extended intervals of the Mesozoic. Such successions have to be taken into account to fully comprehend the (cyclic) nature of the stratigraphic record

    Investigation of Polyurea-Crosslinked Silica Aerogels as a Neuronal Scaffold: A Pilot Study

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    BACKGROUND: Polymer crosslinked aerogels are an attractive class of materials for future implant applications particularly as a biomaterial for the support of nerve growth. The low density and nano-porous structure of this material combined with large surface area, high mechanical strength, and tunable surface properties, make aerogels materials with a high potential in aiding repair of injuries of the peripheral nervous system. however, the interaction of neurons with aerogels remains to be investigated. METHODOLOGY: In this work the attachment and growth of neurons on clear polyurea crosslinked silica aerogels (PCSA) coated with: poly-L-lysine, basement membrane extract (BME), and laminin1 was investigated by means of optical and scanning electron microscopy. After comparing the attachment and growth capability of neurons on these different coatings, laminin1 and BME were chosen for nerve cell attachment and growth on PCSA surfaces. The behavior of neurons on treated petri dish surfaces was used as the control and behavior of neurons on treated PCSA discs was compared against it. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that: 1) untreated PCSA surfaces do not support attachment and growth of nerve cells, 2) a thin application of laminin1 layer onto the PCSA discs adhered well to the PCSA surface while also supporting growth and differentiation of neurons as evidenced by the number of processes extended and b3-tubulin expression, 3) three dimensional porous structure of PCSA remains intact after fixing protocols necessary for preservation of biological samples and 4) laminin1 coating proved to be the most effective method for attaching neurons to the desired regions on PCSA discs. This work provides the basis for potential use of PCSA as a biomaterial scaffold for neural regeneration

    Risk prediction for estrogen receptor-specific breast cancers in two large prospective cohorts

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    Background: Few published breast cancer (BC) risk prediction models consider the heterogeneity of predictor variables between estrogen-receptor positive (ER+) and negative (ER-) tumors. Using data from two large cohorts, we examined whether modeling this heterogeneity could improve prediction. Methods: We built two models, for ER+ (ModelER+) and ER- tumors (ModelER-), respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort. Discrimination (C-statistic) and calibration (the agreement between predicted and observed tumor risks) were assessed both internally and externally in 82,319 postmenopausal women from the Women’s Health Initiative study. We performed decision curve analysis to compare ModelER+ and the Gail model (ModelGail) regarding their applicability in risk assessment for chemoprevention. Results: Parity, number of full-term pregnancies, age at first full-term pregnancy and body height were only associated with ER+ tumors. Menopausal status, age at menarche and at menopause, hormone replacement therapy, postmenopausal body mass index, and alcohol intake were homogeneously associated with ER+ and ER- tumors. Internal validation yielded a C-statistic of 0.64 for ModelER+ and 0.59 for ModelER-. External validation reduced the C-statistic of ModelER+ (0.59) and ModelGail (0.57). In external evaluation of calibration, ModelER+ outperformed the ModelGail: the former led to a 9% overestimation of the risk of ER+ tumors, while the latter yielded a 22% underestimation of the overall BC risk. Compared with the treat-all strategy, ModelER+ produced equal or higher net benefits irrespective of the benefit-to-harm ratio of chemoprevention, while ModelGail did not produce higher net benefits unless the benefit-to-harm ratio was below 50. The clinical applicability, i.e. the area defined by the net benefit curve and the treat-all and treat-none strategies, was 12.7 × 10− 6 for ModelER+ and 3.0 × 10− 6 for ModelGail. Conclusions: Modeling heterogeneous epidemiological risk factors might yield little improvement in BC risk prediction. Nevertheless, a model specifically predictive of ER+ tumor risk could be more applicable than an omnibus model in risk assessment for chemoprevention

    Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies

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    Objective: To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts. Design: Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability). Results: The systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC. Conclusion: Several of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained
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