bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing hypotheses of mitochondrial gene‐tree paraphyly: unravelling mitochondrial capture of the Streak‐breasted Scimitar Babbler (Pomatorhinus ruficollis) by the Taiwan Scimitar Babbler (Pomatorhinus musicus)
Authors: Dong Feng , Zou Fa‐Sheng , Lei Fu‐Min , Liang Wei , Li Shou‐Hsien , Yang Xiao‐Jun
Published: October 2014

Species‐level paraphyly inferred from mitochondrial gene trees is a prevalent phenomenon in taxonomy and systematics, but there are several potential causes that are not easily explained by currently used methods. This study aimed to test the underlying causes behind the observed paraphyly of Streak‐breasted Scimitar Babbler (Pomatorhinus ruficollis) via statistical analyses of four mitochondrial (mtDNA) and nine nuclear (nuDNA) genes. Mitochondrial gene trees show paraphyly ofP. ruficolliswith respect to the Taiwan Scimitar Babbler (Pomatorhinus musicus), but nuclear genealogies support a sister‐group relationship. Predictive coalescent simulations imply several hypothetical explanations, the most likely being mitochondrial capture ofP. ruficollisbyP. musicusfor the observed cyto‐nuclear incongruence. Further approximate Bayesian computation suggests a unidirectional introgression model with substantial level of gene flow fromP. ruficollistoP. musicusduring their initial divergence during the Late Pleistocene. This specific observation frames several potential causes for incongruent outcomes of mitochondrial and nuclear introgression in general, and on the whole, our results underscore the strength of multiple independent loci for species delimitation and importance of testing hypotheses that explain disparate causes of mitochondrial gene‐tree paraphyly.
A balancing act times two: sensing and regulating cell envelope homeostasis in Bacillus subtilis
Authors: Fritz Georg , Mascher Thorsten
Published: October 2014

Bacterial cell wall homeostasis is an intricately coordinated process that ensures that envelope integrity is maintained during cell growth and division, but can also adequately respond to growth‐limiting conditions such as phosphate starvation. In Bacillus subtilis, biosynthesis of the two major cell wall components, peptidoglycan and anionic polymers, is controlled by a pair of paralogous two‐component systems, WalRK and PhoPR respectively. Favorable growth conditions allow for a fast rate of cell wall biosynthesis (WalRK‐ON) and the incorporation of the phosphate‐containing anionic polymer teichoic acids (PhoPR‐OFF). In contrast, growth‐restricted cells under phosphate‐limiting conditions reduce the incorporation of peptidoglycan building blocks (WalRK‐OFF) and switch from the phosphate‐containing teichoic acids to the phosphate‐free anionic polymer teichuronic acid (PhoPR‐ON). Botella et al. (2014) deepen our knowledge on the PhoPR system by identifying one signal that is perceived by its histidine kinase PhoR. In fast‐growing cells, intracellular intermediates of teichoic acid biosynthesis are sensed by the cytoplasmic Per‐Arnt‐Sim domain as an indicator of favorable conditions, thereby inhibiting the autokinase activity of PhoR and keeping the system inactive. Depletion of teichoic acid building blocks under phosphate‐limiting conditions relieves this inhibition, activates PhoPR‐dependent signal transduction and hence the switch to teichuronic acid biosynthesis.
The Value of Theology in a Scientific Age
Authors: Keogh Gary
Published: October 2014

The value of theology as a discipline has been challenged in recent years by a number of high-profile scientists, most prominently perhaps Stephen Hawking and Richard Dawkins. It has been questioned whether theology can bring anything to the table, particularly when compared with the clearly evident successes of modern science. This paper will take this challenge seriously and explore what value theology may have in the context of a scientific age, where the successes of the sciences have clearly reshaped how we think about the world. It will argue that theology offers a space and a language for discourse on the ineffable and intangible aspects of human experience, and can address the implicit philosophical and theological connotations of the scientific worldview.
Beyond mice and men: environmental change, immunity and infections in wild ungulates
Authors: Jolles A. E. , Beechler B. R. , Dolan B. P.
Published: October 2014

In the face of rapid environmental change, anticipating shifts in microparasite and macroparasite dynamics, including emergence events, is an enormous challenge. We argue that immunological studies in natural populations are pivotal to meeting this challenge: many components of environmental change – shifts in biotic assemblages, altered climate patterns and reduced environmental predictability – may affect host immunity. We suggest that wild ungulates can serve as model systems aiding the discovery of immunological mechanisms that link environmental change with parasite transmission dynamics. Our review of eco‐immunological studies in wild ungulates reveals progress in understanding how co‐infections affect immunity and parasite transmission and how environmental and genetic factors interact to shape immunity. Changes in bioavailability of micronutrients have been linked to immunity and health in wild ungulates. Although physiological stress in response to environmental change has been assessed, downstream effects on immunity have not been studied. Moreover, the taxonomic range of ungulates studied is limited to bovids (bighorn sheep, Soay sheep, chamois, musk oxen, bison, African buffalo) and a few cervids (red deer, black‐tailed deer). We discuss areas where future studies in ungulates could lead to significant contributions in understanding the patterns of immunity and infection in natural populations and across species.
Knowledge exchange in networked organizations: does place matter?
Authors: Mabey Chris , Wong Amy L. Y. , Hsieh Linda
Published: October 2014

While many studies of knowledge exchange have been undertaken in private and service organizations, government andR&Denterprises, few have studied scientific inter‐organizational collaborations. Furthermore, in the literature on international networks there has been a tendency to assume that knowledge exchange will be inevitably enhanced by global dispersion. Two linked dynamics deserving further study are the role of geographic proximity and the role of information and communication technologies in facilitating knowledge flow across international networks. Studies of intra‐ and inter‐firm knowledge transfer, managerial work values and cultural norms all point toChina as being a fascinating counterpoint for the way knowledge exchange might occur inEurope. So in this study of theATLAScollaboration, a ‘big science’ global network of 3,500 physicists, we explore the perceptions of two subgroups:UKphysicists working inEurope andChinese scientists based inBeijing andHeFei. Findings from 24 interviews and non‐participant observation reveal that face‐to‐face working at European Organization for Nuclear Research (Geneva) is not without its difficulties, but for a variety of sociocultural reasons, it is primarily theChinese scientists who perceive themselves to be inhibited from full participation in effective knowledge exchange.
Diagnostic role of inflammatory and anti‐inflammatory cytokines and effector molecules of cytotoxic T lymphocytes in tuberculous pleural effusion
Authors: Shu Chin‐Chung , Wang Jann‐Yuan , Hsu Chia‐Lin , Keng Li‐Ta , Tsui Kochung , Lin Jeng‐Feng , Lai Hsin‐Chih , Yu Chong‐Jen , Lee Li‐Na , Luh Kwen‐Tay
Published: October 2014

Background and objective

Early diagnosis of tuberculous pleural effusion (TPE) remains difficult. While some inflammatory markers in pleural effusion (PE) are helpful in diagnosis, the roles of anti‐inflammatory cytokines and effector molecules of cytotoxic T lymphocytes have not been investigated.

Methods

Lymphocyte‐predominant exudative PE samples were assayed for inflammatory and anti‐inflammatory cytokines and effector molecules of cytotoxic T lymphocytes. Logistic regression analysis was used to predict the probability of TPE and identify independently associated factors. Receiver operating characteristic (ROC) curve analysis was applied to determine the optimal cut‐off value for the predicted probability.

Results

Of 95 patients enrolled, 35 had TPE, 46 had malignant PE and 14 had PE due to other aetiologies. Interferon‐γ (IFN‐γ), adenosine deaminase (ADA), decoy receptor (DcR) 3, monocyte chemo‐attractant protein (MCP)‐1, IFN‐induced protein (IP)‐10, granzyme A and perforin were higher in TPE than in PE of other aetiologies. By logistic regression analysis, IFN‐γ ≥ 75 pg/mL, ADA ≥ 40 IU/mL, DcR3 ≥ 9.3 ng/mL and soluble tumour necrosis factor receptor 1 (TNF‐sR1) ≥ 3.2 ng/mL were independent factors associated with TPE. The predicted probability based on the four predictors had an area under the ROC curve of 0.920, with 82.9% sensitivity and 86.7% specificity under the cut‐off value of 0.303. In the TPE group, patients with positive PE/pleural culture for Mycobacterium tuberculosis had higher pleural IFN‐γ, MCP‐1, IP‐10 and perforin than those with positive sputum but negative PE culture.

Conclusions

While pleural interferon‐γ and ADA are conventional markers for diagnosing TPE, simultaneous measurements of DcR3 and TNF‐sR1 can improve the diagnostic efficacy.
Moment Consistency of the Exchangeably Weighted Bootstrap for Semiparametric M‐estimation
Authors: Cheng Guang
Published: October 2014

The bootstrap variance estimate is widely used in semiparametric inferences. However, its theoretical validity is a well‐known open problem. In this paper, we provide a first theoretical study on the bootstrap moment estimates in semiparametric models. Specifically, we establish the bootstrap moment consistency of the Euclidean parameter, which immediately implies the consistency of t‐type bootstrap confidence set. It is worth pointing out that the only additional cost to achieve the bootstrap moment consistency in contrast with the distribution consistency is to simply strengthen the L1 maximal inequality condition required in the latter to the Lp maximal inequality condition for p≥1. The general Lp multiplier inequality developed in this paper is also of independent interest. These general conclusions hold for the bootstrap methods with exchangeable bootstrap weights, for example, non‐parametric bootstrap and Bayesian bootstrap. Our general theory is illustrated in the celebrated Cox regression model.
Homology‐dependent repair is involved in 45S rDNA loss in plant CAF‐1 mutants
Authors: Muchová Veronika , Amiard Simon , Mozgová Iva , Dvořáčková Martina , Gallego Maria E. , White Charles , Fajkus Jiří
Published: October 2014

Arabidopsis thaliana mutants in FAS1 and FAS2 subunits of chromatin assembly factor 1 (CAF1) show progressive loss of 45S rDNA copies and telomeres. We hypothesized that homology‐dependent DNA damage repair (HDR) may contribute to the loss of these repeats in fas mutants. To test this, we generated double mutants by crossing fas mutants with knock‐out mutants in RAD51B, one of the Rad51 paralogs of A. thaliana. Our results show that the absence of RAD51B decreases the rate of rDNA loss, confirming the implication of RAD51B‐dependent recombination in rDNA loss in the CAF1 mutants. Interestingly, this effect is not observed for telomeric repeat loss, which thus differs from that acting in rDNA loss. Involvement of DNA damage repair in rDNA dynamics in fas mutants is further supported by accumulation of double‐stranded breaks (measured as γ‐H2AX foci) in 45S rDNA. Occurrence of the foci is not specific for S‐phase, and is ATM‐independent. While the foci in fas mutants occur both in the transcribed (intranucleolar) and non‐transcribed (nucleoplasmic) fraction of rDNA, double fas rad51b mutants show a specific increase in the number of the intranucleolar foci. These results suggest that the repair of double‐stranded breaks present in the transcribed rDNA region is RAD51B dependent and that this contributes to rDNA repeat loss in fas mutants, presumably via the single‐stranded annealing recombination pathway. Our results also highlight the importance of proper chromatin assembly in the maintenance of genome stability.
Red blood cell transfusion and immune function in critically ill children: a prospective observational study
Authors: Muszynski Jennifer A. , Frazier Elfaridah , Nofziger Ryan , Nateri Jyotsna , Hanson‐Huber Lisa , Steele Lisa , Nicol Kathleen , Spinella Philip C. , Hall Mark W. ,   Pediatric Critical Care Blood Research Network (Blood Net) subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI)
Published: October 2014

Background

Our previous in vitro work showed that stored red blood cells (RBCs) increasingly suppress markers of innate immune function with increased storage time. This multicenter prospective observational study tests the hypothesis that a single RBC transfusion in critically ill children is associated with immune suppression as a function of storage time.

Study Design and Methods

Blood samples were taken immediately before and 24 (±6) hours after a single RBC transfusion ordered as part of routine care. Innate and adaptive immune function was assessed by ex vivo whole blood stimulation with lipopolysaccharide (LPS) and phytohemagglutinin, respectively. Monocyte HLA‐DR expression, regulatory T cells, plasma interleukin (IL)‐6, and IL‐8 levels were also measured.

Results

Thirty‐one transfused critically ill children and eight healthy controls were studied. Critically ill subjects had lower pretransfusion LPS‐induced tumor necrosis factor‐α production capacity compared to healthy controls, indicating innate immune suppression (p < 0.0002). Those who received RBCs stored for not more than 21 days demonstrated recovery of innate immune function (p = 0.02) and decreased plasma IL‐6 levels (p = 0.002) over time compared to children transfused with older blood, who showed persistence of systemic inflammation and innate immune suppression. RBC storage time was not associated with changes in adaptive immune function.

Conclusion

In this pilot cohort of critically ill children, transfusion with older prestorage leukoreduced RBCs was associated with persistence of innate immune suppression and systemic inflammation. This was not seen with fresher RBCs. RBC transfusion had no short‐term association with adaptive immune function. Further studies are warranted to confirm these findings in a larger cohort of patients.
Profound autoimmune hemolysis and Evans syndrome in two asplenic patients with babesiosis
Authors: Shatzel Joseph J. , Donohoe Kelsey , Chu Ngoc‐Quynh , Garratty George , Mody Kabir , Bengtson Elizabeth M. , Dunbar Nancy M.
Published: October 2014

Background

Evans syndrome (ES) is characterized by the simultaneous or sequential presence of multiple autoimmune cytopenias. It is often secondary to rheumatologic disorders or lymphoid malignancies, but has not previously been associated with babesiosis. Here we present two cases of severe cytopenias in asplenic patients precipitated by active babesiosis.

Case Report

The first patient had a history of Hodgkin's lymphoma in remission and autoimmune hemolytic anemia (AIHA) treated by splenectomy 12 years prior who presented with severe AIHA and thrombocytopenia after Babesia infection. The second patient had a history of ES requiring splenectomy, which relapsed after Babesia infection.

Results

The complex presentation and medical histories of both patients made the diagnosis challenging. Both patients’ cytopenias responded to therapy, although the use of immunosuppressive agents in patients with active hematologic infections was challenging and required a multidisciplinary approach.

Conclusion

These two cases illustrate the possibility of babesiosis to not only reactivate ES in asplenic patients, but also precipitate increased levels of immune deregulation, potentially provoking ES, a phenomenon not previously reported.
Epidermolysis bullosa in animals: a review
Authors: Medeiros Gildenor X. , Riet‐Correa Franklin
Published: October 2014

Epidermolysis bullosa (EB) is a hereditary mechanobullous disease of animals and humans, characterized by an extreme fragility of the skin and mucous membranes. The main feature of EB in humans and animals is the formation of blisters and erosions in response to minor mechanical trauma.

Epidermolysis bullosa is caused by mutations in the genes that code for structural proteins of the cytoskeleton of the basal keratinocytes or of the basement membrane zone. Based on the ultrastructural levels of tissue separation, EB is divided into the following three broad categories: epidermolysis bullosa simplex, junctional epidermolysis bullosa and dystrophic epidermolysis bullosa. Human types of EB are divided into several subtypes based on their ultrastructural changes and the mode of inheritance; subtypes are not fully established in animals. In humans, it is estimated that EB affects one in 17,000 live births; the frequency of EB in different animals species is not known.

In all animal species, except in buffalo with epidermolysis bullosa simplex, multifocal ulcers are observed on the gums, hard and soft palates, mucosa of the lips, cheek mucosa and dorsum of the tongue. Dystrophic or absent nails, a frequent sign seen in human patients with EB, corresponds to the deformities and sloughing of the hooves in ungulates and to dystrophy or atrophy of the claws in dogs and cats.

This review covers aspects of the molecular biology, diagnosis, classification, clinical signs and pathology of EB reported in animals.
Longitudinal assessment of T‐lymphocyte subpopulations during generalized demodicosis in dogs and their relationship with remission
Authors: Oliveira Camila D. , Larsson Carlos E. , de Camargo Maristela M.
Published: October 2014

Background

The pathogenesis of canine generalized demodicosis is poorly understood but is thought to involve dysfunction of the immune system. Previous studies showed diminished CD4+ T lymphocyte counts in affected dogs, but none has evaluated this subpopulation through resolution of the disease.

Hypothesis/Objectives

In this longitudinal study, we tested whether quantification of CD4+ cells, CD8+ cells and the ratio of CD4+ to CD8+ cells are good indicators of immunological status and could be used as biomarkers of treatment efficacy and prognosis.

Animals

Sixteen dogs of several breeds with diagnoses of generalized demodicosis, plus 30 age/breedmatched healthy dogs.

Methods

Total lymphocytes, CD4+, CD8+ and CD4+:CD8+ ratio were quantified at four time points: at diagnosis, 30 days after diagnosis (during treatment), at first negative parasitological examination and at clinical cure.

Results

Absolute numbers of CD4+ cells were significantly lower in affected dogs at the time of diagnosis. Absolute numbers of CD4+ and CD8+ cells were significantly augmented in affected animals compared with control dogs after treatment was established, and this persisted until the first negative parasitological examination, at which time the CD4+ counts equalled those of the control group.

Conclusions and clinical importance

Our findings suggest that longitudinal quantification of CD4+ and CD8+ T lymphocytes is a useful indicator of the efficacy of demodicosis treatment.
Evanescent-coupled antireflection coatings for hyper-numerical aperture immersion lithography
Authors: Bourke Levi , Blaikie Richard J.
Published: October 2014

A new form of bottom antireflection coating for hyper-NA photolithography is introduced. The system uses evanescent coupling of energy into a resonant underlayer to provide the out-of-phase backward going wave to destructively interfere. Two example film stacks operating at 405 nm for immersion interference lithography are shown: photoresist/MgF2/Ru/Si and photoresist/CaF2/HfO2/CaF2/SiO2. The first example uses an excitonic resonator and operates with TM polarization. The second example uses a dielectric resonator and operates with TE polarization. The technique is scalable to any wavelength, including 193 nm for immersion photolithography, provided suitable combinations of dielectric and/or excitonic/plasmonic materials are available.
Explicit solutions of the radiative transport equation in the P3 approximation
Authors: Liemert André , Kienle Alwin
Published: October 2014

Purpose:

Explicit solutions of the monoenergetic radiative transport equation in the P3 approximation have been derived which can be evaluated with nearly the same computational effort as needed for solving the standard diffusion equation (DE). In detail, the authors considered the important case of a semi‐infinite medium which is illuminated by a collimated beam of light.

Methods:

A combination of the classic spherical harmonics method and the recently developed method of rotated reference frames is used for solving the P3 equations in closed form.

Results:

The derived solutions are illustrated and compared to exact solutions of the radiative transport equation obtained via the Monte Carlo (MC) method as well as with other approximated analytical solutions. It is shown that for the considered cases which are relevant for biomedical optics applications, the P3 approximation is close to the exact solution of the radiative transport equation.

Conclusions:

The authors derived exact analytical solutions of the P3 equations under consideration of boundary conditions for defining a semi‐infinite medium. The good agreement to Monte Carlo simulations in the investigated domains, for example, in the steady‐state and time domains, as well as the short evaluation time needed suggests that the derived equations can replace the often applied solutions of the diffusion equation for the homogeneous semi‐infinite medium.
Intensity of Physical Activity in the Energy Expenditure of Older Adults
Authors: Colbert Lisa H. , Matthews Charles E. , Schoeller Dale A. , Havighurst Thomas C. , Kim KyungMann
Published: October 2014

This study examined the intensity of activity contributing to physical activity energy expenditure in older adults. In 57 men and women aged ≥ 65, total energy expenditure (TEE) was measured using doubly labeled water and resting metabolic rate was measured using indirect calorimetry to calculate a physical activity index (PAI). Sedentary time and physical activity of light and moderate to vigorous (mod/vig) intensity was measured using an accelerometer. The subjects were 75 ± 7 yrs (mean ± SD) of age and 79% female. Subjects spent 66 ± 8, 25 ± 5, and 9 ± 4% of monitor wear time in sedentary, light, and mod/vig activity per day, respectively. In a mixture regression model, both light (β = 29.6 [15.6–43.6, 95% CI]), p < .001) and mod/vig intensity activity (β = 28.7 [7.4−50.0, 95% CI]), p = .01) were strongly associated with PAI, suggesting that both light and mod/vig intensity activities are major determinants of their physical activity energy expenditure.
Effects of Patterns of Walking Training on Metabolic Health of Untrained Postmenopausal Women
Authors: Di Blasio Andrea , Izzicupo Pascal , D’Angelo Emanuele , Melanzi Sandra , Bucci Ines , Gallina Sabina , Di Baldassarre Angela , Napolitano Giorgio
Published: October 2014

Purpose:

High-intensity aerobic interval training (AIT) has been reported to be more effective than continuous aerobic training (CoAT) to improve metabolic health. The aim of our study was to investigate whether moderate-intensity AIT is more effective than CoAT on metabolic health when applied to a walking training program.

Design/Methods:

Thirty-two postmenopausal women (55.37 ± 3.46 years) were investigated for body composition, plasma glucose, insulin, lipids, adiponectin, HOMA-IR, HOMA-AD, aerobic fitness, dietary habits, and spontaneous physical activity, and randomly assigned to one of two different walking training programs: CoAT or AIT.

Results:

CoAT and AIT elicited the same physiological benefits, including: reduction of plasma glucose, insulin, HOMA-IR and HOMA-AD, and increase of plasma HDL-C, adiponectin, and aerobic fitness.

Conclusions:

An AIT scheme as part of an outdoor walking training program elicits the same physiological adaptations as a CoAT scheme, probably because walking does not promote exercise intensities that elicit greater effects.
Relationships Between Trunk Muscle Strength, Spinal Mobility, and Balance Performance in Older Adults
Authors: Granacher Urs , Lacroix Andre , Roettger Katrin , Gollhofer Albert , Muehlbauer Thomas
Published: October 2014

This study investigated associations between variables of trunk muscle strength (TMS), spinal mobility, and balance in seniors. Thirty-four seniors (sex: 18 female, 16 male; age: 70 ± 4 years; activity level: 13 ± 7 hr/week) were tested for maximal isometric strength (MIS) of the trunk extensors, flexors, lateral flexors, rotators, spinal mobility, and steady-state, reactive, and proactive balance. Significant correlations were detected between all measures of TMS and static steady-state balance (r = .43−.57, p < .05). Significant correlations were observed between specific measures of TMS and dynamic steady-state balance (r = .42−.55, p < .05). No significant correlations were found between all variables of TMS and reactive/proactive balance and between all variables of spinal mobility and balance. Regression analyses revealed that TMS explains between 1–33% of total variance of the respective balance parameters. Findings indicate that TMS is related to measures of steady-state balance which may imply that TMS promoting exercises should be integrated in strength training for seniors.
Development of Burnout Perceptions During Adolescence Among High-Level Athletes: A Developmental and Gendered Perspective
Authors: Isoard-Gautheu Sandrine , Guillet-Descas Emma , Gaudreau Patrick , Chanal Julien
Published: October 2014

This study examined (a) the developmental trajectories of athlete burnout perceptions, (b) the gender differences on these trajectories, and (c) the interactions in the developmental trajectories of the three burnout dimensions. A five-wave longitudinal study was conducted with 895 athletes (47.6% female; Mage = 15.67). Results of multilevel growth models revealed that during adolescence, “reduced sense of accomplishment” linearly decreased and was higher for girls than boys. Moreover, “emotional/physical exhaustion” increased then decreased, and seemed to have been attenuated at time points in which athletes also had higher levels of “sport devaluation.” Finally, “sport devaluation” increased over time with higher increases for girls than boys. Results of our study depicted the general and the gendered shape of the trajectory of burnout perceptions during adolescence, and underlined the advantages of considering the multifaceted nature of burnout to enable a deeper examination of the within-person synergies in the development of the three dimensions.
Effects of 1 Week of Unilateral Ankle Immobilization on Plantar-Flexor Strength, Balance, and Walking Speed: A Pilot Study in Asymptomatic Volunteers
Authors: Caplan Nick , Forbes Andrew , Radha Sarkhell , Stewart Su , Ewen Alistair , Gibson Alan St Clair , Kader Deiary
Published: October 2014

Context:

Ankle immobilization is often used after ankle injury.

Objective:

To determine the influence of 1 week’s unilateral ankle immobilization on plantar-flexor strength, balance, and walking gait in asymptomatic volunteers.

Design:

Repeated-measures laboratory study.

Setting:

University laboratory.

Participants:

6 physically active male participants with no recent history of lower-limb injury.

Interventions:

Participants completed a 1-wk period of ankle immobilization achieved through wearing a below-knee ankle cast. Before the cast was applied, as well as immediately, 24 h, and 48 h after cast removal, their plantar-flexor strength was assessed isokinetically, and they completed a single-leg balance task as a measure of proprioceptive function. An analysis of their walking gait was also completed

Main Outcome Measures:

Peak plantar-flexor torque and balance were used to determine any effect on muscle strength and proprioception after cast removal. Ranges of motion (3D) of the ankle, knee, and hip, as well as walking speed, were used to assess any influence on walking gait.

Results:

After cast removal, plantar-flexor strength was reduced for the majority of participants (P = .063, CI = −33.98 to 1.31) and balance performance was reduced in the immobilized limb (P < .05, CI = 0.84−5.16). Both strength and balance were not significantly different from baseline levels by 48 h. Walking speed was not significantly different immediately after cast removal but increased progressively above baseline walking speed over the following 48 h. Joint ranges of motion were not significantly different at any time point.

Conclusions:

The reduction in strength and balance after such a short period of immobilization suggested compromised central and peripheral neural mechanisms. This suggestion appeared consistent with the delayed increase in walking speed that could occur as a result of the excitability of the neural pathways increasing toward baseline levels.
Comparing Computer-Derived and Human-Observed Scores for the Balance Error Scoring System
Authors: Caccese Jaclyn B. , Kaminski Thomas W.
Published: October 2014

Context:

The Balance Error Scoring System (BESS) is the current standard for assessing postural stability in concussed athletes on the sideline. However, research has questioned the objectivity and validity of the BESS, suggesting that while certain subcategories of the BESS have sufficient reliability to be used in evaluation of postural stability, the total score is not reliable, demonstrating limited interrater and intrarater reliability. Recently, a computerized BESS test was developed to automate scoring.

Objective:

To compare computerderived BESS scores with those taken from 3 trained human scorers.

Design:

Interrater reliability study.

Setting:

Athletic training room.

Patients:

NCAA Division I student athletes (53 male, 58 female; 19 ± 2 y, 168 ± 41 cm, 69 ± 4 kg).

Interventions:

Subjects were asked to perform the BESS while standing on the Tekscan (Boston, MA) MobileMat® BESS. The MobileMat BESS software displayed an error score at the end of each trial. Simultaneously, errors were recorded by 3 separate examiners. Errors were counted using the standard BESS scoring criteria.

Main Outcome Measures:

The number of BESS errors was computed for the 6 stances from the software and each of the 3 human scorers. Interclass correlation coefficients (ICCs) were used to compare errors for each stance scored by the MobileMat BESS software with each of 3 raters individually. The ICC values were converted to Fisher Z scores, averaged, and converted back into ICC values.

Results:

The double-leg, single-leg, and tandem-firm stances resulted in good agreement with human scorers (ICC = .999, .731, and .648). All foam stances resulted in fair agreement.

Conclusions:

Our results suggest that the MobileMat BESS is suitable for identifying BESS errors involving each of the 6 stances of the BESS protocol. Because the MobileMat BESS scores consistently and reliably, this system can be used with confidence by clinicians as an effective alternative to scoring the BESS.
The minimal cadherin-catenin complex binds to actin filaments under force
Authors: Buckley Craig D. , Tan Jiongyi , Anderson Karen L. , Hanein Dorit , Volkmann Niels , Weis William I. , Nelson W. James , Dunn Alexander R.
Published: October 2014

Pulling me apart only makes me stronger

Tension transmitted between neighboring cells can exert profound effects on cell proliferation, differentiation, and tissue organization. Exactly how intercellular mechanical tension is sensed at the molecular level is unknown. One attractive hypothesis is that a linkage between the cell-cell adhesion molecule E-cadherin, its binding partners α- and β-catenin, and actin filaments may act as a tension sensor. However, how this linkage is established at the molecular level is not known. Buckley
et al.
used optical tweezers to determine how mechanical load influences interactions of the cadherin/catenin complex with single actin filaments. The data support a model in which force shifts the interaction from a force-independent, weakly bound state to a highly force-sensitive, strongly bound state. The findings may explain how cells maintain tissue integrity while still being able to move and change shape.

Science
, this issue p.
10.1126/science.1254211
Performance Evaluation of the Elecsys Syphilis Assay for the Detection of Total Antibodies to Treponema pallidum
Authors: Enders Martin , Hunjet Andrea , Gleich Michael , Imdahl Roland , Mühlbacher Annelies , Schennach Harald , Chaiwong Kriangsak , Sakuldamrongpanich Tasanee , Turhan Ajda , Sertöz Rüchan , Wolf Eva , Mayer Wolfgang , Tao Chuanmin , Wang Lan Lan , Semprini Simona , Sambri Vittorio
Published: October 2014

Syphilis is a health problem of increasing incidence in recent years that may have severe complications if not diagnosed and treated at an early stage. There are many diagnostic tests available for syphilis, but there is no gold standard, and diagnosis therefore usually relies upon a combination of tests. In this multicenter study, we evaluated the treponemal Elecsys syphilis assay for use in the diagnosis of syphilis in routine samples, i.e., when syphilis is suspected or during antenatal or blood donation screening. The sensitivity and specificity of the Elecsys syphilis assay were compared head to head with those of other treponemal assays used in routine clinical practice and were assessed in potentially cross-reactive samples from patients with Epstein-Barr virus, HIV, and Lyme disease. In a total of 8,063 syphilis-negative samples collected from routine diagnostic requests and blood donations, the Elecsys syphilis assay had a specificity of 99.88%. In 928 samples previously identified as syphilis positive, the sensitivity was 99.57 to 100% (the result is presented as a range depending on whether four initially indeterminate samples are included in the assessment). The specificity of the Elecsys syphilis assay in patients with other infections was 100%; no false-positive samples were identified.
Pseudo-Outbreak of Actinomyces graevenitzii Associated with Bronchoscopy
Authors: Peaper David R. , Havill Nancy L. , Aniskiewicz Michael , Callan Deborah , Pop Olivia , Towle Dana , Boyce John M.
Published: October 2014

Outbreaks and pseudo-outbreaks of infection related to bronchoscopy typically involve Gram-negative bacteria,
Mycobacterium
species or
Legionella
species. We report an unusual bronchoscopy-related pseudo-outbreak due to
Actinomyces graevenitzii
. Extensive epidemiological and microbiological investigation failed to identify a common source. Strain typing revealed that the cluster was comprised of heterogeneous strains of
A. graevenitzii
. A change in laboratory procedures for
Actinomyces
cultures was coincident with the emergence of the pseudo-outbreak, and we determined that
A. graevenitzii
isolates more readily adopted a white, dry, molar tooth appearance on anaerobic colistin nalidixic acid (CNA) agar which likely facilitated its detection and identification in bronchoscopic specimens. This unusual pseudo-outbreak was related to frequent requests of bronchoscopists for
Actinomyces
cultures combined with a change in microbiology laboratory practices.
Investigations of Mycoplasma pneumoniae Infections in the United States: Trends in Molecular Typing and Macrolide Resistance from 2006 to 2013
Authors: Diaz Maureen H. , Benitez Alvaro J. , Winchell Jonas M.
Published: October 2014

Mycoplasma pneumoniae
is a leading cause of respiratory infections, including community-acquired pneumonia (CAP). Currently, pathogen-specific testing is not routinely performed in the primary care setting, and the United States lacks a systematic surveillance program for
M. pneumoniae
. Documentation of individual cases and clusters typically occurs only when severe illness and/or failure to improve with empirical antibiotic therapy is observed. Outbreaks, some lasting for extended periods and involving a large number of cases, occur regularly. However, many more likely go unrecognized due to the lack of diagnostic testing and structured reporting. We reviewed data from 17 investigations of cases, small clusters, and outbreaks of
M. pneumoniae
infections that were supported by the Centers for Disease Control and Prevention (CDC) between 2006 and 2013. We examined 199
M. pneumoniae
-positive specimens collected during this time period in order to identify trends in antimicrobial resistance and circulating types. Overall, macrolide resistance was identified in approximately 10% of
M. pneumoniae
infections occurring during this time period. Typing of strains revealed cocirculation of multiple multilocus variable-number tandem-repeat analysis (MLVA) and P1 types throughout this period, including diversity in types detected within individual outbreaks. Three MLVA types (4572, 3562, and 3662) accounted for 97% of the infections during the study period. A systematic surveillance program is necessary to understand the burden of
M. pneumoniae
disease in the United States, facilitate case and outbreak identification, and inform appropriate therapeutic and infection control strategies.
Varicella-Zoster Virus-Derived Major Histocompatibility Complex Class I-Restricted Peptide Affinity Is a Determining Factor in the HLA Risk Profile for the Development of Postherpetic Neuralgia
Authors: Meysman Pieter , Ogunjimi Benson , Naulaerts Stefan , Beutels Philippe , Van Tendeloo Viggo , Laukens Kris
Published: October 2014

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster and is typified by a lingering pain that can last months or years after the characteristic herpes zoster rash disappears. It is well known that there are risk factors for the development of PHN, such as its association with certain HLA alleles. In this study, previous HLA genotyping results were collected and subjected to a meta-analysis with increased statistical power. This work shows that the alleles HLA-A*33 and HLA-B*44 are significantly enriched in PHN patients, while HLA-A*02 and HLA-B*40 are significantly depleted. Prediction of the varicella-zoster virus (VZV) peptide affinity for these four HLA variants by using one in-house-developed and two existing state-of-the-art major histocompatibility complex (MHC) class I ligand prediction methods reveals that there is a great difference in their absolute and relative peptide binding repertoires. It was observed that HLA-A*02 displays a high affinity for an ∼7-fold-higher number of VZV peptides than HLA-B*44. Furthermore, after correction for HLA allele-specific limitations, the relative affinity of HLA-A*33 and HLA-B*44 for VZV peptides was found to be significantly lower than those of HLA-A*02 and HLA-B*40. In addition, HLA peptide affinity calculations indicate strong trends for VZV to avoid high-affinity peptides in some of its proteins, independent of the studied HLA allele.

IMPORTANCE
Varicella-zoster virus can cause two distinct diseases: chickenpox (varicella) and shingles (herpes zoster). Varicella is a common disease in young children, while herpes zoster is more frequent in older individuals. A common complication of herpes zoster is postherpetic neuralgia, a persistent and debilitating pain that can remain months up to years after the resolution of the rash. In this study, we show that the relative affinity of HLA variants associated with higher postherpetic neuralgia risk for varicella-zoster virus peptides is lower than that of variants with a lower risk. These results provide new insight into the development of postherpetic neuralgia and strongly support the hypothesis that one of its possible underlying causes is a suboptimal anti-VZV immune response due to weak HLA binding peptide affinity.
T Cell Epitope Clustering in the Highly Immunogenic BZLF1 Antigen of Epstein-Barr Virus
Authors: Rist Melissa J. , Neller Michelle A. , Burrows Jacqueline M. , Burrows Scott R.
Published: October 2014

Polymorphism in the human leukocyte antigen (HLA) loci ensures that the CD8+T cell response to viruses is directed against a diverse range of antigenic epitopes, thereby minimizing the impact of virus escape mutation across the population. The BZLF1 antigen of Epstein-Barr virus is an immunodominant target for CD8+T cells, but the response has been characterized only in the context of a limited number of HLA molecules due to incomplete epitope mapping. We have now greatly expanded the number of defined CD8+T cell epitopes from BZLF1, allowing the response to be evaluated in a much larger proportion of the population. Some regions of the antigen fail to be recognized by CD8+T cells, while others include clusters of overlapping epitopes presented by different HLA molecules. These highly immunogenic regions of BZLF1 include polymorphic sequences, such that up to four overlapping epitopes are impacted by a single amino acid variation common in different regions of the world. This focusing of the immune response to limited regions of the viral protein could be due to sequence similarity to human proteins creating “immune blind spots” through self-tolerance. This study significantly enhances the understanding of the immune response to BZLF1, and the precisely mapped T cell epitopes may be directly exploited in vaccine development and adoptive immunotherapy.

IMPORTANCEEpstein-Barr virus (EBV) is an important human pathogen, associated with several malignancies, including nasopharyngeal carcinoma and Hodgkin lymphoma. T lymphocytes are critical for virus control, and clinical trials aimed at manipulating this arm of the immune system have demonstrated efficacy in treating these EBV-associated diseases. These trials have utilized information on the precise location of viral epitopes for T cell recognition, for either measuring or enhancing responses. In this study, we have characterized the T cell response to the highly immunogenic BZLF1 antigen of EBV by greatly expanding the number of defined T cell epitopes. An unusual clustering of epitopes was identified, highlighting a small region of BZLF1 that is targeted by the immune response of a high proportion of the world's population. This focusing of the immune response could be utilized in developing vaccines/therapies with wide coverage, or it could potentially be exploited by the virus to escape the immune response.
Simian Hemorrhagic Fever Virus Cell Entry Is Dependent on CD163 and Uses a Clathrin-Mediated Endocytosis-Like Pathway
Authors: Caì Yíngyún , Postnikova Elena N. , Bernbaum John G. , Yú Shuǐqìng , Mazur Steven , Deiuliis Nicole M. , Radoshitzky Sheli R. , Lackemeyer Matthew G. , McCluskey Adam , Robinson Phillip J. , Haucke Volker , Wahl-Jensen Victoria , Bailey Adam L. , Lauck Michael , Friedrich Thomas C. , O'Connor David H. , Goldberg Tony L. , Jahrling Peter B. , Kuhn Jens H.
Published: October 2014

Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component.

IMPORTANCE
Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low-pH-dependent, actin-independent endocytosis, likely with the help of a cellular surface protein.
Severe retroperitoneal and intra-abdominal bleeding after stapling procedure for prolapsed haemorrhoids (PPH); diagnosis, treatment and 6-year follow-up of the case
Authors: Safadi Wajdi , Altshuler Alexander , Kiv Sakal , Waksman Igor
Published: October 2014

Procedure for prolapsed haemorrhoids (PPH) is a popular treatment of haemorrhoids. PPH has the advantages of a shorter operation time, minor degree of postoperative pain, shorter hospital stay and quicker recovery but may be followed by several postoperative complications. Rectal bleeding, acute pain, chronic pain, rectovaginal fistula, complete rectal obliteration, rectal stenosis, rectal pocket, tenesmus, faecal urgency, faecal incontinence, rectal perforation, pelvic sepsis and rectal haematoma have all been reported as postoperative complications of PPH. Additionally, one rare complication of the procedure is intra-abdominal bleeding. There are a few case reports describing intra-abdominal bleeding after the procedure. We report a case of a 26-year-old man who developed severe intra-abdominal and retroperitoneal haemorrhage after PPH. The diagnosis was made on the second postoperative day by CT of the abdomen and pelvis. The patient was treated conservatively and had an uneventful recovery.
Improving the follow-up of microbiology results: the origins of the Pink Book
Authors: Boyle Henry , Hunt Charlie , McIlroy Catherine , Qureshi Imran
Published: October 2014

Failure to check microbiology results put patients at risk of prolonged infections, resulting in increased morbidity and mortality from sepsis. There are some electronic systems designed to address this risk although they are rarely used in the hospital setting. In many hospitals the follow-up of microbiology results for discharged patients is reliant upon individual doctor's vigilance or ad hoc lists.

Our intervention, the 'Pink Book', provides a simple, cost effective system to follow-up microbiology results for discharged patients. This simple paper based system enables prompt, effective, efficient follow-up of microbiology results, saving our paediatric department an estimated 1.5 hours per week, £17,440 per year and helping to prevent one case of inadequately treated infection per month.

This project highlights how small scale, simple interventions at the local level, born out of the frustration at existing inefficient systems, can make great improvements to patient safety and the efficiency of healthcare.