bluuebunny/crossref_metadata_2025_split huggingface dataset:
The complexity of managing COPD exacerbations: a grounded theory study of European general practice
Authors: Risør Mette Bech , Spigt Mark , Iversen R , Godycki-Cwirko M , Francis N , Altiner A , Andreeva E , Kung K , Melbye H 
Published: December 2013

ObjectivesTo understand the concerns and challenges faced by general practitioners (GPs) and respiratory physicians about primary care management of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD).Design21 focus group discussions (FGDs) were performed in seven countries with a Grounded Theory approach. Each country performed three rounds of FGDs.SettingPrimary and secondary care in Norway, Germany, Wales, Poland, Russia, The Netherlands, China (Hong Kong).Participants142 GPs and respiratory physicians were chosen to include urban and rural GPs as well as hospital-based and out patient-clinic respiratory physicians.ResultsManagement of acute COPD exacerbations is dealt with within a scope of concerns. These concerns range from ‘dealing with comorbidity’ through ‘having difficult patients’ to ‘confronting a hopeless disease’.The first concern displays medical uncertainty regarding diagnosis, medication and hospitalisation. These clinical processes become blurred by comorbidity and the social context of the patient. The second concern shows how patients receive the label ‘difficult’ exactly because they need complex attention, but even more because they are time consuming, do not take responsibility and are non-compliant. The third concern relates to the emotional reactions by the physicians when confronted with ‘a hopeless disease’ due to the fact that most of the patients do not improve and the treatment slows down the process at best. GPs and respiratory physicians balance these concerns with medical knowledge and practical, situational knowledge, trying to encompass the complexity of a medical condition.ConclusionsKnowing the patient is essential when dealing with comorbidities as well as with difficult relations in the consultations on exacerbations. This study suggests that it is crucial to improve the collaboration between primary and secondary care, in terms of, for example, shared consultations and defined work tasks, which may enhance shared knowledge of patients, medical decision-making and improved management planning.
Associations of HIV infection with insulin and glucose levels in antiretroviral-naïve Rwandan women: a cross-sectional analysis
Authors: Dusingize Jean Claude , Hoover Donald R , Shi Qiuhu , Mutimura Eugene , Kiefer Elizabeth , Anastos Kathryn 
Published: December 2013

ObjectivesThe purpose of these analyses was to determine the associations of HIV infection and related immune dysfunction with a glucose homeostasis in the population of antiretroviral-naïve HIV-infected and uninfected Rwandan women. We hypothesise that insulin resistance and its consequences in the developing countries may be further elevated with HIV infection itself regardless of antiretroviral therapy.Study designCross-sectional analysis of a longitudinal cohort.SettingCommunity-based women's associations.ParticipantsIn 2005, 710 HIV-infected (HIV positive) antiretroviral naïve and 226 HIV-uninfected (HIV negative) women were enrolled in the Rwanda Women's Interassociation Study and Assessment (RWISA). Clinical and demographic parameters, CD4 count, fasting insulin and glucose levels, anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were obtained. Linear models were fit to log-transformed Homeostasis Model Assessment (HOMA) with results exponentiated back to a multiplicative effect on the original scale.Primary outcome measuresThe outcome, insulin resistance, was measured by the HOMA, calculated as fasting insulin (μU/mL)×fasting glucose (mmol/L)⁄22.5.ResultsIn adjusted models, HIV-positive women were less insulin resistant than HIV-negative; an HIV-positive woman tended to have 0.728 times as much (95% CI 0.681 to 0.861) HOMA than a comparable HIV-negative woman. Among the HIV-positive women, those with CD4 <200 cells/µL tended to have 0.741 times as much HOMA (95% CI 0.601 to 0.912) as did comparable women with CD4 >350 cells/µL. The older age was independently associated with a lower HOMA insulin resistance. After adjusting for body mass index, fat and fat-free mass were not independently associated with HOMA.ConclusionsThis study found that HIV infection and more advanced HIV infection (CD4 counts <200 cells/µL) were associated with greater insulin sensitivity in antiretroviral naïve African women. These findings provide baseline information for the interpretation of future studies on the effect of antiretroviral therapy on metabolic insulin sensitivity derangements in African population.
Using routinely collected data to improve immunisation histories
Authors: Allen Luke 
Published: December 2013

AbstractImmunisation is one of the most effective health interventions in existence yet outbreaks of vaccine-preventable diseases continue to occur in developed countries. High rates of cover are needed to provide adequate herd immunity and there is evidence that a significant proportion of paediatric inpatients are not up to date even in areas with high levels of community cover. A proportion of these children will have parents who consciously declined immunisation, however the remaining children represent a vulnerable cohort whose under-immunisation is not routinely identified.Two-hundred consecutive admissions to rural paediatric assessment unit had their routinely documented vaccination histories checked against their records on the regional Child Health Information System (CHIS). 30 children (15%) were not up to date on the CHIS, yet routine clerking only identified 5 of these children (17%). After introduction of a simple system whereby ward clerks and doctors were taught how to access and print full immunisation histories from the CHIS, a further 200 consecutive admissions were audited. A similar number were not up to date (29/200) but the proportion of children with missing immunisations correctly identified in the clerking documentation increased to 52% (15 children). This is a 35% improvement (95% CI; 12-58%).Access to routinely collected data can significantly improve identification of under-immunised children and contribute towards higher levels of individual and herd-immunity.
Reducing the risk of needlestick injuries in hospital
Authors: Denny James 
Published: December 2013

AbstractAfter performing procedures involving sharps, many wards in St George's Hospital have no quick and accessible 'point of care' sharps bin for their safe disposal. Instead one must transport potentially hazardous equipment away from the bedside, risking injury and exposure to persons en route.Results from a questionnaire showed that 73% felt they were indeed poorly placed, 95% felt a portable sharps bin system was a good idea, and 95% felt their introduction would be safer. A one month trial of portable sharps bins on the Acute Medical Unit (AMU) showed that 97% felt that the portable sharps bin system reduced risk to themselves and others, 81% felt safer using them, and 90% felt safer knowing their colleagues were using them too.A recent audit in a six month period within 2012 established there were 148 reported needlestick injuries in St George's Hospital. This quality improvement project showed that a majority consensus felt that a portable sharps bin system would be safer than the system currently used and could potentially help reduce these numbers. This project also comes at a time when new EU legislation calls for safer sharps use and disposal and thus offers a solution to ultimately provide better, safer and more advanced safety practices when disposing of sharp equipment.
Addressing Genetic Tumor Heterogeneity through Computationally Predictive Combination Therapy
Authors: Zhao Boyang , Pritchard Justin R. , Lauffenburger Douglas A. , Hemann Michael T. 
Published: December 2013

Abstract
Recent tumor sequencing data suggest an urgent need to develop a methodology to directly address intratumoral heterogeneity in the design of anticancer treatment regimens. We use RNA interference to model heterogeneous tumors, and demonstrate successful validation of computational predictions for how optimized drug combinations can yield superior effects on these tumors both in vitro and in vivo. Importantly, we discover here that for many such tumors knowledge of the predominant subpopulation is insufficient for determining the best drug combination. Surprisingly, in some cases, the optimal drug combination does not include drugs that would treat any particular subpopulation most effectively, challenging straightforward intuition. We confirm examples of such a case with survival studies in a murine preclinical lymphoma model. Altogether, our approach provides new insights about design principles for combination therapy in the context of intratumoral diversity, data that should inform the development of drug regimens superior for complex tumors.
Significance: This study provides the first example of how combination drug regimens, using existing chemotherapies, can be rationally designed to maximize tumor cell death, while minimizing the outgrowth of clonal subpopulations. Cancer Discov; 4(2); 166–74. ©2013 AACR.
See related commentary by Fedele et al., p. 146
This article is highlighted in the In This Issue feature, p. 131
Clinical Reminders to Providers of Patients With Reduced Left Ventricular Ejection Fraction Increase Defibrillator Referral
Authors: Gupta Anurag , Gholami Parisa , Turakhia Mintu P. , Friday Karen , Heidenreich Paul A. 
Published: December 2013

Background—
Many patients who are candidates for implantable cardioverter defibrillators (ICDs) are not referred for potential implantation. We sought to determine if a simple provider reminder would increase referrals.

Methods and Results—

We identified consecutive patients from January 2007 through July 2010 in the VA Palo Alto Health Care System with a left ventricular ejection fraction <35% on echocardiography. Patients were excluded using available administrative data only (no chart review) if they were known to have an ICD, if they were ≥80 years old, or if they did not have a current primary care or cardiology provider within the system. We randomized patients to no intervention or a clinical note to the provider in the medical record. The outcomes were referral for consideration of defibrillator implantation (primary) and documented discussion (secondary). Of 330 patients with left ventricular ejection fraction ≤35%, 128 were known to have an ICD, 85 were no longer followed in the healthcare system, and 28 were ≥80 years old, leaving 89 patients to be randomized. Forty-six patients were randomized to intervention and 43 to control. Eleven of 46 (24%) intervention patients were referred for consideration of ICD implantation during the following 6 months versus 1 of 43 (2%) control patients (
P
=0.004). Overall, 31 of 46 (67%) intervention patients versus 19 of 43 (44%) control patients had documentation discussing potential candidacy for defibrillators (
P
=0.05).

Conclusions—
In patients with low left ventricular ejection fraction, a simple electronic medical record–based intervention directed to their providers improved the rates of referral for ICD implantation.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01217827.
Emergency Medical Equipment Storage
Authors: Grundgeiger Tobias , Harris Bonnie , Ford Nicholas , Abbey Michael , Sanderson Penelope M. , Venkatesh Balasubramanian 
Published: December 2013

Objective: We tested the effectiveness of an illustrated divider (“the divider”) for bedside emergency equipment drawers in an intensive care unit (ICU). In Study 1, we assessed whether the divider increases completeness and standardizes the locations of emergency equipment within the drawer. In Study 2, we investigated whether the divider decreases nurses’ restocking and retrieval times and decreases their workload. Background: Easy access to fully stocked emergency equipment is important during emergencies. However, inefficient equipment storage and cognitively demanding work settings might mean that drawers are incompletely stocked and access to items is slow. Method: A pre-post-post study investigated drawer completeness and item locations before and after the introduction of the divider to 30 ICU drawers. A subsequent experiment measured item restocking time, item retrieval time, and subjective workload for nurses. Results: At 2 weeks and 10 weeks after the divider was introduced, the completeness of the drawer increased significantly compared with before the divider was introduced. The divider decreased the variability of the locations of the 17 items in the drawer to 16% of its original value. Study 2 showed that restocking times but not retrieval times were significantly faster with the divider present. For both tasks, nurses rated their workload lower with the divider. Conclusions: The divider improved the standardization and completeness of emergency equipment. In addition, restocking times and workload were decreased with the divider. Application: Redesigning storage for certain equipment using human factors design principles can help to speed and standardize restocking and ease access to equipment.
Acute Type-A aortic dissection with patent false lumen through to the abdominal aorta: effects of a conventional elephant trunk on malperfusion syndromes and narrowed true lumen
Authors: Imura H , Tanoue M , Shibata M , Maruyama Y , Shirakawa M , Ochi M 
Published: December 2013

Background: Narrowed true lumen and patent false lumen through to the terminal aorta is a high-risk condition for malperfusion syndromes (MS) in acute type-A aortic dissection. It is important to ascertain how the true and false lumens behave after surgery. Patients and Methods: We retrospectively investigated 45 patients with this pathology. The true lumen sizes at the narrowest levels above and below the superior mesenteric artery were followed by computed tomography after surgery (0-36 months). Results: Thirty-seven MS were seen in 23 patients. Hospital mortality was 8.9%. The narrowed true lumen was not enlarged in the first 6 months with a patent false lumen. The elephant trunk procedure did not improve the true lumen size. An extremely narrowed (≤3mm) true lumen was associated with a significantly high incidence of MS and mortality. Conclusions: High incidences of MS were observed in this particular pathology. An extremely narrowed true lumen was accompanied by a high incidence of MS and mortality.
Repair Integrity and Functional Outcome After Arthroscopic Conversion to a Full-Thickness Rotator Cuff Tear
Authors: Kim Kyung Cheon , Shin Hyun Dae , Cha Soo Min , Park Jun Yeong 
Published: December 2013

Background: A few studies have compared high-grade partial-thickness articular- and bursal-side rotator cuff tears postoperatively. Purpose: To compare the clinical and radiological outcomes of high-grade partial-thickness rotator cuff tears treated with arthroscopic conversion to full-thickness tears, followed by repair. Study Design: Cohort study; Level of evidence, 3. Methods: Forty-three consecutive shoulders with high-grade partial-thickness rotator cuff tears (20 articular- and 23 bursal-side lesions) treated with arthroscopic conversion to full-thickness tears, followed by repair using the suture-bridge technique, were evaluated. The final functional evaluation was conducted at a mean of 35.53 months (range, 24-54 months). Radiological outcomes were evaluated at a minimum of 1 year postoperatively. The following outcome measures were used in this study: the American Shoulder and Elbow Surgeons (ASES) score, the University of California, Los Angeles (UCLA) Shoulder Rating Scale, the Constant score, and range of motion. Results: At the final follow-up, the mean ASES, UCLA, and Constant scores improved significantly to 91.80, 32.70, and 75.85, respectively, in the articular-side group (all P < .001). The mean ASES, UCLA, and Constant scores improved significantly to 90.80, 32.52, and 83.00, respectively, in the bursal-side group (all P < .001). The UCLA and ASES scores did not differ significantly between the 2 groups ( P = .821 and .869, respectively), while the Constant scores did ( P = .048). The retear rate was 0% in the articular-side group and 9.5% in the bursal-side group; this difference was not significant ( P = .204). Conclusion: The arthroscopic repair of partial-thickness bursal-side tears resulted in comparable or superior postoperative functional outcomes compared with that of articular-side tears. However, the postoperative retear rate did not differ significantly between the 2 groups.
Adverse Drug Events in Critically Ill Patients With Cancer
Authors: Nazer Lama H. , Hawari Feras , Al-Najjar Taghreed 
Published: December 2013

Objective: To determine the incidence, characteristics, and outcomes of adverse drug events (ADEs) in critically ill patients with cancer. Methods: This was a 5-month prospective observational study. Patients who were admitted to the adult medical/surgical oncology intensive care unit (ICU) were evaluated for any drug-related adverse events during their ICU stay. An ADE was defined as injury or patient harm resulting from medical intervention related to a drug. Results: The incidence rate of ADEs was 96.5 per 1000 patient days and 35.3 per 100 ICU admissions. Of the reported ADEs, 57 (64.8%) were serious/life threatening, 30 (34.1%) were significant, 1 (1.1%) was fatal, and 14 (15.9%) of all ADEs were considered preventable. The most common drug classes associated with ADEs were antidiabetics, antibiotics, and analgesics/sedatives. The length of stay and presence of renal or respiratory failure were significantly associated with an increased number of ADEs. The length of stay and female sex were significantly associated with the likelihood of developing an ADE. Conclusion: Critically ill patients with cancer are at high risk of developing ADEs. Strategies that reduce the incidence and severity of ADEs are essential to improve the outcomes of this patient population.
A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance
Authors: Tian Ze , D’Arcy Padraig , Wang Xin , Ray Arghya , Tai Yu-Tzu , Hu Yiguo , Carrasco Ruben D. , Richardson Paul , Linder Stig , Chauhan Dharminder , Anderson Kenneth C. 
Published: December 2013

Key PointsDeubiquitylating enzymes USP14 and UCHL5 are involved in the tumorigenesis of MM. b-AP15 is a specific USP14 and UCHL5 inhibitor, which blocks growth and induces apoptosis in MM cells.
The role of Dichaete in transcriptional regulation during Drosophila embryonic development
Authors: Aleksic Jelena , Ferrero Enrico , Fischer Bettina , Shen Shih Pei , Russell Steven 
Published: December 2013

Abstract

Background
Group B Sox domain transcription factors play conserved roles in the specification and development of the nervous system in higher metazoans. However, we know comparatively little about how these transcription factors regulate gene expression, and the analysis of Sox gene function in vertebrates is confounded by functional compensation between three closely related family members. In Drosophila, only two group B Sox genes, Dichaete and SoxN, have been shown to function during embryonic CNS development, providing a simpler system for understanding the functions of this important class of regulators.

Results
Using a combination of transcriptional profiling and genome-wide binding analysis we conservatively identify over 1000 high confidence direct Dichaete target genes in the Drosophila genome. We show that Dichaete plays key roles in CNS development, regulating aspects of the temporal transcription factor sequence that confer neuroblast identity. Dichaete also shows a complex interaction with Prospero in the pathway controlling the switch from stem cell self-renewal to neural differentiation. Dichaete potentially regulates many more genes in the Drosophila genome and was found to be associated with over 2000 mapped regulatory elements.

Conclusions
Our analysis suggests that Dichaete acts as a transcriptional hub, controlling multiple regulatory pathways during CNS development. These include a set of core CNS expressed genes that are also bound by the related Sox2 gene during mammalian CNS development. Furthermore, we identify Dichaete as one of the transcription factors involved in the neural stem cell transcriptional network, with evidence supporting the view that Dichaete is involved in controlling the temporal series of divisions regulating neuroblast identity.
Direct measurement of electrostatic fields using single Teflon nanoparticle attached to AFM tip
Authors: Chang Joe-Ming , Chang Wei-Yu , Chen Fu-Rong , Tseng Fan-Gang 
Published: December 2013

Abstract
A single 210-nm Teflon nanoparticle (sTNP) was attached to the vertex of a silicon nitride (Si3N4) atomic force microscope tip and charged via contact electrification. The charged sTNP can then be considered a point charge and used to measure the electrostatic field adjacent to a parallel plate condenser using 30-nm gold/20-nm titanium as electrodes. This technique can provide a measurement resolution of 250/100 nm along the X- and Z-axes, and the minimum electrostatic force can be measured within 50 pN.

PACS

07.79.Lh, 81.16.-c, 84.37. + q
Quantifying circulating hypoxia-induced RNA transcripts in maternal blood to determine in uterofetal hypoxic status
Authors: Whitehead Clare , Teh Wan Tinn , Walker Susan P , Leung Cheryl , Mendis Sonali , Larmour Luke , Tong Stephen 
Published: December 2013

Abstract

Background
Hypoxia in utero can lead to stillbirth and severe perinatal injury. While current prenatal tests can identify fetuses that are hypoxic, none can determine the severity of hypoxia/acidemia. We hypothesized a hypoxic/acidemic fetus would up-regulate and release hypoxia-induced mRNA from the fetoplacental unit into the maternal circulation, where they can be sampled and quantified. Furthermore, we hypothesized the abundance of hypoxia induced mRNA in the maternal circulation would correlate with severity of fetal hypoxia/acidemia in utero. We therefore examined whether abundance of hypoxia-induced mRNA in the maternal circulation correlates with the degree of fetal hypoxia in utero.

Methods
We performed a prospective study of two cohorts: 1) longitudinal study of pregnant women undergoing an induction of labor (labor induces acute fetal hypoxia) and 2) pregnancies complicated by severe preterm growth restriction (chronic fetal hypoxia). For each cohort, we correlated hypoxia induced mRNA in the maternal blood with degree of fetal hypoxia during its final moments in utero, evidenced by umbilical artery pH or lactate levels obtained at birth. Gestational tissues and maternal bloods were sampled and mRNAs quantified by microarray and RT-PCR.

Results
Hypoxia-induced mRNAs in maternal blood rose across labor, an event that induces acute fetal hypoxia. They exhibited a precipitous increase across the second stage of labor, a particularly hypoxic event. Importantly, a hypoxia gene score (sum of the relative expression of four hypoxia-induced genes) strongly correlated with fetal acidemia at birth. Hypoxia-induced mRNAs were also increased in the blood of women carrying severely growth restricted preterm fetuses, a condition of chronic fetal hypoxia. The hypoxia gene score correlated with the severity of ultrasound Doppler velocimetry abnormalities in fetal vessels. Importantly, the hypoxia gene score (derived from mRNA abundance in maternal blood) was significantly correlated with the degree of fetal acidemia at birth in this growth restriction cohort.

Conclusions
Abundance of mRNAs coding hypoxia-induced genes circulating in maternal blood strongly correlates with degree of fetal hypoxia/acidemia. Measuring hypoxia-induced mRNA in maternal blood may form the basis of a novel non-invasive test to clinically determine the degree of fetal hypoxia/acidemia while in utero.