bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical activity of a new regimen combining gemcitabine and alemtuzumab in high‐risk relapsed/refractory chronic lymphocytic leukemia patients
Authors: Oberic Lucie , Vaillant Willy , Hebraud Benjamin , Recher Christian , Suc Etienne , Houyau Philippe , Laurent Guy , Ysebaert Loic
Published: June 2014

Optimal treatment strategies are lacking in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Gemcitabine has shown activity and acceptable safety profile in B‐cell lymphomas. We present a retrospective case review of gemcitabine and alemtuzumab, every 21 d (for up to six courses) in 27 community‐based patients with high‐risk R/R CLL. Median age was 70 yr (44–83 yr), 55% patients had Binet stage C, deletion 17p (del(17p)) and/or deletion 11q (del(11q)) were found in 65% and 27%, bulky disease in 55.5%, and fludarabine‐refractoriness in 48% of cases, respectively. Overall response rate was 63% (29.6% clinical CR and 33.4% PR). At a median follow‐up of 31 months, median PFS and OS were 15.4 and 24 months. In multivariate analysis, median OS is influenced by prior lines of treatment = 3 and bulky disease. Combination of alemtuzumab and gemcitabine appears to be an active, easy to administrate treatment in routine practice, high‐risk R/R CLL patients.
Determination of the fracture properties of metallic materials using pre‐cracked small punch tests
Authors: Alegre J. M. , Cuesta I. I. , Barbachano H. L.
Published: June 2014

In this paper, the use of pre‐cracked small punch test (p‐SPT) miniature specimens to obtain the fracture parameters of a material is presented. The geometry of the specimens used was square of 10 × 10 mm with a thickness of 0.5 mm. An initial crack‐like notch was created in the SPT specimens by means of a laser micro‐cutting technique. In order to obtain the fracture parameters from p‐SPT specimens three different approaches have been considered here. The first approach is based on the crack tip opening displacement concept, the second is based on the measure of the fracture energy using the area under the load–displacement curve for different crack sizes, and the third approach is based on the direct numerical simulation of the p‐SPT specimen and the numerical calculation of the J‐integral. In order to study the crack initiation in these p‐SPT specimens, several interrupted tests and the subsequent scanning electron microscope analysis have been carried out.

The results indicate that p‐SPT specimens can be used as an alternative method for determining the fracture properties of a material in those cases where there is not enough material to undertake conventional fracture tests. For these p‐SPT specimens, the multi‐specimen method for the determination of the fracture energy is the most promising approach. The results indicate that this small specimen size allows the value of the material toughness, under low constraint conditions to be obtained.
Less means more: nutrient stress leads to higher δ15N ratios in fish
Authors: Bowes Rachel E. , Lafferty M. Holliday , Thorp James H.
Published: June 2014

Isotopic ratios of nitrogen are often used in food‐web studies to determine trophic position (including food chain length) and food sources, with greater ratios of 15N/14N (δ15N) usually considered indicative of higher trophic position. However, fasting and starving animals may also show a progressive increase in δ15N over time as they catabolise their own tissues.

To determine the importance of starvation, we conducted a 4‐month laboratory experiment testing effects of starvation on body condition and isotope ratios in the muscle tissue of freshwater guppies (Poecilia reticulata). We also compared laboratory results and conclusions with analyses of body condition and isotope ratios in various small species of fish collected in four seasons from the Kansas River in north‐eastern Kansas, U.S.A.

Fish starved in our laboratory experiment had significantly higher 15N values and poorer body condition than those fed more regularly. The diverse group of fish species collected in summer (July) from the Kansas River had higher weight‐to‐length ratios and lower 15N values than those retrieved in other seasons. Overall body condition resulting from reduced food consumption explained 44 and 53% of the variability in 15N for field and laboratory fish, respectively.

These results are applicable to a wide variety of food‐web research but are especially pertinent to studies of organisms that undergo large changes in life history, dormancy, extended fasts or periods of significant nutritional allocation to young.
Bioenergy crop productivity and potential climate change mitigation from marginal lands in the United States: An ecosystem modeling perspective
Authors: Qin Zhangcai , Zhuang Qianlai , Cai Ximing
Published: June 2014

Growing biomass feedstocks from marginal lands is becoming an increasingly attractive choice for producing biofuel as an alternative energy to fossil fuels. Here, we used a biogeochemical model at ecosystem scale to estimate crop productivity and greenhouse gas (GHG) emissions from bioenergy crops grown on marginal lands in the United States. Two broadly tested cellulosic crops, switchgrass, and Miscanthus, were assumed to be grown on the abandoned land and mixed crop‐vegetation land with marginal productivity. Production of biomass and biofuel as well as net carbon exchange and nitrous oxide emissions were estimated in a spatially explicit manner. We found that, cellulosic crops, especially Miscanthus could produce a considerable amount of biomass, and the effective ethanol yield is high on these marginal lands. For every hectare of marginal land, switchgrass and Miscanthus could produce 1.0–2.3 kl and 2.9–6.9 kl ethanol, respectively, depending on nitrogen fertilization rate and biofuel conversion efficiency. Nationally, both crop systems act as net GHG sources. Switchgrass has high global warming intensity (100–390 g CO2eq l−1 ethanol), in terms of GHG emissions per unit ethanol produced. Miscanthus, however, emits only 21–36 g CO2eq to produce every liter of ethanol. To reach the mandated cellulosic ethanol target in the United States, growing Miscanthus on the marginal lands could potentially save land and reduce GHG emissions in comparison to growing switchgrass. However, the ecosystem modeling is still limited by data availability and model deficiencies, further efforts should be made to classify crop‐specific marginal land availability, improve model structure, and better integrate ecosystem modeling into life cycle assessment.
Variable access to quality nutrition information regarding inflammatory bowel disease: a survey of patients and health professionals and objective examination of written information
Authors: Prince Alexis C. , Moosa Arifa , Lomer Miranda C. E. , Reidlinger Dianne P. , Whelan Kevin
Published: June 2014

Background

Patients with inflammatory bowel disease (IBD) report a range of nutritional and dietary problems and high‐quality written information should be available on these. There is little research investigating the availability and quality of such information for patients with IBD.

Objective

This study assessed the type and quality of written information on nutrition and diet available to patients with IBD and the opinions of patients and health professionals.

Setting and Participants

Seventy‐two patients with IBD were recruited from a large gastroenterology outpatient centre in England. One hundred dietitians from across the United Kingdom were also recruited.

Methods

Face‐to‐face surveys were conducted with patients with IBD. Questions regarding the use, format and usefulness of dietary information received were probed. Dietitians were surveyed regarding written dietary information used in clinical practice. Samples of IBD‐specific dietary information used across the UK were objectively assessed using two validated tools.

Main Results

The majority of patients rated written information as ‘good’ or ‘very good’, with the most useful information relating to ‘general diet and IBD’. Forty‐nine (49%) dietitians reported gaps in written information available for patients with IBD. Fifty‐three different samples of IBD‐specific information sheets were returned, with widely variable objective quality ratings. Commercially produced written information scored greater than locally produced information (BMA tool, P < 0.05).

Conclusions

Patient access to high‐quality, written, IBD‐specific dietary information is variable. IBD‐specific written nutrition information needs to be developed in accordance with validated tools to empower patients, encourage self‐management and overcome nutritional implications of IBD.
Describing drivers of and barriers to persistence with tiotropium in patients with chronic obstructive pulmonary disease: a mixed-methods approach
Authors: Bereznicki Bonnie J , Peterson Gregory M , Jackson Shane L , Walters Haydn , Hardley Felicity L , Gavagna Guy A , Marshall David C
Published: June 2014

Objective

To understand the factors influencing persistence with tiotropium in patients with chronic obstructive pulmonary disease (COPD).

Methods

Patients classified as ‘persistent’ or ‘non-persistent’ with tiotropium were identified from pharmacy dispensing records. Patients were compared for health status, beliefs and behaviours using data from questionnaires and interviews.

Key findings

Perceptions of the risks and benefits of medication, fear of worsening illness, and the GP's emphasis on the importance of the medication were key determinants of tiotropium persistence.

Conclusions

Perceptions, attitudes and beliefs of patients and doctors influence persistence with tiotropium. These complex interactions need to be targeted to improve persistence with medicines in COPD.
Advanced Chamfering Technology for Edge Strengthening
Authors: Lee Hoikwan , Kim Seungho
Published: June 2014

Damage‐free chamfering method for strengthening a glass edge was introduced and its effect on the edge property was discussed in detail. The chamfered surface was evaluated using an optical microscope, a confocal LSM, and a birefringence measurement system. The mechanical properties were characterized by measuring hardness, Young's modulus, and bending strength. The results revealed that the cut edge of 0.55t thin glass sheet containing median cracks and chips was exfoliated uniformly to a thickness of 200 μm, and a smooth edge surface was created (Ra = 0.03 μm). We also reported that the chamfered surface had a compressive stress enabling hardness and Young's modulus increase, and the edge strength improved from 117 to 199 MPa.
Genetic diversity and population structure of long‐tailed macaque (Macaca fascicularis) populations in Peninsular Malaysia
Authors: Nikzad Sonia , Tan Soon Guan , Yong Seok Yien Christina , Ng Jillian , Alitheen Noorjahan Banu , Khan Razib , Rovie‐Ryan Jeffrine J. , Valdiani Alireza , Khajeaian Parastoo , Kanthaswamy Sree
Published: June 2014

Background

The genetic diversity and structure of long‐tailed macaques (Macaca fascicularis) in Peninsular Malaysia, a widely used non‐human primate species in biomedical research, have not been thoroughly characterized.

Methods

Thirteen sites of wild populations of long‐tailed macaques representing six states were sampled and analyzed with 18 STR markers.

Results

The Sunggala and Penang Island populations showed the highest genetic diversity estimates, while the Jerejak Island population was the most genetically discrete due to isolation from the mainland shelf. Concordant with pairwise Fst estimates, STRUCTURE analyses of the seven PCA‐correlated clusters revealed low to moderate differentiation among the sampling sites. No association between geographic and genetic distances exists, suggesting that the study sites, including island study sites, are genetically if not geographically contiguous.

Conclusions

The status of the genetic structure and composition of long‐tailed macaque populations require further scrutiny to develop this species as an important animal model in biomedical research.
Narcissism and Other‐Derogation in the Absence of Ego Threat
Authors: Park Sun W. , Colvin C. Randall
Published: June 2014

The relation between narcissism and other‐derogation has been examined primarily in the context of ego threat. In three studies, we investigated whether narcissistic individuals derogate others in the absence of ego threat. In Study 1, 79 judges watched four videotaped dyadic interactions and rated the personality of the same four people. In Study 2, 66 judges rated the personality of a friend. In Study 3, 72 judges considered the average Northeastern University student and rated the personality of this hypothetical person. Across the three studies, targets' personality characteristics were described on the 100‐item California Adult Q‐Sort (CAQ; Block, 2008). Judges' ratings of targets were compared to a CAQ prototype of the optimally adjusted person to assess target‐derogation. Judges' narcissism and other‐derogation were positively related in Studies 1 and 2. Narcissism positively predicted and self‐esteem negatively predicted target‐derogation after controlling for each other in Study 3. Narcissistic individuals derogate others more than non‐narcissistic individuals regardless of whether ego threat is present or absent.
Forecasting the Commercial Attractiveness of User‐Generated Designs Using Online Data: An Empirical Study within theLEGOUser Community
Authors: Jensen Morten Berg , Hienerth Christoph , Lettl Christopher
Published: June 2014

Web 2.0 technologies and the rapid emergence of virtual user communities have created new challenges and opportunities for producer firms. The challenges concern the problem of idea overload when a large number of users are empowered to develop their own design creations. At the same time, opportunities arise because firm‐hosted user communities offer a promising source of creativity outside the firms' boundaries. In this paper, we study which data present in firm‐hosted online communities on user‐generated designs and user‐designers can be used to help a focal producer firm to reduce its workload in the selection phase by predicting which user‐generated designs it would most likely perceive as commercially attractive. Prior research emphasizes that among the vast amount of ideas generated in online user communities, it is the lead users' ideas that tend to stick out in terms of commercial attractiveness. Our paper aims to provide the next step by developing a heuristic for filtering commercially attractive ideas that are generated in online user communities. Therefore, prior lead user research is used as a point of reference for our study. This research stream has produced rich insights into the characteristics of users who are capable of developing new products that are commercially attractive from the perspective of a focal producer firm, as well as the characteristics of artifacts that such users tend to develop. Based on prior lead user research, we use theories on problem solving, creativity, and new product adoption to develop hypotheses on the factors that might influence the attractiveness of user‐generated designs from the focal producer firm's perspective in such a setting. Applying multilevel generalized linear modeling, 1799 designs from 116 user‐designers in theLEGOuser community are analyzed. Our findings show that three prominent variables, the complexity of a given design, positive feedback from the community on specific designs, and the intensity of design activity by a user‐designer, can be used by a focal producer firm as filtering heuristics for the selection of promising user‐generated designs. We find an invertedU‐shaped relationship between the complexity of a user‐generated design and its perceived commercial attractiveness. Furthermore, we find a positive relationship between the positive feedback received by a given user‐generated design within the peer community and its perceived commercial attractiveness, as well as aU‐shaped relationship between the intensity of a certain user‐designer's activities and the likelihood that a given design by that user will be perceived as commercially attractive. The study is a first step toward a new Web‐based marketing research approach that can enable firms to filter vast numbers of user‐generated designs more effectively and efficiently.
Psychosocial Functioning and School Achievement of Children With Mild Intellectual Disability in Polish Special, Integrative, and Mainstream Schools
Authors: Szumski Grzegorz , Karwowski Maciej
Published: June 2014

The authors sought to assess the effectiveness of integrative and inclusive education in Poland as well as to determine the relations between the psychosocial functioning and school achievement of pupils with mild intellectual disability attending special, integrative, and mainstream schools. Nearly 900 (n = 859) grade four pupils rated their social and emotional integration within their school and took a school achievement test. Pupils from integrative and mainstream schools achieved significantly higher scores in the school achievement test than pupils from special schools, whereas students from special schools were significantly better integrated emotionally and socially than integrative and mainstream school students. Additionally, emotional integration was a positive predictor for school achievement of pupils attending special schools. Among pupils attending integrative and mainstream schools, the relationship between emotional and social integration and school achievement was more complex and curvilinear: The highest results were achieved by the best and the worst integrated pupils. These findings are discussed in the context of inclusive education theory.
Primary biliary cirrhosis: proposal for a new simple histological scoring system
Authors: Wendum Dominique , Boëlle Pierre‐Yves , Bedossa Pierre , Zafrani Elie‐Serge , Charlotte Frédéric , Saint‐Paul Marie‐Christine , Michalak Sophie , Chazouillères Olivier , Corpechot Christophe
Published: June 2014

Background & Aims

A simple and reproducible evaluation of non diagnostic histological lesions related to prognosis remains crucial in primary biliary cirrhosis (PBC). Presently there is no satisfactory simple scoring system analysing them reliably. We elaborated a semi‐quantitative scoring system that assesses fibrosis, lymphocytic interface hepatitis (LIH) and ductopenia, separately. This study was aimed to evaluate its intra/interobserver reproducibility and its correlation with the main biochemical data.

Methods

Liver biopsies from 33 consecutive newly diagnosed PBC patients were independently analysed by five liver pathologists. Fibrosis was classified into five stages (portal/periportal fibrosis/few septa/numerous septa/cirrhosis) and LIH into four grades. The bile duct ratio (BDR), i.e. ratio of the number of portal tracts with ducts to total number of portal tracts, Ludwig's and Scheuer's stages were evaluated. Intra and interobserver agreements were assessed. Histological results were correlated to the biochemical data.

Results

Most patients had an early disease on clinical and biological parameters. The biopsies measured 23 mm on average (range 12 – 40 mm). Intraobserver reproducibility was substantial for fibrosis (κ = 0.68), LIH (κ = 0.69) and BDR (ICC = 0.69). Interobserver agreement for fibrosis was fair with the 5‐class system (κ = 0.36), moderate with a 4‐class system (κ = 0.56). moderate for LIH (κ = 0.59) and BDR (ICC = 0.50). Ludwig's and Scheuer's staging showed a fair interobserver agreement (κ = 0.32, κ = 0.31 respectively). Our system showed better correlations with biochemistry than Ludwig's and Scheuer's systems did.

Conclusions

This simple scoring system, assessing fibrosis, LIH and BDR separately, has a substantial intraobserver and a moderate interobserver reproducibility. Its prognostic relevance has to be evaluated.
Differential affinities of MinD and MinE to anionic phospholipid influence Min patterning dynamics in vitro
Authors: Vecchiarelli Anthony G. , Li Min , Mizuuchi Michiyo , Mizuuchi Kiyoshi
Published: June 2014

The E. coli Min system forms a cell‐pole‐to‐cell‐pole oscillator that positions the divisome at mid‐cell. The MinD ATPase binds the membrane and recruits the cell division inhibitor MinC. MinE interacts with and releases MinD (and MinC) from the membrane. The chase of MinD by MinE creates the in vivo oscillator that maintains a low level of the division inhibitor at mid‐cell. In vitro reconstitution and visualization of Min proteins on a supported lipid bilayer has provided significant advances in understanding Min patterns in vivo. Here we studied the effects of flow, lipid composition, and salt concentration on Min patterning. Flow and no‐flow conditions both supported Min protein patterns with somewhat different characteristics. Without flow, MinD and MinE formed spiraling waves. MinD and, to a greater extent MinE, have stronger affinities for anionic phospholipid. MinD‐independent binding of MinE to anionic lipid resulted in slower and narrower waves. MinE binding to the bilayer was also more susceptible to changes in ionic strength than MinD. We find that modulating protein diffusion with flow, or membrane binding affinities with changes in lipid composition or salt concentration, can differentially affect the retention time of MinD and MinE, leading to spatiotemporal changes in Min patterning.
An investigation of Candida species isolated from blood cultures during 17 years in a university hospital
Authors: Kazak E. , Akın H. , Ener B. , Sığırlı D. , Özkan Ö. , Gürcüoğlu E. , Yılmaz Emel , Çelebi Solmaz , Akçağlar Sevim , Akalın Halis
Published: June 2014

Candidemia is the most frequent manifestation observed with invasive candidiasis. The aim of this study was to analyse the trends of candidemia in a large tertiary‐care hospital to determine the overall incidence during January 1996–December 2012, as well as to determine the susceptibility of 453 isolates according to the revised Clinical and Laboratory Standards Institute (CLSI) breakpoints. Candidemia episodes in adult and paediatric patients were retrospectively analysed from the laboratory data of Uludağ University Healthcare and Research Hospital. The 17‐year period studied was divided into three periods (1996–2001, 2002–2007 and 2008–2012) for better comparison, and candidemia incidence was determined by the ratio of total number of patients with candidemia per 1000 patients admitted to the hospital and per 10 000 patient days in these three periods. Redefined CLSI M27‐A3 breakpoints were used for interpretation of antifungal susceptibility results. Candidemia incidence was determined as 2.2, 1.7 and 1.5 per 1000 admitted patients during 1996–2001, 2002–2007 and 2008–2012 respectively. A significantly decreased candidemia incidence was obtained in the third period. C. albicans (43.8%) was the most common candidemia agent, followed by C.parapsilosis (26.5%) in all three periods. According to the revised CLSI breakpoints, there was fluconazole resistance in C. albicans, C.parapsilosis, C.tropicalis and C.glabrata species (1.4%, 18.2%, 2.6% and 14.3% respectively). Almost all Candida species were found susceptible to voriconazole except one C.glabrata (7.1%) isolate. Candidemia is an important health problem. Local epidemiological data are determinative in the choice of appropriate antifungal treatment agents.
Pathophysiology and Japanese clinical characteristics in Marfan syndrome
Authors: Fujita Daishi , Takeda Norifumi , Imai Yasushi , Inuzuka Ryo , Komuro Issei , Hirata Yasunobu
Published: June 2014

Marfan syndrome is an autosomal dominant heritable disorder of the connective tissue, caused by mutations of the gene FBN1, which encodes fibrillin‐1, a major component of the microfibrils of the extracellular matrix. Fibrillin‐1 interacts with transforming growth factor‐β (TGF‐β), and dysregulated TGF‐β signaling plays a major role in the development of connective tissue disease and familial aortic aneurysm and dissection, including Marfan syndrome. Losartan, an angiotensin II blocker, has the potential to reduce TGF‐β signaling and is expected to be an additional therapeutic option. Clinical diagnosis is made using the Ghent nosology, which requires comprehensive patient assessment and has been proven to work well, but evaluation of some of the diagnostic criteria by a single physician is difficult and time‐consuming. A Marfan clinic was established at the University of Tokyo Hospital in 2005, together with cardiologists, cardiac surgeons, pediatricians, orthopedists, and ophthalmologists in one place, for the purpose of speedy and accurate evaluation and diagnosis of Marfan syndrome. In this review, we discuss the recent progress in diagnosis and treatment of Marfan syndrome, and the characteristics of Japanese patients with Marfan syndrome.
A Dilemma for Calibrationism
Authors: Schoenfield Miriam
Published: June 2014

The aim of this paper is to describe a problem forcalibrationism: a view about higher order evidence according to which one's credences should be calibrated to one's expected degree of reliability. Calibrationism is attractive, in part, because it explains our intuitive judgments, and provides a strong motivation for certain theories about higher order evidence and peer disagreement. However, I will argue that calibrationism faces a dilemma: There are two versions of the view one might adopt. The first version, I argue, has the implausible consequence that, in a wide range of cases, calibrationism is theonlyconstraint on rational belief. The second version, in addition to having some puzzling consequences, is unmotivated. At the end of the paper I sketch a possible solution.
Reactive sputtering of δ-ZrH2 thin films by high power impulse magnetron sputtering and direct current magnetron sputtering
Authors: Högberg Hans , Tengdelius Lina , Samuelsson Mattias , Eriksson Fredrik , Broitman Esteban , Lu Jun , Jensen Jens , Hultman Lars
Published: June 2014

Reactive sputtering by high power impulse magnetron sputtering (HiPIMS) and direct current magnetron sputtering (DCMS) of a Zr target in Ar/H2 plasmas was employed to deposit Zr-H films on Si(100) substrates, and with H content up to 61 at. % and O contents typically below 0.2 at. % as determined by elastic recoil detection analysis. X-ray photoelectron spectroscopy reveals a chemical shift of ∼0.7 eV to higher binding energies for the Zr-H films compared to pure Zr films, consistent with a charge transfer from Zr to H in a zirconium hydride. X-ray diffraction shows that the films are single-phase δ-ZrH2 (CaF2 type structure) at H content >∼55 at. % and pole figure measurements give a 111 preferred orientation for these films. Scanning electron microscopy cross-section images show a glasslike microstructure for the HiPIMS films, while the DCMS films are columnar. Nanoindentation yield hardness values of 5.5–7 GPa for the δ-ZrH2 films that is slightly harder than the ∼5 GPa determined for Zr films and with coefficients of friction in the range of 0.12–0.18 to compare with the range of 0.4–0.6 obtained for Zr films. Wear resistance testing show that phase-pure δ-ZrH2 films deposited by HiPIMS exhibit up to 50 times lower wear rate compared to those containing a secondary Zr phase. Four-point probe measurements give resistivity values in the range of ∼100–120 μΩ cm for the δ-ZrH2 films, which is slightly higher compared to Zr films with values in the range 70–80 μΩ cm.
Effect of a Reduced-CHO Diet on the Rate of Perceived Exertion Curve During an Incremental Test
Authors: Ferreira Guilherme Assuncao , Osiecki Raul , Lima-Silva Adriano Eduardo , de Angelis-Pereira Michel Cardoso , De-Oliveira Fernando Roberto
Published: June 2014

The objective of this study was to evaluate the effect of a reduced-carbohydrate (reduced-CHO) diet on the rate of perceived exertion (RPE) curve during an incremental test. Nine physically active men performed a progressive incremental test on a cycle ergometer (25 W·2 min−1) after 72 hr on either a control diet (60% CHO) or a reduced-CHO diet (30% CHO). Lactate and RPE thresholds were identified using the Dmax method (DmaxLa and DmaxRPE, respectively). Power output, heart rate and RPE scores in DmaxLa and DmaxRPE were similar between the diets and were not different from each other, regardless of the diet. Lactate values were consistently higher (p < .05) in the control diet compared with the reduced-CHO diet during power output after the lactate breakpoint; however, they were not accompanied by a proportional increase in RPE scores. These results suggest that DmaxRPE and DmaxLa are not dissociated after a short-period reduced-CHO diet, whereas the lactate values after the lactate threshold are reduced with a reduced-CHO diet, although they are not accompanied by alterations in RPE.
Nutritional Recommendations for Divers
Authors: Benardot Dan , Zimmermann Wes , Cox Gregory R. , Marks Saul
Published: June 2014

Competitive diving involves grace, power, balance, and flexibility, which all require satisfying daily energy and nutrient needs. Divers are short, well-muscled, and lean, giving them a distinct biomechanical advantage. Although little diving-specific nutrition research on performance and health outcomes exists, there is concern that divers are excessively focused on body weight and composition, which may result in reduced dietary intake to achieve desired physique goals. This will result in low energy availability, which may have a negative impact on their power-to-weight ratio and health risks. Evidence is increasing that restrictive dietary practices leading to low energy availability also result in micronutrient deficiencies, premature fatigue, frequent injuries, and poor athletic performance. On the basis of daily training demands, estimated energy requirements for male and female divers are 3,500 kcal and 2,650 kcal, respectively. Divers should consume a diet that provides 3–8 g/kg/day of carbohydrate, with the higher values accommodating growth and development. Total daily protein intake (1.2–1.7 g/kg) should be spread evenly throughout the day in 20 to 30 g amounts and timed appropriately after training sessions. Divers should consume nutrient-dense foods and fluids and, with medical supervision, certain dietary supplements (i.e., calcium and iron) may be advisable. Although sweat loss during indoor training is relatively low, divers should follow appropriate fluid-intake strategies to accommodate anticipated sweat losses in hot and humid outdoor settings. A multidisciplinary sports medicine team should be integral to the daily training environment, and suitable foods and fluids should be made available during prolonged practices and competitions.
Olympic Athletes’ Experiences of a Post Games Career Transition Program
Authors: McArdle Siobhain , Moore Phil , Lyons Deirdre
Published: June 2014

Career pathways in high performance sport include a number of emotionally resonant transitions. Sport systems must be able to effectively support the athlete’s endeavors to negotiate such challenges. This study investigated qualitatively the experiences of Olympic athletes who took part in a three-tier, post-games career transition support program. The aim of the program was to increase athletes’ coping resources to successful negotiate the post-Olympic period. Ten athletes who participated in the program were recruited to participate in semi structured individual interviews. Directed content analysis was employed to identify key themes in the data. Athletes perceived two components of the program as particularly helpful, the normalization of the emotional and psychological challenge of the post Games period and the use of problem focused coping to redirect athlete focus to the future. The findings from this study provide a preliminary framework for the planning of future post-Games career transition support programs.
A Qualitative Analysis of Female Collegiate Athletes’ Eating Disorder Recovery Experiences
Authors: Arthur-Cameselle Jessyca N. , Quatromoni Paula A.
Published: June 2014

The purpose of this study was to characterize recovery experiences of female collegiate athletes who have suffered from eating disorders. Participants were 16 collegiate female athletes who experienced recovery from an eating disorder. Participants told their recovery stories in semistructured interviews regarding factors that initiated, assisted, and hindered recovery. The most common turning point to initiate recovery was experiencing negative consequences from the eating disorder. Factors that most frequently assisted recovery included making cognitive and behavioral changes, supportive relationships, and seeking professional care. Hindering factors most commonly included lack of support from others, professional care complaints, and spending time with others with eating disorders. Results suggested that unique features of the sport environment, including coaches’ behavior and team norms, introduce either positive or negative influences on athletes as they work to recover from an eating disorder. Based on these findings, specific treatment and prevention recommendations for athletes are discussed.
Parents’ Perspectives on the Benefits of Sport Participation for Young Children
Authors: Neely Kacey C. , Holt Nicholas L.
Published: June 2014

The overall purpose of this study was to examine parents’ perspectives on the benefits of sport participation for their young children. Specifically, this study addressed two research questions: (1) What benefits do parents perceive their children gain through participation in organized youth sport programs? (2) How do parents think their children acquire these benefits? Twenty-two parents (12 mothers, 10 fathers) of children aged 5-8 years participated in individual semistructured interviews. Data were subjected to qualitative analysis techniques based on the interpretive description methodology. Parents reported their children gained a range of personal, social, and physical benefits from participating in sport because it allowed them to explore their abilities and build positive self-perceptions. Parents indicated they believed children acquired benefits when coaches created a mastery-oriented motivational climate that facilitated exploration. Crucially, parents appeared to play the most important role in their children’s acquisition of benefits by seizing “teachable moments” from sport and reinforcing certain principles in the home environment.
Science Signaling
Podcast: 17 June 2014
Authors: Bae Yong Ho , Assoian Richard K. , VanHook Annalisa M.
Published: June 2014

Stiff substrates prompt cells to activate a signaling network that stiffens the cytoskeleton and promotes proliferation.
Improving Stroke Recovery by Timing Treatment
Authors: Hines Pamela J.
Published: June 2014

A rat model of stroke shows that the rebuilding of spinal circuits in response to training is time-sensitive.
MAPK Methylation Potentiates RAS Signaling
Authors: Ferrarelli Leslie K.
Published: June 2014

Preventing a posttranslational modification in the MAPK pathway may block the growth of RAS-driven cancers.
Pharmacokinetics and Preliminary Safety Study of Pod-Intravaginal Rings Delivering Antiretroviral Combinations for HIV Prophylaxis in a Macaque Model
Authors: Moss John A. , Srinivasan Priya , Smith Thomas J. , Butkyavichene Irina , Lopez Gilbert , Brooks Amanda A. , Martin Amy , Dinh Chuong T. , Smith James M. , Baum Marc M.
Published: June 2014

Preexposure prophylaxis using oral regimens involving the HIV nucleoside reverse transcriptase inhibitors tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) demonstrated efficacy in three clinical trials. Adherence was determined to be a key parameter for success. Incorporation of the TDF-FTC combination into intravaginal rings (IVRs) for sustained mucosal delivery could increase product adherence and efficacy compared with those of oral and vaginal gel formulations. A novel pod-IVR technology capable of delivering multiple drugs is described; this constitutes the first report of an IVR delivering TDF and FTC, as well as a triple-combination IVR delivering TDF, FTC, and the entry inhibitor maraviroc (MVC). The pharmacokinetics and preliminary local safety of the two combination pod-IVRs were evaluated in the pig-tailed macaque model. The devices exhibited sustained release at controlled rates over the 28-day study period. Median steady-state drug levels in vaginal tissues in the TDF-FTC group were 30 μg g
−1
(tenofovir [TFV],
in vivo
hydrolysis product of TDF) and 500 μg g
−1
(FTC) and in the TDF-FTC-MVC group were 10 μg g
−1
(TFV), 150 μg g
−1
(FTC), and 20 μg g
−1
(MVC). No adverse events were observed, and there were no toxicological findings. Mild-to-moderate increases in inflammatory infiltrates were observed in the vaginal tissues of some animals in both the presence and the absence of the IVRs. The IVRs did not disturb the vaginal microbiota, and levels of proinflammatory cytokines remained stable throughout the study. Pod-IVR candidates based on the TDF-FTC combination have potential for the prevention of vaginal HIV acquisition and merit clinical investigation.
RS1 Satellite Phage Promotes Diversity of Toxigenic Vibrio cholerae by Driving CTX Prophage Loss and Elimination of Lysogenic Immunity
Authors: Kamruzzaman M. , Robins William Paul , Bari S. M. Nayeemul , Nahar Shamsun , Mekalanos John J. , Faruque Shah M.
Published: June 2014

In El Tor biotype strains of toxigenic
Vibrio cholerae
, the CTXϕ prophage often resides adjacent to a chromosomally integrated satellite phage genome, RS1, which produces RS1ϕ particles by using CTX prophage-encoded morphogenesis proteins. RS1 encodes RstC, an antirepressor against the CTXϕ repressor RstR, which cooperates with the host-encoded LexA protein to maintain CTXϕ lysogeny. We found that superinfection of toxigenic El Tor strains with RS1ϕ, followed by inoculation of the transductants into the adult rabbit intestine, caused elimination of the resident CTX prophage-producing nontoxigenic derivatives at a high frequency. Further studies using
recA
deletion mutants and a cloned
rstC
gene showed that the excision event was
recA
dependent and that introduction of additional copies of the cloned
rstC
gene instead of infection with RS1ϕ was sufficient to enhance CTXϕ elimination. Our data suggest that once it is excised from the chromosome, the elimination of CTX prophage from host cells is driven by the inability to reestablish CTXϕ lysogeny while RstC is overexpressed. However, with eventual loss of the additional copies of
rstC
, the nontoxigenic derivatives can act as precursors of new toxigenic strains by acquiring the CTX prophage either through reinfection with CTXϕ or by chitin-induced transformation. These results provide new insights into the role of RS1ϕ in
V. cholerae
evolution and the emergence of highly pathogenic clones, such as the variant strains associated with recent devastating epidemics of cholera in Asia, sub-Saharan Africa, and Haiti.
Parasite-Derived Neurotrophic Factor/trans-Sialidase of Trypanosoma cruzi Links Neurotrophic Signaling to Cardiac Innate Immune Response
Authors: Salvador Ryan , Aridgides Daniel , PereiraPerrin Mercio
Published: June 2014

The Chagas' disease parasiteTrypanosoma cruzielicits a potent inflammatory response in acutely infected hearts that keeps parasitism in check and triggers cardiac abnormalities. A most-studied mechanism underlying innate immunity inT. cruziinfection is Toll-like receptor (TLR) activation by lipids and other parasite molecules. However, yet-to-be-identified pathways should exist. Here, we show thatT. cruzistrongly upregulates monocyte chemoattractant protein 1 (MCP-1)/CCL2 and fractalkine (FKN)/CX3CL1 in cellular and mouse models of heart infection. Mechanistically, upregulation of MCP-1 and FKN stems from the interaction of parasite-derived neurotrophic factor (PDNF)/trans-sialidase with neurotrophic receptors TrkA and TrkC, as assessed by pharmacological inhibition, neutralizing antibodies, and gene silencing studies. Administration of a single dose of intravenous PDNF to naive mice results in a dose-dependent increase in MCP-1 and FKN in the heart and liver with pulse-like kinetics that peak at 3 h postinjection. Intravenous PDNF also augments MCP-1 and FKN in TLR signaling-deficient MyD88-knockout mice, underscoring the MyD88-independent action of PDNF. Although single PDNF injections do not increase MCP-1 and FKN receptors, multiple PDNF injections at short intervals up the levels of receptor transcripts in the heart and liver, suggesting that sustained PDNF triggers cell recruitment at infection sites. Thus, given that MCP-1 and FKN are chemokines essential to the recruitment of immune cells to combat inflammation triggers and to enhance tissue repair, our findings uncover a new mechanism in innate immunity againstT. cruziinfection mediated by Trk signaling akin to an endogenous inflammatory and fibrotic pathway resulting from cardiomyocyte-TrkA recognition by matricellular connective tissue growth factor (CTGF/CCN2).
Endotoxin-Induced Endothelial Fibrosis Is Dependent on Expression of Transforming Growth Factors β1 and β2
Authors: Echeverría César , Montorfano Ignacio , Tapia Pablo , Riedel Claudia , Cabello-Verrugio Claudio , Simon Felipe
Published: June 2014

During endotoxemia-induced inflammatory disease, bacterial endotoxins circulate in the bloodstream and interact with endothelial cells (ECs), inducing dysfunction of the ECs. We previously reported that endotoxins induce the conversion of ECs into activated fibroblasts. Through endotoxin-induced endothelial fibrosis, ECs change their morphology and their protein expression pattern, thereby suppressing endothelial markers and upregulating fibrotic proteins. The most commonly used fibrotic inducers are transforming growth factor β1 (TGF-β1) and TGF-β2. However, whether TGF-β1 and TGF-β2 participate in endotoxin-induced endothelial fibrosis remains unknown. We have shown that the endotoxin-induced endothelial fibrosis process is dependent on the TGF-β receptor, ALK5, and the activation of Smad3, a protein that is activated by ALK5 activation, thus suggesting that endotoxin elicits TGF-β production to mediate endotoxin-induced endothelial fibrosis. Therefore, we investigated the dependence of endotoxin-induced endothelial fibrosis on the expression of TGF-β1 and TGF-β2. Endotoxin-treated ECs induced the expression and secretion of TGF-β1 and TGF-β2. TGF-β1 and TGF-β2 downregulation inhibited the endotoxin-induced changes in the endothelial marker VE-cadherin and in the fibrotic proteins α-SMA and fibronectin. Thus, endotoxin induces the production of TGF-β1 and TGF-β2 as a mechanism to promote endotoxin-induced endothelial fibrosis. To the best of our knowledge, this is the first report showing that endotoxin induces endothelial fibrosis via TGF-β secretion, which represents an emerging source of vascular dysfunction. These findings contribute to understanding the molecular mechanism of endotoxin-induced endothelial fibrosis, which could be useful in the treatment of inflammatory diseases.
Ammonium Metabolism Enzymes Aid Helicobacter pylori Acid Resistance
Authors: Miller Erica F. , Maier Robert J.
Published: June 2014

The gastric pathogen
Helicobacter pylori
possesses a highly active urease to support acid tolerance. Urea hydrolysis occurs inside the cytoplasm, resulting in the production of NH
3
that is immediately protonated to form NH
4
+
. This ammonium must be metabolized or effluxed because its presence within the cell is counterproductive to the goal of raising pH while maintaining a viable proton motive force (PMF). Two compatible hypotheses for mitigating intracellular ammonium toxicity include (i) the exit of protonated ammonium outward via the UreI permease, which was shown to facilitate diffusion of both urea and ammonium, and/or (ii) the assimilation of this ammonium, which is supported by evidence that
H. pylori
assimilates urea nitrogen into its amino acid pools. We investigated the second hypothesis by constructing strains with altered expression of the ammonium-assimilating enzymes glutamine synthetase (GS) and glutamate dehydrogenase (GDH) and the ammonium-evolving periplasmic enzymes glutaminase (Ggt) and asparaginase (AsnB).
H. pylori
strains expressing elevated levels of either GS or GDH are more acid tolerant than the wild type, exhibit enhanced ammonium production, and are able to alkalize the medium faster than the wild type. Strains lacking the genes for either Ggt or AsnB are acid sensitive, have 8-fold-lower urea-dependent ammonium production, and are more acid sensitive than the parent. Additionally, we found that purified
H. pylori
GS produces glutamine in the presence of Mg
2+
at a rate similar to that of unadenylated
Escherichia coli
GS. These data reveal that all four enzymes contribute to whole-cell acid resistance in
H. pylori
and are likely important for assimilation and/or efflux of urea-derived ammonium.
Differential nuclear shape dynamics of invasive andnon-invasive breast cancer cells are associated with actin cytoskeleton organization and stability
Authors: Chiotaki Rena , Polioudaki Hara , Theodoropoulos Panayiotis A.
Published: June 2014

Cancer cells often exhibit characteristic aberrations in their nuclear architecture, which are indicative of their malignant potential. In this study, we have examined the nuclear and cytoskeletal composition, attachment configuration dynamics, and osmotic or drug treatment response of invasive (Hs578T and MDA-MB-231) and non-invasive (MCF-10A and MCF-7) breast cancer cell lines. Unlike MCF-10A and MCF-7, Hs578T and MDA-MB-231 cells showed extensive nuclear elasticity and deformability and displayed distinct kinetic profiles during substrate attachment. The nuclear shape of MCF-10A and MCF-7 cells remained almost unaffected upon detachment, hyperosmotic shock, or cytoskeleton depolymerization, while Hs578T and MDA-MB-231 revealed dramatic nuclear contour malformations following actin reorganization.
Natural recruitment, density-dependent juvenile survival, and the potential for additive effects of stock enhancement: an experimental evaluation of stocking northern pike (Esox lucius) fry
Authors: Hühn Daniel , Lübke Kay , Skov Christian , Arlinghaus Robert
Published: June 2014

Density-dependent mortality in young life stages should strongly limit the potential for additive effects caused by stocking of fish sizes that are smaller than size at recruitment into the fishery. Indeed, stocking models have suggested that stocking of fry should not elevate year class strength in self-sustaining stocks. However, limited data based on replicated and controlled experiments are available to support this prediction. We performed a pond experiment (N = 4 per treatment) to compare the stock enhancing outcome of stocking hatchery-reared northern pike (Esox lucius) fry and the natural production of young in self-recruiting pike populations. We also added a treatment where pike fry were stocked into ponds that otherwise did not have pike to mimic the absence of natural recruitment. Fry stocking into self-reproducing stocks did not elevate year class strength over unstocked controls. However, in the absence of competition, year class strength of juveniles in late summer emerging from fry stocking was similar to the production of natural recruits. Overall, we demonstrated the competitive disadvantage of hatchery-reared fry when released into waters already containing natural recruits, the partial replacement of natural recruits by hatchery-reared fry, and the lack of additive effects of stock enhancement in naturally reproducing stocks. A stock-enhancing effect of pike fry stocking may only be expected in the absence of natural recruitment.