Fighting HIV/AIDS: Reconfiguring the State?

The author wishes to thank the anonymous reviewers of the article and the ESRC for funding part of this research

The utility of routine surveillance screening with magnetic resonance imaging (MRI) to detect tumour recurrence in children with low-grade central nervous system (CNS) tumours : a systematic review

Background: Magnetic resonance imaging (MRI) is routinely used as a surveillance tool to detect early asymptomatic tumour recurrence with a view to improving patient outcomes. This systematic review aimed to assess its utility in children with low-grade CNS tumours. Methods: Using standard systematic review methods, twelve databases were searched up to January 2017. Results: Seven retrospective case series studies (n = 370 patients) were included, with average follow-up ranging from 5.6 to 7 years. No randomised controlled trials (RCTs) were identified. Due to study heterogeneity only a descriptive synthesis could be undertaken. Imaging was most frequent in the first year post-surgery (with 2–4 scans) reducing to around half this frequency in year two and annually thereafter for the duration of follow-up. Diagnostic yield ranged from 0.25 to 2%. Recurrence rates ranged from 5 to 41%, with most recurrences asymptomatic (range 65–100%). Collectively, 56% of recurrences had occurred within the first year post-treatment (46% in the first 6-months), 68% by year two and 90% by year five. Following recurrence, 90% of patients underwent treatment changes, mainly repeat surgery (72%). Five-year OS ranged from 96 to 100%, while five-year recurrence-free survival ranged from 67 to 100%. None of the studies reported quality of life measures. Conclusion: This systematic review highlights the paucity of evidence currently available to assess the utility of MRI surveillance despite it being routine clinical practice and costly to patients, their families and healthcare systems. This needs to be evaluated within the context of an RCT

Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial

Purpose Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B). Materials and Methods Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points. Results One hundred sixty patients with RR-HRNB were included. For B random assignment (n = 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P = .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n = 121) and topotecan (n = 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80). Conclusion The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era

Prescribing and deprescribing antihypertensive medication in older people by Dutch general practitioners: a qualitative study

Contains fulltext : 193047.pdf (publisher's version ) (Open Access

What Is Weight Loss After Bariatric Surgery Expressed in Percentage Total Weight Loss (%TWL)? A Systematic Review

Percentage total weight loss (%TWL) might be better than percentage excess weight loss to express weight loss in bariatric surgery. In this systematic review, performed according to the PRISMA statement, results of laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (LRYGB) are assessed in %TWL. A total of 13,426 studies were screened and 49 included, reporting data of 24,760 patients. The results show that, despite limiting data, LRYGB is favorable over LSG in terms of weight loss in short-term follow-up. Although recent guidelines recommend to use %TWL when reporting outcome in bariatric surgery, this study shows that there is still insufficient quality data in %TWL, especially on LSG. The use of %TWL as the primary outcome measure in bariatric surgery should be encouraged. Graphical abstract: [Figure not available: see fulltext.]

Structure-function relationships in the regulation of energy transfer between mitochondria and ATPases in cardiac cells

The present study discusses the role of structural organization of cardiac cells in determining the mechanisms of regulation of oxidative phosphorylation and interaction between mitochondria and ATPases. In permeabilized adult cardiomyocytes, the apparent Km (Michaelis-Menten constant) for ADP in the regulation of respiration is far higher than in mitochondria isolated from the myocardium. Respiration of mitochondria in permeabilized cardiomyocytes is effectively activated by endogenous ADP produced by ATPases from exogenous ATP, and the activation of respiration is associated with a decrease in the apparent Km for ATP in the regulation of ATPase activity compared with this parameter in the absence of oxidative phosphorylation. It has also been shown that a large fraction of the endogenous ADP stimulating respiration remains inaccessible for the exogenous ADP trapping system, consisting of pyruvate kinase and phosphoenolpyruvate, unless the mitochondrial structures are modified by controlled proteolysis. These data point to the endogenous cycling of adenine nucleotides between mitochondria and ATPases. Accordingly, the current hypothesis is that in cardiac cells, mitochondria and ATPases are compartmentalized into functional complexes (ie, intracellular energetic units [ICEUs]), which appear to represent a basic pattern of organization of energy metabolism in these cells. Within the ICEUs, the mitochondria and ATPases interact via different routes: creatine kinase-mediated phosphoryltransfer; adenylate kinase-mediated phosphoryltransfer; and direct ATP and ADP channelling. The function of ICEUs changes not only after selective proteolysis, but also during contraction of cardiomyocytes caused by an increase in cytosolic Ca2+ concentration up to micromolar levels. In these conditions, the apparent Km for exogenous ADP and ATP in the regulation of respiration markedly decreases, and more ADP becomes available for the exogenous pyruvate kinase-phosphoenolpyruvate system, which indicates altered barrier functions of the ICEUs. Thus, structural changes transmitted from the contractile apparatus to mitochondria clearly participate in the regulation of mitochondrial function due to alterations in localized restriction of the diffusion of adenine nucleotides. The importance of strict structural organization in cardiac cells emerged drastically from experiments in which the regulation of mitochondrial respiration was assessed in a novel cardiac cell line, that is, beating and nonbeating HL-1 cells. In these cells, the mitochondrial arrangement is irregular and dynamic, whereas the sarcomeric structures are either absent (in nonbeating HL-1 cells) or only rarely present (in beating HL-1 cells). In parallel, the apparent Km for exogenous ADP in the regulation of respiration was much lower than that in permeabilized primary cardiomyocytes, and trypsin treatment exerted no impact on the low Km value for ADP, in contrast to adult cardiomyocytes where it caused a marked decrease in this parameter. The HL-1 cells were also characterized by the absence of direct exchange of adenine nucleotides. The results further support the concept that the ICEUs in adult cardiomyocytes are products of complex structural organization developed to create the most optimal conditions for effective energy transfer and feedback between mitochondria and ATPases

Round-robin evaluation of nadir ozone profile retrievals: methodology and application to MetOp-A GOME-2

International audienceA methodology for the round-robin evaluation and the geophysical validation of ozone profile data retrieved from nadir UV backscatter satellite measurements is detailed and discussed, consisting of data set content studies, information content studies, co-location studies, and comparisons with reference measurements. Within the European Space Agency's Climate Change Initiative on ozone (Ozone_cci project), the proposed round-robin procedure is applied to two nadir ozone profile data sets retrieved at the Royal Netherlands Meteorological Institute (KNMI) and the Rutherford Appleton Laboratory (RAL, United Kingdom), using their respective OPERA v1.26 and RAL v2.1 optimal estimation algorithms, from MetOp-A GOME-2 (i.e. the second generation Global Ozone Monitoring Experiment on the first Meteorological Operational Satellite) measurements taken in 2008. The ground-based comparisons use ozonesonde and lidar profiles as reference data, acquired by the Network for the Detection of Atmospheric Composition Change (NDACC), Southern Hemisphere Additional Ozonesonde programme (SHADOZ), and other stations of the World Meteorological Organisation's Global Atmosphere Watch (WMO GAW). This direct illustration highlights practical issues that inevitably emerge from discrepancies in e.g. profile representation and vertical smoothing, for which different recipes are investigated and discussed. Several approaches for information content quantification, vertical resolution estimation, and reference profile resampling are compared and applied as well. The paper concludes with compliance estimates of the two GOME-2 ozone profile data sets with user requirements from the Global Climate Observing System (GCOS) and from climate modellers

Comprehensive quality assessment of GOME- and IASI-type multi-mission tropospheric ozone data records

International audienceTropospheric ozone plays a key role in air quality and has a significant impact on the radiation budget of the Earth, both directly and through its chemical influence on other trace gases. Assessments of atmospheric composition change and of associated climate change therefore demand accurate observations of the tropospheric ozone, both on the global and regional scales and both in the longer and shorter term. Such observations have been provided by two series of European nadir-viewing ozone profilers, namely the scattered-light UV-visible spectrometers of the GOME type, launched regularly since 1995 (GOME, SCIAMACHY, OMI, GOME-2 on MetOp-A/B/C, and the upcoming S-5p TROPOMI and Sentinel-5 missions), and the thermal infrared emission sounders of the IASI type, launched regularly since 2006 (IASI on MetOp platforms and IASI-NG on MetOp-SG). In particular, several tro- pospheric ozone data products have been improved and harmonised in the context of the European Space Agency’s Climate Change Initiative (ESA CCI) on ozone (www.esa-ozone-cci.org). To verify their fitness-for-purpose, those tropospheric ozone datasets must undergo a comprehensive quality assessment (QA), including (a) detailed iden- tification of their geographical, vertical and temporal domains of validity, (b) quantification of their potential bias, noise and drift and their dependences on influence quantities, and (c) assessment of the mutual consistency of data from different sounders. For this purpose we have applied to the aforementioned Ozone CCI datasets a versatile QA/validation system developed over years in the context of ESA’s Multi-TASTE and CCI projects, EUMETSAT’s O3M-SAF, and the European Commission’s GEOmon and QA4ECV. For both GOME- and IASI-type climate data records we report on data content studies, information content studies, and comparisons with co-located reference observations from the well established NDACC, SHADOZ, and GAW ozonesonde networks. Dependence of the tropospheric ozone data quality on major influence quantities and perspectives for the future Sentinel missions are discussed

Wishes and needs of community-dwelling older persons concerning general practice: A qualitative study

<div><p>Introduction</p><p>Community-dwelling older persons often experience hindering health complaints that disturb daily activities. If general practitioners (GPs) are unaware of such complaints, this could lead to a mismatch in provided care and needed or expected care. In this qualitative study with community-dwelling older persons we investigated how older persons experience hindering health complaints, how they deal with them, and what they expect from their GP.</p><p>Methods</p><p>Participants (aged ≥80 years) with pain and/or problems with walking/standing were invited to participate in a (group)interview about hindering health problems and expectations from general practice. Data were analysed using the framework method and results were discussed with a client panel.</p><p>Results</p><p>Participants experienced various hindering health complaints in addition to pain and/or problems with walking/standing. Complaints affecting social activities were experienced as the most hindering. Participants actively tried to remain independent and, to achieve this, GPs were expected to be involved and be easily accessible. However, they did not expect specific help from their GP for pain or problems with walking/standing. Suggestions for improvement of care from GPs included optimisation of accessibility (continuous availability by telephone), a yearly check including medication review, open communication, and empathy and support during major life events.</p><p>Conclusions</p><p>According to older persons with hindering health complaints, GPs could improve their accessibility/relationship with patients by: 1) continuous telephonic availability, 2) initiating regular contact with medication reviews, and 3) initiating support during major life events. This might lower the reported barriers to contact the GP for hindering health complaints.</p></div

Baseline Characteristics of The Study Population.

<p>Baseline Characteristics of The Study Population.</p