bluuebunny/crossref_metadata_2025 huggingface dataset:
Video intervention changes parent perception of all-terrain vehicle (ATV) safety for children
Authors: House Taylor , Schwebel David C , Mullins Samantha H , Sutton Andrea J , Swearingen Christopher J , Bai Shasha , Aitken Mary E
Published: February 2016

Background

Children aged <16 years account for 25% of deaths on all-terrain vehicles (ATVs), despite public health and industry warning against paediatric use. Parents often underestimate instability and other risks associated with ATVs.

Objective

To determine if a brief intervention consisting of validated computer simulations of ATV performance with a child driver changes attitudes, beliefs and planned safety behaviours of parents of children who ride ATVs.

Design/methods

Participants were parents of children presenting to a children's hospital emergency department. All participants had children who had ridden an ATV in the past year. Subjects viewed a video simulation of ATVs in scenarios featuring 6-year-old and 10-year-old biofidelic anthropomorphic test devices. Parents completed a survey both before and after viewing the video to report attitudes/beliefs on ATV safety for children, use of safety equipment and family ATV use, as well as risk and safety perception.

Results

Surveys were collected from 99 parents, mostly mothers (79%), Caucasian (61%) and had high school education or less (64%). The intervention shifted parents’ belief in overall ATV safety (48% unsafe pre-intervention, 73% unsafe post-intervention, p<0.001). After viewing the video simulation, parents were almost six times more likely to perceive ATVs as unsafe (OR 5.96, 95% CI 2.32 to 15.31, p<0.001) and many parents (71%) planned to change family ATV safety rules.

Conclusion

Video simulations of ATV performance with child riders changed short-term risk perception and planned safety behaviours of parents whose children ride ATVs. Similar educational interventions hold promise for larger-scale studies in at-risk populations.
Gross examination and reporting of soft tissue tumours: evaluation of compliance with the UK Royal College of Pathologists soft tissue sarcoma dataset
Authors: Shah Chirag , Wang Jayson , Mubako Taka , Fisher Cyril , Thway Khin
Published: February 2016

Aims

Soft tissue tumours are a heterogeneous group of neoplasms that can arise at almost every anatomical site. As they often show similar clinical and radiological findings, histology is the definitive diagnostic method and it is crucial that the surgical pathology report contains accurate, useful information for management and prognostication. The soft tissue sarcoma minimum dataset produced by the Royal College of Pathologists in the UK outlines a structure for handling and reporting soft tissue tumours, including the core data required, and aiding pathologists in forming a consistent reporting approach.

Methods

We assessed the information in surgical pathology reports for soft tissue lesions at a tertiary soft tissue centre, in 1 year prior to the development of this dataset, and 1 year after its release, to audit the comparative adequacy of macroscopic and microscopic information provided, and to assess for differences in reporting since the advent of routine ancillary molecular diagnostic testing.

Results and conclusions

We found that while essential information was always included in reports, more specific details contributing to better quality reports such as more detailed macroscopic descriptions and a higher proportion of clinical summaries with radiological correlation were included in 2011 than 2006, despite increasing workload. Specimen handling, particularly of core biopsies, was also improved, reflecting the increasing need to conserve the maximum amount of patient material for molecular investigations.
Stress-coping skills and neuroticism in apical ballooning syndrome (Takotsubo/stress cardiomyopathy)
Authors: Scantlebury Dawn C , Rohe Daniel E , Best Patricia J M , Lennon Ryan J , Lerman Amir , Prasad Abhiram
Published: February 2016

Introduction

Apical ballooning syndrome (ABS) is typically associated with an antecedent stressful situation. Affected patients have been reported to have higher frequencies of premorbid affective disorders. We hypothesised that patients with ABS would have elevated levels of neuroticism (tendency to experience negative affect) and greater vulnerability to stress.

Methods

In this cross-sectional study, all active participants in the Mayo Clinic ABS prospective follow-up registry were invited to complete the third edition of the NEO Personality Inventory (NEO-PI-3). The NEO-PI-3 is the universally accepted measure of the ‘Five-Factor Model’ of personality. Inventory responses were scored using the NEO-PI-3 computer program and the data were compared with US normative sample used in standardisation of the inventory. Significance was set at 0.0014 to account for multiple comparisons.

Results

Of 106 registry participants approached, 53 completed the inventory. There was no difference in age, gender, time from ABS diagnosis, type of antecedent stressor (emotional, physical or none) or severity of initial illness between the responders and non-responders. Responders had mean Neuroticism T-scores of 48.0±10.6 (95% CI 45.1 to 50.9); p=0.18, when compared with the normal mean of 50. There was also no significant difference in the facet scale of Vulnerability: 46.9±8.4 (44.6 to 49.2), p=0.038, at α=0.0014.

Conclusions

Contrary to our hypothesis, patients with ABS do not manifest higher levels of neuroticism and do not have greater vulnerability to stress than the general population. These findings have implications for the clinicians’ perception of, and approach to, patients with ABS.
Does the timing of cardiac rehabilitation impact fitness outcomes? An observational analysis
Authors: Fell Jennifer , Dale Veronica , Doherty Patrick
Published: February 2016

Objectives

To ascertain the characteristics associated with delayed cardiac rehabilitation (CR) and determine if an association between CR timing and fitness outcomes exists in patients receiving routine care.

Methods

The study used data from the UK National Audit of Cardiac Rehabilitation, a data set which captures information on routine CR practice and patient outcomes. Data from 1 January 2012 to 8 September 2015 were included. Logistic regression models were used to explore the relationship between timing of CR and fitness-related outcomes as measured by patient-reported exercise level (150 min/week: yes/no), Dartmouth quality of life physical fitness scale and the incremental shuttle-walk test.

Results

Based on UK data current CR practice shows that programmes do not always adhere to recommendations on the start of prompt CR, that is, start CR within 28 days of referral (42 days for coronary artery bypass graft (CABG)). Wait time exceeded recommendations in postmyocardial infarction (post-MI), elective percutaneous coronary intervention (PCI), MI-PCI and post-CABG surgery patients. This was particularly pronounced in the medically managed post-MI group, median wait time 40 days. Furthermore, statistical analysis revealed that delayed CR significantly impacts fitness outcomes. For every 1-day increase in CR wait time, patients were 1% less likely to improve across all fitness-related measures (p<0.05).

Conclusions

With the potential for suboptimal patient outcome if starting CR is delayed, efforts should be made to identify and overcome barriers to timely CR provision.
Protein “requirements” beyond the RDA: implications for optimizing health
Authors: Phillips Stuart M. , Chevalier Stéphanie , Leidy Heather J.
Published: February 2016

Substantial evidence supports the increased consumption of high-quality protein to achieve optimal health outcomes. A growing body of research indicates that protein intakes well above the current Recommended Dietary Allowance help to promote healthy aging, appetite regulation, weight management, and goals aligned with athletic performance. Higher protein intakes may help prevent age-related sarcopenia, the loss of muscle mass, and strength that predisposes older adults to frailty, disability, and loss of autonomy. Higher protein diets also improve satiety and lead to greater reductions in body weight and fat mass compared with standard protein diets, and may therefore serve as a successful strategy to help prevent and/or treat obesity. Athletes can also benefit from higher protein intakes to maximize athletic performance given the critical role protein plays in stimulating muscle protein remodelling after exercise. Protein quality, per meal dose, and timing of ingestion are also important considerations. Despite persistent beliefs to the contrary, we can find no evidence-based link between higher protein diets and renal disease or adverse bone health. This brief synopsis highlights recent learnings based on presentations at the 2015 Canadian Nutrition Society conference, Advances in Protein Nutrition across the Lifespan. Current evidence indicates intakes in the range of at least 1.2 to 1.6 g/(kg·day) of high-quality protein is a more ideal target for achieving optimal health outcomes in adults.
Ionomycin induces prostaglandin E2formation in murine osteoblastic MC3T3-E1 cells via mechanisms independent of its ionophoric nature
Authors: Leis Hans Jörg , Windischhofer Werner
Published: February 2016

Ionomycin and A23187 are divalent cation ionophores with a marked preference for calcium. Studies using these ionophores have almost exclusively interpreted their results in the light of calcium elevation. It was the aim of this study to investigate the effects of ionomycin in osteoblatic MC3T3-E1 cells that are not attributable to its ionophoric properties. Thus, we have found that in contrast to A23187, ionomycin shows similar effects on prostaglandin E2formation as bradykinin and endothelin-1, being potentiated by extracellular nickel and inhibited by cholera toxin and pertussis toxin. Our data strongly suggest that inomycin, at least in part, exerts its effects via specific binding to a G-protein coupled receptor, thereby evoking downstream cellular events like arachidonate release with subsequent prostaglandin formation.
Molecular insights into the lichen genusAlectoria(Parmeliaceae) in North America
Authors: McMullin Richard Troy , Lendemer James C. , Braid Heather E. , Newmaster Steven G.
Published: February 2016

Alectoria is a genus of fruticose lichen characterised by the presence of usnic acid and conspicuous raised pseudocyphellae. This genus is particularly diverse and abundant in montane, boreal, and Arctic regions of North America. Because intermediate forms have been reported for several species of Alectoria on the continent, it has been suggested that these species were initially delimited based on the extremes of morphological gradients. Here, we use the results of molecular phylogenetic analyses of two nuclear genes, ITS and Mcm7, with 48 representatives of 9 taxa to examine the delineation of 5 taxa that have been previously shown to be related to, or confused with, A. sarmentosa: A. fallacina, A. imshaugii, A. sarmentosa var. sorediosa, A. sarmentosa subsp. vexillifera, and A. vancouverensis. Alectoria fallacina was found to be well-supported and distantly related to A. sarmentosa. Conversely, the other four taxa were recovered as a single monophyletic group with little internal structure, which did not support the presently defined morphological species. A provisional taxonomic treatment is proposed pending more detailed study at the population level. Alectoria sarmentosa var. sorediosa is recognized at the species level, which necessitates the new combination: A. sorediosa. An updated key to the North American species of Alectoria is also provided.
A eukaryote assemblage intercalated with Marinoan glacial deposits in South Australia
Authors: Le Heron D. P. , Alderton D. H. M. , Collinson M. E. , Grassineau N. , Sykes D. , Trundley A. E.
Published: February 2016

Composite hematite–silica structures recovered from a siltstone bed in the Elatina Formation of South Australia include (1) sub-circular to whorl-shaped forms, (2) elongate to half-moon-shaped forms and (3) and lozenge-shaped forms locally linked into chains. They range from 200 to 500 µm in diameter and are interpreted as eukaryote tests. Evidence for internal etching of a calcite core of some tests indicates that at least some of the hematite–silica fabrics were acquired through replacement. Carbon isotope values of −20‰ δ
13
C are suggestive of precipitation by microbial activity, and imply a change in ambient fluid chemistry associated with a pH reduction. The tests occur within sandstone beds that were deposited on a tidally modulated braidplain during the Marinoan glaciation at the end of the Cryogenian. The quartz grains in the sandstone sample lack the typical textures (surface striae, internal fractures or irregular grain boundaries) expected for glacially transported material. Thus, on textural grounds we argue that the eukaryote tests represent a proglacial ecosystem during a late Cryogenian snowball Earth event.

Supplementary material:
Video files of digital X-ray tomographs (μCT) in the longitudinal and transverse planes are available at:
https://doi.org/10.6084/m9.figshare.c.2209723
.
Widening of normal fault zones due to the inhibition of vertical propagation
Authors: Roche V. , Homberg C. , van der Baan M. , Rocher M.
Published: February 2016

In this paper, we document the early stage of fault-zone development based on detailed observations of mesocale faults in layered rocks. The vertical propagation of the studied faults is stopped by layer-parallel faults contained in a weak layer. This restriction involves a flat-topped throw profile along the fault plane and modifications of the fault structures near the restricted tips, with geometries ranging from planar structures to fault zones characterized by abundant parallel fault segments. The ‘far-field’ displacement (i.e. the sum of the displacement accumulated by all the fault segments and the folding) measured along the restricted faults exhibiting this segmentation may have flat-topped shapes or triangular shapes when fault-related folding is observed above the layer-parallel faults. We develop a model from the observations. In this model, during the course of restriction, a fault forms as a simple isolated planar structure, then parallel fault segments successively initiate to accommodate the increasing displacement. We assume that, eventually, the fault propagates beyond the layer-parallel fault. This model implies first that fault widening is controlled by the fault capacity to propagate vertically in the layered section. Likewise, owing to restriction, fault growth occurs with non-linear increases in maximum displacement, length and thickness.
Hypoxia-induced cardiac injury in dystrophic mice
Authors: Stelter Zachary , Strakova Jana , Yellamilli Amritha , Fischer Kaleb , Sharpe Katharine , Townsend DeWayne
Published: February 2016

Duchenne muscular dystrophy (DMD) is a disease of progressive destruction of striated muscle, resulting in muscle weakness with progressive respiratory and cardiac failure. Respiratory and cardiac disease are the leading causes of death in DMD patients. Previous studies have suggested an important link between cardiac dysfunction and hypoxia in the dystrophic heart; these studies aim to understand the mechanism underlying this connection. Here we demonstrate that anesthetized dystrophic mice display significant mortality following acute exposure to hypoxia. This increased mortality is associated with a significant metabolic acidosis, despite having significantly higher levels of arterial Po2. Chronic hypoxia does not result in mortality, but rather is characterized by marked cardiac fibrosis. Studies in isolated hearts reveal that the contractile function of dystrophic hearts is highly susceptible to short bouts of ischemia, but these hearts tolerate prolonged acidosis better than wild-type hearts, indicating an increased sensitivity of the dystrophic heart to hypoxia. Dystrophic hearts display decreased cardiac efficiency and oxygen extraction. Isolated dystrophic cardiomyocytes and hearts have normal levels of FCCP-induced oxygen consumption, and mitochondrial morphology and content are normal in the dystrophic heart. These studies demonstrate reductions in cardiac efficiency and oxygen extraction of the dystrophic heart. The underlying cause of this reduced oxygen extraction is not clear; however, the current studies suggest that large disruptions of mitochondrial respiratory function or coronary flow regulation are not responsible. This finding is significant, as hypoxia is a common and largely preventable component of DMD that may contribute to the progression of the cardiac disease in DMD patients.
Fractal analysis of alveolarization in hyperoxia-induced rat models of bronchopulmonary dysplasia
Authors: Porzionato Andrea , Guidolin Diego , Macchi Veronica , Sarasin Gloria , Grisafi Davide , Tortorella Cinzia , Dedja Arben , Zaramella Patrizia , De Caro Raffaele
Published: February 2016

No papers are available about potentiality of fractal analysis in quantitative assessment of alveolarization in bronchopulmonary dysplasia (BPD). Thus, we here performed a comparative analysis between fractal [fractal dimension ( D) and lacunarity] and stereological [mean linear intercept ( Lm), total volume of alveolar air spaces, total number of alveoli, mean alveolar volume, total volume and surface area of alveolar septa, and mean alveolar septal thickness] parameters in experimental hyperoxia-induced models of BPD. At birth, rats were distributed between the following groups: 1) rats raised in ambient air for 2 wk; 2) rats exposed to 60% oxygen for 2 wk; 3) rats raised in normoxia for 6 wk; and 4) rats exposed to 60% hyperoxia for 2 wk and to room air for further 4 wk. Normoxic 6-wk rats showed increased D and decreased lacunarity with respect to normoxic 2-wk rats, together with changes in all stereological parameters except for mean alveolar volume. Hyperoxia-exposed 2-wk rats showed significant changes only in total number of alveoli, mean alveolar volume, and lacunarity with respect to equal-in-age normoxic rats. In the comparison between 6-wk rats, the hyperoxia-exposed group showed decreased D and increased lacunarity, together with changes in all stereological parameters except for septal thickness. Analysis of receiver operating characteristic curves showed a comparable discriminatory power of D, lacunarity, and total number of alveoli; Lmand mean alveolar volume were less discriminative. D and lacunarity did not show significant changes when different segmentation thresholds were applied, suggesting that the fractal approach may be fit to automatic image analysis.
MicroRNA expression profiling in skeletal muscle reveals different regulatory patterns in high and low responders to resistance training
Authors: Ogasawara Riki , Akimoto Takayuki , Umeno Tokushi , Sawada Shuji , Hamaoka Takafumi , Fujita Satoshi
Published: February 2016

Large variability exists in muscle adaptive response to resistance exercise (RE) training between individuals. Recent studies have revealed a significant role for microRNAs (miRNAs) in skeletal muscle plasticity. In this study, we investigated how RE affects miRNA expression and whether the variability of muscle hypertrophy to RE training may be attributed to differential miRNA regulation in the skeletal muscle. To screen high and low responders to RE, we had 18 young men perform arm curl exercise training. After screening, all the men performed 12 wk of lower body RE training, but only the high or low responders participated in the acute RE test before training. Muscle biopsies were obtained from the vastus lateralis muscle at baseline, 3 h after acute RE, and after the training period. Total RNA was extracted from the skeletal muscle, and miRNA expression (800 miRNAs) was analyzed. RE training increased the cross-sectional area of the biceps brachii (−1.7–26.1%), quadriceps (2.2–16.8%), and hamstrings (1.6–18.4%). Eighty-five and 102 miRNAs were differentially expressed after acute and chronic RE, respectively ( P < 0.05). Seventeen miRNAs, especially 23b-3p, 26a-5p, 32-5p, 148b-3p, and 376a-3p, were differentially expressed at baseline, and 23 miRNAs, especially let-7a-5p, 95, 148a-3p, and 376a-3p, and 26 miRNAs, especially 30d-5p and 376a-3p, were differentially regulated after acute and chronic RE, respectively, in the skeletal muscle between high and low responders, indicating that the expression patterns of several miRNAs are altered by acute or chronic RE, and that miRNAs are involved in skeletal muscle adaptation to RE training.
Efficient DS-UWB MUD Algorithm Using Code Mapping and RVM
Authors: Shi Pingyan , Liu Xiaohui , Tao Xiaofeng , Ji Jianchao
Published: February 2016

A hybrid multiuser detection (MUD) using code mapping and a wrong code recognition based on relevance vector machine (RVM) for direct sequence ultra wide band (DS-UWB) system is developed to cope with the multiple access interference (MAI) and the computational efficiency. A new MAI suppression mechanism is studied in the following steps: firstly, code mapping, an optimal decision function, is constructed and the output candidate code of the matched filter is mapped to a feature space by the function. In the feature space, simulation results show that the error codes caused by MAI and the single user mapped codes can be classified by a threshold which is related to SNR of the receiver. Then, on the base of code mapping, use RVM to distinguish the wrong codes from the right ones and finally correct them. Compared with the traditional MUD approaches, the proposed method can considerably improve the bit error ratio (BER) performance due to its special MAI suppression mechanism. Simulation results also show that the proposed method can approximately achieve the BER performance of optimal multiuser detection (OMD) and the computational complexity approximately equals the matched filter. Moreover, the proposed method is less sensitive to the number of users.
Factor‐Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors
Authors: Hermann Andreas , Kim Jeong Beom , Srimasorn Sumitra , Zaehres Holm , Reinhardt Peter , Schöler Hans R. , Storch Alexander
Published: February 2016

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of the transcription factors OCT4, SOX2, KLF4, and c‐Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk of chromosomal disruption and to simplify reprogramming, several studies demonstrated that a reduced set of reprogramming factors is sufficient to generate iPSC. We recently showed that a reduction of reprogramming factors in murine cells not only reduces reprogramming efficiency but also may worsen subsequent differentiation. To prove whether this is also true for human cells, we compared the efficiency of neuronal differentiation of iPSC generated from fetal human neural stem cells with either one (OCT4; hiPSC1F-NSC) or two (OCT4, KLF4; hiPSC2F-NSC) reprogramming factors with iPSC produced from human fibroblasts using three (hiPSC3F-FIB) or four reprogramming factors (hiPSC4F-FIB). After four weeks of coculture with PA6 stromal cells, neuronal differentiation of hiPSC1F-NSC and hiPSC2F-NSC was as efficient as iPSC3F-FIB or iPSC4F-FIB. We conclude that a reduction of reprogramming factors in human cells does reduce reprogramming efficiency but does not alter subsequent differentiation into neural lineages. This is of importance for the development of future application of iPSC in cell replacement therapies.
Blindfolded Balance Training in Patients with Parkinson’s Disease: A Sensory-Motor Strategy to Improve the Gait
Authors: Tramontano M. , Bonnì S. , Martino Cinnera A. , Marchetti F. , Caltagirone C. , Koch G. , Peppe A.
Published: February 2016

Aim. Recent evidence suggested that the use of treadmill training may improve gait parameters. Visual deprivation could engage alternative sensory strategies to control dynamic equilibrium and stabilize gait based on vestibulospinal reflexes (VSR). We aimed to investigate the efficacy of a blindfolded balance training (BBT) in the improvement of stride phase percentage reliable gait parameters in patients with Parkinson’s Disease (PD) compared to patients treated with standard physical therapy (PT).Methods. Thirty PD patients were randomized in two groups of 15 patients, one group treated with BBT during two weeks and another group treated with standard PT during eight weeks. We evaluated gait parameters before and after BBT and PT interventions, in terms of double stance, swing, and stance phase percentage.Results. BBT induced an improvement of double stance phase as revealed (decreased percentage of double stance phase during the gait cycle) in comparison to PT. The other gait parameters swing and stance phase did not differ between the two groups.Discussion. These results support the introduction of complementary rehabilitative strategies based on sensory-motor stimulation in the traditional PD patient’s rehabilitation. Further studies are needed to investigate the neurophysiological circuits and mechanism underlying clinical and motor modifications.
Liquid Chromatography with Electrospray Ionization and Tandem Mass Spectrometry Applied in the Quantitative Analysis of Chitin-Derived Glucosamine for a Rapid Estimation of Fungal Biomass in Soil
Authors: Olofsson Madelen A. , Bylund Dan
Published: February 2016

This method employs liquid chromatography-tandem mass spectrometry to rapidly quantify chitin-derived glucosamine for estimating fungal biomass. Analyte retention was achieved using hydrophilic interaction liquid chromatography, with a zwitter-ionic stationary phase (ZIC-HILIC), and isocratic elution using 60% 5 mM ammonium formate buffer (pH 3.0) and 40% ACN. Inclusion of muramic acid and its chromatographic separation from glucosamine enabled calculation of the bacterial contribution to the latter. Galactosamine, an isobaric isomer to glucosamine, found in significant amounts in soil samples, was also investigated. The two isomers form the same precursor and product ions and could not be chromatographically separated using this rapid method. Instead, glucosamine and galactosamine were distinguished mathematically, using the linear relationships describing the differences in product ion intensities for the two analytes. Them/ztransitions of 180→72 and 180→84 were applied for the detection of glucosamine and galactosamine and that of 252→126 for muramic acid. Limits of detection were in the nanomolar range for all included analytes. The total analysis time was 6 min, providing a high sample throughput method.
An Object-Oriented Framework for Versatile Finite Element Based Simulations of Neurostimulation
Authors: Dougherty Edward T. , Turner James C.
Published: February 2016

Computational simulations of transcranial electrical stimulation (TES) are commonly utilized by the neurostimulation community, and while vastly different TES application areas can be investigated, the mathematical equations and physiological characteristics that govern this research are identical. The goal of this work was to develop a robust software framework for TES that efficiently supports the spectrum of computational simulations routinely utilized by the TES community and in addition easily extends to support alternative neurostimulation research objectives. Using well-established object-oriented software engineering techniques, we have designed a software framework based upon the physical and computational aspects of TES. The framework’s versatility is demonstrated with a set of diverse neurostimulation simulations that (i) reinforce the importance of using anisotropic tissue conductivities, (ii) demonstrate the enhanced precision of high-definition stimulation electrodes, and (iii) highlight the benefits of utilizing multigrid solution algorithms. Our approaches result in a framework that facilitates rapid prototyping of real-world, customized TES administrations and supports virtually any clinical, biomedical, or computational aspect of this treatment. Software reuse and maintainability are optimized, and in addition, the same code can be effortlessly augmented to provide support for alternative neurostimulation research endeavors.
Acinetobacter baumanniiInfection and IL-17 Mediated Immunity
Authors: Yan Zihe , Yang Junjun , Hu Renjing , Hu Xichi , Chen Kong
Published: February 2016

Acinetobacter baumanniiis a significant cause of severe hospital-acquired infections with a recent rise in multidrug-resistant infections involving traumatic wounds of military personnel. The interleukin-17 (IL-17) pathway is essential for neutrophil recruitment in response to a variety of pathogens, while the control ofA. baumanniiinfection is known to be dependent on neutrophils. This suggests that IL-17 may play an important role inA. baumanniiinfection; however, this has yet to be studied. Here, we summarize the recent advances in understanding the host-pathogen interaction ofA. baumanniiand propose a potential role of the IL-17 pathway in generating a protective immune response.
Circulating Beta-2 Microglobulin and Risk of Cancer: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Prizment Anna E. , Linabery Amy M. , Lutsey Pamela L. , Selvin Elizabeth , Nelson Heather H. , Folsom Aaron R. , Church Timothy R. , Drake Charles G. , Platz Elizabeth A. , Joshu Corinne
Published: February 2016

Background: Serum β-2 microglobulin (B2M), a major histocompatibility complex class I molecule that is a biomarker of kidney filtration and increased cell turnover, is elevated at the time of diagnosis in hematological and some solid cancers. However, serum B2M was not examined prospectively as a marker for cancer risk. We hypothesized that in a population without a prior cancer diagnosis, serum B2M is associated with risk of cancer (n = 2,436), including colorectal (n = 255), lung (n = 298), breast (n = 424), and prostate (n = 524) cancers, and hematological (n = 176) malignancies.

Methods: The analytical cohort (n = 12,300) was followed for incident cancers from 1990 through 2006. B2M (range, 0.9–57.8 mg/L) was measured in stored serum collected in 1990–1992. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for cancer incidence and mortality in relation to quartiles of B2M.

Results: Adjusting for age, sex, race, center, education, body mass index, smoking, aspirin, and hormone therapy (in women) and comparing highest to lowest B2M quartiles, HRs were 1.25 (1.06–1.47; Ptrend = 0.002) for total cancer risk and 2.21 (1.32–3.70; Ptrend=0.001) for colorectal cancer risk, with similar HRs for colon and rectal cancers. These associations remained after adjustment for an inflammatory biomarker, C-reactive protein, and after excluding the first three years of follow-up. Significant associations were also observed for mortality from total, lung, and hematological cancers.

Conclusions: These findings provide the first evidence that higher serum B2M is associated with increased colorectal cancer risk.

Impact: This study supports B2M as a potential biomarker for colorectal cancer risk. Cancer Epidemiol Biomarkers Prev; 25(4); 657–64. ©2016 AACR.
A Multi-Institution Phase I Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML)
Authors: Padron Eric , Dezern Amy , Andrade-Campos Marcio , Vaddi Kris , Scherle Peggy , Zhang Qing , Ma Yan , Balasis Maria E. , Tinsley Sara , Ramadan Hanadi , Zimmerman Cassandra , Steensma David P. , Roboz Gail J. , Lancet Jeffrey E. , List Alan F. , Sekeres Mikkael A. , Komrokji Rami S.
Published: February 2016

Purpose: To conduct a phase I clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for chronic myelomonocytic leukemia (CMML).

Experimental Design: Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an absolute neutrophil count (ANC) <0.25 × 103 cells/dL and a platelet count <35 × 103 cells/dL. Four cohorts were enrolled using a “rolling six” study design, with doses ranging from 5 to 20 mg twice daily of ruxolitinib in 5-mg dose escalations.

Results: Between March 2013 and January 2015, 20 patients were enrolled and treated with ruxolitinib. Seventy percent of patients had the proliferative subtype and 47% had higher risk disease by the Global MD Anderson Scoring System. Eight patients (42%) received a prior hypomethylating agent. No dose-limiting toxicities for ruxolitinib were identified. One subject had grade (G)3 thrombocytopenia with no other drug-associated G3 or G4 adverse events. The mean duration of therapy was 122 days (range, 28–409 days). Four had hematologic improvement and one patient had a partial response per 2006 International Working Group (IWG) criteria. Five of 9 patients with splenomegaly had a reduction in spleen size. Ten of 11 patients with reported disease-related symptoms had clinically meaningful or complete resolution. When combining IWG and spleen responses, a total response rate of 35% (n = 7) was identified. Correlative analysis demonstrated a reduction in inflammatory cytokines and GM-CSF–dependent STAT5 phosphorylation.

Conclusions: The recommended phase II dose of ruxolitinib is 20 mg twice daily. We demonstrate that ruxolitinib has promising activity in CMML with particular benefit in those with disease-related B symptoms that warrants further study. Clin Cancer Res; 22(15); 3746–54. ©2016 AACR.

See related commentary by Solary, p. 3707
Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas
Authors: Martinho Olga , Campos Marcelo , Ribeiro Guilherme , Penna Valter , Curcelli Emílio C. , Olivieri Marcus V. , Morini Sandra , Scapulatempo Cristovam , Abrahão-Machado Lucas F. , Reis Rui M.
Published: February 2016

Objective: Soft tissue sarcomas (STSs) are heterogeneous tumors displaying multiple and complex molecular abnormalities with no specific pattern. Despite current therapeutic advances, the patients with STS still have a poor outcome, which makes it necessary to find out new prognostic markers. The Raf kinase inhibitory protein (RKIP) has been associated with prognosis in several human neoplasms; however, its role in STS is unknown. Methods: In the present study RKIP expression was assessed by immunohistochemistry in a series of 87 STSs, and its expression profile was associated with the patients' pathological parameters. Results: We found that RKIP is expressed in the cytoplasm of the great majority of cases, and absent in only approximately 18% of cases (16/87). Importantly, we observed that loss of RKIP expression was associated with poor outcome, constituting an independent prognostic marker. Conclusion: This is the first study assessing RKIP expression levels in STS. We showed that loss of RKIP expression is present in a small subset of cases; however, its absence was associated with poor survival and may be a potential marker for STS prognosis.
Demographic and Behavioral Predictors of Severe Fetomaternal Hemorrhage: A Case-Control Study
Authors: Stroustrup Annemarie , Plafkin Callie , Tran Thuy-An , Savitz David A.
Published: February 2016

Background: Fetomaternal hemorrhage (FMH) signifies failure of the placental barrier with whole blood transfer. Fetal anemia following FMH is associated with significant morbidity and mortality. If FMH is identified early, fetal anemia can be treated to minimize adverse outcomes. Risk factors for FMH are not known, limiting efforts to provide targeted screening for FMH. Objective: To identify maternal and/or pregnancy characteristics associated with FMH that are recognizable prior to fetal morbidity. Methods: This is the first published case-control study of FMH. Cases were identified from a prospectively maintained database of all hospital births between 1988 and 2010. Each case was matched to 4 controls by date and time of birth, allowing for assessment of a wide range of clinical and demographic data. Logistic regression modeling was used to assess the association between demographic and clinical characteristics and the diagnosis of FMH. Results: A total of 23 mother-baby pairs impacted by FMH and 92 matched controls were evaluated. Compared to controls, case mothers were more likely to have private insurance and to work outside the home and at night during pregnancy. Cases were more likely to be delivered preterm, but preterm labor was not more common among cases. There was no difference in race/ethnicity of cases compared to controls. Conclusions: Severe FMH is associated with significant morbidity and mortality of the affected neonate. Women with FMH were more likely to work outside the home during pregnancy than women with normal pregnancies. This finding has implications for third-trimester screening of pregnant women who work in strenuous fields.
Prolonged Medical Therapy Increases the Risk of Surgical Complications in Patients with Severe Ulcerative Colitis
Authors: Kimura Hideaki , Kunisaki Reiko , Tatsumi Kenji , Koganei Kazutaka , Sugita Akira , Endo Itaru
Published: February 2016

Aims: To determine the risk factors of surgical complications and the optimal timing of surgery for patients with severe ulcerative colitis (UC). Methods: One hundred one UC patients who had undergone surgery for a severe indication were retrospectively reviewed. Indications included severe disease unresponsive to medical therapy, massive bleeding, toxic megacolon, and colon perforation. Outcomes were compared based on the occurrence or absence of surgical complications. Patients with severe disease unresponsive to medical therapy were investigated separately to determine the optimal timing of surgery. Results: There was no significant difference regarding the use of rescue therapy. The duration of all medical therapy for a severe attack was the only significant factor associated with a surgical complication (p = 0.032). In patients with severe disease unresponsive to medical therapy, the receiver operating characteristic curve analysis showed that 30.5 days was the length of medical therapy after which the risk of surgical complications significantly increased. Conclusions: In patients with severe UC, rescue therapy itself was not related to an increased risk of surgical complications. However, prolonged medical therapy increased the risk of surgical complications. Patients should undergo surgery within 30 days from the institution of medical therapy for a severe attack.
Prolonged Hyperbilirubinemia in a Neonate with a Novel Mutation in the UDP-glucuronosyltransferase 1A1 Gene
Authors: Mu Shu-Chi , Chen Yi-Ling , Tsai Li-Yi , Shih Yung-Luen , Chen En-Sung , Huang Ching-Shan
Published: February 2016

The total bilirubin value of a male infant was 385 μmol/l on day 5. Liver function test results were normal and there was no evidence of sepsis and no hemolysis reaction. Phototherapy was administered and on day 8 the patient's total bilirubin level was 255 μmol/l. Intermittent episodes of hyperbilirubinemia occurred without phototherapy, with the total bilirubin level reaching 335 μmol/l on day 19. A 3-day regimen of phenobarbital was administered and on day 24 his total bilirubin level was 180 μmol/l. The patient was discharged. At the age of 2 months, the total bilirubin value was 27 μmol/l. His direct bilirubin value was <15% of total bilirubin in every determination. A family study of the UDP-glucuronosyltransferase(UGT)1A1 gene showed that the infant carries a homozygous mutation at nucleotide -3279 plus compound heterozygous mutations at nucleotides 782 and 1091. The mutation at nucleotide 782 is a novel finding. Gilbert's syndrome was diagnosed.
Interaction of Insulin Resistance and Related Genetic Variants With Triglyceride-Associated Genetic Variants
Authors: Klimentidis Yann C. , Arora Amit
Published: February 2016

Background—

Several studies suggest that some triglyceride-associated single-nucleotide polymorphisms (SNPs) have pleiotropic and opposite effects on glycemic traits. This potentially implicates them in pathways such as de novo lipogenesis, which is presumably upregulated in the context of insulin resistance. We therefore tested whether the association of triglyceride-associated SNPs with triglyceride levels differs according to one’s level of insulin resistance.

Methods and Results—

In 3 cohort studies (combined n=12 487), we tested the interaction of established triglyceride-associated SNPs (individually and collectively) with several traits related to insulin resistance, on triglyceride levels. We also tested the interaction of triglyceride SNPs with fasting insulin–associated SNPs, individually and collectively, on triglyceride levels. We find significant interactions of a weighted genetic risk score for triglycerides with insulin resistance on triglyceride levels (
P
interaction
=2.73×10
−11
and
P
interaction
=2.48×10
–11
for fasting insulin and homeostasis model assessment of insulin resistance, respectively). The association of the triglyceride genetic risk score with triglyceride levels is >60% stronger among those in the highest tertile of homeostasis model assessment of insulin resistance compared with those in the lowest tertile. Individual SNPs contributing to this trend include those in/near
GCKR
,
CILP2
, and
IRS1
, whereas
PIGV-NROB2
and
LRPAP1
display an opposite trend of interaction. In the pooled data set, we also identify a SNP–by–SNP interaction involving a triglyceride-associated SNP, rs4722551 near
MIR148A
, with a fasting insulin–associated SNP, rs4865796 in
ARL15
(
P
interaction
=4.1×10
−5
).

Conclusions—

Our findings may thus provide genetic evidence for the upregulation of triglyceride levels in insulin-resistant individuals, in addition to identifying specific genetic loci and a SNP–by–SNP interaction implicated in this process.
Management of Critical Limb Ischemia
Authors: Kinlay Scott
Published: February 2016

Critical limb ischemia (CLI) is a clinical syndrome of ischemic pain at rest or tissue loss, such as nonhealing ulcers or gangrene, related to peripheral artery disease. CLI has a high short-term risk of limb loss and cardiovascular events. Noninvasive or invasive angiography help determine the feasibility and approach to arterial revascularization. An endovascular-first approach is often advocated based on a lower procedural risk; however, specific patterns of disease may be best treated by open surgical revascularization. Balloon angioplasty and stenting form the backbone of endovascular techniques, with drug-eluting stents and drug-coated balloons offering low rates of repeat revascularization. Combined antegrade and retrograde approaches can increase success in long total occlusions. Below the knee, angiosome-directed angioplasty may lead to greater wound healing, but failing this, any straight-line flow into the foot is pursued. Hybrid surgical techniques such as iliac stenting and common femoral endarterectomy are commonly used to reduce operative risk. Lower extremity bypass grafting is most successful with a good quality, long, single-segment autogenous vein of at least 3.5-mm diameter. Minor amputations are often required for tissue loss as a part of the treatment strategy. Major amputations (at or above the ankle) limit functional independence, and their prevention is a key goal of CLI therapy. Medical therapy after revascularization targets risk factors for atherosclerosis and assesses wound healing and new or recurrent flow-limiting disease. The ongoing National Institutes of Health–sponsored Best Endovascular Versus Best Surgical Therapy in Patients With Critical Limb Ischemia (BEST-CLI) study is a randomized trial of the contemporary endovascular versus open surgical techniques in patients with CLI.
Impact of Prosthesis‐Patient Mismatch on Left Ventricular Myocardial Mechanics After Transcatheter Aortic Valve Replacement
Authors: Poulin Frédéric , Yingchoncharoen Teerapat , Wilson William M. , Horlick Eric M. , Généreux Philippe , Tuzcu E. Murat , Stewart William , Osten Mark D. , Woo Anna , Thavendiranathan Paaladinesh
Published: February 2016

Background

The aim of this study was to compare left ventricular (
LV
) remodeling using myocardial strain between patients with severe aortic stenosis (
AS
) treated with transcatheter aortic valve replacement (
TAVR
) with and without prosthesis‐patient mismatch (
PPM
).

Methods and Results

In a retrospective study, speckle‐tracking echocardiography was used to measure global longitudinal strain (
GLS
) and strain rate (
GLSR
), circumferential strain, and rotation before and at mid‐term follow‐up post‐
TAVR
. Moderate and severe
PPM
were defined as an effective orifice area ≤0.85 and <0.65 cm
2
/m
2
, respectively. A total of 102 patients (median age, 83 years [77–88]) with severe
AS
were included. At 6±3 months post‐
TAVR
, moderate and severe
PPM
were found in 32 (31%) and 9 (9%) patients. Patients without
PPM
had a significant regression in
LV
mass (from 134±41 to 119±38 g/m
2
;
P
=0.001) at follow‐up whereas those with
PPM
did not. There was a significant improvement in
LV GLS
(−12.8±4.0 to −14.3±4.3%;
P
=0.01),
GLSR
(−0.61±0.20 to −0.73±0.25 second
−1
;
P
<0.001), and early diastolic strain rate (0.52±0.20 to 0.64±0.20 second
−1
;
P
<0.001) in patients without
PPM
, but not in those with
PPM
. After adjustment for pre‐
TAVR
ejection fraction and post‐
TAVR
aortic regurgitation, patients without
PPM
had greater improvement in
LV
longitudinal strain parameters compared to those with
PPM
. After a median follow‐up of 46.1 months (interquartile range, 35.4–60.8), there was no difference in survival between patients with and without
PPM
.

Conclusions

TAVR
was associated with an incidence of
PPM
of 40%. Greater reverse
LV
remodeling using myocardial strain was evident in patients without
PPM
compared to
PPM
. Presence of
PPM
was not associated with mortality.
Supporting the STEM Pipeline: Linking Applied STEM Course-Taking in High School to Declaring a STEM Major in College
Authors: Gottfried Michael A. , Bozick Robert
Published: February 2016

Recently, through the support from the Obama administration, the traditional STEM curricula (science, technology, engineering, and mathematics) in high schools are being updated with integrated, applied STEM courses (e.g., technology and engineering) in order to enhance the “real world” applicability of scientific fields and ultimately to strengthen the link between what students learn in high school and college major choice. Using longitudinal survey and transcript data, this study examines whether taking these applied STEM courses in high school can predict higher odds of declaring a STEM major in college. The findings reveal that taking applied STEM courses in high school is associated with a higher probability of declaring a STEM college major for four-year students. Moreover, applied STEM course-taking is highly predictive of declaring an applied STEM major. Implications are discussed.
The Turning Point of Tolerance: Ethnic Attitudes in a Global Perspective
Authors: Jakobsen Tor Georg , Isaksen Joachim Vogt , Skavhaug Gunn Kari O. , Bakkan Hilde Anderssen
Published: February 2016

Is diversity associated with ethnic aversion? To address this issue we employ a theoretical perspective to explain global patterns in individual ethnic attitudes. We suggest that there is a turning point of tolerance, and this could be why earlier studies differ in their conclusions. In short, we argue that up until a certain point more intergroup contact will lead to increased tolerance. However, when this threshold is reached, any further diversity will lead to less tolerance. This study applies data from all five waves of the World Values Survey, combined with the updated ethnolinguistical fractionalisation index and relevant controls. Our models reveal a threshold effect in non-Western societies, and that ethnically polarised societies are most tolerant. This finding supports the argument that conflicts taking place along ethnic lines are not caused primarily by ethnic hatred, indicating that ethnicity might be used as an instrument to create violent conflict.