What is the Machine Learning?

Applications of machine learning tools to problems of physical interest are often criticized for producing sensitivity at the expense of transparency. To address this concern, we explore a data planing procedure for identifying combinations of variables -- aided by physical intuition -- that can discriminate signal from background. Weights are introduced to smooth away the features in a given variable(s). New networks are then trained on this modified data. Observed decreases in sensitivity diagnose the variable's discriminating power. Planing also allows the investigation of the linear versus non-linear nature of the boundaries between signal and background. We demonstrate the efficacy of this approach using a toy example, followed by an application to an idealized heavy resonance scenario at the Large Hadron Collider. By unpacking the information being utilized by these algorithms, this method puts in context what it means for a machine to learn.Comment: 6 pages, 3 figures. Version published in PRD, discussion adde

Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials

PURPOSE: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS: Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality. RESULTS: Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION: ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.</p

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events

A systematic review of randomised controlled trials of radiotherapy for localised prostate cancer

Background: Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males. A systematic review of randomised controlled trials (RCTs) of radiotherapy and other non-pharmacological management options for localised prostate cancer was undertaken. Methods: A search of thirteen databases was carried out until March 2014.RCTs comparing radiotherapy (brachytherapy (BT) or external beam radiotherapy (EBRT)) to other management options i.e. radical prostatectomy (RP), active surveillance, watchful waiting, high intensity focused ultrasound (HIFU), or cryotherapy; each alone or in combination, e.g. with adjuvant hormone therapy (HT), were included. Methods followed guidance by the Centre for Reviews and Dissemination and the Cochrane Collaboration. Indirect comparisons were calculated using the Butcher method. Results: Thirty-six randomised controlled trials (RCTs, 134 references) were included. EBRT, BT and RP were found to be effective in the management of localised prostate cancer. While higher doses of EBRT seem to be related to favourable survival-related outcomes they might, depending on technique, involve more adverse events, e.g. gastrointestinal and genitourinary toxicity. Combining EBRT with hormone therapy shows a statistically significant advantage regarding overall survival when compared to EBRT alone (Relative risk 1.21, 95% confidence interval 1.12-1.30). Aside from mixed findings regarding urinary function, BT and radical prostatectomy were comparable in terms of quality of life and biochemical progression-free survival while favouring BT regarding patient satisfaction and sexual function. There might be advantages of EBRT (with/without HT) compared to cryoablation (with/without HT). No studies on HIFU were identified. Conclusions: Based on this systematic review, there is no strong evidence to support one therapy over another as EBRT, BT and RP can all be considered as effective mono therapies for localised disease with EBRT also effective for post-operative management. All treatments have unique adverse events profiles. Further large, robust RCTs which report treatment-specific and treatment combination-specific outcomes in defined prostate cancer risk groups following established reporting standards are needed. These will strengthen the evidence base for newer technologies, help reinforce current consensus guidelines and establish greater standardisation across practices

Une substitution de 70% des protéines de Lactosérum par des protéines de Soja permet de maintenir l’effet anabolique du repas dans le muscle squelettique du rat âgé

National audienc

Evaluation of tracers for the authentication of thermal treatments of milks

International audienceFor regulatory purposes, several methods have been proposed for defining biochemical tracers to identify heat treatments to which milks may be submitted. However, none of these methods is universal whereas they are usually restricted to one or two categories of treated milks and are not able to discriminate any unknown sample arriving in a control laboratory. Therefore, Arilait-Recherches and Syndilait (Syndicat National des Laits de Consommation) decided to undertake a study in order to define an efficient discrimination approach applicable to commercial milk samples. About 200 commercial samples were tested, produced in several plants where they received the standard heat treatments here-applied. Five types of heat treatments were studied: pasteurisation, high pasteurisation, direct UHT, indirect UHT, and sterilisation. In order to estimate the effect of storage on long-term storage milks.. samples were submitted to two storage conditions: 90 days at 25 degrees C and 90 days at 35 degrees C. The selected tracers were: furosine; lactulose; native alpha-lactalbumin; denaturised alpha-lactalbumin; percent of denaturised alpha-lactalbumin; FAST index, tryptophan fluorescence, beta-lactoglobulin, and lactoperoxidase: altogether 5000 measurements were collected. Analysis of variance clearly demonstrates that no tracer can be selected to universally discriminate milks from all these technologies. The only possible authentication technique must be based on a multivariate approach. The application of factorial discriminant analysis by combining at least five tracers, gives a possible solution to this question. Most discriminative tracers are those which globally measure the structural modifications of the milk protein rather than those which specifically quantify the metabolites of the Maillard reaction. (c) 2005 Elsevier Ltd. All rights reserved

An Update on the Effects of Glyceollins on Human Health: Possible Anticancer Effects and Underlying Mechanisms

Biologically active plant-based compounds, commonly referred to as phytochemicals, can influence the expression and function of various receptors and transcription factors or signaling pathways that play vital roles in cellular functions and are then involved in human health and diseases. Thus, phytochemicals may have a great potential to prevent and treat chronic diseases. Glyceollins, a group of phytoalexins that are isolated from soybeans, have attracted attention because they exert numerous effects on human functions and diseases, notably anticancer effects. In this review, we have presented an update on the effects of glyceollins in relation to their potential beneficial roles in human health. Despite a growing number of studies suggesting that this new family of phytochemicals can be involved in critical cellular pathways, such as estrogen receptor, protein kinase, and lipid kinase signaling pathways, future investigations will be needed to better understand their molecular mechanisms and their specific significance in biomedical applications

Effects of Galacto-oligosaccharides (GOS) on inflammatory reponse, glycoxidation markers and glycogen content in streptozotocin-diabetic rats.

International audienceIntroduction: Diabetes mellitus results from the loss of tolerance to insulin and alters glycemia and the glycogen content. Oxidative stress and inflammation are linked to theses alterations, especially with insulin-resistance. The therapy management of diabetes includes nutritional recommendations. Several nutrients are developed to improve glycemia, oxidative stress, inflammation and glycogen content. More interestingly, ?-GOS exhibits anti-inflammatory and insulin-sensitive effects in vitro (Efstathiou and Fathi 2010) and in vivo (Boucher et al. 2003). Thus, ?-GOS is a potential functional food for the treatment of diabetes. But, less is known about the in vivo effect of ?-GOS on inflammatory, glycoxidation markers and glycogen content in diabetes. In this context, the aim of this work was to study the effect of ?-GOS developed by Sojasun technologies (from fermented soy product) compared to a synthetic ?-GOS produced by Sigma on inflammatory, glycoxidation markers and glycogen content in a streptozotocin-induced diabetic rat model. Methods: Twenty-four male Wistar streptozotocin-diabetic rat (STZ) were divided into three group: control group, supplemented with natural ?-GOS (20 mg/kg/day) group and supplemented with synthetic ?-GOS (20 mg/kg/day). The supplementation protocol duration was 8 weeks. At the end of the protocol, blood and skeletal muscle (gastrocnemius) were obtained to measure glucose , insulin, fructosamine in plasma and N-(carboxymethyl)lysine, glycogen synthase activity and glycogen content, in muscle. Results-Discussion: Diabetes was confirmed with the measure of insuline and glucose levels. All the diabetic groups had significantly higher glucose and insuline levels compared to control healthy group (data not shown). Insuline level in plasma and storage of glycogen in muscle were increased only in both ?-GOS groups. Fructosamine, TNF?and glycogen synthase activity was also decreased in the two supplemented groups (synthetic ?-GOS and natural ?-GOS). CML remained unchanged in all groups. Natural ?-OGT and synthetic ?-OGT only differed on muscular glucose level: only natural ?-OGT induced a significant decrease in muscular glucose. To conclude, our results suggest that ?-GOS alters positively glucose level, increases the glycogen content in diabetique population, improves glycemic control in the long term and decreases the inflammatory effects in streptozotocin-diabetic rat . Keywords: ?-GOS, inflammatory and glycoxidation markers, diabetes. Acknowledgment : Brittany region References Efstathiou, T. and D. Fathi. Sojasun Technologies. 2010 Boucher J et al. J Physiol Biochem. 59(3):169-73, 200

A fermented soy permeate improves the skeletal muscle glucose level without restoring the glycogen content in streptozotocin-induced diabetic rats

International audienceExercise is essential into the therapeutic management of diabetic patients, but their level of exercise tolerance is lowered due to alterations of glucose metabolism. As soy isoflavones have been shown to improve glucose metabolism, this study aimed to assess the effects of a dietary supplement containing soy isoflavones and alpha-galactooligosaccharides on muscular glucose, glycogen synthase (GSase)and glycogen content in a type 1 diabetic animal model. The dietary supplement tested was a patented compound, Fermented Soy Permeate (FSP), developed by the French Company Sojasun Technologies. Forty male Wistar rats were randomly assigned to control or diabetic groups (streptozotocin, 45?mg/kg). Each group was then divided into placebo or FSP-supplemented groups. Both groups received by oral gavage, respectively, water or diluted FSP (0.1?g/day), daily for a period of 3 weeks. At the end of the protocol, glycemia was noticed after a 24-h fasting period. Glucose, total GSaseand the glycogen content were determined in the skeletal muscle (gastrocnemius). Diabetic animals showed a higher blood glucose concentration, but a lower glucose and glycogen muscle content than controls. Three weeks of FSP consumption allowed to restore the muscle glucose concentration, but failed to reduce glycemia and to normalize the glycogen content in diabetic rats. Furthermore, the glycogen content was increased in FSP-supplemented controls compared to placebo controls. Our results demonstrated that diabetic rats exhibited a depleted muscle glycogen content (-25%). FSP-supplementation normalized the muscle glucose level without restoring the glycogen content in diabetic rats. However, it succeeded to increase it in the control group (+20%)