bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254
Authors: Spinner Christoph D , Felizarta Franco , Rizzardini Giuliano , Philibert Patrick , Mitha Essack , Domingo Pere , Stephan Christoph J , DeGrosky Michelle , Bainbridge Veronica , Zhan Joyce , Dumitrescu Teodora Pene , Jeffrey Jerry L , Xu Jianfeng , Halliday Fiona , Gan Jianjun , Johnson Mark , Gartland Martin , Joshi Samit R , Lataillade Max
Published: January 2022

Background

GSK3640254 (GSK’254) is a next-generation human immunodeficiency virus type 1 (HIV-1) maturation inhibitor with pharmacokinetics (PK) supporting once-daily therapy.

Methods

This phase IIa double-blind (sponsor-unblinded), randomized, placebo-controlled, adaptive study evaluated antiviral effect, safety, tolerability, and PK of once-daily GSK’254 monotherapy administered with food (moderate-fat meal) in HIV-1–positive, treatment-naive adults. In part 1, participants received GSK’254 10 or 200 mg for 10 days. In part 2, participants received GSK’254 40, 80, or 140 mg for 7 days, modified from 10 days by a protocol amendment to decrease potential for resistance-associated mutations (RAMs). The primary endpoint was maximum change from baseline in HIV-1 RNA.

Results

Maximum changes in HIV-1 RNA of −0.4, −1.2, −1.0, −1.5, and −2.0 log10 occurred with GSK’254 10, 40, 80, 140, and 200 mg, respectively. Regardless of dosing duration, doses ≥40 mg resulted in ≥1-log10 declines in HIV-1 RNA. Plasma PK was generally dose proportional to 140 mg but non-proportional between 140 and 200 mg. Four participants in the 200-mg group developed RAMs on day 11 in part 1, 1 with phenotypic resistance. No RAMs occurred in part 2. Adverse events (AEs) were reported by 22 (65%) participants; headache was the most common (n = 4). Two non–drug-related serious AEs occurred. All AEs were of mild-to-moderate intensity, except for 2 grade 3 non–drug-related AEs in 1 participant.

Conclusions

This monotherapy study established a dose–antiviral response relationship for GSK’254. No safety or tolerability concerns were noted. These results supported dose selection for the ongoing phase IIb study (ClinicalTrials.gov: NCT04493216).

Clinical Trials Registration

NCT03784079.
Angiogenic Biomarkers for Risk Stratification in Women with Preeclampsia
Authors: Docheva Nikolina , Arenas Gabriel , Nieman Kristin M , Lopes-Perdigao Joana , Yeo Kiang-Teck J , Rana Sarosh
Published: January 2022

Background

Preeclampsia is a leading cause of maternal and neonatal mortality and morbidity worldwide. Diagnosis of the condition is currently limited to utilization of nonspecific signs and symptoms. However, identification of potential pathogenic biomarkers may support earlier diagnosis and ultimately improved prognosis.

Content

The current models of preeclampsia suggest that the disease has components of abnormal placentation, a degree of angiogenic imbalance and endothelial dysfunction. Angiogenic factors such as soluble fms-like tyrosine kinase-1 and soluble endoglin increase while placental growth factor concentrations decrease in the circulation weeks before the onset of the disease. Multiple studies have looked at the capacity of angiogenic factors for the prediction of preeclampsia and adverse pregnancy outcomes.

The goal of this review is to focus on the role of angiogenic factors in the pathogenesis of preeclampsia and use of angiogenic biomarkers for risk stratification, diagnosis, and prognosis of the disease.
Associations between calcium channel blocker therapy and mortality in heart failure with preserved ejection fraction
Authors: Wang Xinyi , Ju Jianqing , Chen Zhuo , Lin Qian , Zhang Zihao , Li Qiuyi , Zhang Jie , Xu Hao , Chen Keji
Published: January 2022

Aims

Treatment of heart failure with preserved ejection fraction (HFpEF) is urgently needed; however, effective treatments are lacking. Current evidence showed a possible association between the use of calcium channel blockers (CCBs) and improved outcomes in HFpEF patients. We aimed to investigate the impact of CCBs on mortality in patients with HFpEF.

Methods and results

This was a post hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular and noncardiovascular mortality. We analysed hazard ratios (HRs) in patients taking CCBs compared with those not taking CCBs using Cox proportional hazard models. We considered 3440 HFpEF patients. The mean follow-up period was 3.4 ± 1.7 years, and 530 patients died during the study period. All-cause mortality rates in patients taking and not taking CCB were 37.3 and 50.8 events per 1000 person-years, respectively. The adjusted HR for all-cause mortality was significantly lower in those taking CCBs than those not taking CCBs [HR: 0.72, 95% confidence interval (CI): 0.59–0.88, P = 0.001]. The risk of cardiovascular and noncardiovascular mortality was also significantly lower in patients taking CCBs than in those not taking CCBs (HR: 0.75, 95% CI: 0.59–0.96, P = 0.023 and HR: 0.68, 95% CI: 0.49–0.93, P = 0.018, respectively).

Conclusion

The use of CCBs was associated with reduced risks of mortality in patients with HFpEF.
Predictive role of atrial fibrillation in cognitive decline: a systematic review and meta-analysis of 2.8 million individuals
Authors: Koh Yu Han , Lew Leslie Z W , Franke Kyle B , Elliott Adrian D , Lau Dennis H , Thiyagarajah Anand , Linz Dominik , Arstall Margaret , Tully Phillip J , Baune Bernhard T , Munawar Dian A , Mahajan Rajiv
Published: January 2022

Aims

To systematic review and meta-analyse the association and mechanistic links between atrial fibrillation (AF) and cognitive impairment.

Methods and results

PubMed, EMBASE, and Cochrane Library were searched up to 27 March 2021 and yielded 4534 citations. After exclusions, 61 were analysed; 15 and 6 studies reported on the association of AF and cognitive impairment in the general population and post-stroke cohorts, respectively. Thirty-six studies reported on the neuro-pathological changes in patients with AF; of those, 13 reported on silent cerebral infarction (SCI) and 11 reported on cerebral microbleeds (CMB). Atrial fibrillation was associated with 39% increased risk of cognitive impairment in the general population [n = 15: 2 822 974 patients; hazard ratio = 1.39; 95% confidence interval (CI) 1.25–1.53, I2 = 90.3%; follow-up 3.8–25 years]. In the post-stroke cohort, AF was associated with a 2.70-fold increased risk of cognitive impairment [adjusted odds ratio (OR) 2.70; 95% CI 1.66–3.74, I2 = 0.0%; follow-up 0.25–3.78 years]. Atrial fibrillation was associated with cerebral small vessel disease, such as white matter hyperintensities and CMB (n = 8: 3698 patients; OR = 1.38; 95% CI 1.11–1.73, I2 = 0.0%), SCI (n = 13: 6188 patients; OR = 2.11; 95% CI 1.58–2.64, I2 = 0%), and decreased cerebral perfusion and cerebral volume even in the absence of clinical stroke.

Conclusion

Atrial fibrillation is associated with increased risk of cognitive impairment. The association with cerebral small vessel disease and cerebral atrophy secondary to cardioembolism and cerebral hypoperfusion may suggest a plausible link in the absence of clinical stroke. PROSPERO CRD42018109185.
7. Interest Groups, Advocacy, and Policy-Making
Authors: John Peter
Published: January 2022

This chapter describes interest, pressure, or advocacy groups, which organize separately from political parties, seeking to influence public opinion and public policy. It discusses the nature of these groups and what they do, before reviewing the debate on the power of interest groups, in particular whether business has a privileged position. Studies of interest groups show the importance of these groups to the delivery of public policy, which reveals a two-way relationship between groups and the state. There is a complex pattern of governance that makes policy-making complicated and difficult terrain for governments or regional and local agencies. In today's turbulent politics, there is room for new advocacy groups to upset the equilibrium. The very unpredictability of the interest group world and the appearance of actors skilled in the use of social media may provide opportunities to influence the political agenda and to engage in more disruptive politics.
9. Governing from Below
Authors: John Peter
Published: January 2022

This chapter studies a key aspect of delegation in British politics: decentralization and local/national self-government. It deals with local government in England, and government in the devolved territories/nations of Scotland, Wales, and Northern Ireland. Decentralization in British politics has formed into a complex pattern, where there are different dynamics in the various territories: relative centralization in England, power-sharing in Northern Ireland, pragmatic devolution in Wales, and then a strong push towards independence in Scotland. For a question about how centralized or decentralized British politics is, the answer would need to be based on where a person lives, with England rehearsing the conventional arguments about constitutional centralization and the rest of the country increasing decentralization, if not a form of federalism. The chapter then assesses the question of the rationale and general stability of the system, with respect to the integrity of the UK as a whole.
6. Leave It to the Market
Authors: Dryzek John S.
Published: January 2022

Economic rationalism involves the intelligent deployment of market instruments to achieve public ends such as environmental protection and resource conservation. The instruments in question can involve the establishment of private property rights in land, air, and water; “cap and trade” markets in pollution rights (emissions trading); tradeable quotes in resources such as fish; green taxes, such as a carbon tax; and the purchase of offsets to compensate for environmentally damaging behavior. These instruments have been adopted in many countries, though with some resistance from those who believe there is more to life than economic reasoning.
7. Greener Growth
Authors: Dryzek John S.
Published: January 2022

Sustainable development became the dominant discourse in global environmental affairs in the 1980s, spurred by the landmark Brundtland report to the United Nations, and remains widely popular, embodied for example in the Sustainable Development Goals adopted by an assembly of all the world’s countries in 2015. Sustainable development combines ecological protection, economic growth, social justice, and intergenerational equity, which can be sought globally and in perpetuity. “Green growth” becomes possible, while ecological limits and boundaries fade into the background. However, it is necessary for a collective effort that involves governments, international organizations, and non-governmental organizations, and citizens to make this happen. Sustainable development is an integrating discourse that covers local and global environmental issues and a host of economic and development concerns. Beyond this shared discourse, different actors (such as corporations and environmentalists) ascribe different means to the idea. Despite its popularity as a discourse, sustainable development has not actually been achieved anywhere.
Introduction to International Relations: Theories and Approaches
Authors: Sørensen Georg , Møller Jørgen , Jackson Robert
Published: January 2022

Introduction to International Relations provides a concise introduction to the principal international relations theories and approaches, and explores how theory can be used to analyse contemporary issues. Throughout the text, the chapters encourage readers to consider the strengths and weaknesses of the theories presented, and the major points of contention between them. In so doing, the text helps the reader to build a clear understanding of how major theoretical debates link up with each other, and how the structure of the discipline of international relations is established. The book places a strong emphasis throughout on the relationship between theory and practice, carefully explaining how theories organize and shape our view of the world. It also shows how a historical perspective can often refine theories and provide a frame of reference for contemporary problems of international relations. Topics include realism, liberalism, International Society, International Political Economy, social constructivism, post-positivism in international relations, major issues in IPE and IR, foreign policy, and world order. Each chapter ends by discussing how different theories have attempted to integrate or combine international and domfactors in their explanatory frameworks. The final part of the book is dedicated to major global issues and how theory can be used as a tool to analyse and interpret these issues. The text is accompanied by online resources, which include: short case studies, review questions, annotated web links, and a flashcard glossary.
3. The European Council:
Authors: van Middelaar Luuk , Puetter Uwe
Published: January 2022

This chapter discusses the central role of the European Council in European Union (EU) politics and policymaking. Even though it was not listed among the EU’s core institutions until the Treaty of Lisbon, the European Council regularly intervenes in EU decision-making to make other institutional actors follow its guidance. Initially, it was meant to be predominantly an informal institution for direct exchanges between the heads of state or government of the member states. Yet it assumed responsibility for landmark decisions which paved the way for key steps in integration, such as EU enlargements and the euro. The European Council has arguably saved the Union from break-up by acting as its ultimate crisis manager and, at times, has skirted the boundaries of EU law by finding institutional compromises and fixes. The institution plays a guiding role, especially in relation to the Commission and the Council of the European Union, which was formerly known as the Council of Ministers. The European Council devises strategic guidelines for policy development, shapes processes of institutional reform, and breaks impasses when agreement cannot otherwise be found. Since the Treaty of Maastricht, European Council intervention has become a routine in new EU policy areas, such as euro area economic governance and foreign policy. The Treaty of Lisbon assigns the European Council its own full-time president and places the institution right after the European Parliament (EP) in the list of EU institutions. Even though it has shaped European integration since 1975, the European Council did not find much recognition in traditional theories of European integration. This has changed more recently, with renewed debate about intergovernmentalism in EU politics.
Prevalence of Malnutrition, Its Risk Factors, and the Use of Nutrition Support in Patients with Inflammatory Bowel Disease
Authors: Liu Jing , Ge Xiaolong , Ouyang Chunhui , Wang Dongxu , Zhang Xiaoqi , Liang Jie , Zhu Weiming , Cao Qian
Published: January 2022

Background

Malnutrition is prevalent among patients with inflammatory bowel disease (IBD). Nutritional profiles among Asian patients with IBD have seldom been investigated. We assessed the prevalence of and risk factors for malnutrition, use of nutrition support, and sociopsychological status associated with malnutrition among patients with IBD in China.

Methods

Patients with ulcerative colitis and Crohn’s disease (CD) recruited from 43 tertiary referral hospitals were screened for malnutrition and nutrient deficiencies in this cross-sectional study. The use of nutrition support was recorded. The sociopsychological status was assessed by subjective questionnaires. Factors associated with malnutrition were analyzed, and multivariate regression was used to determine independent predictors for malnutrition.

Results

We recruited 1013 patients with a median age of 35.0 years, 58.5% of them had CD, and 61.4% of all patients were male. Overall, 49.5% (n = 501) of patients were diagnosed with malnutrition, including 57.0% of patients with CD, 38.8% of patients with ulcerative colitis, and 44.1% of patients with quiescent or mildly active disease. Nutrient deficiencies were prevalent despite the absence of malnutrition. Malnutrition was associated with adverse sociopsychological status, including decreased social support, higher perceived stress, and impaired quality of life. Moderate to severe disease activity and extensive disease were 2 independent risk factors for malnutrition. In total, 41.6% of patients received nutrition support, and patients with risk factors were more likely to receive nutrition support.

Conclusions

Malnutrition was highly prevalent and associated with adverse consequences in Chinese patients with IBD. Malnutrition screening and early initiation of nutrition support are essential components in IBD care.
Longitudinal Bowel Behavior Assessed by Bowel Ultrasound to Predict Early Response to Anti-TNF Therapy in Patients With Crohn’s Disease: A Pilot Study
Authors: Chen Yu-Jun , Chen Bai-Li , Liang Mei-Juan , Chen Shu-Ling , Li Xue-Hua , Qiu Yun , Pang Lan-Lan , Xia Qing-Qing , He Yao , Zeng Zhi-Rong , Chen Min-Hu , Mao Ren , Xie Xiao-Yan
Published: January 2022

Background

Early changes in bowel behavior during anti-tumor necrosis factor (anti-TNF) induction therapy in Crohn’s disease (CD) are relatively unknown. We determined (1) the onset of changes in bowel behavior in CD patients receiving anti-TNF therapy by ultrasound and (2) the feasibility of shear wave elastography (SWE) in predicting early response to anti-TNF therapy.

Methods

Consecutive ileal or ileocolonic CD patients programmed to initiate anti-TNF therapy were enrolled. Bowel ultrasound was performed at baseline and at weeks 2, 6, and 14. Changes in bowel wall thickness, Doppler signals of the bowel wall (Limberg score), and SWE values were compared using a linear mixed model. Early response to anti-TNF therapy was based on a composite strategy of clinical and colonoscopy assessment at week 14.

Results

Of the 30 patients enrolled in this study, 20 patients achieved a response to anti-TNF therapy at week 14. The bowel wall thickness and SWE value of the response group showed a significant downward trend compared with the nonresponse group (P = .003 and P = .011, respectively). Bowel wall thickness, the Limberg score, and SWE values were significantly reduced as early as week 2 compared with baseline (P < .001, P < .001, and P = .003, respectively) in the response group. Baseline SWE values (21.3 ± 8.7 kPa vs 15.3 ± 4.7 kPa; P = .022) and bowel wall thickness (8.5 ± 2.3 mm vs 6.9 ± 1.5 mm; P = .027) in the nonresponse group were significantly higher than in the response group.

Conclusions

This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as week 2 after starting anti-TNF therapy. Bowel ultrasound together with elasticity imaging could predict early response to anti-TNF therapy.
The impact of pertussis vaccine programme changes on pertussis disease burden in Manitoba, 1992–2017—an age-period-cohort analysis
Authors: Wilkinson Krista , Righolt Christiaan H , Elliott Lawrence J , Fanella Sergio , Mahmud Salaheddin M
Published: January 2022

Background

Changes to pertussis vaccination programmes can have impacts on disease burden that should be estimated independently from factors such as age- and period-related trends. We used age-period-cohort (APC) models to explore pertussis incidence in Manitoba over a 25-year period (1992–2017).

Methods

We identified all laboratory-confirmed cases of pertussis from Manitoba’s Communicable Diseases Database and calculated age-standardized incidence rates. We used APC models to investigate trends in pertussis incidence.

Results

During the study period, 2479 cases were reported. Age-standardized rates were highest during a large outbreak in 1994 (55 cases/100 000 person-years), with much lower peaks in 1998, 2012 and 2016. We saw strong age and cohort effects in the APC models, with a steady decrease in incidence with increasing age and increased risk in the cohort born between 1980 and 1995.

Conclusions

The highest risk for pertussis was consistently in young children, regardless of birth cohort or time period. The 1981 programme change to an adsorbed whole-cell pertussis vaccine with low effectiveness resulted in reduced protection in the 1981–95 birth cohort and contributed to the largest outbreak of disease during the 25-year study period.
Growth of Unbounded Subsets in Nilpotent Groups, Random Mapping Statistics and Geometry of Group Laws
Authors: Greenfeld Be’eri , Lavner Hagai
Published: January 2022

For a group $G$ let $\gamma ^{\max }_G(n)$ denote the maximum number of length-$n$ words over an arbitrary $n$-letter subset of $G$. If $G$ is finitely generated and residually finite, then either $\gamma ^{\max }_G(n)$ is exponentially bounded, if and only if $G$ is virtually abelian, or $\gamma ^{\max }_G(n)\geq ~\left (e^{-\frac {1}{4}}+o(1)\right )n^n$; the latter bound cannot be improved, namely, it is attained for the Heisenberg group. For higher-step free nilpotent groups we have $(1-o(1))n^n\leq \gamma ^{\max }_G(n)\lneq n^n$. As a key ingredient in the proof, we calculate the number of pair histograms of functions $f\colon [n]\rightarrow [n]$ and the probability that a random function $f\colon [n]\rightarrow [n]$ can be uniquely determined by its pair histogram. We analyze group laws of the Heisenberg group by means of closed paths attached to words in the free group and their projected oriented polygons.
Numbers and narratives: how qualitative methods can strengthen the science of paediatric antimicrobial stewardship
Authors: Woods-Hill Charlotte Z. , Xie Anping , Lin John , Wolfe Heather A. , Plattner Alex S. , Malone Sara , Chiotos Kathleen , Szymczak Julia E.
Published: January 2022

Antimicrobial and diagnostic stewardship initiatives have become increasingly important in paediatric settings. The value of qualitative approaches to conduct stewardship work in paediatric patients is being increasingly recognized. This article seeks to provide an introduction to basic elements of qualitative study designs and provide an overview of how these methods have successfully been applied to both antimicrobial and diagnostic stewardship work in paediatric patients. A multidisciplinary team of experts in paediatric infectious diseases, paediatric critical care and qualitative methods has written a perspective piece introducing readers to qualitative stewardship work in children, intended as an overview to highlight the importance of such methods and as a starting point for further work. We describe key differences between qualitative and quantitative methods, and the potential benefits of qualitative approaches. We present examples of qualitative research in five discrete topic areas of high relevance for paediatric stewardship work: provider attitudes; provider prescribing behaviours; stewardship in low-resource settings; parents’ perspectives on stewardship; and stewardship work focusing on select high-risk patients. Finally, we explore the opportunities for multidisciplinary academic collaboration, incorporation of innovative scientific disciplines and young investigator growth through the use of qualitative research in paediatric stewardship. Qualitative approaches can bring rich insights and critically needed new information to antimicrobial and diagnostic stewardship efforts in children. Such methods are an important tool in the armamentarium against worsening antimicrobial resistance, and a major opportunity for investigators interested in moving the needle forward for stewardship in paediatric patients.
Synthetic Cannabinoid Receptor Agonists in Postmortem Casework in Scotland
Authors: Seywright Alice , Irvine Alexander F. D , McKeown Denise A , Wylie Fiona M , Torrance Hazel J
Published: January 2022

Synthetic cannabinoid receptor agonists (SCRAs) have been a concern to forensic toxicologists since their emergence as drugs of abuse in the mid-late 2000s. The extent of their use in Scotland appears to be low especially when compared to other drug groups such as opioids and benzodiazepines. There is a concern, however, that the use is widespread in prison populations in particular. In this work, samples of blood and urine collected during routine postmortem examination between April 2017 and March 2019 were subjected to analysis of SCRA compounds. Circumstantial and demographic information was collected on positive cases to build up a body of evidence for where SCRAs may be most likely to contribute to the cause of death. Thirteen out of 133 cases (10%) tested were positive for one or more compound in one or more matrix. Overall, the detection of 5F-MDMB-PINACA or its O-desmethyl acid metabolite was most common, followed by the metabolite shared by AB-FUBINACA and MMB-FUBINACA. SCRA-positive cases were predominantly males (92%), and the age range of all decedents was 21–49 years old (median 36 years). The majority of cases were certified as drug-related deaths (DRDs, 38%), natural/medical (31%) or suicide (23%), and two of the DRDs mentioned SCRAs specifically in the cause of death. The concentrations of SCRAs detected did not seem to be as important to the determination of the cause of death as their mere presence, but quantitative results were reported (where possible) in order to build up a body of evidence for SCRA concentrations in different case types.
Treatment of a rare recurrent pulmonary arteriovenous malformation after multiple embolization by robotic-assisted thoracoscopic surgery
Authors: Li Tong , Hao Peng , Lv Xiaojing , Tian Hui
Published: January 2022

Pulmonary arteriovenous malformations (PAVMs) are a rare pulmonary arteriovenous direct traffic vascular malformation, which directly connect the pulmonary artery to the pulmonary vein without pulmonary capillary bed. Currently, surgical resection and percutaneous transcatheter embolization are the main mode of treatment. Embolization is gradually becoming the preferred treatment for people with PAVMs, because it is less invasive and easy to repeat. We describe a case of PAVMs with hemoptysis that relapsed again after three times of embolization and then only presented new symptoms of transient ischemic attack. Finally, the patient was treated by Da Vinci robotic-assisted thoracoscopic surgery, and there were no obvious post-operative complications and recurrence. It is the first report of multiple recurrent complex PAVMs and we present our experience with the treatment of recurrent PAVMs.
How the spectral energy distribution and galaxy morphology constrain each other, with application to morphological selection using galaxy colours
Authors: Uzeirbegovic Emir , Martin Garreth , Kaviraj Sugata
Published: January 2022

We introduce an empirical methodology to study how the spectral energy distribution (SED) and galaxy morphology constrain each other and implement this on ∼8000 galaxies from the HST CANDELS survey in the GOODS-South field. We show that the SED does constrain morphology and present a method that quantifies the strength of the link between these two quantities. Two galaxies with very similar SEDs are around three times more likely to also be morphologically similar, with SED constraining morphology most strongly for relatively massive red ellipticals. We apply our methodology to explore likely upper bounds on the efficacy of morphological selection using colour. We show that, under reasonable assumptions, colour selection is relatively ineffective at separating homogeneous morphologies. Even with the use of up to six colours for morphological selection, the average purity in the resultant morphological classes is only around 60 per cent. While the results can be improved by using the whole SED, the gains are not significant, with purity values remaining around 70 per cent or below.
Velocity gradients: magnetic field tomography towards the supernova remnant W44
Authors: Liu Mingrui , Hu Yue , Lazarian A
Published: January 2022

As a novel approach for tracing interstellar magnetic fields, the velocity gradient technique (VGT) has been proven to be effective for probing magnetic fields in the diffuse interstellar medium (ISM). In this work, we verify the VGT in a broader context by applying the technique to a molecular cloud interacting with the supernova remnant (SNR) W44. We probe the magnetic fields with the VGT using CO, $\rm HCO^+$ and H i emission lines and make a comparison with the Planck 353-GHZ dust polarization. We show that the VGT gives an accurate measurement that coheres with the Planck polarization especially in intense molecular gas emission regions. We further study the foreground’s contribution on the polarization that results in misalignment between the VGT and the Planck measurements in low-intensity molecular gas areas. We advance the VGT to achieve magnetic field tomography by decomposing the SNR W44 into various velocity components. We show that W44’s velocity component at v ∼ 45 km s−1 exhibits the largest coverage and gives best agreement with Planck polarization in terms of magnetic field orientation.
Optical properties of Peaked Spectrum radio sources
Authors: Nascimento R S , Rodríguez-Ardila A , Dahmer-Hahn L , Fonseca-Faria M A , Riffel R , Marinello M , Beuchert T , Callingham J R
Published: January 2022

In this work, we study the optical properties of compact radio sources selected from the literature in order to determine the impact of the radio-jet in their circumnuclear environment. Our sample includes 58 Compact Steep Spectrum (CSS) and GigaHertz Peaked Spectrum (GPS) and 14 Megahertz-Peaked spectrum (MPS) radio sources located at z ≤ 1. The radio luminosity (LR) of the sample varies between Log LR ∼ 23.2 and 27.7 W Hz−1. We obtained optical spectra for all sources from SDSS-DR12 and performed a stellar population synthesis using the starlight code. We derived stellar masses (M⋆), ages 〈t⋆〉, star formation rates (SFR), metallicities 〈Z⋆〉 and internal reddening AV for all young AGNs of our sample. A visual inspection of the SDSS images was made to assign a morphological class for each source. Our results indicate that the sample is dominated by intermediate to old stellar populations and there is no strong correlation between optical and radio properties of these sources. Also, we found that young AGNs can be hosted by elliptical, spiral and interacting galaxies, confirming recent findings. When comparing the optical properties of CSS/GPS and MPS sources, we do not find any significant difference. Finally, the Mid-Infrared WISE colours analysis suggests that the compact radio sources defined as powerful AGNs are, in general, gas-rich systems.
A case of clinically amyopathic dermatomyositis that was refractory to intensive immunosuppressive therapy including tofacitinib, but successfully treated with plasma exchange therapy
Authors: Hiraoka Daisuke , Ishizaki Jun , Horie Kenta , Matsumoto Takuya , Suemori Koichiro , Takenaka Katsuto , Hasegawa Hitoshi
Published: January 2022

Clinically amyopathic dermatomyositis (CADM) patients often develop rapidly progressive interstitial lung disease (RP-ILD). A high level of anti-melanoma differentiation-associated gene 5 antibodies (anti-MDA5 Ab) before treatment is associated with RP-ILD development, a poor treatment response, and poor survival. The prognosis of CADM patients remains poor due to ILD even with combined intensive immunosuppressive therapy. Recently, several additional therapies, including tofacitinib (TOF) and plasma exchange (PE) therapy, have been reported to be effective. We herein report a case of CADM-ILD with a high level of anti-MDA5 Ab that was refractory to combined intensive immunosuppressive therapy including TOF, but successfully treated with PE. The following are possible reasons why TOF was ineffective: (1) cytokines that were not suppressed by TOF played an important role in RP-ILD; (2) TOF was administered later than previously reported; and (3) TOF did not suppress pathological substances such as antibodies. On the other hand, PE removes cytokines and various pathological substances. Therefore, PE may be a more reasonable additional therapy for intractable CADM-ILD.
A population study of clinical trial accrual for women and minorities in neuro-oncology following the NIH Revitalization Act
Authors: Reihl Sheantel J , Patil Nirav , Morshed Ramin A , Mehari Mulki , Aabedi Alexander , Chukwueke Ugonma N , Porter Alyx B , Fontil Valy , Cioffi Gino , Waite Kristin , Kruchko Carol , Ostrom Quinn , Barnholtz-Sloan Jill , Hervey-Jumper Shawn L
Published: January 2022

Background

The NIH Revitalization Act, implemented 29 years ago, set to improve the representation of women and minorities in clinical trials. In this study, we investigate progress made in all phase therapeutic clinical trials for neuroepithelial CNS tumors stratified by demographic-specific age-adjusted disease incidence and mortality. Additionally, we identify workforce characteristics associated with clinical trials meeting established accrual benchmarks.

Methods

Registry study of published clinical trials for World Health Organization defined neuroepithelial CNS tumors between January 2000 and December 2019. Study participants were obtained from PubMed and ClinicalTrials.gov. Population-based data originated from the CBTRUS for incidence analyses. SEER-18 Incidence-Based Mortality data was used for mortality analysis. Descriptive statistics, Fisher exact, and χ 2 tests were used for data analysis.

Results

Among 662 published clinical trials representing 49 907 participants, 62.5% of participants were men and 37.5% women (P < .0001) representing a mortality specific over-accrual for men (P = .001). Whites, Asians, Blacks, and Hispanics represented 91.7%, 1.5%, 2.6%, and 1.7% of trial participants. Compared with mortality, Blacks (47% of expected mortality, P = .008), Hispanics (17% of expected mortality, P < .001) and Asians (33% of expected mortality, P < .001) were underrepresented compared with Whites (114% of expected mortality, P < .001). Clinical trials meeting accrual benchmarks for race included minority authorship.

Conclusions

Following the Revitalization Act, minorities and women remain underrepresented in therapeutic clinical trials for neuroepithelial tumors, relative to disease incidence and mortality. Study accrual has improved with time. This study provides a framework for clinical trial accrual efforts and offers guidance regarding workforce considerations associated with enrollment of underserved patients.
The Mood Boost from Tobacco Cigarettes is More Erratic with the Additions of Cannabis and Alcohol
Authors: Kendall Ashley D , Hedeker Donald , Diviak Kathleen R , Mermelstein Robin J
Published: January 2022

Introduction

A large body of literature indicates that nicotine results in an acute mood “boost,” including increased positive affect and decreased negative affect. Young adults frequently engage in polysubstance use of cigarettes with cannabis and alcohol—a trend that is likely to accelerate with the expanding legalization of cannabis. However, little is known about whether polysubstance use, defined here as combustible tobacco cigarette use within the same hour as cannabis and alcohol, is associated with changes in the nicotine mood boost. The present study aimed to address this gap.

Methods

Young adults (N = 202, 52% female, mean age = 21 years at time 1) provided ecological moments assessment (EMA) reports of cigarette use over two 7-day bursts spaced 1 year apart. In each report, participants rated mood levels before and after smoking, and indicated cannabis and alcohol use. Mixed-effects location-scale modeling simultaneously tested changes in mood levels and variability related to smoking events with cannabis and/or alcohol compared with smoking-only events.

Results

From before to after smoking, positive affect increased and negative affect decreased, on average. Overall, the additions of cannabis and/or alcohol had nonsignificant associations with these mean changes. However, polysubstance use, as well as cigarette-cannabis co-use, were each associated with significantly greater within-person variability in the positive and negative affect changes related to smoking.

Conclusions

The mood benefits associated with smoking were more erratic in the contexts of polysubstance use and cigarette-cannabis co-use. Potential implications for young adults’ long-term nicotine use trajectories are discussed.

Implications

Among young adults who smoke cigarettes, the mood “boost” from smoking may be more erratic—which is to say, more likely to be either amplified or attenuated—with the additions of cannabis and alcohol together, or cannabis alone. On occasions when young adults seek out cannabis and alcohol to enhance their smoking mood boost, but instead experience a dampening effect, they might consume more nicotine, contributing over time to greater dependence. Future investigation is warranted, with particular attention to nicotine-cannabis co-use.
Treatment Patterns, Health Care Resource Utilization, and Cost in Patients with Myelofibrosis in the United States
Authors: Copher Ronda , Kee Arianna , Gerds Aaron
Published: January 2022

Background

This study analyses treatment patterns, health care resource utilization (HCRU), and costs in patients with myelofibrosis (MF) and a subgroup treated with ruxolitinib (RUX).

Materials and Methods

Treatment patterns, all-cause and MF-related HCRU, and costs were analyzed in adults with MF with continuous enrollment in a commercial or the Medicare Advantage health plan in the pre-index period, defined as the 12 months immediately prior to the index date (date of primary or secondary MF diagnosis), and the post-index period, defined as ≥6 months following the index date. In a subgroup analysis, outcomes were analyzed in patients treated with optimal RUX (OPT RUX, ≥30 mg) and suboptimal RUX (SUB RUX, <30 mg) in the pre-index RUX period, defined as the 3 months immediately prior to the index RUX date (first date for an RUX claim), and the post-index RUX period, defined as ≥6 months following the index RUX date.

Results

Of 2830 patients with an MF diagnosis, 1191 met eligibility requirements. The median age of patients was 72 years, 54% were male, and comorbidities were frequent. Sixty percent of patients received ≥1 line of therapy (LOT), of which 46% (n = 331) had ≥2 LOTs during the post-index MF period. Costs increased considerably 6-month pre-index to 6-month post-index (all-cause: cause ($24,216 to $48,966) and MF-related ($16,502 to $39,383), driven by inpatient stays and pharmacy costs. In the subgroup analysis, patients treated with RUX (n = 495) experienced significant disease burden and high costs, regardless of dose. A shorter duration of therapy and a higher rate of discontinuation were observed in patients treated with SUB RUX (n = 191) versus OPT RUX (n = 304).

Conclusion

These findings suggest a significant disease and economic impacts associated with MF patients that persists with RUX therapy, highlighting the need for additional therapeutic options for MF.
The Role of Triacylglycerol in the Protection of Cells against Lipotoxicity under Drought in Lolium multiflorum/Festuca
arundinacea Introgression Forms
Authors: Perlikowski Dawid , Lechowicz Katarzyna , Skirycz Aleksandra , Michaelis Änna , Pawłowicz Izabela , Kosmala Arkadiusz
Published: January 2022

Triacylglycerol is a key lipid compound involved in maintaining homeostasis of both membrane lipids and free fatty acids (FFA) in plant cells under adverse environmental conditions. However, its role in the process of lipid remodeling has not been fully recognized, especially in monocots, including grass species. For our study, two closely related introgression forms of Lolium multiflorum (Italian ryegrass) and Festuca arundinacea (tall fescue), distinct in their level of drought tolerance, were selected as plant models to study rearrangements in plant lipidome under water deficit and further re-watering. The low drought tolerant (LDT) form revealed an elevated level of cellular membrane damage accompanied by an increased content of polyunsaturated FFA and triacylglycerol under water deficit, compared with the high drought tolerant (HDT) form. However, the LDT introgression form demonstrated also the ability to regenerate its membranes after stress cessation. The obtained results clearly indicated that accumulation of triacylglycerol under advanced drought in the LDT form could serve as a cellular protective mechanism against overaccumulation of toxic polyunsaturated FFA and other lipid intermediates. Furthermore, accumulation of triacylglycerol under drought conditions could serve also as storage of substrates required for further regeneration of membranes after stress cessation. The rearrangements in triacylglycerol metabolism were supported by the upregulation of several genes, involved in a biosynthesis of triacylglycerol. With respect to this process, diacylglycerol O-acyltransferase DGAT2 seems to play the most important role in the analyzed grasses.
Optimal Capital Structure with Imperfect Competition
Authors: Matveyev Egor , Zhdanov Alexei
Published: January 2022

We develop a model of optimal capital structure in imperfectly competitive markets by focusing on a duopoly. The model endogenizes both the financing and investment decisions of firms. We show that in equilibrium the industry leader uses debt conservatively, while the follower uses debt more aggressively and, as the result, defaults first. The model generates novel predictions about the leverage choices of the leader and the follower, their default likelihood, and the degree of leverage dispersion between competing firms. These predictions are strongly supported by the data. (JEL G13, G34, L13)
SLICC-Frailty Index is independently associated with impaired physical function, activities of daily living and quality of life measures
Authors: Keramiotou Kyriaki , Anagnostou Christos , Konstantonis George , Fragiadaki Kalliopi , Kataxaki Evangelia , Sfikakis Petros P , Tektonidou Maria G
Published: January 2022

Objective

The SLICC Frailty Index (SLICC-FI) was developed to assess health deficits including disease activity, organ damage, comorbidities and functional status. We examined any relationship between SLICC-FI and objective physical function measures, activities of daily living performance and quality of life in SLE.

Methods

SLICC-FI was estimated using data from patient files and patient-reported questionnaires. Jamar Dynamometer, pinch gauge and Purdue pegboard test measured grip strength, pinch strength and dexterity, respectively. Activities of daily living performance was assessed by the Disabilities of Arm, Shoulder and Hand (DASH) questionnaire and HAQ. Quality of life was evaluated by LupusQol questionnaire.

Results

This cross-sectional study included 240 SLE patients (90% female, mean (s.d.) age: 47.63 (13.01), median (IQR) disease duration: 9 (4–16)). Mean (s.d.) SLICC-FI was 0.09 (0.06). Forty-three (17.9%) patients were classified as robust, 105 (43.8%) as relatively less fit, 77 (32.1%) as least fit and 15 (6.2%) as frail. In univariate analysis, SLICC-FI was significantly associated with DASH and HAQ with an inverse association with grip strength, pinch strength and all purdue scores (all P < 0.001). A negative correlation was found between SLICC-FI score and all LupusQoL domain scores (all P < 0.001). All associations remained statistically significant in multivariate regression analysis, after adjustment for age, disease duration, SLEDAI-2K, SLICC, immunosuppressives, corticosteroids and Charlson score.

Conclusion

SLICC-FI is independently associated with poor physical function and activities of daily living performance and impaired quality of life and may help to identify patients in need of additional interventions beyond routine care.
Automatic analysis of muscular activity in the flexor digitorum superficialis muscles: a fast screening method for rapid eye movement sleep without atonia
Authors: Cesari Matteo , Heidbreder Anna , Gaig Carles , Bergmann Melanie , Brandauer Elisabeth , Iranzo Alex , Holzknecht Evi , Santamaria Joan , Högl Birgit , Stefani Ambra
Published: January 2022

Study objectives

To identify a fast and reliable method for rapid eye movement (REM) sleep without atonia (RWA) quantification.

Methods

We analyzed 36 video-polysomnographies (v-PSGs) of isolated REM sleep behavior disorder (iRBD) patients and 35 controls’ v-PSGs. Patients diagnosed with RBD had: i) RWA, quantified with a reference method, i.e. automatic and artifact-corrected 3-s Sleep Innsbruck Barcelona (SINBAR) index in REM sleep periods (RSPs, i.e. manually selected portions of REM sleep); and ii) v-PSG-documented RBD behaviors. We quantified RWA with other (semi)-automated methods requiring less human intervention than the reference one: the indices proposed by the SINBAR group (the 3-s and 30-s phasic flexor digitorum superficialis (FDS), phasic/”any”/tonic mentalis), and the REM atonia, short and long muscle activity indices (in mentalis/submentalis/FDS muscles). They were calculated in whole REM sleep (i.e. REM sleep scored following international guidelines), in RSPs, with and without manual artifact correction. Area under curves (AUC) discriminating iRBD from controls were computed. Using published cut-offs, the indices’ sensitivity and specificity for iRBD identification were calculated. Apnea-hypopnea index in REM sleep (AHIREM) was considered in the analyses.

Results

RWA indices from FDS muscles alone had the highest AUCs and all of them had 100% sensitivity. Without manual RSP selection and artifact correction, the “30-s phasic FDS” and the “FDS long muscle activity” had the highest specificity (85%) with AHIREM < 15/h. RWA indices were less reliable when AHIREM≥15/h.

Conclusions

If AHIREM<15/h, FDS muscular activity in whole REM sleep and without artifact correction is fast and reliable to rule out RWA.