Are They Really Lost? "True" Status and Reasons for Treatment Discontinuation among HIV Infected Patients on Antiretroviral Therapy Considered Lost to Follow Up in Urban Malawi

INTRODUCTION Patients who are lost to follow-up (LTFU) while on antiretroviral therapy (ART) pose challenges to the long-term success of ART programs. We describe the extent to which patients considered LTFU are misclassified as true disengagement from care when they are still alive on ART and explain reasons for ART discontinuation using our active tracing program to further improve ART retention programs and policies. METHODS We identified adult ART patients who missed clinic appointment by more than 3 weeks between January 2006 and December 2010, assuming that such patients would miss their doses of antiretroviral drugs. Patients considered LTFU who consented during ART registration were traced by phone or home visits; true ART status after tracing was documented. Reasons for ART discontinuation were also recorded for those who stopped ART. RESULTS Of the 4,560 suspected LTFU cases, 1,384 (30%) could not be traced. Of the 3,176 successfully traced patients, 952 (30%) were dead and 2,224 (70%) were alive, of which 2,183 (99.5%) started ART according to phone-based self-reports or physical verification during in-person interviews. Of those who started ART, 957 (44%) stopped ART and 1,226 (56%) reported still taking ART at the time of interview by sourcing drugs from another clinic, using alternative ART sources or making brief ART interruptions. Among 940 cases with reasons for ART discontinuations, failure to remember (17%), too weak/sick (12%), travel (46%), and lack of transport to the clinic (16%) were frequently cited; reasons differed by gender. CONCLUSION The LTFU category comprises sizeable proportions of patients still taking ART that may potentially bias retention estimates and misdirect resources at the clinic and national levels if not properly accounted for. Clinics should consider further decentralization efforts, increasing drug allocations for frequent travels, and improving communication on patient transfers between clinics to increase retention and adherence.

Isotopes Trace Biogeochemistry and Sources of Cu and Zn in an intertidal soil

River floodplain soils are sinks and potential sources for toxic trace metals like Cu and Zn. We hypothesize that stable Cu and Zn isotope ratios reflect both the mobilization and the sources of metals. We determined the soil properties, the concentrations and partitioning of Cu and Zn, and variations in δ65Cu and δ66Zn values in a core obtained from an Aquic Udifluvent developed on a freshwater intertidal mudflat of the River Elbe, Germany. The core was sampled at 2 cm intervals to a depth of 34 cm, which corresponds to approximately 9 yr of sedimentation. Elevated concentrations of Cu (up to 320 μg g−1) and Zn (up to 2080 μg g−1) indicated anthropogenic pollution. At the time of sampling the redox conditions changed from oxic (Eh 200 to 400 mV, above 22 cm deep) to strongly anoxic conditions (-100 to -200 mV, below 22 cm deep). The δ65Cu values varied systematically with depth (from -0.02 to 0.16‰) and were correlated with the Fe, C, and N concentrations. Although pre-depositional variations cannot be ruled out, the systematic variation with depth suggests post-sedimentation fractionation of δ65Cu in response to seasonally variable organic matter deposition and redox conditions. In contrast, the δ66ZnIRMM values were uniform (from -0.07 to 0.01‰) throughout the core, indicating that the Zn isotopes did not significantly fractionate after deposition and that the Zn sources were homogeneous throughout the sedimentation.

Prediction of 1-year mortality in patients with acute coronary syndromes undergoing percutaneous coronary intervention: validation of the logistic clinical SYNTAX (Synergy Between Percutaneous Coronary Interventions With Taxus and Cardiac Surgery) score

OBJECTIVES This study sought to validate the Logistic Clinical SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score in patients with non-ST-segment elevation acute coronary syndromes (ACS), in order to further legitimize its clinical application. BACKGROUND The Logistic Clinical SYNTAX score allows for an individualized prediction of 1-year mortality in patients undergoing contemporary percutaneous coronary intervention. It is composed of a "Core" Model (anatomical SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction), and "Extended" Model (composed of an additional 6 clinical variables), and has previously been cross validated in 7 contemporary stent trials (>6,000 patients). METHODS One-year all-cause death was analyzed in 2,627 patients undergoing percutaneous coronary intervention from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. Mortality predictions from the Core and Extended Models were studied with respect to discrimination, that is, separation of those with and without 1-year all-cause death (assessed by the concordance [C] statistic), and calibration, that is, agreement between observed and predicted outcomes (assessed with validation plots). Decision curve analyses, which weight the harms (false positives) against benefits (true positives) of using a risk score to make mortality predictions, were undertaken to assess clinical usefulness. RESULTS In the ACUITY trial, the median SYNTAX score was 9.0 (interquartile range 5.0 to 16.0); approximately 40% of patients had 3-vessel disease, 29% diabetes, and 85% underwent drug-eluting stent implantation. Validation plots confirmed agreement between observed and predicted mortality. The Core and Extended Models demonstrated substantial improvements in the discriminative ability for 1-year all-cause death compared with the anatomical SYNTAX score in isolation (C-statistics: SYNTAX score: 0.64, 95% confidence interval [CI]: 0.56 to 0.71; Core Model: 0.74, 95% CI: 0.66 to 0.79; Extended Model: 0.77, 95% CI: 0.70 to 0.83). Decision curve analyses confirmed the increasing ability to correctly identify patients who would die at 1 year with the Extended Model versus the Core Model versus the anatomical SYNTAX score, over a wide range of thresholds for mortality risk predictions. CONCLUSIONS Compared to the anatomical SYNTAX score alone, the Core and Extended Models of the Logistic Clinical SYNTAX score more accurately predicted individual 1-year mortality in patients presenting with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention. These findings support the clinical application of the Logistic Clinical SYNTAX score.

Assessing and mapping LD and SLM to directly support the planning and scaling up of SLM interventions to combat desertification

Global investment in Sustainable Land Management (SLM) has been substantial, but knowledge gaps remain. Overviews of where land degradation (LD) is taking place and how land users are addressing the problem using SLM are still lacking for most individual countries and regions. Relevant maps focus more on LD than SLM, and they have been compiled using different methods. This makes it impossible to compare the benefits of SLM interventions and prevents informed decision-making on how best to invest in land. To fill this knowledge gap, a standardised mapping method has been collaboratively developed by the World Overview of Conservation Approaches and Technologies (WOCAT), FAO’s Land Degradation Assessment in Drylands (LADA) project, and the EU’s Mitigating Desertification and Remediating Degraded Land (DESIRE) project. The method generates information on the distribution and characteristics of LD and SLM activities and can be applied at the village, national, or regional level. It is based on participatory expert assessment, documents, and surveys. These data sources are spatially displayed across a land-use systems base map. By enabling mapping of the DPSIR framework (Driving Forces-Pressures-State-Impacts-Responses) for degradation and conservation, the method provides key information for decision-making. It may also be used to monitor LD and conservation following project implementation. This contribution explains the mapping method, highlighting findings made at different levels (national and local) in South Africa and the Mediterranean region. Keywords: Mapping, Decision Support, Land Degradation, Sustainable Land Management, Ecosystem Services, Participatory Expert Assessment

Jatropha mahafalensis oil from Madagascar: properties and suitability as liquid biofuel

Access to affordable and renewable sources of energy is crucial to reducing poverty and enhancing rural development in countries of the global South. Straight vegetable oil was recently identified as a possible alternative to conventional biomass for rural energy supply. In this context, the Jatropha curcas Linn. species has been extensively investigated with regard to its potential as a biofuel feedstock. In contrast, only little is known about Jatropha mahafalensis Jum. & H. Perrier, which is an indigenous and endemic representative of the Jatropha genus in Madagascar. This paper explores the potential and suitability of J. mahafalensis as a biofuel feedstock. Seed samples were collected in the area of Soalara in south-western Madagascar in February and September 2011. Two agro-ecological zones (coastal area and calcareous plateau) and two plant age groups (below and above 10 years) were considered. These four sample groups were analyzed with regard to oil properties, element contents, and fatty acid profiles. Measured values differed greatly between the two harvests, probably owing to different climatic or storage conditions. No direct relation between age of trees or location and oil quality could be established. The analyses indicate that J. mahafalensis oil can be used in oil lamps, cooking stoves and stationary combustion engines for electrification or for biodiesel production. However, modifications in storage and extraction methods, as well as further processing steps are necessary to enable its utilization as a straight vegetable oil and feedstock for biodiesel production. If these technical requirements can be met, and if it turns out that J. mahafalensis oil is economically competitive in comparison with firewood, charcoal, paraffin and petroleum, it can be considered as a promising feedstock for rural energy supply.

Validation and reclassification of MGAP and GAP in hospital settings using data from the Trauma Audit and Research Network.

BACKGROUND Recently, two simple clinical scores were published to predict survival in trauma patients. Both scores may successfully guide major trauma triage, but neither has been independently validated in a hospital setting. METHODS This is a cohort study with 30-day mortality as the primary outcome to validate two new trauma scores-Mechanism, Glasgow Coma Scale (GCS), Age, and Pressure (MGAP) score and GCS, Age and Pressure (GAP) score-using data from the UK Trauma Audit and Research Network. First, an assessment of discrimination, using the area under the receiver operating characteristic (ROC) curve, and calibration, comparing mortality rates with those originally published, were performed. Second, we calculated sensitivity, specificity, predictive values, and likelihood ratios for prognostic score performance. Third, we propose new cutoffs for the risk categories. RESULTS A total of 79,807 adult (≥16 years) major trauma patients (2000-2010) were included; 5,474 (6.9%) died. Mean (SD) age was 51.5 (22.4) years, median GCS score was 15 (interquartile range, 15-15), and median Injury Severity Score (ISS) was 9 (interquartile range, 9-16). More than 50% of the patients had a low-risk GAP or MGAP score (1% mortality). With regard to discrimination, areas under the ROC curve were 87.2% for GAP score (95% confidence interval, 86.7-87.7) and 86.8% for MGAP score (95% confidence interval, 86.2-87.3). With regard to calibration, 2,390 (3.3%), 1,900 (28.5%), and 1,184 (72.2%) patients died in the low, medium, and high GAP risk categories, respectively. In the low- and medium-risk groups, these were almost double the previously published rates. For MGAP, 1,861 (2.8%), 1,455 (15.2%), and 2,158 (58.6%) patients died in the low-, medium-, and high-risk categories, consonant with results originally published. Reclassifying score point cutoffs improved likelihood ratios, sensitivity and specificity, as well as areas under the ROC curve. CONCLUSION We found both scores to be valid triage tools to stratify emergency department patients, according to their risk of death. MGAP calibrated better, but GAP slightly improved discrimination. The newly proposed cutoffs better differentiate risk classification and may therefore facilitate hospital resource allocation. LEVEL OF EVIDENCE Prognostic study, level II.

Pulsed versus continuous wave CO2 laser excisions of 100 oral fibrous hyperplasias: a randomized controlled clinical and histopathological study

BACKGROUND In experimental animal studies, pulsing the CO2 laser beam has been shown to reduce the thermal damage zone of excised oral mucosal tissue. However, there is still controversy over whether this is borne out under clinical conditions. OBJECTIVE To compare the outcome following excisional biopsies of fibrous hyperplasias using a pulsed (cf) versus a continuous wave (cw) CO2 laser mode regarding the thermal damage zone, duration of surgeries, intra- and postoperative complications, postoperative pain sensation, scarring and/or relapse during the initial 6 months. MATERIALS AND METHODS One hundred Swiss-resident patients with a fibrous hyperplasia in their buccal mucosa were randomly assigned to the cw mode (5 W) or the cf mode (140 Hz, 400 microseconds, 33 mJ, 4.62 W) group. All excisions were performed by one single oral surgeon. Postoperative pain (2 weeks) was recorded by visual analogue scale (VAS; ranging from 0 to 100). Intake of analgesics and postoperative complications were recorded in a standardized study form. The maximum width of the collateral thermal damage zone was measured (µm) in excision specimens by one pathologist. Intraoral photographs at 6-month follow-up examinations were evaluated regarding scarring (yes/no). RESULTS Median duration of the excision was 65 seconds in the cw and 81 seconds in the cf group (P = 0.13). Intraoperative bleeding occurred in 16.3% of the patients in the cw and 17.7% of the cf group. The median value of the thermal damage zone was 161(±228) μm in the cw and 152(± 105) μm in the cf group (P = 0.68). The reported postoperative complications included swelling in 19% and minor bleeding in 6% without significant differences between the two laser modes. When comparing each day separately or the combined mean VAS scores of both groups between Days 1-3, 1-7, and 1-15, there were no significant differences. However, more patients of the cw group (25%) took analgesics than patients of the cf group (9.8%) resulting in a borderline significance (P = 0.04). Scarring at the excision site was found in 50.6% of 77 patients after 6 months, and more scars were identified in cases treated with the cf mode (P = 0.03). CONCLUSIONS Excision of fibrous hyperplasias performed with a CO2 laser demonstrated a good clinical outcome and long-term predictability with a low risk of recurrence regardless of the laser mode (cf or cw) used. Scarring after 6 months was only seen in 50.6% of the cases and was slightly more frequent in the cf mode group. Based on the findings of the present study, a safety border of 1 mm appears sufficient for both laser modes especially when performing a biopsy of a suspicious soft tissue lesion to ensure a proper histopathological examination.

Laser ablation and induced nano-particle synthesis

Laser pulses are largely used for processing and analysis of materials and in particular for nano-particle synthesis. This paper addresses fundamentals of the generation of nano-materials following specific thermodynamic paths of the irradiated material. Computer simulations using the hydro code MULTI and the SESAME equation of state have been performed to follow the dynamics of a target initially heated by a short laser pulse over a distance comparable to the metal skin depth.

Exploring the validity and reliability of a questionnaire for evaluating virtual patient design with a special emphasis on fostering clinical reasoning

Background: Virtual patients (VPs) are increasingly used to train clinical reasoning. So far, no validated evaluation instruments for VP design are available. Aims: We examined the validity of an instrument for assessing the perception of VP design by learners. Methods: Three sources of validity evidence were examined: (i) Content was examined based on theory of clinical reasoning and an international VP expert team. (ii) The response process was explored in think-aloud pilot studies with medical students and in content analyses of free text questions accompanying each item of the instrument. (iii) Internal structure was assessed by exploratory factor analysis (EFA) and inter-rater reliability by generalizability analysis. Results: Content analysis was reasonably supported by the theoretical foundation and the VP expert team. The think-aloud studies and analysis of free text comments supported the validity of the instrument. In the EFA, using 2547 student evaluations of a total of 78 VPs, a three-factor model showed a reasonable fit with the data. At least 200 student responses are needed to obtain a reliable evaluation of a VP on all three factors. Conclusion: The instrument has the potential to provide valid information about VP design, provided that many responses per VP are available.

Measurement of the electroweak production of dijets in association with a Z-boson and distributions sensitive to vector boson fusion in proton-proton collisions at √s = 8 TeV using the ATLAS detector

Measurements of fiducial cross sections for the electroweak production of two jets in association with a Z-boson are presented. The measurements are performed using 20.3 fb−1 of proton-proton collision data collected at a centre-of-mass energy of p s = 8TeV by the ATLAS experiment at the Large Hadron Collider. The electroweak component is extracted by a fit to the dijet invariant mass distribution in a fiducial region chosen to enhance the electroweak contribution over the dominant background in which the jets are produced via the strong interaction. The electroweak cross sections measured in two fiducial regions are in good agreement with the Standard Model expectations and the background-only hypothesis is rejected with significance above the 5ơ level. The electroweak process includes the vector boson fusion production of a Z-boson and the data are used to place limits on anomalous triple gauge boson couplings. In addition, measurements of cross sections and differential distributions for inclusive Z-boson-plus-dijet production are performed in five fiducial regions, each with different sensitivity to the electroweak contribution. The results are corrected for detector effects and compared to predictions from the Sherpa and Powheg event generators.

In vitro differentiation of mouse granulocytes. Programmed Cell Death: Methods and Protocols

Granulocytes are central players of the immune system and, once activated, a tightly controlled balance between effector functions and cell removal by apoptosis guarantees maximal host benefit with least possible collateral damage to healthy tissue. Granulocytes are end-differentiated cells that cannot be maintained in culture for prolonged times. Isolating primary granulocytes is inefficient and challenging when working with mice, and especially so for the lowly abundant eosinophil and basophils subtypes. Here we describe an in vitro protocol to massively expand mouse derived myeloid progenitors and to differentiate them ‘on demand’ and in large numbers into mature neutrophils or basophils.

Impact of Software Settings on Multiple-Breath Washout Outcomes

BACKGROUND AND OBJECTIVES Multiple-breath washout (MBW) is an attractive test to assess ventilation inhomogeneity, a marker of peripheral lung disease. Standardization of MBW is hampered as little data exists on possible measurement bias. We aimed to identify potential sources of measurement bias based on MBW software settings. METHODS We used unprocessed data from nitrogen (N2) MBW (Exhalyzer D, Eco Medics AG) applied in 30 children aged 5-18 years: 10 with CF, 10 formerly preterm, and 10 healthy controls. This setup calculates the tracer gas N2 mainly from measured O2 and CO2concentrations. The following software settings for MBW signal processing were changed by at least 5 units or >10% in both directions or completely switched off: (i) environmental conditions, (ii) apparatus dead space, (iii) O2 and CO2 signal correction, and (iv) signal alignment (delay time). Primary outcome was the change in lung clearance index (LCI) compared to LCI calculated with the settings as recommended. A change in LCI exceeding 10% was considered relevant. RESULTS Changes in both environmental and dead space settings resulted in uniform but modest LCI changes and exceeded >10% in only two measurements. Changes in signal alignment and O2 signal correction had the most relevant impact on LCI. Decrease of O2 delay time by 40 ms (7%) lead to a mean LCI increase of 12%, with >10% LCI change in 60% of the children. Increase of O2 delay time by 40 ms resulted in mean LCI decrease of 9% with LCI changing >10% in 43% of the children. CONCLUSIONS Accurate LCI results depend crucially on signal processing settings in MBW software. Especially correct signal delay times are possible sources of incorrect LCI measurements. Algorithms of signal processing and signal alignment should thus be optimized to avoid susceptibility of MBW measurements to this significant measurement bias.

Detection efficiency of microchannel plates for e(-) and pi(-) in the momentum range from 17.5 to 345 MeV/c

High-energy e(-) and pi(-) were measured by the multichannel plate (MCP) detector at the PiM1 beam line of the High Intensity Proton Accelerator Facilities located at the Paul Scherrer Institute, Villigen, Switzerland. The measurements provide the absolute detection efficiencies for these particles: 5.8% +/- 0.5% for electrons in the beam momenta range 17.5-300 MeV/c and 6.0% +/- 1.3% for pions in the beam momenta range 172-345 MeV/c. The pulse height distribution determined from the measurements is close to an exponential function with negative exponent, indicating that the particles penetrated the MCP material before producing the signal somewhere inside the channel. Low charge extraction and nominal gains of the MCP detector observed in this study are consistent with the proposed mechanism of the signal formation by penetrating radiation. A very similar MCP ion detector will be used in the Neutral Ion Mass (NIM) spectrometer designed for the JUICE mission of European Space Agency (ESA) to the Jupiter system, to perform measurements of the chemical composition of the Galilean moon exospheres. The detection efficiency for penetrating radiation determined in the present studies is important for the optimisation of the radiation shielding of the NIM detector against the high-rate and high-energy electrons trapped in Jupiter's magnetic field. Furthermore, the current studies indicate that MCP detectors can be useful to measure high-energy particle beams at high temporal resolution. (C) 2015 AIP Publishing LLC.

Methods for preparing and counting biochemical varves

Four different preparation and counting methods for biochemical varves were compared in order to assess counting errors and to standardize these techniques. The properties of two embedding methods, namely the shock-freeze, freeze-dry and the water-acetone-epoxy-exchange method, are discussed. Varve counts were carried out on fresh sediment and on sediment thin-sections, on the latter by manual and by automated counting using image-analysis software. Counting on fresh sediment and using image-analysis generally underestimated the number of varves, especially in sections with inconspicuous varves. A comparison between multiple varve counts carried out by a single analyst and different analysts showed no significant differences in the mean varve counts.