bluuebunny/crossref_metadata_2025_split huggingface dataset:
New RHCE variant alleles encoding the D– – phenotype
Authors: Ochoa‐Garay Gorka , Moulds Joann M. , Cote Jacqueline , Kresie Lesley , Garaizar Adirane , Goldman Mindy , Wynn Polly 
Published: September 2013

BackgroundVariant alleles that do not produce RhCE antigens are rare. Consequently, they pose a challenge to transfusion when found in alloimmunized patients and make blood units valuable when found in donors.Study Design and MethodsFive index cases and their relatives were studied by both serologic and molecular techniques. Genomic DNA was subjected to microarray genotyping, sequencing, exon scanning, and/or copy number determination assays to identify the RHCE allele(s) responsible for their D+ C− c− E– e− (D– –) phenotype.ResultsThe five apparent D– – phenotypes were confirmed by molecular methods. Three of them contained unreported RHCE‐null alleles, namely, RHCE*Ce‐D(3‐9)‐Ce, RHCE*Ce87_93insT, and RHCE*cE221A.ConclusionMolecular analysis of D– – phenotypes allows the identification of new RHCE‐null variants. Conversely, detection of described RHCE‐null variants facilitates confirmation of D– – phenotypes in patients and donors, helping improve transfusion safety.
Development and Validation of Turbulence Ingestion Prediction Capability of TONBROD
Authors: Paul Brent S. , Uhlman James S. 
Published: September 2013

With alternative energy becoming more prevalent the acoustic impact of machinery used to generate the energy is of interest. The noise produced from wind turbines is an important factor in the design as it can affect nearby communities. A numerical tool has been developed to predict the unsteady thrust and directly radiated noise from a single or multi-blade row turbomachine, which can easily be applied to a wind turbine.
The tool, called TONBROD, can predict blade rate and turbulence ingestion noise, however only the latter is of concern for this work. An asymptotic approach is used to quickly and efficiently predict the unsteady force on each blade from the chopping of incoming turbulence (e.g. turbulence ingestion noise). This force is then used to estimate the radiated noise. A user can prescribe the incoming turbulence intensity (circumferentially and radially varying) and integral length scale (circumferentially uniform but radially varying) that is then modified by the upstream blade row and advected to the downstream blade row through semi-empirical formulations. A prediction of the resulting unsteady force and noise is then made for either blade row. The asymptotic theory is briefly discussed and then the prediction of radiated noise for both homogeneous and inhomogeneous turbulence is compared to experimental data. It is shown that the method provides good results.
A framework to measure myocardial extracellular volume fraction using dual‐phase low dose CT images
Authors: Liu Yixun , Liu Songtao , Nacif Marcelo S. , Sibley Christopher T. , Bluemke David A. , Summers Ronald M. , Yao Jianhua 
Published: September 2013

Purpose:Myocardial extracellular volume fraction (ECVF) is a surrogate imaging biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular remodeling. Low dose cardiac CT is emerging as a promising modality to detect diffuse interstitial myocardial fibrosis due to its fast acquisition and low radiation; however, the insufficient contrast in the low dose CT images poses great challenge to measure ECVF from the image.Methods:To deal with this difficulty, the authors present a complete ECVF measurement framework including a point‐guided myocardial modeling, a deformable model‐based myocardium segmentation, nonrigid registration of pre‐ and post‐CT, and ECVF calculation.Results:The proposed method was evaluated on 20 patients by two observers. Compared to the manually delineated reference segmentations, the accuracy of our segmentation in terms of true positive volume fraction (TPVF), false positive volume fraction (FPVF), and average surface distance (ASD), were 92.18% ± 3.52%, 0.31% ± 0.10%, 0.69 ± 0.14 mm, respectively. The interobserver variability measured by concordance correlation coefficient regarding TPVF, FPVF, and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement. Bland‐Altman method showed 95% limits of agreement between ECVF at CT and ECVF at MR.Conclusions:The proposed framework demonstrates its efficiency, accuracy, and noninvasiveness in ECVF measurement and dramatically advances the ECVF at cardiac CT toward its clinical use.
Mineralization in calcified plaque is like that of cortical bone—Further evidence from ultrashort echo time (UTE) magnetic resonance imaging of carotid plaque calcification and cortical bone
Authors: Du Jiang , Peterson Michael , Kansal Nikhil , Bydder Graeme M. , Kahn Andrew 
Published: September 2013

Purpose:This study aims to investigate carotid plaque calcification (CPC) using two‐dimensional (2D) and 3D ultrashort echo time (UTE) magnetic resonance imaging (MRI) sequences and compare T1, T2*, water concentration, and bone mineral density (BMD) of CPC with those of cortical bone.Methods:Twelve carotid plaque specimens and eight tibial cortical bone samples were imaged with UTE sequences. Adiabatic inversion recovery prepared UTE (IR‐UTE) acquisitions were used for T2* measurement. Saturation recovery prepared UTE acquisitions were used for T1 measurement. Water concentration was measured by comparing signal from CPC and bone with that from a phantom. BMD was measured withμ CT. Conventional gradient echo and fast spin echo images were also acquired for comparison.Results:Our studies show that CPC and cortical bone have similar T1 and BMD values but different T2* and water concentration. For CPC T2*s ranged from 0.31 to 3.87 ms, T1s ranged from 114 to 332 ms, water concentrations ranged from 6.4% to 17.6%, and BMD ranged from 977 to 1319 mg/ml. For cortical bone T2*s ranged from 0.33 to 0.45 ms, T1s ranged from 198 to 254 ms, water concentrations ranged from 24.7% to 33.8%, and mineral densities ranged from 970 to 1287 mg/ml. On average CPC shows about 5% longer T1, 5% lower BMD, 440% longer T2*, and 130% lower water concentration when compared to human cortical bone.Conclusions:CPC bears remarkable similarities with cortical bone in terms of BMD and T1. CPC shows a higher mean T2* and a lower mean water concentration.
Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate
Authors: Almazán Fernando , DeDiego Marta L. , Sola Isabel , Zuñiga Sonia , Nieto-Torres Jose L. , Marquez-Jurado Silvia , Andrés German , Enjuanes Luis 
Published: September 2013

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus infecting humans that is associated with acute pneumonia, occasional renal failure, and a high mortality rate and is considered a threat to public health. The construction of a full-length infectious cDNA clone of the MERS-CoV genome in a bacterial artificial chromosome is reported here, providing a reverse genetics system to study the molecular biology of the virus and to develop attenuated viruses as vaccine candidates. Following transfection with the cDNA clone, infectious virus was rescued in both Vero A66 and Huh-7 cells. Recombinant MERS-CoVs (rMERS-CoVs) lacking the accessory genes 3, 4a, 4b, and 5 were successfully rescued from cDNA clones with these genes deleted. The mutant viruses presented growth kinetics similar to those of the wild-type virus, indicating that accessory genes were not essential for MERS-CoV replication in cell cultures. In contrast, an engineered mutant virus lacking the structural E protein (rMERS-CoV-ΔE) was not successfully rescued, since viral infectivity was lost at early passages. Interestingly, the rMERS-CoV-ΔE genome replicated after cDNA clone was transfected into cells. The infectious virus was rescued and propagated in cells expressing the E protein in
trans
, indicating that this virus was replication competent and propagation defective. Therefore, the rMERS-CoV-ΔE mutant virus is potentially a safe and promising vaccine candidate to prevent MERS-CoV infection.

IMPORTANCE
Since the emergence of MERS-CoV in the Arabian Peninsula during the summer of 2012, it has already spread to 10 different countries, infecting around 94 persons and showing a mortality rate higher than 50%. This article describes the development of the first reverse genetics system for MERS-CoV, based on the construction of an infectious cDNA clone inserted into a bacterial artificial chromosome. Using this system, a collection of rMERS-CoV deletion mutants has been generated. Interestingly, one of the mutants with the E gene deleted was a replication-competent, propagation-defective virus that could only be grown in the laboratory by providing E protein in
trans
, whereas it would only survive a single virus infection cycle
in vivo
. This virus constitutes a vaccine candidate that may represent a balance between safety and efficacy for the induction of mucosal immunity, which is needed to prevent MERS-CoV infection.
Proton-Dependent Gating and Proton Uptake by Wzx Support O-Antigen-Subunit Antiport Across the Bacterial Inner Membrane
Authors: Islam Salim T. , Eckford Paul D. W. , Jones Michelle L. , Nugent Timothy , Bear Christine E. , Vogel Christian , Lam Joseph S. 
Published: September 2013

ABSTRACT

Wzx flippases are crucial for bacterial cell surface polysaccharide assembly as they transport undecaprenyl pyrophosphate-linked sugar repeat units from the cytoplasmic to the periplasmic leaflets of the inner membrane (IM) for final assembly. Our recently reported three-dimensional (3D) model structure of Wzx from
Pseudomonas aeruginosa
PAO1 (Wzx

Pa

) displayed a cationic internal vestibule and functionally essential acidic amino acids within transmembrane segment bundles. Herein, we examined the intrinsic transport function of Wzx

Pa

following its purification and reconstitution in phospholipid liposomes. Wzx

Pa

was capable of mediating anion flux, consistent with its cationic interior. This flux was electrogenic and modified by extraliposomal pH. Mutation of the above-mentioned acidic residues (E61, D269, and D359) reduced proton (H
+
)-modified anion flux, showing the role of these amino acid side chains in H
+
-dependent transport. Wzx also mediated acidification of the proteoliposome interior in the presence of an outward anion gradient. These results indicate H
+
-dependent gating and H
+
uptake by Wzx

Pa

and allow for the first H
+
-dependent antiport mechanism to be proposed for lipid-linked oligosaccharide translocation across the bacterial IM.

IMPORTANCE
Many bacterial cell surface polysaccharides that are important for survival and virulence are synthesized at the periplasmic leaflet of the inner membrane (IM) using precursors produced in the cytoplasm. Wzx flippases are responsible for translocation of lipid-linked sugar repeat units across the IM and had been previously suggested to simply facilitate passive substrate diffusion. Through our characterization of purified Wzx in a reconstitution system described herein, we have observed protein-dependent intrinsic transport producing a change in the electrical potential of the system, with H
+
identified as the coupling ion. These results provide the first evidence for coupled (i.e., secondary active) transport by these proteins and, in conjunction with structural data, allow for an antiport mechanism to be proposed for the directed transport of lipid-linked sugar substrates across the IM. These findings bring our understanding of lipid-linked polysaccharide transporter proteins more in line with the efflux pumps to which they are evolutionarily related.
The proportion of clinically relevant alarms decreases as patient clinical severity decreases in intensive care units: a pilot study
Authors: Inokuchi Ryota , Sato Hajime , Nanjo Yuko , Echigo Masahiro , Tanaka Aoi , Ishii Takeshi , Matsubara Takehiro , Doi Kent , Gunshin Masataka , Hiruma Takahiro , Nakamura Kensuke , Shinohara Kazuaki , Kitsuta Yoichi , Nakajima Susumu , Umezu Mitsuo , Yahagi Naoki 
Published: September 2013

ObjectivesTo determine (1) the proportion and number of clinically relevant alarms based on the type of monitoring device; (2) whether patient clinical severity, based on the sequential organ failure assessment (SOFA) score, affects the proportion of clinically relevant alarms and to suggest; (3) methods for reducing clinically irrelevant alarms in an intensive care unit (ICU).DesignA prospective, observational clinical study.SettingA medical ICU at the University of Tokyo Hospital in Tokyo, Japan.ParticipantsAll patients who were admitted directly to the ICU, aged ≥18 years, and not refused active treatment were registered between January and February 2012.MethodsThe alarms, alarm settings, alarm messages, waveforms and video recordings were acquired in real time and saved continuously. All alarms were annotated with respect to technical and clinical validity.Results18 ICU patients were monitored. During 2697 patient-monitored hours, 11 591 alarms were annotated. Only 740 (6.4%) alarms were considered to be clinically relevant. The monitoring devices that triggered alarms the most often were the direct measurement of arterial pressure (33.5%), oxygen saturation (24.2%), and electrocardiogram (22.9%). The numbers of relevant alarms were 12.4% (direct measurement of arterial pressure), 2.4% (oxygen saturation) and 5.3% (electrocardiogram). Positive correlations were established between patient clinical severities and the proportion of relevant alarms. The total number of irrelevant alarms could be reduced by 21.4% by evaluating their technical relevance.ConclusionsWe demonstrated that (1) the types of devices that alarm the most frequently were direct measurements of arterial pressure, oxygen saturation and ECG, and most of those alarms were not clinically relevant; (2) the proportion of clinically relevant alarms decreased as the patients’ status improved and (3) the irrelevance alarms can be considerably reduced by evaluating their technical relevance.
PP45 Developing Recommendations to Improve the Effectiveness of Multidisciplinary Team Meetings for Patients with Chronic Diseases
Authors: Nic a’ Bháird C , Wallace I , Xanthopoulou P , Barber J , Clarke A , Lanceley A , Ardron D , Harris M , Blazeby J , Ferlie E , Gibbs S , King M , Livingston G , Michie S , Prentice A , Raine R 
Published: September 2013

BackgroundMultidisciplinary team meetings (MDMs) have been endorsed by the Department of Health as the core model for managing chronic diseases. It is believed that MDMs ensure higher quality decision making and improved outcomes. However, the evidence underpinning the development of MDMs is not strong and the degree to which MDMs have been absorbed into clinical practice varies widely across conditions and settings. We conducted a large mixed-methods study of multidisciplinary teams in chronic diseases to examine and explore determinants of effective decision making. We applied a transparent and explicit consensus development method to develop recommendations, based on our results, to improve MDM decision making and effectiveness.MethodsWe collected qualitative and quantitative data from 12 multidisciplinary teams (gynaecological, skin and haematological cancers, mental health, memory clinics and heart failure). Data included non-participant observation of 370 MDMs and follow up of medical records, 53 interviews with healthcare professionals and 20 patient interviews. We triangulated these datasets to increase the internal validity and consistency of our findings. Over the course of successive analytic meetings we identified patterns of convergence to develop a coherent framework for understanding our findings. Based on this analysis we derived a series of potential recommendations for discussion and rating by an expert consensus development panel including policy makers, healthcare professionals and patient representatives.ResultsIssues for discussion by the consensus panel included: whether or not patients should attend MDMs; how patient perspectives can be best represented; determining which patients, and indeed whether all patients should be included for discussion; suggestions for improvements in MDM processes, including the structure and co-ordination of MDMs; whether functions such as teaching and emotional support for team members have a valid role in the MDM, and if so, how best to incorporate them. The issue of how to incorporate multi-morbidity in disease specific MDMs was also considered.ConclusionWe have conducted the largest study of its kind in this area and the first to examine and compare MDMs for different chronic diseases. In addition, the use of a diverse range of qualitative and quantitative data allowed an unprecedented breadth and depth of data to be explored. This produced wide ranging, important and feasible recommendations to improve the effectiveness of MDMs which, the data suggest are generalisable to different patient groups.
PP50 Body Mass Index, Waist Circumference and Incident Coronary Heart Disease in the Million Women Study
Authors: Canoy D , Cairns B J , Balkwill A , Wright F L , Reeves G , Green J , Beral V 
Published: September 2013

BackgroundBody mass index (BMI) and waist circumference are measures of total and abdominal adiposity, respectively, and both relate to coronary heart disease (CHD) risk. However, these measures are highly correlated, and require large-scale studies to reliably examine their separate associations with incident CHD. We examined the prospective relation of BMI and waist circumference with incident CHD in a large UK population-based cohort.Methods0.5 million women (mean age = 60 years) without vascular disease or cancer completed a health and lifestyle questionnaire (1999 to 2005), and were followed prospectively for 5 years on average. Adjusted relative risks and cumulative incidence (first coronary hospitalisation or death) from age 55 to 74 years were calculated using Cox regression. Plasma apolipoproteins were assayed in 6,295 randomly selected participants.ResultsOver 10,000 women had a first coronary event during follow-up. The risk for incident CHD increased with both increasing BMI and waist circumference. When BMI and waist circumference were cross-classified by one another, the risk for incident CHD increased with increasing BMI within each waist circumference category (< 70, 70–79.9, ≥ 79 cm) (P for trend < 0.05); similarly, the risk increased with increasing waist circumference within each BMI category (<25, 25–29.9, ≥30 kg/m2) (P for trend < 0.05). The cumulative CHD incidence was lowest in women with BMI < 25 kg/m2and waist circumference < 70 cm, with 7% developing CHD between ages 55 and 74 years, and highest in women with BMI ≥ 30 kg/m2and waist circumference ≥ 80 cm, with 12% developing CHD. Similar associations were observed for apolipo protein B to A1 ratio which increased with increasing BMI and waist circumference particularly in non-obese women (P for trend <0.05).ConclusionIn this large cohort of UK women, BMI and waist circumference are separately and independently associated with incident coronary disease. An atherogenic pattern of apolipoprotein profile may partly mediate these associations.
PP51 Association between Overweight/Obesity and Health Care Utilisation Among Older Adults: Results from the Irish Longitudinal Study of Ageing
Authors: McHugh S , Normand C , Browne J , Kearney P 
Published: September 2013

BackgroundGiven the ageing population and rising prevalence of obesity, the aim was to examine the association between body mass index (BMI) and health care utilisation in older Irish adults.MethodsBaseline cross-sectional data from the Irish Longitudinal Study of Ageing (TILDA) were analysed. A clustered sample of addresses was chosen from all residential addresses in the Republic of Ireland. All household residents aged 50 or over and their spouses/partners were eligible to participate. A response rate of 62% was achieved, based on the proportion of selected households including an eligible participant who was successfully interviewed (total n = 6282 households). BMI was measured objectively using standard methods. WHO classifications were used to categorise BMI as normal (BMI 18.5 – 24.99 kg/m2), overweight (BMI 25 – 29.99 kg/m2) or obese (> 30 kg/m2). Those classified as underweight (n = 32) were excluded from analysis which was conducted using Stata v12.ResultsPreliminary analysis was based on the 5873 individuals aged 50 and over, who participated in the health assessment. Applying sample weights, 49% of the population are male (n = 2701) with a mean age of 63.1 years. The mean age of females was 64.1 years. Most participants were overweight (43%) or obese (35.7%). Unadjusted comparisons between normal, overweight and obese groups suggest a significant association with high GP use (≥4 visits) and the use of out-patient hospital services. Almost 50% of obese individuals had ≥4 visits to the GP in the previous 12 months, compared to 36% of normal and 39% of overweight individuals (p = 0.000). Similarly, 47% of obese individuals had visited hospital out-patient services compared to 41% of overweight and 39% of normal weight individuals (p = 0.003). There were also significant associations between BMI and hospitalisation (p = 0.02) and receiving a prostate exam (p = 0.04). There was no significant association between BMI category and use of emergency department (p = 0.1428) or attending mammography screening (p = 0.8959).DiscussionPreliminary analysis suggests increased use of health services among older adults who are overweight or obese. Multivariate analysis will be conducted to examine whether overweight/obesity is an independent predictor of health service use in this population.