Background
Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative ...groups. In order to define a better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children's Oncology Group (COG).
Methods
We retrospectively identified patients with ARMS N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised ifosfamide + vincristine + dactinomycin + doxorubicin (IVADo), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531, it consisted of either vincristine + dactinomycin + cyclophosphamide (VAC) or VAC alternating with vincristine + irinotecan (VI). Local treatment was similar in both protocols.
Results
The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced Intergroup Rhabdomyosarcoma Study Group (IRS) and large tumors predominated. There were no differences in outcomes between the two groups: 5‐year event‐free survival (EFS), 49% (95% confidence interval CI: 39‐59) and 44% (95% CI: 30‐58), and overall survival (OS), 51% (95% CI: 41‐61) and 53.6% (95% CI: 40‐68) in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1‐positive tumors was significantly inferior to those with FOXO1‐negative (49.3% vs 73%, P = .034). In contrast, in ARST0531, EFS of patients with FOXO1‐positive tumors was 45% compared with 43.8% for those with FOXO1‐negative.
Conclusions
The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion‐negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients.
Background Walking capacity measured by a treadmill test (TT) reflects the patient's maximal capacity in a controlled setting and is part of the physical exercise capacity (PEC). Daily physical ...activity (PA) is defined as the total of actively freely produced movements per day. A lower PA level has been increasingly recognized as a strong predictor of increased morbidity and mortality in patients with intermittent claudication (IC). Recent insights suggested that an increased PEC does not automatically lead to an increase in daily PA. However, the precise relation between PEC and PA in patients with IC is still unclear. Methods A cross-sectional study was conducted to assess the association between several PEC outcomes and PA in a general IC population. PEC was determined by well-established tests (Gardner-Skinner TT, a physical performance battery, a timed up-and-go test, and a 6-minute walk test distance). PA was obtained during 7 consecutive days using a triaxial accelerometer (Dynaport MoveMonitor; McRoberts BV, The Hague, The Netherlands). Five PA components (lying, sitting, standing, shuffling, and locomotion) and four parameters (total duration, number of periods, mean duration per period, and mean movement intensity per period) were analysed. Correlation coefficients between PEC and PA components were calculated. Results Data of 46 patients were available for analysis. Patients were sedentary (sitting and lying) during 81% of the day and were physically active (standing, shuffling, and locomotion) for the remaining 19% of the time. Correlations between PEC outcomes and PA ranged from very weak (0.025) to moderate (0.663). Moderate correlations (as therefore assumed to be relevant) were only found for outcomes of both the TT and 6-minute walk test and the locomotion components of PA. For instance, functional claudication distance (measured by TT) and number of steps per day correlated reasonably well (Spearman correlation ρ = 0.663; P < .01). Conclusions Exercise capacity and PA correlate minimally in patients with IC. PA may be preferred as a novel outcome measure and future treatment target in patients with IC.
Freshwater biota experience physiological challenges in regions affected by salinization, but often the effects on particular species are poorly understood. Freshwater turtles are of particular ...concern as they appear to have limited ability to cope with environmental conditions that are hyperosmotic to their body fluids. Here, we determined the physiological responses of two Australian freshwater chelid turtles,
and
, exposed to freshwater (0‰) and brackish water (15‰, representing a hyperosmotic environment). Brackish water is common in the Murray-Darling River Basin within the natural range of these species in Australia during periods of drought, yet it is unknown how well these species tolerate saline conditions. We hypothesized that these turtles would be unable to maintain homeostasis in the 15‰ water treatment and would suffer osmotic loss of water, increased ionic concentrations and a decrease in body mass. Results revealed that these turtles had elevated plasma concentrations of sodium, chloride, urea and uric acid in the plasma. Plasma ionic concentrations increased proportionally more in
than in
. Individuals of both species reduced feeding in 15‰ water, indicating that behaviour may provide an additional means for freshwater turtles to limit ion/solute influx when in hyperosmotic environments. This osmoregulatory behaviour may allow for persistence of turtles in regions affected by salinization; however, growth rates and body condition may be affected in the long term. Although we demonstrate that these turtles have mechanisms to survive temporarily in saline waters, it is likely that sustained salinization of waterways will exceed their short- to medium-term capacity to survive increased salt levels, making salinization a potentially key threatening process for these freshwater reptiles.
Comparative ultrastructure of majoid spermatozoa belonging to 23 species, in 19 genera and five families, is considered, with new data on Schizophrys aspera; S. rufescens (Majidae, Majinae); ...Camposcia retusa (Inachidae); Pyromaia tuberculata (Inachoididae); and Huenia heraldica and Menaethius monoceros (Epialtidae, Epialtinae). The oregoniid Chionoecetes opilio, and inachids Cyrtomaia furici, Platymaia rebierei, Macropodia longirostris and Inachus phalangium, possibly with Camposcia retusa, but not Podochela riisei, appear to form a group. Within the inachids, Macropodia and Inachus are especially close. A domed central acrosome zone, seen in most inachid sperm, in majines (both Schizophrys species), in pisines (Oxypleurodon orbiculatus and O. stuckiae) and epialtines (Huenia heraldica and Menaethius monoceros), appears to be an autapomorphy of these majoids. A peripheral acrosome zone is seen in the inachid Grypacheus hyalinus, two inachoidids (P. tuberculata and Stenorhynchus seticornis) and the majid Maja squinado. Pyromaia tuberculata differs from other inachoidids in having a slightly dome‐shaped operculum. The mithracine Macrocoeloma trispinosum (Majidae) sperm more closely resembles Inachoididae, than Inachidae. Spermatologically, the family Majidae and the subfamily Majinae are not homogeneous. Spermatozoal ultrastructure does not support a majoid–hymenosomatid relationship and is equivocal with regard to the placement of Cryptochiridae in either the Thoracotremata or Heterotremata, the prominent operculum strongly differentiates cryptochirids from Majoidea.
Abstract Objectives Several systematic reviews have focused on the role of preoperative exercise therapy (PET) in various fields of surgical care. Aims of the present scoping review are to summarize ...research findings and to identify gaps in existing literature. Methods Two authors independently conducted a comprehensive literature search on systematic reviews regarding PET. The risk of bias was assessed using “the methodology checklist for systematic reviews and meta-analyses of the Scottish Intercollegiate Guidelines Network (SIGN).” Findings of the included systematic reviews were summarized according to type of surgery and type of PET. Results Twenty-one reviews on PET with a low risk of bias were included. Seven reviews investigated PET in multiple surgical fields and 14 in just a single surgical field. PET was studied before cardiac surgery (n = 9), orthopedic surgery (n = 8), abdominal surgery (n = 8), thoracic surgery (n = 8), vascular surgery (n = 3), and urologic surgery (n = 1). Conclusion Overall, it seems that PET exerts beneficial effects on physical fitness and postoperative outcome measures. Gaps in current literature are the heterogeneity in selected patient populations and outcome measures as well as lack of guidelines on the specific PET regimes. Therefore, there is increasing need for multicenter randomized trials with specifically designed PET programs and a carefully selected patient population to strengthen current evidence.
Background Thousands of common single nucleotide polymorphisms (SNPs) are weakly associated with schizophrenia. It is likely that subsets of disease-associated SNPs are associated with distinct ...heritable disease-associated phenotypes. Therefore, we examined the shared genetic susceptibility modulating schizophrenia and brain volume. Methods Odds ratios for genome-wide SNP data were calculated in the sample collected by the Psychiatric Genome-wide Association Study Consortium (8690 schizophrenia patients and 11,831 control subjects, excluding subjects from the present study). These were used to calculate individual polygenic schizophrenia (risk) scores in an independent sample of 152 schizophrenia patients and 142 healthy control subjects with available structural magnetic resonance imaging scans. Results In the entire group, the polygenic schizophrenia score was significantly associated with total brain volume ( R2 =.048, p =1.6×10−4 ) and white matter volume ( R2 =.051, p =8.6×10−5 ) equally in patients and control subjects. The number of (independent) SNPs that substantially influenced both disease risk and white matter ( n =2020) was much smaller than the entire set of SNPs that modulated disease status ( n =14,751). From the set of 2020 SNPs, a group of 186 SNPs showed most evidence for association with white matter volume and an explorative functional analysis showed that these SNPs were located in genes with neuronal functions. Conclusions These results indicate that a relatively small subset of schizophrenia genetic risk variants is related to the (normal) development of white matter. This, in turn, suggests that disruptions in white matter growth increase the susceptibility to develop schizophrenia.
BackgroundIt is unclear whether supervised exercise therapy (SET), home based exercise therapy (HBET), and endovascular revascularisation (ER) for intermittent claudication (IC) have a meaningful ...impact on physical activity, despite extensive research on their effect on walking performance. MethodsMultiple databases were searched systematically up to May 2018 for randomised controlled trials with objective measurements of physical activity in patients with IC. A Bayesian network meta-analysis was performed comparing the change in physical activity between baseline and follow up between treatments (SET, HBET, ER) and control (usual care). The standardised mean difference (SMD) with 95% credible interval (CI) was calculated as a summary statistic and converted into steps per day to aid interpretation. ResultsEight trials involving 656 patients with IC investigating the short-term effect of treatment on daily physical activity were included. Both SET (SMD 0.41, 95% CI 0.10–0.72: this corresponds to a difference of + 803 steps/day on a pedometer) and HBET (SMD 0.50, 95% CI 0.18–0.88: + 980 steps/day) displayed a benefit over control, based on evidence of moderate and low quality, respectively. The benefit of ER compared with control was SMD 0.36 (95% CI –0.22 to 0.99: + 705 steps/day), but only one trial supplied direct evidence, resulting in a low rating of the quality of evidence. Comparisons between treatments yielded no statistically significant differences. The results were robust to several sensitivity analyses. ConclusionSET improves daily physical activity levels in patients with IC over control. HBET may have a similar benefit, while invasive treatment failed to lead to a statistically significant improvement of physical activity compared with control. However, the underlying quality of evidence for comparisons with ER and HBET is low, impeding definite conclusions.
Peripheral artery disease (PAD) is underdiagnosed in primary care settings, partly because of limited accuracy of the Doppler ankle-brachial index (ABI). This study aimed to assess the diagnostic ...accuracy of an automated oscillometric ABI device compared with reference standard vascular laboratory Doppler ABI equipment and to examine the influence of oscillometric errors on performance.
Consecutive patients who were referred to a large general hospital for an ABI measurement were invited to participate. In each patient, the oscillometric analysis was followed by the Doppler analysis. Legs with incompressible ankle arteries were excluded from analysis. ABI values were compared using the Bland-Altman method. Oscillometric errors were defined as the incapacity of the oscillometer to report a value of ABI. A receiver operating characteristic curve was constructed, and the area under the curve was computed.
A total of 201 patients participated. The Bland-Altman plot showed a mean difference of 0.05 ± 0.12 (limits of agreement, −0.20 to 0.29), representing a small ABI overestimation after oscillometry. Oscillometric errors occurred more commonly in limbs with PAD than in limbs without PAD (28% and 7%, respectively; P < .001). Considering a 0.9 threshold and after oscillometric error exclusion, the oscillometric ABI showed a 74% sensitivity and a 97% specificity for a diagnosis of PAD. When oscillometric errors were considered as abnormal ABIs, sensitivity increased to 86% and specificity was maintained at 95%. The receiver operating characteristic curve showed an area under the curve of 0.96. The best oscillometric ABI cutoff point was 1.00. Using this threshold and when considering oscillometric errors as abnormal ABIs, sensitivity improved to 94% while maintaining specificity at 92%.
Oscillometric ABI showed good diagnostic accuracy compared with the reference standard. However, the high incidence of oscillometric errors and the challenges to correctly interpret readings may limit the use of the oscillometric method in PAD diagnosis.
An ensemble of regional climate model (RCM) runs from the EU HighNoon project are used to project future air temperatures and precipitation on a 25
km grid for the Ganges basin in northern India, ...with a view to assessing impact of climate change on water resources and determining what multi-sector adaptation measures and policies might be adopted at different spatial scales.
The RCM results suggest an increase in mean annual temperature, averaged over the Ganges basin, in the range 1–4
°C over the period from 2000 to 2050, using the SRES A1B forcing scenario. Projections of precipitation indicate that natural variability dominates the climate change signal and there is considerable uncertainty concerning change in regional annual mean precipitation by 2050. The RCMs do suggest an increase in annual mean precipitation in this region to 2050, but lack significant trend. Glaciers in headwater tributary basins of the Ganges appear to be continuing to decline but it is not clear whether meltwater runoff continues to increase. The predicted changes in precipitation and temperature will probably not lead to significant increase in water availability to 2050, but the timing of runoff from snowmelt will likely occur earlier in spring and summer. Water availability is subject to decadal variability, with much uncertainty in the contribution from climate change.
Although global social-economic scenarios show trends to urbanization, locally these trends are less evident and in some districts rural population is increasing. Falling groundwater levels in the Ganges plain may prevent expansion of irrigated areas for food supply. Changes in socio-economic development in combination with projected changes in timing of runoff outside the monsoon period will make difficult choices for water managers.
Because of the uncertainty in future water availability trends, decreasing vulnerability by augmenting resilience is the preferred way to adapt to climate change. Adaptive policies are required to increase society's capacity to adapt to both anticipated and unanticipated conditions. Integrated solutions are needed, consistent at various spatial scales, to assure robust and sustainable future use of resources. For water resources this is at the river basin scale. At present adaptation measures in India are planned at national and state level, not taking into account the physical boundaries of water systems. To increase resilience adaptation plans should be made locally specific. However, as it is expected that the partitioning of water over the different sectors and regions will be the biggest constraint, a consistent water use plan at catchment and river basin scale may be the best solution. A policy enabling such river basin planning is essential.
The Vascular Quality of Life Questionnaire-6 (VascuQoL-6) is a short, disease specific instrument used to determine health related quality of life (HRQoL) in patients with peripheral arterial ...disease. This study aimed to assess the minimally important difference (MID) and substantial clinical benefit (SCB) of the VascuQoL-6 in Dutch patients with intermittent claudication (IC) receiving supervised exercise therapy (SET).
Consecutive patients with IC who were recruited from a single centre between January 2016 and December 2016 completed the VascuQoL-6 before initiation and after three months of SET. They subsequently answered an anchor question rating their current health status as much improved, improved, unchanged, deteriorated, or much deteriorated, compared with baseline. The MID for improvement and deterioration and SCB were calculated using anchor based and distribution based methods.
A total of 124 patients with IC (58% male, mean age 68 years) completed the study protocol. Baseline VascuQoL-6 scores increased from 16.3 ± 4.4 to 18.7 ± 3.8 after three months of SET (p < .001). MID values ranged from +2.0 to +3.8 points regarding HRQoL improvement and from +0.2 to -2.2 points regarding HRQoL deterioration. The SCB ranged from +3.7 to +5.0 points. Depending on the MID approach, 32% – 41% of patients achieved a clinically meaningful improvement in HRQoL.
Approximately one in three patients with IC reported a clinically meaningful improvement in HRQoL after three months of SET. The range of MID and SCB values provides caregivers with an idea of how much change in VascuQoL-6 scores is considered relevant or substantial by their patients. Applying cutoff points for MID and SCB may optimise the interpretation of trial results and may help to set a benchmark for success of SET.
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