bluuebunny/crossref_metadata_2025 huggingface dataset:
Community Social Organization and Military Families: Theoretical Perspectives on Transitions, Contexts, and Resilience
Authors: Mancini Jay A. , O'Neal Catherine Walker , Martin James A. , Bowen Gary L.
Published: May 2018

The social organization theory of action and change accounts for transitions families face in community contexts. This perspective aligns with family stress and resilience theories, including the contextual model of family stress. Our discussion focuses on transitions of military families, including the continually changing nature of military family life. The military environment provides an opportunity for understanding family vulnerability and resilience from a community perspective, in effect, a perspective centered on contexts. Contexts include matters that families have control over and those they are unable to affect. The roles of shared responsibility and collective competence in moving families and communities forward are discussed, as are pivotal roles of informal networks and formal systems. Findings that align with this theorizing include influence of the military system and culture on families, as well as how sense of community emerges as a pivotal factor for family well‐being.
The Creation of Military Family Leisure Experiences
Authors: Melton Karen K. , Townsend Jasmine , Hodge Camilla J.
Published: May 2018

This article provides a theoretical model that positions family leisure experiences as a mechanism for positive family outcomes and resilience in military families. The article integrates the Creation of Family Experiences (CFE) framework with literature on military families, family leisure, and structured experiences. The CFE framework is a conceptual model that provides a lens for examining the context of family activities in order to better identify benefits for human development and family relations. When contextualized within military settings, the CFE can be used to understand and systematically optimize military family leisure experiences. It is critical to consider the experiences of military families (e.g., relocation, deployment, reunion) and how those experiences interact with family leisure experiences to produce resilient families. Future research and practice should consider this application of the CFE framework when seeking to explain, support, and program recreation‐based activities for military families.
Dematerialization and the Circular Economy: Comparing Strategies to Reduce Material Impacts of the Consumer Electronic Product Ecosystem
Authors: Kasulaitis Barbara V. , Babbitt Callie W. , Krock Andrew K.
Published: May 2018

The rapid technological evolution and adoption of consumer electronics highlights a growing need for adaptive methodologies to evaluate material consumption at the intersection of technological change and increasing consumption. While dematerialization and the circular economy (CE) have both been proposed to mitigate increasing material consumption, recent research has shown that these methods may be ineffective at achieving net material use reduction: When focused on specific products, these methods neglect the effects of complex interactions among and increasing consumption of consumer electronic products. The research presented here develops and applies a material flow analysis aimed at evaluating an entire “product ecosystem,” thereby including the effects of increasing consumption, product trade‐offs, and technological innovations. Results are then used to evaluate the potential efficacy of “natural” dematerialization (occurring as technology advances or smaller products substitute for larger ones) and CE (closing the loop between secondary material supply and primary material demand). Results show that material consumption by the ecosystem of electronics commonly used by U.S. households peaked in 2000. This consumption relies on increasingly diverse materials, including gold, cobalt, and indium, for whom secondary supply is still negligible, particularly given low recovery rates, often less than 1%. Potential circularity metrics of material “dilution,” “dispersion,” and “demand mismatch” are also evaluated, and indicate that CE approaches aimed at closing the loop on consumer electronic material still face several critical barriers particularly related to design and efficient recycling infrastructure.
Estimating Private Equity Returns from Limited Partner Cash Flows
Authors: ANG ANDREW , CHEN BINGXU , GOETZMANN WILLIAM N. , PHALIPPOU LUDOVIC
Published: May 2018

We introduce a methodology to estimate the historical time series of returns to investment in private equity funds. The approach requires only an unbalanced panel of cash contributions and distributions accruing to limited partners and is robust to sparse data. We decompose private equity returns from 1994 to 2015 into a component due to traded factors and a time‐varying private equity premium not spanned by publicly traded factors. We find cyclicality in private equity returns that differs according to fund type and is consistent with the conjecture that capital market segmentation contributes to private equity returns.
The role of different visual characters of weevils signalling aposematism to sympatric lizard predators
Authors: Lee C.‐Y. , Yo S.‐P. , Clark R. W. , Hsu J.‐Y. , Liao C.‐P. , Tseng H.‐Y. , Huang W.‐S.
Published: May 2018

Prey often use conspicuous or aposematic coloration to advertise their unprofitability to potential predators. Although most research focuses on coloration, other characteristics, such as the shape or size of markings, or general body shape and appearance, can be used by predators to recognize unprofitable prey. These more general characters may be especially important in cases where predators are sympatric with radiations of aposematic species or populations that have variable colours or patterns; predators are likely to learn avoidance using traits that are consistent across these species, rather than learning multiple types of patterns separately. Here, we conducted a series of feeding experiments using unprofitable weevils (Pachyrhynchus tobafolius) with bright blue spots as prey, and sympatric insectivorous lizards (Japalura swinhonis) as predators. We modified the number, size, shape and colour of spots of weevils, as well as their general appearance, to test which characters are important for aposematism. Unchanged weevils were attacked infrequently, and altering the presence, colour or size of spots did not change lizard behaviour. However, prey with manipulated body appearance were attacked more often, and more quickly. Our study suggests that the general appearance and characteristic shape of weevils are more important for aposematism towards lizards than the brightly coloured spots. Our results may explain why the colour, stripes and spot patterns are so variable among sympatric weevils in a particular habitat.
Metabolic disorders across hepatocellular carcinoma in Italy
Authors: Morisco Filomena , Guarino Maria , Valvano Maria R. , Auriemma Francesco , Farinati Fabio , Giannini Edoardo G. , Ciccarese Francesca , Tovoli Francesco , Rapaccini Gian Ludovico , Di Marco Maria , Caturelli Eugenio , Zoli Marco , Borzio Franco , Sacco Rodolfo , Cabibbo Giuseppe , Felder Martina , Benvengù Luisa , Gasbarrini Antonio , Svegliati Baroni Gianluca , Foschi Francesco G. , Biasini Elisabetta , Masotto Alberto , Virdone Roberto , Marra Fabio , Caporaso Nicola , Trevisani Franco ,   the Italian Liver Cancer (ITA.LI.CA) group
Published: May 2018

Background

Metabolic disorders are well‐known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology.

Methods

We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0‐1, 2 and 3‐5 metabolic features.

Results

As compared with patients with 0‐1 metabolic features, patients with 3‐5 features showed lower percentage of HCC diagnosis on surveillance (P = .021), larger tumours (P = .038), better liver function (higher percentage of Child‐Pugh class A [P = .007] and MELD < 10 [P = .003]), higher percentage of metastasis (P = .024) and lower percentage of portal vein thrombosis (P = .010). The BCLC stage and treatment options were similar among the 3 groups, with the exception of a less frequent access to loco‐regional therapies for BCLC stage B patients with 3‐5 features (P = .012). Overall survival and survival according to BCLC stage and/or treatment did not significantly differ among the 3 groups. Only using a probabilistic sensitivity analysis, diabetic patients showed a lower survival (P = .046). MELD score, HCC morphology, nodule size, BCLC stage, portal vein thrombosis and metastasis were independent predictors of lead‐time adjusted survival.

Conclusions

Our “real world” study suggests that metabolic disorders shape the clinical presentation of HCC but do not seem to play a major role in setting patient survival.
Focus group discussions of registered nurses’ perceptions of challenges in the medication administration process
Authors: Härkänen Marja , Blignaut Alwiena , Vehviläinen‐Julkunen Katri
Published: May 2018

Medication administration (MA) holds a great threat to patient safety, as MA errors remain a global problem. Nurses are key role players in the MA process and can give valuable information from the grassroots level. The aim of the present study was to describe registered nurses’ perceptions related to challenges in the MA process. Focus group interviews with registered nurses (n = 20) in two central hospitals in Finland were conducted in 2015. Inductive content analysis was performed. Nurses described multiple challenges during MA, which made the process demanding. These were organized under five themes: (i) medications; (ii) collaboration between health‐care professionals; (iii) resources and work environment; (iv) skills and education; and (v) patient‐related factors. The MA process is prone to errors, and registered nurses described many challenges related to MA. While nurses are responsible for their various work‐related tasks and the maintenance of patient safety through applicable procedures and effective collaboration, health systems and hospital management should be stewards of patient safety by ensuring adequate staffing levels and providing educational resources related to the MA process.
Morphologic mimicry: acantholytic squamous cell carcinoma in nondermal locations—a literature review
Authors: Mohammad Mustafa , Wilcox Rebecca
Published: May 2018

Acantholytic squamous cell carcinoma (acantholytic SCC) is a variant of SCC in which acantholysis develops owing to the loss of desmosomal adhesion proteins. This loss of cell–cell adhesion leads to morphologic changes that have the potential to mimic other tumor types, such as angiosarcoma or signet ring cell adenocarcinoma. Acantholytic SCC characteristically occurs in sun‐exposed skin of elderly patients; however, it can occur in nondermal locations. We present a review of the literature describing cases of nondermal acantholytic SCC.
Can you make my goals easier to achieve? Effects of partner instrumentality on goal pursuit and relationship satisfaction
Authors: Cappuzzello Angela C. , Gere Judith
Published: May 2018

Goal pursuits are strongly influenced by romantic partners, and a partner's instrumentality to goals may be particularly important for goal pursuit. This study examined the effects of partner instrumentality on goal‐related effort, goal progress, goal commitment, and relationship satisfaction over time. It also examined whether relationship satisfaction moderated the effects of partner instrumentality on goal pursuit processes. Newly dating romantic partners (N = 59 couples) reported on their goals and relationship satisfaction at two assessments 3 months apart. Multilevel models indicated that partner instrumentality predicted increases in progress over time but only for those high in relationship satisfaction. Partner instrumentality also predicted increases in one's own relationship satisfaction but was unrelated to changes in the partner's satisfaction. These findings suggest that partner instrumentality benefits increased goal progress, particularly for those with satisfying relationships, and further increases relationship satisfaction.
Leaf anatomy does not explain apparent short‐term responses of mesophyll conductance to light and CO2 in tobacco
Authors: Carriquí Marc , Douthe Cyril , Molins Arántzazu , Flexas Jaume
Published: May 2018

Mesophyll conductance to CO2 (gm), a key photosynthetic trait, is strongly constrained by leaf anatomy. Leaf anatomical parameters such as cell wall thickness and chloroplast area exposed to the mesophyll intercellular airspace have been demonstrated to determine gm in species with diverging phylogeny, leaf structure and ontogeny. However, the potential implication of leaf anatomy, especially chloroplast movement, on the short‐term response of gm to rapid changes (i.e. seconds to minutes) under different environmental conditions (CO2, light or temperature) has not been examined. The aim of this study was to determine whether the observed rapid variations of gm in response to variations of light and CO2 could be explained by changes in any leaf anatomical arrangements. When compared to high light and ambient CO2, the values of gm estimated by chlorophyll fluorescence decreased under high CO2 and increased at low CO2, while it decreased with decreasing light. Nevertheless, no changes in anatomical parameters, including chloroplast distribution, were found. Hence, the gm estimated by analytical models based on anatomical parameters was constant under varying light and CO2. Considering this discrepancy between anatomy and chlorophyll fluorescence estimates, it is concluded that apparent fast gm variations should be due to artefacts in its estimation and/or to changes in the biochemical components acting on diffusional properties of the leaf (e.g. aquaporins and carbonic anhydrase).
Enigmatic clastic pipe swarms and implications for fluidization dynamics in aeolian deposits
Authors: Chan Marjorie A. , Hasiotis Stephen T. , Parrish Judith T.
Published: May 2018

Soft‐sediment deformation of contorted and massive sandstone is common throughout much of the siliciclastic record, but clastic pipes represent a distinctive class of pressurized synsedimentary features. Remarkable centimetre to metre‐scale clastic pipe exposures in the Jurassic Navajo Sandstone of Utah (USA) establish a range of pipe sizes, expressions and relationships to the host rock in an erg margin setting, traditionally thought to be just a dry desert system. In particular, the field and laboratory characterizations of cylindrical pipes show internal concentric, annular rings that imply water fluidization, with alignment of long grain axes due to shear flow along pipe margins. Central interior parts of decimetre‐scale pipes appear massive in plan view, but display weakly developed pseudobedding from post‐pressure release, gravitational settling in the cross‐sectional view. Deformation features of conjugate fractures, ring faults, hypotrochoid patterns (geometric arcs and circles) and breccia in the host material reflect both brittle and ductile behaviour in response to the fluidization and injection of the clastic pipes. The stratigraphic context of individual pipes and the stratabound intervals of pipe features imply dynamic deformation nearly coincident with deposition in this Early Jurassic aeolian system related to multiple factors of groundwater expulsion, timing and local host sediment properties that influenced pipe development. Although the pipe features might be easily overlooked as a smaller scale feature of soft‐sediment deformation in dune deposits, these are valuable environmental indications of disrupted fluid pathways within porous, reservoir quality sands, associated with possible combinations of periodic springs, high water‐table conditions and strong ground‐motion events. These pipe examples may be important analogues where exposures are not so clear, with applications to diverse modern and ancient clastic settings internationally on Earth as well as in planetary explorations such as on Mars.
Emotions and Nationalism: Armenian Genocide as a Case Study
Authors: Adar Sinem
Published: May 2018

Until recently, sociologists have paid surprisingly little attention to the relationship between emotions and nationalism. Existing accounts remain homogeneous, linear and nonrelational. To remedy this gap, this article compares public controversies in Turkey over the Armenian genocide at two historical moments: its semi‐centennial anniversary in 1965, and the publication of an article in 2004 by the Armenian‐Turkish journalist Hrant Dink that led to his assassination in 2007. It demonstrates that the genocide, and the conflicting epistemic structures that it incites, is a source of anxiety for Armenians due to their actual displacement within the nation. It is also a source of anxiety for Turks due to the perceived threat of displacement within the nation. These relational anxieties over the nation played an important role, during these two events, in reproducing hierarchical and exclusionary configurations, experiences, and representations of nationhood. During the 1965 semi‐centennial, Armenians reacted to the mainstream Turkish public's anxieties by pledging their loyalty to the state. Dink's assassination in 2007, on the other hand, showcases how an attempt by the excluded to redefine the what and who of the nation united otherwise separate social sections around a nationalist front.
HLA‐B*15:436, a novel variant of HLA‐B*15, discovered in a Taiwanese individual
Authors: Yang K. L. , Lin P. Y.
Published: May 2018

Nucleotide substitutions in codons 43 and 45 of HLA‐B*15:18:01:01 result in a new allele, HLA‐B*15:436.
Evaluation of the functional properties of cryopreserved buffy coat–derived monocytes for monocyte monolayer assay
Authors: Kipkeu Betty J. , Shyian Melissa L. , da Silveira Cavalcante Luciana , Duong Trang T. , Yeung Rae S.M. , Binnington Beth , Branch Donald R. , Acker Jason P. , Holovati Jelena L.
Published: May 2018

BACKGROUND

Monocyte monolayer assay (MMA) is a compatibility testing method for evaluating the clinical significance of red blood cell (RBC) alloantibodies. Time‐consuming monocyte isolation procedures and requirement for fresh monocytes have limited application of the MMA. The aim of this study was to develop and assess the utility and efficacy of cryopreserved buffy coat (BC)‐derived monocytes for MMA application.

STUDY DESIGN AND METHODS

Peripheral blood mononuclear cells (PBMNCs) were isolated from BC or peripheral blood (PB) and pooled and BC PBMNCs were cryopreserved. Monocytes from pooled PBMNCs were incubated with anti‐D–sensitized, anti‐Scianna2 (Sc2)–sensitized, anti‐AnWj–sensitized, or anti‐Jra–sensitized RBCs or lipopolysaccharide (LPS). MMA phagocytic index (PI) and membrane integrity were determined microscopically, and cytokine release was measured by Luminex technology.

RESULTS

PBMNC isolation rates from fresh BC and PB were not comparable (67.4 ± 6.3 and 75.8 ± 7.7% respectively, p = 0.024). There was no significant difference in PBMNC membrane integrity (fresh PB, 100%; fresh BC, 100%; cryopreserved BC, 95.2 ± 1.2%), postwash recovery (fresh PB, 85.9 ± 3.1; fresh BC, 86.9 ± 6.7; cryopreserved BC, 84.8 ± 5.1), or monocyte PI (fresh PB, 82 ± 10; fresh BC, 77 ± 11; cryopreserved BC = 80 ± 6). Monocytes from pooled cryopreserved BC PBMNCs reacted with RBCs sensitized with anti‐D and RBC alloantibodies, including anti‐Sc2, anti‐Jra, and anti‐AnWj.

CONCLUSIONS

Monocytes from pooled cryopreserved BC PBMNCs can be used reliably to evaluate phagocytic responses of sensitized RBCs and to assess clinical significance of RBC alloantibodies.
Rho kinase collaborates with p21‐activated kinase to regulate actin polymerization and contraction in airway smooth muscle
Authors: Zhang Wenwu , Bhetwal Bhupal P. , Gunst Susan J.
Published: May 2018

Key points

The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F‐actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction.

Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation.

We find that ROCK regulates airway smooth muscle contraction by activating the serine–threonine kinase Pak, which mediates the activation of Cdc42 and neuronal Wiskott–Aldrich syndrome protein (N‐WASp). N‐WASP transmits signals from Cdc42 to the Arp2/3 complex for the nucleation of actin filaments.

These results demonstrate a novel molecular function for ROCK in the regulation of Pak and Cdc42 activation that is critical for the processes of actin polymerization and contractility in airway smooth muscle.

Rho kinase (ROCK), a RhoA GTPase effector, can regulate the contraction of airway and other smooth muscle tissues. In some tissues, ROCK can inhibit myosin regulatory light chain (RLC) phosphatase, which increases the phosphorylation of myosin RLC and promotes smooth muscle contraction. ROCK can also regulate cell motility and migration by affecting F‐actin dynamics. Actin polymerization is stimulated by contractile agonists in airway smooth muscle tissues and is required for contractile tension development in addition to myosin RLC phosphorylation. We investigated the mechanisms by which ROCK regulates the contractility of tracheal smooth muscle tissues by expressing a kinase‐inactive mutant of ROCK, ROCK‐K121G, in the tissues or by treating them with the ROCK inhibitor H‐1152P. Our results show no role for ROCK in the regulation of non‐muscle or smooth muscle myosin RLC phosphorylation during contractile stimulation in this tissue. We found that ROCK regulates airway smooth muscle contraction by mediating activation of p21‐activated kinase (Pak), a serine–threonine kinase, to promote actin polymerization. Pak catalyses paxillin phosphorylation on Ser273 and coupling of the GIT1–βPIX–Pak signalling module to paxillin, which activates the guanine nucleotide exchange factor (GEF) activity of βPIX towards Cdc42. Cdc42 is required for the activation of neuronal Wiskott–Aldrich syndrome protein (N‐WASp), which transmits signals from Cdc42 to the Arp2/3 complex for the nucleation of actin filaments. Our results demonstrate a novel molecular function for ROCK in the regulation of Pak and Cdc42 activation that is critical for the processes of actin polymerization and contractility in airway smooth muscle.
Preterm growth restriction and bronchopulmonary dysplasia: the vascular hypothesis and related physiology
Authors: Sehgal Arvind , Gwini Stella M. , Menahem Samuel , Allison Beth J. , Miller Suzanne L. , Polglase Graeme R.
Published: May 2018

Key points

Approximately 5–10% pregnancies are affected by fetal growth restriction.

Preterm infants affected by fetal growth restriction have a higher incidence of bronchopulmonary dysplasia.

The present study is the first to measure pulmonary artery thickness and stiffness.

The findings show that impaired vasculogenesis may be a contributory factor in the higher incidence of bronchopulmonary dysplasia in preterm growth restricted infants.

The study addresses the mechanistic link between fetal programming and vascular architecture and mechanics.

Bronchopulmonary dysplasia is the most common respiratory sequelae of prematurity and histopathologically features fewer, dysmorphic pulmonary arteries. The present study aimed to characterize pulmonary artery mechanics and cardiac function in preterm infants with fetal growth restriction (FGR) compared to those appropriate for gestational age (AGA) in the early neonatal period. This prospective study reviewed 40 preterm infants between 28 to 32 weeks gestational age (GA). Twenty infants had a birthweight <10th centile and were compared with 20 preterm AGA infants. A single high resolution echocardiogram was performed to measure right pulmonary arterial and right ventricular (RV) indices. The GA and birthweight of FGR and AGA infants were 29.8 ± 1.3 vs. 30 ± 0.9 weeks (P = 0.78) and 923.4 g ± 168 vs. 1403 g ± 237 (P < 0.001), respectively. Assessments were made at 10.5 ± 1.3 days after birth. The FGR infants had significantly thicker right pulmonary artery inferior wall (843.5 ± 68 vs. 761 ± 40 μm, P < 0.001) with reduced pulsatility (51.6 ± 7.6 μm vs. 59.7 ± 7.5 μm, P = 0.001). The RV contractility [fractional area change (28.7 ± 3.8% vs 32.5 ± 3.1%, P = 0.001), tricuspid annular peak systolic excursion (TAPSE) (5.2 ± 0.3% vs. 5.9 ± 0.7%, P = 0.0002) and myocardial performance index (0.35 ± 0.03 vs. 0.28 ± 0.02, P < 0.001)] was significantly impaired in FGR infants. Significant correlation between RV longitudinal contractility (TAPSE) and time to peak velocity/RV ejection time (measure of RV afterload) was noted (r2 = 0.5, P < 0.001). Altered pulmonary vascular mechanics and cardiac performance reflect maladaptive changes in response to utero‐placental insufficiency. Whether managing pulmonary vascular disease will alter clinical outcomes remains to be studied prospectively.
Effect of Prior Fatiguing Sport-Specific Exercise on Field Hockey Passing Ability
Authors: Hollville Enzo , Le Croller Vincent , Hirasawa Yoshihiro , Husson Rémi , Rabita Giuseppe , Brocherie Franck
Published: May 2018

Purpose: To evaluate the effect of multiple sets of repeated-sprint-ability (RSA)-induced fatigue on subsequent passing-skill performance in field hockey players. Methods: A total of 10 elite U-21 (under-21) male field hockey players performed 5 sets of a combination of RSA test (6 × 20 m, 20 s of passive recovery) followed by a 1-min passing-skill test (passing reception with subsequent passes at a predesigned target). Data on fastest sprint time and cumulated sprint time for RSA test; total number of balls played, targeted, and passing accuracy (number of balls targeted/total number of balls played) for passing-skill test; heart rate (HR), blood lactate concentration (BLa), and rating of perceived exertion (RPE)  were collected throughout the protocol. Results: RSA performance was significantly impaired from set 1 to set 5 (fastest sprint time +4.1%, P < .001; cumulated sprint time +2.3%, P < .01). For a similar average number of balls played (12.8 [1.4]) during each set, number of balls targeted (−1.7%, P < .05) and passing accuracy (−3.1%, P < .05) decreased up to the third set before reimproving over the last 2 sets. Psychophysiological responses (HR, BLa, and RPE) progressively increased (P < .05) toward protocol cessation. The decrease in passing accuracy with increasing RSA cumulated sprint time was fitted to a 2nd-order polynomial function (r2 = .94, P < .05). Conclusion: Multiple-set RSA-induced fatigue was accompanied by passing-skill adjustment variation, suggesting a complex interaction between physiological and psychological/cognitive function to preserve passing skill under fatigued condition.
Dose–Response Relationship Between Training Load and Changes in Aerobic Fitness in Professional Youth Soccer Players
Authors: Fitzpatrick John F. , Hicks Kirsty M. , Hayes Philip R.
Published: May 2018

Purpose: To compare the dose–response relationship between traditional arbitrary speed thresholds versus an individualized approach, with changes in aerobic fitness in professional youth soccer players. Methods: A total of 14 youth soccer players completed a 1500-m time trial to estimate maximal aerobic speed (MAS, km·h−1) at the start and at the end of a 6-week period. Training load was monitored on a daily basis during this study. External load measures were total distance covered and total acceleration and deceleration distance >2 m·s−2. Arbitrary high-speed running measures were meters covered and time spent at >17 km·h−1 (m > high-speed distance, t > high-speed distance) and 21 km·h−1 (m > very-high-speed distance, t > very-high-speed distance). Individualized high-speed running measures were meters covered and time spent at >MAS km·h−1 (m > MAS, t > MAS) and 30% anaerobic speed reserve (m > 30ASR, t > 30ASR). In addition, internal load measures were also collected: heart rate exertion and rating of perceived exertion. Linear regression analysis was used to establish the dose–response relationship between mean weekly training load and changes in aerobic fitness. Results: Very large associations were found between t > MAS and changes in aerobic fitness (R2 = .59). Large associations were found for t > 30ASR (R2 = .38) and m > MAS (R2 = .25). Unclear associations were found for all other variables. Conclusion: An individualized approach to monitoring training load, in particular t > MAS, may be a more appropriate method than using traditional arbitrary speed thresholds when monitoring the dose–response relationship between training load and changes in aerobic fitness.
Identifying and Quantifying the Unintended Variability in Common Systematic Observation Instruments to Measure Youth Physical Activity
Authors: Weaver Robert G. , Beighle Aaron , Erwin Heather , Whitfield Michelle , Beets Michael W. , Hardin James W.
Published: May 2018

Background: Direct observation protocols may introduce variability in physical activity estimates. Methods: Thirty-five physical education lessons were video recorded and coded using the System for Observing Fitness Instruction Time (SOFIT). A multistep process examined variability in moderate to vigorous physical activity (MVPA%; walking + vigorous/total scans). Initially, per-SOFIT protocol MVPA% (MVPA%SOFIT) estimates were produced for each lesson. Second, true MVPA% (mean MVPA% of all students using all observations, MVPA%true) estimates were calculated. Third, MVPA% (MVPA%perm) was calculated based on all permutations of students and observation order. Fourth, physical education lessons were divided into 2 groups with 5 lessons from each group randomly selected 10,000 times. Group MVPA%perm differences between the 10 selected lessons were compared with the MVPA%true difference between group 1 and group 2. Results: Across all lessons, 10,212,600 permutations were possible (average 291,789 combinations per lesson; range = 73,440–570,024). Across lessons, the average absolute difference between MVPA%true and MVPA%SOFIT estimates was ±4.8% (range = 0.1%–17.5%). Permutations, based on students selected and observation order, indicated that the mean range of MVPA%perm estimates was 41.6% within a lesson (range = 29.8%–55.9%). Differences in MVPA% estimates between the randomly selected groups of lessons varied by 32.0%. Conclusion: MVPA% estimates from focal child observation should be interpreted with caution.
Hungarian science troubled by nationalism
Authors: Karáth Kata
Published: May 2018

Government standoff with Central European University is coming to a head.
Finding the first horse tamers
Authors: Price Michael
Published: May 2018

Genes suggest that Central Asian hunter-gatherers, not famed Yamnaya herders, first domesticated horses.
A new cancer immunotherapy suffers a setback
Authors: Garber Ken
Published: May 2018

An exciting drug failed in a large trial, triggering a retreat and raising questions about the field's frantic pace.
Small but mighty
Authors: Leslie Mitch
Published: May 2018

Miniature antibodies discovered in sharks and camels are a boon for research and perhaps medicine.
An anatomic transcriptional atlas of human glioblastoma
Authors: Puchalski Ralph B. , Shah Nameeta , Miller Jeremy , Dalley Rachel , Nomura Steve R. , Yoon Jae-Guen , Smith Kimberly A. , Lankerovich Michael , Bertagnolli Darren , Bickley Kris , Boe Andrew F. , Brouner Krissy , Butler Stephanie , Caldejon Shiella , Chapin Mike , Datta Suvro , Dee Nick , Desta Tsega , Dolbeare Tim , Dotson Nadezhda , Ebbert Amanda , Feng David , Feng Xu , Fisher Michael , Gee Garrett , Goldy Jeff , Gourley Lindsey , Gregor Benjamin W. , Gu Guangyu , Hejazinia Nika , Hohmann John , Hothi Parvinder , Howard Robert , Joines Kevin , Kriedberg Ali , Kuan Leonard , Lau Chris , Lee Felix , Lee Hwahyung , Lemon Tracy , Long Fuhui , Mastan Naveed , Mott Erika , Murthy Chantal , Ngo Kiet , Olson Eric , Reding Melissa , Riley Zack , Rosen David , Sandman David , Shapovalova Nadiya , Slaughterbeck Clifford R. , Sodt Andrew , Stockdale Graham , Szafer Aaron , Wakeman Wayne , Wohnoutka Paul E. , White Steven J. , Marsh Don , Rostomily Robert C. , Ng Lydia , Dang Chinh , Jones Allan , Keogh Bart , Gittleman Haley R. , Barnholtz-Sloan Jill S. , Cimino Patrick J. , Uppin Megha S. , Keene C. Dirk , Farrokhi Farrokh R. , Lathia Justin D. , Berens Michael E. , Iavarone Antonio , Bernard Amy , Lein Ed , Phillips John W. , Rostad Steven W. , Cobbs Charles , Hawrylycz Michael J. , Foltz Greg D.
Published: May 2018

Anatomically correct tumor genomics

Glioblastoma is the most lethal form of human brain cancer. The genomic alterations and gene expression profiles characterizing this tumor type have been widely studied. Puchalski
et al.
created the Ivy Glioblastoma Atlas, a freely available online resource for the research community. The atlas, a collaborative effort between bioinformaticians and pathologists, maps molecular features of glioblastomas, such as transcriptional signatures, to histologically defined anatomical regions of the tumors. The relationships identified in this atlas, in conjunction with associated databases of clinical and genomic information, could provide new insights into the pathogenesis, diagnosis, and treatment of glioblastoma.

Science
, this issue p.
660
Fish reproductive-energy output increases disproportionately with body size
Authors: Barneche Diego R. , Robertson D. Ross , White Craig R. , Marshall Dustin J.
Published: May 2018

Big mamas matter for fish

The theoretical relationship between reproduction and body size has assumed that total mass relates directly to fecundity, regardless of the number of individuals involved. This assumption leads to fisheries management practices that suggest that one large female fish can be replaced by several smaller females. However, this assumption is incorrect. Barnecheet al.show that larger females are far more productive than the same weight's worth of smaller females. Management practices that ignore the value of large females could contribute to unexplained declines seen in some fish stocks.

Science, this issue p.642
A proposed global metric to aid mercury pollution policy
Authors: Selin Noelle E.
Published: May 2018

The Minamata Convention needs policy-relevant insight
The hidden biodiversity of amphibian pathogens
Authors: Lips Karen
Published: May 2018

Discovery of additional amphibian chytrid pathogens increases conservation concerns
Metabolite regulates differentiation
Authors: Trefely Sophie , Wellen Kathryn E.
Published: May 2018

Compartmentalized NAD
+
metabolism regulates transcription to control adipogenesis
In Vitro
Activity of Clofazimine against Nontuberculous Mycobacteria Isolated in Beijing, China
Authors: Luo Jingjing , Yu Xia , Jiang Guanglu , Fu Yuhong , Huo Fengmin , Ma Yifeng , Wang Fen , Shang Yuanyuan , Liang Qian , Xue Yi , Huang Hairong
Published: May 2018

Due to the natural resistance of nontuberculous mycobacteria (NTM) to many antibiotics, the treatment of diseases caused by NTM is often long-term but unsuccessful. The main goal of this study was to evaluate the
in vitro
susceptibilities to clofazimine of 209 isolates consisting of different NTM species isolated in Beijing, China. Furthermore, 47 reference strains were also tested, including 30 rapidly growing mycobacterium (RGM) species and 17 slowly growing mycobacterium (SGM) species. The potential molecular mechanism contributing to clofazimine resistance of NTM was investigated as well. Clofazimine exhibited excellent activity against both reference strains and clinical isolates of different SGM species, and most of the strains had MICs far below 1 μg/ml. Although the majority of the clinical isolates of
Mycobacterium abscessus
and
Mycobacterium fortuitum
had MICs higher than 2 μg/ml, 17 out of the 30 reference strains of different RGM species had MICs below 1 μg/ml
in vitro
. According to the MIC distributions, the tentative epidemiological cutoff (ECOFF) values for
Mycobacterium kansasii
,
Mycobacterium avium
, and
Mycobacterium intracellulare
were defined at 0.5 μg/ml, 1 μg/ml, and 2 μg/ml, respectively. Intriguingly, single-direction cross-resistance between bedaquiline- and clofazimine (Cfz)-resistant isolates was observed among the tested NTM species. This study demonstrates that clofazimine had strong activity against most SGM species
in vitro
, as well as some RGM species. The data provide important insights into the possible clinical application of Cfz to treat NTM infections.
In Vitro
Activity of Imipenem-Relebactam against Clinical Isolates of Gram-Negative Bacilli Isolated in Hospital Laboratories in the United States as Part of the SMART 2016 Program
Authors: Karlowsky James A. , Lob Sibylle H. , Kazmierczak Krystyna M. , Young Katherine , Motyl Mary R. , Sahm Daniel F.
Published: May 2018

Relebactam is a non-β-lactam, bicyclic diazabicyclooctane β-lactamase inhibitor of class A and class C β-lactamases, including
Klebsiella pneumoniae
carbapenemases (KPCs). It is in phase 3 clinical development in combination with imipenem/cilastatin. The
in vitro
activities of imipenem-relebactam, imipenem, and comparators were determined using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method for isolates of
Enterobacteriaceae
(
n
= 3,419) and
Pseudomonas aeruginosa
(
n
= 896) collected in 2016 by 21 U.S. hospital laboratories participating in the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Relebactam was tested at a fixed concentration of 4 μg/ml. Imipenem-relebactam MICs were interpreted using CLSI breakpoints for imipenem. Rates of susceptibility to imipenem-relebactam and imipenem for non-
Proteeae
Enterobacteriaceae
(
n
= 3,143) and
P. aeruginosa
were 99.1% (3,115/3,143) and 95.9% (3,013/3,143) and were 94.4% (846/896) and 74.7% (669/896), respectively. Relebactam restored imipenem susceptibility to 78.5% (102/130) of imipenem-nonsusceptible non-
Proteeae
Enterobacteriaceae
and to 78.0% (177/227) of imipenem-nonsusceptible
P. aeruginosa
isolates. Susceptibility to imipenem-relebactam was 98.2% (444/452) and 82.2% (217/264) for multidrug-resistant (MDR) non-
Proteeae
Enterobacteriaceae
and MDR
P. aeruginosa
, respectively. Given the ability of relebactam to restore susceptibility to imipenem in nonsusceptible isolates of both non-
Proteeae
Enterobacteriaceae
and
P. aeruginosa
and to demonstrate potent activity against current MDR isolates of both non-
Proteeae
Enterobacteriaceae
and
P. aeruginosa
, further development of imipenem-relebactam appears warranted.
Efficacy, Biodistribution, and Nephrotoxicity of Experimental Amphotericin B-Deoxycholate Formulations for Pulmonary Aspergillosis
Authors: López-Sánchez Alicia , Pérez-Cantero Alba , Torrado-Salmerón Carlos , Martin-Vicente Adela , García-Herrero Víctor , González-Nicolás María Ángeles , Lázaro Alberto , Tejedor Alberto , Torrado-Santiago Santiago , García-Rodríguez Juan José , Capilla Javier , Torrado Susana
Published: May 2018

An experimental micellar formulation of 1:1.5 amphotericin B-sodium deoxycholate (AMB:DCH 1:1.5) was obtained and characterized to determine its aggregation state and particle size. The biodistribution, nephrotoxicity, and efficacy against pulmonary aspergillosis in a murine model were studied and compared to the liposomal commercial formulation of amphotericin B after intravenous administration. The administration of 5 mg/kg AMB:DCH 1:1.5 presented 2.8-fold-higher lung concentrations (18.125 ± 3.985 μg/g after 6 daily doses) and lower kidney exposure (0.391 ± 0.167 μg/g) than liposomal commercial amphotericin B (6.567 ± 1.536 and 5.374 ± 1.157 μg/g in lungs and kidneys, respectively). The different biodistribution of AMB:DCH micelle systems compared to liposomal commercial amphotericin B was attributed to their different morphologies and particle sizes. The efficacy study has shown that both drugs administered at 5 mg/kg produced similar survival percentages and reductions of fungal burden. A slightly lower nephrotoxicity, associated with amphotericin B, was observed with AMB:DCH 1:1.5 than the one induced by the liposomal commercial formulation. However, AMB:DCH 1:1.5 reached higher AMB concentrations in lungs, which could represent a therapeutic advantage over liposomal commercial amphotericin B-based treatment of pulmonary aspergillosis. These results are encouraging to explore the usefulness of AMB:DCH 1:1.5 against this disease.
Nitric Oxide-Releasing Macromolecule Exhibits Broad-Spectrum Antifungal Activity and Utility as a Topical Treatment for Superficial Fungal Infections
Authors: Stasko Nathan , McHale Kimberly , Hollenbach Stanley J. , Martin Megan , Doxey Ryan
Published: May 2018

Cutaneous and superficial fungal infections affecting the skin, nails, and hair of humans are caused primarily by dermatophytes of the genera
Trichophyton
and
Epidermophyton
or by yeasts of the genera
Candida
and
Malassezia.
Onychomycosis is a common fungal infection of the nail that frequently coexists with tinea pedis, the most prevalent mycotic skin infection. Efficacy rates for current topical onychomycosis therapies are hampered by low drug penetration across the nail plate, which is theoretically obviated with nitric oxide (NO)-based topical therapies. The Nitricil technology platform is comprised of polysiloxane-based macromolecules that stably release therapeutic levels of NO. In the reported studies, NVN1000, the lead candidate of the platform, was assessed for its spectrum of
in vitro
activity against a broad range of filamentous fungi and yeast species commonly associated with cutaneous fungal infections. Time-kill assays demonstrated that NVN1000 exhibited fungicidal activity as early as 4 h. Additionally, the penetration of several unique NVN1000 NO-releasing drug product formulations (gel, cream, and lacquer) was evaluated following a single topical application in an
in vitro
infected human nail assay, with all formulations showing similar inhibition of fungal growth. Repeated topical application in this model demonstrated that a lower-strength dose of NO could achieve the same efficacy as a higher-strength dose after 7 days. Together, these
in vitro
results demonstrate that NO-releasing treatments rapidly penetrate the nail plate and eradicate the fungal infection, representing promising novel topical therapies for the treatment of onychomycosis and other cutaneous fungal infections.
Microbial Mineralization of Montmorillonite in Low-Permeability Oil Reservoirs for Microbial Enhanced Oil Recovery
Authors: Cui Kai , Sun Shanshan , Xiao Meng , Liu Tongjing , Xu Quanshu , Dong Honghong , Wang Di , Gong Yejing , Sha Te , Hou Jirui , Zhang Zhongzhi , Fu Pengcheng
Published: May 2018

Microbial mineralization is ubiquitous in the natural environment. Microbes in low-permeability reservoirs are able to facilitate alteration of the structure and phase of the Fe-poor minerals by reducing Fe(III) and inhibiting clay swelling, which is still poorly studied. This study aimed to reveal the interaction mechanism between Fe(III)-reducing bacterial strains and Ca-montmorillonite under anaerobic conditions and to investigate the extent and rates of Fe(III) reduction and phase changes with their activities. Application of Fe(III)-reducing bacteria will provide a new way to inhibit clay swelling, to elevate reservoir permeability, and to reduce pore throat resistance after water flooding for enhanced oil recovery in low-permeability reservoirs.
Differential Production of Psl in Planktonic Cells Leads to Two Distinctive Attachment Phenotypes in Pseudomonas aeruginosa
Authors: Yang Shuai , Cheng Xinyi , Jin Zhenyu , Xia Aiguo , Ni Lei , Zhang Rongrong , Jin Fan
Published: May 2018

The attachment of planktonic cells to surfaces is the first and most crucial step in biofilm formation. In this paper, we show that planktonic cells ofPseudomonas aeruginosadifferently attach to surfaces. Typically, in the later exponential phase, approximately 80% of the cells can quickly attach to surfaces within 15 min, whereas approximately 20% of the cells slowly attach to surfaces, which greatly affects the initial stage of biofilm formation in the presence of flows. This is because fast-attaching cells are more likely to attach on surfaces to form microcolonies, whereas slow-attaching cells are more likely to remain in the mobile phase. This scenario is different from the previous understanding of biofilm formation in the initial stage, in which planktonic cells were thought to uniformly attach to surfaces. Most notably, the results of this study show that the different attachment manner of planktonic cells to surfaces affects the subsequent stages of biofilm formation. This research highlights that the phenotypic variations in planktonic cells plays significant roles in various stages of biofilm formation.
Equine Myxovirus Resistance Protein 2 Restricts Lentiviral Replication by Blocking Nuclear Uptake of Capsid Protein
Authors: Ji Shuang , Na Lei , Ren Huiling , Wang Yujie , Wang Xiaojun
Published: May 2018

Previous research has shown that the antiviral ability of Mx2s is confined to primates, particularly humans. EIAV has been shown to be insensitive to restriction by human MxB. Here, we describe the function of equine Mx2. This protein plays an important role in the suppression of EIAV, HIV-1, and SIVs. The antiviral activity of eqMx2 depends on its subcellular location as well as its capsid binding capacity. Our results showed that following viral infection, eqMx2 changes its original cytoplasmic location and accumulates at the nuclear envelope, where it binds to the viral capsid and blocks the nuclear entry of reverse-transcribed proviral DNAs. In contrast, huMxB does not bind to the EIAV capsid and shows no EIAV restriction effect. These studies expand our understanding of the function of the equine Mx2 protein.
Five Residues in the Apical Loop of the Respiratory Syncytial Virus Fusion Protein F
2
Subunit Are Critical for Its Fusion Activity
Authors: Hicks Stephanie N. , Chaiwatpongsakorn Supranee , Costello Heather M. , McLellan Jason S. , Ray William , Peeples Mark E.
Published: May 2018

RSV infects virtually every child by the age of 3 years, causing nearly 33 million acute lower respiratory tract infections (ALRI) worldwide each year in children younger than 5 years of age (H. Nair et al., Lancet 375:1545–1555, 2010). RSV is also the second leading cause of respiratory system-related death in the elderly (A. R. Falsey and E. E. Walsh, Drugs Aging 22:577–587, 2005; A. R. Falsey, P. A. Hennessey, M. A. Formica, C. Cox, and E. E. Walsh, N Engl J Med 352:1749–1759, 2005). The monoclonal antibody palivizumab is approved for prophylactic use in some at-risk infants, but healthy infants remain unprotected. Furthermore, its expense limits its use primarily to developed countries. No vaccine or effective small-molecule drug is approved for preventing disease or treating infection (H. M. Costello, W. Ray, S. Chaiwatpongsakorn, and M. E. Peeples, Infect Disord Drug Targets, 12:110–128, 2012). The essential residues identified in the apical domain of F
2
are adjacent to the apical portion of F
1
, which, upon triggering, refolds into a long heptad repeat A (HRA) structure with the fusion peptide at its N terminus. These essential residues in F
2
are likely involved in triggering and/or refolding of the F protein and, as such, may be ideal targets for antiviral drug development.