bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary microvascular dysfunction results in impaired coronary flow reserve and altered oxygen balance in a swine model of INOCA with multiple risk factors
Authors: Sorop O , Van De Wouw J , Van Drie R.W.A , Joles J.A , Verhaar M.C , Merkus D , Duncker D.J
Published: November 2020

Introduction

Comorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD) and may contribute to myocardial “Ischemia and No Obstructive Coronary Artery disease” (INOCA).

Purpose

We studied myocardial perfusion and oxygen delivery using a novel swine model with multiple comorbidities.

Methods

DM (streptozotocin), HFD (high fat diet) and CKD (renal embolization), were induced in 12 female swine (DM+HFD+CKD), while 12 healthy female swine on a normal diet served as controls (CON). After 6 months, in the absence of coronary atherosclerosis, myocardial perfusion and function were studied at rest and during treadmill exercise. Results DM+HFD+CKD animals showed hyperglycemia, hypercholesterolemia and impaired kidney function. During exercise, DM+HFD+CKD demonstrated impaired myocardial blood flow and oxygen delivery, necessitating higher myocardial oxygen extraction (despite reduced capillary density), resulting in lower coronary venous oxygen levels, (Fig. 1). These perturbations were associated with lower myocardial efficiency, requiring higher oxygen consumption for a given level of myocardial work (Fig. 1), lower myocardial lactate consumption, stroke volume and LVdP/dtmax, suggestive of myocardial ischemia and dysfunction. Furthermore DM+HFD+CKD showed a reduction in adenosine-recruitable coronary flow reserve (2.69±0.26 vs 3.64±0.2 in CON, p<0.05), which was exclusively the result of an increase in basal coronary blood flow, while maximal coronary flow per gram of myocardium was maintained. The latter was consistent with the unchanged arteriolar wall/lumen ratio, arteriolar density and peri-arteriolar collagen content. eNOS blockade indicated loss of NO bioavailability in DM+HFD+CKD swine in vivo (Fig. 1), which was supported by blunted endothelium-dependent vasodilation to bradykinin in isolated small arteries. These findings suggest that changes in coronary microvascular function rather than structure contributed to the perturbations in myocardial oxygen delivery.

Conclusion

Common comorbidities result in CMD and impaired NO bioavailability rather than structural alterations in the microvasculature in swine, in the absence of appreciable atherosclerosis. These alterations are severe enough to produce perturbations in myocardial oxygen balance and coronary metabolism and function, particularly during exercise, resembling key features of INOCA.

Figure 1

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): This study was supported by grants from the European Commission FP7-Health-2010 grant MEDIA-261409, the Netherlands CardioVascular Research Initiative: an initiative with support of the Dutch Heart Foundation [CVON2014-11 (RECONNECT)].
Adipokine omentin-1 enhances atherosclerotic plaque stability by binding to macrophage integrin receptor
Authors: Wang Z.J , Lin X.Z , Zhou Y.J
Published: November 2020

Background

Omentin-1 is a novel cytokine which is primarily released by epicardial adipose tissues, and the molecule structure analysis revealed that it contained a fibrinogen-like domain. Clinical studies considered that the expression of omentin-1 is tightly associated with the development of cardiovascular diseases. In this research, we sought to investigate the effect of omentin-1 on already-established atherosclerotic lesion in ApoE−/− mouse and find out the cellular receptor of omentin-1 in macrophages.

Methods

We investigated the effect of omentin-1 on the plaque phenotype by implanting the ALZET minipump (which can continuously inject omentin-1 solution into mice's jugular vein) in western diet-treated ApoE−/− mice. To validate the conjugation of omentin-1 to integrin receptor αvβ3 and αvβ5, we performed immunoprecipitation experiment. Confocal microscopy was used to verify the spatial co-localization of omentin-1 and integrin receptors.

Results

In vivo studies showed that the administration of omentin-1 increased the collagen content and the average fibrous cap thickness of atherosclerotic plaque in ApoE−/− mice. Omentin-1 mitigated the formation of necrotic cores within the plaque, and reduced the foam cell infiltration concomitantly. Immunohistochemistry analysis of the atherosclerotic lesion from the aorta of mice revealed that the intravenous infusion of omentin-1 can suppress expression of inflammatory cytokines in vivo. Immunoprecipitation experiment and confocal microscopy analysis confirmed the binding of omentin-1 to integrin receptor αvβ3 and αvβ5. To further study the mechanism by which omentin-1 had exerted its protective function, we used human myeloid leukemia mononuclear cell line (THP1) and oxidized low density lipoprotein (ox-LDL) to establish macrophage-derived foam cell model in vitro. Cell studies demonstrated that omentin-1 can attenuated the apoptosis and inflammatory cytokines secretion in ox-LDL-induced macrophages. Besides, omentin-1 can promote the phosphorylation of integrin-relevant signaling pathway in macrophage. After adding the cilengitide (inhibitor of integrin receptor αvβ3 and αvβ5) or intervening the expression of integrin subunit αv, the phenomenon induced by omentin-1 were potently suppressed. Moreover, flowcytometry analysis provided the evidence that omentin-1 had a negative effect on macrophage efferocytosis ability.

Conclusions

The administration of adipokine omentin-1 can inhibit the necrotic cores formation and pro-inflammatory cytokines expression within the atherosclerotic lesion. The mechanism might be the inhibition of apoptosis and the secretion of pro-inflammatory cytokines in macrophage by binding to integrin receptor αvβ3 and αvβ5.

Effect of omentin-1 on AS plaques.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): National natural science foundation of China
Alarmin-activated B cells accelerate atherosclerosis after myocardial infarction via plasma cell-immunoglobulin dependent mechanisms
Authors: Kyaw T , Loveland P , Kanellakis P , Cao A , Huang A , Peter K , Toh B.H , Bobik A
Published: November 2020

Introduction

Myocardial infarction (MI) accelerates atherosclerosis and for years greatly increases the risk of recurrent cardiovascular events, such as stroke and MI. B cell-derived autoantibodies produced in response to MI also persist for years.

Purpose

We investigated the role of B cells in adaptive immune responses to MI.

Methods

We used an apolipoprotein-E-deficient (ApoE−/−) mouse model of MI-accelerated atherosclerosis to assess the importance of B cells using loss and gain of function approaches. In loss of function experiment, after inducing an MI we depleted B cells using an anti-CD20 antibody. Gain of function experiments involve transfers of purified MI-B cells from different donor mice, isolated one week after MI, into atherosclerotic ApoE−/− mice.

Results

Depletion of B cells in MI mice prevented immunoglobulin G accumulation in plaques and MI-induced acceleration of atherosclerosis. Adoptive transfer of wildtype MI-B cells into atherosclerotic ApoE−/− mice greatly increased IgG accumulation in plaque and accelerated atherosclerosis in recipient mice. Cytokines that promote humoral immunity were also greatly increased in B cells activated by MI. These cells formed germinal centres within the spleen where they differentiated into antibody-producing plasma cells. Transfer of MI-B cells deficient in Blimp-1, the transcriptional repressor that drives their terminal differentiation to antibody-producing plasma cells failed to accelerate atherosclerosis in recipient mice. Alarmins released from infarcted heart were responsible for activation of B cells via toll-like receptors; transfer of MI-B cells deficient in MyD88, the canonical adaptor protein for inflammatory signaling downstream of toll-like receptors, prevented acceleration of atherosclerosis in recipient mice.

Conclusion

Our data implicate early B cell activation and autoantibodies as a central cause for accelerated atherosclerosis post MI and identifies novel therapeutic strategies towards preventing recurrent cardiovascular events such as MI and stroke.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Health and Medical Research Council of Australia
Selective inhibition of Histone deacetylases reverses vascular remodelling and improves right ventricle function in pulmonary hypertension
Authors: Kurakula K.B , Sun X.Q , Van Der Feen D.E , Hagdorn Q.A.J , Bogaard H.J , Berger R.M , Goumans M.J
Published: November 2020

Introduction

Pulmonary arterial hypertension (PAH) is a progressive fatal disease characterized by abnormal remodelling of pulmonary vessels, leading to increased vascular resistance and right ventricle (RV) failure. This abnormal vascular remodelling is associated with endothelial cell dysfunction, increased proliferation of smooth muscle cells, inflammation, and disturbed transforming growth factor beta (TGF-β) signalling. Histone deacetylases (HDACs) have been shown to promote proliferation and inflammation in vascular cells. Although inhibition of HDACs using small molecule inhibitors attenuated vascular remodeling, these inhibitors worsened RV function in animal models of PAH. Therefore, we aim to validate Quisinostat, a selective inhibitor of HDACs whether it could reverse vascular remodeling in the lungs and improves RV function.

Objective

To determine the effect of Quisinostat on vascular remodelling and RV function in PAH.

Methods and results

We found that HDAC1 expression is increased in lungs of PAH patients. Inhibition of HDACs activity by Quisinostat significantly decreased TGF-β signaling and strongly decreased proliferation and inflammation in microvascular endothelial cells (MVECs). In addition, conditioned medium from Quisinostat treated PAH MVECs inhibited the growth of healthy smooth muscle cells. Quisinostat reversed abnormal vascular remodelling in the MCT-shunt and Sugen Hypoxia rat models of severe angioproliferative PAH, and improved RV function. Finally, Quisinostat improved the RV function in rats with RV pressure load induced by pulmonary artery banding. Importantly, Quisinostat exhibited no systemic and cardio toxic effects in vivo.

Conclusions

Our data demonstrate that selective inhibition of HDACs reverses vascular remodeling in the lungs and improves RV function. These data support the establishment of a clinical trial with Quisinostat in patients with PAH.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Dutch Lung Foundation
Lower plasma melatonin levels predict worse long-term survival in pulmonary arterial hypertension
Authors: Cai Z , Klein T , Geenen L.W , Tu L , Tian S , Van Den Bosch A.E , De Rijke Y.B , Reiss I.K.M , Boersma E , Duncker D.J , Boomars K.A , Guignabert C , Merkus D
Published: November 2020

Background

Exogenous melatonin has been reported to be beneficial in the treatment of pulmonary hypertension (PH) in animal models. Multiple mechanisms may be involved, with melatonin exerting anti-oxidant and anti-inflammatory effects, as well as inducing vasodilation and cardio-protection. However, endogenous levels of melatonin in treatment-naïve pulmonary arterial hypertension (PAH) patients and their clinical significance are still unknown.

Methods and results

Plasma levels of endogenous melatonin were measured by liquid chromatography-tandem mass spectrometry in treatment-naïve PAH patients (n=43) and healthy controls (n=111). Melatonin levels were higher in PAH patients when compared with controls (Median 118.9 [IQR 109.3–147.7] versus 108.0 [102.3–115.2] pM, P<0.001) (Figure 1A). The overall mortality was 26% (11/43) during a median long-term follow-up of 42 [IQR: 32–58] months. When PAH patients were stratified into 4 groups according to the quartiles of melatonin levels, the mortality from below 1st quartile to above 4th quartile was 55% (6/11), 10% (1/10), 0% (0/12), and 40% (4/10), respectively (Figure 1B). Kaplan-Meier analysis further showed that patients with melatonin levels below the 1st quartile (<109.3 pM) had a worse long-term survival than patients with melatonin levels above the 1st quartile (Mean survival times were 46 [95% CI: 30–65] versus 68 [58–77] months, Log-rank, p=0.026) (Figure 1C).

Conclusion

Endogenous melatonin levels were increased in treatment-naïve PAH patients, and lower levels of melatonin were associated with worse long-term survival in patient with PAH, however, whether exogenous melatonin supplements may be effective as a therapeutic strategy in human PAH remains to be established.

Figure 1

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): This work was supported by the China Scholarship Council (201606230252) as well as the Netherlands CardioVascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2014-11, RECONNECT), and German Center for Cardiovascular Research (DZHK81Z0600207). Instrumentation support was received from AB Sciex, ltd. for LC-MS/MS analyses performed in this study.
Impact of the gut microbiome on the atorvastatin-dependent modulation of the serum lipidome
Authors: Roessler J , Zimmermann F , Schmidt D , Escher U , Jasina A , Heimesaat M.M , Gast M , Poller W , Giral-Arnal H , Schumann P , Leistner D.M , Landmesser U , Haghikia A
Published: November 2020

Background and aims

The modulation of serum lipids, in particular of the low-density lipoprotein cholesterol (LDL-C), by statins varies between individuals. The mechanisms regulating this interindividual variation are only poorly understood. Here, we investigated the relation between the gut microbiome and the regulatory properties of atorvastatin on the serum lipidome using mice with depleted gut microbiome.

Methods

Over a period of 6 weeks, mice (C57BL/6) with either an intact (conventional mice, CONV, n=24) or antibiotic-based depleted gut microbiome (antibiotic treated mice, ABS, n=16) were put on standard chow diet (SCD) or high fat diet (HFD), respectively. During the last 4 weeks of treatment atorvastatin (Ator, 10mg/kg body weight/day) or control vehicle was administered via daily oral gavage. Blood lipids (total cholesterol, VLDL, LDL-C, HDL-C) and serum sphingolipids were compared among the groups. The expressions of hepatic and intestinal genes involved in cholesterol metabolism were analyzed by qRT-PCR. Alterations in the gut microbiota profile of mice with intact gut microbiome were examined using 16S RNA qRT-PCR.

Results

In CONV mice, HFD led to significantly increased blood LDL-C levels as compared with SCD (HFD: 36.8±1.4 mg/dl vs. SCD: 22.0±1.8 mg/dl; P<0.01). In CONV mice atorvastatin treatment significantly reduced blood LDL-C levels after HFD, whereas in ABS mice the LDL-C lowering effect of atorvastatin was markedly attenuated (CONV+HFD+Ator: 31.0±1.8 mg/dl vs. ABS+HFD+Ator: 46.4±3 mg/dl; P<0.01). A significant reduction in the abundance of several plasma lipids, in particular sphingolipids and glycerophospholipids upon atorvastatin treatment was observed in CONV mice, but not in ABS mice. The expressions of distinct hepatic and intestinal cholesterol-regulating genes (ldlr, srebp2, pcsk9 and npc1l1) upon atorvastatin treatment were significantly altered in gut microbiota depleted mice. In response to HFD a decrease in the relative abundance of the bacterial phyla Bacteroides and an increase in the relative abundance of Firmicutes was observed. The altered ratio between Bacteroides and Firmicutes in HFD fed mice was partly reversed upon atorvastatin treatment.

Conclusions

Our findings indicate a crucial role of the gut microbiome for the regulatory properties of atorvastatin on the serum lipidome and, in turn, support a critical impact of atorvastatin on the gut microbial composition. The results provide novel insights into potential microbiota related mechanisms underlying interindividual variation in modulation of the serum lipidome by statins, given interindividual differences in microbiome composition and function.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): German Heart Research Foundation
Effect of testosterone on lipid metabolism and endothelium in men with type 2 diabetes mellitus and hypogonadism
Authors: Khripun I , Vorobyev S , Khripun A , Kogan M , Demidova A , Belousov I
Published: November 2020

Background

To date, knowledge about the effects of testosterone (T) on the cardiovascular system of men remains controversial and requires additional research. Especially the putative impact of T replacement therapy (TRT) on lipid metabolism and endothelial dysfunction as a starting mechanism for the development of cardiovascular pathology in men with type 2 diabetes mellitus (T2DM) presenting with T deficiency has to be elucidated.

The aim of this work was to evaluate the effect of T replacement therapy on lipid metabolism and function of endothelium in men with T2DM and hypogonadism.

Methods

The study included 95 men (mean age 55,3±2,4 years) with T2DM and late onset hypogonadism, established according to EAU 2015 criteria. Parameters of carbohydrate and lipid metabolism, as well as ultrasound assessment of flow-mediated dilatation of the brachial artery (FMD-BA) and intima-media thickness (IMT) of brachial arteries were performed at baseline and after 9 months. Patients were randomized into 2 groups: 1 - 45 men receiving TRT, using 1% transdermal T-gel and 2 (control group) - 50 men, who were not assigned to TRT. Statistical analysis was carried out using the Wilcoxon - test for repeated measurements (STATISTICA 10 software package).

Results

During the treatment period no serious adverse events were registered. The study revealed a significant decrease in HbA1c (p<0.001), total cholesterol (p=0.009), triglycerides (p=0.004) and LDL (p=0.01) levels as well as an increase in HDL level (p=0.001) in the 1st group vs baseline and compared to the 2nd one. There was a decrease in IMT (from 1.0 [0.8; 1.1] to 0.7 [0.6; 0.9] mm, p=0.002) in the 1st group compared to the 2nd (p<0.001). The endothelium-dependent FMD-BA increased 1.5 - fold in men applying T-Gel vs baseline as well as compared to the control group at the time point of follow- up (p<0.001). At the same time TRT leaded to acceleration of the time until maximal vasodilation – it became twice faster (from 120 [90; 120] to 60 [60; 90] sec, p<0.001) compared to baseline and the 2nd group (p<0.001). Linear blood flow velocity increased markedly in the 1st group compared to the 2nd at the time point of follow-up (p=0.03).

Conclusion

TRT in men with T2DM and T deficiency leads to an improvement in carbohydrate and lipid metabolism together with a significant decrease in IMT and enhancement of endothelium vasomotor function, seems to facilitate a reduction in cardiovascular risk.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Russian Science Foundation
The de Winter’s pattern revisited: a case series
Authors: John Thadathilankal-Jess , Pecoraro Alfonso , Weich Hellmuth , Joubert Lloyd , Griffiths Bradley , Herbst Philip
Published: November 2020

Background

The de Winter’s electrocardiogram (ECG) pattern signifying proximal left anterior descending (LAD) artery occlusion was first described in 2008. The ECG changes were thought to be static and mechanisms for this were suggested. In addition, the optimal management of these patients was reported to be via a primary percutaneous coronary intervention (PCI) strategy.

Case summary

Case 1: A 48-year-old gentleman presented with a 2-h history of ischaemic chest pain with initial de Winter’s pattern on ECG. This progressed to anterior ST-elevation myocardial infarction (STEMI) complicated by ventricular fibrillation. Emergency angiography revealed a mid-vessel LAD occlusion which was successfully reperfused. Case 2: A 34-year-old female presented with a 2-h history of ischaemic chest pain with initial ECG showing a de Winter’s pattern. Due to concerns of performing PCI timeously, a pharmacoinvasive strategy of reperfusion was adopted with resolution of the de Winter’s pattern. Urgent angiography revealed a proximal LAD lesion which was successfully stented.

Discussion

The two cases highlight that the de Winter’s pattern may in fact not be static, but rather lie along the continuum of ischaemia and may evolve into STEMI. In addition, we provide further evidence that if primary PCI cannot be offered in a timeous manner, thrombolytic therapy may be considered in such patients. The de Winter’s pattern remains a high-risk ECG pattern that requires early recognition and intervention.
Methods for estimating tuberculosis incidence and mortality by age and sex
Authors: Dodd Peter J , Sismanidis Charalambos , Glaziou Philippe
Published: November 2020

Aims

To develop methods to disaggregate World Health Orgagnization estimates of tuberculosis (TB) incidence and mortality for each country by sex and age.

Methods

For countries where incidence estimates derived from a factor adjustment of notifications and case detection ratio over 0.85, or with <1000 reported TB cases, we disaggregated incidence proportional to notifications. For each other country, a prior was constructed using a hierarchical model of age-stratified prevalence survey data, meta-analysis of sex ratios, and mathematical modelling for children under 15 years. Samples from this prior were used to disaggregate incidence and accepted if incidence exceeded notifications in each age/sex category. Results were inspected and, if implausible, incidence was disaggregated proportional to notifications. Mortality was disaggregated proportional to patterns in vital registration (VR) data in countries with VR data. Where VR data were lacking, a case-fatality ratio (CFR) approach was applied to estimated incidence, with separate CFRs by HIV/ART status, child/adult age groups, and anti-TB treatment status. Uncertainty in all disaggregated country estimates was constructed to be consistent with corresponding overall uncertainty.

Results

We generated disaggregated results for 216 countries. For 125 countries, incidence disaggregation was based on notifications. Of the rest, accepted samples from the prior were considered implausible in 4 countries. For 72 countries, mortality disaggregation was based on VR data; the rest were based on the CFR approach.

Conclusions

While multi-stage, this approach is comparatively simple in overall logic. Disaggregated estimates have relatively larger uncertainty and should be used with caution.
A ΔSOC-based equalization strategy applied to industry
Authors: Wang Maonan , Chang Chun , Ji Feng
Published: November 2020

The voltage-based equalization strategy is widely used in the industry because the voltage (U) of the battery cell is very easy to obtain, but it is difficult to provide an accurate parameter for the battery management system (BMS). This study proposes a new equalization strategy, which is based on the difference between the state of charge (SOC) of any two battery cells in the battery pack, that is, a ΔSOC-based equalization strategy. The new strategy is not only as simple as the voltage-based equalization strategy, but it can also provide an accurate parameter for the BMS. Simply put, using the relationship between the open circuit voltage and the SOC of the battery pack, the proposed strategy can convert the difference between the voltage of the battery cells into ΔSOC, which renders a good performance. Additionally, the required parameters are all from the BMS, and no additional calculation is required, which makes the strategy as simple as the voltage-based balancing strategy. The four experiments show that the relative errors of ΔSOC estimated by the ΔSOC-based equalization strategy are 0.37%, 0.39%, 0.1% and 0.17%, and thereby demonstrate that the ΔSOC-based equalization strategy proposed in this study shows promise in replacing the voltage-based equalization strategy within the industry to obtain better performance.
Not All Terror Is Alike: How Right-Wing Extremist and Islamist Terror Threat Affect Anti-immigration Party Support
Authors: Jacobs Laura , van Spanje Joost
Published: November 2020

Terror threat has been theorized to affect political attitudes. Most prior studies have focused exclusively on Islamist terror threat, while effects of right-wing extremist terrorism on voting behavior have been understudied. We argue that effects on the propensity to vote (PTV) for an anti-immigration party (AIP) depend on the type of threat and is moderated by right-wing authoritarianism (RWA) and internal motivation to control prejudice (IMCP). Using a cross-country experiment in Germany, the Netherlands, and Sweden (N = 1,187), we find that Islamist terror threat increases PTV for AIPs amongst voters high in RWA; similarly, right-wing extremist terror threat reduces PTV for AIPs amongst participants high in RWA. IMCP did not moderate the relationship between terror threat and PTV for an AIP.
A nonconforming pressure-robust finite element method for the Stokes equations on anisotropic meshes
Authors: Apel Thomas , Kempf Volker , Linke Alexander , Merdon Christian
Published: November 2020

Most classical finite element schemes for the (Navier–)Stokes equations are neither pressure-robust, nor are they inf-sup stable on general anisotropic triangulations. A lack of pressure-robustness may lead to large velocity errors, whenever the Stokes momentum balance is dominated by a strong and complicated pressure gradient. It is a consequence of a method, which does not exactly satisfy the divergence constraint. However, inf-sup stable schemes can often be made pressure-robust just by a recent, modified discretization of the exterior force term, using ${\boldsymbol{H}}(\operatorname{div})$-conforming velocity reconstruction operators. This approach has so far only been analyzed on shape-regular triangulations. The novelty of the present contribution is that the reconstruction approach for the Crouzeix–Raviart method, which has a stable Fortin operator on arbitrary meshes, is combined with results on the interpolation error on anisotropic elements for reconstruction operators of Raviart–Thomas and Brezzi–Douglas–Marini type, generalizing the method to a large class of anisotropic triangulations. Numerical examples confirm the theoretical results in a two- and a three-dimensional test case.
Misconceptions and Misrepresentation: Challenging UK Media Reports of Recent Visits of UN Special Procedures
Authors: Smith Rhona
Published: November 2020

With headlines referencing ‘U.N.ACCEPTABLE Clueless UN official’, ‘“loopy” UN inspector’ and ‘UN meddler’, it is clear that UN special procedure mandate holders can be subjected to negative national press coverage when visiting the United Kingdom. Indeed, some media outlets border on vitriolic in their coverage of mandate holders’ visits and reports. This paper argues that a number of misconceptions and misunderstandings explain some of this media coverage. UN special procedure mandate holders are not employed by the UN, nor are they dispatched by the UN to investigate the UK. Rather they are independent and receive no payment for their time or work. Actual visits are funded from the UN general budget and the UK is not alone being examined and critiqued. In explaining some of the misconceptions and misunderstandings, the paper clarifies the role of special rapporteurs and the contribution they make to the UN.
Combining quantitative trait locus and co-expression analysis allowed identification of new candidates for oil accumulation in rapeseed
Authors: Cui Yixin , Zeng Xiao , Xiong Qing , Wei Dayong , Liao Jinghang , Xu Yang , Chen Guanqun , Zhou Yonghong , Dong Hongli , Wan Huafang , Liu Zhi , Li Jiana , Guo Liang , Jung Christian , He Yajun , Qian Wei
Published: November 2020

In crops there are quantitative trait loci (QTLs) in which some of the causal quantitative trait genes (QTGs) have not been functionally characterized even in the model plant Arabidopsis. We propose an approach to delineate QTGs in rapeseed by coordinating expression of genes located within QTLs and known orthologs related to traits from Arabidopsis. Using this method in developing siliques 15 d after pollination in 71 lines of rapeseed, we established an acyl-lipid metabolism co-expression network with 21 modules composed of 270 known acyl-lipid genes and 3503 new genes. The core module harbored 76 known genes involved in fatty acid and triacylglycerol biosynthesis and 671 new genes involved in sucrose transport, carbon metabolism, amino acid metabolism, seed storage protein processes, seed maturation, and phytohormone metabolism. Moreover, the core module closely associated with the modules of photosynthesis and carbon metabolism. From the co-expression network, we selected 12 hub genes to identify their putative Arabidopsis orthologs. These putative orthologs were functionally analysed using Arabidopsis knockout and overexpression lines. Four knockout mutants exhibited lower seed oil content, while the seed oil content in 10 overexpression lines was significantly increased. Therefore, combining gene co-expression network analysis and QTL mapping, this study provides new insights into the detection of QTGs and into acyl-lipid metabolism in rapeseed.
Frame definability, canonicity and cut elimination in common sense modal predicate logics
Authors: Sawasaki Takahiro , Sano Katsuhiko
Published: November 2020

The paper presents semantically complete Hilbert-style systems for some variants of common sense modal predicate logic proposed by van Benthem and further developed by Seligman. The paper also investigates frame definability in the logics and shows what axiom schema is canonical in the logics. In addition to these semantic investigations on the logics, the paper provides the sequent calculi for some of the logics which enjoy cut elimination theorem.
Creating Resilient Classrooms and Schools
Authors: Doll Beth , Ni Hong
Published: November 2020

This chapter describes the Resilient Classrooms protocol for fostering classroom environments that promote students’ emotional well-being and academic success. Descriptions relate key elements of developmental resilience research to the 4 Resilient Classrooms steps: collecting student surveys describing relationships and support for self-agency in the classroom; consulting with students and colleagues to make sense of the survey data; creating and carrying out a plan to modify classroom routines and practices to strengthen supports for resilience; and re-administering the surveys to assess the impact of the plan. An example of a Resilient Classrooms project in Beijing, China, illustrates the acceptability and viability of the Resilient Classrooms protocol in other cultures.
Strengthening the Quality of Preschool, Childcare, and Parenting
Authors: Hong Soo-Young , Hatton-Bowers Holly , Knoche Lisa
Published: November 2020

Early childhood is a critical period during which children learn to regulate and manage emotions and behaviors, develop and maintain social relationships, and interact effectively with others. In this chapter, the authors describe research-based supports for young children’s emotional well-being and positive behavior, promising strategies and interventions used in early care and education settings, the well-being of early childhood educators that impacts children’s emotional competence, and the importance of engaging families in promoting children’s emotional well-being and positive behavior. This chapter uses a systemic lens and emphasizes the importance of collaborative partnerships between parents and early childhood educators in supporting young children’s emotional well-being and positive behavior.
Teaching Emotional Self-Regulation to Children and Adolescents
Authors: Lazarus Philip J. , Costa Annela
Published: November 2020

Emotional self-regulation is the ability to modify emotional reactions and their subsequent expression through behaviors by being able to recognize, understand, and integrate emotional information. Characteristics of poor emotional self-regulation include heightened emotional responses, difficulty focusing attention or inhibiting behaviors, and low tolerance levels accompanied by high frustration. Poor emotional self-regulation has been associated with a plethora of mental health problems, which includes conduct disorders, anxiety, depression, substance abuse, eating disorders, and nonsuicidal self-injury. In this chapter, the authors discuss how emotional self-regulation develops and its impact on children and youth. Further, they describe practical universal and targeted strategies to increase competence in emotional self-regulation. A case is presented, based on research evidence, that emotional self-regulation skills can be taught and learned, and children benefit by developing skills to manage their emotions. Furthermore, schools are ideal places to help students become more adroit in these skills.
Building a Foundation for Trauma-Informed Schools
Authors: Lazarus Philip J. , Overstreet Stacy , Rossen Eric
Published: November 2020

Trauma-informed schools reflect a national movement to respond to the significant prevalence and impact of trauma in youth by providing a framework for effective practices, interventions, and systems-change strategies. The aim of trauma-informed schools is to establish learning environments that enable children who are exposed to trauma to develop caring relationships with adults, learn to modulate their emotions, and achieve at high levels. In this chapter, the authors define trauma and discuss the impact of traumatic experiences on children’s lives, utilize a case example to illustrate the factors that can influence children’s reactions to trauma, provide an overview of essential considerations in the development of trauma-informed schools, review best practices for screening and assessment for trauma in schools, and summarize lessons learned in supporting children impacted by trauma.
Enfranchising Socially Marginalized Students
Authors: Sullivan Amanda L. , Pham Andy V. , Weeks Mollie , Nguyen Thuy , Dong Quennie
Published: November 2020

Some of the most vulnerable children in schools, such as immigrants, refugees, and students from economically disadvantaged backgrounds, experience disenfranchisement and marginalization due to practices and policies that restrict rights and privileges based on their minoritized or economic statuses. Moreover, these children encounter a plethora of risk factors, environmental stressors, and traumatic experiences that have significant implications for school mental health. Thus, there is a great need to highlight culturally responsive practices and school-based interventions that enfranchise vulnerable youth. The chapter first outlines the historical and sociopolitical contexts relating to marginalization of youth from diverse backgrounds. Examples of culturally adapted interventions and programs are discussed with a focus on multitier support to reduce inequity and bolster resilience. Lastly, recommendations are provided for school mental health providers and stakeholders using inclusive education and advocacy to support the unique challenges and needs of those historically disenfranchised within the educational system.
Implementing Statewide Practices That Promote Student Wellness and Resilience
Authors: Noltemeyer Amity , Meehan Cricket , Jordan Emily , Petrasek Michael
Published: November 2020

Wellness and resilience promotion efforts are often an underutilized opportunity to address the mental health needs of children and youth. Organizations and individuals with state-level reach are ideally poised to develop and disseminate infrastructure, training, and resources to support wellness and resilience promotion efforts. This chapter highlights 8 key systems and practices that can inform and support such statewide efforts. Examples within Ohio, a recipient of 2 federal grants to support behavioral and mental health promotion, are used to illustrate the eight systems and practices. The chapter incorporates recommendations for others seeking to promote wellness and resilience in their respective contexts.
Using Universal Screening to Monitor Students’ Social, Emotional, and Behavioral Health
Authors: Eklund Katie , Kilgus Stephen P. , Meyer Lauren , Barber Alexandra
Published: November 2020

As many youths will display symptoms of social-emotional or behavioral (SEB) health concerns during their childhood or adolescence, schools are called upon to provide supports to students who have demonstrated barriers to learning. Universal screening has been identified as one strategy to enhance the accurate identification of students struggling with SEB concerns. Universal screening measures take on a variety of formats but often include some type of brief behavior rating completed by a teacher, parent, or student to assess individual student functioning. The current chapter provides an overview of universal screening for SEB concerns. Available screening measures are reviewed, along with the psychometric evidence supporting each measure (e.g., validity, reliability, diagnostic accuracy). Procedural considerations are examined, including administration frequency and duration, screening informant selection, and parental consent protocols. Finally, a procedural framework is provided that outlines how to link screening results to evidence-based interventions.
Accessing Targeted and Intensive Mental Health Services
Authors: Hughes Tammy L. , Mazzotta Maggie B.
Published: November 2020

One in five children and adolescents experience a mental health disorder during their school-aged years. Given that almost all children attend school, this setting offers the opportunity to deliver a wide range of services including universal prevention programs, targeted support for at-risk youth, and tailored individual treatments that can be coordinated with community and family supports. However, there is debate about what is a schools’ responsibility. Schools prioritize services on issues that interfere with the youth’s educational gains. Yet, there are major differences in perspectives about what is an educational matter. This autonomy means that children in some districts receive services while other children in other districts do not. This chapter offers readers a full picture of the challenges schools address and how to work within these systems. How to negotiate and coordinate with school teams to address child mental health needs is detailed.
Culturally Informed Therapy for Schizophrenia
Authors: Weisman de Mamani Amy , McLaughlin Merranda , Altamirano Olivia , Lopez Daisy , Ahmad Salman Shaheen
Published: November 2020

This book is primarily designed for clinicians and researchers interested in learning how to conduct an empirically supported culturally informed therapy for schizophrenia (CIT-S) that integrates core components of evidenced-based family therapy. It is estimated that approximately 1% of adults in the United States will be diagnosed with schizophrenia or a related schizophrenia spectrum disorder. Without treatment, prognosis is generally poor. Fortunately, traditional family therapies have shown increasing promise in reducing relapse rates and improving mental health for this population. As more and more societies become multicultural, however, there is an increasing expectation that mental health providers will also be prepared to meet the needs of unique and culturally diverse clients in an efficient, skillful, and culturally relevant manner. CIT-S is a 15-week, family-focused, cognitive behavioral approach for managing schizophrenia spectrum disorders. The intervention draws upon clients’ cultural beliefs, practices, and traditions to help them conceptualize and manage mental illness. It aims to improve the quality of clients’ lives in a manner that is in line with their values and takes into account their cultural norms when discussing important issues and addressing challenges (such as mental illness) within the family. CIT-S contains five distinct modules: (a) family collectivism, (b) psychoeducation, (c) spirituality, (d) communication training, and (e) problem-solving. For each module, a detailed rationale, background information, therapy instructions, suggested homework assignments, and a sample case vignette are provided in an accessible, easy-to-use manner.
Introduction
Authors: Mamani Amy Weisman de , McLaughlin Merranda , Altamirano Olivia , Lopez Daisy , Ahmad Salman Shaheen
Published: November 2020

This chapter serves as an orientation to this book, a 15-week, family-focused, cognitive-behavioral approach for managing schizophrenia spectrum disorders. The chapter begins with an overview of the book’s purpose, which is to offer a how-to approach for conducting culturally informed therapy for schizophrenia (CIT-S). CIT-S is a treatment that draws upon clients’ own cultural beliefs, practices, and traditions to help people with schizophrenia and their loved ones to better manage the illness and improve the quality of their lives. Next, the suggested credentials for individuals who wish to deliver the intervention are discussed. This is followed by a description of the organization of the book and a brief overview of each of the nine chapters. Finally, a glossary of important terms and phrases that are used throughout the book is provided.
Module 3—Spirituality (Sessions 7–9)
Authors: Mamani Amy Weisman de , McLaughlin Merranda , Altamirano Olivia , Lopez Daisy , Ahmad Salman Shaheen
Published: November 2020

Mounting evidence indicates that religion/spirituality (R/S) have multiple mental and physical health benefits for those who practice them, including for individuals living with schizophrenia and their families. This chapter introduces the spirituality module, which is aimed at creating a collaborative family environment that may utilize R/S to facilitate recovery. The chapter includes a rationale and goals for addressing R/S in culturally informed therapy for schizophrenia, ways of exploring individual family members’ beliefs and values surrounding R/S, and helping to build up adaptive aspects of R/S coping while correcting maladaptive uses of R/S. Sharing meaningful prayers and symbols is encouraged to develop therapist understanding and to reinforce the benefits of R/S for clients. Differences in how family members perceive and practice R/S are explored, guided by detailed handouts. A case illustration of a Muslim American father–son pair demonstrates the process.
Module 5—Problem-Solving (Sessions 13–15)
Authors: Mamani Amy Weisman de , McLaughlin Merranda , Altamirano Olivia , Lopez Daisy , Ahmad Salman Shaheen
Published: November 2020

This chapter is designed to help clinicians teach clients an efficient, step-by-step approach for problem-solving. Family members are first taught to systematically examine their beliefs and values to help them identify issues worth tackling (e.g., to pick their battles wisely). Next, clients are taught a systematic technique, using detailed handouts, for operationalizing their chosen problems, identifying the best solution or set of solutions, and developing a plan to implement the solution/s. In subsequent sessions, clinicians are instructed to help families revise their implementation strategy, if needed, or move on to tackle a new problem. Several examples of relevant problem-solving homework assignments that families can complete together are provided. The chapter concludes with a case example of problem-solving with a Jewish mother and her adult daughter.
Additional Considerations
Authors: Mamani Amy Weisman de , McLaughlin Merranda , Altamirano Olivia , Lopez Daisy , Ahmad Salman Shaheen
Published: November 2020

This chapter discusses topics and obstacles not otherwise examined in previous chapters. For example, the chapter highlights research addressing whether clinician–client match on race/ethnicity and/or other cultural beliefs and values impacts therapy efficacy. More specifically, the chapter addresses how to deal with challenging families and clients, including those that are unmedicated, highly symptomatic, and/or who endorse delusional thought content. The difficult challenge of what to do when one or more family members wishes to distance themselves from their relative with mental illness is also addressed. Suggestions and skills that can be used for these and other difficult situations are discussed. Excerpts and example quotes are also provided for addressing difficulties such as inconsistent attendance, homework incompletion, or other difficulties that may be encountered during therapy.
Integrated CIT-S Illustration
Authors: Mamani Amy Weisman de , McLaughlin Merranda , Altamirano Olivia , Lopez Daisy , Ahmad Salman Shaheen
Published: November 2020

This chapter illustrates a session-by-session progression through culturally informed therapy for schizophrenia (CIT-S). The case illustration of a mixed-race couple of White (Irish) and Native American (Arapaho) ancestries aims to demonstrate different aspects of a client’s illness and her treatment using CIT-S. The chapter includes examples of how a therapist may help clients navigate difficulties surrounding family, culture, illness, and religion/spirituality in ways that cater to the individual living with schizophrenia and foster his or her recovery. The importance of a low-key home environment, adjusting expectations, and including family members or caregivers as part of the healing process are highlighted. Ways to avoid or cope with the negative consequences of some common cognitive difficulties and communication deficits faced by individuals living with schizophrenia are practiced with the couple. Ideas for prayers commonly encountered in CIT-S are found at the beginning and end of each session.
Is there enough star formation in simulated protoclusters?
Authors: Lim Seunghwan , Scott Douglas , Babul Arif , Barnes David J , Kay Scott T , McCarthy Ian G , Rennehan Douglas , Vogelsberger Mark
Published: November 2020

As progenitors of the most massive objects, protoclusters are key to tracing the evolution and star formation history of the Universe, and are responsible for ${\gtrsim }\, 20$ per cent of the cosmic star formation at $z\, {\gt }\, 2$. Using a combination of state-of-the-art hydrodynamical simulations and empirical models, we show that current galaxy formation models do not produce enough star formation in protoclusters to match observations. We find that the star formation rates (SFRs) predicted from the models are an order of magnitude lower than what is seen in observations, despite the relatively good agreement found for their mass-accretion histories, specifically that they lie on an evolutionary path to become Coma-like clusters at $z\, {\simeq }\, 0$. Using a well-studied protocluster core at $z\, {=}\, 4.3$ as a test case, we find that star formation efficiency of protocluster galaxies is higher than predicted by the models. We show that a large part of the discrepancy can be attributed to a dependence of SFR on the numerical resolution of the simulations, with a roughly factor of 3 drop in SFR when the spatial resolution decreases by a factor of 4. We also present predictions up to $z\, {\simeq }\, 7$. Compared to lower redshifts, we find that centrals (the most massive member galaxies) are more distinct from the other galaxies, while protocluster galaxies are less distinct from field galaxies. All these results suggest that, as a rare and extreme population at high z, protoclusters can help constrain galaxy formation models tuned to match the average population at $z\, {\simeq }\, 0$.