bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Rebel Group Ideology on Wartime Sexual Violence
Authors: Sarwari Mehwish
Published: August 2020

Does rebel group ideology influence variation in wartime sexual violence? While existing studies have explored country-level and conflict-specific factors to explain wartime sexual violence, it is important to recognize that rebels vary in their characteristics and sexual violence behavior. Specifically, rebel groups differ in their values regarding gender equality. I argue that the ideological preferences held by rebels and their foreign supporters can influence sexual violence during armed conflict. Particularly, I make the claim that rebels influenced by a leftist ideology are less likely to commit wartime sexual violence, whereas religious groups, Islamist and non-Islamist, are more likely to perpetrate such violence. Using a statistical analysis to explore the effects of ideology of rebel groups on sexual violence during the period of 1989–2008, I find that leftist rebels commit lower levels of wartime sexual violence. Furthermore, findings reveal that leftist organizations that receive support from leftist third parties are less likely to perpetrate sexual violence. Religious rebels who receive support from conservative supporters, on the other hand, are more likely to commit sexual violence.
Economic Crises and Terrorism: Analyzing Competing Economic Pressures on Terrorism in Russia
Authors: Omelicheva Mariya , Webb Clayton
Published: August 2020

The prevailing academic consensus holds that economic hardship does not motivate terrorism. We argue that this academic consensus is misguided because it assumes a single causal pathway connecting the economy to terrorism. In addition, most tests rely on national-level macroeconomic measures of economic performance that are not well suited to capturing individual-level decision-making processes that motivate people to engage in political violence. We argue that shifts in economic performance have heterogeneous effects on terrorist activity. The suffering caused by economic hardship energizes pre-existing grievances and generates feelings of anger and resentment toward the government, making affected individuals susceptible to violent radicalization. Economic crises also increase opportunities for terrorist recruitment by weakening institutions for coping with the consequences of sharp economic downturns. On the other hand, the economic losses caused by crises reduce the resources available to terrorist groups. These competing pressures are difficult to observe at the national level and are not equally reflected in all measures of economic performance. We test these arguments using a novel dataset of terrorist attacks and terrorist crimes in the Russian federal subjects between 2008 and 2016. We find evidence to support opportunity- and resource-based arguments for terrorism. These findings suggest a need to rethink the academic consensus on terrorism and a need to problematize the theoretical and empirical approaches that brought us to the prevailing consensus.
Olive Schreiner, Marie Corelli and the Anxieties of Female Authorship
Authors: Gill Clare
Published: August 2020

This article explores the competing models of gendered authorship emerging from Marie Corelli’s multiple print encounters with Olive Schreiner. Where Schreiner is cast by Corelli as the modish darling of a snobbish literary intelligentsia, who is beloved by critics and ignored by readers, Corelli herself emerges from her writings about Schreiner as the democratic author par excellence, a writer for the people rather than the press. In spite of the clear common ground that bridged their experience as celebrity authors, Corelli, in her writings about Schreiner, sought only to elucidate the ideological and artistic gulf that she identified as existing between them. As this essay will show, Corelli’s public resistance to Schreiner was a strike not only against an unfair male literary system of which she perceived Schreiner to be an arbitrary beneficiary, but also a rejection of the rhetoric of literary value that emerged in Britain during the fin de siècle. What Corelli failed to understand was that to be a woman writer at this time, however successful, was to occupy an ambiguous position within dominant, masculinist discourses of artistic distinction. A fuller exploration of Schreiner and Corelli’s positions within and experiences of the late-Victorian literary marketplace not only reveals the frailty of Correlli’s oppositional construction in real terms, but also signals the extent to which it was their shared status as women writers that was the key determinant shaping their respective experiences of professional authorship.
Investigation of the Sterility of Diluent in Prefilled Syringes Used for Vaccine Reconstitution at Department of Defense Recruit Training Sites
Authors: Chao Chien-Chung , Zhang Zhiwen , Belinskaya Tatyana , Jiang Le , Morrison Brian J , Rivera Jose Garcia , Chen Hua-Wei , Ching Wei-Mei
Published: August 2020

Introduction

Measles, mumps, and rubella (MMR) and varicella (VAR) vaccines are the two vaccines administered in large recruit training sites (RTS) that require a single-use syringe to be prefilled with the diluent (ie water) before vaccine reconstitution. Since there are no preservatives in either MMR or VAR vaccines, it is critical to maintain the diluent sterile to ensure the sterility of the reconstituted vaccine. The Department of Defense/Defense Health Agency has instructions on reconstitution of lyophilized vaccines and guidelines for their storage. Vaccine manufacturers provide instructions on how to properly store the diluent. However, there is no clear guidance or standard operating procedures regarding the best practice for preparation and storage of the syringes prefilled with diluent. Various RTS across all four services have their respective routines to best fit their vaccination requirements. Currently, there are no available data on the sterility status of the diluent prepared using these various routines before they are used to reconstitute vaccines.

Materials and Methods

We investigated the sterility of the diluent (ie water) in prefilled syringes prepared using routines practiced at various RTS. Diluent was drawn up into single syringes and was kept under various conditions (4 °C or room temperature for overnight up to 24 hours) used by various RTS. At indicated time, diluent was injected into sterile vials and the sterility of the diluent was determined by monitoring the presence/growth of bacteria (including aerobic bacteria, mycoplasma, and an obligate intracellular bacterium, Coxiella burnetii), fungi, and viruses for up to 21 days after inoculation into proper and specific culture media. Both traditional cell culture and molecular assays were used to demonstrate the presence or absence of contamination that may compromise the sterility of the diluent.

Results

Our results demonstrate that the diluent, after being drawn up to fill the syringe, maintains sterility after storage for overnight up to 24 hours at room temperature or 4 °C with or without recapping the syringes, suggesting that current vaccine reconstitution routines practiced at large military RTS are safe.

Conclusions

Our results demonstrate that in spite of variations in current practices used in various RTS, the diluent in the prefilled syringe tested from each site maintains its sterility and was determined to be safe for use in military health system-wide vaccine reconstitution.
The Importance of Validating Sleep Behavior Models for Fatigue Management Software in Military Aviation
Authors: Paul Michel A , Hursh Steven R , Love Ryan J
Published: August 2020

Introduction

The propensity for air mobility missions to exhaust aircrews is strongly dependent on operational tempo. Most flying is performed during periods of low to moderate operational tempo, but a major flight safety risk can emerge when operational tempo becomes very high. This risk can be managed by software tools that contain fatigue and sleep behavior modeling, but optimization/validation of the model using the specific target population is required to ensure that the modeled predictions are accurate. The goal of the study was to validate the sleep behavior model settings for a fatigue modeling tool that is used within the RCAF, the Fatigue Avoidance Scheduling Tool, taking into account the organizational requirements for pre- and postflight routines, especially within the Air Mobility force.

Materials and methods

Four Royal Canadian Air Force Air Mobility Squadrons from Canadian Forces Base Trenton took part in this trial over a 3-month period (May 3 to August 21, 2016). All 22 missions of the trial included long-range transmeridian flights. All members of the participating aircrew wore wrist actigraphs to measure their sleep. We compared cognitive effectiveness modeling scenarios (preharmonization) based on the SAFTE-FAST sleep behavior model with its default settings against cognitive effectiveness modeling scenarios based on actigraphically-measured sleep. The measured sleep was then harmonized against the predicted sleep to optimize accuracy of the sleep behavior algorithm. During the harmonization process, the “Autosleep” prediction settings were optimized to match the actigraphically-measured sleep timings.

Results

Prior to the harmonization effort, the sleep behavior algorithm overpredicted the sleep obtained by CAF Aircrews. The most significant adjustment to the sleep behavior model was the increase in commute time to account for briefing, flight planning, debriefing, and postflight activities. Following harmonization, the sleep behavior model provided nearly perfect estimates of overall fatigue risk against missions modeled with actigraphically-measured sleep. For both measured and predicted sleep, most of the time in flight was in a low-fatigue, high-cognitive effectiveness state (90%–95% cognitive effectiveness).

Conclusions

Current Fatigue Risk Management Systems require accurate fatigue and sleep behavior modeling, which can only be achieved by studying specific target populations to determine their culture of work/rest routines, and optimizing sleep behavior model settings accordingly.
Subcutaneous Perforation of Recurrent Gastric Fistula After Abdominoplasty with Scar Revision
Authors: DeSoucy Erik S , Nelson Vincente S
Published: August 2020

This case represents an unusual, and previously unreported, complication of delayed leakage of gastric contents into the subcutaneous tissues 2 years after division of a gastrostomy tube tract during abdominoplasty. Our patient required urgent exploration for contamination control and closure of the fistula and recovered fully. Persistent gastrocutaneous fistula is uncommon in adults and even less common is recannulization of a fistula track after initial closure. A thorough review of operative history and comparison to previous imaging were crucial for appropriate diagnosis and operative planning. Formal closure of gastrostomy tube sites during scar revision and abdominoplasty may help prevent the complication of delayed gastrostomy tube tract rupture into the subcutaneous tissues.
Are Nonsynonymous Transversions Generally More Deleterious than Nonsynonymous Transitions?
Authors: Zou Zhengting , Zhang Jianzhi
Published: August 2020

It has been suggested that, due to the structure of the genetic code, nonsynonymous transitions are less likely than transversions to cause radical changes in amino acid physicochemical properties so are on average less deleterious. This view was supported by some but not all mutagenesis experiments. Because laboratory measures of fitness effects have limited sensitivities and relative frequencies of different mutations in mutagenesis studies may not match those in nature, we here revisit this issue using comparative genomics. We extend the standard codon model of sequence evolution by adding the parameter η that quantifies the ratio of the fixation probability of transitional nonsynonymous mutations to that of transversional nonsynonymous mutations. We then estimate η from the concatenated alignment of all protein-coding DNA sequences of two closely related genomes. Surprisingly, η ranges from 0.13 to 2.0 across 90 species pairs sampled from the tree of life, with 51 incidences of η < 1 and 30 incidences of η >1 that are statistically significant. Hence, whether nonsynonymous transversions are overall more deleterious than nonsynonymous transitions is species-dependent. Because the corresponding groups of amino acid replacements differ between nonsynonymous transitions and transversions, η is influenced by the relative exchangeabilities of amino acid pairs. Indeed, an extensive search reveals that the large variation in η is primarily explainable by the recently reported among-species disparity in amino acid exchangeabilities. These findings demonstrate that genome-wide nucleotide substitution patterns in coding sequences have species-specific features and are more variable among evolutionary lineages than are currently thought.
Do Combination Antiretroviral Therapy Regimens for HIV Infection Feature Diverse T-Cell Phenotypes and Inflammatory Profiles?
Authors: Tincati Camilla , Mondatore Debora , Bai Francesca , d’Arminio Monforte Antonella , Marchetti Giulia
Published: August 2020

Immune abnormalities featuring HIV infection persist despite the use of effective combination antiretroviral therapy (cART) and may be linked to the development of noninfectious comorbidities. The aim of the present narrative, nonsystematic literature review is to understand whether cART regimens account for qualitative differences in immune reconstitution. Many studies have reported differences in T-cell homeostasis, inflammation, coagulation, and microbial translocation parameters across cART classes and in the course of triple vs dual regimens, yet such evidence is conflicting and not consistent. Possible reasons for discrepant results in the literature are the paucity of randomized controlled clinical trials, the relatively short follow-up of observational studies, the lack of clinical validation of the numerous inflammatory biomarkers utilized, and the absence of research on the effects of cART in tissues. We are currently thus unable to establish if cART classes and regimens are truly accountable for the differences observed in immune/inflammation parameters in different clinical settings. Questions still remain as to whether an early introduction of cART, specifically in the acute stage of disease, or newer drugs and novel dual drug regimens are able to significantly impact the quality of immune reconstitution and the risk of disease progression in HIV-infected subjects.
A Systematic Review of Treatment and Outcomes of Pregnant Women With COVID-19—A Call for Clinical Trials
Authors: Pastick Katelyn A , Nicol Melanie R , Smyth Elizabeth , Zash Rebecca , Boulware David R , Rajasingham Radha , McDonald Emily G
Published: August 2020

Background

Data pertaining to COVID-19 in pregnancy are limited; to better inform clinicians, we collated data from COVID-19 cases during pregnancy and summarized clinical trials enrolling this population.

Methods

We performed a systematic literature review of PubMed/MEDLINE to identify cases of COVID-19 in pregnancy or the postpartum period and associated outcomes. We then evaluated the proportion of COVID-19 clinical trials (from ClinicalTrials.gov) excluding pregnant or breastfeeding persons (both through June 29, 2020).

Results

We identified 11 308 published cases of COVID-19 during pregnancy. Of those reporting disease severity, 21% (416/1999) were severe/critical. Maternal and neonatal survival were reassuring (98% [10 437/10 597] and 99% [1155/1163], respectively). Neonatal disease was rare, with only 41 possible cases of infection reported in the literature. Of 2351 ongoing COVID-19 therapeutic clinical trials, 1282 were enrolling persons of reproductive age and 65% (829/1282) excluded pregnant persons. Pregnancy was an exclusion criterion for 69% (75/109) of chloroquine/hydroxychloroquine, 80% (28/35) of lopinavir/ritonavir, and 48% (44/91) of convalescent plasma studies. We identified 48 actively recruiting or completed drug trials reporting inclusion of this population.

Conclusions

There are limited published reports of COVID-19 in pregnancy despite more than 14 million cases worldwide. To date, clinical outcomes appear reassuring, but data related to important long-term outcomes are missing or not yet reported. The large number of clinical trials excluding pregnant persons, despite interventions with safety data in pregnancy, is concerning. In addition to observational cohort studies, pregnancy-specific adaptive clinical trials could be designed to identify safe and effective treatments.
Impact of Pharmacy Type on HIV Viral Suppression: A Retrospective Cross-Sectional Cohort Study
Authors: Havens Joshua P , Sayles Harlan , Fadul Nada , Bares Sara H
Published: August 2020

Background

People with HIV (PWH) use various pharmacy types beyond traditional local pharmacies. Some specialized pharmacies offer additive adherence services such as refill reminders, expedited delivery, and adherence packaging.

Methods

This single-center, retrospective cohort study evaluated the impact of pharmacy type on the gain or loss of HIV viral suppression (VS; HIV RNA ≤50 copies/mL). Patients (≥19 years) were categorized by VS and pharmacy type: HIV-specialized (additive adherence/delivery services) vs traditional (without adherence/delivery services). Fisher exact tests examined the effect of pharmacy type on differences in VS between years, and logistic regression models identified possible predictors of gaining or losing VS.

Results

During 2017–2018, no differences were observed for the gain or loss of VS across pharmacy types (VS gain vs continued viremia, P = .393; VS loss vs continued VS, P = .064). Predictors for the gain of VS included antiretroviral therapy adherence as percentage of days covered (PDC; adjusted odds ratio [aOR], 1.05; P < .001) and Federal Poverty Level 100%–138% (FPL; aOR, 0.17; P = .032). Predictors for the loss of VS included use of protease inhibitor (aOR, 2.85; P = .013), ≥1 other illicit substance including tobacco (aOR, 2.96; P = .024), PDC (aOR, 0.95; P < .001), FPL 139%–200% (aOR, 0.09; P = .031), and CD4 >200 cells/ccm (aOR, 0.19; P = .013).

Conclusions

The gain or loss of VS among PWH in this retrospective cohort was not impacted by pharmacy transitions within the 2-year study period. However, PDC, FPL, illicit substance use, protease inhibitor use, and CD4 >200 cells/ccm were identified as factors associated with changes in VS.
The Clinical Impact of Rapid Molecular Microbiological Diagnostics for Pathogen and Resistance Gene Identification in Patients With Sepsis: A Systematic Review
Authors: D’Onofrio Valentino , Salimans Lene , Bedenić Branka , Cartuyvels Reinoud , Barišić Ivan , Gyssens Inge C
Published: August 2020

Fast microbiological diagnostics (MDx) are needed to ensure early targeted antimicrobial treatment in sepsis. This systematic review focuses on the impact on antimicrobial management and patient outcomes of MDx for pathogen and resistance gene identification compared with blood cultures. PubMed was searched for clinical studies using either whole blood directly or after short-term incubation. Twenty-five articles were retrieved describing the outcomes of 8 different MDx. Three interventional studies showed a significant increase in appropriateness of antimicrobial therapy and a nonsignificant change in time to appropriate therapy. Impact on mortality was conflicting. Length of stay was significantly lower in 2 studies. A significant decrease in antimicrobial cost was demonstrated in 6 studies. The limitations of this systematic review include the low number and observed heterogeneity of clinical studies. In conclusion, potential benefits of MDx regarding antimicrobial management and some patient outcomes were reported. More rigorous intervention studies are needed focusing on the direct benefits for patients.
GABAergic but not Antidepressant Medications Increase Risk for Clostridioides difficile Infection in a National Cohort of Veterans
Authors: Lalani Falak , Young Eric H , Panchal Rupesh M , Reveles Kelly R
Published: August 2020

Background

Clostridioides difficile infection (CDI) is primarily mediated by alterations in the host gut ecosystem. While antibiotic use is the primary risk factor for CDI, other medications that modulate the gut ecosystem, particularly those targeting the gut–brain axis, could impact CDI risk. This study aimed to investigate the association between recent antidepressant and gamma-aminobutyric acid (GABA)–ergic medication use with CDI risk in a national cohort of United States veterans.

Methods

This was a retrospective case–control study of patients seen in Veterans Health Administration facilities from October 2002 to September 2014. CDI and non-CDI control patients were propensity score matched 1:1 using a maximum caliper of 0.0001. Antidepressant and GABAergic medication use 90 days before cohort inclusion were analyzed for CDI association using bivariable and multivariable logistic regression models.

Results

A total of 85 831 patients were included, and 9287 CDI and 9287 control patients were propensity score matched. Antidepressant use overall was not significantly associated with CDI risk (odds ratio [OR], 1.05; 95% CI, 0.98–1.12), although GABAergic medication use was associated with increased risk (OR, 1.81; 95% CI, 1.70–1.92). In multivariable models of individual medications/classes, benzodiazepines had the strongest CDI association (OR, 1.91; 95% CI, 1.77–2.07). SSRIs (OR, 0.88; 95% CI, 0.81–0.95) and bupropion (OR, 0.67; 95% CI, 0.57–0.78) were negatively associated with CDI.

Conclusions

In this national study of veterans, GABAergic medication use was a positive predictor of CDI risk, though antidepressant use was not. Further research is needed to understand biological mechanisms, and confirmatory studies are needed to validate these findings.
Lower Mortality Associated With Adjuvant Corticosteroid Therapy in Non-HIV-Infected Patients With Pneumocystis jirovecii Pneumonia: A Single-Institution Retrospective US Cohort Study
Authors: Mundo William , Morales-Shnaider Louis , Tewahade Selam , Wagner Eric , Archuleta Solana , Bandali Mohamed , Chadalawada Sindhu , Johnson Steven C , Franco-Paredes Carlos , Shapiro Leland , Henao-Martínez Andrés F
Published: August 2020

Background

Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids in these patients is uncertain. This study aimed to determine if corticosteroids would reduce mortality in a cohort of HIV-negative PJP patients.

Methods

We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995 and 2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify mortality predictors.

Results

Common underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), and solid organ transplantation (10.7%). HIV-negative patients had higher rates and durations of mechanical ventilation and intensive care unit stay. Survival was significantly increased in HIV-negative patients receiving adjuvant corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (P = .034). In an adjusted multivariable model, no adjuvant corticosteroid use was associated with higher mortality (odds ratio, 13.5; 95% CI, 1.1–158.5; P = .039) regardless of HIV status.

Conclusions

We found substantial mortality among HIV-negative patients with PJP, and adjuvant corticosteroid use was associated with decreased mortality. Response to corticosteroids is best established in HIV-infected patients, but emerging reports suggest a similar beneficial response in PJP patients without HIV infection. Further prospective studies may establish a more definitive role of the addition of corticosteroids among HIV-negative patients with PJP.
Identifying Enteropathogens in Children with Acute Gastroenteritis Presenting with Isolated Vomiting–Appetite Study
Authors: Lee Bonita , Pang Xiao-Li , Zhuo Ran , Parsons Brendon , Chui Linda , Xie Jianling , Lowerison Karen , Osterreicher Lara , Ali Samina , Freedman Stephen ,   APPETITE (Alberta Provincial Pediatric EnTeric Infection TEam)
Published: August 2020

Background

As diarrheal stool samples are the recommended specimen for testing in acute gastroenteritis (AGE), etiological investigations are rarely performed in children presenting with isolated vomiting. This study identifies enteropathogens in children with AGE presenting with isolated vomiting.

Methods

Children <18 years old with ≥3 episodes of vomiting/diarrhea in 24 hours and <7 days of symptoms were recruited in 2 pediatric emergency departments, a public health clinic and via Health Link, a provincial nurse advice phone line. Rectal swabs and stool samples were collected and tested using the Luminex xTAG GPP, an in-house 5-virus RT-qPCR panel and enteric bacterial culture. Vomiting and diarrhea data were collected at enrollment (day 0) and at day 14.

Results

Between Dec 9, 2014 and Apr 14, 2016, 2,184 children were enrolled and tested: 784 (36%) presented with isolated vomiting, 250 (11%) with isolated diarrhea (ID), 1,138 (52%) with both vomiting and diarrhea (V&D), 12 had missing data. The detection of enteropathogens was 56% when presenting with isolated vomiting, 55% with ID and 83% with V&D. Of the 784 children with isolated vomiting, 54% (n = 424) had one or more viruses: the most common was norovirus (NoV) (n = 244, 50%), followed by adenovirus (Adv) (91, 19%), rotavirus (Rota) (57, 12%), sapovirus (84, 17%) and astrovirus (10, 2%). Fifty-eight cases had >1 virus; co-infection with NoV and Adv was the most common (n = 23). Ten of these 424 patients also had enteric bacteria (2 Aeromonas, 2 ETEC, 2 Salmonella, 2 Yersinia, 1 Campylobacter, 1 E coli O157) and 8/9 (89%) of these patients reported development of diarrhea at day 14. In comparison, 212/383 (55%) of patients with virus only reported diarrhea at follow up. Enteric bacteria with no virus was detected in 11 patients (3 Aeromonas, 3 Salmonella, 3 STEC, 1 Campylobacter, 1 E coli O157) and 3/10 of these patients reported diarrhea.

Conclusion

Over 50% of AGE presented with isolated vomiting had enteric virus identified in stool or rectal swabs, representing a significant pathogen-based disease burden not previously included in healthcare planning (e.g., Rota vaccine). NoV was the predominant agent followed by Adv and Rota. Finding enteric bacteria in these cases is novel and requires further study.

Disclosures

All authors: No reported disclosures.
Small Airway Wall Thickening Assessed by Computerized Tomography Is Associated With Low Lung Function in Chinese Carbon Black Packers
Authors: Cao Xue , Lin Li , Sood Akshay , Ma Qianli , Zhang Xiangyun , Liu Yuansheng , Liu Hong , Li Yanting , Wang Tao , Tang Jinglong , Jiang Menghui , Zhang Rong , Yu Shanfa , Yu Zhiqiang , Zheng Yuxin , Han Wei , Leng Shuguang
Published: August 2020

Nanoscale carbon black as virtually pure elemental carbon can deposit deep in the lungs and cause pulmonary injury. Airway remodeling assessed using computed tomography (CT) correlates well with spirometry in patients with obstructive lung diseases. Structural airway changes caused by carbon black exposure remain unknown. Wall and lumen areas of sixth and ninth generations of airways in 4 lobes were quantified using end-inhalation CT scans in 58 current carbon black packers (CBPs) and 95 non-CBPs. Carbon content in airway macrophage (CCAM) in sputum was quantified to assess the dose-response. Environmental monitoring and CCAM showed a much higher level of elemental carbon exposure in CBPs, which was associated with higher wall area and lower lumen area with no change in total airway area for either airway generation. This suggested small airway wall thickening is a major feature of airway remodeling in CBPs. When compared with wall or lumen areas, wall area percent (WA%) was not affected by subject characteristics or lobar location and had greater measurement reproducibility. The effect of carbon black exposure status on WA% did not differ by lobes. CCAM was associated with WA% in a dose-dependent manner. CBPs had lower FEV1 (forced expiratory volume in 1 s) than non-CBPs and mediation analysis identified that a large portion (41–72%) of the FEV1 reduction associated with carbon black exposure could be explained by WA%. Small airway wall thickening as a major imaging change detected by CT may underlie the pathology of lung function impairment caused by carbon black exposure.
Capital Allocation in Developing Countries
Authors: David Joel M , Venkateswaran Venky , Cusolito Ana Paula , Didier Tatiana
Published: August 2020

This paper investigates the sources of capital misallocation across a group of developing and developed countries, using the empirical methodology developed in David and Venkateswaran (2019. “The Sources of Capital Misallocation.” American Economic Review 109 (7): 2531–67). The main findings are: (i) technological frictions—namely, adjustment costs and uncertainty—account for only a modest share of the observed misallocation; (ii) heterogeneity in firm-level technologies potentially explains between one-quarter and one-half, but (iii) dispersion in markups is much smaller; (iv) after accounting for these factors, on average, at least 50 percent of misallocation within each country remains unexplained, suggesting a large role for additional—potentially distortionary—factors. These factors are largely attributable to a component that is correlated with firm size/productivity and one that is essentially permanent to the firm. They exhibit strong negative correlations with income per capita and direct measures of the quality of the business environment from the World Bank Doing Business Report. The paper reports a broad set of moments describing firm-level investment dynamics and detailed parameter estimates on a country-by-country basis with an eye towards future work in this area.
Effect of Exercise on Cardiovascular Function Following Spinal Cord Injury
Authors: Liu Shujia , Wang Yi , Niebauer Josef
Published: August 2020

Spinal cord injury (SCI) is associated with a reduced level of physical activity, deterioration of patient body composition, metabolic profile, quality of life, and psychological functioning. As a result, risk of cardiovascular disease (CVD) increases and CVD-related death occurs at an earlier age than in individuals without SCI. Regular participation in exercise has been shown to exert beneficial effects also in patients with SCI. In this review, we analyze and discuss the effects of regular exercise training in SCI on cardiovascular function, autonomic function of the cardiovascular system, arterial stiffness, metabolism, inflammation, and gene expression.
IMPACT OF CORONAVIRUS DISEASE PANDEMIC ON INTRAVITREAL INJECTIONS TREATMENT FOR MACULAR DISEASES
Authors: Viola Francesco , Milella Paolo , Pozzo Giuffrida Francesco , Ganci Simone , Invernizzi Alessandro
Published: August 2020

Purpose:

To describe our managing strategy for COVID-19 emergency, to evaluate the adherence to intravitreal treatment (AtT) rate during the outbreak in a referral hospital in Milan, and to correlate it with patients' clinical features.

Methods:

The AtT rate of patients with scheduled intravitreal injections during the COVID-19 outbreak from February 23, 2020 to March 31, 2020 was compared with the previous trimester and with March 2019. The impact of age, sex, visual function, and diagnosis on the AtT rate during unlocked/locked weeks (from March 8th) was evaluated.

Results:

Of 650 consecutive patients with scheduled intravitreal injections, the AtT rate during the COVID-19 outbreak was 0.37. This was significantly lower compared with AtT registered in the previous trimester (0.92) and in the same weeks in 2019 (0.90) (both P < 0.001). Patients adherent to treatment were significantly younger (P < 0.001) and had a lower best-corrected visual acuity in the fellow eye (P = 0.046). During the lockdown weeks, the AtT rate was significantly lower than in the two unlocked weeks (0.19 vs. 0.73, P < 0.001). In addition, the AtT rate in patients classified as “emergent” during the lockdown weeks was 0.60.

Conclusion:

These preliminary results can help the retina specialist community to foresee this unique scenario and to develop successful management strategies.
REVIEW OF OPHTHALMIC AND BREASTFEEDING MEDICINE EVIDENCE
Authors: Dalal Prarthana J. , Patel Aloka L. , Carle Michelle , Rajanala Alekya , Gill Manjot K.
Published: August 2020

Background/Purpose:

There is limited research regarding the consequences of treating lactating mothers with intravitreal anti–vascular endothelial growth factor (VEGF) agents. Balancing the need for vision-saving treatment, the benefits of breastfeeding, and the concern for affecting the newborn can present a conflict for both mothers and ophthalmologists. This review summarizes the state of the literature regarding the use of intravitreal anti-VEGF agents during breastfeeding along with details about their pharmacology.

Results:

Bevacizumab and aflibercept have Fc domains subjecting them to FcRn recycling and extending their half-life compared with ranibizumab which is an antibody fragment and lacks the Fc domain. Case reports and small studies have shown that ranibizumab has the lowest serum concentration after intravitreal injection and the least effect on plasma-free VEGF concentrations and breastmilk VEGF levels.

Conclusion:

Clinical and pharmacologic data suggest that ranibizumab has less systemic circulation and effect on maternal serum and breastmilk VEGF levels when compared to bevacizumab and aflibercept. However, there is significant need for further research on the degree and duration to which intravitreal agents circulate systemically, what fraction is transferred into breastmilk and is absorbed, and whether this results in any functional adverse effects to the infant. Other factors to consider in the medical decision-making of lactating mothers necessitating intravitreal anti-VEGF treatment include the gestational and post-natal age of the child and whether it is feasible to avoid breastfeeding for the half-life duration of the intravitreal agent rather than ceasing breastfeeding altogether.
Acupuncture alleviates chronic pain and comorbid conditions in a mouse model of neuropathic pain: the involvement of DNA methylation in the prefrontal cortex
Authors: Jang Jae-Hwan , Song Eun-Mo , Do Young-Ho , Ahn Sora , Oh Ju-Young , Hwang Tae-Yeon , Ryu Yeonhee , Jeon Songhee , Song Mi-Yeon , Park Hi-Joon
Published: August 2020

Chronic pain reduces life quality and is an important clinical problem associated with emotional and cognitive dysfunction. Epigenetic regulation of DNA methylation is involved in the induction of abnormal behaviors and pathological gene expression. We examined whether acupuncture can restore epigenetic changes caused by chronic pain, and identified the underlying mechanisms in neuropathic pain mice. Acupuncture treatment for 6 months (3 days/week) improved mechanical/cold allodynia and the emotional/cognitive dysfunction caused by left partial sciatic nerve ligation (PSNL)-induced neuropathic pain. The effects of acupuncture were associated with global DNA methylation recovery in the prefrontal cortex (PFC). Analysis of DNA methylation patterns in PFC indicated that 1364 overlapping genes among 4442 and 4416 methylated genes in the PSNL vs sham and PSNL vs acupuncture points groups, respectively, were highly associated with the DNA methylation process. Acupuncture restored the reduced expression of 5-methylcytosine, methyl-cytosine-phospho-guanine binding protein 2, and DNA methyltransferase family enzymes induced by PSNL in PFC. Methylation levels of Nr4a1 and Chkb associated with mitochondrial dysfunction were decreased in PFC of the PSNL mice, and increased by acupuncture. By contrast, high expression of Nr4a1 and Chkb mRNA in PSNL mice decreased after acupuncture. We also found that acupuncture inhibited the expression of Ras pathway-related genes such as Rasgrp1 and Rassf1. Finally, the expression of Nr4a1, Rasgrp1, Rassf1, and Chkb mRNA increased in the neuronal cells treated with Mecp2 small interfering RNA. These results suggest that acupuncture can relieve chronic pain-induced comorbid conditions by altering DNA methylation of Nr4a1, Rasgrp1, Rassf1, and Chkb in the PFC.
Psychometric Properties of the Turkish Version of the Dietary Sodium Restriction Questionnaire
Authors: Korkmaz Ebru Konal , Ardahan Melek
Published: August 2020

Background

Sodium restriction is the primary nonpharmacological treatment in heart failure (HF) to prevent rehospitalization and reduce HF symptom burden. Despite the importance of restricting sodium in the diet, the prevalence of nonadherence to a low-sodium diet has been known to be high. To reduce the high prevalence of nonadherence, we have to know the facilitating and challenging factors. The planned behavior theory shows those factors, including attitudes, social norms, and perceived behavioral control. The Dietary Sodium Restriction Questionnaire (DSRQ) was developed based on the planned behavior theory. However, in Turkey, the psychometric properties of this instrument have not been studied yet. Therefore, the aim of this study was to conduct a psychometric testing of the Turkish version of the DSRQ among patients with HF.

Methods

Data were collected from 300 patients who were recommended a sodium-restricted diet because of a diagnosis of HF. Validity was tested using content validity index, Kendall W, and exploratory and confirmatory factor analyses. Reliability was tested using item-total and interitem correlations, Cronbach's α coefficient of reliability, independent-sample t test, and test-retest analysis.

Results

The exploratory factor analysis revealed that 3 factors accounted for 78.2% of the explained variance. The factor loads ranged between 0.67 and 0.96. The results of the confirmatory factor analysis showed goodness-of-fit indices greater than 0.90, with a root-mean-square error of approximation less than 0.10 and a root-mean-square residual of 0.05. The Cronbach's α coefficient for DSRQ was 0.92 and for each subscale was as follows: attitude and subjective norm, 0.97; perceived external behavior control, 0.89; and perceived internal behavior control, 0.83.

Conclusions

The DSRQ is a valid and reliable instrument in assessing the attitudes, beliefs, and perceived behavioral control related to following a low-sodium diet of patients with HF in the Turkish population.
Anti-inflammatory Combination Therapy for the Treatment of Schizophrenia
Authors: Buchanan Robert W. , Weiner Elaine , Kelly Deanna L. , Gold James M. , Chen Shuo , Zaranski Jennifer , Blatt Frank , Wehring Heidi , Carpenter William T.
Published: August 2020

Background

Despite adequate antipsychotic treatment, most people with schizophrenia continue to exhibit persistent positive and negative symptoms and cognitive impairments. The current study was designed to examine the efficacy and safety of adjunctive anti-inflammatory combination therapy for these illness manifestations.

Methods

Thirty-nine people with either Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, schizophrenia or schizoaffective disorder were entered into a 12-week double-blind, 2-arm, triple-dummy, placebo-controlled, randomized clinical trial: 19 were randomized to anti-inflammatory combination therapy and 20 were randomized to placebo. The Brief Psychiatric Rating Scale positive symptom item total score was used to assess positive symptom change, the Scale for the Assessment of Negative Symptoms total score was used to assess negative symptom change, the Calgary Depression Scale total score was used to assess depressive symptom change, and the MATRICS Consensus Cognitive Battery was used to assess neuropsychological test performance.

Results

There was a significant time effect for Brief Psychiatric Rating Scale positive symptom item score (t
226 = −2.66, P = 0.008), but the treatment (t
54=1.52, P = 0.13) and treatment × time (t
223 = 0.47, P = 0.64) effects were not significant. There were no significant time (t
144 = 0.53, P = 0.72), treatment (t
58=0.48, P = 0.63), or treatment × time (t
143 = −0.20, P = 0.84) effects for the Scale for the Assessment of Negative Symptoms total score; or for any of the other symptom measures. There were no significant group differences in the change in the MATRICS Consensus Cognitive Battery composite score over the course of the study (F
1,26=2.20, P = 0.15).

Conclusions

The study results suggest that there is no significant benefit of combined anti-inflammatory treatment for persistent positive symptoms or negative symptoms or cognitive impairments (clinicaltrials.gov trial number: NCT01514682).
Cycle Threshold to Test Positivity in COVID-19 for Return to Work Clearance in Health Care Workers
Authors: Domeracki Sandra , Clapp Robert N. , Taylor Kristopher , Lu Chuanyi M. , Lampiris Harry , Blanc Paul D.
Published: August 2020

Objective:

To ascertain whether reverse transcriptase polymerase chain reaction (RT-PCR) cycle amplifications until detection, the cycle threshold (Ct), could help inform return to work (RTW) strategies for health care workers (HCWs) recovering from COVID-19 infection.

Methods:

Sequential Ct data from COVID-19 nasal pharyngeal (NP) RT-PCR testing in all COVID-19 positive HCWs at a single institution. Analysis of Ct in relation to time until negative testing for RTW clearance.

Results:

Data for 12 employees showed that time elapsed until RT-PCR test-based RTW clearance ranged from 7 to 57 days (median, 34.5 days). Lower initial Ct correlated with the total time elapsed until clearance (r = –0.80; P = 0.002).

Conclusion:

Considering the RT-PCR Ct, which correlates with the estimated viral load, may help inform RTW planning and decision making beyond solely relying on dichotomized positive/negative results.
Vitamin D Supplementation in COVID-19 Patients: A Clinical Case Series
Authors: Ohaegbulam Kim C. , Swalih Mohamed , Patel Pranavkumar , Smith Miriam A. , Perrin Richard
Published: August 2020

Background:

Coronavirus disease 2019 (COVID-19) has infected more than 4.4 million people and caused more than 300,000 deaths partly through acute respiratory distress syndrome with propensity to affect African American and Hispanic communities disproportionately. Patients with worse outcomes have exhibited higher blood plasma levels of proinflammatory cytokines. Activation of the vitamin D receptor expressed on immune cells has been shown to directly reduce the secretion of inflammatory cytokines, such as interleukin-6, and indirectly affect C-reactive protein.

Areas of Uncertainty:

The significance of the vitamin D pathway in patients diagnosed with COVID-19.

Therapeutic Innovation:

Vitamin D supplementation in patients after diagnosis of COVID-19.

Patients and Pharmacological Interventions:

We report 4 vitamin D deficient patients diagnosed with COVID-19 in April 2020 who were provided with either cholecalciferol of 1000 IU daily (standard dose) or ergocalciferol 50,000 IU daily for 5 days (high dose) as part of supplementation.

Clinical Outcomes:

Patients that received a high dose of vitamin D supplementation achieved normalization of vitamin D levels and improved clinical recovery evidenced by shorter lengths of stay, lower oxygen requirements, and a reduction in inflammatory marker status.

Conclusions:

Vitamin D supplementation may serve as a viable alternative for curtailing acute respiratory distress syndrome in patients in underserved communities where resources to expensive and sought-after medications may be scarce. Randomized clinical trials will serve as an appropriate vessel to validate the efficacy of the therapeutic regimen and dissection of the pathway.
Prevention of adverse drug effects: a pharmacogenomic approach
Authors: Scott Erika N. , Hasbullah Jafar S. , Carleton Bruce C. , Ross Colin J.D.
Published: August 2020

Purpose of review

Adverse drug reactions (ADRs) are a serious burden and can negatively impact patient quality of life. One of these ADRs, anthracycline-induced cardiotoxicity (ACT), occurs in up to 65% of treated patients and can lead to congestive heart failure. Pharmacogenetic studies have helped to reveal the mechanisms of ACT and, consequently, inform current strategies to prevent ACT in the clinic.

Recent findings

Many pharmacogenetic studies have been conducted for ACT, but few have led to the development of clinical practice guidelines and clinical genetic testing for ACT. This is, in part, because of lack of replication in independent patient cohorts and/or validation of an affected biological pathway. Recent advances in pharmacogenetic studies have been made through the use of novel methods that directly implicate dysregulated genes and perturbed biological pathways in response to anthracycline treatment.

Furthering the understanding of the genetics and altered biological pathways of ACT through these novel methods can inform clinical treatment strategies and enable refinement of current clinical practice guidelines. This can therefore lead to improvement in clinical pharmacogenetic testing for further reduction of the incidence of ACT in pediatric cancer patients taking anthracyclines.
FETOS
Authors: Hanot Quentin , Wieczorek Valerie , Wypych Marion , Machuron François , Thevenon André
Published: August 2020

Objective

Thoracic outlet syndrome is caused by the compression of blood vessels and nerves leading to the upper limbs; the level of functional discomfort in activities of daily living can be significant. This discomfort has been evaluated using a variety of nonspecific scales, prompting the development a specific self-questionnaire (“Functional Evaluation in Thoracic Outlet Syndrome). Here, the scale’s test-retest reliability, sensitivity to change, and criterion validity were assessed.

Design

Between May 2015 and July 2017, a total of 37 patients were assessed during an intensive rehabilitation program. The Functional Evaluation in Thoracic Outlet Syndrome self-questionnaire comprises 16 items rated on a 4-point scale: impossible, major discomfort, moderate discomfort, or no difficulty. A total score is then calculated and the usual level of discomfort is rated on a numerical scale. The questionnaire was completed on day (D)1, D2, and the day of discharge.

Results

The questionnaire showed very good test-retest reliability, with an overall correlation coefficient above 0.91. The overall score was highly sensitive to change, with a significant median improvement (−5.89) between D1 and discharge (P < 0.001). Of the 16 items, 9 showed significant scalability in their individual sensitivity to change. The criterion validity was moderate: the coefficient for the correlation with the numerical scale was 0.68 on D1 (P < 0.001), 0.55 on D2 (P < 0.001), and 0.69 at discharge (P < 0.001).

Conclusions

The Functional Evaluation in Thoracic Outlet Syndrome self-questionnaire is a quick, simple way of assessing the impact of thoracic outlet syndrome on activities of daily living. The overall score and most of the items displayed good reproducibility and sensitivity to change.