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Introduction : Limited data describe outcomes on second-line antiretroviral therapy (ART) among children globally. Our objective was to contribute data on outcomes among children living with HIV after initiation of second-line ART in the context of routine care within a large global cohort collaboration. Methods : Patient-level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow-up were summarized for children who switched to second-line ART after starting a standard first-line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub-Saharan Africa (SSA). Cumulative incidences of mortality and loss to follow-up (LTFU) were estimated using a competing risks framework. Results : Of the 85,389 children on first-line ART, 3,555 (4%) switched to second-line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second-line regimens were protease inhibitor-based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow-up after switch to second-line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second-line ranged from 235 cells/mm(3) in SSA to 828 cells/mm(3) in North America. Improvements in CD4 counts were observed over two years of follow-up, particularly in regions with lower CD4 counts at second-line switch. Improvements in weight-for-age z-scores were not observed during follow-up. Cumulative incidence of LTFU at two years was

Background : Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. Methods : In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. Findings : At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90.0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3.9 years (IQR 1.6-6.9) and 82 885 (88.8%) patients initiated NNRTI-based and 10 466 (11.2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4.2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3.1% (95% CI 3.0-3.2), but this estimate varied widely depending on the cohort monitoring strategy, from 6.8% (6.5-7.2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0.8% (0.6-1.0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p

Terrestrial laser scanning (TLS) is providing exciting new ways to quantify tree and forest structure, particularly above-ground biomass (AGB). We show how TLS can address some of the key uncertainties and limitations of current approaches to estimating AGB based on empirical allometric scaling equations (ASEs) that underpin all large-scale estimates of AGB. TLS provides extremely detailed non-destructive measurements of tree form independent of tree size and shape. We show examples of three-dimensional (3D) TLS measurements from various tropical and temperate forests and describe how the resulting TLS point clouds can be used to produce quantitative 3D models of branch and trunk size, shape and distribution. These models can drastically improve estimates of AGB, provide new, improved large-scale ASEs, and deliver insights into a range of fundamental tree properties related to structure. Large quantities of detailed measurements of individual 3D tree structure also have the potential to open new and exciting avenues of research in areas where difficulties of measurement have until now prevented statistical approaches to detecting and understanding underlying patterns of scaling, form and function. We discuss these opportunities and some of the challenges that remain to be overcome to enable wider adoption of TLS methods. publishedVersion

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Fragestellung: Die bisherige Standardbildgebung zur Diagnostik von Wirbelsäulenerkrankungen ist neben einer nativ-radiologischen Aufnahme des entsprechenden Wirbelsäulenabschnitts die Magnetresonanz-Tomographie (MRT). Ein Nachteil dieser war bisher, dass diese Aufnahmen statische Bilder in[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2015)

Purpose: The purpose of this study was to determine the accuracy of dynamic lumbosacral-MRI compared to upright myelography to detect segmental dural compression. Methods and Materials: 95 patients were screened for the study. Seventeen patients complaining of low back pain and clinically suspected dural compression qualified for the study. These patients underwent myelography and dynamic lumbosacral-MRI with an open-configuration 0.25 T tilting system. Images were obtained in supine and upright position for both modalities. Two independent readers evaluated the myelography images and the lumbosacral- MRI on a persegment basis with regard to segmental dural compression. Reference standard was a consensus reading of myelography in upright position. Reader agreement was assessed by correlation statistics (Cohen's kappa) and diagnostic accuracy was calculated on a persegment basis. Results: Myelography in upright position showed 35 segmental dural compressions. Lumbosacral-MRI showed 30 segmental dural compressions in supine and 33 in upright position. The agreement between the readers for Myelography in supine and upright position was 0.881 and 0.808 respectively. The inter-rater agreement for MRI in supine and upright position was 0.895 and 0.747. MRI sensitivity/specificity in upright position were 80%/92% for reader 1 and 74.3%/96% for reader 2; in supine position 77.1%/96% for reader 1 and 74.1%/98% for reader 2. Conclusion: Dynamic MRI with an open-configuration, low-field tilting MRI system is a feasible and promising tool to study lumbosacral dural compression. We demonstrated that this MR technology performed highly specific compared to upright myelography, but had some limitations regarding sensitivity. Interobserver agreement was comparable to myelography.

Spinal canal stenosis is a dynamic phenomenon that becomes apparent during spinal loading. Current diagnostic procedures have considerable short comings in diagnosing the disease to full extend, as they are performed in supine situation. Upright MRI imaging might overcome this diagnostic gap.This study investigated the lumbar neuroforamenal diameter, spinal canal diameter, vertebral body translation, and vertebral body angles in 3 different body positions using upright MRI imaging.Fifteen subjects were enrolled in this study. A dynamic MRI in 3 different body positions (at 0 degrees supine, 80 degrees upright, and 80 degrees upright+hyperlordosis posture) was taken using a 0.25T open-configuration scanner equipped with a rotatable examination bed allowing a true standing MRI.The mean diameter of the neuroforamen at L5/S1 in 0 degrees position was 8.4mm on the right and 8.8mm on the left, in 80 degrees position 7.3mm on the right and 7.2mm on the left, and in 80 degrees position with hyperlordosis 6.6mm (P

Orientadora: Denise Cybis Fontana; Coorientador: Genei Antonio Dalmago.

O cultivo de arroz irrigado no Rio Grande do Sul caracteriza-se pela permanência de lâmina de irrigação sobre o solo, o que ocasiona perdas de agrotóxicos na ocorrência de chuvas; portanto, o adequado manejo de irrigação pode influenciar na redução do transporte destes para o ambiente. O objetivo deste trabalho foi avaliar o efeito de diferentes manejos de irrigação no extravasamento da água e no transporte e persistência de clomazone, thiamethoxam, imidacloprid, trifloxystrobin e propiconazol em lavoura de arroz irrigado. Os tratamentos arranjados em esquema fatorial consistiram nos manejos de irrigação por inundação contínua, intermitente e por banhos (fator A) e pelos agrotóxicos mencionados (fator B). Determinou-se o volume total de água extravasada e a taxa de dissipação e transporte desses agrotóxicos. Devido ao maior armazenamento de água da chuva, quando comparadas com a irrigação contínua, as irrigações intermitente e por banhos proporcionaram diminuição de 53 e 95% do volume de água perdida, resultando, respectivamente, em redução de 49 e 64% na massa total de agrotóxicos transportados para o ambiente, em relação ao total aplicado na lavoura. A massa de agrotóxico transportada não ultrapassou 3% do total aplicado, e as maiores concentrações de agrotóxicos em água ocorreram próximo à sua aplicação. Com base nesses resultados, salienta-se que os manejos de irrigação intermitente e por banhos minimizam o transporte de agrotóxicos para o ambiente. Rice crop in the state of Rio Grande do Sul is characterized by the presence of water layer on the soil, which can cause pesticide runoff during the occurrence of rainfall. Thus, proper irrigation management can reduce pesticide transport into the environment. The objective of this study was to evaluate the effect of different irrigation managements on water runoff, transport and dissipation of clomazone, thiamethoxam, imidacloprid, trifloxystrobin, and propiconazol. The treatments were arranged in a factorial scheme and consisted of continuous flooding, intermittent flooding, and flushing irrigation (factor A) and by the application of the pesticides listed above (factor B). Total water runoff, and pesticide transport and dissipation rate were evaluated. Due to the larger rainfall storage, compared with continuous flooding, intermittent flooding and flushing irrigation provided a reduction of 53 and 95% of water runoff, resulting, respectively, in a reduction of 49 and 64% of the total mass transported into the environment in relation to the total applied in the field. The pesticide mass transported was lower than 3% of the total amount applied. Based on these results, it could be concluded that intermittent flooding and flushing irrigation minimize pesticide transport into the environment.Since the highest pesticide concentrations occur close to application time, it is of fundamental importance to conduct proper irrigation management providing maximum permanence in the environment.

O cultivo de arroz irrigado no Rio Grande do Sul caracteriza-se pela permanência de lâmina de irrigação sobre o solo, o que ocasiona perdas de agrotóxicos na ocorrência de chuvas; portanto, o adequado manejo de irrigação pode influenciar na redução do transporte destes para o ambiente. O objetivo deste trabalho foi avaliar o efeito de diferentes manejos de irrigação no extravasamento da água e no transporte e persistência de clomazone, thiamethoxam, imidacloprid, trifloxystrobin e propiconazol em lavoura de arroz irrigado. Os tratamentos arranjados em esquema fatorial consistiram nos manejos de irrigação por inundação contínua, intermitente e por banhos (fator A) e pelos agrotóxicos mencionados (fator B). Determinou-se o volume total de água extravasada e a taxa de dissipação e transporte desses agrotóxicos. Devido ao maior armazenamento de água da chuva, quando comparadas com a irrigação contínua, as irrigações intermitente e por banhos proporcionaram diminuição de 53 e 95% do volume de água perdida, resultando, respectivamente, em redução de 49 e 64% na massa total de agrotóxicos transportados para o ambiente, em relação ao total aplicado na lavoura. A massa de agrotóxico transportada não ultrapassou 3% do total aplicado, e as maiores concentrações de agrotóxicos em água ocorreram próximo à sua aplicação. Com base nesses resultados, salienta-se que os manejos de irrigação intermitente e por banhos minimizam o transporte de agrotóxicos para o ambiente.

Fragestellung: Die Rekonstruktion der korakoklavikulären Bänder (KKB) mittels autologer Sehnentransplantate wird zunehmend zur Behandlung von Akromioklavikulargelenksverletzungen durchgeführt. Es existieren unterschiedliche Verfahren zur Befestigung der Transplantate am Processus [for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 75. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 97. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 52. Tagung des Berufsverbandes der Fachärzte für Orthopädie

Fragestellung: Die anatomische Rekonstruktion der korakoklavikulären Bänder zur Behandlung von ACG- Luxationen bietet biomechanisch, verglichen mit alternativen Verfahren, die höchste Stabilität. Ansatz und Ursprung der CC-Bänder sind gut beschrieben. Wenig ist jedoch bisher[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 74. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 96. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 51. Tagung des Berufsverbandes der Fachärzte für Orthopädie

This article presents an overview of regulations, guidelines and societal debates in eight member states of the EC about a) embryonic and fetal tissue transplantation (EFTT), and b) the use of human embryonic stem cells (hES cells) for research into cell therapy, including 'therapeutic' cloning. There appears to be a broad acceptance of EFTT in these countries. In most countries guidance has been developed. There is a 'strong' consensus about some of the central conditions for 'good clinical practice' regarding EFTT. International differences concern, amongst others, some of the informed consent issues involved, and the questions whether an intermediary organisation is necessary, whether the methods of abortion may be influenced by the possible use of EFT, and whether EFTT should only be used for the experimental treatment of rare disorders. The potential use of hES cells for research into cell therapy has given a new impetus to the debate about (human) embryo research. The therapeutic prospects with regard to the retrieval and research use of hES cells appear to function as a catalyst for the introduction of less restrictive regulations concerning research with spare embryos, at least in some European countries. It remains to be seen whether the prospect of treating patients suffering from serious disorders with transplants produced by therapeutic cloning will decrease the societal and moral resistance to allowing the generation of embryos for 'instrumental' use.

The reason why a few myeloma cells egress from the bone marrow (BM) into peripheral blood (PB) remains unknown. Here, we investigated molecular hallmarks of circulating tumor cells (CTCs) to identify the events leading to myeloma trafficking into the bloodstream. After using next-generation flow to isolate matched CTCs and BM tumor cells from 32 patients, we found high correlation in gene expression at single-cell and bulk levels (r ≥ 0.94, P = 10−16), with only 55 genes differentially expressed between CTCs and BM tumor cells. CTCs overexpressed genes involved in inflammation, hypoxia, or epithelial–mesenchymal transition, whereas genes related with proliferation were downregulated in CTCs. The cancer stem cell marker CD44 was overexpressed in CTCs, and its knockdown significantly reduced migration of MM cells towards SDF1-α and their adhesion to fibronectin. Approximately half (29/55) of genes differentially expressed in CTCs were prognostic in patients with newly-diagnosed myeloma (n = 553; CoMMpass). In a multivariate analysis including the R-ISS, overexpression of CENPF and LGALS1 was significantly associated with inferior survival. Altogether, these results help understanding the presence of CTCs in PB and suggest that hypoxic BM niches together with a pro-inflammatory microenvironment induce an arrest in proliferation, forcing tumor cells to circulate in PB and seek other BM niches to continue growing., This study was supported by the Centro de Investigación Biomédica en Red —Área de Oncología— del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00489, and CB16/12/00400), Cancer Research UK, FCAECC and AIRC under the Accelerator Award Programme, Instituto de Salud Carlos III and Asociación Española Contra el Cáncer by ERA-NET TRANSCAN-2 Programme (AC17/00101), the Black Swan Research Initiative of the International Myeloma Foundation, the European Research Council (ERC) 2015 Starting Grant (MYELOMANEXT, 680200), the Czech Science Foundation through Project No. 19-25354Y, the European Regional Development Fund—Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868), and the Ministry of Health of the Czech Republic (15-29667A).

INTRODUCTION: A growing body of evidence indicates that risk of CV events is higher in HIV-infected patients (HIV?) when compared to HIV-uninfected persons (HIV-). This enhanced risk may in part be mediated through preclinical CV damage. Large artery stiffness, a well-documented marker of arterial damage and predictor of adverse CV prognosis, is usually assessed by measuring aortic pulse wave velocity (PWV). Several studies examined arterial stiffness in HIV? with inconsistent results. In a previous meta-analysis, showing increased arterial stiffness in HIV? than in HIV- subjects, studies assessing aortic and peripheral PWV were pooled together. This may be misleading, because only the former has a demonstrated prognostic significance. AIM: We performed a new meta-analysis with the aim to evaluate the influence of HIV-infection and its therapy only on aortic PWV (aPWV). METHODS: A literature search was performed in PubMed, Google Scholar, Web of Science and Medline for articles, also in abstract form, concerning the effect of HIV infection and ART on aortic stiffness. The standardized mean difference (SMD) and corresponding 95% confidence intervals were calculated for aortic PWV in different comparison groups, which contained naive HIV? versus HIV-, HIV? receiving ART versus HIV- and HIV? receiving ART versus naive HIV?. Statistical heterogeneity, assessed by Q test and I2 statistic, was observed in all these comparisons. Therefore, both the fixed and random effect models were implemented, even if only the results of the latter were presented. RESULTS: In a total of 11 studies, naive HIV? (n = 566) showed increased aPWV compared to HIV- (n = 816): SMD = 0.386 (0.197–0.575), p.001. Nine studies were identified comparing HIV? treated with ART (n = 631) to HIV- (n = 637) showing higher values of aPWV in the former than in latter: SMD = 0.681 (0.396–0.967), p.001. In 8 studies HIV? treated with ART (n = 599) exhibited greater aPWV values than those of naive HIV? (n = 325): SMD = 0.259 (0.006–0.512), p.04. CONCLUSIONS: Our meta-analysis seems to suggest that HIV infection per se and even more ART may impair aortic distensibility.