Pacing, packing and sex-based differences in Olympic and IAAF World Championship marathons

The aim of this study was to describe pacing profiles and packing behaviours of athletes in Olympic and World Championship marathons. Finishing and split times were collated for 673 men and 549 women across nine competitions. Mean speeds for each intermediate 5 km and end 2.2 km segments were calculated. Medallists of both sexes maintained even-paced running from 10 km onwards whereas slower finishers dropped off the lead pack at approximately half-distance. Athletes who ran with the same opponents throughout slowed the least in the second half (P < .001, men: ES ≥ 1.19; women: ES ≥ 1.06), whereas other strategies such as moving between packs or running alone were less successful. Overall, women slowed less (P < .001, ES = 0.44) and were more likely to run a negative split (P < .001), and their more conservative start meant fewer women dropped out (P < .001). This also meant that women medallists sped up in the final 2.2 km, which might have decided the medal positions. Marathon runners are advised to identify rivals with similar abilities and ambitions to run alongside provided they start conservatively. Coaches should note important sex-based differences in tactics adopted and design training programmes accordingly

Thermoluminescence of zircon: a kinetic model

The mineral zircon, ZrSiO4, belongs to a class of promising materials for geochronometry by means of thermoluminescence (TL) dating. The development of a reliable and reproducible method for TL dating with zircon requires detailed knowledge of the processes taking place during exposure to ionizing radiation, long-term storage, annealing at moderate temperatures and heating at a constant rate (TL measurements). To understand these processes one needs a kinetic model of TL. This paper is devoted to the construction of such amodel. The goal is to study the qualitative behaviour of the system and to determine the parameters and processes controlling TL phenomena of zircon. The model considers the following processes: (i) Filling of electron and hole traps at the excitation stage as a function of the dose rate and the dose for both (low dose rate) natural and (high dose rate) laboratory irradiation. (ii) Time dependence of TL fading in samples irradiated under laboratory conditions. (iii) Short time annealing at a given temperature. (iv) Heating of the irradiated sample to simulate TL experiments both after laboratory and natural irradiation. The input parameters of the model, such as the types and concentrations of the TL centres and the energy distributions of the hole and electron traps, were obtained by analysing the experimental data on fading of the TL-emission spectra of samples from different geological locations. Electron paramagnetic resonance (EPR) data were used to establish the nature of the TL centres. Glow curves and 3D TL emission spectra are simulated and compared with the experimental data on time-dependent TL fading. The saturation and annealing behaviour of filled trap concentrations has been considered in the framework of the proposed kinetic model and comparedwith the EPR data associated with the rare-earth ions Tb3+ and Dy3+, which play a crucial role as hole traps and recombination centres. Inaddition, the behaviour of some of the SiOmn− centres has been compared with simulation results.

Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes

<p>Abstract</p> <p>Background</p> <p>Escalating trends of obesity and associated type 2 diabetes (T2D) has prompted an increase in the use of alternative and complementary functional foods. <it>Momordica charantia </it>or bitter melon (BM) that is traditionally used to treat diabetes and complications has been demonstrated to alleviate hyperglycemia as well as reduce adiposity in rodents. However, its effects on human adipocytes remain unknown. The objective of our study was to investigate the effects of BM juice (BMJ) on lipid accumulation and adipocyte differentiation transcription factors in primary human differentiating preadipocytes and adipocytes.</p> <p>Methods</p> <p>Commercially available cryopreserved primary human preadipocytes were treated with and without BMJ during and after differentiation. Cytotoxicity, lipid accumulation, and adipogenic genes mRNA expression was measured by commercial enzymatic assay kits and semi-quantitative RT-PCR (RT-PCR).</p> <p>Results</p> <p>Preadipocytes treated with varying concentrations of BMJ during differentiation demonstrated significant reduction in lipid content with a concomitant reduction in mRNA expression of adipocyte transcription factors such as, peroxisome proliferator-associated receptor γ (PPARγ) and sterol regulatory element-binding protein 1c (SREBP-1c) and adipocytokine, resistin. Similarly, adipocytes treated with BMJ for 48 h demonstrated reduced lipid content, perilipin mRNA expression, and increased lipolysis as measured by the release of glycerol.</p> <p>Conclusion</p> <p>Our data suggests that BMJ is a potent inhibitor of lipogenesis and stimulator of lipolysis activity in human adipocytes. BMJ may therefore prove to be an effective complementary or alternative therapy to reduce adipogenesis in humans.</p

INTEND II randomized clinical trial of intraoperative duct endoscopy in pathological nipple discharge.

Background The majority of lesions resulting in pathological nipple discharge are benign. Conventional surgery is undirected and targeting the causative lesion by duct endoscopy may enable more accurate surgery with fewer complications.Methods Patients requiring microdochectomy and/or major duct excision were randomized to duct endoscopy or no duct endoscopy before surgery. Primary endpoints were successful visualization of the pathological lesion in patients randomized to duct endoscopy, and a comparison of the causative pathology between the two groups. The secondary endpoint was to compare the specimen size between groups.Results A total of 68 breasts were studied in 66 patients; there were 31 breasts in the duct endoscopy group and 37 in the no-endoscopy group. Median age was 49 (range 19-81) years. Follow-up was 5·4 (i.q.r. 3·3-8·9) years in the duct endoscopy group and 5·7 (3·1-9·0) years in no-endoscopy group. Duct endoscopy had a sensitivity of 80 (95 per cent c.i. 52 to 96) per cent, specificity of 71 (44 to 90) per cent, positive predictive value of 71 (44 to 90) per cent and negative predictive value of 80 (52 to 96) per cent in identifying any lesion. There was no difference in causative pathology between the groups. Median volume of the surgical resection specimen did not differ between groups.Conclusion Diagnostic duct endoscopy is useful for identifying causative lesions of nipple discharge. Duct endoscopy did not influence the pathological yield of benign or malignant diagnoses nor surgical resection volumes. Registered as INTEND II in CancerHelp UK clinical trials database (https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-changes-inside-the-breast-ducts-of-women-who-have-nipple-discharge)

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

Cooperative AUV Navigation using a Single Maneuvering Surface Craft

In this paper we describe the experimental implementation of an online algorithm for cooperative localization of submerged autonomous underwater vehicles (AUVs) supported by an autonomous surface craft. Maintaining accurate localization of an AUV is difficult because electronic signals, such as GPS, are highly attenuated by water. The usual solution to the problem is to utilize expensive navigation sensors to slow the rate of dead-reckoning divergence. We investigate an alternative approach that utilizes the position information of a surface vehicle to bound the error and uncertainty of the on-board position estimates of a low-cost AUV. This approach uses the Woods Hole Oceanographic Institution (WHOI) acoustic modem to exchange vehicle location estimates while simultaneously estimating inter-vehicle range. A study of the system observability is presented so as to motivate both the choice of filtering approach and surface vehicle path planning. The first contribution of this paper is to the presentation of an experiment in which an extended Kalman filter (EKF) implementation of the concept ran online on-board an OceanServer Iver2 AUV while supported by an autonomous surface vehicle moving adaptively. The second contribution of this paper is to provide a quantitative performance comparison of three estimators: particle filtering (PF), non-linear least-squares optimization (NLS), and the EKF for a mission using three autonomous surface craft (two operating in the AUV role). Our results indicate that the PF and NLS estimators outperform the EKF, with NLS providing the best performance.United States. Office of Naval Research (Grant N000140711102)United States. Office of Naval Research. Multidisciplinary University Research InitiativeSingapore. National Research FoundationSingapore-MIT Alliance for Research and Technology. Center for Environmental Sensing and Monitorin

Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer.

The identification of early-stage breast cancer patients at high risk of relapse would allow tailoring of adjuvant therapy approaches. We assessed whether analysis of circulating tumor DNA (ctDNA) in plasma can be used to monitor for minimal residual disease (MRD) in breast cancer. In a prospective cohort of 55 early breast cancer patients receiving neoadjuvant chemotherapy, detection of ctDNA in plasma after completion of apparently curative treatment-either at a single postsurgical time point or with serial follow-up plasma samples-predicted metastatic relapse with high accuracy [hazard ratio, 25.1 (confidence interval, 4.08 to 130.5; log-rank P < 0.0001) or 12.0 (confidence interval, 3.36 to 43.07; log-rank P < 0.0001), respectively]. Mutation tracking in serial samples increased sensitivity for the prediction of relapse, with a median lead time of 7.9 months over clinical relapse. We further demonstrated that targeted capture sequencing analysis of ctDNA could define the genetic events of MRD, and that MRD sequencing predicted the genetic events of the subsequent metastatic relapse more accurately than sequencing of the primary cancer. Mutation tracking can therefore identify early breast cancer patients at high risk of relapse. Subsequent adjuvant therapeutic interventions could be tailored to the genetic events present in the MRD, a therapeutic approach that could in part combat the challenge posed by intratumor genetic heterogeneity

Daily consumption of a fruit and vegetable smoothie alters facial skin color

Consumption of dietary carotenoids or carotenoid supplements can alter the color (yellowness) of human skin through increased carotenoid deposition in the skin. As fruit and vegetables are the main dietary sources of carotenoids, skin yellowness may be a function of regular fruit and vegetable consumption. However, most previous studies have used tablets or capsules to supplement carotenoid intake, and less is known of the impact of increased fruit and vegetable consumption on skin color. Here, we examined skin color changes in an Asian population (Malaysian Chinese ethnicity) over a six week dietary intervention with a carotenoid-rich fruit smoothie. Eighty one university students (34 males, 47 females; mean age 20.48) were assigned randomly to consuming either a fruit smoothie (intervention group) or mineral water (control group) daily for six weeks. Participants’ skin yellowness (CIELab b*), redness (a*) and luminance (L*) were measured at baseline, twice during the intervention period and at a two-week follow-up, using a handheld reflectance spectrophotometer. Results showed a large increment in skin yellowness (p<0.001) and slight increment in skin redness (p<0.001) after 4 weeks of intervention for participants in the intervention group. Skin yellowness and skin redness remained elevated at the two week follow up measurement. In conclusion, intervention with a carotenoid-rich fruit smoothie is associated with increased skin redness and yellowness in an Asian population. Changes in the reflectance spectrum of the skin suggest that this color change was caused by carotenoid deposition in the skin