Increased complexities in visual search behavior in skilled players for a self-paced aiming task

The badminton serve is an important shot for winning a rally in a match. It combines good technique with the ability to accurately integrate visual information from the shuttle, racket, opponent, and intended landing point. Despite its importance and repercussive nature, to date no study has looked at the visual search behaviors during badminton service in the singles discipline. Unlike anticipatory tasks (e.g., shot returns), the serve presents an opportunity to explore the role of visual search behaviors in movement control for self-paced tasks. Accordingly, this study examined skill-related differences in visual behavior during the badminton singles serve. Skilled (n D 12) and less skilled (n D 12) participants performed 30 serves to a live opponent, while real-time eye movements were captured using a mobile gaze registration system. Frame-by-frame analyses of 662 serves were made and the skilled players took a longer preparatory time before serving. Visual behavior of the skilled players was characterized by significantly greater number of fixations on more areas of interest per trial than the less skilled. In addition, the skilled players spent a significantly longer time fixating on the court and net, whereas the less skilled players found the shuttle to be more informative. Quiet eye (QE) duration (indicative of superior sports performance) however, did not differ significantly between groups which has implications on the perceived importance of QE in the badminton serve. Moreover, while visual behavior differed by skill level, considerable individual differences were also observed especially within the skilled players. This augments the need for not just group-level analyses, but individualized analysis for a more accurate representation of visual behavior. Findings from this study thus provide an insight to the possible visual search strategies as players serve in net-barrier games. Moreover, this study highlighted an important aspect of badminton relating to deception and the implications of interpreting visual behavior of players

A method for accurate detection of genomic microdeletions using real-time quantitative PCR

BACKGROUND: Quantitative Polymerase Chain Reaction (qPCR) is a well-established method for quantifying levels of gene expression, but has not been routinely applied to the detection of constitutional copy number alterations of human genomic DNA. Microdeletions or microduplications of the human genome are associated with a variety of genetic disorders. Although, clinical laboratories routinely use fluorescence in situ hybridization (FISH) to identify such cryptic genomic alterations, there remains a significant number of individuals in which constitutional genomic imbalance is suspected, based on clinical parameters, but cannot be readily detected using current cytogenetic techniques. RESULTS: In this study, a novel application for real-time qPCR is presented that can be used to reproducibly detect chromosomal microdeletions and microduplications. This approach was applied to DNA from a series of patient samples and controls to validate genomic copy number alteration at cytoband 22q11. The study group comprised 12 patients with clinical symptoms of chromosome 22q11 deletion syndrome (22q11DS), 1 patient trisomic for 22q11 and 4 normal controls. 6 of the patients (group 1) had known hemizygous deletions, as detected by standard diagnostic FISH, whilst the remaining 6 patients (group 2) were classified as 22q11DS negative using the clinical FISH assay. Screening of the patients and controls with a set of 10 real time qPCR primers, spanning the 22q11.2-deleted region and flanking sequence, confirmed the FISH assay results for all patients with 100% concordance. Moreover, this qPCR enabled a refinement of the region of deletion at 22q11. Analysis of DNA from chromosome 22 trisomic sample demonstrated genomic duplication within 22q11. CONCLUSION: In this paper we present a qPCR approach for the detection of chromosomal microdeletions and microduplications. The strategic use of in silico modelling for qPCR primer design to avoid regions of repetitive DNA, whilst providing a level of genomic resolution greater than standard cytogenetic assays. The implementation of qPCR detection in clinical laboratories will address the need to replace complex, expensive and time consuming FISH screening to detect genomic microdeletions or duplications of clinical importance

Effects of caffeine supplementation on performance in ball games

Although a large body of evidence exists documenting the ergogenic properties of caffeine, most studies have focused on endurance performance. However, findings from endurance sports cannot be generalized to performance in ball games where, apart from having a high level of endurance, successful athletic performances require a combination of physiological, technical and cognitive capabilities. The purpose of this review was to critically evaluate studies that have examined the effect of a single dose of caffeine in isolation on one or more of the following performance measures: total distance, sprint performance, agility, vertical jump performance and accuracy in ball games. Searches of three major databases resulted in 19 studies (invasion games: 13; net-barrier games: 6) that evaluated the acute effects of caffeine on human participants, provided the caffeine dose administered, and included a ball games specific task or simulated match. Improvements in sprint performance were observed in 8 of 10 studies (80%), and vertical jump in 7 of 8 studies (88%). Equivocal results were reported for distance covered, agility and accuracy. Minor side effects were reported in 4 of 19 studies reviewed. Pre-exercise caffeine ingestion between 3.0 and 6.0 mg/kg of body mass appears to be a safe ergogenic aid for athletes in ball games. However, the efficacy of caffeine varies depending on various factors, including, but not limited to, the nature of the game, physical status and caffeine habituation. More research is warranted to clarify the effects of caffeine on performance measures unique to ball games, such as agility and accuracy. It is essential that athletes, coaches and practitioners evaluate the risk-benefit ratio of caffeine ingestion strategies on an individual case-by-case basis

The accelerated path of ceritinib: Translating pre-clinical development into clinical efficacy

Abstract The discovery of anaplastic lymphoma kinase ( ALK )-rearranged non–small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011. However, despite its clinical efficacy, resistance to crizotinib invariably develops. There is now a next generation of ALK inhibitors, including two that have been approved—ceritinib and alectinib—and others that are in development—brigatinib, lorlatinib and X-396. Ceritinib and the other next-generation ALK inhibitors are more potent than crizotinib and can overcome tumor cell resistance mechanisms. Ceritinib gained US Food and Drug Administration approval in 2014 following accelerated review for the treatment of patients with ALK -positive ( ALK +) metastatic NSCLC who have progressed on or are intolerant to crizotinib. In pre-clinical studies, it demonstrated more potent inhibition of ALK than crizotinib in enzymatic assays, more durable responses in xenograft models and the ability to potently overcome crizotinib resistance mutations in vitro (including the gatekeeper mutation). There is also evidence for ceritinib penetration across the blood-brain barrier. In clinical trials, ceritinib has demonstrated durable responses and progression-free survival in ALK-inhibitor–pre-treated and –naive NSCLC patients, including high overall and intracranial response rates in those with central nervous system metastases. Selective gastrointestinal toxicity of ceritinib, such as diarrhea, nausea and vomiting is generally manageable with prophylactic medication and prompt dose reduction or interruption. Future progress in treating ALK + NSCLC will focus on determining the optimal sequencing of therapies and strategies to overcome acquired resistance, an ongoing challenge in treating ALK -mutation–driven tumors

Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer

Nivolumab; Docetaxel; Cáncer de pulmónNivolumab; Docetaxel; Lung cancerNivolumab; Docetaxel; Càncer de pulmóPURPOSE Immunotherapy has revolutionized the treatment of advanced non–small-cell lung cancer (NSCLC). In two phase III trials (CheckMate 017 and CheckMate 057), nivolumab showed an improvement in overall survival (OS) and favorable safety versus docetaxel in patients with previously treated, advanced squamous and nonsquamous NSCLC, respectively. We report 5-year pooled efficacy and safety from these trials. METHODS Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG PS ≤ 1, and progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg once every 2 weeks) or docetaxel (75 mg/m2 once every 3 weeks) until progression or unacceptable toxicity. The primary end point for both trials was OS; secondary end points included progression-free survival (PFS) and safety. Exploratory landmark analyses were investigated. RESULTS After the minimum follow-up of 64.2 and 64.5 months for CheckMate 017 and 057, respectively, 50 nivolumab-treated patients and nine docetaxel-treated patients were alive. Five-year pooled OS rates were 13.4% versus 2.6%, respectively; 5-year PFS rates were 8.0% versus 0%, respectively. Nivolumab-treated patients without disease progression at 2 and 3 years had an 82.0% and 93.0% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression-free at 5 years, respectively. Treatment-related adverse events (TRAEs) were reported in 8 of 31 (25.8%) nivolumab-treated patients between 3–5 years of follow-up, seven of whom experienced new events; one (3.2%) TRAE was grade 3, and there were no grade 4 TRAEs. CONCLUSION At 5 years, nivolumab continued to demonstrate a survival benefit versus docetaxel, exhibiting a five-fold increase in OS rate, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a programmed death-1 inhibitor in previously treated, advanced NSCLC

Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort.

Purpose Treatment with pembrolizumab, an anti-programmed death-1 antibody, at 10 mg/kg administered once every 2 weeks, displayed durable antitumor activity in programmed death-ligand 1 (PD-L1) -positive recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 trial. Results from the expansion cohort, in which patients with HNSCC, irrespective of biomarker status, received a fixed dose of pembrolizumab at a less frequent dosing schedule, are reported. Patients and Methods Patients with R/M HNSCC, irrespective of PD-L1 or human papillomavirus status, received pembrolizumab 200 mg intravenously once every 3 weeks. Imaging was performed every 8 weeks. Primary end points were overall response rate (ORR) per central imaging vendor (Response Evaluation Criteria in Solid Tumors v1.1) and safety. Secondary end points included progression-free survival, overall survival, and association of response and PD-L1 expression. Patients who received one or more doses of pembrolizumab were included in analyses. Results Of 132 patients enrolled, median age was 60 years (range, 25 to 84 years), 83% were male, and 57% received two or more lines of therapy for R/M disease. ORR was 18% (95% CI, 12 to 26) by central imaging vendor and 20% (95% CI, 13 to 28) by investigator review. Median duration of response was not reached (range, ≥ 2 to ≥ 11 months). Six-month progression-free survival and overall survival rates were 23% and 59%, respectively. By using tumor and immune cells, a statistically significant increase in ORR was observed for PD-L1-positive versus -negative patients (22% v 4%; P = .021). Treatment-related adverse events of any grade and grade ≥ 3 events occurred in 62% and 9% of patients, respectively. Conclusion Fixed-dose pembrolizumab 200 mg administered once every 3 weeks was well tolerated and yielded a clinically meaningful ORR with evidence of durable responses, which supports further development of this regimen in patients with advanced HNSCC

TILLING for allergen reduction and improvement of quality traits in peanut (Arachis hypogaea L.)

<p>Abstract</p> <p>Background</p> <p>Allergic reactions to peanuts (<it>Arachis hypogaea </it>L.) can cause severe symptoms and in some cases can be fatal, but avoidance is difficult due to the prevalence of peanut-derived products in processed foods. One strategy of reducing the allergenicity of peanuts is to alter or eliminate the allergenic proteins through mutagenesis. Other seed quality traits could be improved by altering biosynthetic enzyme activities. Targeting Induced Local Lesions in Genomes (TILLING), a reverse-genetics approach, was used to identify mutations affecting seed traits in peanut.</p> <p>Results</p> <p>Two similar copies of a major allergen gene, <it>Ara h 1</it>, have been identified in tetraploid peanut, one in each subgenome. The same situation has been shown for major allergen <it>Ara h 2</it>. Due to the challenge of discriminating between homeologous genes in allotetraploid peanut, nested PCR was employed, in which both gene copies were amplified using unlabeled primers. This was followed by a second PCR using gene-specific labeled primers, heteroduplex formation, CEL1 nuclease digestion, and electrophoretic detection of labeled fragments. Using ethyl methanesulfonate (EMS) as a mutagen, a mutation frequency of 1 SNP/967 kb (3,420 M₂individuals screened) was observed. The most significant mutations identified were a disrupted start codon in <it>Ara h 2.02 </it>and a premature stop codon in <it>Ara h 1.02</it>. Homozygous individuals were recovered in succeeding generations for each of these mutations, and elimination of Ara h 2.02 protein was confirmed. Several Ara h 1 protein isoforms were eliminated or reduced according to 2D gel analyses. TILLING also was used to identify mutations in fatty acid desaturase <it>AhFAD2 </it>(also present in two copies), a gene which controls the ratio of oleic to linoleic acid in the seed. A frameshift mutation was identified, resulting in truncation and inactivation of AhFAD2B protein. A mutation in <it>AhFAD2A </it>was predicted to restore function to the normally inactive enzyme.</p> <p>Conclusions</p> <p>This work represents the first steps toward the goal of creating a peanut cultivar with reduced allergenicity. TILLING in peanut can be extended to virtually any gene, and could be used to modify other traits such as nutritional properties of the seed, as shown in this study.</p

Development of a bi-national Great Lakes coastal wetland and land use map using three-season PALSAR and landsat imagery

Methods using extensive field data and three-season Landsat TM and PALSAR imagery were developed to map wetland type and identify potential wetland stressors (i.e., adjacent land use) for the United States and Canadian Laurentian coastal Great Lakes. The mapped area included the coastline to 10 km inland to capture the region hydrologically connected to the Great Lakes. Maps were developed in cooperation with the overarching Great Lakes Consortium plan to provide a comprehensive regional baseline map suitable for coastal wetland assessment and management by agencies at the local, tribal, state, and federal levels. The goal was to provide not only land use and land cover (LULC) baseline data at moderate spatial resolution (20–30 m), but a repeatable methodology to monitor change into the future. The prime focus was on mapping wetland ecosystem types, such as emergent wetland and forested wetland, as well as to delineate wetland monocultures (Typha, Phragmites, Schoenoplectus) and differentiate peatlands (fens and bogs) from other wetland types. The overall accuracy for the coastal Great Lakes map of all five lake basins was 94%, with a range of 86% to 96% by individual lake basin (Huron, Ontario, Michigan, Erie and Superior)

Anteproyecto arquitectónico de un Centro Hotelero Ecoturístico en la finca San Benito en el municipio de El Tuma, departamento de Matagalpa

Presenta un diseño de anteproyecto de centro hotelero ecoturístico en la finca San Benito en el municipio de El Tuma, departamento de Matagalpa, con esta propuesta se pretende crear una edificación que cuente con todos los parámetros y normas específicas para el ecoturismo, favoreciendo así a los locales y extranjeros

Neurofilament-lysosomal genetic intersections in the cortical network of stuttering

The neurobiological underpinnings of stuttering, a speech disorder characterized by disrupted speech fluency, remain unclear. While recent developments in the field have afforded researchers the ability to pinpoint several genetic profiles associated with stuttering, how these specific genetic backgrounds impact neuronal circuits and how they generate or facilitate the emergence of stuttered speech remains unknown. In this study, we identified the large-scale cortical network that characterizes stuttering using functional connectivity MRI and graph theory. We performed a spatial similarity analysis that examines whether the topology of the stuttering cortical network intersects with genetic expression levels of previously reported genes for stuttering from the protein-coding transcriptome data of the Allen Human Brain Atlas. We found that GNPTG – a gene involved in the mannose-6-phosphate lysosomal targeting pathways – was significantly co-localized with the stuttering cortical network. An enrichment analysis demonstrated that the genes identified with the stuttering cortical network shared a significantly overrepresented biological functionality of Neurofilament Cytoskeleton Organization (NEFH, NEFL and INA). The relationship between lysosomal pathways, cytoskeleton organization, and stuttering, was investigated by comparing the genetic interactome between GNPTG and the neurofilament genes implicated in the current study. We found that genes of the interactome network, including CDK5, SNCA, and ACTB, act as functional links between lysosomal and neurofilament genes. These findings support the notion that stuttering is due to a lysosomal dysfunction, which has deleterious effects on the neurofilament organization of the speech neuronal circuits. They help to elucidate the intriguing, unsolved link between lysosomal mutations and the presence of stuttering