bluuebunny/crossref_metadata_2025_split huggingface dataset:
BspK, a Serine Protease from the Predatory Bacterium Bdellovibrio bacteriovorus with Utility for Analysis of Therapeutic Antibodies
Authors: Bratanis Eleni , Molina Henrik , Naegeli Andreas , Collin Mattias , Lood Rolf 
Published: December 2016

ABSTRACTThe development of therapeutic and diagnostic antibodies is a rapidly growing field of research, being the fastest expanding group of products on the pharmaceutical market, and appropriate quality controls are crucial for their application. We have identified and characterized the serine protease termed BspK (Bdellovibrioserine protease K) fromBdellovibrio bacteriovorusand here show its activity on antibodies. Mutation of the serine residue at position 230 rendered the protease inactive. Further investigations of BspK enzymatic characteristics revealed autoproteolytic activity, resulting in numerous cleavage products. Two of the autoproteolytic cleavage sites in the BspK fusion protein were investigated in more detail and corresponded to cleavage after K28and K210in the N- and C-terminal parts of BspK, respectively. Further, BspK displayed stable enzymatic activity on IgG within the pH range of 6.0 to 9.5 and was inhibited in the presence of ZnCl2. BspK demonstrated preferential hydrolysis of human IgG1 compared to other immunoglobulins and isotypes, with hydrolysis of the heavy chain at position K226generating two separate Fab fragments and an intact IgG Fc domain. Finally, we show that BspK preferentially cleaves its substrates C-terminally to lysines similar to the protease LysC. However, BspK displays a unique cleavage profile compared to several currently used proteases on the market.IMPORTANCEThe rapid development of novel therapeutic antibodies is partly hindered by difficulties in assessing their quality and safety. The lack of tools and methods facilitating such quality controls obstructs and delays the process of product approval, eventually affecting the patients in need of treatment. These difficulties in product evaluations indicate a need for new and comprehensive tools for such analysis. Additionally, recent concerns raised regarding the limitations of established products on the market (e.g., trypsin) further highlight a general need for a larger array of proteases with novel cleavage profiles to meet current and future needs, within both the life science industry and the academic research community.
Dynamics of Virus Distribution in a Defined Swine Production Network Using Enteric Viruses as Molecular Markers
Authors: Lachapelle Virginie , Letellier Ann , Fravalo Philippe , Brassard Julie , L'Homme Yvan 
Published: December 2016

ABSTRACT
Modern swine production systems represent complex and dynamic networks involving numerous stakeholders. For instance, livestock transporters carry live animals between fattening sites, abattoirs, and other premises on a daily basis. This interconnected system may increase the risk of microbial spread within and between networks, although little information is available in that regard. In the present study, a swine network composed of 10 finishing farms, one abattoir, and three types of stakeholders (veterinarians, livestock transporters, and nutritional technicians) in Quebec, Canada, was selected to investigate specific vectors and reservoirs of enteric viruses. Environmental samples were collected from the premises over a 12-month period. Samples were screened using targeted reverse transcription-PCR and sequencing of two selected viral markers, group A rotaviruses (RVA) and porcine astroviruses (PoAstV), both prevalent and genetically heterogeneous swine enteric viruses. The results revealed frequent contamination of farm sites (21.4 to 100%), livestock transporter vehicles (30.6 to 68.8%) and, most importantly, the abattoir yard (46.7 to 94.1%), depending on the sample types. Although high levels of strain diversity for both viruses were found, identical PoAstV and RVA strains were detected in specific samples from farms, the abattoir yard, and the livestock transporter vehicle, suggesting interconnections between these premises and transporters. Overall, the results from this study underscore the potential role of abattoirs and livestock transport as a reservoir and transmission route for enteric viruses within and between animal production networks, respectively.

IMPORTANCE
Using rotaviruses and astroviruses as markers of enteric contamination in a swine network has revealed the potential role of abattoirs and livestock transporters as a reservoir and vectors of enteric pathogens. The results from this study highlight the importance of tightening biosecurity measures. For instance, implementing sanitary vacancy between animal batches and emphasizing washing, disinfection, and drying procedures on farms and for transportation vehicles, as well as giving limited access and circulation of vehicles throughout the production premises, are some examples of measures that should be applied properly. The results also emphasize the need to closely monitor the dynamics of enteric contamination in the swine industry in order to better understand and potentially prevent the spread of infectious diseases. This is especially relevant when a virulent and economically damaging agent is involved, as seen with the recent introduction of the porcine epidemic diarrhea virus in the country.
Anti-adalimumab antibodies in psoriasis: lack of clinical utility and laboratory evidence
Authors: Lombardi G , Perego S , Sansoni V , Diani M , Banfi G , Altomare G 
Published: December 2016

ObjectiveAdalimumab has proven effective in psoriasis; however, secondary failure may result from the drug's immunogenicity. Prevalence data on the immunogenicity of biologicals, and of adalimumab in particular, are highly variable. We investigated the prevalence of anti-adalimumab antibodies and the association with clinical indexes and tumour necrosis factor α (TNFα) serum levels in psoriatic patients.DesignCase–control, longitudinal.SettingSingle centre.ParticipantsPatient groups: I (n=20) receiving biological therapies after switching from adalimumab; II (n=30) ongoing adalimumab therapy; III (n=30) novel adalimumab therapy; IV (n=15) biological therapies other than adalimumab.Healthy subjects: (group V; n=15) never treated with immunosuppressants or biologicals.InterventionsAll groups were tested at enrolment. Group II was also tested at 12 months, and group III at 1, 3, and 6 months.Primary and secondary outcome measuresStandard clinical evaluations (Psoriasis Area Severity Index (PASI)), blood samples and two-site ELISA-based measurement of serum adalimumab trough levels, anti-adalimumab antibodies and TNFα.ResultsThe false-positive rate was 23% for adalimumab detection and 22% for anti-adalimumab antibodies in patients naïve to adalimumab. Spurious positivity for anti-adalimumab antibodies (one-time-point positivity in group III during follow-up) accounted for 33% of the total. The prevalence of anti-drug antibodies was highest (87%) in group I patients. No correlations were found between the presence of anti-adalimumab antibodies or adalimumab levels and changes in PASI scores.ConclusionsHigh variability of results, high prevalence of false-positives and lack of association between anti-adalimumab antibodies and TNFα level/PASI score limit this assay's usefulness. Accurate clinical evaluation is key to early identification of treatment failures.
Automatic identification of type 2 diabetes, hypertension, ischaemic heart disease, heart failure and their levels of severity from Italian General Practitioners' electronic medical records: a validation study
Authors: Gini Rosa , Schuemie Martijn J , Mazzaglia Giampiero , Lapi Francesco , Francesconi Paolo , Pasqua Alessandro , Bianchini Elisa , Montalbano Carmelo , Roberto Giuseppe , Barletta Valentina , Cricelli Iacopo , Cricelli Claudio , Dal Co Giulia , Bellentani Mariadonata , Sturkenboom Miriam , Klazinga Niek 
Published: December 2016

ObjectivesThe Italian project MATRICE aimed to assess how well cases of type 2 diabetes (T2DM), hypertension, ischaemic heart disease (IHD) and heart failure (HF) and their levels of severity can be automatically extracted from the Health Search/CSD Longitudinal Patient Database (HSD). From the medical records of the general practitioners (GP) who volunteered to participate, cases were extracted by algorithms based on diagnosis codes, keywords, drug prescriptions and results of diagnostic tests. A random sample of identified cases was validated by interviewing their GPs.SettingHSD is a database of primary care medical records. A panel of 12 GPs participated in this validation study.Participants300 patients were sampled for each disease, except for HF, where 243 patients were assessed.Outcome measuresThe positive predictive value (PPV) was assessed for the presence/absence of each condition against the GP's response to the questionnaire, and Cohen's κ was calculated for agreement on the severity level.ResultsThe PPV was 100% (99% to 100%) for T2DM and hypertension, 98% (96% to 100%) for IHD and 55% (49% to 61%) for HF. Cohen's kappa for agreement on the severity level was 0.70 for T2DM and 0.69 for hypertension and IHD.ConclusionsThis study shows that individuals with T2DM, hypertension or IHD can be validly identified in HSD by automated identification algorithms. Automatic queries for levels of severity of the same diseases compare well with the corresponding clinical definitions, but some misclassification occurs. For HF, further research is needed to refine the current algorithm.
Provider and service-user perspectives of volunteer health-worker service provision in Ayeyarwady Region, Myanmar: a qualitative study
Authors: Watt Nicola , Yupar Aye , Sender Paul , Campbell Fiona , Legido-Quigley Helena , Howard Natasha 
Published: December 2016

ObjectivesTo explore perspectives and reported experiences of service users, community providers and policymakers related to volunteer health-worker services provision in a rural area of Myanmar.MethodsA qualitative interview study was conducted in rural communities with 54 service users and 17 community providers in Ayeyarwady Region, Myanmar, and with 14 national managers and policymakers in Yangon Myanmar. Topics included reasons for seeking health services, views and experiences, and comparison with experiences of other services. Data were analysed thematically using deductive and inductive coding.ResultsAccessibility and affordability were important to all participants. Service users described the particular relevance of trust, familiarity and acceptability in choosing a provider. Perceived quality and effectiveness were necessary for trust to develop. Perceived value of volunteers was a cross-cutting dimension, which was interpreted differently by different participants.ConclusionsResults suggest that volunteers are appropriate and valued, and support ‘availability’, ‘accessibility’ and ‘acceptability’ as dimensions of health services access in this setting. However, social complexities should be considered to ensure effective service delivery. Further research into trust-building, developing quality perceptions and resulting service-user choices would be useful to inform effective policy and planning.
Our current approach to root cause analysis: is it contributing to our failure to improve patient safety?
Authors: Kellogg Kathryn M , Hettinger Zach , Shah Manish , Wears Robert L , Sellers Craig R , Squires Melissa , Fairbanks Rollin J 
Published: December 2016

BackgroundDespite over a decade of efforts to reduce the adverse event rate in healthcare, the rate has remained relatively unchanged. Root cause analysis (RCA) is a process used by hospitals in an attempt to reduce adverse event rates; however, the outputs of this process have not been well studied in healthcare. This study aimed to examine the types of solutions proposed in RCAs over an 8-year period at a major academic medical institution.MethodsAll state-reportable adverse events were gathered, and those for which an RCA was performed were analysed. A consensus rating process was used to determine a severity rating for each case. A qualitative approach was used to categorise the types of solutions proposed by the RCA team in each case and descriptive statistics were calculated.Results302 RCAs were reviewed. The most common event types involved a procedure complication, followed by cardiopulmonary arrest, neurological deficit and retained foreign body. In 106 RCAs, solutions were proposed. A large proportion (38.7%) of RCAs with solutions proposed involved a patient death. Of the 731 proposed solutions, the most common solution types were training (20%), process change (19.6%) and policy reinforcement (15.2%). We found that multiple event types were repeated in the study period, despite repeated RCAs.ConclusionsThis study found that the most commonly proposed solutions were weaker actions, which were less likely to decrease event recurrence. These findings support recent attempts to improve the RCA process and to develop guidance for the creation of effective and sustainable solutions to be used by RCA teams.
The impact of child restraint legislation on the incidence of severe paediatric injury in Chile
Authors: Nazif-Muñoz J Ignacio , Gariépy Geneviève , Falconer James , Gong Annie , Macpherson Alison 
Published: December 2016

BackgroundThe objective of this study is to determine the association between Chile's 2005 child restraint legislation (CRL) and the incidence of severe paediatric motor vehicle-related injury.MethodsWe analysed motor vehicle injury data from Chile's Road Safety Commission from 2000 to 2012 to determine the association between Chile's 2005 CRL and severe paediatric injury. Using Poisson time-series models we assessed the effect of the law on two outcome variables: (1) severely injured children per vehicle fleet; and (2) severely injured children per population.ResultsChile's 2005 CRL is significantly associated with a 24% reduction in severely injured children per vehicle, and 19% reduction in severely injured children per population in the 1st year of its enactment. In 2007 this law is also significantly associated with a 17% decrease in severely injured children per vehicle, and with an 11% decrease in severely injured children per population. However, this legislation had a short-term effect since no reductions in severely injured children per vehicle were observed after 2009 and no reductions for severely injured children per population were registered after 2008.ConclusionsThis is the first study to examine the association between CRL and severe paediatric injury in a Latin-American country. This study suggests that Chile's CRL was only effective in the short term. To support this type of reforms in the long term, other measures such as police enforcement, public information campaigns and involvement of public health professionals in educating parents about the benefits of using child restraints should be considered.
Intra-abdominalCandidaspp infection in acute abdomen in a quality assurance (QA)-certified academic setting
Authors: Rodolico Vito , Di Carlo Paola , Gulotta Gaspare , D'Arpa Francesco , Salamone Giuseppe , Cocorullo Gianfranco , Agrusa Antonino , Giammanco Anna , Sergi Consolato 
Published: December 2016

AimsTo evaluate the contribution of light microscopy to detectingCandidaspp infection in patients with complicated intra-abdominal infections (IAIs) admitted for acute abdomen to a quality assurance (QA)-certified surgical emergency ward.MethodsWe conducted a retrospective study (2008–2012) of 809 abdominal intraoperative or biopsy tissue specimens obtained from patients admitted with acute abdomen and microbiological samples positive forCandidaspp. Demographic data, mortality, comorbidities, specimen type, microscopy results, special histological staining performed, antimicrobial therapy were collected and analysed. Any comments at the multidisciplinary team meeting was recorded in minutes of and approved.ResultsSixty-six patients with complicated IAIs due toCandidaspp were identified (39 male, 27 female, mean±SD age 75±20 years).Candida albicanswas isolated in 35 cases andCandida non-albicansspp in 31 cases.Candidaspp were isolated from blood in 50% of all selected microbiological specimens. Patients were stratified according toCandidaspp(albicansvsnon-albicans), underlying cancer disease and no previous antimicrobial administration, and a positive correlation withC. albicansisolation was found (p=0.009 and p=0.048, respectively). Out of 41 cases with microscopic evaluation, we identified yeast forms, pseudohyphae or both, indicative ofCandidaspp, in 23. Identification ofCandidaspp in histological specimens was higher inC. albicanscases than inC. non-albicanscases (73% vs 37.5%). Microscopy allowed prompt treatment of all patients.ConclusionsLight microscopy still has great diagnostic significance, being a solid QA step. It provides rapid information and clues in patients who may harbour impaired defence mechanisms, concurrent chronic conditions and/or cancer.
Is being in paid work beyond state pension age beneficial for health? Evidence from England using a life-course approach
Authors: Di Gessa Giorgio , Corna Laurie M , Platts Loretta G , Worts Diana , McDonough Peggy , Sacker Amanda , Price Debora , Glaser Karen 
Published: December 2016

BackgroundGiven the current policy emphasis in many Western societies on extending working lives, we investigated the health effects of being in paid work beyond state pension age (SPA). Until now, work has largely focused on the health of those who exit the labour force early.MethodsOur data come from waves 2–4 of the English Longitudinal Study of Ageing, including the life history interview at wave 3. Using logistic and linear regression models, we assessed the longitudinal associations between being in paid work beyond SPA and 3 measures of health (depression, a latent measure of somatic health and sleep disturbance) among men aged 65–74 and women aged 60–69. Our analyses controlled for baseline health and socioeconomic characteristics, as well as for work histories and health in adulthood and childhood.ResultsApproximately a quarter of women and 15% of men were in paid work beyond SPA. Descriptive bivariate analyses suggested that men and women in paid work were more likely to report better health at follow-up. However, once baseline socioeconomic characteristics as well as adulthood and baseline health and labour market histories were accounted for, the health benefits of working beyond SPA were no longer significant.ConclusionsPotential health benefits of working beyond SPA need to be considered in the light of the fact that those who report good health and are more socioeconomically advantaged are more likely to be working beyond SPA to begin with.
Constructing diagnostic likelihood: clinical decisions using subjective versus statistical probability
Authors: Kinnear John , Jackson Ruth 
Published: December 2016

ABSTRACTBackgroundAlthough physicians are highly trained in the application of evidence-based medicine, and are assumed to make rational decisions, there is evidence that their decision making is prone to biases. One of the biases that has been shown to affect accuracy of judgements is that of representativeness and base-rate neglect, where the saliency of a person’s features leads to overestimation of their likelihood of belonging to a group. This results in the substitution of ‘subjective’ probability for statistical probability.MethodsThis study examines clinicians’ propensity to make estimations of subjective probability when presented with clinical information that is considered typical of a medical condition. The strength of the representativeness bias is tested by presenting choices in textual and graphic form. Understanding of statistical probability is also tested by omitting all clinical information.ResultsFor the questions that included clinical information, 46.7% and 45.5% of clinicians made judgements of statistical probability, respectively. Where the question omitted clinical information, 79.9% of clinicians made a judgement consistent with statistical probability. There was a statistically significant difference in responses to the questions with and without representativeness information (χ2 (1, n=254)=54.45, p&lt;0.0001).ConclusionsPhysicians are strongly influenced by a representativeness bias, leading to base-rate neglect, even though they understand the application of statistical probability. One of the causes for this representativeness bias may be the way clinical medicine is taught where stereotypic presentations are emphasised in diagnostic decision making.
Age-adjusted D-dimer excludes pulmonary embolism and reduces unnecessary radiation exposure in older adults: retrospective study
Authors: Nobes Jennifer , Messow Claudia-Martina , Khan Mohammed , Hrobar Petr , Isles Chris 
Published: December 2016

ABSTRACTBackgroundPatients in whom a diagnosis of pulmonary embolism (PE) is suspected and whose D-dimers are elevated frequently require CT pulmonary angiogram (CTPA) for diagnosis. Because D-dimer rises with age, an age-adjusted D-dimer threshold may prevent unnecessary radiation exposure from CTPA in older patients.ObjectiveTo determine the efficacy and safety of implementing an age-adjusted D-dimer threshold to exclude PE.Design, settings and patientsRetrospective comparison of conventional and age-adjusted D-dimer thresholds in 1000 consecutive patients who had both D-dimer and CTPA.Main outcome measuresConventional and age-adjusted D-dimer thresholds for excluding PE were &lt;250 ng/mL and 5× age for patients older than 50 years, respectively. We defined patients as unlikely to have PE using the revised Geneva score (RGS) and two different categories of clinical risk: RGS ≤5 and RGS ≤10.ResultsWe diagnosed PE by CTPA in 244 (24.4%) patients. 3/86 patients (3.5%) whose D-dimer was below the conventional threshold of 250 ng/mL had PE (RGS 3, 9 and 14), all of which were judged to be light clot load (group 1). 3/108 patients (2.8%) whose D-dimer lay between 250 ng/mL and the age-adjusted threshold had PE (RGS 6, 8 and 9), all of which were again judged to be light clot load (group 2). 62/108 group 2 patients with RGS ≤5 were considered unlikely to have PE as were 102/108 using the RGS clinical risk category ≤10. None of the 62 patients with RGS ≤5 had PE while 3/102 patients with RGS ≤10 had PE. 236/806 patients (29.3%) whose D-dimer was above the age-adjusted threshold had PE (group 3).ConclusionsIn a consecutive series of 1000 patients, an RGS ≤5 and an age-adjusted D-dimer would have led to 62 fewer CTPA at a cost of no missed PEs.