bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Lower Blood Pressure Goals on Left Ventricular Structure and Function in Patients With Subclinical Hypertensive Heart Disease
Authors: Levy Phillip D , Burla Michael J , Twiner Michael J , Marinica Alexander L , Mahn James J , Reed Brian , Brody Aaron , Ehrman Robert , Brodsky Allie , Zhang Yiying , Nasser Samar A , Flack John M
Published: July 2020

BACKGROUND

Subclinical hypertensive heart disease (SHHD) is a precursor to heart failure. Blood pressure (BP) reduction is an important component of secondary disease prevention in patients with SHHD. Treating patients with SHHD utilizing a more intensive BP target (120/80 mm Hg), may lead to improved cardiac function but there has been limited study of this, particularly in African Americans (AAs).

METHODS

We conducted a single center, randomized controlled trial where subjects with uncontrolled, asymptomatic hypertension, and SHHD not managed by a primary care physician were randomized to standard (<140/90 mm Hg) or intensive (<120/80 mm Hg) BP therapy groups with quarterly follow-up for 12 months. The primary outcome was the differences of BP reduction between these 2 groups and the secondary outcome was the improvement in echocardiographic measures at 12 months.

RESULTS

Patients (95% AAs, 65% male, mean age 49.4) were randomized to the standard (n = 65) or the intensive (n = 58) BP therapy groups. Despite significant reductions in systolic BP (sBP) from baseline (−10.9 vs. −19.1 mm Hg, respectively) (P < 0.05), no significant differences were noted between intention-to-treat groups (P = 0.33) or the proportion with resolution of SHHD (P = 0.31). However, on post hoc analysis, achievement of a sBP <130 mm Hg was associated with significant reduction in indexed left ventricular mass (−6.91 gm/m2.7; P = 0.008) which remained significant on mixed effect modeling (P = 0.031).

CONCLUSIONS

In post hoc analysis, sBP <130 mm Hg in predominantly AA patients with SHHD was associated with improved cardiac function and reverse remodeling and may help to explain preventative effects of lower BP goals.

CLINICAL TRIALS REGISTRATION

Trial Number NCT00689819.
YIF1B mutations cause a post-natal neurodevelopmental syndrome associated with Golgi and primary cilium alterations
Authors: Diaz Jorge , Gérard Xavier , Emerit Michel-Boris , Areias Julie , Geny David , Dégardin Julie , Simonutti Manuel , Guerquin Marie-Justine , Collin Thibault , Viollet Cécile , Billard Jean-Marie , Métin Christine , Hubert Laurence , Larti Farzaneh , Kahrizi Kimia , Jobling Rebekah , Agolini Emanuele , Shaheen Ranad , Zigler Alban , Rouiller-Fabre Virginie , Rozet Jean-Michel , Picaud Serge , Novelli Antonio , Alameer Seham , Najmabadi Hossein , Cohn Ronald , Munnich Arnold , Barth Magalie , Lugli Licia , Alkuraya Fowzan S , Blaser Susan , Gashlan Maha , Besmond Claude , Darmon Michèle , Masson Justine
Published: July 2020

Human post-natal neurodevelopmental delay is often associated with cerebral alterations that can lead, by themselves or associated with peripheral deficits, to premature death. Here, we report the clinical features of 10 patients from six independent families with mutations in the autosomal YIF1B gene encoding a ubiquitous protein involved in anterograde traffic from the endoplasmic reticulum to the cell membrane, and in Golgi apparatus morphology. The patients displayed global developmental delay, motor delay, visual deficits with brain MRI evidence of ventricle enlargement, myelination alterations and cerebellar atrophy. A similar profile was observed in the Yif1b knockout (KO) mouse model developed to identify the cellular alterations involved in the clinical defects. In the CNS, mice lacking Yif1b displayed neuronal reduction, altered myelination of the motor cortex, cerebellar atrophy, enlargement of the ventricles, and subcellular alterations of endoplasmic reticulum and Golgi apparatus compartments. Remarkably, although YIF1B was not detected in primary cilia, biallelic YIF1B mutations caused primary cilia abnormalities in skin fibroblasts from both patients and Yif1b-KO mice, and in ciliary architectural components in the Yif1b-KO brain. Consequently, our findings identify YIF1B as an essential gene in early post-natal development in human, and provide a new genetic target that should be tested in patients developing a neurodevelopmental delay during the first year of life. Thus, our work is the first description of a functional deficit linking Golgipathies and ciliopathies, diseases so far associated exclusively to mutations in genes coding for proteins expressed within the primary cilium or related ultrastructures. We therefore propose that these pathologies should be considered as belonging to a larger class of neurodevelopmental diseases depending on proteins involved in the trafficking of proteins towards specific cell membrane compartments.
Differential cross-seeding properties of tau and α-synuclein in mouse models of tauopathy and synucleinopathy
Authors: Williams Tosha , Sorrentino Zachary , Weinrich Mary , Giasson Benoit I , Chakrabarty Paramita
Published: July 2020

Co-occurrence of tau and α-synuclein pathologies in a subset of Alzheimer’s disease patients has led to the idea that mixed pathologies may play a unique characteristic role in the Alzheimer’s disease neurodegenerative cascade. To understand the aetiology of such mixed pathologies, we investigated cross-seeding by human recombinant tau and human recombinant α-synuclein fibrillar species in a mouse model of tauopathy (Line PS19) or synucleinopathy (Line M20). Unilateral hippocampal injection of tau fibrils or α-synuclein fibrils, and to a lesser extent tau + α-synuclein copolymer fibrils prepared from co-incubating individual recombinant monomers, induced robust phosphorylated tau pathology in PS19 mice relative to control mice. Though the tau + α-synuclein copolymer fibrils did not modulate induction of pathologies at the site of injection, examination of the whole brain showed that these copolymers exacerbated neuroanatomic transmission of seeded tau pathology compared to tau fibril-injected mice. Only α-synuclein fibrils, but not tau alone or tau + α-synuclein copolymers, triggered modest levels of endogenous phosphorylated α-synuclein pathology. Overall, data from the PS19 mice suggest that human α-synuclein fibrils can efficiently cross-seed human tau and have a modest priming effect on mouse α-synuclein, and the presence of tau fibrils does not exacerbate the priming process. In M20 mice, unilateral hippocampal injection of α-synuclein fibrils or tau fibrils induced robust bilateral phosphorylated α-synuclein pathology, while tau + α-synuclein copolymer injection resulted in restricted phosphorylated α-synuclein pathology predominantly in the ipsilateral cortex. This suggests that human tau fibrils can also induce human α-synuclein pathogenesis, and the presence of combinatorial seeds is not synergistic. None of these aggregates induced phosphorylated tau pathology in M20 mice, showing that mouse tau cannot be primed efficiently by human tau fibrils or human α-synuclein fibrils. Neuropathological analysis of the whole brain of M20 mice showed that tau + α-synuclein copolymer-injected mice had lower abundance of bilaterally transmitted α-synuclein pathologies relative to α-synuclein fibril-injected mice. Thus, the tau + α-synuclein copolymer fibrils show robust transmission properties preferentially in rodent model of tauopathies but not in synucleinopathy, probably signifying an enhanced cooperative relationship between tau and α-synuclein in the tau seeding process. Together, our data highlight the unique cross-seeding properties of tau and αSyn in neurodegenerative proteinopathies.
A Confirmed Case of SARS-CoV-2 Pneumonia With Negative Routine Reverse Transcriptase–Polymerase Chain Reaction and Virus Variation in Guangzhou, China
Authors: Li Zhengtu , Li Yinhu , Chen Lingdan , Li Shaoqiang , Yu Le , Zhu Airu , Yang Feng , Jiang Qian , Chen Liyan , Zhao Jincun , Lu Wenju , Zhong Nanshan , Ye Feng
Published: July 2020

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is a newly recognized disease, and its diagnosis is primarily confirmed by routine reverse transcriptase -polymerase chain reaction (RT-PCR) detection of SARS-CoV-2.

Methods

However, we report a confirmed case of SARS-CoV-2 pneumonia with a negative routine RT-PCR.

Results

This case was finally diagnosed by nanopore sequencing combined with antibody of SARS-CoV-2. Simultaneously, the ORF and NP gene variations of SARS-CoV-2 were found.

Conclusions

This case highlighted that false-negative results could be present in routine RT-PCR diagnosis, especially with virus variation. Currently, nanopore pathogen sequencing and antibody detection have been found to be effective in clinical diagnosis.
Disruption of actin dynamics regulated by Rho effector mDia1 attenuates pressure overload-induced cardiac hypertrophic responses and exacerbates dysfunction
Authors: Abe Ichitaro , Terabayashi Takeshi , Hanada Katsuhiro , Kondo Hidekazu , Teshima Yasushi , Ishii Yumi , Miyoshi Miho , Kira Shintaro , Saito Shotaro , Tsuchimochi Hirotsugu , Shirai Mikiyasu , Yufu Kunio , Arakane Motoki , Daa Tsutomu , Thumkeo Dean , Narumiya Shuh , Takahashi Naohiko , Ishizaki Toshimasa
Published: July 2020

Aims

Cardiac hypertrophy is a compensatory response to pressure overload, leading to heart failure. Recent studies have demonstrated that Rho is immediately activated in left ventricles after pressure overload and that Rho signalling plays crucial regulatory roles in actin cytoskeleton rearrangement during cardiac hypertrophic responses. However, the mechanisms by which Rho and its downstream proteins control actin dynamics during hypertrophic responses remain not fully understood. In this study, we identified the pivotal roles of mammalian homologue of Drosophila diaphanous (mDia) 1, a Rho-effector molecule, in pressure overload-induced ventricular hypertrophy.

Methods and results 

Male wild-type (WT) and mDia1-knockout (mDia1KO) mice (10–12 weeks old) were subjected to a transverse aortic constriction (TAC) or sham operation. The heart weight/tibia length ratio, cardiomyocyte cross-sectional area, left ventricular wall thickness, and expression of hypertrophy-specific genes were significantly decreased in mDia1KO mice 3 weeks after TAC, and the mortality rate was higher at 12 weeks. Echocardiography indicated that mDia1 deletion increased the severity of heart failure 8 weeks after TAC. Importantly, we could not observe apparent defects in cardiac hypertrophic responses in mDia3-knockout mice. Microarray analysis revealed that mDia1 was involved in the induction of hypertrophy-related genes, including immediate early genes, in pressure overloaded hearts. Loss of mDia1 attenuated activation of the mechanotransduction pathway in TAC-operated mice hearts. We also found that mDia1 was involved in stretch-induced activation of the mechanotransduction pathway and gene expression of c-fos in neonatal rat ventricular cardiomyocytes (NRVMs). mDia1 regulated the filamentous/globular (F/G)-actin ratio in response to pressure overload in mice. Additionally, increases in nuclear myocardin-related transcription factors and serum response factor were perturbed in response to pressure overload in mDia1KO mice and to mechanical stretch in mDia1 depleted NRVMs.

Conclusion 

mDia1, through actin dynamics, is involved in compensatory cardiac hypertrophy in response to pressure overload.
Idiopathic ventricular fibrillation: the ongoing quest for diagnostic refinement
Authors: Conte Giulio , Giudicessi John R , Ackerman Michael J
Published: July 2020

Prior to the recognition of distinct clinical entities, such as Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and long QT syndrome, all sudden cardiac arrest (SCA) survivors with ventricular fibrillation (VF) and apparently structurally normal hearts were labelled as idiopathic ventricular fibrillation (IVF). Over the last three decades, the definition of IVF has changed substantially, mostly as result of the identification of the spectrum of SCA-predisposing genetic heart diseases (GHDs), and the molecular evidence, by post-mortem genetic analysis (aka, the molecular autopsy), of cardiac channelopathies as the pathogenic basis for up to 35% of unexplained cases of sudden cardiac death (SCD) in the young. The evolution of the definition of IVF over time has led to a progressively greater awareness of the need for an extensive diagnostic assessment in unexplained SCA survivors. Nevertheless, GHDs are still underdiagnosed among SCA survivors, due to the underuse of pharmacological challenges (i.e. sodium channel blocker test), misrecognition of electrocardiogram (ECG) abnormalities/patterns (i.e. early repolarization pattern or exercise-induced ventricular bigeminy) or errors in the measurement of ECG parameters (e.g. the heart-rate corrected QT interval). In this review, we discuss the epidemiology, diagnostic approaches, and the controversies related to role of the genetic background in unexplained SCA survivors with a default diagnosis of IVF.
Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings
Authors: Gasperetti Alessio , Biffi Mauro , Duru Firat , Schiavone Marco , Ziacchi Matteo , Mitacchione Gianfranco , Lavalle Carlo , Saguner Ardan , Lanfranchi Antonio , Casalini Giacomo , Tocci Marco , Fabbricatore Davide , Salghetti Francesca , Mariani Marco Valerio , Busana Mattia , Bellia Alfonso , Cogliati Chiara Beatrice , Viale Pierluigi , Antinori Spinello , Galli Massimo , Galiè Nazzareno , Tondo Claudio , Forleo Giovanni Battista
Published: July 2020

Aims

The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 patients undergoing hydroxychloroquine (HCQ) therapy in different clinical settings.

Methods and results

COVID-19 patients at seven institutions receiving HCQ therapy from whom a baseline and at least one ECG at 48+ h were available were enrolled in the study. QT/QTc prolongation, QT-associated and QT-independent arrhythmic events, arrhythmic mortality, and overall mortality during HCQ therapy were assessed. A total of 649 COVID-19 patients (61.9 ± 18.7 years, 46.1% males) were enrolled. HCQ therapy was administrated as a home therapy regimen in 126 (19.4%) patients, and as an in-hospital-treatment to 495 (76.3%) hospitalized and 28 (4.3%) intensive care unit (ICU) patients. At 36–72 and at 96+ h after the first HCQ dose, 358 and 404 ECGs were obtained, respectively. A significant QT/QTc interval prolongation was observed (P < 0.001), but the magnitude of the increase was modest [+13 (9–16) ms]. Baseline QT/QTc length and presence of fever (P = 0.001) at admission represented the most important determinants of QT/QTc prolongation. No arrhythmic-related deaths were reported. The overall major ventricular arrhythmia rate was low (1.1%), with all events found not to be related to QT or HCQ therapy at a centralized event evaluation. No differences in QT/QTc prolongation and QT-related arrhythmias were observed across different clinical settings, with non-QT-related arrhythmias being more common in the intensive care setting.

Conclusion

HCQ administration is safe for a short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attributable arrhythmic deaths.
Development and Validation of an Inflammatory-Frailty Index for Kidney Transplantation
Authors: Haugen Christine E , Gross Alden , Chu Nadia M , Norman Silas P , Brennan Daniel C , Xue Qian-Li , Walston Jeremy , Segev Dorry L , McAdams-DeMarco Mara
Published: July 2020

Background

Physical frailty phenotype is characterized by decreased physiologic reserve to stressors and associated with poor outcomes, such as delirium and mortality, that may result from post-kidney transplant (KT) inflammation. Despite a hypothesized underlying pro-inflammatory state, conventional measures of frailty typically do not incorporate inflammatory biomarkers directly. Among KT candidates and recipients, we evaluated the inclusion of inflammatory biomarkers with traditional physical frailty phenotype components.

Methods

Among 1154 KT candidates and recipients with measures of physical frailty phenotype and inflammation (interleukin 6 [IL6], tumor necrosis factor alpha [TNFα], C-reactive protein [CRP]) at 2 transplant centers (2009–2017), we evaluated construct validity of inflammatory-frailty using latent class analysis. Inflammatory-frailty measures combined 5 physical frailty phenotype components plus the addition of an individual inflammatory biomarkers, separately (highest tertiles) as a sixth component. We then used Kaplan–Meier methods and adjusted Cox proportional hazards to assess post-KT mortality risk by inflammatory-frailty (n = 378); Harrell’s C-statistics assessed risk prediction (discrimination).

Results

Based on fit criteria, a 2-class solution (frail vs nonfrail) for inflammatory-frailty was the best-fitting model. Five-year survival (frail vs nonfrail) was: 81% versus 93% (IL6-frailty), 87% versus 89% (CRP-frailty), and 83% versus 91% (TNFα-frailty). Mortality was 2.07-fold higher for IL6-frail recipients (95% CI: 1.03–4.19, p = .04); there were no associations between the mortality and the other inflammatory-frailty indices (TNFα-frail: 1.88, 95% CI: 0.95–3.74, p = .07; CRP-frail: 1.02, 95% CI: 0.52–2.03, p = .95). However, none of the frailty-inflammatory indices (all C-statistics = 0.71) improved post-KT mortality risk prediction over the physical frailty phenotype (C-statistics = 0.70).

Conclusions

Measurement of IL6-frailty at transplantation can inform which patients should be targeted for pre-KT interventions. However, the traditional physical frailty phenotype is sufficient for post-KT mortality risk prediction.
Oriented pre-stack inverse Q filtering for resolution enhancements of seismic data
Authors: Liu Guochang , Li Chao , Rao Ying , Chen Xiaohong
Published: July 2020

Seismic attenuation is one of the main factors responsible for degradation of the resolution of seismic data. During seismic wave propagation in attenuation medium, the energy of signal components seriously decreases, especially those with higher frequencies. The seismic attenuation and resolution reduction are generally compensated for with inverse Q filtering in the frequency or time domain. However, the implementation of pre-stack inverse Q filtering is challenging because the traveltime in each layer is not easy to obtain for the pre-stack seismic gather, unless the accurate velocity model is known. In this study, we propose an inverse Q filtering method for the pre-stack seismic gather that uses the local slope and warped mapping to determine the propagation path, and Taylor-expansion-based division is used to stabilize the inversion. The local slope can determine the reflection events with the same ray path, and the inverse warped mapping can transform the attenuation factor from the ${t_0} - p$ (zero-offset traveltime to ray parameter) domain to the $t - x$ (traveltime and offset) domain. The attenuation factor in the ${t_0} - p$ domain is easy to calculate because the traveltimes and Q values in each layer are known. The proposed oriented pre-stack inverse Q filtering method is velocity-independent and suitable for a depth varying Q model. The synthetic and real data examples demonstrated that the method can effectively correct the attenuation and dispersion of seismic waves, and can obtain pre-stack seismic gathers with high resolution.
Correction of cilia structure and function alleviates multi-organ pathology in Bardet–Biedl syndrome mice
Authors: Husson Hervé , Bukanov Nikolay O , Moreno Sarah , Smith Mandy M , Richards Brenda , Zhu Cheng , Picariello Tyler , Park Hyejung , Wang Bing , Natoli Thomas A , Smith Laurie A , Zanotti Stefano , Russo Ryan J , Madden Stephen L , Klinger Katherine W , Modur Vijay , Ibraghimov-Beskrovnaya Oxana
Published: July 2020

Bardet–Biedl syndrome (BBS) is a pleiotropic autosomal recessive ciliopathy affecting multiple organs. The development of potential disease-modifying therapy for BBS will require concurrent targeting of multi-systemic manifestations. Here, we show for the first time that monosialodihexosylganglioside accumulates in Bbs2−/− cilia, indicating impairment of glycosphingolipid (GSL) metabolism in BBS. Consequently, we tested whether BBS pathology in Bbs2−/− mice can be reversed by targeting the underlying ciliary defect via reduction of GSL metabolism. Inhibition of GSL synthesis with the glucosylceramide synthase inhibitor Genz-667161 decreases the obesity, liver disease, retinal degeneration and olfaction defect in Bbs2−/− mice. These effects are secondary to preservation of ciliary structure and signaling, and stimulation of cellular differentiation. In conclusion, reduction of GSL metabolism resolves the multi-organ pathology of Bbs2−/− mice by directly preserving ciliary structure and function towards a normal phenotype. Since this approach does not rely on the correction of the underlying genetic mutation, it might translate successfully as a treatment for other ciliopathies.
Impact of perceived social norms on farmers’ behavior of cultivated land protection: an empirical analysis based on mediating effect model
Authors: Qiu Wenwen , Zhong Zhangbao , Huang Ya
Published: July 2020

In this study, the impact of social norms on farmers’ behavior of cultivated land protection and the related mechanism was investigated in terms of direct effect and mediating effect and further verified by logistic and mediation effect estimation of different organic fertilizer application behaviors. An empirical analysis of the data collected from Xiajin County of Shandong, China, revealed that (1) perceived social norms can exert significant and positive effects on the behavior of farmers in cultivated land protection; (2) social norms can stimulate farmers to adopt cultivated land protection behaviors by affecting their related value cognition, risk confidence and skills; and (3) the mediating mechanisms varied in the impact of perceived social norms on different cultivated land protection behaviors, with farmyard manure application being significantly moderated by value cognition, risk confidence and skills, in contrast to a major impact of social network on the application of commercial organic fertilizers. This study enriched the theoretical interpretation of the impact of social norms on farmers’ behavior of cultivated land protection and provided useful information on activation of farmers’ cultivated land protection behavior to promote the sustainable development of agriculture.
Experimental Transmission of Plasmodium malariae to Anopheles gambiae
Authors: Pinilla Yudi T , Boussougou-Sambe Stravensky T , Gräßle Sarah , Ngossanga Barclaye , Doumba-Ndalembouly Ange G , Weierich Andrea , Bingoulou Gedeon , Malinga Emma G , Nguiffo-Nguete Daniel , Ntoumi Francine , Djogbénou Luc , Issifou Saadou , Wondji Charles S , Adegnika Ayola A , Borrmann Steffen ,   COMAL Study Group, Nzoughe-Nzeng Theo , Edoa Jean Ronald , N’Noh Elsy Dansou , Zinsou Jeannot , Ndo Cyrille , Nkemngo Francis , Tchouakoui Magellan , Tchapga Williams , Ayuk Renette , Ntabi Jacques Mbama , Koukouikila-Koussounda Felix , Agonhossou Romuald , Akoton Romaric Bidossessi , Akpeyedje Yannelle Dossou , Beck Katharina , Saison Nathanael , Hoffmann Anton
Published: July 2020

Our current knowledge of the clinical burden, biology, and transmission of Plasmodium malariae is extremely scarce. To start addressing some of those questions, we experimentally infected Anopheles gambiae mosquitoes with fresh P. malariae isolates obtained from asymptomatic individuals in Lambaréné, Gabon. The proportion of mosquitoes infected via direct membrane feeding assay with either P. malariae monoinfections (16% [19 of 121]) or coinfections (28% [31 of 112]) was higher after serum replacement than in parallel groups without serum replacement (4% [4 of 102] and 4% [2 of 45], respectively; P < .01). Our results show that isolates from asymptomatic carriers can be used for experimental studies of P. malariae transmission.
Implication of a High Risk for Type 2 Vaccine-Derived Poliovirus Emergence and Transmission After the Switch From Trivalent to Bivalent Oral Poliovirus Vaccine
Authors: Yan Dongmei , Wang Dongyan , Zhang Yong , Li Xiaolei , Tang Haishu , Guan Jing , Song Yang , Zhu Shuangli , Xu Wenbo
Published: July 2020

Background

China implemented the globally synchronized switch from trivalent oral poliovirus vaccine (tOPV) to bivalent OPV (bOPV) and introduced 1 dose of inactivated poliovirus vaccine on 1 May 2016. We assessed the impact of the switch on the immunity level against poliovirus, especially type 2.

Methods

Children born between 2014 and 2017, who were brought to the hospitals in Urumqi city, Xinjiang Province in 2017, were enrolled and blood samples were collected to test for antibody titers against poliovirus. A comparison of seroprevalence between the children born before (preswitch group) and after the switch (postswitch group) was performed to assess the impact of the switch on the immunity level against polio.

Results

A total of 172 subjects were enrolled. The overall seroprevalences were 98.8%, 79.1%, and 98.3% for types 1, 2, and 3, respectively. Seroprevalence for type 2 significantly decreased from 91.6% in the preswitch group to 67.4% in the postswitch group, but no statistically significant change was observed for both types 1 and 3.

Conclusions

The switch from tOPV to bOPV can provide high-level immunity against types 1 and 3 but not against type 2, indicating a high risk of type 2 vaccine-derived poliovirus emergence and transmission.
Recommendations for Intersectoral Collaboration for the Prevention and Control of Vector-Borne Diseases: Results From a Modified Delphi Process
Authors: Antonio Carl Abelardo T , Bermudez Amiel Nazer C , Cochon Kim L , Reyes Ma Sophia Graciela L , Torres Chelseah Denise H , Liao Sophia Anne S P , Ortega Dorothy Jean N , Silang Abegail Visia Marie C , Uezono Deinzel R , Roxas Evalyn A , Salamat Maria Sonia S
Published: July 2020

Background

Intersectoral collaboration in the context of the prevention and control of vector-borne diseases has been broadly described in both the literature and the current global strategy by the World Health Organization. Our aim was to develop a framework that will distill the currently known multiple models of collaboration.

Methods

Qualitative content analysis and logic modeling of data abstracted from 69 studies included in a scoping review done by the authors were used to develop 9 recommendation statements that summarized the composition and attributes of multisectoral approaches, which were then subjected to a modified Delphi process with 6 experts in the fields of health policy and infectious diseases.

Results

Consensus for all statements was achieved during the first round. The recommendation statements were on (1–3) sectoral engagement to supplement government efforts and augment public financing; (4) development of interventions for most systems levels; (5–6) investment in human resource, including training; (7–8) intersectoral action to implement strategies and ensure sustainability of initiatives; and (9) research to support prevention and control efforts.

Conclusions

The core of intersectoral action to prevent vector-borne diseases is collaboration among multiple stakeholders to develop, implement, and evaluate initiatives at multiple levels of intervention.
Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review
Authors: Jacobs Tom G , Svensson Elin M , Musiime Victor , Rojo Pablo , Dooley Kelly E , McIlleron Helen , Aarnoutse Rob E , Burger David M , Turkova Anna , Colbers Angela ,   the WHO Paediatric Antiretroviral Working Group, Abrams Elaine , Archary Moherndran , Belew Yodit , Best Brookie , Burger David , Burry Jessica , Capparelli Edmund , Carpenter Deborah , Casas Esther , Clayden Polly , Clarke Diana , Cressey Tim , Colbers Angela , Dangarembizi Mutsa , Denti Paolo , Diop Karim , Ecker Andrea , Essajee Shaffiq , Giaquinto Carlo , Gibb Diana , Hazra Rohan , Kim Maria , Lallemant Marc , Lee Janice , Lewis Linda , Lockman Shahin , Mirochnick Mark , Mofenson Lynne , Musiime Victor , Obimbo Elizabeth , Ojoo Atieno , Pascual Fernando , Penazzato Martina , Pinto Jorge , Rakhmanina Natella , Rojo Pablo , Ruel Ted , Siberry George , Sugandhi Nandita , Turkova Anna , Vicari Marissa , Watkins Melynda , Wolf Hilary
Published: July 2020

Introduction

Management of concomitant use of ART and TB drugs is difficult because of the many drug–drug interactions (DDIs) between the medications. This systematic review provides an overview of the current state of knowledge about the pharmacokinetics (PK) of ART and TB treatment in children with HIV/TB co-infection, and identifies knowledge gaps.

Methods

We searched Embase and PubMed, and systematically searched abstract books of relevant conferences, following PRISMA guidelines. Studies not reporting PK parameters, investigating medicines that are not available any longer or not including children with HIV/TB co-infection were excluded. All studies were assessed for quality.

Results

In total, 47 studies met the inclusion criteria. No dose adjustments are necessary for efavirenz during concomitant first-line TB treatment use, but intersubject PK variability was high, especially in children <3 years of age. Super-boosted lopinavir/ritonavir (ratio 1:1) resulted in adequate lopinavir trough concentrations during rifampicin co-administration. Double-dosed raltegravir can be given with rifampicin in children >4 weeks old as well as twice-daily dolutegravir (instead of once daily) in children older than 6 years. Exposure to some TB drugs (ethambutol and rifampicin) was reduced in the setting of HIV infection, regardless of ART use. Only limited PK data of second-line TB drugs with ART in children who are HIV infected have been published.

Conclusions

Whereas integrase inhibitors seem favourable in older children, there are limited options for ART in young children (<3 years) receiving rifampicin-based TB therapy. The PK of TB drugs in HIV-infected children warrants further research.
Effects of zinc propionate supplementation on growth performance, skeletal muscle fiber, and receptor characteristics in beef steers
Authors: Wellmann Kimberly B , Baggerman Jessica O , Burson W Clay , Smith Zachary K , Kim Jongkyoo , Hergenreder Jerilyn E , Rounds Whitney , Bernhard Bryan C , Johnson Bradley J
Published: July 2020

A randomized complete block design experiment with 32 yearling crossbred steers (average body weight [BW] = 442 ± 17.0 kg) fed a steam-flaked corn-based diet was used to evaluate the effects of dietary Zn (KemTRACE Zn propionate 27; Kemin Industries, Inc., Des Moines, IA) supplementation on live growth performance, skeletal muscle fiber, and beta-adrenergic receptor (β-AR) characteristics during the finishing phase. Steers were blocked by BW (n = 4 blocks; 8 steers/block), assigned to pens (n = 4 steers/pen), and randomly assigned to the following treatments: control (CON; 0.0 g/[head (hd) · d] of additional Zn) or additional dietary Zn (ZnP; 1.0 g/[hd · d] additional Zn). The basal diet contained Zn (60 ppm dry matter basis) from ZnSO4; additional Zn was top-dressed at feeding. Ractopamine hydrochloride (RH; Optaflexx: Elanco Animal Health, Greenfield, IN) was included at 300 mg/(hd · d) for the final 28 d of the 111-d feeding period. Longissimus muscle biopsy samples, BW, and blood were obtained on days 0, 42, 79, and 107. Final BW was collected prior to shipping on day 111. Biopsy samples were used for immunohistochemical (IHC), mRNA, and protein analysis. Serum urea nitrogen (SUN) and nonesterified fatty acid (NEFA) concentrations were measured. Steers fed ZnP had a greater average daily gain (P = 0.02) and gain to feed ratio (G:F; P = 0.03) during the RH feeding period compared with CON. There were no differences (P > 0.05) in other growth performance variables, carcass traits, mRNA abundance, or relative protein concentration for fiber type and β-AR. Fiber types I and IIA had no differences in the cross-sectional area; however, the IIX area was greater for CON (P < 0.04) compared with ZnP and increased (P < 0.02) over time. There were no differences between treatments for the β1-AR density (P > 0.05) in skeletal muscle tissue throughout the study. A treatment × day interaction was observed in β2-AR density (P = 0.02) and β3-AR density (P = 0.02) during the RH feeding period, where the abundance of the receptors increased with ZnP but did not change in CON. Compared with CON, ZnP had greater (P < 0.01) mean NEFA concentrations. Mean SUN concentrations did increase by day (P < 0.01). Additional dietary Zn, supplied as Zn propionate, upregulates β2-AR and β3-AR and improves growth performance in feedlot steers during the RH feeding period, likely through a shift of resource utilization from lipogenesis to muscle maintenance and hypertrophy.
The Homelessness Crisis and Burn Injuries: A Cohort Study
Authors: Vrouwe Sebastian Q , Johnson Maxwell B , Pham Christopher H , Lane Christianne J , Garner Warren L , Gillenwater T Justin , Yenikomshian Haig A
Published: July 2020

The United States is facing a growing homelessness crisis. We characterize the demographics and outcomes of homeless patients who sustain burn injury and compare them to a cohort of domiciled patients. A retrospective cohort study was performed at the Los Angeles County + University of Southern California Regional Burn Center for consecutive acute burn admissions in adults from June 1, 2015, to December 31, 2018. Patients were categorized as either domiciled or homeless at the time of their injury. Prevalence rates were estimated using data from the regional homeless count. From 881 admissions, 751 (85%) had stable housing and 130 (15%) were homeless. The rate of burn injury requiring hospitalization for homeless adults was estimated at 88 per 100,000 persons. Homeless patients had a significantly larger median burn size (7 vs 5%, P < .05) and a greater rate of flame burns (68 vs 42%, P < .001). For the homeless, rates of assault and self-inflicted injury were 4- (18 vs 4%, P < .001) and 2-fold higher (9 vs 4%, P < .001), respectively. Homeless patients had higher rates of mental illness (32 vs 12%, P < .001) and substance abuse (88 vs 22%, P < .001), and were less likely to follow-up as outpatients (54 vs 87%, P < .001). There was no difference in mortality. Homeless patients had a longer median length of stay (LOS; 11 vs 7 days, P < .001) without significant differences in LOS per percentage TBSA. Homeless individuals should be considered a high-risk population for burn injury. This distinction serves as a call to action for the development of burn prevention strategies.
Descriptive epidemiology of incidence and mortality of primary liver cancer in 185 countries: evidence from GLOBOCAN 2018
Authors: Sharma Rajesh
Published: July 2020

Purpose

This study aims to examine the burden of primary liver cancer in 185 countries in 2018.

Methods

The estimates of incidence, mortality and prevalence of primary liver cancer were procured from GLOBOCAN 2018. The development status of a country was measured using the human development index—a composite indicator of income per capita, education and life expectancy.

Results

Globally, primary liver cancer resulted in an estimated 781 631 deaths at age-standardized mortality rate of 8.5/100 000, and 841 080 cases were estimated to be diagnosed in 2018. Males accounted for 596 574 cases and 548 375 deaths, which is more than twice the burden of primary liver cancer in females (cases: 244 506; deaths: 233 456). The global age-standardized incidence rate was 9.3/100 000 in 2018, varying from Morocco (1.1/100 000) to Mongolia (93.7/100 000). There were remarkable variations in terms of age-standardized mortality rate, too, which ranged from 1/100 000 in Nepal to 75.4/100 000 in Mongolia. East Asia was the top region contributing 55.6% of global cases and 54.7% of global deaths.

Conclusions

Since majority of the primary liver cancer burden pertains to hepatocellular carcinoma and screening approaches are yet to be fully proven, the policy focus must be on prevention approaches through the hepatitis-B vaccine, early detection of hepatitis-C infection, reduced alcohol consumption, obesity control, reduced aflatoxin exposure and containment of other modifiable risk factors.
The KMOS Lens-Amplified Spectroscopic Survey (KLASS): kinematics and clumpiness of low-mass galaxies at cosmic noon
Authors: Girard M , Mason C A , Fontana A , Dessauges-Zavadsky M , Morishita T , Amorín R , Fisher D B , Jones T , Schaerer D , Schmidt K B , Treu T , Vulcani B
Published: July 2020

We present results from the KMOS Lens-Amplified Spectroscopic Survey (KLASS), an ESO Very Large Telescope (VLT) large program using gravitational lensing to study the spatially resolved kinematics of 44 star-forming galaxies at 0.6 < z < 2.3 with a stellar mass of 8.1 < log(M⋆/M⊙) < 11.0. These galaxies are located behind six galaxy clusters selected from the Hubble Space Telescope Grism Lens-Amplified Survey from Space (GLASS). We find that the majority of the galaxies show a rotating disc, but most of the rotation-dominated galaxies only have a low υ rot/σ0 ratio (median of υrot/σ0 ∼ 2.5). We explore the Tully–Fisher relation by adopting the circular velocity, $V_{\mathrm{ circ}}=(\upsilon _{\mathrm{ rot}}^2+3.4\sigma _0^2)^{1/2}$, to account for pressure support. We find that our sample follows a Tully–Fisher relation with a positive zero-point offset of +0.18 dex compared to the local relation, consistent with more gas-rich galaxies that still have to convert most of their gas into stars. We find a strong correlation between the velocity dispersion and stellar mass in the KLASS sample. When combining our data to other surveys from the literature, we see an increase of the velocity dispersion with stellar mass at all redshift. We obtain an increase of υrot/σ0 with stellar mass at 0.5 < z < 1.0. This could indicate that massive galaxies settle into regular rotating discs before the low-mass galaxies. For higher redshift (z > 1), we find a weak increase or flat trend. We find no clear trend between the rest-frame UV clumpiness and the velocity dispersion and υrot/σ0. This could suggest that the kinematic properties of galaxies evolve after the clumps formed in the galaxy disc or that the clumps can form in different physical conditions.
Estimating local seeing at Observatorio Astronómico Nacional in San Pedro Mártir using CFD simulations of the atmospheric boundary layer
Authors: Sánchez García R , Richer M G , Gómez Martínez R , Avila R
Published: July 2020

We present computational fluid dynamics simulations of the atmospheric boundary layer (ABL) at the Observatorio Astronómico Nacional in the Sierra San Pedro Mártir (OAN-SPM) whose objective is to model the seeing observed at the site. We constrain the simulations using observations of the seeing, the vertical profile of the wind speed, and the vertical profile of the temperature, the first two resolved as a function of wind direction. We successfully model the seeing observed under typical wind conditions for each direction by adopting input profiles of the wind speed, the turbulent kinetic energy, and the energy dissipation. The resulting vertical profiles of the index of refraction structure constant are qualitatively similar to the mean profile derived from studies at the site.
The formation times and building blocks of Milky Way-mass galaxies in the FIRE simulations
Authors: Santistevan Isaiah B , Wetzel Andrew , El-Badry Kareem , Bland-Hawthorn Joss , Boylan-Kolchin Michael , Bailin Jeremy , Faucher-Giguère Claude-André , Benincasa Samantha
Published: July 2020

Surveys of the Milky Way (MW) and M31 enable detailed studies of stellar populations across ages and metallicities, with the goal of reconstructing formation histories across cosmic time. These surveys motivate key questions for galactic archaeology in a cosmological context: When did the main progenitor of an MW/M31-mass galaxy form, and what were the galactic building blocks that formed it? We investigate the formation times and progenitor galaxies of MW/M31-mass galaxies using the Feedback In Realistic Environments-2 cosmological simulations, including six isolated MW/M31-mass galaxies and six galaxies in Local Group (LG)-like pairs at z = 0. We examine main progenitor ‘formation’ based on two metrics: (1) transition from primarily ex-situ to in-situ stellar mass growth and (2) mass dominance compared to other progenitors. We find that the main progenitor of an MW/M31-mass galaxy emerged typically at z ∼ 3–4 ($11.6\!\!-\!\!12.2\, \rm {Gyr}$ ago), while stars in the bulge region (inner 2 kpc) at z = 0 formed primarily in a single main progenitor at z ≲ 5 (${\lesssim} \!12.6\, \rm {Gyr}$ ago). Compared with isolated hosts, the main progenitors of LG-like paired hosts emerged significantly earlier (Δz ∼ 2, $\Delta t\!\sim \!1.6\, \rm {Gyr}$), with ∼4× higher stellar mass at all z ≳ 4 (${\gtrsim} \!12.2\, \rm {Gyr}$ ago). This highlights the importance of environment in MW/M31-mass galaxy formation, especially at early times. On average, about 100 galaxies with $\rm {\it{ M}}_\rm {star}\!\gtrsim \!10^5\, \rm {M}_\odot$ went into building a typical MW/M31-mass system. Thus, surviving satellites represent a highly incomplete census (by ∼5×) of the progenitor population.
The effect of non-linear mutual friction on pulsar glitch sizes and rise times
Authors: Celora T , Khomenko V , Antonelli M , Haskell B
Published: July 2020

Observations of pulsar glitches have the potential to provide constraints on the dynamics of the high density interior of neutron stars. However, to do so, realistic glitch models must be constructed and compared to the data. We take a step towards this goal by testing non-linear models for the mutual friction force, which is responsible for the exchange of angular momentum between the neutron superfluid and the observable normal component in a glitch. In particular, we consider a non-linear dependence of the drag force on the relative velocity between superfluid vortices and the normal component, in which the contributions of both kelvin and phonon excitations are included. This non-linear model produces qualitatively new features, and is able to reproduce the observed bimodal distribution of glitch sizes in the pulsar population. The model also suggests that the differences in size distributions in individual pulsars may be due to the glitches being triggered in regions with different pinning strengths, as stronger pinning leads to higher vortex velocities and a qualitatively different mutual friction coupling with respect to the weak pinning case. Glitches in pulsars that appear to glitch quasi-periodically with similar sizes may thus be due to the same mechanisms as smaller events in pulsars that have no preferred glitch size, but simply originate in stronger pinning regions, possibly in the core of the star.
The low-luminosity Type II SN 2016aqf: a well-monitored spectral evolution of the Ni/Fe abundance ratio
Authors: Müller-Bravo Tomás E , Gutiérrez Claudia P , Sullivan Mark , Jerkstrand Anders , Anderson Joseph P , González-Gaitán Santiago , Sollerman Jesper , Arcavi Iair , Burke Jamison , Galbany Lluís , Gal-Yam Avishay , Gromadzki Mariusz , Hiramatsu Daichi , Hosseinzadeh Griffin , Howell D Andrew , Inserra Cosimo , Kankare Erki , Kozyreva Alexandra , McCully Curtis , Nicholl Matt , Smartt Stephen , Valenti Stefano , Young Dave R
Published: July 2020

Low-luminosity Type II supernovae (LL SNe II) make up the low explosion energy end of core-collapse SNe, but their study and physical understanding remain limited. We present SN 2016aqf, an LL SN II with extensive spectral and photometric coverage. We measure a V-band peak magnitude of −14.58 mag, a plateau duration of ∼100 d, and an inferred 56Ni mass of 0.008 ± 0.002 M⊙. The peak bolometric luminosity, Lbol ≈ 1041.4 erg s−1, and its spectral evolution are typical of other SNe in the class. Using our late-time spectra, we measure the [O i] λλ6300, 6364 lines, which we compare against SN II spectral synthesis models to constrain the progenitor zero-age main-sequence mass. We find this to be 12 ± 3 M⊙. Our extensive late-time spectral coverage of the [Fe ii] λ7155 and [Ni ii] λ7378 lines permits a measurement of the Ni/Fe abundance ratio, a parameter sensitive to the inner progenitor structure and explosion mechanism dynamics. We measure a constant abundance ratio evolution of $0.081^{+0.009}_{-0.010}$ and argue that the best epochs to measure the ratio are at ∼200–300 d after explosion. We place this measurement in the context of a large sample of SNe II and compare against various physical, light-curve, and spectral parameters, in search of trends that might allow indirect ways of constraining this ratio. We do not find correlations predicted by theoretical models; however, this may be the result of the exact choice of parameters and explosion mechanism in the models, the simplicity of them, and/or primordial contamination in the measured abundance ratio.
Machine learning classification of Kuiper belt populations
Authors: Smullen Rachel A , Volk Kathryn
Published: July 2020

In the outer Solar system, the Kuiper belt contains dynamical subpopulations sculpted by a combination of planet formation and migration and gravitational perturbations from the present-day giant planet configuration. The subdivision of observed Kuiper belt objects (KBOs) into different dynamical classes is based on their current orbital evolution in numerical integrations of their orbits. Here, we demonstrate that machine learning algorithms are a promising tool for reducing both the computational time and human effort required for this classification. Using a Gradient Boosting Classifier, a type of machine learning regression tree classifier trained on features derived from short numerical simulations, we sort observed KBOs into four broad, dynamically distinct populations – classical, resonant, detached, and scattering – with a >97 per cent accuracy for the testing set of 542 securely classified KBOs. Over 80 per cent of these objects have a >3σ probability of class membership, indicating that the machine learning method is classifying based on the fundamental dynamical features of each population. We also demonstrate how, by using computational savings over traditional methods, we can quickly derive a distribution of class membership by examining an ensemble of object clones drawn from the observational errors. We find two major reasons for misclassification: inherent ambiguity in the orbit of the object – for instance, an object that is on the edge of resonance – and a lack of representative examples in the training set. This work provides a promising avenue to explore for fast and accurate classification of the thousands of new KBOs expected to be found by surveys in the coming decade.