bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a Low‐risk Mild Traumatic Brain Injury and Intracranial Hemorrhage Emergency Department Observation Protocol
Authors: Yun Brian J. , Borczuk Pierre , Wang Lulu , Dorner Stephen , White Benjamin A. , Raja Ali S. 
Published: November 2017

AbstractObjectivesAmong emergency physicians, there is wide variation in admitting practices for patients who suffered a mild traumatic brain injury (TBI) with an intracranial hemorrhage (ICH). The purpose of this study was to evaluate the effects of implementing a protocol in the emergency department (ED) observation unit for patients with mild TBI and ICH.MethodsThis retrospective cohort study was approved by the institutional review board. Study subjects were patients ≥ 18 years of age with an International Classification of Diseases code corresponding to a traumatic ICH and admitted to an ED observation unit (EDOU) of an urban, academic Level I trauma center between February 1, 2015, and January 31, 2017. Patient data and discharge disposition were abstracted from the electronic health record, and imaging data, from the final neuroradiologist report. To measure kappa, two abstractors independently collected data for presence of neuro deficit from a 10% random sample of the medical charts. Using a multivariable logistic regression model with a propensity score of the probability of placement in the EDOU before and after protocol implementation as a covariate, we sought to determine the pre‐post effects of implementing a protocol on the composite outcome of admission to the floor, intensive care unit, or operating room from the EDOU and the proportion of patients with worsening findings on repeat computed tomography (CT) head scan in the EDOU.ResultsA total of 379 patients were identified during the study period; 83 were excluded as they were found to have no ICH on chart review. Inter‐rater reliability kappa statistic was 0.63 for 30 charts. Among the 296 patients who remained eligible and comprised the study population, 143 were in the preprotocol period and 153 after protocol implementation. The EDOU protocol was associated with an independently statistically significant decreased odds ratio (OR) for admission or worsening ICH on repeat CT scan (OR = 0.45, 95% confidence interval [CI] = 0.25–0.82, p = 0.009) in the observation unit. After a stay in the EDOU, 26% (37/143) of patients required an inpatient admission before implementation of the protocol and 13% (20/153) of patients required an inpatient admission after protocol implementation. There was no statistically significant difference in log transformed EDOU length of stay (LOS) between the groups after adjusting for propensity score (p = 0.34).ConclusionsWhile there was no difference in EDOU LOS, implementing a low‐risk mild TBI and ICH protocol in the EDOU may decrease the rate of inpatient admissions from the EDOU. A protocol‐driven observation unit may help physicians by standardizing eligibility criteria and by providing guidance on management. As the propensity score method limits our ability to create a straightforward predictive model, a future larger study should validate the results.
Risk of Past Year Injury Related to Hours of Exposure to an Elevated Blood Alcohol Concentration and Average Monthly Alcohol Volume: Data from 4 National Alcohol Surveys (2000 to 2015)
Authors: Cherpitel Cheryl J. , Ye Yu , Kerr William C. 
Published: November 2017

BackgroundWhile a strong association exists between alcohol and injury in emergency department (ED) studies, these studies are not representative of the general population.MethodsThe association of injury with the number of hours of exposure to a blood alcohol concentration (BAC) ≥ 0.05 and average monthly volume in drinks, both based on self‐report of quantity and frequency of drinking in the last year, in a merged sample of respondents (n = 29,571) from 4 U.S. National Alcohol Surveys (2000 to 2015) are analyzed. Risk curves based on categorical step function and fractional polynomial modeling were analyzed separately by gender, and by age and race/ethnicity for males.ResultsRisk of injury increased at 1 hour of a BAC exposure of ≥ 0.05 and at an average monthly volume of 1 drink. Risk of injury for spirits increased to an average daily volume of 1 drink, but no association was found for injury risk and average volume for either wine or beer. Risk of injury increased with both exposure hours and monthly volume among males, but little association was found for either consumption measure with risk of injury for females. Among males, increased risk of injury was greater for whites than for blacks or Hispanics for BAC exposure; Hispanics showed a continued elevated risk up to 8 hours of exposure. After peaking at a monthly volume of 1 drink, injury risk decreased substantially for blacks, but was more gradual for whites, while risk increased very slightly for Hispanics to about 4 drinks per day. Males aged 18 to 29 showed the largest increase in risk associated with the number of hours of exposure to a BAC of ≥0.05, with risk doubling at 1 hour of exposure, but subsequently falling.ConclusionsWhile findings here are weaker than those from ED studies and likely due to the context of drinking, risk of injury appears to increase at relatively low levels of consumption, suggesting the importance of preventive efforts to reduce injury not only for heavier drinkers but also for more moderate drinkers.
The effect of inspections, rotations and client preferences on staffing decisions
Authors: Moroney Robyn , Knechel W. Robert , Dowling Carlin 
Published: November 2017

AbstractWith increased regulatory focus on audits and concerns about whether audit regulation is achieving its stated aims, it is timely to investigate how regulator inspection of audit files and partner rotations may be affecting staffing decisions. This is an important issue, which affects all audits, as the calibre of staff allocated across engagements impacts the quality of audit work delivered. This study reports the results of an experiment where auditor participants allocate staff across two audits, where regulation anticipated (none, inspection, rotation) and a client request for the best staff (absent, present) are manipulated between‐subjects. We find that auditors allocate lower calibre staff when neither an inspection nor rotation is anticipated than when either is anticipated. When an inspection is anticipated, auditors allocate staff with more knowledge and compliance skills. When a rotation is anticipated, auditors allocate staff with more people skills. A client request for the best staff only has an effect when a partner is due to be rotated, where auditors allocate staff with more people skills in response to the client request. Our findings provide greater understanding of staffing decisions, which may affect audit quality if concerns around audit inspections and partner rotations are perceived by auditors as more important than the underlying risk or complexity of an engagement when allocating staff.
Chronic pain and opioid abuse: Factors associated with health‐related quality of life
Authors: Jones Jermaine D. , Vogelman Jonathan S. , Luba Rachel , Mumtaz Mudassir , Comer Sandra D. 
Published: November 2017

Background and ObjectivesWhile research on the separate relationships between health‐related quality of life (HRQOL) and chronic pain, and HRQOL and opioid abuse has been sparse, even less work has investigated the factors associated with HRQOL in individuals who have both chronic pain and meet criteria for opioid use disorder. The data presented in this analysis should allow a better understanding the factors important to quality of life among this dual‐diagnosed population.MethodsIndividuals with dual diagnoses of chronic pain and opioid use disorder were recruited for clinical research studies at Columbia University Medical Center. Participants (n = 47) completed inventories to assess pain (Brief Pain Inventory), opioid (ab)use, and depression (Beck Depression Inventory). Variable from these and other inventories, along with demographic factors (age, race, sex, pain severity, depressive symptoms, duration of opioid use, route of opioid use, amount of opioid use) were entered into a regression analysis in order to identify the strongest predictors of SF‐36 Health Survey score.ResultsIn the bivariate analysis we found that demographic and drug use variables were rarely associated with HRQOL. Typically, ratings of pain severity and pain interference were the best predictors. In the multivariate analysis, we found that across the several HRQOL dimensions greater Brief Pain Inventory (BPI) ratings of pain “interference” and Beck Depression Inventory (BDI) scores were consistently associated with lower HRQOL.Conclusions and Scientific SignificanceThese data suggest that insufficient pain management and depression are significant variables contributing to lower quality of life among individuals with chronic pain and opioid use disorder. (Am J Addict 2017;26:815–821)
The microenvironment of naked mole‐rat burrows in East Africa
Authors: Holtze Susanne , Braude Stanton , Lemma Alemayehu , Koch Rosie , Morhart Michaela , Szafranski Karol , Platzer Matthias , Alemayehu Fitsum , Goeritz Frank , Hildebrandt Thomas Bernd 
Published: November 2017

AbstractNaked mole‐rats (Heterocephalus glaber) can be extremely long‐lived and are resistant to cancer. Hence, they have been proposed as a model organism for delayed ageing. Adaptation to a constant hypoxic and hypercapnic environment has been suggested as reason for their apparent ability to tolerate oxidative stress. Nevertheless, little is known about the natural habitat to which the species evolved. Naked mole‐rat burrow environments were assessed in Ethiopia and Kenya. Despite reported thermolability of naked mole‐rats, skin temperature upon capture varied (23.7–35.4°C), mostly within the species’ thermoneutral zone, demonstrating their ability to maintain homoiothermy even under wide fluctuations of burrow temperature (24.6–48.8°C) and humidity (31.2%–92.8%), which are far greater than previously reported. Burrow temperature regularly alternates during the daytime and night‐time, driving convective currents that circulate air in the tunnels. Consequently, concentrations of CO2 and O2 in burrows only slightly deviated from surface atmosphere. This contradicts the assumption of constant hypoxia/hypercapnia in subterranean burrows. In addition to diffusion, animal movement and occasional wind‐driven ventilation, our data support the temperature‐driven convective model of circulation. The naked mole‐rat burrow is a relatively normoxic subterranean microenvironment with considerable fluctuations in temperature and humidity.
Renal hypoxia in kidney disease: Cause or consequence?
Authors: Ow C. P. C. , Ngo J. P. , Ullah M. M. , Hilliard L. M. , Evans R. G. 
Published: November 2017

AbstractTissue hypoxia has been proposed as an important factor in the pathophysiology of both chronic kidney disease (CKD) and acute kidney injury (AKI), initiating and propagating a vicious cycle of tubular injury, vascular rarefaction, and fibrosis and thus exacerbation of hypoxia. Here, we critically evaluate this proposition by systematically reviewing the literature relevant to the following six questions: (i) Is kidney disease always associated with tissue hypoxia? (ii) Does tissue hypoxia drive signalling cascades that lead to tissue damage and dysfunction? (iii) Does tissue hypoxia per se lead to kidney disease? (iv) Does tissue hypoxia precede pathology? (v) Does tissue hypoxia colocalize with pathology? (vi) Does prevention of tissue hypoxia prevent kidney disease? We conclude that tissue hypoxia is a common feature of both AKI and CKD. Furthermore, at least under in vitro conditions, renal tissue hypoxia drives signalling cascades that lead to tissue damage and dysfunction. Tissue hypoxia itself can lead to renal pathology, independent of other known risk factors for kidney disease. There is also some evidence that tissue hypoxia precedes renal pathology, at least in some forms of kidney disease. However, we have made relatively little progress in determining the spatial relationships between tissue hypoxia and pathological processes (i.e. colocalization) or whether therapies targeted to reduce tissue hypoxia can prevent or delay the progression of renal disease. Thus, the hypothesis that tissue hypoxia is a “common pathway” to both AKI and CKD still remains to be adequately tested.
The I in autism: Severity and social functioning in autism are related to self‐processing
Authors: Gillespie‐Smith Karri , Ballantyne Carrie , Branigan Holly P. , Turk David J. , Cunningham Sheila J. 
Published: November 2017

It is well established that children with autism spectrum disorder (ASD) show impaired understanding of others and deficits within social functioning. However, it is still unknown whether self‐processing is related to these impairments and to what extent self impacts social functioning and communication. Using an ownership paradigm, we show that children with ASD and chronological‐ and verbal‐age‐matched typically developing (TD) children do show the self‐referential effect in memory. In addition, the self‐bias was dependent on symptom severity and socio‐communicative ability. Children with milder ASD symptoms were more likely to have a high self‐bias, consistent with a low attention to others relative to self. In contrast, severe ASD symptoms were associated with reduced self‐bias, consistent with an ‘absent‐self’ hypothesis. These findings indicate that deficits in self‐processing may be related to impairments in social cognition for those on the lower end of the autism spectrum.
Statement of contribution

What is already known on this subject?

Impaired self‐processing in autism is linked to social and cognitive deficits.

There are discrepancies across the literature, with reports of both intact and impaired self‐processing in autism.

Ownership tasks are developmentally appropriate and have shown to induce self‐memory bias in young children.

What does this study add?

Using an ownership task, children with autism showed a significant self‐memory bias, greater than typical peers.

Severity was negatively correlated with level of self‐bias, potentially explaining the previous discrepancies.

Severe autism symptoms are associated with an ‘absent self’, and mild autism symptoms reduce attention to others.
Improving the efficacy of proteasome inhibitors in the treatment of renal cell carcinoma by combination with the human immunodeficiency virus (HIV)‐protease inhibitors lopinavir or nelfinavir
Authors: Abt Dominik , Besse Andrej , Sedlarikova Lenka , Kraus Marianne , Bader Juergen , Silzle Tobias , Vodinska Martina , Slaby Ondrej , Schmid Hans‐Peter , Engeler Daniel Stephan , Driessen Christoph , Besse Lenka 
Published: November 2017

ObjectivesTo assess the potential of second‐generation proteasome inhibition by carfilzomib and its combination with the human immunodeficiency virus (HIV) protease inhibitors (HIV‐PIs) lopinavir and nelfinavir in vitro for improved treatment of clear cell renal cell cancer (ccRCC).Materials and MethodsCytotoxicity, reactive oxygen species (ROS) production, and unfolded protein response (UPR) activation of proteasome inhibitors, HIV‐PIs, and their combination were assessed in three cell lines and primary cells derived from three ccRCC tumours by MTS assay, flow cytometry, quantitative reverse transcriptase‐polymerase chain reaction and western blot, respectively. Proteasome activity was determined by activity based probes. Flow cytometry was used to assess apoptosis by annexin V/propidium iodide assay and ATP‐binding cassette sub‐family B member 1 (ABCB1) activity by MitoTracker™ Green FM efflux assay (Thermo Fisher Scientific, MA, USA).ResultsLopinavir and nelfinavir significantly increased the cytotoxic effect of carfilzomib in all cell lines and primary cells. ABCB1 efflux pump inhibition, induction of ROS production, and UPR pre‐activation by lopinavir were identified as underlying mechanisms of this strong synergistic effect. Combined treatment led to unresolved protein stress, increased activation of pro‐apoptotic UPR pathway, and a significant increase in apoptosis.ConclusionThe combination of the proteasome inhibitor carfilzomib and the HIV‐PIs lopinavir and nelfinavir has a strong synergistic cytotoxic activity against ccRCCin vitro at therapeutically relevant drug concentrations. This effect is most likely explained by synergistic UPR triggering and ABCB1‐modulation caused by HIV‐PIs. Our findings suggest that combined treatment of second‐generation proteasome inhibitors and HIV‐PIs should be investigated in patients with metastatic RCC within a clinical trial.
Simultaneous use of erythropoietin and LFM‐A13 as a new therapeutic approach for colorectal cancer
Authors: Tankiewicz‐Kwedlo Anna , Hermanowicz Justyna Magdalena , Domaniewski Tomasz , Pawlak Krystyna , Rusak Małgorzata , Pryczynicz Anna , Surazynski Arkadiusz , Kaminski Tomasz , Kazberuk Adam , Pawlak Dariusz 
Published: November 2017

Background and PurposeBruton's tyrosine kinase (Btk) is a non‐receptor tyrosine kinase involved in the activation of signalling pathways responsible for cell maturation and viability. Btk has previously been reported to be overexpressed in colon cancers. This kind of cancer is often accompanied by anaemia, which is treated with an erythropoietin supplement. The goal of the present study was to assess the effects of combination therapy with erythropoietin β (Epo) and LFM‐A13 (Btk inhibitor) on colon cancer in in vitro and in vivo models.Experimental ApproachDLD‐1 and HT‐29 human colon adenocarcinoma cells were cultured with Epo and LFM‐A13. Cell number and viability, and mRNA and protein levels of Epo receptors, Btk and Akt were assessed. Nude mice were inoculated with adenocarcinoma cells and treated with Epo and LFM‐A13.Key ResultsThe combination of Epo and LFM‐A13 mostly exerted a synergistic inhibitory effect on colon cancer cell growth. The therapeutic scheme used effectively killed the cancer cells and attenuated the Btk signalling pathways. Epo + LFM‐A13 also prevented the normal process of microtubule assembly during mitosis by down‐regulating the expression of Polo‐like kinase 1. The combination of Epo and LFM‐A13 significantly reduced the growth rate of tumour cells, while it showed high safety profile, inducing no nephrotoxicity, hepatotoxicity or changes in the haematological parameters.Conclusion and ImplicationsEpo significantly enhances the antitumour activity of LFM‐A13, indicating that a combination of Epo and LFM‐A13 has potential as an effective therapeutic approach for patients with colorectal cancer.
Quantifying the relationship between inhibition of VEGF receptor 2, drug‐induced blood pressure elevation and hypertension
Authors: Collins Teresa , Gray Kelly , Bista Michal , Skinner Matt , Hardy Christopher , Wang Haiyun , Mettetal Jerome T , Harmer Alexander R 
Published: November 2017

Background and PurposeSeveral anti‐angiogenic cancer drugs that inhibit VEGF receptor (VEGFR) signalling for efficacy are associated with a 15–60% incidence of hypertension. Tyrosine kinase inhibitors (TKIs) that have off‐target activity at VEGFR‐2 may also cause blood pressure elevation as an undesirable side effect. Therefore, the ability to translate VEGFR‐2 off‐target potency into blood pressure elevation would be useful in development of novel TKIs. Here, we have sought to quantify the relationship between VEGFR‐2 inhibition and blood pressure elevation for a range of kinase inhibitors.Experimental ApproachPorcine aortic endothelial cells overexpressing VEGFR‐2 (PAE) were used to determine IC50 for VEGFR‐2 phosphorylation. These IC50 values were compared with published reports of exposure attained during clinical use and the corresponding incidence of all‐grade hypertension. Unbound average plasma concentration (Cav,u) was selected to be the most appropriate pharmacokinetic parameter. The pharmacokinetic‐pharmacodynamic (PKPD) relationship for blood pressure elevation was investigated for selected kinase inhibitors, using data derived either from clinical papers or from rat telemetry experiments.Key ResultsAll‐grade hypertension was predominantly observed when the Cav,u was >0.1‐fold of the VEGFR‐2 (PAE) IC50. Furthermore, based on the PKPD analysis, an exposure‐dependent blood pressure elevation >1 mmHg was observed only when the Cav,u was >0.1‐fold of the VEGFR‐2 (PAE) IC50.Conclusions and ImplicationsTaken together, these data show that the risk of blood pressure elevation is proportional to the amount of VEGFR‐2 inhibition, and a margin of >10‐fold between VEGFR‐2 IC50 and Cav,u appears to confer a minimal risk of hypertension.
Fostering a culture of family‐centred care: Child welfare professionals' beliefs about fathers, family instability, and the value of relationship education
Authors: Mallette Jacquelyn K. , Futris Ted G. , Schramm David G. 
Published: November 2017

AbstractGuided by the Cultural Competence Attainment Model, the purpose of this study is to examine how socio‐demographic and work characteristics are associated with variations in child welfare professionals' (CWPs) attitudes about father involvement and family instability and how these attitudes are linked with whether they view relationship and marriage education as relevant to their efforts to support families. Drawing from a sample of 624 CWPs and using latent profile analysis, the results revealed three latent classes of CWPs, with most professionals being labelled as either “moderately” or “highly” concerned about father involvement and family instability, with a smaller class of professionals labelled as having less concern about these family issues. Those labelled as highly concerned tended to be older, male, African American, married, and had worked longer in the child welfare field. As well, those labelled as highly concerned were more likely to agree that strengthening the couple and coparenting relationship would benefit children and were most amenable to receiving RME training. Implications for relationship and marriage education training for child welfare professionals and other practitioners are provided.
Bayesian Occam's Razor Is a Razor of the People
Authors: Blanchard Thomas , Lombrozo Tania , Nichols Shaun 
Published: November 2017

AbstractOccam's razor—the idea that all else being equal, we should pick the simpler hypothesis—plays a prominent role in ordinary and scientific inference. But why are simpler hypotheses better? One attractive hypothesis known as Bayesian Occam's razor (BOR) is that more complex hypotheses tend to be more flexible—they can accommodate a wider range of possible data—and that flexibility is automatically penalized by Bayesian inference. In two experiments, we provide evidence that people's intuitive probabilistic and explanatory judgments follow the prescriptions of BOR. In particular, people's judgments are consistent with the two most distinctive characteristics of BOR: They penalize hypotheses as a function not only of their numbers of free parameters but also as a function of the size of the parameter space, and they penalize those hypotheses even when their parameters can be “tuned” to fit the data better than comparatively simpler hypotheses.