Glutathione deficiency in HIV infection

The tripeptide glutathione (GSH) is the quantitatively most important cysteine derivative of low molecular weight and has numerous important cellular functions. Decreased plasma cysteine and cystine concentrations, decreased intracellular GSH levels, and increased plasma glutamate levels have been found in HIV-infected persons at all stages of the disease and in rhesus macaques within 2 weeks after infection with the closely related simian immunodeficiency virus (SIVmac2). Elevated glutamate levels inhibit the membrane transport of cystine and aggravate thereby the consequences of the cysteine deficiency. Complementary experiments In laboratory animals have shown that glutathione potentiates T cell functions in vivo and in vitro. And studies with healthy human subjects have shown that persons with a combination of a higher than median plasma cystine and lower than median glutamate level have significantly more CD4 T cells than persons with low cystine and high glutamate levels. On the basis of these findings we have proposed that the immunopathology of HIV infection may be largely the consequence of a virus-induced dysregulation of plasma amino acid concentrations. Studies on the mechanistic details revealed that the cysteine and intracellular glutathione deficiency may have several immunologically relevant consequences that affect the antigen presenting cells as well as the responding T lymphocytes. The redox regulation of the transcription factor NFκB accounts at least for some of the consequences.Biomedical Reviews 1993; 2: 9-13

Phase measurement with classical light

In this paper we investigate whether it is in general possible to substitute maximally path-entangled states, namely NOON-states by classical light in a Doppleron-type resonant multiphoton detection processes by studying adaptive phase measurement with classical light. We show that multiphoton detection probability using classical light coincides with that of NOON-states and the multiphoton absorbtion rate is not hindered by the spatially unconstrained photons of the classical light in our scheme. We prove that the optimal phase variance with classical light can be achieved and scales the same as that using NOON-states.Comment: 7 pages, 3 figure

Climacteric Lowers Plasma Levels of Platelet-Derived Microparticles: A Pilot Study in Pre-versus Postmenopausal Women

Background: Climacteric increases the risk of thrombotic events by alteration of plasmatic coagulation. Up to now, less is known about changes in platelet-(PMP) and endothelial cell-derived microparticles (EMP). Methods: In this prospective study, plasma levels of microparticles (MP) were compared in 21 premenopausal and 19 postmenopausal women. Results: No altered numbers of total MP or EMP were measured within the study groups. However, the plasma values of CD61-exposing MP from platelets/megakaryocytes were higher in premenopausal women (5,364 x 10(6)/l, range 4,384-17,167) as compared to postmenopausal women (3,808 x 10(6)/l, range 2,009-8,850; p = 0.020). This differentiation was also significant for the subgroup of premenopausal women without hormonal contraceptives (5,364 x 10(6)/l, range 4,223-15,916; p = 0.047; n = 15). Furthermore, in premenopausal women, higher plasma levels of PMP exposing CD62P were also present as compared to postmenopausal women (288 x 10(6)/l, range 139-462, vs. 121 x 10(6)/l, range 74-284; p = 0.024). This difference was also true for CD63+ PMP levels (281 x 10(6)/l, range 182-551, vs. 137 x 10(6)/l, range 64-432; p = 0.015). Conclusion: Climacteric lowers the level of PMP but has no impact on the number of EMP in women. These data suggest that PMP and EMP do not play a significant role in enhancing the risk of thrombotic events in healthy, postmenopausal women. Copyright (C) 2012 S. Karger AG, Base

Diffuse reflectance spectroscopy for estimating soil properties: A technology for the 21st century

Spectroscopic measurements of soil samples are reliable because they are highly repeatable and reproducible. They characterise the samples' mineral-organic composition. Estimates of concentrations of soil constituents are inevitably less precise than estimates obtained conventionally by chemical analysis. But the cost of each spectroscopic estimate is at most one-tenth of the cost of a chemical determination. Spectroscopy is cost-effective when we need many data, despite the costs and errors of calibration. Soil spectroscopists understand the risks of over-fitting models to highly dimensional multivariate spectra and have command of the mathematical and statistical methods to avoid them. Machine learning has fast become an algorithmic alternative to statistical analysis for estimating concentrations of soil constituents from reflectance spectra. As with any modelling, we need judicious implementation of machine learning as it also carries the risk of over-fitting predictions to irrelevant elements of the spectra. To use the methods confidently, we need to validate the outcomes with appropriately sampled, independent data sets. Not all machine learning should be considered 'black boxes'. Their interpretability depends on the algorithm, and some are highly interpretable and explainable. Some are difficult to interpret because of complex transformations or their huge and complicated network of parameters. But there is rapidly advancing research on explainable machine learning, and these methods are finding applications in soil science and spectroscopy. In many parts of the world, soil and environmental scientists recognise the merits of soil spectroscopy. They are building spectral libraries on which they can draw to localise the modelling and derive soil information for new projects within their domains. We hope our article gives readers a more balanced and optimistic perspective of soil spectroscopy and its future. Highlights Spectroscopy is reliable because it is a highly repeatable and reproducible analytical technique. Spectra are calibrated to estimate concentrations of soil properties with known error. Spectroscopy is cost-effective for estimating soil properties. Machine learning is becoming ever more powerful for extracting accurate information from spectra, and methods for interpreting the models exist. Large libraries of soil spectra provide information that can be used locally to aid estimates from new samples

The Brazilian Soil Spectral Service (BraSpecS): A User-Friendly System for Global Soil Spectra Communication

Although many Soil Spectral Libraries (SSLs) have been created globally, these libraries still have not been operationalized for end-users. To address this limitation, this study created an online Brazilian Soil Spectral Service (BraSpecS). The system was based on the Brazilian Soil Spectral Library (BSSL) with samples collected in the Visible–Near–Short-wave infrared (vis–NIR–SWIR) and Midinfrared (MIR) ranges. The interactive platform allows users to find spectra, act as custodians of the data, and estimate several soil properties and classification. The system was tested by 500 Brazilian and 65 international users. Users accessed the platform (besbbr.com.br), uploaded their spectra, and received soil organic carbon (SOC) and clay content prediction results via email. The BraSpecS prediction provided good results for Brazilian data, but performed variably for other countries. Prediction for countries outside of Brazil using local spectra (External Country Soil Spectral Libraries, ExCSSL) mostly showed greater performance than BraSpecS. Clay R2 ranged from 0.5 (BraSpecS) to 0.8 (ExCSSL) in vis–NIR–SWIR, but BraSpecS MIR models were more accurate in most situations. The development of external models based on the fusion of local samples with BSSL formed the Global Soil Spectral Library (GSSL). The GSSL models improved soil properties prediction for different countries. Nevertheless, the proposed system needs to be continually updated with new spectra so they can be applied broadly. Accordingly, the online system is dynamic, users can contribute their data and the models will adapt to local information. Our community-driven web platform allows users to predict soil attributes without learning soil spectral modeling, which will invite end-users to utilize this powerful technique

Coding of procedures documented by general practitioners in Swedish primary care-an explorative study using two procedure coding systems

<p>Abstract</p> <p>Background</p> <p>Procedures documented by general practitioners in primary care have not been studied in relation to procedure coding systems. We aimed to describe procedures documented by Swedish general practitioners in electronic patient records and to compare them to the Swedish Classification of Health Interventions (KVÅ) and SNOMED CT.</p> <p>Methods</p> <p>Procedures in 200 record entries were identified, coded, assessed in relation to two procedure coding systems and analysed.</p> <p>Results</p> <p>417 procedures found in the 200 electronic patient record entries were coded with 36 different Classification of Health Interventions categories and 148 different SNOMED CT concepts. 22.8% of the procedures could not be coded with any Classification of Health Interventions category and 4.3% could not be coded with any SNOMED CT concept. 206 procedure-concept/category pairs were assessed as a complete match in SNOMED CT compared to 10 in the Classification of Health Interventions.</p> <p>Conclusions</p> <p>Procedures documented by general practitioners were present in nearly all electronic patient record entries. Almost all procedures could be coded using SNOMED CT.</p> <p>Classification of Health Interventions covered the procedures to a lesser extent and with a much lower degree of concordance. SNOMED CT is a more flexible terminology system that can be used for different purposes for procedure coding in primary care.</p

Deep vein thrombosis and pulmonary embolism: a prospective, observational study to evaluate diagnostic performance of the Tina-quant D-Dimer Gen.2 assay

BackgroundD-Dimer testing is a diagnostic tool for exclusion of deep vein thrombosis (DVT) and pulmonary embolism (PE). This study evaluated the diagnostic performance of the Tina-quant® D-Dimer Gen.2 assay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) in patients with low/intermediate pre-test probability of DVT/PE using standard, age-, and clinical probability-adjusted cut-offs.MethodsIn this prospective, observational, multicenter study (July 2017–August 2019), plasma samples were collected from hospital emergency departments and specialist referral centers. DVT/PE was diagnosed under hospital standard procedures and imaging protocols. A standard D-dimer cut-off of 0.5 µg fibrinogen equivalent units (FEU)/ml was combined with the three-level Wells score; cut-offs adjusted for age (age × 0.01 µg FEU/ml for patients &gt;50 years) and clinical probability (1 µg FEU/ml for low probability) were also evaluated. An assay comparison was conducted in a subset of samples using the Tina-quant D-Dimer Gen.2 assay and the previously established routine laboratory assay, STA-Liatest D-Di Plus assay (Stago Deutschland GmbH, Düsseldorf, Germany).Results2,897 patients were enrolled; 2,516 completed the study (DVT cohort: 1,741 PE cohort: 775). Clinical assessment plus D-dimer testing using the standard cut-off resulted in 317 (DVT) and 230 (PE) false positives, and zero (DVT) and one (PE) false negatives. Negative predictive value (NPV) was 100.0% (95% confidence interval [CI]: 99.7%–100.0%) and 99.8% (95% CI: 98.8%–100.0%) for DVT and PE, respectively. After age-adjustment, NPV was 99.9% (95% CI: 99.6%–100.0%) and 99.1% (95% CI: 97.8–99.7) for DVT and PE, respectively. False positive rates decreased (&gt;50%) in clinical probability-adjusted analyses vs. primary analysis. In the assay comparison, the performances of the two assays were comparable.ConclusionThe Tina-quant D-Dimer Gen.2 assay and standard D-dimer cut-off level combined with the three-level Wells score accurately identified patients with a very low probability of DVT/PE

Minimally invasive computer-navigated total hip arthroplasty, following the concept of femur first and combined anteversion: design of a blinded randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Impingement can be a serious complication after total hip arthroplasty (THA), and is one of the major causes of postoperative pain, dislocation, aseptic loosening, and implant breakage. Minimally invasive THA and computer-navigated surgery were introduced several years ago. We have developed a novel, computer-assisted operation method for THA following the concept of "femur first"/"combined anteversion", which incorporates various aspects of performing a functional optimization of the cup position, and comprehensively addresses range of motion (ROM) as well as cup containment and alignment parameters. Hence, the purpose of this study is to assess whether the artificial joint's ROM can be improved by this computer-assisted operation method. Second, the clinical and radiological outcome will be evaluated.</p> <p>Methods/Design</p> <p>A registered patient- and observer-blinded randomized controlled trial will be conducted. Patients between the ages of 50 and 75 admitted for primary unilateral THA will be included. Patients will be randomly allocated to either receive minimally invasive computer-navigated "femur first" THA or the conventional minimally invasive THA procedure. Self-reported functional status and health-related quality of life (questionnaires) will be assessed both preoperatively and postoperatively. Perioperative complications will be registered. Radiographic evaluation will take place up to 6 weeks postoperatively with a computed tomography (CT) scan. Component position will be evaluated by an independent external institute on a 3D reconstruction of the femur/pelvis using image-processing software. Postoperative ROM will be calculated by an algorithm which automatically determines bony and prosthetic impingements.</p> <p>Discussion</p> <p>In the past, computer navigation has improved the accuracy of component positioning. So far, there are only few objective data quantifying the risks and benefits of computer navigated THA. Therefore, this study has been designed to compare minimally invasive computer-navigated "femur first" THA with a conventional technique for minimally invasive THA. The results of this trial will be presented as soon as they become available.</p> <p>Trial registration number</p> <p>DRKS00000739</p

A short-term in situ CO2 enrichment experiment on Heron Island (GBR)

Ocean acidification poses multiple challenges for coral reefs on molecular to ecological scales, yet previous experimental studies of the impact of projected CO2 concentrations have mostly been done in aquarium systems with corals removed from their natural ecosystem and placed under artificial light and seawater conditions. The Coral–Proto Free Ocean Carbon Enrichment System (CP-FOCE) uses a network of sensors to monitor conditions within each flume and maintain experimental pH as an offset from environmental pH using feedback control on the injection of low pH seawater. Carbonate chemistry conditions maintained in the −0.06 and −0.22 pH offset treatments were significantly different than environmental conditions. The results from this short-term experiment suggest that the CP-FOCE is an important new experimental system to study in situ impacts of ocean acidification on coral reef ecosystems

Environmental factors in early childhood are associated with multiple sclerosis: a case-control study

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with increasing incidence mainly in high-income countries. One explanation of this phenomenon may be a higher prevalence of allergic and autoimmune diseases in industrialized countries as a consequence of otherwise beneficial advances in sanitation (hygiene hypothesis). We investigated environmental factors in early childhood associated with MS.</p> <p>Methods</p> <p>A case-control study was performed of 245 MS patients and 296 population-based controls in Berlin. The study participants completed a standardized questionnaire on environmental factors in childhood and youth, including aspects of personal and community hygiene. Multivariable logistic regression analysis was performed to investigate factors in childhood and youth associated with the occurrence of MS.</p> <p>Results</p> <p>Mean age was 46 years (range, 20-80) in the MS group and 42 years (range 18-80) in the control group, of which 73.9% in the MS and 61.5% in the control group were female. The multivariable analysis showed that having at least two older siblings (OR 0.54; p = 0.05, for individuals with two older siblings compared to individuals without older siblings), attending a day-care center (OR 0.5; p = 0.004) and growing up in an urban center with more than 100, 000 inhabitants (OR 0.43; p = 0.009) were factors independently associated with a lower chance for MS.</p> <p>Conclusions</p> <p>The hygiene hypothesis may play a role in the occurrence of MS and could explain disease distribution and increasing incidence.</p