bluuebunny/crossref_metadata_2025 huggingface dataset:
Ankle Injuries in the Pediatric Athlete
Authors: Erickson John B. , Samora Walter P. , Klingele Kevin E.
Published: November 2016

Foot and ankle injuries are the second most common reason for young athletes to present to a primary care physician, and account for up to 30% of visits to sports medicine clinics in this population. Heightened performance expectations placed on today’s young athletes have led to intense training and competition demands. With increasing rates of sport participation among children and adolescents, it is important for treating physicians to have an understanding of the evaluation and management of ankle injuries seen in the pediatric athlete. In treating young athletes it is important to keep in mind the unique developmental and anatomic differences between the skeletally mature and skeletally immature ankle. These differences predispose young athletes to unique injuries not seen in adults. These include injuries that result from congenital or developmental variations, acute injuries, and overuse type injuries.
Anterior Cruciate Ligament Reconstruction in Pediatric and Adolescent Patients Using Quadriceps Tendon Autograft
Authors: Albright Jay , Lepon Ariel Kiyomi , Mayer Stephanie
Published: November 2016

Many techniques for reconstruction of pediatric and adolescent anterior cruciate ligament (ACL) ruptures have been described, yet the best technique to reproduce normal kinematics of the knee while causing minimal growth disturbance is not definitively determined. We describe a technique which adapts the Allen Anderson technique for all-inside, all-epiphyseal, anatomic ACL reconstruction. However, this technique uses a novel quadriceps tendon—patellar bone—autograft to provide the best-possible patient outcomes. ACL reconstruction advancement in pediatrics is important as an increasing number of adolescent athletes experience ACL rupture and desire to return to sport.
Overuse Injuries in the Pediatric Population
Authors: Wu Mark , Fallon Ryan , Heyworth Benton E.
Published: November 2016

Athletic overuse injuries are becoming an increasingly common entity in the active pediatric population. The prevalence of these injuries may be attributed to the combination of an underdeveloped musculoskeletal system, increased participation in competitive sport at a younger age, and increased duration and intensity of training. Many of these injuries may go unreported and/or undiagnosed, as they do not all result in time lost from sports, and are not always appreciated on imaging. Left unrecognized, untreated, or poorly managed, overuse injuries can have long-term health consequences for young athletes. The purpose of this review is to provide a summary of the most recent literature pertaining to the diagnosis and management of several common pediatric overuse injuries. These specific injuries include Little League shoulder and elbow, osteochondritis dissecans of the elbow, stress fractures of the lumbar spine (spondylolysis), femoral neck and tibial shaft stress fractures, Osgood-Schlatter disease, and Sever disease.
The Role of Duodenal Inflammation in Functional Dyspepsia
Authors: Walker Marjorie M. , Talley Nicholas J.
Published: November 2016

Functional dyspepsia (FD) is common and significantly impairs quality of life. Symptoms of FD are considered to originate from the gastroduodenal region, classified by the Rome criteria as disorders of brain-gut interaction without structural alteration. However, it is now apparent that FD is a number of syndromes, the epigastric pain syndrome (bothersome epigastric pain or epigastric burning) and the postprandial distress syndrome (with bothersome postprandial fullness or early satiation) and there are wide-ranging symptoms and severity. The origin of these troublesome symptoms is now considered to be a result of disrupted gastroduodenal neuropathophysiology. The complexity of the syndrome indicates that there must be different triggers, supported by the limited efficacy of the many treatments available. Current research based on evidence by association suggests that duodenal contents, including the duodenal microbiome, pathogens, and allergy may be triggers of FD. Recent studies have also shown that systemic responses of increased circulating lymphocytes and elevated proinflammatory cytokines and subtle inflammation in the duodenum may accompany the onset and persistence of symptoms. This inflammatory phenotype is characterized by innate inflammation, an eosinophil infiltrate in the duodenum in FD in those with postprandial distress syndrome. Routine histopathology practice does not quantify these cells so the status of FD is not yet appreciated as an inflammatory condition. Thus functional is becoming inflammatory and this breakthrough in understanding that functional does not necessarily mean no, but subtle pathology, may improve therapeutic options, which are currently aimed at symptom relief rather than targeted at underlying pathology.
Comparing the Contributions of Acute and Postacute Care Facility Characteristics to Outcomes After Hospitalization for Hip Fracture
Authors: Neuman Mark D. , Silber Jeffrey H. , Passarella Molly R. , Werner Rachel M.
Published: November 2016

Objective:

To quantify the contribution of acute versus postacute care factors to survival and functional outcomes after hip fracture.

Design, Setting, and Participants:

Retrospective cohort study using Medicare data; subjects included previously ambulatory nursing home residents hospitalized for hip fracture between 2005 and 2009.

Methods:

We used logistic regression to measure the associations of hospital and nursing home factors with functional and survival outcomes at 30 and 180 days among patients discharged to a nursing facility; we quantified the contribution of hospital versus nursing home factors to outcomes by the ω statistic.

Results:

Among 45,996 hospitalized patients, 1814 (3.9%) died during hospitalization. A total of 42,781 (93%) were discharged alive to a nursing home. Of these, 12,126 (28%) died within 180 days and 20,479 (48%) died or were newly unable to walk within 180 days. Hospital characteristics were not consistently associated with outcomes. Multiple nursing home characteristics predicted 30- and 180-day outcomes, including bed count, chain membership, and performance on selected quality measures. Nursing home factors explained 3 times more variation in the odds of 30-day mortality than did hospital factors [ω, hospital vs. nursing home: 0.32; 95% confidence interval (CI), 0.11, 0.96], 7 times more variation in the odds of 180-day mortality (ω: 0.15; 95% CI, 0.04, 0.61), and 8 times more variation in the odds of 180-day death or new dependence in locomotion (ω: 0.12; 95% CI, 0.05, 0.31).

Conclusions:

Nursing home factors explain a larger proportion of the variation in clinical outcomes following hip fracture than do hospital factors.
Verbal Communication During Airway Management and Emergent Endotracheal Intubation: Observations of Team Behavior Among Multi-institutional Pediatric Intensive Care Unit In Situ Simulations
Authors: Rozenfeld Ranna A. , Nannicelli Anna P. , Brown Alexandra R. , Eppich Walter J. , Woods Donna M. , Lestrud Steven O. , Noah Zehava L. , Holl Jane L.
Published: November 2016

Objective

To assess health-care teams’ verbal communication, an observable teamwork behavior, during simulations involving pediatric emergency airway management and intubation.

Methods

We conducted video-recorded, risk-informed in situ simulations at 5 hospitals with pediatric intensive care units in the Chicago, Illinois, area. Clinicians participated in their clinical roles (eg, attending physician, bedside nurse) and had access to hospital operational systems (eg, electronic health record, medical imaging, laboratory services). Video-recordings were transcribed; 3 pediatric critical care physicians analyzed the transcripts to assess preintubation communication: (a) the declaration of an airway emergency, (b) intubation medication request(s), and (c) preintubation medication administration.

Results

Ten pediatric intensive care unit simulations were analyzed. Statements to notify the care team of an airway emergency varied widely. In 3 simulations, a dosage for every medication was verbalized in the physician’s initial medication request; however, in 4 simulations, a nurse was the first to verbalize the medication dosage(s) before administration. In 6 of the simulations where preintubation medications were administered, multiple requests for medications were verbalized. A clinician verbally confirmed that each medication was administered in only 2 of the simulations.

Conclusions

No uniform statement was identified to declare an airway emergency among the care teams. Preintubation medication dosages were not consistently included in intubation medication orders, and frequently, there were multiple requests to obtain medications. Using standardized language to declare an airway emergency and verbally communicating medication requests and dosages and confirming administration may improve the quality of care in this critical event.
A Patient Reported Approach to Identify Medical Errors and Improve Patient Safety in the Emergency Department
Authors: Glickman Seth W. , Mehrotra Abhi , Shea Christopher M. , Mayer Celeste , Strickler Jeffrey , Pabers Sandra , Larson James , Goldstein Brian , Mandelkehr Larry , Cairns Charles B. , Pines Jesse M. , Schulman Kevin A.
Published: November 2016

Objective

Medical errors in the emergency department (ED) occur frequently. Yet, common adverse event detection methods, such as voluntary reporting, miss 90% of adverse events. Our objective was to demonstrate the use of patient-reported data in the ED to assess patient safety, including medical errors.

Methods

Analysis of patient-reported survey data collected over a 1-year period in a large, academic emergency department. All patients who provided a valid e-mail or cell phone number received a brief electronic survey within 24 hours of their ED encounter by e-mail or text message with Web link. Patients were asked about ED safety-related processes.

Results

From Aug 2012 to July 2013, we sent 52,693 surveys and received 7103 responses (e-mail response rate 25.8%), including 2836 free-text comments (44% of respondents). Approximately 242 (8.5%) of 2836 comments were classified as potential safety issues, including 12 adverse events, 40 near-misses, 23 errors with minimal risk of harm, and 167 general safety issues (eg, gaps in care transitions). Of the 40 near misses, 35 (75.0%) of 40 were preventable. Of the 52 adverse events or near misses, 5 (9.6%) were also identified via an existing patient occurrence reporting system.

Conclusions

A patient-reported approach to assess ED-patient safety yields important, complementary, and potentially actionable safety information.
Compelled Disclosure of Confidential Information in Patient Safety Research
Authors: Du Li , Murdoch Blake , Chiu Carina , Caulfield Timothy
Published: November 2016

The protection of confidential research data is of key importance to clinical patient safety research. A review of selected Canadian and American case law indicates that although the relationship between researcher and participant has not been recognized as privileged, court-ordered disclosure of confidential research information seems to be a rare occurrence. In this review, we examine how confidentiality issues are presented in informed consent form templates and in relevant research ethics policies. We find an agreement among research policy documents that all information gathered should be treated as confidential, unless otherwise required by law. Confidentiality provisions in informed consent forms reflect the reality that in some cases, the law can compel disclosure of confidential data. There is, therefore, a potential tension between the law and existing research ethics policy. It has been suggested that researchers have an ethical and possibly legal duty to actively resist disclosure requests. We conclude that it is reasonable for researchers to disclose, as part of the informed consent process, how rare successful disclosure demands are and that steps will be taken to oppose such demands.
Effect of Implementing a Standardized Shoulder Dystocia Documentation Form on Quality of Delivery Notes
Authors: Zuckerwise Lisa C. , Hustedt Madison M. , Lipkind Heather S. , Funai Edmund F. , Raab Cheryl A. , Pettker Christian M.
Published: November 2016

Objectives

Complete and accurate documentation by the delivering provider in cases of shoulder dystocia is critical for providing clinical information and care to the patient and protecting providers from litigation risks. Standardized forms improve inclusion of certain data elements in the medical record, but the impact on subsequent narrative notes is unknown. We aimed to determine if implementation of a standardized shoulder dystocia documentation form improves obstetric provider written narrative delivery notes.

Methods

In February 2005, our institution introduced a mandatory, standardized shoulder dystocia form containing 29 discrete data points relevant to shoulder dystocia documentation. We identified all deliveries complicated by shoulder dystocia from 1 year before and 4 years after implementation of this form and analyzed medical records for inclusion of delivery information in both the required form and the narrative delivery notes.

Results

We identified 52 cases before and 100 cases after implementation of the standardized form. Inclusion of elements from the form in narrative delivery notes increased significantly after implementation (P = 0.01). Elements present at higher rates included prepregnancy maternal weight (13% before vs 28% after, P = 0.043), total maternal weight gain (19% vs 36%, P = 0.03), estimated fetal weight (60% vs 77%, P = 0.03), duration of active labor (40% vs 65%, P < 0.01), duration of second stage (27% vs 52%, P < 0.01), and time of delivery from head to body (4% vs 30%, P < 0.01).

Conclusions

Use of a mandatory shoulder dystocia documentation form is associated with significant improvement in the comprehensiveness of delivering provider narrative notes and may encourage more complete and accurate charting. Such improvements can allow for more complete and accurate explanation of events to patients and better demonstrate adherence to standards of care in the management of shoulder dystocia and may improve litigation defensibility.
Synthesis and characterization of azo-guanidine based alcoholic media naked eye DNA sensor
Authors: Altaf Ataf Ali , Hashmat Uzma , Yousaf Muhammad , Lal Bhajan , Ullah Shafiq , Holder Alvin A. , Badshah Amin
Published: November 2016

DNA sensing always has an open meadow of curiosity for biotechnologists and other researchers. Recently, in this field, we have introduced an emerging class of molecules containing azo and guanidine functionalities. In this study, we have synthesized three new compounds (
UA1
,
UA6
and
UA7
) for potential application in DNA sensing in alcoholic medium. The synthesized materials were characterized by elemental analysis, FTIR, UV-visible,
1
H NMR and
13
C NMR spectroscopies. Their DNA sensing potential were investigated by UV-visible spectroscopy. The insight of interaction with DNA was further investigated by electrochemical (cyclic voltammetry) and hydrodynamic (viscosity) studies. The results showed that compounds have moderate DNA binding properties, with the binding constants range being 7.2 × 10
3
, 2.4 × 10
3
and 0.2 × 10
3
 M
−1
, for
UA1
,
UA6
and
UA7
, respectively. Upon binding with DNA, there was a change in colour (a blue shift in the
λ
max
value) which was observable with a naked eye. These results indicated the potential of synthesized compounds as DNA sensors with detection limit 1.8, 5.8 and 4.0 ng µl
−1
for
UA1
,
UA6
and
UA7
, respectively.
Parasite-microbiota interactions potentially affect intestinal communities in wild mammals
Authors: Aivelo Tuomas , Norberg Anna
Published: November 2016

Detecting interaction between species is notoriously difficult, and disentangling species associations in host-related gut communities is especially challenging. Nevertheless, due to contemporary methods, including metabarcoding and 16S sequencing, collecting observational data on community composition has become easier and much more common. We studied the previously collected data sets of intestinal microbiota and parasite compositions within longitudinally followed mouse lemurs by analysing the potential interactions with diversity metrics and novel joint species distribution modelling. Both methods showed consistent statistical association between certain parasite species and microbiotal composition. Both unicellularEimeriasp. and cestodeHymenolepis diminutahad an effect on diversity of gut microbiota. These parasite species also had negative associations with several bacterial orders. In comparison, closely related speciesH. nanadid not have an effect on diversity, and it had positive associations with several bacterial orders. Our results reveal potential interactions between some, but not all, intestinal parasites and gut microbiota. While environmental variables explained almost half of the total variation, of which almost half could be explained by traits of parasites and microbiota, there were no clear patterns regarding mouse lemur individual variables explaining variation in the occurrence patterns of parasite and microbiota significantly. Our results provide new hypothesis for interactions between and among parasites and microbiota to be tested further with experimental studies.
Pre-Hospital Midazolam for Treatment of Status Epilepticus Before and After the Rapid Anticonvulsant Medication Prior to Arrival Trial: A National Observational Cohort Study
Authors: Shtull-Leber Eytan , Silbergleit Robert , Meurer William J.
Published: November 2016

Background

Implementation of evidence-based treatment for pre-hospital status epilepticus can improve outcomes. We hypothesized that publication of a pivotal pre-hospital clinical trial (RAMPART), demonstrating superiority of intramuscular midazolam over intravenous lorazepam, altered the national utilization rates of midazolam for pre-hospital treatment of status epilepticus, while upholding its safety and efficacy outside the trial setting.

Methods and Findings

This is a retrospective, observational cohort study of pre-hospital patient encounters throughout the United States in the National Emergency Medicine Services Information System database, from January 2010 through December 2014. We compared the rates and odds of midazolam use as the first-line treatment for status epilepticus among all adult and pediatric benzodiazepine-treated seizures before and after RAMPART publication (February 2012). Secondary analyses were conducted for rates of airway interventions and rescue therapy, as proxies for safety and efficacy of seizure termination. 156,539 benzodiazepine-treated seizures were identified. Midazolam use increased from 26.1% in January 2010 to 61.7% in December 2014 (difference +35.6%, 95% CI, 32.7%-38.4%). The annual rate of midazolam adoption increased significantly from 5.9% per year to 8.9% per year after the publication of RAMPART (difference +3.0% per year; 95%CI, 1.6%-4.5% per year; adjusted OR 1.24; 95%CI, 1.17-1.32). Overall frequency of rescue therapy and airway interventions changed little after the publication of RAMPART.

Conclusions

These data are consistent with effective, ongoing, but incomplete clinical translation of the RAMPART results. The effects of the trial, however, cannot be isolated. The safety and effectiveness of midazolam for treatment of seizures in prehospital clinical practice appear consistent with trial data, which should encourage continuing increases in utilization.
Isoflurane produces antidepressant effects and induces TrkB signaling in rodents
Authors: Antila Hanna , Ryazantseva Maria , Popova Dina , Sipilä Pia , Guirado Ramon , Kohtala Samuel , Yalcin Ipek , Lindholm Jesse , Vesa Liisa , Sato Vinicius , Cordeira Joshua , Autio Henri , Kislin Mikhail , Rios Maribel , Joca Sâmia , Casarotto Plinio , Khiroug Leonard , Lauri Sari , Taira Tomi , Castrén Eero , Rantamäki Tomi
Published: November 2016

A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3β (GSK3β). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.
Longitudinal genomic surveillance ofPlasmodium falciparummalaria parasites reveals complex genomic architecture of emerging artemisinin resistance in western Thailand
Authors: Cerqueira Gustavo C. , Cheeseman Ian H. , Schaffner Steve F. , Nair Shalini , McDew-White Marina , Phyo Aung Pyae , Ashley Elizabeth A. , Melnikov Alexandre , Rogov Peter , Birren Bruce W. , Nosten François , Anderson Timothy J.C. , Neafsey Daniel E.
Published: November 2016

Background

Artemisinin-based combination therapies are the first line of treatment forPlasmodium falciparuminfections worldwide, but artemisinin resistance (ART-R) has risen rapidly in in Southeast Asia over the last decade. Mutations inkelch13have been associated with artemisinin (ART) resistance in this region. To explore the power of longitudinal genomic surveillance to detect signals inkelch13and other loci that contribute to ART or partner drug resistance, we retrospectively sequenced the genomes of 194P. falciparumisolates from five sites in Northwest Thailand, bracketing the era in which there was a rapid increase in ART-R in this region (2001–2014).

Results

We evaluated statistical metrics for temporal change in the frequency of individual SNPs, assuming that SNPs associated with resistance should increase frequency over this period. AfterKelch13-C580Y, the strongest temporal change was seen at a SNP in phosphatidylinositol 4-kinase (PI4K), situated in a pathway recently implicated in the ART-R mechanism. However, other loci exhibit temporal signatures nearly as strong, and warrant further investigation for involvement in ART-R evolution. Through genome–wide association analysis we also identified a variant in a kelch-domain–containing gene on chromosome 10 that may epistatically modulate ART-R.

Conclusions

This analysis demonstrates the potential of a longitudinal genomic surveillance approach to detect resistance-associated loci and improve our mechanistic understanding of how resistance develops. Evidence for additional genomic regions outside of thekelch13locus associated with ART-R parasites may yield new molecular markers for resistance surveillance and may retard the emergence or spread of ART-R in African parasite populations.
The Tension-sensitive Ion Transport Activity of MSL8 is Critical for its Function in Pollen Hydration and Germination
Authors: Hamilton Eric S. , Haswell Elizabeth S.
Published: November 2016

All cells respond to osmotic challenges, including those imposed during normal growth and development. Mechanosensitive (MS) ion channels provide a conserved mechanism for regulating osmotic forces by conducting ions in response to increased membrane tension. We previously demonstrated that the MS ion channel MscS-Like 8 (MSL8) is required for pollen to survive multiple osmotic challenges that occur during the normal process of fertilization, and that it can inhibit pollen germination. However, it remained unclear whether these physiological functions required ion flux through a mechanically gated channel provided by MSL8. We introduced two point mutations into the predicted pore-lining domain of MSL8 that disrupted normal channel function in different ways. The Ile711Ser mutation increased the tension threshold of the MSL8 channel while leaving conductance unchanged, and the Phe720Leu mutation severely disrupted the MSL8 channel. Both of these mutations impaired the ability of MSL8 to preserve pollen viability during hydration and to maintain the integrity of the pollen tube when expressed at endogenous levels. When overexpressed in amsl8-4null background, MSL8I711Scould partially rescue loss-of-function phenotypes, while MSL8F720Lcould not. When overexpressed in the wild type Lerbackground, MSL8I711Ssuppressed pollen germination, similar to wild type MSL8. In contrast, MSL8F720Lfailed to suppress pollen germination and increased pollen bursting, thereby phenocopying themsl8-4mutant. Thus, an intact MSL8 channel is required to for normal pollen function during hydration and germination. These data establish MSL8 as the first plant MS channel to fulfill previously established criteria for assignment as a mechanotransducer.
tRNA-derived small RNAs target transposable element transcripts
Authors: Choudury Sarah , Slotkin R. Keith , Martinez German
Published: November 2016

tRNA-derived RNA fragments (tRFs) are 18-26 nucleotide small RNAs that are not random degradation products, but are rather specifically cleaved from mature tRNA transcripts. Abundant in stressed or viral-infected cells, the function and potential targets of tRFs are not known. We identified that in the unstressed wild-type male gamete containing pollen of flowering plants, and analogous reproductive structure in non-flowering plant species, tRFs accumulate to high levels. In the reference plantArabidopsis thaliana, tRFs are cleaved by Dicer-like 1 and incorporated into Argonaute1 (AGO1), akin to a microRNA. We utilized the fact that many plant small RNAs direct cleavage of their target transcripts to demonstrate that where the tRF-AGO1 complex acts to specifically target and cleave endogenous transposable element (TE) mRNAs produced from transcriptionally active TEs. The data presented here demonstrate that tRFs arebona-fideregulatory microRNA-like small RNAs involved in the regulation of genome stability through the targeting of TE transcripts.
A positive association between population genetic differentiation and speciation rates in New World birds
Authors: Harvey Michael G. , Seeholzer Glenn F. , Smith Brian Tilston , Rabosky Daniel L. , Cuervo Andrés M. , Klicka John T. , Brumfield Robb T.
Published: November 2016

Although an implicit assumption of speciation biology is that population differentiation is an important stage of evolutionary diversification, its true significance remains largely untested. If population differentiation within a species is related to its speciation rate over evolutionary time, the causes of differentiation could also be driving dynamics of organismal diversity across time and space. Alternatively, geographic variants might be short-lived entities with rates of formation that are unlinked to speciation rates, in which case the causes of differentiation would have only ephemeral impacts. Combining population genetics datasets including 17,746 individuals from 176 New World bird species with speciation rates estimated from phylogenetic data, we show that the population differentiation rates within species predict their speciation rates over long timescales. Although relatively little variance in speciation rate is explained by population differentiation rate, the relationship between the two is robust to diverse strategies of sampling and analyzing both population-level and species-level datasets. Population differentiation occurs at least three to five times faster than speciation, suggesting that most populations are ephemeral. Population differentiation and speciation rates are more tightly linked in tropical species than temperate species, consistent with a history of more stable diversification dynamics through time in the Tropics. Overall, our results suggest investigations into the processes responsible for population differentiation can reveal factors that contribute to broad-scale patterns of diversity.
Engineering Genetically-Encoded Mineralization and Magnetism via Directed Evolution
Authors: Liu Xueliang , Lopez Paola A. , Giessen Tobias W. , Giles Michael , Way Jeffrey C. , Silver Pamela A.
Published: November 2016

Genetically encoding the synthesis of functional nanomaterials such as magnetic nanoparticles enables sensitive and non-invasive biological sensing and control. Via directed evolution of the natural iron-sequestering ferritin protein, we discovered key mutations that lead to significantly enhanced cellular magnetism, resulting in increased physical attraction of ferritin-expressing cells to magnets and increased contrast for cellular magnetic resonance imaging (MRI). The magnetic mutants further demonstrate increased iron biomineralization measured by a novel fluorescent genetic sensor for intracellular free iron. In addition, we engineeredEscherichia colicells with multiple genomic knockouts to increase cellular accumulation of various metals. Lastly to explore further protein candidates for biomagnetism, we characterized members of the DUF892 family using the iron sensor and magnetic columns, confirming their intracellular iron sequestration that results in increased cellular magnetization.
Interaction of CCR4–NOT with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis
Authors: Yang Cheng-Yuan , Ramamoorthy Senthilkumar , Boller Sören , Rosenbaum Marc , Rodriguez Gil Alfonso , Mittler Gerhard , Imai Yumiko , Kuba Keiji , Grosschedl Rudolf
Published: November 2016

Transcription factor EBF1 (early B-cell factor 1) regulates early B-cell differentiation by poising or activating lineage-specific genes and repressing genes associated with alternative cell fates. To identify proteins that regulate the diverse functions of EBF1, we used SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry of proteins associated with endogenous EBF1 in pro-B cells. This analysis identified most components of the multifunctional CCR4–NOT complex, which regulates transcription and mRNA degradation. CNOT3 interacts with EBF1, and we identified histidine 240 in EBF1 as a critical residue for this interaction. Complementation of Ebf1−/− progenitors with EBF1H240A revealed a partial block of pro-B-cell differentiation and altered expression of specific EBF1 target genes that show either reduced transcription or increased mRNA stability. Most deregulated EBF1 target genes show normal occupancy by EBF1H240A, but we also detected genes with altered occupancy, suggesting that the CCR4–NOT complex affects multiple activities of EBF1. Mice with conditional Cnot3 inactivation recapitulate the block of early B-cell differentiation, which we found to be associated with an impaired autoregulation of Ebf1 and reduced expression of pre-B-cell receptor components. Thus, the interaction of the CCR4–NOT complex with EBF1 diversifies the function of EBF1 in a context-dependent manner and may coordinate transcriptional and post-transcriptional gene regulation.
The pleiotropic deubiquitinase Ubp3 confers aneuploidy tolerance
Authors: Dodgson Stacie E. , Santaguida Stefano , Kim Sharon , Sheltzer Jason , Amon Angelika
Published: November 2016

Aneuploidy—or an unbalanced karyotype in which whole chromosomes are gained or lost—causes reduced fitness at both the cellular and organismal levels but is also a hallmark of human cancers. Aneuploidy causes a variety of cellular stresses, including genomic instability, proteotoxic and oxidative stresses, and impaired protein trafficking. The deubiquitinase Ubp3, which was identified by a genome-wide screen for gene deletions that impair the fitness of aneuploid yeast, is a key regulator of aneuploid cell homeostasis. We show that deletion of UBP3 exacerbates both karyotype-specific phenotypes and global stresses of aneuploid cells, including oxidative and proteotoxic stress. Indeed, Ubp3 is essential for proper proteasome function in euploid cells, and deletion of this deubiquitinase leads to further proteasome-mediated proteotoxicity in aneuploid yeast. Notably, the importance of UBP3 in aneuploid cells is conserved. Depletion of the human homolog of UBP3, USP10, is detrimental to the fitness of human cells upon chromosome missegregation, and this fitness defect is accompanied by autophagy inhibition. We thus used a genome-wide screen in yeast to identify a guardian of aneuploid cell fitness conserved across species. We propose that interfering with Ubp3/USP10 function could be a productive avenue in the development of novel cancer therapeutics.
Convergence or divergence? Corporate climate-change reporting in China
Authors: Yang Helen Hong , Farley Alan
Published: November 2016

Purpose

This paper aims to investigate the extent international and domestic guidelines have influenced the content of corporate environmental reporting (CER) in the context of China’s radical institutional transition from bureaucratic secrecy to openness, marked by the first nationwide guidelines on Open Government Information (OGI) and Open Environment Information (OEI), effective in 2008.

Design/methodology/approach

The study develops a research instrument that captures international and Chinese national guidelines pertaining to environmental information disclosure. This instrument is used to analyse 471 reports of leading 100 listed Chinese companies for the critical period between 2006 and 2010. Chi-square test statistics are used to analyse the significance of differences in reporting items supported by Chinese guidelines versus those supported by international reporting guidelines only.

Findings

Partial convergence in climate-change reporting co-exists with divergent China specific interpretation of climate change. The coercive institutional influences of the Chinese government’s guidance in OGI and OEI led to the rapid growth of CER in 2008 compared to 2006, despite compliance being voluntary.

Originality/value

The study is innovative in explicitly measuring any changes in reporting relative to the potential for additional reporting. Such a method more accurately evaluates the effect of institutional influences on reporting. The study provides a fresh profile of the content and the reporting medium of CER, with a particular focus on climate change in the Chinese context. The findings highlight research into CER based on annual reports risks results being incomplete and misleading. Findings have practical implications for policy makers in other emerging economies.
Voluntary disclosure of intangibles and analysts’ earnings forecasts and recommendations
Authors: Maaloul Anis , Ben Amar Walid , Zeghal Daniel
Published: November 2016

Purpose

The purpose of this paper is to investigate the relationship between voluntary disclosure of intangibles and financial analysts’ earnings forecasts properties.

Design/methodology/approach

Disclosures about intangible assets were hand-collected through content analysis of annual reports of a sample of US non-financial firms, while analysts’ earnings forecasts properties were collected from Bloomberg Professional database. The authors relied on correlation and multivariate regression analyses to test the research hypotheses.

Findings

The results show that increased intangible disclosures affect analysts’ earnings forecasts accuracy, dispersion, and favourable consensus recommendations. However, this effect varies according to the nature of intangible assets.

Practical implications

The results may be of interest to different market participants such as corporate managers, financial analysts, and standards setting bodies that recently published guidelines on voluntary disclosure of intangibles.

Originality/value

This study develops a new comprehensive index to measure the content of narrative disclosures about a large number of intangibles, such as human, structural, and relational assets. The findings contribute to the current debate on the value-relevance of narrative disclosures on intangibles to investors and financial analysts.
The use of generalized audit software by Egyptian external auditors
Authors: Kim Hyo-Jeong , Kotb Amr , Eldaly Mohamed Khaled
Published: November 2016

Purpose

The purpose of this paper is to explore: the actual usage of generalized audit software (GAS) features among Egyptian external auditors, through the technology acceptance model (TAM); how the conceptual complexity of GAS features impact its actual usage; and what factors influencing the GAS use by Egyptian external auditors.

Design/methodology/approach

External audit professionals at 12 international audit firms, including the Big 4 and eight medium-sized firms, in Egypt were surveyed.

Findings

The results show that the basic features including database queries, ratio analysis, and audit sampling were higher in GAS use, perceived usefulness, and perceived ease of use among Egyptian external auditors than the advanced features: digital analysis, regression/ANOVA, and data mining classification. The structural equation modelling analysis by GAS features suggests that perceived ease of use has a stronger effect on GAS use when the conceptual complexity of GAS features is high. The analysis also support that the use of GAS by Egyptian external auditors is more affected by co-worker, supervisor, or organization through perceived usefulness, but not by job relevance, output quality, and result demonstration.

Research limitations/implications

Although Egyptian external auditors participated in this study may limit the extent to which the findings may be generalized, the responses provide an insight into the actual usage of GAS features by external auditors and the impact of conceptual complexity of GAS features, which is consistent with the literature concerning the relatively low level of utilizing the advanced features of GAS by internal auditors, suggesting that the issues revealed should be of concern.

Practical implications

The results reported in this paper are useful to audit software developers and audit firms in their understanding of factors influencing GAS usage in a different audit context.

Originality/value

The study adds value to prior research by providing context-contingent insight into the application of TAM in an unexplored audit context.
Service flexibility: conceptualizing value creation in service
Authors: Brozovic Danilo , Nordin Fredrik , Kindström Daniel
Published: November 2016

Purpose

The purpose of this paper is to analyze the subject-specific literature on service and flexibility and derive a conceptualization of the linkages between provider flexibility and customers’ value creation.

Design/methodology/approach

The authors analyze existing perspectives on service and flexibility and propose linkages between provider flexibility and customer value creation.

Findings

Drawing on the service logic literature, and utilizing real-world examples, this paper advances propositions and a conceptual model of how flexibility can contribute to value creation.

Research limitations/implications

This paper establishes the basis for a practical and applicable flexibility perspective on value creation. It is particularly important for service-oriented providers and other firms operating in dynamic contexts.

Practical implications

The propositions and conceptual model offer suggestions on the manner in which provider flexibility contributes to customer value creation. Contextual influences that moderate provider flexibility in value creation are also included.

Originality/value

This paper contributes a novel perspective on service, which may serve as the starting point for the development of a more formal flexibility perspective on value creation.
Renal function in HIV/HBV co‐infected and HBV mono‐infected patients on a long‐term treatment with tenofovir in real life setting
Authors: Milazzo Laura , Gervasoni Cristina , Falvella Felicia Stefania , Cattaneo Dario , Mazzali Cristina , Ronzi Paola , Binda Francesca , Cheli Stefania , Sollima Salvatore , Antinori Spinello
Published: November 2016

The human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co‐infection is likely to be associated with an increased risk of kidney disease, due to the additional factors that may affect renal function in the HIV population. We aimed to evaluate renal toxicity in HIV/HBV and HBV mono‐infected patients on long‐term therapy with tenofovir (TDF) and to explore the association of polymorphisms in ATP‐binding cassette (ABCC)2, ABCC4, ABCC10 with the development of renal dysfunction. From September 2006 to November 2014, 44 HIV/HBV co‐infected and 34 HBV mono‐infected patients were commenced on TDF. Data of renal safety were retrospectively collected and analyzed. ABCC2, ABCC4 and ABCC10 genotypes were identified by real‐time PCR. Over 60 months of observation, there was a significant increase in mean creatinine levels from baseline (P<.01) that was not significantly different between the two study groups. Moreover, a significant decline in estimated glomerular filtration rate (eGFR) was observed from baseline (P<.01), and it was significantly greater in HBV mono‐infected than co‐infected patients (P=.03). The distribution of ABCC2, ABCC4 and ABCC10 genotypes among a subgroup of 34 patients did not show significant association with eGFR decline <90 mL/min per 1.73 m2. Although our findings showed a statistically significant decrease in eGFR with long‐term use of TDF, its clinical impact seems to be modest. The role of genetic factors to identify patients at greater risk for developing tenofovir‐induced renal toxicity needs to be further investigated.
Challenges of Implementing a Communication‐and‐Resolution Program Where Multiple Organizations Must Cooperate
Authors: Mello Michelle M. , Armstrong Sarah J. , Greenberg Yelena , McCotter Patricia I. , Gallagher Thomas H.
Published: November 2016

Objective

To implement a communication‐and‐resolution program (CRP) in a setting in which liability insurers and health care facilities must collaborate to resolve incidents involving a facility and separately insured clinicians.

Study Setting

Six hospitals and clinics and a liability insurer in Washington State.

Study Design

Sites designed and implemented CRPs and contributed information about cases and operational challenges over 20 months. Data were qualitatively analyzed.

Data Collection Methods

Data from interviews with personnel responsible for CRP implementation were triangulated with data on program cases collected by sites and notes recorded during meetings with sites and among project team members.

Principal Findings

Sites experienced small victories in resolving particular cases and streamlining some working relationships, but they were unable to successfully implement a collaborative CRP. Barriers included the insurer's distance from the point of care, passive rather than active support from top leaders, coordinating across departments and organizations, workload, nonparticipation by some physicians, and overcoming distrust.

Conclusions

Operating CRPs where multiple organizations must collaborate can be highly challenging. Success likely requires several preconditions, including preexisting trust among organizations, active leadership engagement, physicians' commitment to participate, mechanisms for quickly transmitting information to insurers, tolerance for missteps, and clear protocols for joint investigations and resolutions.
Integrated Approach to Reduce Perinatal Adverse Events: Standardized Processes, Interdisciplinary Teamwork Training, and Performance Feedback
Authors: Riley William , Begun James W. , Meredith Les , Miller Kristi K. , Connolly Kathy , Price Rebecca , Muri Janet H. , McCullough Mac , Davis Stanley
Published: November 2016

Objective

To improve safety practices and reduce adverse events in perinatal units of acute care hospitals.

Data Sources

Primary data collected from perinatal units of 14 hospitals participating in the intervention between 2008 and 2012. Baseline secondary data collected from the same hospitals between 2006 and 2007.

Study Design

A prospective study involving 342,754 deliveries was conducted using a quality improvement collaborative that supported three primary interventions. Primary measures include adoption of three standardized care processes and four measures of outcomes.

Data Collection Methods

Chart audits were conducted to measure the implementation of standardized care processes. Outcome measures were collected and validated by the National Perinatal Information Center.

Principal Findings

The hospital perinatal units increased use of all three care processes, raising consolidated overall use from 38 to 81 percent between 2008 and 2012. The harms measured by the Adverse Outcome Index decreased 14 percent, and a run chart analysis revealed two special causes associated with the interventions.

Conclusions

This study demonstrates the ability of hospital perinatal staff to implement efforts to reduce perinatal harm using a quality improvement collaborative. Findings help inform the relationship between the use of standardized care processes, teamwork training, and improved perinatal outcomes, and suggest that a multiplicity of integrated strategies, rather than a single intervention, may be essential to achieve high reliability.
Evaluation of Cross‐contamination of Nylon Bags with Heavy‐loaded Gasoline Fire Debris and with Automotive Paint Thinner
Authors: Belchior Filipa , Andrews Stephen P.
Published: November 2016

Nylon bags are used for packaging fire debris in several countries, particularly in Europe. The possibility of cross‐contamination during transport from the fire scene to the laboratory, in normal casework conditions in the U.K., was studied for two brands of nylon bags, using simulated heavy‐loaded fire debris. Three experiments were carried out with each brand, using as sample a piece of cotton fabric soaked with gasoline. One experiment was carried out using automotive paint thinner (oxygenated solvent). Each sample was sealed in a nylon bag and stored in contact with eight empty bags. The empty bags were analysed at regular intervals for a period of time up to 8 weeks, using SPME and GC/MS. Cross‐contamination was found for components of gasoline (toluene and C2‐alkylbenzenes) in the two brands of nylon bags used, after 4 days and 2 weeks. Cross‐contamination using automotive topcoat thinner was detected after 2 days.
RISK, RACE, AND RECIDIVISM: PREDICTIVE BIAS AND DISPARATE IMPACT*
Authors: SKEEM JENNIFER L. , LOWENKAMP CHRISTOPHER T.
Published: November 2016

One way to unwind mass incarceration without compromising public safety is to use risk assessment instruments in sentencing and corrections. Although these instruments figure prominently in current reforms, critics argue that benefits in crime control will be offset by an adverse effect on racial minorities. Based on a sample of 34,794 federal offenders, we examine the relationships among race, risk assessment [the Post Conviction Risk Assessment (PCRA)], and future arrest. First, application of well‐established principles of psychological science revealed little evidence of test bias for the PCRA—the instrument strongly predicts arrest for both Black and White offenders, and a given score has essentially the same meaning—that is, the same probability of recidivism—across groups. Second, Black offenders obtain higher average PCRA scores than do White offenders (d = .34; 13.5 percent nonoverlap in groups’ scores), so some applications could create disparate impact. Third, most (66 percent) of the racial difference in PCRA scores is attributable to criminal history—which is already embedded in sentencing guidelines. Finally, criminal history is not a proxy for race, but instead it mediates the relationship between race and future arrest. Data are more helpful than rhetoric if the goal is to improve practice at this opportune moment in history.