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1.  Increasing evidence that bats actively forage at wind turbines 
PeerJ  2017;5:e3985.
Although the ultimate causes of high bat fatalities at wind farms are not well understood, several lines of evidence suggest that bats are attracted to wind turbines. One hypothesis is that bats would be attracted to turbines as a foraging resource if the insects that bats prey upon are commonly present on and around the turbine towers. To investigate the role that foraging activity may play in bat fatalities, we conducted a series of surveys at a wind farm in the southern Great Plains of the US from 2011–2016. From acoustic monitoring we recorded foraging activity, including feeding buzzes indicative of prey capture, in the immediate vicinity of turbine towers from all six bat species known to be present at this site. From insect surveys we found Lepidoptera, Coleoptera, and Orthoptera in consistently high proportions over several years suggesting that food resources for bats were consistently available at wind turbines. We used DNA barcoding techniques to assess bat diet composition of (1) stomach contents from 47 eastern red bat (Lasiurus borealis) and 24 hoary bat (Lasiurus cinereus) carcasses collected in fatality searches, and (2) fecal pellets from 23 eastern red bats that were found on turbine towers, transformers, and tower doors. We found that the majority of the eastern red bat and hoary bat stomachs, the two bat species most commonly found in fatality searches at this site, were full or partially full, indicating that the bats were likely killed while foraging. Although Lepidoptera and Orthoptera dominated the diets of these two bat species, both consumed a range of prey items with individual bats having from one to six insect species in their stomachs at the time of death. The prey items identified from eastern red bat fecal pellets showed similar results. A comparison of the turbine insect community to the diet analysis results revealed that the most abundant insects at wind turbines, including terrestrial insects such as crickets and several important crop pests, were also commonly eaten by eastern red and hoary bats. Collectively, these findings suggest that bats are actively foraging around wind turbines and that measures to minimize bat fatalities should be broadly implemented at wind facilities.
doi:10.7717/peerj.3985
PMCID: PMC5672837
Bat behavior; DNA barcoding; Bat conservation; Foraging ecology; Wind power; Energy development; Wind energy; Tree bats
2.  Differential regulation of IFNα, IFNβ and IFNε gene expression in human cervical epithelial cells 
Cell & Bioscience  2017;7:57.
Interferonε (IFNε) is a unique type I IFN that has distinct functions from IFNα/β. IFNε is constitutively expressed at mucosal tissues, including the female genital mucosa, and is reported to be modulated by estrogen and seminal plasma. However, its regulation by cytokines, including TNFα, IL-1β, IL-6, IL-8, IL-17, IL-22 and IFNα, which are commonly present in the female genital mucosa, is not well documented in freshly isolated primary cervical cells from tissues. We determined the effect of these cytokines on gene expression of type I IFNs in an immortalized endocervical epithelial cell line (A2EN) and in primary cervical epithelial cells. Several pro-inflammatory cytokines were found to induce IFNε, and TNFα induced the strongest response in both cell types. Pretreatment of cells with the IκB inhibitor, which blocks the NF-κB pathway, suppressed TNFα-mediated IFNε gene induction and promoter activation. Expression of IFNα, IFNβ, and IFNε was differentially regulated in response to various cytokines. Taken together, our results show that regulation of these IFNs depends on cell type, cytokine concentration, and incubation time, highlighting the complexity of the cytokine network in the cervical epithelium.
doi:10.1186/s13578-017-0185-z
PMCID: PMC5667464
3.  Interpreting Mobile and Handheld Air Sensor Readings in Relation to Air Quality Standards and Health Effect Reference Values: Tackling the Challenges 
Atmosphere  2017;8(10):182.
The US Environmental Protection Agency (EPA) and other federal agencies face a number of challenges in interpreting and reconciling short-duration (seconds to minutes) readings from mobile and handheld air sensors with the longer duration averages (hours to days) associated with the National Ambient Air Quality Standards (NAAQS) for the criteria pollutants-particulate matter (PM), ozone, carbon monoxide, lead, nitrogen oxides, and sulfur oxides. Similar issues are equally relevant to the hazardous air pollutants (HAPs) where chemical-specific health effect reference values are the best indicators of exposure limits; values which are often based on a lifetime of continuous exposure. A multi-agency, staff-level Air Sensors Health Group (ASHG) was convened in 2013. ASHG represents a multi-institutional collaboration of Federal agencies devoted to discovery and discussion of sensor technologies, interpretation of sensor data, defining the state of sensor-related science across each institution, and provides consultation on how sensors might effectively be used to meet a wide range of research and decision support needs. ASHG focuses on several fronts: improving the understanding of what hand-held sensor technologies may be able to deliver; communicating what hand-held sensor readings can provide to a number of audiences; the challenges of how to integrate data generated by multiple entities using new and unproven technologies; and defining best practices in communicating health-related messages to various audiences. This review summarizes the challenges, successes, and promising tools of those initial ASHG efforts and Federal agency progress on crafting similar products for use with other NAAQS pollutants and the HAPs. NOTE: The opinions expressed are those of the authors and do not necessary represent the opinions of their Federal Agencies or the US Government. Mention of product names does not constitute endorsement.
doi:10.3390/atmos8100182
PMCID: PMC5662140
air pollutants; ambient air; indoor air; citizen science; toxic chemicals
4.  Characterization of CD31 expression on murine and human neonatal T lymphocytes during development and activation 
Pediatric research  2017;82(1):133-140.
Background
CD31, expressed by the majority of the neonatal T cell pool, is involved in modulation of T-cell Receptor signalling by increasing the threshold for T cell activation. Therefore, CD31 could modulate neonatal tolerance and adaptive immune responses.
Methods
Lymphocytes were harvested from murine neonates at different ages, human late preterm and term cord blood, and adult peripheral blood. Human samples were activated over a five-day period to simulate acute inflammation. Mice were infected with influenza; lungs and spleens were harvested at days 6 and 9 post-infection and analyzed by flow cytometry.
Results
CD31 expressing neonatal murine CD4+ and CD8a+ T cells increase over the first week of life. Upon in vitro stimulation, human infants’ CD4+ and CD8a+ T cells shed CD31 faster in comparison to adults. In the context of acute infection, mice infected at 3-days old have an increased number of naive and activated CD31+ T lymphocytes at the site of infection at day 6 and 9 post-infection, as compared to 7-days old; however, the opposite is true in the periphery.
Conclusion
Differences in trafficking of CD31+ Cytotoxic T Lymphocytes (CTLs) during acute influenza infection could modulate tolerance and contribute to a dampened adaptive immune response in neonates.
doi:10.1038/pr.2017.81
PMCID: PMC5509503  PMID: 28355204
5.  Complete Genome Sequences of Cluster A Mycobacteriophages BobSwaget, Fred313, KADY, Lokk, MyraDee, Stagni, and StepMih 
Genome Announcements  2017;5(43):e01182-17.
ABSTRACT
Seven mycobacteriophages from distinct geographical locations were isolated, using Mycobacterium smegmatis mc2155 as the host, and then purified and sequenced. All of the genomes are related to cluster A mycobacteriophages, BobSwaget and Lokk in subcluster A2; Fred313, KADY, Stagni, and StepMih in subcluster A3; and MyraDee in subcluster A18, the first phage to be assigned to that subcluster.
doi:10.1128/genomeA.01182-17
PMCID: PMC5658500  PMID: 29074662
6.  Examining the Role of Supportive Family Connection in Violence Exposure Among Male Youth in Urban Environments 
Journal of interpersonal violence  2016;0886260516646094.
Family connection has demonstrated protective effects on violence perpetration, victimization, and witnessing in the general U.S. adolescent population. However, several studies examining the impact of family connection on violence exposure in adolescents living in low-resource urban environments have failed to demonstrate similar protective effects. We interviewed male youth in low-resource neighborhoods in Philadelphia recruited through household random sampling. Adjusted logistic regression was used to test whether a supportive relationship with an adult family member was inversely associated with violence involvement and violence witnessing. In 283 youth participants aged 10 to 24 years, 33% reported high violence involvement, 30% reported high violence witnessing, and 17% reported both. Youth who identified at least one supportive adult family member were significantly less likely to report violence involvement (odds ratio [OR] = 0.35; 95% confidence interval [CI] = [0.18, 0.69]) and violence witnessing (OR = 0.46; 95% CI = [0.24, 0.88]). Youth with two supportive parents, and those with supportive mothers only, also demonstrated significant inverse associations with violence involvement. Supportive parental relationships were inversely but not significantly related to witnessing violence. The findings suggest that supportive parental relationships may not prevent youth in low-resource neighborhoods from witnessing violence but may help prevent direct violence involvement. Next studies should be designed such that the mechanisms that confer protection can be identified, and should identify opportunities to bolster family connection that may reduce adolescent violence involvement among youth in low-resource urban environments.
doi:10.1177/0886260516646094
PMCID: PMC5077680  PMID: 27112505
violence; adolescent; urban; family relations
7.  Adjuvant Trametinib Delays the Outgrowth of Occult Pancreatic Cancer in a Mouse Model of Patient-Derived Liver Metastasis 
Annals of surgical oncology  2016;23(6):1993-2000.
Purpose
Most patients with pancreatic ductal adenocarcinoma (PDAC) die within 5 years following resection plus adjuvant gemcitabine (Gem) from outgrowth of occult metastases. We hypothesized that inhibition of the KRAS pathway with the MEK inhibitor trametinib would inhibit the outgrowth of occult liver metastases in a preclinical model.
Methods
Liver metastases harvested from two patients with PDAC (Tumors 608, 366) were implanted orthotopically in mice. Tumor cell lines were derived and transduced with lentiviruses encoding luciferase and injected into spleens of mice generating microscopic liver metastases. Growth kinetics of liver metastases were measured with bioluminescent imaging and time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS) were determined.
Results
Trametinib (0.3 mg/kg BID) significantly prolonged OS versus control (Tumor 608: 114 vs. 43 days, p < 0.001; Tumor 366: not reached vs. 167 days, p = 0.0488). In vivo target validation demonstrated trametinib significantly reduced phosphorylated-ERK and expression of the ERK-responsive gene DUSP6. In a randomized, preclinical trial, mice were randomized to: (1) control, (2) adjuvant Gem (100 mg/kg IP, Q3 days) × 7 days followed by surveillance, or (3) adjuvant Gem followed by trametinib. Sequential Gem-trametinib significantly decreased metastatic cell outgrowth and increased TTP and PFS.
Conclusions
Treatment of mice bearing micrometastases with trametinib significantly delayed tumor outgrowth by effectively inhibiting KRAS-MEK-ERK signaling. In a randomized, preclinical, murine trial adjuvant sequential Gem followed by trametinib inhibited occult metastatic cell outgrowth in the liver and increased PFS versus adjuvant Gem alone. An adjuvant trial of sequential Gem-trametinib is being planned in patients with resected PDAC.
doi:10.1245/s10434-016-5116-4
PMCID: PMC5637098  PMID: 26847682
8.  Performance of the ATLAS track reconstruction algorithms in dense environments in LHC Run 2 
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K. | Haddad, N. | Hadef, A. | Hageböck, S. | Hagihara, M. | Hakobyan, H. | Haleem, M. | Haley, J. | Halladjian, G. | Hallewell, G. D. | Hamacher, K. | Hamal, P. | Hamano, K. | Hamilton, A.
With the increase in energy of the Large Hadron Collider to a centre-of-mass energy of 13 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {TeV}$$\end{document}TeV for Run 2, events with dense environments, such as in the cores of high-energy jets, became a focus for new physics searches as well as measurements of the Standard Model. These environments are characterized by charged-particle separations of the order of the tracking detectors sensor granularity. Basic track quantities are compared between 3.2 fb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1 of data collected by the ATLAS experiment and simulation of proton–proton collisions producing high-transverse-momentum jets at a centre-of-mass energy of 13 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {TeV}$$\end{document}TeV. The impact of charged-particle separations and multiplicities on the track reconstruction performance is discussed. The track reconstruction efficiency in the cores of jets with transverse momenta between 200 and 1600 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {GeV}$$\end{document}GeV is quantified using a novel, data-driven, method. The method uses the energy loss, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text { d}}{} \textit{E}/d\textit{x}$$\end{document}dE/dx, to identify pixel clusters originating from two charged particles. Of the charged particles creating these clusters, the measured fraction that fail to be reconstructed is \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0.061 \pm 0.006\ {\text {(stat.)}} \pm 0.014\ {\text {(syst.)}}$$\end{document}0.061±0.006(stat.)±0.014(syst.) and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0.093 \pm 0.017\ {\text {(stat.)}}\pm 0.021\ {\text {(syst.)}}$$\end{document}0.093±0.017(stat.)±0.021(syst.) for jet transverse momenta of 200–400 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {GeV}$$\end{document}GeV and 1400–1600 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {GeV}$$\end{document}GeV, respectively.
doi:10.1140/epjc/s10052-017-5225-7
PMCID: PMC5638380
9.  Natural history of falls in an incident cohort of Parkinson’s disease: early evolution, risk and protective features 
Journal of Neurology  2017;264(11):2268-2276.
The natural history of falls in early Parkinson’s disease (PD) is poorly understood despite the profound effect of falls on outcome. The primary aim of this study was to describe the natural history of falls, and characterise fallers over 54 months in 99 newly diagnosed people with PD. Seventy-nine (79.7%) participants fell over 54 months and 20 (20.3%) remained falls-naïve. Twenty six (26.2%) reported retrospective falls at baseline. Gait outcomes, disease severity and self-efficacy significantly discriminated across groups. Subjective cognitive complaints emerged as the only significant cognitive predictor. Without exception, outcomes were better for non-fallers compared with fallers at any time point. Between group differences for 54 month fallers and non-fallers were influenced by the inclusion of retrospective fallers and showed a broader range of discriminant characteristics, notably stance time variability and balance self-efficacy. Single fallers (n = 7) were significantly younger than recurrent fallers (n = 58) by almost 15 years (P = 0.013). Baseline performance in early PD discriminates fallers over 54 months, thereby identifying those at risk of falls. Clinical profiles for established and emergent fallers are to some extent distinct. These results reiterate the need for timely interventions to improve postural control and gait.
doi:10.1007/s00415-017-8620-y
PMCID: PMC5656700  PMID: 28948348
Parkinson’s disease; Falls; Prognosis; Characteristics
10.  Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4+ T Cells 
Infection and Immunity  2017;85(4):e01023-16.
ABSTRACT
Tuberculosis (TB) due to Mycobacterium tuberculosis remains a major global infectious disease problem, and a more efficacious vaccine is urgently needed for the control and prevention of disease caused by this organism. We previously reported that a genetically modified strain of Mycobacterium smegmatis called IKEPLUS is a promising TB vaccine candidate. Since protective immunity induced by IKEPLUS is dependent on antigen-specific CD4+ T cell memory, we hypothesized that the specificity of the CD4+ T cell response was a critical feature of this protection. Using in vitro assays of interferon gamma production (enzyme-linked immunosorbent spot [ELISPOT] assays) by splenocytes from IKEPLUS-immunized C57BL/6J mice, we identified an immunogenic peptide within the mycobacterial ribosomal large subunit protein RplJ, encoded by the Rv0651 gene. In a complementary approach, we generated major histocompatibility complex (MHC) class II-restricted T cell hybridomas from IKEPLUS-immunized mice. Screening of these T cell hybridomas against IKEPLUS and ribosomes enriched from IKEPLUS suggested that the CD4+ T cell response in IKEPLUS-immunized mice was dominated by the recognition of multiple components of the mycobacterial ribosome. Importantly, CD4+ T cells specific for mycobacterial ribosomes accumulate to significant levels in the lungs of IKEPLUS-immunized mice following aerosol challenge with virulent M. tuberculosis, consistent with a role for these T cells in protective host immunity in TB. The identification of CD4+ T cell responses to defined ribosomal protein epitopes expands the range of antigenic targets for adaptive immune responses to M. tuberculosis and may help to inform the design of more effective vaccines against tuberculosis.
doi:10.1128/IAI.01023-16
PMCID: PMC5364311  PMID: 28115505
T cells; antigen; epitope; ribosome; tuberculosis
11.  Body composition at birth and its relationship with neonatal anthropometric ratios: the newborn body composition study of the INTERGROWTH-21st project 
Pediatric Research  2017;82(2):305-316.
Background
We aimed to describe newborn body composition and identify which anthropometric ratio (weight/length; BMI; or ponderal index, PI) best predicts fat mass (FM) and fat-free mass (FFM).
Methods
Air-displacement plethysmography (PEA POD) was used to estimate FM, FFM, and body fat percentage (BF%). Associations between FFM, FM, and BF% and weight/length, BMI, and PI were evaluated in 1,019 newborns using multivariate regression analysis. Charts for FM, FFM, and BF% were generated using a prescriptive subsample (n=247). Standards for the best-predicting anthropometric ratio were calculated utilizing the same population used for the INTERGROWTH-21st Newborn Size Standards (n=20,479).
Results
FFM and FM increased consistently during late pregnancy. Differential FM, BF%, and FFM patterns were observed for those born preterm (34+0−36+6 weeks’ gestation) and with impaired intrauterine growth. Weight/length by gestational age (GA) was a better predictor of FFM and FM (adjusted R2=0.92 and 0.71, respectively) than BMI or PI, independent of sex, GA, and timing of measurement. Results were almost identical when only preterm newborns were studied. We present sex-specific centiles for weight/length ratio for GA.
Conclusions
Weight/length best predicts newborn FFM and FM. There are differential FM, FFM, and BF% patterns by sex, GA, and size at birth.
doi:10.1038/pr.2017.52
PMCID: PMC5605677  PMID: 28445454
12.  Nevus count associations with pigmentary phenotype, histopathological melanoma characteristics and survival from melanoma 
International journal of cancer  2016;139(6):1217-1222.
Although nevus count is an established risk factor for melanoma, relationships between nevus number and patient and tumor characteristics have not been well studied and the influence of nevus count on melanoma-specific survival is equivocal. Using data from the Genes, Environment, and Melanoma (GEM) study, a large population-based study of primary cutaneous melanoma, we evaluated associations between number of nevi and patient features, including sun-sensitivity summarized in a phenotypic index, and tumor characteristics, and we assessed the association of nevus count with melanoma-specific survival. Higher nevus counts were independently and positively associated with male gender and younger age at diagnosis and inversely associated with lentigo maligna histology. We observed a borderline significant trend of poorer melanoma-specific survival with increasing quartile of nevus count, but little or no association between number of nevi and pigmentary phenotypic characteristics or prognostic tumor features.
doi:10.1002/ijc.30157
PMCID: PMC4939099  PMID: 27101944
13.  Challenges facing the veterinary profession in Ireland: 2. On-farm use of veterinary antimicrobials 
Background
Antimicrobial resistance has emerged in recent years as a significant public health threat, which requires both an ethical and a scientific approach. In a recent Policy Delphi study, on-farm use of antimicrobials was a key concern identified by veterinary professionals in Ireland. In this case study (the second in a series of three resulting from a research workshop exploring the challenges facing the veterinary profession in Ireland; the other two case studies investigate clinical veterinary services and emergency/casualty slaughter certification) we aim to provide a value-based reflection on the constraints and possible opportunities for responsible use of veterinary antimicrobials in Ireland.
Results
Using a qualitative focus group approach, this study gathered evidence from relevant stakeholders, namely veterinarians working in public and private organisations, a representative from the veterinary regulatory body, a dairy farmer and a general medical practitioner. Three overarching constraints to prudent on-farm use of veterinary antimicrobials emerged from the thematic analysis: ‘Defective regulations’, ‘Lack of knowledge and values’ regarding farmers and vets and ‘Farm-centred concerns’, including economic and husbandry concerns. Conversely, three main themes which reflect possible opportunities to the barriers were identified: ‘Improved regulations’, ‘Education’ and ‘Herd health management’.
Conclusions
Five main recommendations arose from this study based on the perspectives of the study participants including: a) the potential for regulatory change to facilitate an increase in the number of yearly visits of veterinarians to farms and to implement electronic prescribing and shorter validity of prescriptions; b) a ‘One Health’ education plan; c) improved professional guidance on responsible use of veterinary antimicrobials; d) improved on-farm herd health management practices; and e) the promotion of a ‘One Farm-One Vet’ policy. These findings may assist Veterinary Council of Ireland and other competent authorities when revising recommendations concerning the prudent use of veterinary antimicrobials in farmed animals.
Electronic supplementary material
The online version of this article (10.1186/s13620-017-0106-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s13620-017-0106-9
PMCID: PMC5602862  PMID: 28932389
Antimicrobial resistance; Focus group; Ireland; One health; Professional ethics; Veterinary ethics; Veterinary prescriptions
14.  Local genes for local bacteria: Evidence of allopatry in the genomes of transatlantic Campylobacter populations 
Molecular Ecology  2017;26(17):4497-4508.
Abstract
The genetic structure of bacterial populations can be related to geographical locations of isolation. In some species, there is a strong correlation between geographical distance and genetic distance, which can be caused by different evolutionary mechanisms. Patterns of ancient admixture in Helicobacter pylori can be reconstructed in concordance with past human migration, whereas in Mycobacterium tuberculosis it is the lack of recombination that causes allopatric clusters. In Campylobacter, analyses of genomic data and molecular typing have been successful in determining the reservoir host species, but not geographical origin. We investigated biogeographical variation in highly recombining genes to determine the extent of clustering between genomes from geographically distinct Campylobacter populations. Whole‐genome sequences from 294 Campylobacter isolates from North America and the UK were analysed. Isolates from within the same country shared more recently recombined DNA than isolates from different countries. Using 15 UK/American closely matched pairs of isolates that shared ancestors, we identify regions that have frequently and recently recombined to test their correlation with geographical origin. The seven genes that demonstrated the greatest clustering by geography were used in an attribution model to infer geographical origin which was tested using a further 383 UK clinical isolates to detect signatures of recent foreign travel. Patient records indicated that in 46 cases, travel abroad had occurred <2 weeks prior to sampling, and genomic analysis identified that 34 (74%) of these isolates were of a non‐UK origin. Identification of biogeographical markers in Campylobacter genomes will contribute to improved source attribution of clinical Campylobacter infection and inform intervention strategies to reduce campylobacteriosis.
doi:10.1111/mec.14176
PMCID: PMC5600125  PMID: 28493321
allopatry; Campylobacter; genomics; phylogeny; recombination; source attribution
15.  Sheep grazing in the North Atlantic region: A long-term perspective on environmental sustainability 
Ambio  2016;45(5):551-566.
Sheep grazing is an important part of agriculture in the North Atlantic region, defined here as the Faroe Islands, Greenland, Iceland, Norway and Scotland. This process has played a key role in shaping the landscape and biodiversity of the region, sometimes with major environmental consequences, and has also been instrumental in the development of its rural economy and culture. In this review, we present results of the first interdisciplinary study taking a long-term perspective on sheep management, resource economy and the ecological impacts of sheep grazing, showing that sustainability boundaries are most likely to be exceeded in fragile environments where financial support is linked to the number of sheep produced. The sustainability of sheep grazing can be enhanced by a management regime that promotes grazing densities appropriate to the site and supported by area-based subsidy systems, thus minimizing environmental degradation, encouraging biodiversity and preserving the integrity of ecosystem processes.
doi:10.1007/s13280-016-0771-z
PMCID: PMC4980316  PMID: 26932602
Atlantic region; Management; Nordic agriculture; Rural economy; Sheep grazing; Sustainability
16.  Magnetic Resonance Imaging Scoring Of An Experimental Model Of Post-Traumatic Osteoarthritis In The Equine Carpus 
Magnetic resonance imaging (MRI) is the most sensitive imaging modality to detect the early changes of osteoarthritis. Currently, there is no quantifiable method to tract these pathological changes over time in the horse. The objective of this experimental study was to characterize the progression of MRI changes in an equine model of post-traumatic osteoarthritis using a semi-quantitative scoring system for whole-organ evaluation of the middle carpal joint. On day 0, an osteochondral fragment was created in one middle carpal joint (OCI) and the contralateral joint (CON) was sham-operated in 10 horses. On day 14, study horses resumed exercise on a high-speed treadmill until the completion of the study (day 98). High-field MRI examinations were performed on days 0 (pre-osteochondral fragmentation), 14, and 98 and scored by three blinded observers using consensus agreement. Images were scored based on 15 independent articular features, and scores were compared between and within groups. On days 14 and 98, OCI joints had significantly (p ≤ 0.05) higher whole-organ median scores (29.0 and 31.5, respectively), compared to CON joints (21.5 and 20.0, respectively). On day 14, OCI joints showed significant increases in high signal bone lesion scores, and osteochondral fragment number and size. On day 98, high-signal bone lesions, low-signal bone lesions, osteophyte formation, cartilage signal abnormality, subchondral bone irregularity, joint effusion, and synovial thickening scores were significantly increased in OCI joints. Study results suggest the MRI whole-organ scoring system reported here may be used to identify onset and progression of pathological changes following osteochondral injury.
doi:10.1111/vru.12369
PMCID: PMC5016209  PMID: 27198611
Equine; Carpus; MRI; Osteoarthritis; Semi-quantitative Scoring System
17.  Effects of Marital Status and Economic Resources on Survival After Cancer: A Population-Based Study 
Cancer  2016;122(10):1618-1625.
BACKGROUND
Although married cancer patients have more favorable survival than unmarried patients, reasons underlying this association are not fully understood. The authors evaluated the role of economic resources, including health insurance status and neighborhood socioeconomic status (nSES), in a large California cohort.
METHODS
From the California Cancer Registry, we identified 783,167 cancer patients (386,607 deaths) who were diagnosed during 2000 through 2009 with a first primary, invasive cancer of the 10 most common sites of cancer-related death for each sex and were followed through 2012. Age-stratified and stage-stratified Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality associated with marital status, adjusted for cancer site, race/ethnicity, and treatment.
RESULTS
Compared with married patients, unmarried patients had an elevated risk of mortality that was higher among males (HR, 1.27; 95% CI, 1.26–1.29) than among females (HR, 1.19; 95% CI, 1.18–1.20; Pinteraction < .001). Adjustment for insurance status and nSES reduced the marital status HRs to 1.22 for males and 1.15 for females. There was some evidence of synergistic effects of marital status, insurance, and nSES, with relatively higher risks observed for unmarried status among those who were under-insured and living in high nSES areas compared with those who were under-insured and living in low nSES areas (Pinteraction = 6.8 × 10−9 among males and 8.2 × 10−8 among females).
CONCLUSIONS
The worse survival of unmarried than married cancer patients appears to be minimally explained by differences in economic resources.
doi:10.1002/cncr.29885
PMCID: PMC5558592  PMID: 27065317
health insurance; marriage; mortality; neighborhood socioeconomic status; race/ethnicity
18.  Risk factors predicting outcomes for primary refractory hodgkin lymphoma patients treated with salvage chemotherapy and autologous stem cell transplantation 
British journal of haematology  2016;175(3):440-447.
Summary
We aimed to identify risk factors that predict functional imaging (FI) response to salvage chemotherapy and evaluate outcomes following autologous stem cell transplant (ASCT) in primary refractory Hodgkin Lymphoma (HL). From 1 October 1994 to 10 July 2015, 192 primary refractory HL patients were treated on sequential second line protocols. Event-free survival (EFS) and overall survival (OS) were calculated from the date of histological confirmation of refractory disease. Covariates were analysed for relationship with FI response and EFS. By intent-to-treat, the median EFS was 8·9 years and OS 10·4 years with 41% having positive post-salvage FI. On multivariate analysis, the presence of B symptoms and bulk ≥5 cm predicted for positive FI, with odds ratios of 2·15 and 2·03, respectively. For the 167 (87%) transplanted patients, 60% had a negative pre-ASCT FI. Median EFS and OS were not reached with at a median follow-up of 3·6 years in surviving patients. Both stage IV refractory disease and persistent FI abnormality pre-ASCT were associated with worse outcomes: 3-year EFS was 84%, 54% and 28% for zero, 1 and 2 risk factors, respectively (P < 0·001). Further studies are needed to validate our prognostic model and to determine optimal therapy for patients with multiple risk factors.
doi:10.1111/bjh.14245
PMCID: PMC5554509  PMID: 27377168
hodgkin lymphoma; autologous stem cell transplant; primary refractory; positron emission tomography
19.  A novel whole-bacterial enzyme linked-immunosorbant assay to quantify Chlamydia trachomatis specific antibodies reveals distinct differences between systemic and genital compartments 
PLoS ONE  2017;12(8):e0183101.
Chlamydia trachomatis (CT) is the leading sexually transmitted bacterial infection. The continued global burden of CT infection strongly predicates the need for a vaccine to supplement current chlamydial control programs. The correlates of protection against CT are currently unknown, but they must be carefully defined to guide vaccine design. The localized nature of chlamydial infection in columnar epithelial cells of the genital tract necessitates investigation of immunity at the site of infection. The purpose of this study was to develop a sensitive whole bacterial enzyme-linked immunosorbent assay (ELISA) to quantify and compare CT-specific IgG and IgA in sera and genital secretions from CT-infected women. To achieve this, elementary bodies (EBs) from two of the most common genital serovars (D and E) were attached to poly-L-lysine-coated microtiter plates with glutaraldehyde. EB attachment and integrity were verified by the presence of outer membrane antigens and the absence of bacterial cytoplasmic antigens. EB-specific IgG and IgA standards were developed by pooling sera with high titers of CT-specific antibodies from infected women. Serum, endocervical and vaginal secretions, and endocervical cytobrush specimens from CT-infected women were used to quantify CT-specific IgG and IgA which were then normalized to total IgG and IgA, respectively. Analyses of paired serum and genital samples revealed significantly higher proportions of EB-specific antibodies in genital secretions compared to sera. Cervical and vaginal secretions and cytobrush specimens had similar proportions of EB-specific antibodies, suggesting any one of these genital sampling techniques could be used to quantify CT-specific antibodies when appropriate normalization methodologies are implemented. Overall, these results illustrate the need to investigate genital tract CT antibody responses, and our assay provides a useful quantitative tool to assess natural immunity in defined clinical groups and CT vaccine trials.
doi:10.1371/journal.pone.0183101
PMCID: PMC5552291  PMID: 28797112
20.  Fiducial, total and differential cross-section measurements of t-channel single top-quark production in pp collisions at 8 TeV using data collected by the ATLAS detector 
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M. | Blackburn, D. | Blair, R. E. | Blazek, T. | Bloch, I. | Blocker, C. | Blue, A. | Blum, W. | Blumenschein, U. | Blunier, S. | Bobbink, G. J. | Bobrovnikov, V. S. | Bocchetta, S. S. | Bocci, A. | Bock, C. | Boehler, M. | Boerner, D. | Bogaerts, J. A. | Bogavac, D. | Bogdanchikov, A. G. | Bohm, C. | Boisvert, V. | Bokan, P. | Bold, T. | Boldyrev, A. S. | Bomben, M. | Bona, M. | Boonekamp, M. | Borisov, A. | Borissov, G. | Bortfeldt, J. | Bortoletto, D. | Bortolotto, V. | Bos, K. | Boscherini, D. | Bosman, M. | Sola, J. D. Bossio | Boudreau, J. | Bouffard, J. | Bouhova-Thacker, E. V. | Boumediene, D. | Bourdarios, C. | Boutle, S. K. | Boveia, A. | Boyd, J. | Boyko, I. R. | Bracinik, J. | Brandt, A. | Brandt, G. | Brandt, O. | Bratzler, U. | Brau, B. | Brau, J. E. | Madden, W. D. Breaden | Brendlinger, K. | Brennan, A. J. | Brenner, L. | Brenner, R. | Bressler, S. | Bristow, T. M. | Britton, D. | Britzger, D. | Brochu, F. 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Detailed measurements of t-channel single top-quark production are presented. They use 20.2 fb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1 of data collected by the ATLAS experiment in proton–proton collisions at a centre-of-mass energy of 8 TeV at the LHC. Total, fiducial and differential cross-sections are measured for both top-quark and top-antiquark production. The fiducial cross-section is measured with a precision of 5.8% (top quark) and 7.8% (top antiquark), respectively. The total cross-sections are measured to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma _{\text {tot}} (tq) = 56.7^{+4.3}_{-3.8}\;\mathrm{pb}$$\end{document}σtot(tq)=56.7-3.8+4.3pb for top-quark production and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma _{\text {tot}} (\bar{t} q) = 32.9^{+3.0}_{-2.7}\;\mathrm{pb}$$\end{document}σtot(t¯q)=32.9-2.7+3.0pb for top-antiquark production, in agreement with the Standard Model prediction. In addition, the ratio of top-quark to top-antiquark production cross-sections is determined to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$R_t=1.72 \pm 0.09$$\end{document}Rt=1.72±0.09. The differential cross-sections as a function of the transverse momentum and rapidity of both the top quark and the top antiquark are measured at both the parton and particle levels. The transverse momentum and rapidity differential cross-sections of the accompanying jet from the t-channel scattering are measured at particle level. All measurements are compared to various Monte Carlo predictions as well as to fixed-order QCD calculations where available.
doi:10.1140/epjc/s10052-017-5061-9
PMCID: PMC5589447
21.  Challenges facing the veterinary profession in Ireland: 3. emergency and casualty slaughter certification 
Background
Veterinarians are faced with significant conflicts of interest when issuing certificates for the transport and slaughter of acutely injured and casualty livestock. In a recent Policy Delphi study, emergency and casualty slaughter certification was a key concern identified by veterinary professionals in Ireland. In this case study (the third in a series of three resulting from a research workshop exploring challenges facing the veterinary profession in Ireland; the other two case studies investigate clinical veterinary services and the on-farm use of veterinary antimicrobials), we aim to provide a value-based reflection on the constraints and opportunities for best practice in emergency and casualty slaughter certification in Ireland.
Results
Using a qualitative focus group approach, this study gathered evidence from relevant stakeholders, namely a representative from the regulatory body, local authority veterinarians with research experience in emergency slaughter, an animal welfare research scientist, official veterinarians from the competent authority, a private veterinary practitioner, and a member of a farming organisation. Results revealed a conflict between the responsibility of private veterinary practitioners (PVPs) to safeguard the welfare of acutely injured bovines on-farm and the client’s commercial concerns. As a consequence, some PVPs may feel under pressure to certify, for example, an acutely injured animal for casualty slaughter instead of recommending either on-farm emergency slaughter or disposal by the knackery service. Among Official Veterinarians, there are concerns about the pressure within processing plants to accept acutely injured livestock as casualty animals. Confusion pertaining to legislation and definition of fitness to travel also contribute to these dilemmas.
Conclusions
Conflicts of interest arise due to the gap between governance and provision to facilitate on-farm emergency slaughter of livestock. Increased availability and acceptance of on-farm emergency slaughter by Food Business Operators (FBOs) would mitigate the need to certify acutely injured animals fit for transport and slaughter and thereby safeguard animal welfare. In the absence of nationwide availability and acceptance of on-farm emergency slaughter by FBOs, consideration should be given to methods to encourage all those involved in the food chain to prioritise animal welfare when in conflict with the commercial value of the animal. Training and guidelines for PVPs on the regulatory landscape and ethical decision-making should become available. The reintroduction of the fallen animal scheme should be considered to support farm animal welfare.
doi:10.1186/s13620-017-0102-0
PMCID: PMC5545023
Animal welfare; Casualty slaughter; Certification; Emergency slaughter; Focus group; Ireland; Veterinary ethics; Veterinary profession
22.  Stability of mild cognitive impairment in newly diagnosed Parkinson's disease 
Background
Mild cognitive impairment (MCI) is common in early Parkinson's disease (PD). We evaluated the stability of PD-MCI over time to determine its clinical utility as a marker of disease.
Methods
212 newly diagnosed participants with PD were recruited into a longitudinal study and reassessed after 18 and 36 months. Participants completed a range of clinical and neuropsychological assessments. PD-MCI was classified using Movement Disorders Society Task Force level I (Montreal Cognitive Assessment <26) and level II (using cut-offs of 1, 1.5 and 2SD) criteria.
Results
After 36 months, 75% of participants returned; 8% of patients had developed a dementia all of which were previously PD-MCI. Applying level I criteria, 70% were cognitively stable, 19% cognitively declined and 11% improved over 36 months. Applying level II criteria (1, 1.5 and 2SD), 25% were cognitively stable, 41% cognitively declined, 15% improved and 19% fluctuated over 36 months. 18% of participants reverted to normal cognition from PD-MCI.
Discussion
Cognitive impairment in PD is complex, with some individuals' function fluctuating over time and some reverting to normal cognition. PD-MCI level I criteria may have greater clinical convenience, but more comprehensive level II criteria with 2SD cut-offs may offer greater diagnostic certainty.
doi:10.1136/jnnp-2016-315099
PMCID: PMC5537517  PMID: 28250029
PARKINSON'S DISEASE; DEMENTIA; COGNITION
23.  Differences in Marital Status and Mortality by Race/Ethnicity and Nativity Among California Cancer Patients 
Cancer  2016;122(10):1570-1578.
Background
It has been observed that married cancer patients have lower mortality rates than unmarried patients, but data for different racial/ethnic groups are scarce. The authors examined the risk of overall mortality associated with marital status across racial/ethnic groups and sex in data from the California Cancer Registry.
Methods
California Cancer Registry data for all first primary invasive cancers diagnosed from 2000 through 2009 for the 10 most common sites of cancer-related death for non-Hispanic whites (NHWs), blacks, Asians/Pacific Islanders (APIs), and Hispanics were used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for marital status in relation to overall mortality by race/ethnicity and sex. The study cohort included 393,470 male and 389,697 female cancer patients and 204,007 and 182,600 deaths from all causes, respectively, through December 31, 2012.
Results
All-cause mortality was higher in unmarried patients than in married patients, but there was significant variation by race/ethnicity. Adjusted HRs (95% CIs) ranged from 1.24 (95% CI, 1.23-1.26) in NHWs to 1.11 (95% CI, 1.07-1.15) in APIs among males and from 1.17 (95% CI, 1.15-1.18) in NHWs to 1.07 (95% CI, 1.04-1.11) in APIs among females. All-cause mortality associated with unmarried status compared with married status was higher in US-born API and Hispanic men and women relative to their foreign-born counterparts.
Conclusions
For patients who have the cancers that contribute most to mortality, being unmarried is associated with worse overall survival compared with being married, with up to 24% higher mortality among NHW males but only 6% higher mortality among foreign-born Hispanic and API females. Future research should pursue the identification of factors underlying these associations to inform targeted interventions for unmarried cancer patients.
doi:10.1002/cncr.29886
PMCID: PMC5523959  PMID: 27065455
marriage; mortality; nativity; neighborhood socioeconomic status; race/ethnicity
24.  Topological cell clustering in the ATLAS calorimeters and its performance in LHC Run 1 
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The reconstruction of the signal from hadrons and jets emerging from the proton–proton collisions at the Large Hadron Collider (LHC) and entering the ATLAS calorimeters is based on a three-dimensional topological clustering of individual calorimeter cell signals. The cluster formation follows cell signal-significance patterns generated by electromagnetic and hadronic showers. In this, the clustering algorithm implicitly performs a topological noise suppression by removing cells with insignificant signals which are not in close proximity to cells with significant signals. The resulting topological cell clusters have shape and location information, which is exploited to apply a local energy calibration and corrections depending on the nature of the cluster. Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS.
doi:10.1140/epjc/s10052-017-5004-5
PMCID: PMC5586976
25.  Student perception of group dynamics predicts individual performance: Comfort and equity matter 
PLoS ONE  2017;12(7):e0181336.
Active learning in college classes and participation in the workforce frequently hinge on small group work. However, group dynamics vary, ranging from equitable collaboration to dysfunctional groups dominated by one individual. To explore how group dynamics impact student learning, we asked students in a large-enrollment university biology class to self-report their experience during in-class group work. Specifically, we asked students whether there was a friend in their group, whether they were comfortable in their group, and whether someone dominated their group. Surveys were administered after students participated in two different types of intentionally constructed group activities: 1) a loosely-structured activity wherein students worked together for an entire class period (termed the ‘single-group’ activity), or 2) a highly-structured ‘jigsaw’ activity wherein students first independently mastered different subtopics, then formed new groups to peer-teach their respective subtopics. We measured content mastery by the change in score on identical pre-/post-tests. We then investigated whether activity type or student demographics predicted the likelihood of reporting working with a dominator, being comfortable in their group, or working with a friend. We found that students who more strongly agreed that they worked with a dominator were 17.8% less likely to answer an additional question correct on the 8-question post-test. Similarly, when students were comfortable in their group, content mastery increased by 27.5%. Working with a friend was the single biggest predictor of student comfort, although working with a friend did not impact performance. Finally, we found that students were 67% less likely to agree that someone dominated their group during the jigsaw activities than during the single group activities. We conclude that group activities that rely on positive interdependence, and include turn-taking and have explicit prompts for students to explain their reasoning, such as our jigsaw, can help reduce the negative impact of inequitable groups.
doi:10.1371/journal.pone.0181336
PMCID: PMC5519092  PMID: 28727749

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