Collaborative Innovations in Childhood Cancer Therapies.

The outcome for children with cancer has improved significantly over the past 60 years, with more than 80% of patients today becoming 5-year survivors. Despite this progress, cancer remains the leading cause of death from disease in children in the United States and Europe, with significant short- and long-term toxicity of treatment continuing to impact most children. While the past 15 years have witnessed dramatic scientific innovation for certain cancers in adult patients, pediatric cancer treatment innovation lags increasingly behind. To help bridge the adult-pediatric therapeutic development gap, collaborative efforts are essential among stakeholders within and outside the pediatric oncology community. Prioritizing collaboration in areas such as cancer characterization, target identification and validation, drug discovery, and approaches to currently "undruggable" targets is imperative to improving the outcomes for children with cancer.

Novel Use of Botulinum Toxin in Long-Standing Adductor-Related Groin Pain: A Case Series.

BACKGROUND: Adductor-related groin pain (ARGP) is the most common groin injury in athletes. If conservative treatment fails, then adductor tenotomy to relieve tension can be considered. The use of botulinum toxin A (BoNT-A) has shown good results in other musculoskeletal pathologies. OBJECTIVE: Assess the effectiveness of BoNT-A injections in ARGP in cases where usual treatment has failed. DESIGN: Retrospective cohort study. SETTING: Orthopedic Medicine and Rehabilitation Unit, University of Bordeaux. PARTICIPANTS: Fifty patients treated by BoNT-A injection in ARGP after failure of medical and/or surgical treatment were included in this study. INTERVENTIONS: One or several adductor muscles were injected with BoNT-A, according to clinical evaluation using ultrasound and electrical stimulation guidance. Patients were followed up at 1, 3, 6, and 12 months. MAIN OUTCOME MEASURES: The primary assessment criterion was the improvement of Hip and Groin Outcome Score subscales at day 30. Secondary outcomes included pain intensity and impact on sport, work, and quality of life (QoL), the Blazina scale, and side effects. RESULTS: All the first 50 injected patients (45 male and 5 female patients) were included. A significant improvement was noted regarding the majority of Hip and Groin Outcome Score subscales at day 30 ( P < 0.05). Pain intensity and its impacts were both significantly reduced ( P < 0.001): less sport and professional disability and lower impact on QoL. Severity of symptoms assessed by the Blazina scale was significantly reduced ( P < 0.001). The improvements remained significant until 1-year postinjection. CONCLUSIONS: BoNT-A is promising as a new treatment for ARGP but should be fully assessed in a randomized controlled trial.

The need of operational paradigms for frailty in older persons: the SPRINTT project.

The exploration of frailty as a pre-disability geriatric condition represents one of the most promising research arenas of modern medicine. Frailty is today indicated as a paradigmatic condition around which the traditional healthcare systems might be re-shaped and optimized in order to address the complexities and peculiarities of elders. Unfortunately, the lack of consensus around a single operational definition has limited the clinical implementation of frailty in clinical practice. In these last years, growing attention (even beyond the traditional boundaries of geriatric medicine) has been given to physical performance measures. These instruments have shown to be predictive of negative health-related events and able to support an accurate estimation of the "biological age" in late life. The strong construct of physical performance measures also makes them particularly suitable for the assessment of the frailty status. Furthermore, the adoption of physical performance measures may help render the frailty condition more organ-specific (i.e., centred on the skeletal muscle quality) and less heterogeneous than currently perceived. The translation of the frailty concept by means of physical performance measures implicitly represents an attempt to go beyond traditional paradigms. In this context, the recently funded "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) project (largely based on such a novel approach) may indeed fill an important gap in the field and provide key insights for counteracting the disabling cascade in the elderly.

Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project).

OBJECTIVE: To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia. DESIGN: Evaluator blinded, randomised controlled trial. SETTING: 16 clinical sites across 11 European countries, January 2016 to 31 October 2019. PARTICIPANTS: 1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls). INTERVENTIONS: The multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months. MAIN OUTCOME MEASURES: The primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3-7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes. RESULTS: Mean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; P<0.001) and 1.0 point (95% confidence interval 0.5 to 1.6 points; P<0.001) in favour of the multicomponent intervention at 24 and 36 months, respectively. The decline in handgrip strength at 24 months was smaller in women assigned to the multicomponent intervention than to control (0.9 kg, 95% confidence interval 0.1 to 1.6 kg; P=0.028). Women in the multicomponent intervention arm lost 0.24 kg and 0.49 kg less appendicular lean mass than controls at 24 months (95% confidence interval 0.10 to 0.39 kg; P<0.001) and 36 months (0.26 to 0.73 kg; P<0.001), respectively. Serious adverse events occurred in 237/605 (39.2%) participants assigned to the multicomponent intervention and 216/600 (36.0%) controls (risk ratio 1.09, 95% confidence interval 0.94 to 1.26). In participants with SPPB scores of 8 or 9, mobility disability occurred in 46/155 (29.7%) in the multicomponent intervention and 38/159 (23.9%) controls (hazard ratio 1.25, 95% confidence interval 0.79 to 1.95; P=0.34). CONCLUSIONS: A multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people. TRIAL REGISTRATION: ClinicalTrials.gov NCT02582138.

Iterative Training of Neural Networks for Intra Prediction.

This paper presents an iterative training of neural networks for intra prediction in a block-based image and video codec. First, the neural networks are trained on blocks arising from the codec partitioning of images, each paired with its context. Then, iteratively, blocks are collected from the partitioning of images via the codec including the neural networks trained at the previous iteration, each paired with its context, and the neural networks are retrained on the new pairs. Thanks to this training, the neural networks can learn intra prediction functions that both stand out from those already in the initial codec and boost the codec in terms of rate-distortion. Moreover, the iterative process allows the design of training data cleansings essential for the neural network training. When the iteratively trained neural networks are put into H.265 (HM-16.15), -4.2% of mean BD-rate reduction is obtained, i.e. -1.8% above the state-of-the-art. By moving them into H.266 (VTM-5.0), the mean BD-rate reduction reaches -1.9%.