bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambush Killings of the Police, 1970–2018: A Longitudinal Examination of the “War on Cops” Debate
Authors: White Michael D.
Published: May 2020

Over the last few years, there has been a series of high-profile, premeditated ambush attacks on police, which has led some to conclude there is a “war on cops.” Unfortunately, prior research has not examined the prevalence of police ambushes over an extended period of time, and the most recent study only analyzed the phenomenon through 2013. Moreover, the “war on cops” thesis implies a very specific motivation for an ambush: hatred of police or desire to seek vengeance in response to police killings of citizens. Prior research has not sufficiently explored the motivations of ambush attacks, or whether recent trends in ambushes are linked to a “war on cops” motive. I investigate ambush killings of police from 1970 to 2018 using data from the Officer Down Memorial Page in an attempt to address these research gaps. I apply a temporal coding scheme of when the attack occurred to isolate killings of police that are consistent with the International Association of Chiefs of Police definition of an ambush. Results from linear regression show that the annual rates of ambush killings of police have declined by more than 90% since 1970. Although ambushes spiked in 2016 and 2018 to the highest rates in 20 years, interrupted time series analysis indicates no statistically significant increase post-2013. Spikes have also occurred in nonambush killings since 2014. Police leaders and researchers should monitor trends in ambush and nonambush killings of police, as the recent spikes may presage the emergence of a chronic problem.
The effect of inventory turnover on financial performance in the US restaurant industry: The moderating role of exposure to commodity price risk
Authors: Park Eunhye (Olivia) , Kim Woo-Hyuk
Published: May 2020

Despite the importance of efficiently managing inventory in the restaurant business, evidence of satisfactory inventory turnover in the restaurant industry remains limited. This study examined the relationship between inventory turnover and firm performance as well as the moderating role of exposure to commodity price risk therein. We collected data representing publicly traded US restaurant companies from the Mergent Online’s database for the period from 1999 to 2015. The results indicate there is a positive relationship between inventory turnover and corporate financial performance. Moreover, we found that the interaction effect of exposure to commodity price risk on the relationship between inventory turnover and firms’ profitability. To our knowledge, this is the first study empirically examining the adoption of inventory management by the restaurant industry. Also, these findings provide the importance of effective inventory management based on the specific type of restaurants.
A new cumulative fatigue damage model under biaxial loading
Authors: Shen Chen , Talha Abderrahim , Hamdi Adel , Benseddiq Noureddine
Published: May 2020

Criteria of fatigue damage play a key role in life prediction of structures subjected to random loadings. In previous works, a cumulative damage model called damage stress model was developed. This model takes into account not only the loading history but also the nonlinear evolution of damage. Damage stress model improved its predictive capability of fatigue life for several materials such as steels and aluminum alloys. In this paper, a new approach of cumulative damage, based upon the damage stress model parameter, is investigated for different loading paths under finite life regime. To build the new damage indicator, the damage stress model parameter is coupled with an equivalent stress formulated via Sines, Dang Van and Robert fatigue criteria, respectively. The relevance of the proposed model is examined using series of biaxial tests performed on cruciform specimens made of an aluminum alloy. Several types of loadings composed of constant amplitude fatigue, cumulative fatigue with two/three blocks and repeated blocks were set up. Good agreement is highlighted when the prediction, obtained with the proposed model, is compared to our experimental data.
Gait Analysis of Patients After Allogeneic Hematopoietic Cell Transplantation Reveals Impairments of Functional Performance
Authors: Kneis Sarah , Straub Elisa , Walz Isabelle Daniela , von Olshausen Philipp , Wehrle Anja , Gollhofer Albert , Bertz Hartmut
Published: May 2020

Background: After allogeneic hematopoietic cell transplantation (alloHCT), patients often report functional impairments like reduced gait speed and muscle weakness. These impairments can increase the risk of adverse health events similar to elderly populations. However, they have not been quantified in patients after alloHCT (PATs). Methods: We compared fear of falling (Falls Efficacy Scale–International) and temporal gait parameters recorded on a 10-m walkway at preferred and maximum gait speed and under dual-task walking of 16 PATs (aged 31-73 years) with 15 age-matched control participants (CONs) and 17 seniors (SENs, aged >73 years). Results: Groups’ gait parameters especially differed during the maximum speed condition: PATs walked slower and required more steps/10 m than CONs. PATs exhibited greater stride, stance, and swing times than CONs. PATs’ swing time was even longer than SENs’. The PATs’ ability to accelerate their gait speed from preferred to fast was smaller compared with CONs’. PATs reported a greater fear of falling than CONs and SENs. Conclusion: Gait analysis of alloHCT patients has revealed impairments of functional performance. Patients presented a diminished ability to accelerate gait and extending steps possibly related to a notable strength deficit that impairs power-generation abilities from lower extremities. Furthermore, patients reported a greater fear of falling than control participants and even seniors. Slowing locomotion could be a risk-preventive safety strategy. Since functional disadvantages may put alloHCT patients at a higher risk of frailty, reinforcing appropriate physical exercises already during and after alloHCT could prevent adverse health events and reduce the risk of premature functional aging.
Microbial extracellular RNAs and their roles in human diseases
Authors: Lee Heon-Jin
Published: May 2020

Extracellular RNAs (exRNAs) are released by extracellular vesicles, small membranous nanoparticles secreted by all cell types. When transported into cells, exRNAs can modulate gene expression or cellular responses in the target cells since many small RNAs have regulatory functions. Indeed, it is widely acknowledged that endogenous exRNAs in the human body are related to various diseases. However, microbial exRNAs have been less studied, and their connection to host diseases has just begun to be explored. In this review, I will discuss analytical methods for exRNAs and the potential use of exRNAs as disease biomarkers. I also consider current progress in understanding the regulation of host mechanisms by microbial exRNAs as inter-kingdom communication, efforts to utilize extracellular vesicles as therapeutic vehicles loaded with engineered RNA cargos, and a putative connection between microbial exRNA-based regulation of host responses and human diseases such as Alzheimer’s. This overview aims to present novel insights into pathogenesis with regard to the function of microbial exRNAs as “disease-relevant travelers.”

Impact statement

The number of commensal bacteria in the body surpasses the number of actual human cells. Thus, various interactions between microbes and human cells constitute an inevitable phenomenon. Recent evidence has led to bacterial extracellular RNAs (exRNAs) being proposed as good candidates for microbe–host inter-kingdom communication tools as they can modulate the expression of host genes. However, research findings on the relevance of interactions between extracellular RNA and human diseases are still in their infancy. Nevertheless, substantial data suggest that microbial exRNAs are implicated in various human diseases both at local and distant sites. By exploring various scenarios for the involvement of microbial exRNAs in human diseases, we may better understand the role of exRNAs as “communication signals” for diseases and thereby develop novel therapeutic strategies by using them and their carrier extracellular vesicles.
Enabling trustworthy personal data protection in eHealth and well-being services through privacy-by-design
Authors: Robles Tomás , Bordel Borja , Alcarria Ramón , Sánchez-de-Rivera Diego
Published: May 2020

Users are each day more aware of their privacy and data protection. Although this problem is transversal to every digital service, it is especially relevant when critical and personal information is managed, as in eHealth and well-being services. During the last years, many different innovative services in this area have been proposed. However, data management challenges are still in need of a solution. In general, data are directly sent to services but no trustworthy instruments to recover these data or remove them from services are available. In this scheme, services become the users’ data owners although users keep the rights to access, modify, and be forgotten. Nevertheless, the adequate implementation of these rights is not guaranteed, as services use the received data with commercial purposes. In order to address and solve this situation, we propose a new trustworthy personal data protection mechanism for well-being services, based on privacy-by-design technologies. This new mechanism is based on Blockchain networks and indirection functions and tokens. Blockchain networks execute transparent smart contracts, where users’ rights are codified, and store the users’ personal data which are never sent or given to external services. Besides, permissions and privacy restrictions designed by users to be applied to their data and services consuming them are also implemented in these smart contracts. Finally, an experimental validation is also described to evaluate the Quality of Experience (in terms of user satisfaction) and Quality of Service (in terms of processing delay) compared to traditional service provision solutions.
Lung Retraction for Exposure of Lateral Wall Vessels in Off-Pump Bypass Grafting
Authors: Kapoor Lalit , Kumar Devraj , Kumar Sathish , Gayen Rakesh , Ganguly Somnath , Narayan Pradeep
Published: May 2020

One of the major challenges in off-pump coronary artery bypass grafting (OPCAB) is ensuring adequate exposure of the lateral wall vessels. In most cases when the left pleura is opened during harvesting of the left internal thoracic artery , the lung frequently obscures the view. Reducing the tidal volume is practised by certain surgeons, which however in the presence of a single lumen tube affects both lungs and is best avoided in OPCAB. We describe a technique that allows adequate exposure of the circumflex artery and its branches without compromising the tidal volume.
Obturator bypass using a ringed polytetrafluoroethylene graft for inguinal graft infection
Authors: Gwon Jun G , Han Youngjin , Cho Yong-Pil , Kwon Tae-Won
Published: May 2020

Objective

Inguinal vascular graft infections are high-risk events that cannot be controlled medically but require surgical intervention. This study reviewed the long-term clinical outcomes of obturator bypass using a ringed polytetrafluoroethylene graft for inguinal graft infection.

Methods

A total of eight consecutive patients who underwent obturator bypass using a ringed polytetrafluoroethylene graft for inguinal prosthetic graft infection at a single medical center between January 2006 and October 2017 were retrospectively analyzed. The demographics, clinical characteristics, surgical procedure, and clinical outcomes were evaluated.

Results

There was no perioperative death; however, there were three operative complications. On the 1st and 9th postoperative day, two patients underwent hematoma evacuation in the pelvic cavity, and the other patient underwent suture reinforcement for partial dehiscence of the distal anastomosis on the 49th postoperative day. The median length of hospital stay was 14.5 (range, 7–29) days. Only one graft occlusion was observed at postoperative month 40; however, there were no ischemic symptoms. There were no limb amputations and postoperative deaths during the long-term follow-up period. There were no infections of the previous residual and obturator bypass grafts and inguinal infection during the follow-up period of 49 (range, 7–154) months.

Conclusion

Obturator bypass for inguinal graft infection is feasible and durable with excellent long-term outcomes. However, perioperative bleeding should be taken into consideration.
Contested spaces – shared places: A South African perspective
Authors: Vandeyar Saloshna
Published: May 2020

This article presents an account of how contested spaces: shared places have played out in the South African education context by tracing how the historical, political, social and educational contexts of South Africa created and determined shared places. The article draws on findings from a range of research projects that I conducted over the past 15 years and that utilised the meta-theoretical framework of social constructivism and the methodological framework of qualitative case studies, narrative inquiry and portraiture. Findings from this collection of research studies reveal that the creation and evolution of shared spaces though activated by political, social and educational policy intent that was good and at times exceptional, ‘knowledge in the blood’ coupled with a passion for power witnessed policy in action transform these shared spaces into largely contested spaces. Intriguingly, within these spaces sparks of ‘goodness’ emerged that hold promise for a brighter future.
Cost-effectiveness of adding atezolizumab to first-line chemotherapy in patients with advanced triple-negative breast cancer
Authors: Wu Bin , Ma Fei
Published: May 2020

Background:

The effectiveness of atezolizumab plus nab-paclitaxel for advanced triple-negative breast cancer (TNBC) has been demonstrated. We aimed to evaluate its cost-effectiveness on advanced TNBC from the US payer perspective.

Methods:

A Markov model was adopted to project the disease course of newly diagnosed advanced TNBC. The clinical data were gathered from the IMpassion130 trial. Cost and health preference data were derived from the literature. The incremental cost-effectiveness ratio (ICER) was measured, and one-way sensitivity analysis and probabilistic sensitivity analysis were performed for exploring the model uncertainties.

Results:

Our results demonstrated that atezolizumab plus nab-paclitaxel augmented versus nab-paclitaxel therapy cost $104,278 and $149,465 and yielded an additional 0.371 and 0.762 of quality-adjusted life year (QALY) in in all patients with unknown PD-L1 status and subpopulation with PD-L1-positive, respectively, which led to an ICER of $281,448 and $196,073 per QALY gained. In all patients with unknown PD-L1 status, atezolizumab plus nab-paclitaxel treatment guiding by PD-L1 expression testing resulted in an ICER of $183,508 per QALY gained. Atezolizumab plus nab-paclitaxel could maintain a trend of positive incremental net health benefits and >50% probabilities of cost-effectiveness at the threshold of $200,000/QALY in more than half of subgroups with PD-L1-positive. One-way and probabilistic sensitivity analyses revealed the results were most sensitive to the hazard ratios (HRs) of overall survival (OS) of atezolizumab plus nab-paclitaxel versus nab-paclitaxel treatment.

Conclusion:

The atezolizumab plus nab-paclitaxel treatment is likely to be a cost-effective option compared with chemotherapy based on nab-paclitaxel for the patients with PD-L1-positive advanced TNBC.
Power of the People’s Parties and a post-Soviet Parliament: Regional infrastructural, economic, and ethnic networks of power in contemporary Mongolia
Authors: Smith Marissa J
Published: May 2020

In 1994, the new Orkhon Province was created, transforming the status of the Soviet-established federal municipality Erdenet, a major copper-mining center responsible for much of the country’s export revenues and central to ongoing Mongolian–Russian relations. Rather than representing increased participation in national government for Erdenet residents, many of whom are members of transborder minority ethnicities with ties to remote parts of the country, the formation of the province has been controversial locally, as it has meant the introduction of provincial governors, de facto appointed by the Prime Minister. At the same time, the People’s Parties descending from the single state party of the socialist era have in fact been successful at maintaining their networks across the country, and often fielded successful candidates for seats representing Orkhon. Representatives have included the director of a large local construction firm who also held the post of director of foreign trade within the mining enterprise (2008 to 2012, 2016 to present), the son of the mining enterprise’s former General Director (2012 to present), and a politician long based in Ulaanbaatar but central to the MPRP (2016 to present). The situation demonstrates the tension in Mongolian governance between Ulaanbaatar-based centralization and vertical integration on the one hand (also pursued through attempts to privatize the mining enterprise) and the independence of constituencies integrated with regional infrastructural, economic, and ethnic networks built up through long histories of international imperial entanglements on the other.
Designing for Patient Safety and Efficiency: Simulation-Based Hospital Design Testing
Authors: Colman Nora , Edmond Mary Bond , Dalpiaz Ashley , Walter Sarah , Miller David C. , Hebbar Kiran
Published: May 2020

Objective:

In the schematic design phase of a new freestanding children’s hospital, Simulation-based Hospital Design Testing (SbHDT) was used to evaluate the proposed design of 11 clinical areas. The purpose of this article is to describe the SbHDT process and how it can help identify and mitigate safety concerns during the facility design process.

Background:

In the design of new healthcare facilities, the ability to mitigate risk in the preconstruction period is imperative. SbHDT in a full-scale cardboard mock-up can be used to proactively test the complex interface between people and the built environment.

Method:

This study was a prospective investigation of SbHDT in the schematic design planning phase for a 400-bed freestanding children’s hospital where frontline staff simulated episodes of care. Latent conditions related to design were identified through structured debriefing. Failure mode and effect analysis was used to categorize and prioritize simulation findings and was used by the architect team to inform design solutions. A second round of testing was conducted in order to validate design changes.

Results:

A statistically significant reduction in criticality scores between Round 1 ( n = 201, median = 16.14, SD = 5.8) and Round 2 ( n = 201, median score of 7.68, SD = 5.26, p < .001) was identified. Bivariate analysis also demonstrated a statistically significant reduction in very high/high criticality scores between Round 1 and Round 2.

Conclusions:

SbHDT in the schematic phase of design planning was effective in mitigating risk related to design prototypes through effective identification of latent conditions and validation of design changes.
Building a theory by induction: The example of goal setting theory
Authors: Locke Edwin A. , Latham Gary P.
Published: May 2020

This article discusses the development of goal setting theory through induction. The processes such as formulating concepts and definitions, measurement issues, data gathering, data integration and presentation, identifying moderators and mediators, resolving contradictions, noting issues in application, expansions and extensions, and the role of induction in deduction are explained. A multi-decade effort that involves these processes led to a useful theory that has withstood the test of time.
Analyzing value creation in electronic retailing: The case of Digikala–Part A
Authors: Hanafizadeh Payam , Mehri Saeedeh , Hasanabadi Hamid
Published: May 2020

Many e-commerce businesses are emerging in the form of start-ups in Iran. Plenty of these businesses fail to gain significant market share. Electronic retail stores are among the most commonly used electronic business models. Despite the many challenges facing e-retailers due to market changes and customer preferences, Digikala has been ranked as the most popular and most visited website and has managed to gain over 85% of the Iranian retail market. In addition, Digikala is one of the largest electronic retailers in the Middle East. This study aims at analyzing value creation in Digikala in order to overcome these challenges and answering the following question: What value does Digikala create?
Secondary sclerosing cholangitis in critically ill patients has a poor outcome but lower tumour incidence than primary sclerosing cholangitis
Authors: Kirstein Martha M , Book Thorsten , Manns Michael P , von Hahn Thomas , Voigtländer Torsten
Published: May 2020

Background

Secondary sclerosing cholangitis in critically ill patients (SSC‐CIP) is an emerging disease with grim prognosis.

Objective

Our aim was the analysis of prognostic factors, long‐term outcome and risk of tumour development in SSC‐CIP compared with primary sclerosing cholangitis (PSC) patients.

Methods

Retrospective analysis between 2008 and 2018.

Results

One hundred and eleven patients with SSC‐CIP and 408 PSC patients were identified. Median orthotopic liver transplantation (OLT)‐free survival was 16 months for SSC‐CIP and 147 months for PSC (p  < 0.001). OLT was performed in 18/111 SSC‐CIP compared with 166/408 PSC patients (p  < 0.001). Malignant tumours were detected in 17.9% of PSC patients (73/408) compared with 2.7% (3/111) in SSC‐CIP (p  < 0.001). In multivariate Cox regression analysis low levels of C‐reactive protein (hazard ratio 4.687 (95% confidence interval (CI) 1.144–19.199, p  = 0.032) were significantly associated with a prolonged survival whereas higher age (hazard ratio 0.488 (95% CI 0.23–1.038), p  = 0.062) showed a trend for shorter survival in SSC‐CIP. For PSC malignancies (hazard ratio 0.42 (95% CI 0.313–0.575), p  < 0.001) and higher age (hazard ratio 0.709 (95% CI 0.544–0.922), p  = 0.01) were associated with a shorter OLT‐free survival.

Conclusion

SSC‐CIP is characterized by acute onset of liver disease and poor prognosis but with lower tumour incidence compared with PSC.
Towards a physically motivated planetary accounting framework
Authors: Barbosa Miguel , Bertolami Orfeu , Francisco Frederico
Published: May 2020

In this work, we present a physically motivated Planetary Accounting Framework for the Earth System. We show that the impact of the human activity in terms of the planetary boundary variables can be accounted for in our Landau–Ginzburg phase transition physical formulation. We then use the interaction between climate change and ocean acidification mechanisms to exemplify the relation of the concentration and flux of substances of the planetary boundary variables, as proposed by the accounting framework of Meyer and Newman, with the underlying thermodynamic transformation, quantifiable by the Landau–Ginzburg inspired model.
Evaluation of a web-based, tailored intervention to encourage help-seeking for lung cancer symptoms: a randomised controlled trial
Authors: Mueller Julia , Davies Alan , Jay Caroline , Harper Simon , Todd Chris
Published: May 2020

Background

People with lung cancer often wait for several months before presenting symptoms to health services. Some patients report seeking information online to help them appraise symptoms. No research has evaluated whether websites about lung cancer present information in an optimal manner to encourage help-seeking.

Objective

To evaluate the effectiveness of an online, tailored, theory-based intervention in encouraging help-seeking behaviour among people with potential lung cancer symptoms.

Methods

The intervention consisted of a specialised website which provided tailored information about lung cancer and included a component to address beliefs about help-seeking, based on the Theory of Planned Behaviour (TPB-component). Individuals with undiagnosed symptoms were randomised to receive information about lung cancer in a factorial design (tailored/untailored × TPB-component/no TPB-component). Pre and post viewing webpages, participants reported perceived likelihood of seeking help. Data were analysed using robust mixed factorial ANOVA.

Results

Data from 253 participants (73.9% female) were analysed. No effect for the TPB-component was found ( p = 0.16), nor for tailoring ( p = 0.27). Self-reported likelihood of seeking help increased significantly from pre to post ( p < 0.001), regardless of tailoring and TPB-components.

Conclusion

Self-reported likelihood of seeking help for potential lung cancer symptoms may increase after viewing information online. This does not appear to be affected by information tailoring and components to address beliefs. However, intentions remained unchanged in the majority of the sample. This suggests further efforts are needed to improve lung cancer websites if they are to be a useful resource for those seeking advice about their symptoms.
Within- and Between-Persons Effects of Self-Esteem and Affective State as Antecedents and Consequences of Dysfunctional Behaviors in the Everyday Lives of Patients With Borderline Personality Disorder
Authors: Santangelo Philip S. , Holtmann Jana , Hosoya Georg , Bohus Martin , Kockler Tobias D. , Koudela-Hamila Susanne , Eid Michael , Ebner-Priemer Ulrich W.
Published: May 2020

Dysfunctional behaviors are conceptualized as maladaptive affective coping attempts in borderline personality disorder (BPD). The recent benefits-and-barriers model extended the affective function assumption by adding self-esteem as a barrier to engaging in dysfunctional behaviors. Patients with BPD ( N = 119) carried e-diaries to report their current self-esteem, emotional valence, tense arousal, and whether they engaged in dysfunctional behaviors 12 times a day for 4 days. Dynamic structural equation modeling revealed that on the within-person level, high momentary negative affect predicted dysfunctional behaviors, and on the between-person level, low trait self-esteem predicted dysfunctional behaviors. We also found an association between engaging in dysfunctional behaviors and momentary self-esteem and trait levels of valence and tense arousal. Moreover, our results indicate a deterioration of, rather than relief from, negative affective state after dysfunctional behaviors. These findings highlight the importance of emotion-regulation skills and reestablishing a positive self-view as important treatment targets to reduce dysfunctional behaviors in BPD.
Free convective heat transfer in Jeffrey fluid with suspended nanoparticles and Cattaneo–Christov heat flux
Authors: Vasu B , Ray Atul Kumar , Gorla Rama SR
Published: May 2020

Free convection flow of Jeffrey nanofluid past a vertical plate with sinusoidal variations of surface temperature and species concentration is presented. The study of heat transfer and nanofluid transport has been done by employing Cattaneo–Christov heat flux model and Buongiorno model, respectively. Equations governing the flow are non-dimensionalized using appropriate transformations. Furthermore, the method of local similarity and local non-similarity is used to reduce the equations into non-linear coupled system of equations which are then solved by homotopy analysis method. The obtained results are validated by comparing with the existing results available in the literature. The numerical results are found to be in good agreement. The effects of varying the physical parameters such as Deborah Number, Prandtl number, Schmidt number, thermophoresis parameter, Brownian motion parameter and buoyancy ratio parameter are obtained and presented graphically. The effect of sinusoidal variation of surface temperature and species concentration on the skin friction coefficient, Nusselt number and Sherwood number is also shown. Velocity for Jeffrey nanofluid is more than the Newtonian nanofluid while temperature and nanoparticle concentration for Jeffrey nanofluid is less than the Newtonian nanofluid. Raising value of thermal relaxation times leads to an increase in the heat transfer coefficient. It is observed that temperature of Cattaneo–Christov heat flux model is less than that in classical Fourier’s model away from the vertical wall. These types of boundary layer flow problems are found in vertical film solar energy collector, grain storage, transportation and power generation, thermal insulation, gas production, petroleum resources, geothermal reservoirs.
Evaluation of the pharmacokinetic interaction and safety of ubrogepant coadministered with acetaminophen or nonsteroidal anti-inflammatory drugs: A randomized trial
Authors: Jakate Abhijeet , Boinpally Ramesh , Butler Matthew , Lu Kaifeng , Womack Kristi , McGeeney Danielle , Periclou Antonia
Published: May 2020

Background:

Ubrogepant is a novel, oral calcitonin gene–related peptide receptor antagonist approved by the US Food and Drug Administration for acute treatment of migraine with or without aura in adults.

Objectives:

To assess potential pharmacokinetic (PK) drug–drug interactions in healthy participants and inform the safety and tolerability of ubrogepant alone and in combination with acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) in healthy participants and participants with migraine.

Methods:

Two phase 1, three-way crossover studies randomized healthy adults to 100 mg ubrogepant alone, 1000 mg acetaminophen or 500 mg naproxen alone, and 100 mg ubrogepant plus 1000 mg acetaminophen or 500 mg naproxen. Geometric mean ratios (GMRs) and 90% confidence intervals were calculated based on statistical comparison of maximum plasma drug concentration ( C max) and area under the plasma drug concentration–time curve (AUC) for treatment in combination versus alone. Two phase 3 randomized trials included adults with migraine. Treatment-emergent adverse events (TEAEs) were evaluated.

Results:

Time to C max and terminal elimination half-life for all treatments were unchanged when coadministered. Ubrogepant C max and AUC increased by approximately 40% when coadministered with acetaminophen. Acetaminophen C max decreased by 24% (GMR = 0.76) when coadministered with ubrogepant. There were no significant PK interactions between ubrogepant and naproxen. TEAE rates in the acetaminophen and NSAID rescue medication groups were similar to ubrogepant alone.

Conclusions:

Coadministration of ubrogepant and acetaminophen resulted in a statistically significant increase in ubrogepant exposure and a decrease in acetaminophen C max; however, these changes were not clinically relevant. No statistically or clinically relevant changes in PK were associated with ubrogepant and naproxen coadministration. No safety concerns were identified for ubrogepant alone or in combination with acetaminophen or NSAIDs.
Epidermal growth factor receptor–dependent DNA repair promotes murine and human hematopoietic regeneration
Authors: Fang Tiancheng , Zhang Yurun , Chang Vivian Y. , Roos Martina , Termini Christina M. , Signaevskaia Lia , Quarmyne Mamle , Lin Paulina K. , Pang Amara , Kan Jenny , Yan Xiao , Javier Anna , Pohl Katherine , Zhao Liman , Scott Peter , Himburg Heather A. , Chute John P.
Published: May 2020

Chemotherapy and irradiation cause DNA damage to hematopoietic stem cells (HSCs), leading to HSC depletion and dysfunction and the risk of malignant transformation over time. Extrinsic regulation of HSC DNA repair is not well understood, and therapies to augment HSC DNA repair following myelosuppression remain undeveloped. We report that epidermal growth factor receptor (EGFR) regulates DNA repair in HSCs following irradiation via activation of the DNA-dependent protein kinase–catalytic subunit (DNA-PKcs) and nonhomologous end joining (NHEJ). We show that hematopoietic regeneration in vivo following total body irradiation is dependent upon EGFR-mediated repair of DNA damage via activation of DNA-PKcs. Conditional deletion of EGFR in hematopoietic stem and progenitor cells (HSPCs) significantly decreased DNA-PKcs activity following irradiation, causing increased HSC DNA damage and depressed HSC recovery over time. Systemic administration of epidermal growth factor (EGF) promoted HSC DNA repair and rapid hematologic recovery in chemotherapy-treated mice and had no effect on acute myeloid leukemia growth in vivo. Further, EGF treatment drove the recovery of human HSCs capable of multilineage in vivo repopulation following radiation injury. Whole-genome sequencing analysis revealed no increase in coding region mutations in HSPCs from EGF-treated mice, but increased intergenic copy number variant mutations were detected. These studies demonstrate that EGF promotes HSC DNA repair and hematopoietic regeneration in vivo via augmentation of NHEJ. EGF has therapeutic potential to promote human hematopoietic regeneration, and further studies are warranted to assess long-term hematopoietic effects.
Nosocomial outbreak of COVID-19 pneumonia in Wuhan, China
Authors: Wang Xiaorong , Zhou Qiong , He Yukun , Liu Lingbo , Ma Xinqian , Wei Xiaoshan , Jiang Nanchuan , Liang Limei , Zheng Yali , Ma Ling , Xu Yu , Yang Dong , Zhang Jianchu , Yang Bohan , Jiang Ning , Deng Tao , Zhai Bingbing , Gao Yang , Liu Wenxuan , Bai Xinghua , Pan Tao , Wang Guoqing , Chang Yujun , Zhang Zhi , Shi Huanzhong , Ma Wan-Li , Gao Zhancheng
Published: May 2020

Background

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infected over 3300 healthcare workers in early 2020 in China. Little information is known about nosocomial infections of healthcare workers in the initial period. We analysed data from healthcare workers with nosocomial infections in Wuhan Union Hospital (Wuhan, China) and their family members.

Methods

We collected and analysed data on exposure history, illness timelines and epidemiological characteristics from 25 healthcare workers with laboratory-confirmed coronavirus disease 2019 (COVID-19) and two healthcare workers in whom COVID-19 was highly suspected, as well as 10 of their family members with COVID-19, between 5 January and 12 February 2020. The demographics and clinical features of the 35 laboratory-confirmed cases were investigated and viral RNA of 12 cases was sequenced and analysed.

Results

Nine clusters were found among the patients. All patients showed mild to moderate clinical manifestation and recovered without deterioration. The mean period of incubation was 4.5 days, the mean±sdclinical onset serial interval (COSI) was 5.2±3.2 days, and the median virus shedding time was 18.5 days. Complete genomic sequences of 12 different coronavirus strains demonstrated that the viral structure, with small irrelevant mutations, was stable in the transmission chains and showed remarkable traits of infectious traceability.

Conclusions

SARS-CoV-2 can be rapidly transmitted from person to person, regardless of whether they have symptoms, in both hospital settings and social activities, based on the short period of incubation and COSI. The public health service should take practical measures to curb the spread, including isolation of cases, tracing close contacts, and containment of severe epidemic areas. Besides this, healthcare workers should be alert during the epidemic and self-quarantine if self-suspected of infection.
A major genetic determinant of autoimmune diseases is associated with the presence of autoantibodies in hypersensitivity pneumonitis
Authors: Buendía-Roldán Ivette , Santiago-Ruiz Luis , Pérez-Rubio Gloria , Mejía Mayra , Rojas-Serrano Jorge , Ambrocio-Ortiz Enrique , Benítez-Valdez Geovanni , Selman Moisés , Falfán-Valencia Ramcés
Published: May 2020

Background

Hypersensitivity pneumonitis is an immune-mediated disease triggered by exposure to organic particles in susceptible individuals. It has been reported that a subgroup of patients with hypersensitivity pneumonitis develops autoantibodies with or without clinical manifestations of autoimmune disease. However, the mechanisms involved in this process and the effect of the autoantibodies on clinical course in hypersensitivity pneumonitis is unknown. We evaluated the association between human leukocyte antigen (HLA) class II alleles and hypersensitivity pneumonitis patients with and without autoantibodies.

Methods

170 hypersensitivity pneumonitis patients were included. We analysed the presence of antinuclear antibodies, rheumatoid factor, anti-SSA/Ro, anti-SSB/La and anti-CCP at the time of diagnosis. In addition, in a subset of patients we evaluated anti-Scl-70, anti-neutrophil cytoplasmic antibody, and anti-DNA. HLA typing was performed using PCR sequence-specific primers in a high-resolution modality, includingHLA-DRB1andHLA-DQB1loci. Statistical analysis was performed employing Epi-Info v7 and SPSS v20.

Results

60 hypersensitivity pneumonitis patients showed sera autoantibodies (HPAbs+), and 110 hypersensitivity pneumonitis patients did not (HPAbs−). The frequency of the alleleHLA-DRB1*03:01was remarkably increased in the HPAbs+group (10.8%versus0.45%; OR 30.14, 95% CI 3.83–237.1; p=1.65×10-4after Bonferroni's correction). Likewise, we found that the haplotypeDRB1*03:01-DQB1*02:01, which is part of the 8.1 ancestral haplotype, a major genetic determinant of autoimmune diseases, confers significant risk to develop autoantibodies (OR 19.23, 95% CI 2.37–155.9; p=0.0088 after Bonferroni's correction). In addition, theHLA-DRB1*03:01allele was associated with higher mortality in patients with hypersensitivity pneumonitis (adjusted OR 5.9, 95% CI 1.05–33.05; p=0.043).

Conclusions

A subset of hypersensitivity pneumonitis patients presents circulating autoantibodies and higher mortality that are associated with some alleles of 8.1 ancestral haplotype.
Normal spirometry predictive values for the Western Indian adult population
Authors: Agarwal Dhiraj , Parker Richard A. , Pinnock Hilary , Roy Sudipto , Ghorpade Deesha , Salvi Sundeep , Khatavkar Parag , Juvekar Sanjay
Published: May 2020

Interpretation of spirometry involves comparing lung function parameters with predicted values to determine the presence/severity of the disease. The Global Lung Function Initiative (GLI) derived reference equations for healthy individuals aged 3–95 years from multiple populations but highlighted India as a “particular group” for whom further data are needed. We aimed to derive predictive equations for spirometry in a rural Western Indian adult population.

We used spirometry data previously collected (2008–2012) from 1258 healthy adults (aged 18 years and over) by the Vadu Health and Demographic Surveillance System. We constructed sex-stratified prediction equations for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC using the Generalised Additive Model for Location, Scale and Shape (GAMLSS) method to derive the best fitting model of each outcome as a function of age and height.

When compared with GLI Ethnicity Codes 1 (White Caucasian) and 5 (Other/Mixed), the Western Indian adult population appears to have lower lung volumes on average, though the FEV1/FVC ratio is comparable. Both age and height were predictive of mean FEV1and FVC; and for females, the variability of response was also dependent on age. FEV1/FVC appears to have a very strong age effect, highlighting the limitations of using a fixed 0.7 cut-off value.

The use of GLI normal values may result in overdiagnosis of lung disease in this population. We recommend that the values and equations generated from this study should be used by physicians in their routine practice for diagnosing disease and its severity in adults from the Western Indian population.
High Photon Absorptivity of Quantum Dot Infrared Photodetectors Achieved by the Surface Plasmon Effect of Metal Nanohole Array
Authors: Liu Hongmei , Kang Yongqiang , Meng Tianhua , Tian Cuifeng , Wei Guodong
Published: May 2020

With the increasing demand for small-scale photodetector devices, quantum dot–based infrared photodetectors have attracted more and more attention in the past decades. In this work, periodic metal nanohole array structures are introduced to the quantum dot infrared photodetectors to enhance the photon absorptivity performance via the surface plasmon enhancement effect in order to overcome the bottleneck of low optical absorption efficiency that exists in conventional photodetectors. The results demonstrate that the optimized metal nanohole array structures can greatly enhance the photon absorptivity up to 86.47% in the specific photodetectors, which is 1.89 times than that of conventional photodetectors without the metal array structures. The large enhancement of the absorptivity can be attributed to the local coupling surface plasmon effect caused by the metal nanohole array structures. It is believed that the study can provide certain theoretical guidance for high-performance nanoscale quantum dot–based infrared photodetectors.
Prehospital acute traumatic pain assessment and management practices in the Western Cape, South Africa: a retrospective review
Authors: Lourens Andrit , Parker Romy , Hodkinson Peter
Published: May 2020

Background

Trauma is a common aetiology of acute pain in the emergency setting, and traumatic injuries have been recognised as a global public health crisis leading to numerous deaths and disabilities. This study aimed to identify the prevalence of acute pain among high acuity trauma patients presenting to a public sector emergency medical service and to describe prehospital acute traumatic pain assessment and management practices amongst emergency care providers in the Western Cape Province, South Africa.

Methods

A retrospective review of electronic patient care reports of trauma patients treated by the South African Western Cape Emergency Medical Services between January 1 and December 31, 2017 was conducted. Stratified random sampling was utilised to select 2401 trauma patients out of 24,575 that met the inclusion criteria.

Results

Of the 2401 patients reviewed, 435 (18.1%) had a pain score recorded, of which 423 (97.2%) were experiencing pain. An additional 8.1% (n = 194) of patients had pain or tenderness mentioned in the working diagnosis but no pain score noted. Eighty-one (18.6%) patients experienced mild pain, 175 (40.2%) moderate pain and 167 (38.2%) severe pain. No association was found between a pain score recorded and age group (≤ 14 versus > 14 years) (p = 0.649) or gender (p = 0.139). Only 7.6% of patients with moderate-to-severe pain and 2.8% of all trauma patients received any form of analgesic medication. No association was found between the administration of analgesia and age group (≤ 14 versus > 14 years) (p = 0.151) or gender (p = 0.054). Patients were more likely to receive analgesia if they had a pain score recorded (p < 0.001), were managed by advanced life support practitioners (p < 0.001) or had severe pain (p = 0.001).

Conclusion

Acute trauma pain assessment and management practices in this prehospital cohort are less well established than reported elsewhere and whether this reflects emergency care training, institutional culture, scopes of practice or analgesic resources, requires further research. Emergency medical services need to monitor and promote quality pain care, enhance pain education and ensure that all levels of emergency care providers have access to analgesic medication approved for prehospital use. Clear and rational guidelines would enable better pain management by all cadres of providers, for all levels of pain.
Main findings and advances in bioinformatics and biomedical engineering- IWBBIO 2018
Authors: Valenzuela Olga , Rojas Fernando , Rojas Ignacio , Glosekotter Peter
Published: May 2020

In the current supplement, we are proud to present seventeen relevant contributions from the 6th International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO 2018), which was held during April 25-27, 2018 in Granada (Spain). These contributions have been chosen because of their quality and the importance of their findings.
Toronto aortic stenosis quality of life questionnaire (TASQ): validation in TAVI patients
Authors: Styra Rima , Dimas Michelle , Svitak Kathy , Kapoor Mamta , Osten Mark , Ouzounian Maral , Devins Gerald , Deckert Amy , Horlick Eric
Published: May 2020

Background

Aortic stenosis (AS) is a common cardiac condition whose prevalence increases with age. The symptom burden associated with severe aortic stenosis (AS) can introduce significant lifestyle disruptions and if left untreated can lead to a poor prognosis. Quality of life (QoL) is an important consideration in these patients. The TASQ is a QoL tool that was developed for aortic stenosis patients. We evaluated the psychometric properties of this specific questionnaire in patients who underwent transcatheter aortic valve implantation (TAVI), which is a therapeutic option for patients with severe aortic stenosis (AS).

Methods

The properties of the TASQ in measuring QoL were evaluated in AS patients undergoing TAVI. Patients presenting for the TAVI procedure (N = 62) were evaluated pre-TAVI, at discharge, 1-month, and 3-month follow-ups. Demographic information as well as caregiver status, and daily activities were recorded. In addition to the TASQ, they completed the KCCQ (Kansas City Cardiomyopathy Questionnaire) and the IIRS (Illness Intrusiveness Rating Scale).

Results

The TASQ is a 16-item self-administered questionnaire that assesses AS-specific QoL across five domains: physical symptoms; physical limitations; emotional impact; social limitations, and health expectations. TASQ subscales are internally consistent (α = 0.74–0.96) and showed significant improvements from baseline across assessments (p < 0.001). Construct validity evidence was demonstrated by correlations consistent with theoretically derived hypotheses across time points.

Conclusions

The TASQ is a brief measure of AS-specific QoL that is sensitive to change in patients undergoing TAVI. Items on the TASQ capture important QoL concerns reported by AS patients, suggesting this is a measure of relevant and meaningful outcomes for this patient population. Detection of early improvements in QoL by the TASQ is promising, with important implications for the evaluation of procedural outcomes in this population.