Summary
Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. ...However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference ‘Diet and Cardiometabolic Health – Beyond Calories’, and this paper summarizes the presentations and follow‐up discussions. Regarding the health effects of dietary fat, sugar and non‐nutritive sweeteners, it is concluded that food‐specific saturated fatty acids and sugar‐sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential ‘beyond calories’ mechanisms may lead to new strategies for attenuating the obesity crisis.
Journal of Physics D: Applied Physics published the first Plasma Roadmap in 2012 consisting of the individual perspectives of 16 leading experts in the various sub-fields of low temperature plasma ...science and technology. The 2017 Plasma Roadmap is the first update of a planned series of periodic updates of the Plasma Roadmap. The continuously growing interdisciplinary nature of the low temperature plasma field and its equally broad range of applications are making it increasingly difficult to identify major challenges that encompass all of the many sub-fields and applications. This intellectual diversity is ultimately a strength of the field. The current state of the art for the 19 sub-fields addressed in this roadmap demonstrates the enviable track record of the low temperature plasma field in the development of plasmas as an enabling technology for a vast range of technologies that underpin our modern society. At the same time, the many important scientific and technological challenges shared in this roadmap show that the path forward is not only scientifically rich but has the potential to make wide and far reaching contributions to many societal challenges.
The European Organisation for Research and Treatment of Cancer (EORTC) 22033-26033 clinical trial (NCT00182819) investigated whether initial temozolomide (TMZ) chemotherapy confers survival advantage ...compared with radiotherapy (RT) in low-grade glioma (LGG) patients. In this study, we performed gene expression profiling on tissues from this trial to identify markers associated with progression-free survival (PFS) and treatment response.
Gene expression profiling, performed on 195 samples, was used to assign tumours to one of six intrinsic glioma subtypes (IGSs; molecularly similar tumours as previously defined using unsupervised expression analysis) and to determine the composition of immune infiltrate. DNA copy number changes were determined using OncoScan arrays.
We confirm that IGSs are prognostic in the EORTC22033-26033 clinical trial. Specific genetic changes segregate in distinct IGSs: most samples assigned to IGS-9 have IDH-mutations and 1p19q codeletion, samples assigned to IGS-17 have IDH-mutations without 1p19q codeletion and samples assigned to other intrinsic subtypes often are IDH-wildtype. A trend towards benefit from RT was observed for samples assigned to IGS-9 (hazard ratio HR for TMZ is 1.90, P = 0.065) but not for samples assigned to IGS-17 (HR 0.87, P = 0.62). We did not identify genes significantly associated with PFS within intrinsic subtypes, although follow-up time is limited. We also show that LGGs and glioblastomas differ in their immune infiltrate, which suggests that LGGs are less amenable to checkpoint inhibitor–type immune therapies. Gene expression analysis also allows identification of relatively rare subtypes. Indeed, one patient with a pilocytic astrocytoma was identified.
IGSs are prognostic for PFS in EORTC22033-26033 clinical trial samples.
•EORTC 22033-26033 examined whether temozolomide (TMZ) improves survival v. radiotherapy (RT) in low-grade glioma patients.•This study investigates the transcriptome of samples included in this study.•Expression-based intrinsic glioma subtypes (IGSs) are prognostic and genetic changes segregate in distinct IGSs.•Our study is important as it provides an independent method for prognostic classification of molecularly similar tumours.•We did not observe benefit from RT or TMZ treatment in any of the subtypes.
STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation ...therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.
We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.
Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69–0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57–0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59–0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression).
The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.
COVID-19 continues to represent the single biggest challenge to contemporary community sport globally. Compliance with social distancing policies, strict return-to-play protocols, and COVID-19 ...specific training has, perhaps, forever changed the way that children and young people engage in organised sport. Within this context, and while many children and families seek to re-engage with community sport, we (researchers and sport practitioners) have an obligation to ask questions about how the pandemic has impacted youth sport, understand the short- and long-term consequences, and explore what (if any) opportunities can be seized to assist and improve future participation and retention. The aim of this paper was to present an in-depth exploration of the impact of COVID-19 on youth sport in South Australia.
Within an interpretive descriptive methodology, this qualitative investigation draws on rich, individual interview and focus group data with 39 youth (ages 15-18), parents, coaches, and sport administrators. A reflexive thematic analysis was undertaken, leading to the development of four substantive themes.
We conceptualised the '4 Rs' to advance theoretical understandings about the pandemic's impact on youth sport, including the themes 'recognising struggle', 'reconnection', 're-engaging after restrictions, and 'reimagining sport'. The themes captured insights about a decline in mental wellbeing and physical activity, an increase in family connectedness, the challenge for sports to attract volunteers and participants back into sport, and the opportunities to reset values and philosophies underpinning the provision of youth sport.
The findings provide valuable insight into the youth sport setting as a result of the global pandemic and suggest that families, sporting clubs and sporting organisations require additional resources and tools (for example, support for parents to facilitate their children's training at home during lockdown) to aid recovery efforts and to ensure the survival and prosperity of youth sport into the future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite ...instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation.
After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n=3016)—N0147 (NCT00079274) and PETACC3 (NCT00026273)—was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n=1499), and also externally in different population cohorts of chemotherapy-treated (n=949) or -untreated (n=1080) CC patients, and an additional series without treatment annotation (n=782).
TNM staging, MSI and BRAFV600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0.61–0.68 in the TNM alone model to 0.63–0.71 in models with added molecular markers, 0.65–0.73 with clinicopathological features and 0.66–0.74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0.64 for the TNM alone model to 0.67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively.
Incorporation of MSI, BRAFV600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases prediction accuracy in multivariable models that include clinicopathological features, particularly in chemotherapy-treated patients.
Summary
Background
Chronic plaque psoriasis is the most common type of psoriasis and is characterized by redness, thickness and scaling. First‐line management is with topical treatments.
Objectives
...Our objective was to establish the effectiveness, tolerability and safety of topical treatments for people with chronic plaque psoriasis of the scalp, assessing placebo‐controlled trials of all treatments and head‐to‐head trials that assessed vitamin D analogues.
Methods
As part of a Cochrane review of topical treatments for psoriasis, we systematically searched electronic databases for randomized controlled trials. The review included 26 randomized controlled trials of treatments for psoriasis of the scalp with 8020 participants. Trials used several measures to assess changes in psoriasis severity: these were combined using the standardized mean difference metric and interpreted by reporting as a six‐point global improvement score.
Results
On effectiveness grounds, very potent or potent steroid treatments should be preferred to vitamin D3 analogue with approximately an average 10% additional improvement on a six‐point scale. Vitamin D3 analogue combined with potent steroid appears slightly more effective than potent steroid monotherapy (3% additional improvement on a six‐point scale). Rates of withdrawal from treatment and adverse events in trials were generally low and similar to those for placebo. There remains uncertainty about the atrophic potential of corticosteroid treatments for scalp psoriasis.
Conclusions
Corticosteroids are more effective than vitamin D analogues and similarly tolerated. However, further research is needed to inform long‐term maintenance treatment and provide appropriate safety data.
What's already known about this topic?
Psoriasis of the scalp affects up to 79% of people with chronic plaque psoriasis.
Despite the range of treatment options, psoriasis of the scalp is a difficult condition to manage.
What does this study add?
Very potent corticosteroids are more effective than potent steroids and vitamin D analogues either as monotherapy or combination therapy.
However, the atrophic potential of corticosteroid treatments for scalp psoriasis remains uncertain.
We present an atlas of mid-infrared (mid-IR) ∼ 7.5-13 μm spectra of 45 local active galactic nuclei (AGN) obtained with CanariCam on the 10.4 m Gran Telescopio CANARIAS (GTC) as part of an ESO/GTC ...large programme. The sample includes Seyferts and other low-luminosity AGN (LLAGN) at a median distance of 35 Mpc and luminous AGN, namely PG quasars, (U)LIRGs, and radio galaxies (RG) at a median distance of 254 Mpc. To date, this is the largest mid-IR spectroscopic catalogue of local AGN at sub-arcsecond resolution (median 0.3 arcsec). The goal of this work is to give an overview of the spectroscopic properties of the sample. The nuclear 12 μm luminosities of the AGN span more than four orders of magnitude, νL
12 μm ∼ 3 × 1041–1046 erg s−1. In a simple mid-IR spectral index versus strength of the 9.7 μm silicate feature diagram most LLAGN, Seyfert nuclei, PG quasars, and RGs lie in the region occupied by clumpy torus model tracks. However, the mid-IR spectra of some might include contributions from other mechanisms. Most (U)LIRG nuclei in our sample have deeper silicate features and flatter spectral indices than predicted by these models suggesting deeply embedded dust heating sources and/or contribution from star formation. The 11.3 μm polycyclic aromatic hydrocarbon (PAH) feature is clearly detected in approximately half of the Seyfert nuclei, LLAGN, and (U)LIRGs. While the RG, PG quasars, and (U)LIRGs in our sample have similar nuclear νL
12 μm, we do not detect nuclear PAH emission in the RGs and PG quasars.
Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate ...cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP versus SOC+DocP.
Recruitment to SOC+DocP and SOC+AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for≥2years and RT to the primary tumour. Stratified randomisation allocated pts 2:1:2 to SOC; SOC+docetaxel 75mg/m2 3-weekly×6+prednisolone 10mg daily; or SOC+abiraterone acetate 1000mg+prednisolone 5mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC+AAP, and HR>1 favours SOC+DocP.
A total of 566 consenting patients were contemporaneously randomised: 189 SOC+DocP and 377 SOC+AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8–10; 449 (79%) WHO performance status 0; median age 66years and median PSA 56ng/ml. With median follow-up 4years, 149 deaths were reported. For overall survival, HR=1.16 (95% CI 0.82–1.65); failure-free survival HR=0.51 (95% CI 0.39–0.67); progression-free survival HR=0.65 (95% CI 0.48–0.88); metastasis-free survival HR=0.77 (95% CI 0.57–1.03); prostate cancer-specific survival HR=1.02 (0.70–1.49); and symptomatic skeletal events HR=0.83 (95% CI 0.55–1.25). In the safety population, the proportion reporting≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC+DocP, and 40%, 7% and 1% SOC+AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm.
This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs.
Clinicaltrials.gov: NCT00268476.
PDF
