bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Bulk and Single-Cell Profiling of Premanufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy
Authors: Chen Gregory M. , Chen Changya , Das Rajat K. , Gao Peng , Chen Chia-Hui , Bandyopadhyay Shovik , Ding Yang-Yang , Uzun Yasin , Yu Wenbao , Zhu Qin , Myers Regina M. , Grupp Stephan A. , Barrett David M. , Tan Kai
Published: April 2021

The adoptive transfer of chimeric antigen receptor (CAR) T cells represents a breakthrough in clinical oncology, yet both between- and within-patient differences in autologously derived T cells are a major contributor to therapy failure. To interrogate the molecular determinants of clinical CAR T-cell persistence, we extensively characterized the premanufacture T cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy. We performed RNA-sequencing analysis on sorted T-cell subsets from all 71 patients, followed by paired Cellular Indexing of Transcriptomes and Epitopes (CITE) sequencing and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on T cells from six of these patients. We found that chronic IFN signaling regulated by IRF7 was associated with poor CAR T-cell persistence across T-cell subsets, and that the TCF7 regulon not only associates with the favorable naïve T-cell state, but is maintained in effector T cells among patients with long-term CAR T-cell persistence. These findings provide key insights into the underlying molecular determinants of clinical CAR T-cell function.

Significance:

To improve clinical outcomes for CAR T-cell therapy, there is a need to understand the molecular determinants of CAR T-cell persistence. These data represent the largest clinically annotated molecular atlas in CAR T-cell therapy to date, and significantly advance our understanding of the mechanisms underlying therapeutic efficacy.

This article is highlighted in the In This Issue feature, p. 2113
Regulatory T-cell Transcriptomic Reprogramming Characterizes Adverse Events by Checkpoint Inhibitors in Solid Tumors
Authors: Grigoriou Maria , Banos Aggelos , Hatzioannou Aikaterini , Kloetgen Andreas , Kouzis Panagiotis , Aggouraki Despoina , Zakopoulou Roubini , Bamias Giorgos , Kassi Eva , Mavroudis Dimitrios , Bamias Aristotelis , Boumpas Dimitrios T. , Tsirigos Aristotelis , Gogas Helen , Alissafi Themis , Verginis Panayotis
Published: April 2021

Immune checkpoint inhibitors (ICI), which target immune regulatory pathways to unleash antitumor responses, have revolutionized cancer immunotherapy. Despite the remarkable success of ICI immunotherapy, a significant proportion of patients whose tumors respond to these treatments develop immune-related adverse events (irAE) resembling autoimmune diseases. Although the clinical spectrum of irAEs is well characterized, their successful management remains empiric. This is in part because the pathogenic mechanisms involved in the breakdown of peripheral tolerance and induction of irAEs remain elusive. Herein, we focused on regulatory T cells (Treg) in individuals with irAEs because these cells are vital for maintenance of peripheral tolerance, appear expanded in the peripheral blood of individuals with cancer, and abundantly express checkpoint molecules, hence representing direct targets of ICI immunotherapy. Our data demonstrate an intense transcriptomic reprogramming of CD4+CD25+CD127− Tregs in the blood of individuals with advanced metastatic melanoma who develop irAEs following ICI immunotherapy, with a characteristic inflammatory, apoptotic, and metabolic signature. This inflammatory signature was shared by Tregs from individuals with different types of cancer developing irAEs and individuals with autoimmune diseases. Our findings suggest that inflammatory Treg reprogramming is a feature of immunotherapy-induced irAEs, and this may facilitate translational approaches aiming to induce robust antitumor immunity without disturbing peripheral tolerance.
Benefits and Harms of Hypertension and High-Normal Labels: A Randomized Experiment
Authors: Muscat Danielle Marie , Morris Georgina May , Bell Katy , Cvejic Erin , Smith Jenna , Jansen Jesse , Thomas Rae , Bonner Carissa , Doust Jenny , McCaffery Kirsten
Published: April 2021

Background:

Recent US guidelines lowered the threshold for diagnosing hypertension while other international guidelines use alternative/no labels for the same group (blood pressure [BP], <140/90 mm Hg). We investigated potential benefits and harms of hypertension and high-normal BP labels, compared with control, among people at lower risk of cardiovascular disease.

Methods:

We conducted a randomized experiment using a national sample of Australians (n=1318) 40 to 50 years of age recruited from an online panel. Participants were randomized to 1 of 3 hypothetical scenarios where a general practitioner told them they had a BP reading of 135/85 mm Hg, using either hypertension/high-normal BP/control (general BP description) labels. Participants were then randomized to receive an additional absolute risk description or nothing. Primary outcomes were willingness to change diet and worry. Secondary outcomes included exercise/medication intentions, risk perceptions, and other psychosocial outcomes.

Results:

There was no difference in willingness to change diet across label groups (
P
=0.22). The hypertension label (mean difference [MD], 0.74 [95% CI, 0.41–1.06];
P
<0.001) and high-normal BP label (MD, 0.45 [95% CI, 0.12–0.78];
P
=0.008) had increased worry about cardiovascular disease risk compared with control. There was no evidence that either label increased willingness to exercise (
P
=0.80). However, the hypertension (MD, 0.20 [95% CI, 0.04–0.36];
P
=0.014), but not high-normal label (MD, 0.06 [95% CI, −0.10 to 0.21];
P
=0.49), increased willingness to accept BP-lowering medication compared with control. Psychosocial differences including lower control, higher risk perceptions, and more negative affect were found for the hypertension and high-normal labels compared with control. Providing absolute risk information decreased willingness to change diet (MD, 0.25 [95% CI, 0.10–0.41];
P
=0.001) and increase exercise (MD, 0.28 [95% CI, 0.11–0.45];
P
=0.001) in the hypertension group.

Conclusions:

Neither hypertension nor high-normal labels motivated participants to change their diet or exercise more than control, but both labels had adverse psychosocial outcomes. Labeling people with systolic BP of 130 to 140 mm Hg, who are otherwise at low risk of cardiovascular disease, may cause harms that outweigh benefit.

Registration:

URL:
http://www.anzctr.org.au/
; Unique identifier: ACTRN12618001700224.
Bariatric Surgery and Cardiovascular Outcomes in Patients With Obesity and Cardiovascular Disease:
Authors: Doumouras Aristithes G. , Wong Jorge A. , Paterson J. Michael , Lee Yung , Sivapathasundaram Branavan , Tarride Jean-Eric , Thabane Lehana , Hong Dennis , Yusuf Salim , Anvari Mehran
Published: April 2021

Background:

Bariatric surgery has been shown to significantly reduce cardiovascular risk factors. However, whether surgery can reduce major adverse cardiovascular events (MACE), especially in patients with established cardiovascular disease, remains poorly understood. The present study aims to determine the association between bariatric surgery and MACE among patients with cardiovascular disease and severe obesity.

Methods:

This was a propensity score–matched cohort study using province-wide multiple-linked administrative databases in Ontario, Canada. Patients with previous ischemic heart disease or heart failure who received bariatric surgery were matched on age, sex, heart failure history, and a propensity score to similar controls from a primary care medical record database in a 1:1 ratio. The primary outcome was the incidence of extended MACE (first occurrence of all-cause mortality, myocardial infarction, coronary revascularization, cerebrovascular events, and heart failure hospitalization). Secondary outcome included 3-component MACE (myocardial infarction, ischemic stroke, and all-cause mortality). Outcomes were evaluated through a combination of matching via propensity score and subsequent multivariable adjustment.

Results:

A total of 2638 patients (n=1319 in each group) were included, with a median follow-up time of 4.6 years. The primary outcome occurred in 11.5% (151/1319) of the surgery group and 19.6% (259/1319) of the controls (adjusted hazard ratio [HR], 0.58 [95% CI, 0.48–0.71];
P
<0.001). The association was notable for those with heart failure (HR, 0.44 [95% CI, 0.31–0.62];
P
<0.001; absolute risk difference, 19.3% [95% CI, 12.0%–26.7%]) and in those with ischemic heart disease (HR, 0.60 [95% CI, 0.48–0.74];
P
<0.001; absolute risk difference, 7.5% [95% CI, 4.7%–10.5%]). Surgery was also associated with a lower incidence of the secondary outcome (HR, 0.66 [95% CI, 0.52–0.84];
P
=0.001) and cardiovascular mortality (HR, 0.35 [95% CI, 0.15–0.80];
P
=0.001).

Conclusions:

Bariatric surgery was associated with a lower incidence of MACE in patients with cardiovascular disease and obesity. These findings require confirmation by a large-scale randomized trial.
Neutrophil Extracellular Traps Promote the Development of Intracranial Aneurysm Rupture
Authors: Korai Masaaki , Purcell James , Kamio Yoshinobu , Mitsui Kazuha , Furukawa Hajime , Yokosuka Kimihiko , Miyamoto Takeshi , Sato Hitomi , Sato Hiroki , Eguchi Satoru , Ai Jinglu , Lawton Michael T. , Hashimoto Tomoki
Published: April 2021

Potential roles for neutrophils in the pathophysiology of intracranial aneurysm have long been suggested by clinical observations. The presence of neutrophil enzymes in the aneurysm wall has been associated with significant increases in rupture risk. However, the mechanisms by which neutrophils may promote aneurysm rupture are not well understood. Neutrophil extracellular traps (NETs) were implicated in many diseases that involve inflammation and tissue remodeling, including atherosclerosis, vasculitis, and abdominal aortic aneurysm. Therefore, we hypothesized that NETs may promote the rupture of intracranial aneurysm, and that removal of NETs can reduce the rate of rupture. We employed both pharmacological and genetic approaches for the disruption of NETs and used a mouse model of intracranial aneurysm to investigate the roles of NETs in the development of intracranial aneurysm rupture. Here, we showed that NETs are detected in human intracranial aneurysms. Both global and granulocyte-specific knockout of peptidyl arginine deiminase 4 (an enzyme essential for NET formation) reduced the rate of aneurysm rupture. Pharmacological blockade of the NET formation by Cl-amidine also reduced the rate of aneurysm rupture. In addition, the resolution of already formed NETs by deoxyribonuclease was effective against aneurysm rupture. Inhibition of NETs formation with Cl-amidine decreased mRNA expression of proinflammatory cytokines (intercellular adhesion molecule 1 [ICAM-1], interleukin 1 beta [IL-1β], monocyte chemoattractant protein-1 [MCP-1], and tumor necrosis factor alpha [TNF-α]) in cerebral arteries. These data suggest that NETs promote the rupture of intracranial aneurysm. Pharmacological removal of NETs, by inhibition of peptidyl arginine deiminase 4 or resolution of already-formed NETs, may represent a potential therapeutic strategy for preventing aneurysmal rupture.
Decreased 11β-Hydroxysteroid Dehydrogenase Type 2 Expression in the Kidney May Contribute to Nicotine/Smoking-Induced Blood Pressure Elevation in Mice
Authors: Wang Ying , Wang Jian , Yang Rong , Wang Piwen , Porche Rene , Kim Samuel , Lutfy Kabirullah , Liu Limei , Friedman Theodore C. , Jiang Meisheng , Liu Yanjun
Published: April 2021

Chronic nicotine exposure significantly increases hypertensive risk in smokers, but the underlying mechanisms are poorly understood. In the kidneys, 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) catalyzes the conversion from active into inactive glucocorticoids and plays a pivotal role in the regulation of blood pressure. We hypothesized that nicotine-induced blood pressure elevation is in part mediated by change in renal 11β-HSD2 leading to higher MR (mineralocorticoid receptor) occupancy. Here, we show that nicotine exposure markedly decreased the expression and activity of renal 11β-HSD2 and increased the mean systolic arterial pressure in C57BL/6J mice. Reduction of renal 11β-HSD2 expression by nicotine was correlated with the suppression of C/EBPβ (CCAAT/enhancer-binding protein-β) and activation of Akt protein kinase phosphorylation (pThr
308
Akt/PKB) within the kidney. Conversely, nicotine-treated mice had elevated renal MR and epithelial sodium channel-α abundance. Treatment with the MR antagonist spironolactone significantly decreased the elevated mean systolic blood pressure and corrected ENaC along with inhibition of pThr
308
Akt/PKB within the kidney in nicotine-treated mice. Suppression of Akt/PKB activation by spironolactone was accompanied by upregulation of renal C/EBPβ and amelioration of nicotine-mediated reduction of 11β-HSD2. Addition of nicotine to mouse renal cortical collecting duct M1 cells downregulated 11β-HSD2 and stimulated MR expression, and these effects are likely mediated by activation of Akt coupled inhibition of C/EBPβ. These findings suggest that nicotine-mediated suppression of 11β-HSD2 in the kidney may contribute to the development of nicotine/smoking-induced hypertension through decreasing the intrarenal deactivation of glucocorticoids. Spironolactone may prove useful in protecting against the hypertensive risks of nicotine/smoking.
Preventing Recurrent Preeclampsia by Tailored Treatment of Nonphysiologic Hemodynamic Adjustments to Pregnancy
Authors: Mulder Eva G. , Ghossein-Doha Chahinda , Cauffman Ella , Lopes van Balen Veronica A. , Schiffer Veronique M.M.M. , Alers Robert-Jan , Oben Jolien , Smits Luc , van Kuijk Sander M.J. , Spaanderman Marc E.A.
Published: April 2021

Preeclampsia is often preceded by abnormal hemodynamic changes with heterogeneous patterns in the first half of pregnancy. We assessed the effect of timely tailored correction of nonphysiological hemodynamic changes on preventing preeclampsia in a high-risk population. Primiparous women with a history of preeclampsia were invited to participate in a longitudinal program in their next pregnancy, including repeated hemodynamic assessments at 12-, 16-, 20- and 30-week gestation additional to regular pregnancy checkups. When at least 2 of the hemodynamic variables were not within physiological reference values, the hemodynamic imbalance between cardiac output and peripheral vascular resistance was counteracted with either labetalol, methyldopa, or nifedipine using a simple treatment algorithm. Normogram-guided women (n=157) were matched to 157 women receiving care as usual (power, 80%; α=0.05). Risk of recurrent preeclampsia was analyzed with logistic regression adjusted for daily low-dose aspirin or calcium supplementation. Hemodynamic changes were considered nonphysiological in 90% of women in the normogram-guided group. Twelve percent of these women developed recurrent preeclampsia compared with 22% in the care-as-usual group (adjusted odds ratio, 0.47 [95% CI, 0.25–0.88]). There were no differences between groups in gestational age at delivery (38
1
and 38
2
weeks in the normogram-guided and care-as-usual groups, respectively) and neonatal birth weight (3148 and 3180 g in the normogram-guided and care-as-usual groups, respectively). Tailored circulatory normalization of nonphysiological hemodynamic changes during pregnancy halves the risk of recurrent preeclampsia, without disadvantageous effects on offspring outcome. This simple and innovative treatment strategy may also be beneficial to other women at increased risk for preeclampsia in pregnancy.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04216706.
Relationship Between Blood Pressure and Incident Cardiovascular Disease: Linear and Nonlinear Mendelian Randomization Analyses
Authors: Malik Rainer , Georgakis Marios K. , Vujkovic Marijana , Damrauer Scott M. , Elliott Paul , Karhunen Ville , Giontella Alice , Fava Cristiano , Hellwege Jacklyn N. , Shuey Megan M. , Edwards Todd L. , Rogne Tormod , Åsvold Bjørn O. , Brumpton Ben M. , Burgess Stephen , Dichgans Martin , Gill Dipender
Published: April 2021

Observational studies exploring whether there is a nonlinear effect of blood pressure on cardiovascular disease (CVD) risk are hindered by confounding. This limitation can be overcome by leveraging randomly allocated genetic variants in nonlinear Mendelian randomization analyses. Based on their association with blood pressure traits in a genome-wide association study of 299 024 European ancestry individuals, we selected 253 genetic variants to proxy the effect of modifying systolic and diastolic blood pressure. Considering the outcomes of incident coronary artery disease, stroke and the combined outcome of CVD, linear and nonlinear Mendelian randomization analyses were performed on 255 714 European ancestry participants without a history of CVD or antihypertensive medication use. There was no evidence favoring nonlinear relationships of genetically proxied systolic and diastolic blood pressure with the cardiovascular outcomes over linear relationships. For every 10-mm Hg increase in genetically proxied systolic blood pressure, risk of incident CVD increased by 49% (hazard ratio, 1.49 [95% CI, 1.38–1.61]), with similar estimates obtained for coronary artery disease (hazard ratio, 1.50 [95% CI, 1.38–1.63]) and stroke (hazard ratio, 1.44 [95% CI, 1.22–1.70]). Genetically proxied blood pressure had a similar relationship with CVD in men and women. These findings provide evidence to support that even for individuals who do not have elevated blood pressure, public health interventions achieving persistent blood pressure reduction will be of considerable benefit in the primary prevention of CVD.
Spot Urine Formulas to Estimate 24-Hour Urinary Sodium Excretion Alter the Dietary Sodium and Blood Pressure Relationship
Authors: Naser Abu Mohd , He Feng J. , Rahman Mahbubur , Campbell Norm R.C.
Published: April 2021

We evaluated the relationship between estimated 24-hour urinary sodium excretion from the Kawasaki, Tanaka, and INTERSALT (International Study of Sodium, Potassium, and Blood Pressure) formulas and blood pressure (BP). We pooled 10 034 person-visit data from 3 cohort studies in Bangladesh that had measured 24-hour urine sodium (m-24hUNa), potassium, creatinine excretion, and BP. We used m-24hUNa, potassium, and creatinine where necessary, rather than spot urine values in the formulas. Bland-Altman plots were used to determine the bias associated with formula-estimated sodium relative to m-24hUNa. We compared the sodium excretion and BP relationships from m-24hUNa versus formula-estimated sodium excretions, using restricted cubic spline plots for adjusted multilevel linear models. All formulas overestimated 24-hour sodium at lower levels but underestimated 24-hour sodium at higher levels. There was a linear relationship between m-24hUNa excretion and systolic BP, while estimated sodium excretion from all 3 formulas had a J-shaped relationship with systolic BP. The relationships between urine sodium excretion and diastolic BP were more complex but were also altered by using formulas. All formulas had associations with BP when a sex-specific constant sodium concentration was inserted in place of measured sodium. Since we used the m-24hUNa, potassium, and creatinine concentrations in formulas, the J-shaped relationships are due to intrinsic problems in the formulas, not due to spot urine sampling. Formula-estimated 24-hour urine sodium excretion should not be used to examine the relationship between sodium excretion and BP since they alter the real associations.
Impact of the 2017 American Academy of Pediatrics’ Clinical Practice Guideline on the Identification and Risk Stratification of Youth at Increased Cardiovascular Disease Risk
Authors: Brady Tammy M. , Altemose Kathleen , Urbina Elaine M.
Published: April 2021

The updated clinical practice guideline (CPG) published by the American Academy of Pediatrics in 2017 introduced significant changes to the diagnostic and evaluative approach towards children with elevated blood pressure. The goals of this review were to summarize the current evidence regarding the impact of the new CPG on the identification and risk stratification of children at increased cardiovascular disease risk. Universally, the new CPG definitions of abnormal blood pressure led to more children classified as having a hypertensive blood pressure when compared with alternative definitions. Youth who moved to a higher blood pressure stage with the CPG typically had worse cardiometabolic profiles and more comorbidites. The association of CPG-defined hypertension and concurrent intermediate cardiovascular disease outcomes such as left ventricular hypertrophy and increased pulse wave velocity remains unclear; however, longitudinal data suggests an improved identification of those at greatest risk for adult cardiovascular disease with the CPG definitions. The majority of studies reviewed used blood pressure from one encounter, not replicate blood pressures from multiple visits, to define an abnormal or hypertensive blood pressure. Therefore, future studies investigating the prevalence of confirmed hypertension and the association between confirmed hypertension and outcomes are needed to optimally characterize the performance of the new CPG on identifying children at cardiovascular disease risk.
Which Acute Ischemic Stroke Patients Are Fast Progressors?
Authors: Ospel Johanna M. , Hill Michael D. , Kappelhof Manon , Demchuk Andrew M. , Menon Bijoy K. , Mayank Arnuv , Dowlatshahi Dar , Frei Don , Rempel Jeremy L. , Baxter Blaise , Goyal Mayank
Published: April 2021

Background and Purpose:

Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics.

Methods:

Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail.

Results:

Fast infarct progression occurred in 15 of 43 included patients (34.9%). Fast progressors had worse collaterals (poor in 3/15 [20%] versus 0/28 patients,
P
=0.021) and more carotid-T or -L occlusions (8/15 [53.4%] versus 3/28[10.7%],
P
=0.021). In 8 out of 15 (53.3%), occlusion site and circle of Willis configuration prevented collateral flow via the anterior or posterior cerebral artery.

Conclusions:

Most patients with fast infarct progression had terminal carotid occlusions and impaired collateral flow via the anterior or posterior cerebral artery, indicating that occlusion location and intracranial vascular anatomy are relevant for infarct progression.
TÜKETİCİLERİN MARKAYI TEKRAR TERCİH ETME EĞİLİMİNİN HİZMET KALİTE ALGISI PERSPEKTİFİNDEN DEĞERLENDİRİLMESİ
Authors: ÇINAR Dilaysu , ORTANCA Buket Deniz
Published: April 2021

Bu çalışmanın temel amacı, firma
tarafından sunulan hizmetin kalitesine yönelik oluşan algılamaların
tüketicilerin markayı tekrar tercih etme eğilimi üzerinde nasıl bir etkiye
sahip olduğunu irdelemektir. Bu amaç doğrultusunda yapılan çalışma sonucunda,
markayı tekrar tercih etme eğilimi düzeyi ile güven ve heveslilik boyutu
arasında yüksek düzeyde, empati ve güvenilirlik boyutu arasında orta düzeyde ve
fiziksel özellikler boyutu arasında düşük düzeyde anlamlı bir ilişki olduğu
bulunulmuştur. Sonuç olarak, çalışmada, hizmet kalite algısını oluşturan her
bir faktörün düzeyi arttıkça tüketicilerin de markayı tekrar tercih etme
eğiliminin arttığı gözlemlenmiştir.
HANEHALKI SORUMLUSU VE YOKSULLUK: PROBİT MODEL
Authors: YAKICI AYAN Tuba , DEĞİRMENCİ Nurdan
Published: April 2021

Bu çalışmada Türkiye’de yoksulluğu etkileyen hanehalkı sorumlusunun demografik özellikleri probit model yöntemi ile belirlenmiştir. Analiz verileri Türkiye İstatistik Kurumuna ait 2017 yılı hane halkı gelir ve yaşam koşulları araştırması fert ve hane anketlerinden sondaj ve birleştirme yoluyla elde edilmiştir. Ardından 22869 kayıt arasından bölgelere göre tabakalı örnekleme yöntemi ile 761 kayıt seçilmiştir. Ele alınan değişkenler arasından hanehalkı sorumlusunun faaliyet durumu, genel sağlık durumu ve hane nüfusu hanenin yoksulluk olasılığını pozitif etkilerken, buna karşın hanehalkı sorumlusunun eğitim düzeyi, yaşı ve hanehalkı sorumlusunun kadın olması ise negatif etki yapmaktadır.
Anahtar Kelimler: Yoksulluk, Demografik faktörler, Probit model
Jel Kodları: C35, I32,J12
Possibilities for Justice and Equity in Human Rights and Climate Law: Benefit-Sharing in Climate Finance
Authors: Bouwer Kim
Published: April 2021

This article examines benefit-sharing in the context of climate finance. Both benefit-sharing and climate finance are complex, heterogeneous, and fast-developing fields, where the interaction of international human rights law and climate law can create both clarity and confusion. Benefit-sharing as a means for greater equity and fairness is increasingly used or included in materials on climate finance, despite lacking clear conceptualization in this context. The article does three things. First, it establishes benefit-sharing as an emerging obligation in human rights law and environmental law. Second, it explores how benefit-sharing appears in the climate regime, with a view to determining whether benefit-sharing has a distinct meaning in this context – and, if so, what it is. The article argues that both the meaning and the practice of benefit-sharing in climate finance are incoherent. Third, the article interrogates the possibilities and problems of adopting universalized norms of benefit-sharing in this context, and suggests some places where norms might be beneficial.
Impacts of Detoured Madden-Julian Oscillations on the South Pacific Convergence Zone
Authors: Zhou Lei , Ruan Ruomei , Murtugudde Raghu
Published: April 2021

Madden-Julian Oscillations (MJOs) are a major component of tropical intraseasonal variabilities. There are two paths for MJOs across the Maritime Continent; one is a detoured route into the Southern Hemisphere and the other one is around the equator across the Maritime Continent. Here, it is shown that the detoured and non-detoured MJOs have significantly different impacts on the South Pacific convergence zone (SPCZ). The detoured MJOs trigger strong cross-equatorial meridional winds from the Northern Hemisphere into the Southern Hemisphere. The associated meridional moisture and energy transports due to the background states carried by the intraseasonal meridional winds are favorable for reinforcing the SPCZ. In contrast, the influences of non-detoured MJOs on either hemisphere or the meridional transports across the equator are much weaker. The detoured MJOs can extend their impacts to the surrounding regions by shedding Rossby waves. Due to different background vorticity during detoured MJOs in boreal winter, more ray paths of Rossby waves traverse the Maritime Continent connecting the southern Pacific Ocean and the eastern Indian Ocean, but far fewer Rossby wave paths traverse Australia. Further studies on such processes are expected to contribute to a better understanding of extreme climate and natural disasters on the rim of the southern Pacific and Indian Oceans.
Interaction of near-inertial waves with an anticyclonic vortex
Authors: Kafiabad Hossein A. , Vanneste Jacques , Young William R.
Published: April 2021

Anticyclonic vortices focus and trap near-inertial waves so that near-inertial energy levels are elevated within the vortex core. Some aspects of this process, including the nonlinear modification of the vortex by the wave, are explained by the existence of trapped near-inertial eigenmodes. These vortex eigenmodes are easily excited by an initialwave with horizontal scale much larger than that of the vortex radius. We study this process using a wave-averaged model of near-inertial dynamics and compare its theoretical predictions with numerical solutions of the three-dimensional Boussinesq equations. In the linear approximation, the model predicts the eigenmode frequencies and spatial structures, and a near-inertial wave energy signature that is characterized by an approximately time-periodic, azimuthally invariant pattern. The wave-averaged model represents the nonlinear feedback of the waves on the vortex via a wave-induced contribution to the potential vorticity that is proportional to the Laplacian of the kinetic energy density of the waves. When this is taken into account, the modal frequency is predicted to increase linearly with the energy of the initial excitation. Both linear and nonlinear predictions agree convincingly with the Boussinesq results.
Best Practices for Comparing Ocean Turbulence Measurements across Spatiotemporal Scales
Authors: Whalen Caitlin B.
Published: April 2021

The turbulent energy dissipation rate in the ocean can be measured by using rapidly sampling microstructure shear probes, or by applying a finescale parameterization to coarser-resolution density and/or shear profiles. The two techniques require measurements that are on different spatiotemporal scales and generate dissipation rate estimates that also differ in spatiotemporal scale. Since the distribution of the measured energy dissipation rate is closer to lognormal than normal and fluctuates with the strength of the turbulence, averaging the two approaches on equivalent spatiotemporal scales is critical for accurately comparing the two methods. Here, microstructure data from the 1997 Brazil Basin Tracer Release Experiment (BBTRE) is used to demonstrate that comparing averages of the dissipation rate on different spatiotemporal scales can generate spurious discrepancies of up to a factor of order 10 in regions of strong turbulence and smaller biases of up to a factor of 2 in the presence of weaker turbulence.
Divorce and female labour force participation: Do women who expect an upcoming divorce increase their employment? Evidence from Flanders
Authors: Thielemans Gert , Mortelmans Dimitri
Published: April 2021

Women who expect an upcoming divorce have the possibility of taking action in order to protect themselves against the projected negative financial consequences. In this paper we investigate whether they do. Using retrospective data for a sample of 884 divorced women from the Divorce in Flanders (DiF)-survey, we estimate the difference in the probability that women increase their employment intensity surrounding the time a couple stops living together between women who expected the divorce and those who did not. We find that in the year leading up to the factual separation, women who expect the divorce are three to five times more likely to increase their employment. Our results suggest that when anticipatory employment behaviour is not considered when researching the negative consequences of relationship dissolution, both the magnitude of the downturn as well as the time to recovery is likely underestimated for a large group of women.
Love and basketball: Audience response to a professional athlete’s mental health proclamation
Authors: Pavelko Rachelle L , Wang Tianjiao (Grace)
Published: April 2021

Objective:

On 6 March 2018, the Cleveland Cavaliers power forward Kevin Love penned an op-ed for The Players’ Tribune. In big, bold letters, the title, ‘Everyone Is Going Through Something’ gave way to his proclamation of personal mental health struggles. This study assessed the impact of Love’s personal mental health testimony on the audience.

Design:

Content analysis of Instagram user’s responses to Love’s 2018 announcement of panic disorder.

Setting:

Data were collected on 19 June 2018. Comments on Love’s post were manually copied into an Excel spreadsheet. Due to Instagram’s ‘top comments’ and ‘newest first’ algorithms that determine both the visibility and order of user responses, not all comments were accessible for analysis. A total of 1,234 comments served as the sample.

Method:

Two trained coders analysed the comments for exhibitions of audience involvement with Love, emotional responses and perceptions of social biases surrounding mental illness.

Results:

Social media users who expressed hope were more likely to share their own mental health experiences. In addition, users who expressed hope were significantly more likely to mention wanting to reduce social bias surrounding discussion of mental health than posts without hope.

Conclusion:

Building on previous work that determined social media users can respond to a celebrity’s physical health testimonial with positive, future-oriented emotions, this study established that the same response can exist when analysing a celebrity’s mental health testimonial.
Delivering bad news fairly: The influence of core self-evaluations and anxiety for the enactment of interpersonal justice
Authors: Hillebrandt Annika , Saldanha Maria Francisca , Brady Daniel L , Barclay Laurie J
Published: April 2021

What motivates managers to deliver bad news in a just manner and why do some managers fail to treat recipients of bad news with dignity and respect? Given the importance of delivering bad news in a just manner, answering these questions is critical to promote justice in the workplace. Drawing on appraisal theories of emotions, we propose that people with higher core self-evaluations may be less likely to deliver bad news in an interpersonally just manner. This is because these actors are more likely to appraise the delivery of bad news as a situation in which they have high coping potential and are therefore less likely to experience anxiety. However, we propose that anxiety can be important for propelling the enactment of interpersonal justice. We test our predictions across three studies (with four samples of full-time managers and employees). Theoretical and practical contributions include enhancing our understanding of who is motivated to enact interpersonal justice, why they are motivated to do so, and how to enhance justice in the workplace. Our findings also challenge the assumption that negative emotions are necessarily dysfunctional for the enactment of interpersonal justice and instead highlight the facilitative role of anxiety in this context.
Mauriac syndrome: A failure of parent or physician
Authors: Yadav Jaivinder , Kumar Rakesh , Gupta Saniya , Gupta Atul , Yadav Arti , Dayal Devi
Published: April 2021

Mauriac syndrome is rare; we share our experience of nine patients who presented at a young age with malnutrition, short stature, abdominal distention and deranged liver function.
Hybrid-driven control of networked switched systems with random cyber attacks
Authors: Liu Yonghui , Jin Jiahui
Published: April 2021

This paper considers security control for a class of networked switched systems subject to random cyber attacks. To alleviate the burden of the networked transmission, a hybrid-driven communication strategy is employed. Moreover, based on the hybrid-triggered control scheme, a state-feedback controller and a switching signal depending on the average dwell time are designed simultaneously. It is shown that the switched systems are mean-square exponentially stable despite the presence of the random cyber attacks. Finally, a numerical example is exploited to demonstrate the effectiveness of the proposed method.
Postinflammatory Medial Meatal Fibrosis: Histopathologic Features and Outcomes of Surgical Management
Authors: Mantsopoulos Konstantinos , Thimsen Vivian , Müller Sarina Katrin , Sievert Matti , Goncalves Miguel , Iro Heinrich , Agaimy Abbas , Hornung Joachim
Published: April 2021

Objectives:

The aims of our study were to investigate the clinical and audiometric outcome of the surgical treatment of postinflammatory medial meatal fibrosis (PIMMF) and to review the histopathologic changes in the specimens of the fibrotic plug, in order to try to shed light on the pathogenesis of the disease.

Materials and Methods:

The clinical records and the histopathologic specimens of all patients who underwent tympanomeatoplasty for PIMMF at the ENT Clinic of the University of Erlangen between 2006 and 2020 were evaluated retrospectively.

Results:

Thirty-four patients (41 primary surgical procedures) made up our study cohort. Of this, 28 cases were managed by means of meatoplasty and 13 cases with tympanomeatoplasty. The mean preoperative air–bone gap (ABG) was 27.8 dB (10-44 dB). Postoperative ABG was significantly improved compared to preoperative values at both short- and long-term follow-ups ( P < .001 for both). No significant difference was noted between short-term and long-term ABG ( P = .240). An ABG ≤20 dB was achieved in 65.8% of patients (short term) and 50% (long term). The overall rate of revision surgery for restenosis was 29.3% (12/41). Histopathologic reevaluation of the fibrotic plugs revealed a mosaic of patterns with frequent occurrence of secondary cholesteatoma-like lesions and keloid-like tissue changes. Lichenoid submucosal inflammation and increased ectopic ceruminous gland lobules were seen less frequently.

Discussion:

The moderate long-term outcome of surgical management and the identification of histologic changes with therapeutic implications might pave the way for alternative nonsurgical treatment options.
Virtue Rhetoric in Investor Communications: Setting Up for a Letdown?
Authors: Zachary Miles A. , Connelly Brian L. , Payne G. Tyge , Tribble Lori L.
Published: April 2021

Many companies prominently espouse their virtuous character in communications with investors, with a view toward influencing investor perceptions about the firm’s standards of behavior. While there are benefits to investors perceiving an organization to be virtuous, what happens if the firm violates those standards by engaging in unethical behavior? In this study, we use expectancy violations theory to argue that virtue rhetoric sets investors up for disappointment. When an organization claims to be virtuous but then acts unethically, investors respond to the ethics violation more negatively than they would otherwise. We also theorize about scenarios where investors may overlook unethical behavior or intensify their disapproval of it. To test our ideas, we assemble a unique sample of unethical events committed by S&P 500 companies over a 12-year period, combined with analysis of the virtue rhetoric found in their annual letters to shareholders. Our main finding is that investor reaction to unethical behavior is more negative for companies that claimed to be virtuous prior to the violation than for those that did not make such claims. This relationship is less strong when the company has high expected future value.
Science Communication as a Boundary Space: An Interactive Installation about the Social Responsibility of Science
Authors: Horst Maja
Published: April 2021

Science communication has traditionally been seen as a means of crossing the boundary of science: moving scientific knowledge into the public. This paper presents an alternative understanding. Drawing upon a particular case of social science communication in the form of an interactive installation about the social responsibility of science, it develops the concept of boundary space where phenomena can simultaneously belong to science and nonscience. In addition, the paper describes how the installation functions as a space for interaction between knowledge communication and knowledge production. The paper argues that we should understand science communication as a social practice, which allows scientists and nonscientists to cooperate in performing science as an important part of society. The aim is to add a new kind of analysis to traditional criticisms of deficit-thinking and popularization by asking what can we say more about science communication if we understand it as part of (rather than separated in time and space from) science as a social activity.
Stigma in Bipolar Affective Disorder: A Systematic Quantitative Literature Review of Indian Studies
Authors: Pal Arghya , Saxena Vrinda , Avinash Priyaranjan
Published: April 2021

Background:

Bipolar affective disorder (BPAD) is one of the most common severe mental illnesses that cause morbidity. Stigma can negatively influence the disease experience in patients with BPAD. Significant differences are observed in the attributes of stigma across the various sociocultural milieus. The current review was thus conducted to compile the evidence regarding the burden and correlates of various forms of stigma in BPAD in India.

Methods:

An exhaustive literature review was conducted in PubMed, MedIND, and Google Scholar to identify Indian studies conducted on stigma in BPAD. The broad themes in various forms of stigma were identified (qualitative analysis). Quantitative analysis of measures of stigma was done, calculating the effect size in BPAD and comparator groups (schizophrenia and anxiety disorders) using standardized mean difference.

Results:

Overall, 12 studies could be identified for qualitative analysis, and 5 were used for quantitative analysis. Overall, the current evidence points out that the stigma in BPAD is less than that in schizophrenia but more than that in anxiety disorders. Internalized stigma in BPAD is correlated with poor self-esteem, reduced community participation, and low quality of life. Caregivers of patients with BPAD also experience significant stigma.

Conclusions:

The review shows that stigma in BPAD is substantial. It also draws attention to the fact that the research regarding stigma in BPAD is lagging behind. This review also provides a platform to develop an intervention in the Indian scenario, where further research should be carried out.
Multivariate Generalized Linear Mixed-Effects Models for the Analysis of Clinical Trial–Based Cost-Effectiveness Data
Authors: Achana Felix , Gallacher Daniel , Oppong Raymond , Kim Sungwook , Petrou Stavros , Mason James , Crowther Michael
Published: April 2021

Economic evaluations conducted alongside randomized controlled trials are a popular vehicle for generating high-quality evidence on the incremental cost-effectiveness of competing health care interventions. Typically, in these studies, resource use (and by extension, economic costs) and clinical (or preference-based health) outcomes data are collected prospectively for trial participants to estimate the joint distribution of incremental costs and incremental benefits associated with the intervention. In this article, we extend the generalized linear mixed-model framework to enable simultaneous modeling of multiple outcomes of mixed data types, such as those typically encountered in trial-based economic evaluations, taking into account correlation of outcomes due to repeated measurements on the same individual and other clustering effects. We provide new wrapper functions to estimate the models in Stata and R by maximum and restricted maximum quasi-likelihood and compare the performance of the new routines with alternative implementations across a range of statistical programming packages. Empirical applications using observed and simulated data from clinical trials suggest that the new methods produce broadly similar results as compared with Stata’s merlin and gsem commands and a Bayesian implementation in WinBUGS. We highlight that, although these empirical applications primarily focus on trial-based economic evaluations, the new methods presented can be generalized to other health economic investigations characterized by multivariate hierarchical data structures.
Hemodynamic impact of molecular adsorbent recirculating system in refractory vasoplegic shock due to calcium channel blocker poisoning
Authors: Beyls Christophe , Malaquin Stéphanie , Huette Pierre , Mary Aurélien , Besserve Patricia , Roger Pierre-Alexandre , Bernasinski Michaël , Guilbart Mathieu , Abou-Arab Osama , Dupont Hervé , Mahjoub Yazine
Published: April 2021

Objective:

To report the hemodynamic effect of to the molecular adsorbent recirculating system (MARS™) therapy for patients in refractory vasoplegic shock due to calcium channel blocker (CCB) poisoning

Methods:

We report a retrospective cohort of patients who were hospitalized for CCB poisoning with refractory vasoplegic shock and treated by MARS therapy, at Amiens Hospital University, from January 2010 to December 2019. Improvement in hemodynamic was assessed by dynamic changes in mean arterial pressure (MAP) and norepinephrine levels over a 24-h period after MARS therapy. Cardiac function was assessed by transthoracic echocardiography.

Results:

MARS therapy was performed on seven patients for CCB poisoning. CCB poisoning included nicardipine ( n = 3, 43%) amlodipine ( n = 3, 43%), and verapamil ( n = 1, 14%). The median time to start MARS therapy was 24 [14–27] h after drug ingestion and 6 [2–9] h after ICU admission. Cardiac output was preserved for all patients. MAP values improved from 56 [43–58] to 65 [61–78] 16 mmHg ( p = 0.005). Norepinephrine dose significantly decreased from 3.2 [0.8–10] µg/kg/min to 1.2 [0.1–1.9] µg/kg/min ( p = 0.008) and lactate level decreased from 3.2 [2.4–3.4] mmol/l−1 to 1.6 [0.9–2.2] mmol/l−1 ( p = 0.008). The median length of ICU stay was 4 (2–7) days and hospital stay was 4 (4–16) days. No complication related to the MARS therapy were reported. No patient died and all were discharged from the hospital.

Conclusion:

We reported the largest case-series of MARS therapy for refractory vasoplegic shock due to CCB poisoning. We observed that MARS therapy was associated with an improvement of hemodynamic parameters.
Comparative performance analysis of support vector regression and artificial neural network for prediction of municipal solid waste generation
Authors: Jassim Majeed S , Coskuner Gulnur , Zontul Metin
Published: April 2021

The evolution of machine learning (ML) algorithms provides researchers and engineers with state-of-the-art tools to dynamically model complex relationships. The design and operation of municipal solid waste (MSW) management systems require accurate estimation of generation rates. In this study, we applied rapid, non-linear and non-parametric data driven ML algorithms independently, multi-layer perceptron artificial neural network (MLP-ANN) and support vector regression (SVR) models to predict annual MSW generation rates in Bahrain. Models were trained and tested with MSW generation data for period of 1997–2019. The population, gross domestic product, annual tourist numbers, annual electricity consumption and total annual CO2 emissions were selected as explanatory variables and incorporated into developed models. The zero score normalization (ZSN) and minimum maximum normalization (MMN) methods were utilized to improve the quality of data and subsequently enhances the performance of ML algorithms. Statistical metrics were employed to discriminate performance of MLP-ANN and SVR models. The linear, polynomial, radial basis function (RBF) and sigmoid kernel functions were investigated to find the optimal SVR model. Results showed that RBF-SVR model with R2 value of 0.97% and 4.82% and absolute forecasting error (AFE) for the period of 2008 and 2019 exhibits superior prediction and robustness in comparison to MLP-ANN. The efficacy of MLP-ANN model was also reasonably successful with R2 value of 0.94. It was shown that MMN pre-processing generated optimal MLP-ANN model while ZSN pre-processing produced optimal RBF-SVR model. This work also highlights the importance of application of ML modelling approaches to plan and implement their roadmap for waste management systems by policymakers.
Annotated Bibliography: Sexual Orientation and Gender Identity Issues in Educational Ministry
Authors: Severe Michael K.
Published: April 2021

The following short annotated bibliography is a starting place for locating resources regarding sexual orientation and gender identity issues in educational ministry.