bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the Heat Treatment Condition of Steel AISI 4140 on Its Frictional Contact Behavior in Dry Metal Cutting
Authors: Buchkremer Stefan , Klocke Fritz , Döbbeler Benjamin
Published: April 2016

In this work, the impact of the heat treatment condition of steel AISI 4140 on its frictional contact behavior with coated cemented carbide and cubic boron nitride (CBN) in dry metal cutting is experimentally investigated. Two different kinds of tests were performed. The frictional behavior was investigated under conditions very similar to metal cutting on a frictional test bench, which was installed on a broaching machine. Additionally, orthogonal cutting processes with linear workpiece geometries were conducted on the same machine. The cutting experiments included observations of cutting forces, high-speed filming of chip formation, chip thickness ratio analysis as well as a comprehensive metallographic characterization of the chips and workpiece surfaces. The impacts of the undeformed chip thickness and cutting speed were investigated individually for coated cemented carbide and CBN as cutting materials. The frictional examinations delivered the Coulomb friction coefficients for all four combinations of work and cutting materials as a function of the relative velocity. The identified frictional behaviors explain the dependencies of forces, chip thicknesses, and surface microstructures on the tool and process conditions during the cutting tests.
Ultrasonic Inspection of Electrofusion Joints of Large Polyethylene Pipes in Nuclear Power Plants
Authors: Zheng Jinyang , Hou Dongsheng , Guo Weican , Miao Xiaoming , Zhou Yaoda , Shi Jianfeng
Published: April 2016

High-density polyethylene (HDPE) pipe has many advantages such as good flexibility, corrosion resistance, and long service life. It has been introduced into nuclear power plants for transportation of cooling water in U.S. and Europe. Recently, four HDPE pipelines (PE4710) were used in essential cooling water system with operating pressure of 0.6 MPa and operating temperature of no more than 60 °C in a newly established AP1000 nuclear power plant in Zhejiang, China. The outside diameter and thickness are 30 in. and 3.3 in., respectively, which are much larger and thicker than traditional HDPE pipe for natural gas. This brought forward a challenge for nondestructive testing (NDT) and safety assessment of such pipes. In this paper, a solution for inspecting electrofusion (EF) joints of thick-walled HDPE pipes is presented, and the results of an on-site inspection of the nuclear power plant are revealed. To expand the thickness up-limit of previously developed ultrasonic-phased array instrument, an optimization method was proposed by calculating weighing effects of different testing parameters and introducing the concept of overall performance according to practical requirement, by comprehensively considering sensitivity, penetration, signal-to-noise ratio (SNR), resolution, and accuracy. Typical defects were found in field inspection. The result shows that the presented technique is capable of inspecting EF joints for connecting large-size HDPE pipes used in nuclear power plants.
Effects of atmospheric-pressure discharge type on ionic wind velocity for needle-to-cylinder electrode
Authors: Li Hua , Guo Chaoqun , Li Yukai , Hong Xialei , Zhu Jianmin , Chen Zhencheng
Published: April 2016

A needle-to-cylinder electrode configuration was proposed to generate an ionic wind at atmospheric pressure. Experiments were conducted with negative voltage ranging from 0 to −20 000 V at atmospheric pressure and room temperature. Negative corona, glow, and arc discharges in ambient air were achieved without external airflow, as confirmed by some typical characteristics of their discharge waveforms and images. The experiments indicate that: (1) the discharge current in a glow discharge is larger than that in a corona discharge; (2) the ionic wind velocity does not increase monotonically with increasing discharge current; and (3) the ionic wind velocity increases with increasing voltage in the corona discharge phase, while decreasing in the glow discharge phase. A detailed study was conducted on why varying behaviors occur for these different types of air discharges and how they affect electrohydrodynamic flow. The results help in establishing a guide for electrohydrodynamic design.
Using worksheets to solve the Einstein equation
Authors: Moore Thomas A.
Published: April 2016

This article describes how one can use worksheets to guide undergraduate students through the process of finding solutions to specific cases of the Einstein equation of general relativity. The worksheets provide expressions for a metric's Christoffel symbols and Ricci tensor components for fairly general metrics. Students can use a worksheet to adapt these expressions to specific cases where symmetry or other considerations constrain the metric components' dependencies, and then use the worksheet's results to reduce the Einstein equation to a set of simpler differential equations that they can solve. This article illustrates the process for both a diagonal metric and a metric with one off-diagonal element.
Why does a ball fall?: A new visualization for Einstein's model of gravity
Authors: Gould Roy R.
Published: April 2016

Many physics teachers seek a simple illustration of Einstein's model of gravity, suitable for the introductory physics classroom. In this article, we show that an ordinary wall map of the world can be used to contrast Newton's and Einstein's explanations for why a ball falls when released. Trajectories on the map are analogous to the trajectories of the ball through spacetime, because the geometry of the map is remarkably similar to the geometry of spacetime near Earth's surface. To aid in the pedagogy, we focus on the concept of scale rather than curvature. We show that, contrary to popular visualizations of Einstein's model, it is primarily the warping of time, not space, that causes a ball to fall, and we address the question of why we do not see the distortion of spacetime around us. Finally, we recover Newton's results for the falling ball from our geometrical treatment.
Using graphical and pictorial representations to teach introductory astronomy students about the detection of extrasolar planets via gravitational microlensing
Authors: Wallace Colin S. , Chambers Timothy G. , Prather Edward E. , Brissenden Gina
Published: April 2016

The detection and study of extrasolar planets is an exciting and thriving field in modern astrophysics and an increasingly popular topic in introductory astronomy courses. One detection method relies on searching for stars whose light has been gravitationally microlensed by an extrasolar planet. In order to facilitate instructors' abilities to bring this interesting mix of general relativity and extrasolar planet detection into the introductory astronomy classroom, we have developed a new Lecture-Tutorial called “Detecting Exoplanets with Gravitational Microlensing.” In this paper, we describe how this new Lecture-Tutorial's representations of astrophysical phenomena, which we selected and created based on theoretically motivated considerations of their pedagogical affordances, are used to help introductory astronomy students develop more expert-like reasoning abilities.
Dose-Response of Sodium Bicarbonate Ingestion Highlights Individuality in Time Course of Blood Analyte Responses
Authors: Jones Rebecca Louise , Stellingwerff Trent , Artioli Guilherme Giannini , Saunders Bryan , Cooper Simon , Sale Craig
Published: April 2016

To defend against hydrogen cation accumulation and muscle fatigue during exercise, sodium bicarbonate (NaHCO3) ingestion is commonplace. The individualized dose-response relationship between NaHCO3 ingestion and blood biochemistry is unclear. The present study investigated the bicarbonate, pH, base excess and sodium responses to NaHCO3 ingestion. Sixteen healthy males (23 ± 2 years; 78.6 ± 15.1 kg) attended three randomized order-balanced, nonblinded sessions, ingesting a single dose of either 0.1, 0.2 or 0.3 g·kg-1BM of NaHCO3 (Intralabs, UK). Fingertip capillary blood was obtained at baseline and every 10 min for 1 hr, then every 15 min for a further 2 hr. There was a significant main effect of both time and condition for all assessed blood analytes (p ≤ .001). Blood analyte responses were significantly lower following 0.1 g·kg-1BM compared with 0.2 g·kg-1BM; bicarbonate concentrations and base excess were highest following ingestion of 0.3 g·kg-1BM (p ≤ .01). Bicarbonate concentrations and pH significantly increased from baseline following all doses; the higher the dose the greater the increase. Large interindividual variability was shown in the magnitude of the increase in bicarbonate concentrations following each dose (+2.0–5; +5.1–8.1; and +6.0–12.3 mmol·L-1 for 0.1, 0.2 and 0.3 g·kg-1BM) and in the range of time to peak concentrations (30–150; 40–165; and 75–180 min for 0.1, 0.2 and 0.3 g·kg-1BM). The variability in bicarbonate responses was not affected by normalization to body mass. These results challenge current practices relating to NaHCO3 supplementation and clearly show the need for athletes to individualize their ingestion protocol and trial varying dosages before competition.
The Assessment of Total Energy Expenditure During a 14-Day In-Season Period of Professional Rugby League Players Using the Doubly Labelled Water Method
Authors: Morehen James Cameron , Bradley Warren Jeremy , Clarke Jon , Twist Craig , Hambly Catherine , Speakman John Roger , Morton James Peter , Close Graeme Leonard
Published: April 2016

Rugby League is a high-intensity collision sport competed over 80 min. Training loads are monitored to maximize recovery and assist in the design of nutritional strategies although no data are available on the total energy expenditure (TEE) of players. We therefore assessed resting metabolic rate (RMR) and TEE in six Super League players over 2 consecutive weeks in-season including one game per week. Fasted RMR was assessed followed by a baseline urine sample before oral administration of a bolus dose of hydrogen (deuterium 2H) and oxygen (18O) stable isotopes in the form of water (2H218O). Every 24 hr thereafter, players provided urine for analysis of TEE via DLW method. Individual training load was quantified using session rating of perceived exertion (sRPE) and data were analyzed using magnitude-based inferences. There were unclear differences in RMR between forwards and backs (7.7 ± 0.5 cf. 8.0 ± 0.3 MJ, respectively). Indirect calorimetry produced RMR values most likely lower than predictive equations (7.9 ± 0.4 cf. 9.2 ± 0.4 MJ, respectively). A most likely increase in TEE from Week 1 to 2 was observed (17.9 ± 2.1 cf. 24.2 ± 3.4 MJ) explained by a most likelyincrease in weekly sRPE (432 ± 19 cf. 555 ± 22 AU), respectively. The difference in TEE between forward and backs was unclear (21.6 ± 4.2 cf. 20.5 ± 4.9 MJ, respectively). We report greater TEE than previously reported in rugby that could be explained by the ability of DLW to account for all match and training-related activities that contributes to TEE.
Combination of Weight-Bearing Training and Anti-MSTN Polyclonal Antibody Improve Bone Quality In Rats
Authors: Tang Liang , Gao Xiaohang , Yang Xiaoying , Zhang Didi , Zhang Xiaojun , Du Haiping , Han Yanqi , Sun Lijun
Published: April 2016

Weight-bearing exercise is beneficial to bone health. Myostatin (MSTN) deficiency has a positive effect on bone formation. We wondered if a combination of weight-bearing training and polyclonal antibody for MSTN (MsAb) would augment bone formation to a greater degree than single treatment. In this study, rats were randomly assigned to four groups: Control, weight-bearing training (WT), MsAb, and WT+MsAb. The trained rats ran at 15 m/min bearing with 35% of their body weight, 40 min/day (2 min of running followed by 2 min of rest), 6 days/week, for 8 weeks. The rats with MsAb were injected once a week with MsAb for 8 weeks. MicroCT analysis showed that compared with the MsAb group, WT+MsAb significantly enhanced cortical bone mineral density (BMD) (p < .01), bone volume over total volume (BV/TV) (p < .01), trabecular thickness (p < .05), and reduced trabecular separation (Tb.Sp) (p < .01). Compared with the WT group, WT+MsAb significantly increased trabecular BMD (p < .05), BV/TV (p < .05), and decreased Tb.Sp (p < .05). Three-point bending test demonstrated that MsAb failed to improve bone biomechanical properties (p > .05), weight-bearing training significantly increased energy absorption (p < .05) and elastic modulus (p < .05). However, when they combined, biomechanical properties including maximum load (p < .05), stiffness (p < .05), elastic modulus (p < .01) and energy absorption (p < .01) were all significantly enhanced. In conclusion, the combination of weight-bearing training and MsAb have a greater positive effect on bone than treatment with either MsAb or weight-bearing training alone, suggesting that resistance training in combination with MSTN antagonists could be an effective approach for improving bone health and reducing osteoporosis risk.
Daily Distribution of Carbohydrate, Protein and Fat Intake in Elite Youth Academy Soccer Players Over a 7-Day Training Period
Authors: Naughton Robert J. , Drust Barry , O’Boyle Andy , Morgans Ryland , Abayomi Julie , Davies Ian G. , Morton James P. , Mahon Elizabeth
Published: April 2016

While traditional approaches to dietary analysis in athletes have focused on total daily energy and macronutrient intake, it is now thought that daily distribution of these parameters can also influence training adaptations. Using 7-day food diaries, we quantified the total daily macronutrient intake and distribution in elite youth soccer players from the English Premier League in U18 (n = 13), U15/16 (n = 25) and U13/14 squads (n = 21). Total energy (43.1 ± 10.3, 32.6 ± 7.9, 28.1 ± 6.8 kcal·kg-1·day-1), CHO (6 ± 1.2, 4.7 ± 1.4, 3.2 ± 1.3 g·kg- 1·day-1) and fat (1.3 ± 0.5, 0.9 ± 0.3, 0.9 ± 0.3 g·kg-1·day-1) intake exhibited hierarchical differences (p < .05) such that U13/14 > U15/16 > U18. In addition, CHO intake in U18s was lower (p < .05) at breakfast, dinner and snacks when compared with both squads but no differences were apparent at lunch. Furthermore, the U15/16s reported lower relative daily protein intake than the U13/14s and U18s (1.6 ± 0.3 vs. 2.2 ± 0.5, 2.0 ± 0.3 g·kg-1). A skewed distribution (p < .05) of daily protein intake was observed in all squads, with a hierarchical order of dinner (~0.6 g·kg-1) > lunch (~0.5 g·kg-1) > breakfast (~0.3 g·kg-1). We conclude elite youth soccer players do not meet current CHO guidelines. Although daily protein targets are achieved, we report a skewed daily distribution in all ages such that dinner > lunch > breakfast. Our data suggest that dietary advice for elite youth players should focus on both total daily macronutrient intake and optimal daily distribution patterns.
Case Study: Nutrition Planning and Intake for Marathon des Sables—A Series of Five Runners
Authors: McCubbin Alan J. , Cox Gregory R. , Broad Elizabeth M.
Published: April 2016

This case study describes the nutrition plans, intakes and experiences of five ultra-marathon runners who completed the Marathon des Sables in 2011 and 2013; age 37 (28–43) y, height 184 (180–190) cm, body mass 77.5 (71–85.5) kg, marathon personal best 3:08 (2:40–3:32). MdS is a 7-day, six-stage ultra-running stage race held in the Sahara Desert (total distance of timed stages 1–5 was 233.2 km in 2011, 223.4 km in 2013). Competitors are required to carry all equipment and food (except water) for the race duration, a minimum of 8,360 kJ/day and total pack weight of 6.5–15 kg. Total food mass carried was 4.2 (3.8–4.7) kg or 0.7 (0.5–1.1) kg/day. Planned energy (13,550 (10,323–18,142) kJ/day), protein (1.3 (0.8–1.8) g/kg/day), and carbohydrate (6.2 (4.3–9.2) g/kg/day) intakes on the fully self-sufficient days were slightly below guideline recommendations, due to the need to balance nutritional needs with food mass to be carried. Energy density was 1,636 (1,475–1,814) kJ/100g. 98.5% of the planned food was consumed. Fluid consumption was ad libitum with no symptoms or medical treatment required for dehydration or hyponatremia. During-stage carbohydrate intake was 42 (20–64) g/hour. Key issues encountered by runners included difficulty consuming foods due to dry mouth, and unpalatability of sweet foods (energy gels, sports drinks) when heated in the sun. Final classification of the runners ranged from 11th to 175th of 970 finishers in 2013, and 132nd of 805 in 2011. The described pattern of intake and macronutrient quantities were positively appraised by the five runners.
Achieving Expertise in Sport: Deliberate Practice, Adaptation, and Periodization of Training
Authors: Lidor Ronnie , Tenenbaum Gershon , Ziv Gal , Issurin Vladimir
Published: April 2016

Deliberate practice (DP), an activity aimed at enhancing an individual’s performance, has been reported to be crucial for achieving a state of expertise in various domains, such as education, music, and sport. In this article, the relationships between DP and the process of athletic performance adaptation are explored by elaborating on the main principle of the theory of training—periodization. We argue that periodization should be considered as a mechanism for ensuring DP, and that the implementation of periodization principles (cycles and phases) in DP activities can facilitate adaptation processes leading to expert performance. We describe the characteristics and features of DP, review a series of studies on DP and athletic performance (N = 21), discuss the importance of periodization in sport training, and outline a number of benefits of periodization. A model that emphasizes the link between periodization and DP activities in each phase of sport development is proposed, and a number of research approaches to address periodization are discussed.
Senior Games: Service-Learning With Older Adults in a Sport Setting
Authors: Martin Tiesha , Warner Stacy , Das Bhibha
Published: April 2016

Many higher education institutions incorporate service-learning programs because of the positive outcomes they produce for students. However, limited research has assessed the outcomes of service-learning for students working with older adults in a sport setting. Using a discourse analysis approach, this study examined the outcomes of volunteering with the Greenville-Pitt County Senior Games for 55 students enrolled in a physical activity and aging course. The results revealed that students’ perceptions about older adults’ Physical Abilities and Competitiveness and their view of Sport as a Social Event changed as a result of the service-learning experience. Students also cited Humanizing the Older Adult Experience and Learning by Doing as positive outcomes of the experience. The research findings suggest that service-learning with older adults in a sport setting can help better prepare students to serve the aging population. The implications and opportunities for Sport Management instructors are highlighted.
Laminopathies disrupt epigenomic developmental programs and cell fate
Authors: Perovanovic Jelena , Dell’Orso Stefania , Gnochi Viola F. , Jaiswal Jyoti K. , Sartorelli Vittorio , Vigouroux Corinne , Mamchaoui Kamel , Mouly Vincent , Bonne Gisèle , Hoffman Eric P.
Published: April 2016

Mutations in lamin A/C and emerin change myogenic cell fate by disrupting heterochromatin tethering to the nuclear envelope.
Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency
Authors: De Ravin Suk See , Wu Xiaolin , Moir Susan , Kardava Lela , Anaya-O’Brien Sandra , Kwatemaa Nana , Littel Patricia , Theobald Narda , Choi Uimook , Su Ling , Marquesen Martha , Hilligoss Dianne , Lee Janet , Buckner Clarissa M. , Zarember Kol A. , O’Connor Geraldine , McVicar Daniel , Kuhns Douglas , Throm Robert E. , Zhou Sheng , Notarangelo Luigi D. , Hanson I. Celine , Cowan Mort J. , Kang Elizabeth , Hadigan Coleen , Meagher Michael , Gray John T. , Sorrentino Brian P. , Malech Harry L.
Published: April 2016

Lentiviral gene therapy with conditioning achieves humoral reconstitution in older SCID-X1 patients.
Amelioration of sepsis by TIE2 activation–induced vascular protection
Authors: Han Sangyeul , Lee Seung-Jun , Kim Kyung Eun , Lee Hyo Seon , Oh Nuri , Park Inwon , Ko Eun , Oh Seung Ja , Lee Yoon-Sook , Kim David , Lee Seungjoo , Lee Dae Hyun , Lee Kwang-Hoon , Chae Su Young , Lee Jung-Hoon , Kim Su-Jin , Kim Hyung-Chan , Kim Seokkyun , Kim Sung Hyun , Kim Chungho , Nakaoka Yoshikazu , He Yulong , Augustin Hellmut G. , Hu Junhao , Song Paul H. , Kim Yong-In , Kim Pilhan , Kim Injune , Koh Gou Young
Published: April 2016

Vascular protection through TIE2 activation is a potential treatment strategy to ameliorate sepsis.
Chemical Genomics Identifies the PERK-Mediated Unfolded Protein Stress Response as a Cellular Target for Influenza Virus Inhibition
Authors: Landeras-Bueno Sara , Fernández Yolanda , Falcón Ana , Oliveros Juan Carlos , Ortín Juan
Published: April 2016

Influenza A viruses generate annual epidemics and occasional pandemics of respiratory disease with important consequences for human health and the economy. Therefore, a large effort has been devoted to the development of new anti-influenza virus drugs directed to viral targets, as well as to the identification of cellular targets amenable to anti-influenza virus therapy. Here we have addressed the identification of such potential cellular targets by screening collections of drugs approved for human use. We reasoned that screening with a green fluorescent protein-based recombinant replicon system would identify cellular targets involved in virus transcription/replication and/or gene expression and hence address an early stage of virus infection. By using such a strategy, we identified Montelukast (MK) as an inhibitor of virus multiplication. MK inhibited virus gene expression but did not alter viral RNA synthesisin vitroor viral RNA accumulationin vivo. The low selectivity index of MK prevented its use as an antiviral, but it was sufficient to identify a new cellular pathway suitable for anti-influenza virus intervention. By deep sequencing of RNA isolated from mock- and virus-infected human cells, treated with MK or left untreated, we showed that it stimulates the PERK-mediated unfolded protein stress response. The phosphorylation of PERK was partly inhibited in virus-infected cells but stimulated in MK-treated cells. Accordingly, pharmacological inhibition of PERK phosphorylation led to increased viral gene expression, while inhibition of PERK phosphatase reduced viral protein synthesis. These results suggest the PERK-mediated unfolded protein response as a potential cellular target to modulate influenza virus infection.

IMPORTANCEInfluenza A viruses are responsible for annual epidemics and occasional pandemics with important consequences for human health and the economy. The unfolded protein response is a defense mechanism fired by cells when the demand of protein synthesis and folding is excessive, for instance, during an acute virus infection. In this report, we show that influenza virus downregulates the unfolded protein response mediated by the PERK sensor, while Montelukast, a drug used to treat asthma in humans, specifically stimulated this response and downregulated viral protein synthesis and multiplication. Accordingly, we show that PERK phosphorylation was reduced in virus-infected cells and increased in cells treated with Montelukast. Hence, our studies suggest that modulation of the PERK-mediated unfolded protein response is a target for influenza virus inhibition.
Computational Analysis Reveals a Key Regulator of Cryptococcal Virulence and Determinant of Host Response
Authors: Gish Stacey R. , Maier Ezekiel J. , Haynes Brian C. , Santiago-Tirado Felipe H. , Srikanta Deepa L. , Ma Cynthia Z. , Li Lucy X. , Williams Matthew , Crouch Erika C. , Khader Shabaana A. , Brent Michael R. , Doering Tamara L.
Published: April 2016

Cryptococcus neoformans
is a ubiquitous, opportunistic fungal pathogen that kills over 600,000 people annually. Here, we report integrated computational and experimental investigations of the role and mechanisms of transcriptional regulation in cryptococcal infection. Major cryptococcal virulence traits include melanin production and the development of a large polysaccharide capsule upon host entry; shed capsule polysaccharides also impair host defenses. We found that both transcription and translation are required for capsule growth and that Usv101 is a master regulator of pathogenesis, regulating melanin production, capsule growth, and capsule shedding. It does this by directly regulating genes encoding glycoactive enzymes and genes encoding three other transcription factors that are essential for capsule growth:
GAT201
,
RIM101
, and
SP1
. Murine infection with cryptococci lacking Usv101 significantly alters the kinetics and pathogenesis of disease, with extended survival and, unexpectedly, death by pneumonia rather than meningitis. Our approaches and findings will inform studies of other pathogenic microbes.

IMPORTANCE
Cryptococcus neoformans
causes fatal meningitis in immunocompromised individuals, mainly HIV positive, killing over 600,000 each year. A unique feature of this yeast, which makes it particularly virulent, is its polysaccharide capsule; this structure impedes host efforts to combat infection. Capsule size and structure respond to environmental conditions, such as those encountered in an infected host. We have combined computational and experimental tools to elucidate capsule regulation, which we show primarily occurs at the transcriptional level. We also demonstrate that loss of a novel transcription factor alters virulence factor expression and host cell interactions, changing the lethal condition from meningitis to pneumonia with an exacerbated host response. We further demonstrate the relevant targets of regulation and kinetically map key regulatory and host interactions. Our work elucidates mechanisms of capsule regulation, provides methods and resources to the research community, and demonstrates an altered pathogenic outcome that resembles some human conditions.
Duplex DNA-Invading γ-Modified Peptide Nucleic Acids Enable Rapid Identification of Bloodstream Infections in Whole Blood
Authors: Nölling Jörk , Rapireddy Srinivas , Amburg Joel I. , Crawford Elizabeth M. , Prakash Ranjit A. , Rabson Arthur R. , Tang Yi-Wei , Singer Alon
Published: April 2016

Bloodstream infections are a leading cause of morbidity and mortality. Early and targeted antimicrobial intervention is lifesaving, yet current diagnostic approaches fail to provide actionable information within a clinically viable time frame due to their reliance on blood culturing. Here, we present a novel pathogen identification (PID) platform that features the use of duplex DNA-invading γ-modified peptide nucleic acids (γPNAs) for the rapid identification of bacterial and fungal pathogens directly from blood, without culturing. The PID platform provides species-level information in under 2.5 hours while reaching single-CFU-per-milliliter sensitivity across the entire 21-pathogen panel. The clinical utility of the PID platform was demonstrated through assessment of 61 clinical specimens, which showed >95% sensitivity and >90% overall correlation to blood culture findings. This rapid γPNA-based platform promises to improve patient care by enabling the administration of a targeted first-line antimicrobial intervention.

IMPORTANCE
Bloodstream infections continue to be a major cause of death for hospitalized patients, despite significant improvements in both the availability of treatment options as well their application. Since early and targeted antimicrobial intervention is one of the prime determinants of patient outcome, the rapid identification of the pathogen can be lifesaving. Unfortunately, current diagnostic approaches for identifying these infections all rely on time-consuming blood culture, which precludes immediate intervention with a targeted antimicrobial. To address this, we have developed and characterized a new and comprehensive methodology, from patient specimen to result, for the rapid identification of both bacterial and fungal pathogens without the need for culturing. We anticipate broad interest in our work, given the novelty of our technical approach combined with an immense unmet need.
Antimicrobial Resistance in Agriculture
Authors: Thanner Sophie , Drissner David , Walsh Fiona
Published: April 2016

In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans.
Imaging characteristics and findings in thyroglossal duct cyst cancer and concurrent thyroid cancer
Authors: Shemen Larry , Sherman Craig Harvey , Yurovitsky Alyssa
Published: April 2016

Thyroglossal duct cyst cancer is rare, while synchronous thyroglossal duct cyst cancer with thyroid cancer is still rarer. The radiographic features of this case are instructive and crucial when evaluating a thyroglossal duct cyst.
Aerobic exercise ameliorates cognitive function in older adults with mild cognitive impairment: a systematic review and meta-analysis of randomised controlled trials
Authors: Zheng Guohua , Xia Rui , Zhou Wenji , Tao Jing , Chen Lidian
Published: April 2016

Objective

To evaluate the effect of aerobic exercise on cognitive function in people with mild cognitive impairment (MCI).

Design

Systematic review and meta-analysis of aerobic exercise intervention for cognitive function in older adults with MCI.

Data sources

PubMed, EMBASE, SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang and Chinese Science and Technology Periodical (VIP) databases from their inception to 31 January 2015, the Cochrane Central Register of Controlled Trials (Cochrane Library, 2015, Issue 3) and the reference lists of all retrieved articles.

Eligibility criteria

Randomised controlled trials, older adults with MCI, aerobic exercises compared with no specific exercise intervention for global cognitive ability and any specific domains of cognition.

Data synthesis

Meta-analysis was conducted with RevMan V.5.3 software using the fixed-effect model for the available data without significant heterogeneity, or the random-effect model was used if appropriate.

Results

11 studies were identified involving 1497 participants. Meta-analysis showed that aerobic exercise significantly improved global cognitive ability (Mini-Mental State Examination (MMSE) scores: MD=0.98, 95% CI 0.5 to 1.45, p<0.0001; Montreal Cognitive Assessment (MoCA) scores: MD=2.7, 95% CI 1.11 to 4.29, p=0.0009); weakly, positively improve memory (immediately recall: SMD=0.29, 95% CI 0.13 to 0.46, p=0.0005; delay recall: SMD=0.22, 95% CI 0.09 to 0.34, p=0.0005). No significant improvement was found in other domains of cognition.

Conclusions

Aerobic exercise led to an improvement in global cognitive ability and had a positive effect with a small effect size on memory in people with MCI. However, owing to the limitations of the included studies, these findings should be interpreted cautiously.
Pleiotropic effects of sitagliptin versus voglibose in patients with type 2 diabetes inadequately controlled via diet and/or a single oral antihyperglycemic agent: a multicenter, randomized trial
Authors: Matsushima Yukiko , Takeshita Yumie , Kita Yuki , Otoda Toshiki , Kato Ken-ichiro , Toyama-Wakakuri Hitomi , Akahori Hiroshi , Shimizu Akiko , Hamaguchi Erika , Nishimura Yasuyuki , Kanamori Takehiro , Kaneko Shuichi , Takamura Toshinari
Published: April 2016

Purpose

A step-up strategy for diet therapy and/or single oral antihyperglycemic agent (OHA) regimens has not yet been established. The aim of this study was to evaluate hemoglobin A1c (HbA1c) as a primary end point, and the pleiotropic effects on metabolic and cardiovascular parameters as secondary end points, of sitagliptin versus voglibose in patients with type 2 diabetes with inadequate glycemic control while on diet therapy and/or treatment with a single OHA.

Methods

In this multicenter, randomized, open-label, parallel-group trial, a total of 260 patients with inadequately controlled type 2 diabetes (HbA1c levels >6.9%) were randomly assigned to receive either sitagliptin (50 mg, once daily) or voglibose (0.6 mg, thrice daily) for 12 weeks. The primary end point was HbA1c levels.

Results

Patients receiving sitagliptin showed a significantly greater decrease in HbA1c levels (−0.78±0.69%) compared with those receiving voglibose (−0.30±0.78%). Sitagliptin treatment also lowered serum alkaline phosphatase levels and increased serum creatinine, uric acid, cystatin-C and homeostasis model assessment-β values. Voglibose increased low-density lipoprotein-cholesterol levels and altered serum levels of several fatty acids, and increased Δ-5 desaturase activity. Both drugs increased serum adiponectin. The incidence of adverse events (AEs) was significantly lower in the sitagliptin group, due to the decreased incidence of gastrointestinal AEs.

Conclusions

Sitagliptin shows superior antihyperglycemic effects compared with voglibose as a first-line or second-line therapy. However, both agents possess unique pleiotropic effects that lead to reduced cardiovascular risk in Japanese people with type 2 diabetes.

Trial registration number

UMIN 000003503.
Bystander cricothyrotomy with ballpoint pen: a fresh cadaveric feasibility study
Authors: Kisser Ulrich , Braun Christian , Huber Astrid , Stelter Klaus
Published: April 2016

Objective

In motion pictures and anecdotal reports, ballpoint pens have been used for life-saving cricothyroidotomies. The objective of this study was to examine the widespread belief that ballpoint pens can perforate the skin and cricothyroid ligament and could be used as substitute tracheostomy sets in an emergency setting.

Methods

Three different ballpoint pens were examined regarding their inner diameter, their demountability to form a cannula and their airflow properties. Ten medical laypersons were asked to try to puncture the trachea through the skin and the cricothyroid ligament in 10 fresh cadavers just using the ballpoint pens.

Results

Two of three pens had inner diameters of >3 mm and were both suitable as cannulas in a tracheotomy. All participants could perforate the skin with both ballpoint pens. However, almost no one could penetrate through the cricothyroid ligament or the ventral wall of the trachea, except for one participant. He performed the tracheostomy after three attempts in >5 min with a lot of patience and force.

Conclusions

A cricothyroidotomy just with a ballpoint pen is virtually impossible. First, the airflow resistance in commercially available ballpoint pens is too high to produce effective ventilation. Second, the cricothyroid ligament is too strong to be penetrated by ballpoint pens.
EGFR mutation detection on routine cytological smears of non-small cell lung cancer by digital PCR: a validation study
Authors: Malapelle Umberto , de Luca Caterina , Vigliar Elena , Ambrosio Francesca , Rocco Danilo , Pisapia Pasquale , Bellevicine Claudio , Troncone Giancarlo
Published: April 2016

Highly sensitive genotyping techniques are useful to detect epidermal growth factor receptor (EGFR) mutations on lung cancer cytological samples, when these specimens feature only few neoplastic cells. This study aimed to validate digital PCR (dPCR) methodology on cytological material. In plasmid model system, dPCR allowed for the detection of a minimal percentage (1%) of EGFR mutant alleles. Cytological samples (n=30), with neoplastic cell percentage ranging from 10% to 80% and yielding a quantity of extracted DNA ranging from 1.75 to 60 ng/µL were selected. Results previously generated by fragment length and TaqMan assays (n=8 exon 19 deletions, n=2 L858R mutations and n=20 wild-type DNA) were compared with those obtained by dPCR. Data were highly concordant (96.6%). However, dPCR detected an additional L858R mutation that had been missed by TaqMan assay on a paucicellular smear. This mutation was confirmed by cloning PCR products and sequencing. Thus, dPCR can reliably be used to increase EGFR mutation detection rate on scarcely cellular lung cancer smears.
The association between visual impairment and the risk of mortality: a meta-analysis of prospective studies
Authors: Zhang Tong , Jiang Wenjie , Song Xinyuan , Zhang Dongfeng
Published: April 2016

Background

The findings from prospective studies on visual impairment (VI) and the risk of mortality are not consistent.

Objective

A meta-analysis of prospective studies was conducted to quantitatively summarise the evidence about the association between VI and the risk of mortality.

Methods

Pertinent studies were identified by a search of PubMed, Web of Science and the Chinese National Knowledge Infrastructure and Wanfang databases up to December 2015. The random-effect model was used to combine study-specific relative risks (RRs) and 95% CIs. Meta-regression and subgroup analysis were conducted to explore potential sources of heterogeneity. Publication bias was estimated by Egger's test and the funnel plot. Dose–response relationship was assessed by restricted cubic spline functions.

Results

This meta-analysis contained 29 prospective studies including 269 839 participants and 67 061 deaths. Compared to the no VI, the highest VI level was significantly associated with an increased risk of mortality (RR: 1.36, 95% CI 1.25 to 1.46). The association remained significant in participants older than 65 years (RR: 1.28, 95% CI 1.18 to 1.39), and a significant association was also observed in men (RR: 1.29, 95% CI 1.07 to 1.54) and women (RR: 1.39, 95% CI 1.14 to 1.70), respectively. For dose–response analysis, a linear relation was found between visual acuity (VA) and the risk of mortality. For every 0.1 Logarithm of the Minimum Angle of Resolution (LogMAR) increment, the risk of mortality increased by 4% (RR: 1.04, 95% CI 1.01 to 1.06).

Conclusions

VI was significantly associated with an increased risk of mortality.
Management and outcome of spontaneous cerebral venous sinus thrombosis in a 5-year consecutive single-institution cohort
Authors: Lee Darrin J , Ahmadpour Arjang , Binyamin Tamar , Dahlin Brian C , Shahlaie Kiarash , Waldau Ben
Published: April 2016

Background

Cerebral venous sinus thrombosis (CVST) is an uncommon form of stroke with a variable presentation, ranging from headaches, to coma and death. Although the American Stroke Association has developed guidelines for the treatment of CVST, data are sparse on the outcome after treatment with anticoagulation, thrombolysis, and thrombectomy.

Methods

In this retrospective review, we describe the 5-year UC Davis experience with spontaneous CVST.

Results

Forty-one patients (mean age 37.5±23.1, range 0–96 years; 29 female) were identified with CVST. The majority of cases involved the transverse sinus (75.6%), sigmoid sinus (58.5%), and superior sagittal sinus (29.3%). The most common form of treatment was anticoagulation or antiplatelet therapy (n=35), while six patients were managed by observation alone. The overall 1-year modified Rankin score (mRS) was 1.4±1.5. Male patients and patients with a poor admission mRS had a worse outcome. Outcome was unaffected by hypercoagulable state, number of dural sinuses involved, the presence of intracranial hemorrhage, or seizures. Two patients who underwent anticoagulation therapy also required endovascular thrombectomy; both patients had a 1-year mRS of ≤2. Two patients underwent direct open surgical canalization of the superior sagittal sinus with varying outcomes (mRS 2 vs mRS 6).

Conclusions

In our series, the majority (92.9%) of patients with spontaneous dural sinus thrombosis had a favorable clinical outcome as defined by a mRS ≤2. Further prospective studies are needed to study the impact of anticoagulation on the clinical course of the disease.
Cardiac rehabilitation using the Family-Centered Empowerment Model versus home-based cardiac rehabilitation in patients with myocardial infarction: a randomised controlled trial
Authors: Vahedian-Azimi Amir , Miller Andrew C , Hajiesmaieli Mohammadreza , Kangasniemi Mari , Alhani Fatemah , Jelvehmoghaddam Hosseinali , Fathi Mohammad , Farzanegan Behrooz , Ardehali Seyed H , Hatamian Sevak , Gahremani Mehdi , Mosavinasab Seyed M M , Rostami Zohreh , Madani Seyed J , Izadi Morteza
Published: April 2016

Objective

To determine if a hybrid cardiac rehabilitation (CR) programme using the Family-Centered Empowerment Model (FCEM) as compared with standard CR will improve patient quality of life, perceived stress and state anxiety of patients with myocardial infarction (MI).

Methods

We conducted a randomised controlled trial in which patients received either standard home CR or CR using the FCEM strategy. Patient empowerment was measured with FCEM questionnaires preintervention and postintervention for a total of 9 assessments. Quality of life, perceived stress, and state and trait anxiety were assessed using the 36-Item Short Form Health Survey (SF-36), the 14-item Perceived Stress, and the 20-item State and 20-item Trait Anxiety questionnaires, respectively.

Results

70 patients were randomised. Baseline characteristics were similar. Ejection fraction was significantly higher in the intervention group at measurements 2 (p=0.01) and 3 (p=0.001). Exercise tolerance measured as walking distance was significantly improved in the intervention group throughout the study. The quality of life results in the FCEM group showed significant improvement both within the group over time (p<0.0001) and when compared with control (p<0.0001). Similarly, the perceived stress and state anxiety results showed significant improvement both within the FCEM group over time (p<0.0001) and when compared with control (p<0.0001). No significant difference was found either within or between groups for trait anxiety.

Conclusions

The family-centred empowerment model may be an effective hybrid cardiac rehabilitation method for improving the physical and mental health of patients post-MI; however, further study is needed to validate these findings. Clinical Trials.gov identifierNCT02402582.

Trial registration number

NCT02402582.
Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration
Authors: Schiff Michael , Weinblatt Michael E , Valente Robert , Citera Gustavo , Maldonado Michael , Massarotti Elena , Yazici Yusuf , Fleischmann Roy
Published: April 2016

Objectives

To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial.

Methods

Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) ≤2.8, Simplified Disease Activity Index (SDAI) ≤3.3, Routine Assessment of Patient Index Data 3 (RAPID3) ≤3.0, Boolean score ≤1), low disease activity (CDAI <10, SDAI <11, RAPID3 ≤6.0), Health Assessment Questionnaire-Disability Index response and American College of Rheumatology responses were evaluated by baseline disease duration (≤6 vs >6 months). Disease Activity Score 28 (C-reactive protein) <2.6 or ≤3.2 and radiographic non-progression in patients achieving remission were also evaluated.

Results

A total of 646 patients were randomised and treated (abatacept, n=318; adalimumab, n=328). In both treatment groups, comparable responses were achieved in patients with early rheumatoid arthritis (≤6 months) and in those with later disease (>6 months) across multiple clinical measures.

Conclusions

Abatacept or adalimumab with background methotrexate were associated with similar onset and sustainability of response over 2 years. Patients treated early or later in the disease course achieved comparable clinical responses.

Trial registration number

NCT00929864, Post-results.
Gentiana lutea L. subsp. lutea seed germination: natural versus controlled conditions
Authors: Cuena-Lombraña Alba , Porceddu Marco , Dettori Caterina Angela , Bacchetta Gianluigi
Published: April 2016

Gentiana lutea L. subsp. lutea is a geophyte that occurs in the central-southern European mountains. We investigated its germination ecophysiology with the main aim of evaluating seed germination behaviour under controlled and natural conditions. Seeds from four natural sites were tested for germination requirements under a range of different temperatures, and by comparing the results with those obtained under both cold stratification at 5 °C and treatment with GA3. We simultaneously carried out germination tests at each collecting site, and soil temperatures were recorded. Our results indicate that germination under controlled conditions is limited by high temperatures (25 °C), below which GA3 has a remarkable effect on germination percentages. Cold stratification did not have an influence on the germination response, thus suggesting that a temperature of 5 °C is not sufficient to break seed dormancy; this result was supported by soil temperatures. Gentiana lutea created a short-term persistent seed bank, and seeds mainly germinated in their first year. The germination under controlled conditions was similar in all accessions, while different responses were found in the field, where a potential influence of the aspect was observed. These findings underscore the importance of understanding germination behaviour in the field to define the real thermal requirements of a taxon.
An unusual sponge – microbe – synsedimentary cement framework in a Late Ordovician reef, Southampton Island (Nunavut, Canada)
Authors: Castagner Ariane , Desrochers André , Lavoie Denis
Published: April 2016

A large, resistant buildup at the top of the Upper Ordovician (Hirnantian?) Red Head Rapids Formation on Southampton Island (Nunavut, Arctic Canada) is dominated by massive boundstone and cementstone facies. These massive facies have more in common with the sponge–microbial reefs that dominated worldwide in the Early Ordovician, including the following primary components: early calcified sponge material, microbial elements, and synsedimentary cement. A close spatial relationship between sponge and microbial framework elements suggests that a poorly preserved decaying sponge framework provided substrates for the attachment and development of microbes and that the microbes played essential roles as reef consolidators. Centimetre-scale colonial metazoans are present and locally intergrown with the sponge and microbial components. Other mound-dwelling invertebrates or calcareous algae are rare. Although altered now to calcite, cement fabrics suggest that aragonite was ubiquitous as seafloor precipitate. Prior to its subaerial exposure in the latest Ordovician, the Red Head Rapids Formation buildup developed on the margin of a shallow-marine evaporative epicratonic basin where a diverse community of reef-building metazoans was unable to flourish.