bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the safety and efficacy of suction‐tip forceps, a new tool for laparoscopic surgery, for gastric cancer
Authors: Sakurazawa Nobuyuki , Harada Jun‐ichiro , Ando Fumihiko , Arai Hiroki , Kuge Komei , Matsumoto Satoshi , Kawano Youichi , Matsuda Akihisa , Suzuki Hideyuki , Yoshida Hiroshi
Published: September 2020

Introduction

Laparoscopic surgery is a minimally invasive surgery; however, obstacles to its functional optimization remain. Surgical ports can accommodate only one instrument at a time so complex exchange manipulations are necessary during surgery which increases operation times and patient risk. We developed a new laparoscopic instrument that functions as both forceps and a suction tube, which renders intraoperative tool exchange unnecessary. This pilot study was undertaken to evaluate the safety and efficacy of this novel dual‐function device in laparoscopic surgery for gastric cancer.

Methods

This single‐center pilot study assessed patient safety during and after laparoscopic distal gastrectomy for gastric cancer with the suction‐forceps using intraoperative video and clinical follow‐up, respectively. To evaluate instrument efficacy, we measured the time interval between the start of any bleeding and the start of aspiration (“suction access time”) and compared this time with that of a conventional surgical setup.

Results

In total 15 patients participated, with all procedures being successful. No excess tissue damage occurred during surgery. Suction access time was significantly shorter in cases of bleeding when the suction‐tip forceps were used for aspiration (2.01 seconds) compared to an ordinary suction tube (12.5 seconds; P < .01).

Conclusion

These findings suggest that our new suction‐tip forceps are a useful, safe, and efficacious operative tool. This surgical innovation may considerably simplify gastric laparoscopic surgery. This pilot study was registered with Japan Clinical Trial Registration on 22 June 2017 (registration number: UMIN000027879).
Baclofen destabilises breathing during sleep in healthy humans: A randomised, controlled, double‐blind crossover trial
Authors: Straus Christian , Teulier Marion , Morel Sébastien , Wattiez Nicolas , Hajage David , Giboin Caroline , Charbit Beny , Dasque Eric , Bodineau Laurence , Chenuel Bruno , Straus Nicolas , Attali Valérie , Similowski Thomas
Published: September 2020

Aims

Periodic breathing is frequent in patients with severe heart failure. Apart from being an indicator of severity, periodic breathing has its own deleterious consequences (sleep‐related oxygen desaturations, sleep fragmentation), which justifies attempts to correct it irrespective of the underlying disease. Animal models and human data suggest that baclofen can reconfigure respiratory central pattern generators. We hypothesised that baclofen, a GABAB agonist, may thus be able to correct periodic breathing in humans.

Methods

Healthy volunteers were exposed to hypoxia during sleep. Participants who developed periodic breathing (n = 14 [53 screened]) were randomly assigned to double‐blind oral baclofen (progressively increased to 60 mg/d) or placebo. The primary outcome was the coefficient of variation (CoVar) of respiratory cycle total time considered as an indicator of breathing irregularity. Secondary outcomes included the CoVar of tidal volume, apnoea–hypopnoea index, sleep fragmentation index and ventilatory complexity (noise limit).

Results

The analysis was conducted in 9 subjects after exclusion of incomplete datasets. CoVar of respiratory cycle total time significantly increased with baclofen during non‐rapid eye movement sleep (median with placebo 56.00% [37.63–78.95]; baclofen 85.42% [68.37–86.40], P = .020; significant difference during the N1‐N2 phases of sleep but not during the N3 phase). CoVar of tidal volume significantly increased during N1‐N2 sleep. The apnoea–hypopnoea index, sleep fragmentation index and ventilatory complexity were not significantly different between placebo and baclofen.

Conclusion

Baclofen did not stabilise breathing in our model. On the contrary, it increased respiratory variability. Baclofen should probably not be used in patients with or at risk of periodic breathing.
A meta‐analysis of the influence of ADRB2 genetic polymorphisms on albuterol (salbutamol) therapy in patients with asthma
Authors: Hikino Keiko , Kobayashi Shinobu , Ota Erika , Mushiroda Taisei , Urayama Kevin Y. , Kobayashi Tohru
Published: September 2020

Aims

The associations of 2 nonsynonymous single nucleotide polymorphisms (Arg16Gly and Gln27Glu) in the adrenoceptor β2 (ADRB2) gene with response after albuterol use are conflicting. We conducted a meta‐analysis to examine the cumulative evidence of the effects of these 2 variants on percent forced expiratory volume in 1 second (FEV1.0%) after albuterol use in asthma patients.

Methods

We conducted a comprehensive literature search using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify studies examining the association between ADRB2 Arg16Gly and Gln27Glu and FEV1.0% shortly after albuterol administration. The individual study results were combined with weights based on the inverse variance method. This systematic review was registered in the PROSPERO (registration number: CRD42019074554).

Results

Among 273 initial studies identified, 7 studies met the inclusion criteria for quantitative evaluation. Results of the overall meta‐analysis indicated no statistically significant mean difference of FEV1.0% between genotypes of Arg16Gly and Gln27Glu. In subgroup analyses, significant associations were found for Arg16Gly GG (vs AA) among studies where no methacholine bronchoconstriction was conducted (mean difference, −3.92; 95% confidence interval, −7.29 to −0.54; I2 = 0%), and for Arg16Gly GG (vs GA) among studies that included patients with no comorbidities (mean difference, −1.93; 95% confidence interval, −3.77 to −0.10; I2 = 0%).

Conclusion

Synthesis of the studies to date shows weak evidence for an association between ADRB2 Arg16Gly and Gln27Glu and FEV1.0% after albuterol use, results of which underscore significant heterogeneity across studies and the need for careful design and sample size considerations.
Assertiveness and adaptation: Prospective teachers’ social competence development and its significance for occupational well‐being
Authors: Carstensen Bastian , Klusmann Uta
Published: September 2020

Background

Difficult social interactions with students are reported to be among the main stressors of beginning teachers, and although social competence has been suggested to represent a vital resource for their transition into practice and early‐career adaptation, this assumption has rarely been empirically studied.

Aim

We conducted two studies to investigate the predictive validity and development of prospective and beginning teachers’ social competence. In Study 1, we examined, whether social competence predicts beginning teachers’ emotional exhaustion. Study 2 investigated whether university teacher training contributes to social competence development among prospective teachers.

Sample

The samples of both studies are based on large‐scale assessments. Participants in Study 1 were 1,758 beginning teachers who had been tracked since their entry into university teacher training. Study 2 included 831 prospective teachers who were surveyed over a total period of two years.

Methods

Data were analysed utilizing a structural equation modelling approach (Study 1) and latent change score modelling (Study 2).

Results

The results of Study 1 revealed that social competence negatively predicts emotional exhaustion. Further, beginning teachers’ reports of classroom management functioned as a mediator within that relationship. According to the findings in Study 2, prospective teachers showed no significant enhancements of social competence within one year of university teacher training. However, there was a significant change considering the two‐year interval.

Conclusions

Social competence, as a predictor of occupational well‐being, may constitute one important resource for the early‐career adaptation of beginning teachers. However, efforts to promote social competence within university teacher training should be increased.
The impact of teacher engagement in an interactive webinar series on the effectiveness of financial literacy education
Authors: Compen Boukje , De Witte Kristof , Schelfhout Wouter
Published: September 2020

This study examines whether online teacher professional development (OTPD), in the form of an interactive webinar series that encourages collaborative learning, improves student achievement. We conducted a randomised controlled trial with 1102 students, 45 teachers and 30 secondary schools in Flanders, Belgium. As a basis for the study, we developed a digital learning path aimed at improving student scores on financial literacy–a multidimensional key competence recently integrated into the curriculum. We demonstrate that the learning path improves student learning outcomes and that enhanced teacher involvement in this programme does not increase learning outcomes unless the teachers participate in the OTPD initiative. Teacher engagement in the webinar series generated student learning outcomes 0.39 standard deviations higher than those of students whose teachers did not receive this intervention, thus, confirming the effectiveness of the OTPD initiative. This effect was found immediately after programme implementation, and it persisted until at least 6 weeks later. As an underlying mechanism, we observe that engagement in the webinar series enhances teachers' self‐efficacy. Classroom observations suggest that engagement increases the frequency of providing students with content‐related help.
Effects of an immersive virtual reality‐based classroom on students’ learning performance in science lessons
Authors: Liu Ruixue , Wang Lei , Lei Jing , Wang Qiu , Ren Youqun
Published: September 2020

The increased availability and development of immersive technologies have given students growing opportunities to engage in different educational subjects. However, there is a lack of empirical research exploring the educational influence of using Immersive Virtual Reality (IVR) in science classrooms. To address this gap, this study developed a series of IVR‐based science lessons for middle‐school students and further examined these lessons’ effects on learning performance. Our quasi‐experimental approach employed a pretest and posttest to measure academic achievement and questionnaires to measure engagement and technology acceptance. A total of 90 sixth‐grade students from two classes were randomly assigned to the experimental and control groups. The experimental group engaged with the science lessons using Head‐Mounted Displays, whereas the control group learned the same material through traditional teaching methods. The results revealed that the experimental group obtained significantly higher academic achievement and engagement scores (cognitive, behavioral, emotional and social) than the control group. Moreover, the experimental group had a high level of technology acceptance for IVR usage in classrooms. Our study provides empirical evidence for IVR’s use in science education. Furthermore, it also sheds light on how to develop and implement an IVR‐based classroom for formal educational purposes.

Practitioner Notes

What is already known about this topic?

Virtual Reality (VR) technology has been applied to different educational subjects and there is some empirical evidence indicating its potential benefits for students’ learning.

VR is considered to have potential for educational uses in classrooms.

Many studies have applied non‐immersive VR to science subjects, but few have focused on the use of Immersive VR (IVR) in everyday classrooms.

What this paper adds

We developed and implemented an IVR‐based teaching platform containing a set of systematic science lessons that students can engage in with Head‐Mounted Displays in classrooms.

The results revealed that adopting IVR science lessons in the classroom can improve students’ academic achievement and engagement.

Implications for practice and/or policy

This study contributes to identifying the positive influences of an IVR‐based classroom on students’ science academic achievement and engagement.

The results provide practical insights into developing and implementing an IVR‐based classroom for educational purposes.

This study offers a concrete example of using IVR in middle‐school classrooms for formal science education.
Benefits of being ambivalent: The relationship between trait ambivalence and attribution biases
Authors: Schneider Iris K. , Novin Sheida , van Harreveld Frenk , Genschow Oliver
Published: September 2020

Ambivalence refers to the experience of having both positive and negative thoughts and feelings at the same time about the same object, person, or issue. Although ambivalence research has focused extensively on negative consequences, recently, scholars turned their lens to the positive effects of ambivalence, demonstrating beneficial effects on judgements and decision‐making processes. So far, this work has focused on state ambivalence, which is ambivalence as a direct response to a specific stimulus. However, there are substantial individual differences in ambivalence: Some people are just more ambivalent than others. Taking a first step in understanding how these individual differences relate to judgement and decision‐making, we examine the relationship between trait ambivalence and cognitive bias in social judgements tasks. Specifically, we look at two of the most pervasive and consequential attribution biases in person perception: correspondence bias and self‐serving bias. We find a negative relationship between trait ambivalence and correspondence bias. The higher individuals are in trait ambivalence, the smaller their bias towards attributing behaviour to a person’s disposition (Study 1A and B). We find the same for self‐serving bias (Study 2A and B). In sum, we show that trait ambivalence is negatively related to cognitive bias in person perception.
Identification and characterization of a novel adiponectin receptor agonist adipo anti‐inflammation agonist and its anti‐inflammatory effects in vitro and in vivo
Authors: Qiu Wei , Wu Hongle , Hu Zhekai , Wu Xingwen , Tu Maxwell , Fang Fuchun , Zhu Xiaofang , Liu Yao , Lian Junxiang , Valverde Paloma , Van Dyke Thomas , Steffensen Bjorn , Dong Lily Q. , Tu Qisheng , Zhou Xuedong , Chen Jake
Published: September 2020

Background and Purpose

Adiponectin (APN) is an adipokine secreted from adipocytes that binds to APN receptors AdipoR1 and AdipoR2 and exerts an anti‐inflammatory response through mechanisms not fully understood. There is a need to develop small molecules that activate AdipoR1 and AdipoR2 and to be used to inhibit the inflammatory response in lipopolysaccharide (LPS)‐induced endotoxemia and other inflammatory disorders.

Experimental Approach

We designed 10 new structural analogues of an AdipoR agonist, AdipoRon (APR), and assessed their anti‐inflammatory properties. Bone marrow‐derived macrophages (BMMs) and peritoneal macrophages (PEMs) were isolated from mice. Levels of pro‐inflammatory cytokines were measured by reverse transcription and real‐time quantitative polymerase chain reaction (qRT‐PCR), enzyme‐linked immunosorbent assay (ELISA) and microarray in LPS‐induced endotoxemia mice and diet‐induced obesity (DIO) mice in which systemic inflammation prevails. Western blotting, immunohistochemistry (IHC), siRNA interference and immunoprecipitation were used to detect signalling pathways.

Key Results

A novel APN receptor agonist named adipo anti‐inflammation agonist (AdipoAI) strongly suppresses inflammation in DIO and endotoxemia mice, as well as in cultured macrophages. We also found that AdipoAI attenuated the association of AdipoR1 and APPL1 via myeloid differentiation marker 88 (MyD88) signalling, thus inhibiting activation of nuclear factor kappa B (NF‐κB), mitogen‐activated protein kinase (MAPK) and c‐Maf pathways and limiting the production of pro‐inflammatory cytokines in LPS‐induced macrophages.

Conclusion and Implications

AdipoAI is a promising alternative therapeutic approach to APN and APR to suppress inflammation in LPS‐induced endotoxemia and other inflammatory disorders via distinct signalling pathways.
Commentary: What is unsought will go undetected – a commentary on Rodin et al. (2020)
Authors: Malik Osman
Published: September 2020

Rodin et al.'s study (2020) on the belief, knowledge and attitudes about tics amongst health professionals in Uganda is a preliminary yet an important step towards challenging the current thinking amongst clinicians and academics working with tics, which is that tics are hardly seen in or are absent in the sub‐Saharan African population and it has been psotulated that this phenomenon is considered to be explained by genetics.
Sensitivity to Visual‐Tactile Colocation on the Body Prior to Skilled Reaching in Early Infancy
Authors: Begum Ali Jannath , Thomas Rhiannon L. , Mullen Raymond Stephanie , Bremner Andrew J.
Published: September 2020

Two experiments examined perceptual colocation of visual and tactile stimuli in young infants. Experiment 1 compared 4‐ (n = 15) and 6‐month‐old (n = 12) infants’ visual preferences for visual‐tactile stimulus pairs presented across the same or different feet. The 4‐ and 6‐month‐olds showed, respectively, preferences for colocated and noncolocated conditions, demonstrating sensitivity to visual‐tactile colocation on their feet. This extends previous findings of visual‐tactile perceptual colocation on the hands in older infants. Control conditions excluded the possibility that both 6‐ (Experiment 1), and 4‐month‐olds (Experiment 2, n = 12) perceived colocation on the basis of an undifferentiated supramodal coding of spatial distance between stimuli. Bimodal perception of visual‐tactile colocation is available by 4 months of age, that is, prior to the development of skilled reaching.
Nation Branding for China: Global Brokers in International Real Estate in China
Authors: Badaró Máximo
Published: September 2020

In this article I examine “nation branding” strategies in the marketing of international real estate in China. In their push to secure Chinese customers on global markets worldwide, many Western corporate actors incorporate commercial strategies that aim to enhance the appeal of the nations and cities where the sale properties are located. Their marketing narratives equate investment in foreign real estate with an investment in “quality of life”, and promote the figure of the “immigrant investor” as a way of belonging to foreign countries. The analysis focuses on the competing narratives, insecurities and hesitations of foreign real estate agencies working on China’s international real estate market. The article is based on fieldwork I conducted in China between 2014 and 2016, observing international real estate trade shows, conducting interviews with real estate agents, and reviewing promotional materials.
Economics of household food waste
Authors: Lusk Jayson L. , Ellison Brenna
Published: September 2020

Food waste has drawn increasing public attention, and the high levels of estimated waste are largely considered to be a failure of our current food system. Recently, economists have begun to weigh in, showing food waste can emerge as the result of a complex equilibrium affected by consumers’ preferences for convenience; expectations about future food prices and availability; food safety concerns; producers’ costs of holding inventory, transportation, and storage; government regulation; and technology. If food waste is a form of inefficiency, there are either strong economic motivations to reduce waste, or unmeasured costs or preferences affecting waste decisions. If consumers have behavioral biases, suffer from information asymmetries, or do not pay the full cost of their waste, there may be a role for government intervention to reduce waste, but most empirical models in the literature have not articulated or quantified the extent of the deadweight loss from the market failures in relation to food waste. In some cases, waste reduction efforts could harm producers if overall demand for food is reduced or harm consumers if overconsumption is encouraged, quality or safety degrades, or supply disruptions occur. Technological innovations, which lower the cost of storage or extend shelf life have the potential to improve both consumer and producer welfare.
POINTS OR PRISON? THE EFFECTS OF DIFFERENT SANCTIONS ON DRIVING BEHAVIOR
Authors: Bruzzone Silvia , Castriota Stefano , Tonin Mirco
Published: September 2020

We compare two reforms aimed at reducing road accidents in Italy. The Penalty Points System (PPS) provides drivers with a score and curtails points after infractions. The license is temporarily suspended when points are exhausted. Losing points is easy, but the penalty is mild. The Road Homicide (RH) introduces heavy penalties in the rare event of injuries and/or fatalities. In terms of probability and intensity of the penalty the two policies are therefore diametrically opposed. We find that injuries and fatalities decrease more with PPS than with RH. Comparing costs and benefits, we conclude that strong penalties are not beneficial. (JEL D91, K14, K42, R41)
Coupling property rights with responsibilities to improve conservation outcomes across land and seascapes
Authors: Moon Katie , Marsh Dru , Cvitanovic Christopher
Published: September 2020

Protecting biodiversity in the face of contemporary conservation challenges requires actions across all land and sea tenures. In seeking improved conservation outcomes across these tenures, we undertook a multidisciplinary review of the property law, conservation and environmental ethics literature. Our review revealed three major threats of property rights to conservation: a focus on tangible goods at the expense of intangible services, a focus on the plot rather than the land or seascape and a focus on rights over responsibilities. Our analysis reveals that overcoming these threats requires a blending of the construct of property with both ecological principles and social values. To this end, we offer a practical, solutions‐focused approach that seeks to determine who has a responsibility, to whom they owe that responsibility and how that responsibility can be ascribed. This approach couples specific property rights with defined responsibilities owed to resource systems to support current and future beneficiaries. A formal recognition of the responsibilities that accompany rights can set the baseline of what society should be able to expect from rights‐holders. From this baseline, policy instruments can be more appropriately applied, supporting landholders in their responsibilities and where necessary, providing compensation for activities that extend beyond their responsibilities.
CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos
Authors: Ju Jia‐Qian , Li Xiao‐Han , Pan Meng‐Hao , Xu Yao , Sun Ming‐Hong , Xu Yi , Sun Shao‐Chen
Published: September 2020

Objectives

DNA damage and errors of accurate chromosome segregation lead to aneuploidy and foetal defects. DNA repair and the spindle assembly checkpoint (SAC) are the mechanisms developed to protect from these defects. Checkpoint kinase 1 (CHK1) is reported to be an important DNA damage response protein in multiple models, but its functions remain unclear in early mouse embryos.

Materials and Methods

Immunofluorescence staining, immunoblotting and real‐time reverse transcription polymerase chain reaction were used to perform the analyses. Reactive oxygen species levels and Annexin‐V were also detected.

Results

Loss of CHK1 activity accelerated progress of the cell cycle at the first cleavage; however, it disturbed the development of early embryos to the morula/blastocyst stages. Further analysis indicated that CHK1 participated in spindle assembly and chromosome alignment, possibly due to its regulation of kinetochore‐microtubule attachment and recruitment of BubR1 and p‐Aurora B to the kinetochores, indicating its role in SAC activity. Loss of CHK1 activity led to embryonic DNA damage and oxidative stress, which further induced early apoptosis and autophagy, indicating that CHK1 is responsible for interphase DNA damage repair.

Conclusions

Our results indicate that CHK1 is a key regulator of the SAC and DNA damage repair during early embryonic development in mice.
MiR‐22‐3p inhibits fibrotic cataract through inactivation of HDAC6 and increase of α‐tubulin acetylation
Authors: Wang Xiaoran , Wang Liping , Sun Yan , Chen Baoxin , Xiong Lang , Chen Jieping , Huang Mi , Wu Jing , Tan Xuhua , Zheng Yingfeng , Huang Shan , Liu Yizhi
Published: September 2020

Objectives

Fibrotic cataract, including posterior capsule opacification (PCO) and anterior subcapsular cataract (ASC), renders millions of people visually impaired worldwide. However, the underlying mechanism remains poorly understood. Here, we report a miRNA‐based regulatory pathway that controls pathological fibrosis of lens epithelium.

Materials and methods

Expression of miR‐22‐3p and histone deacetylase 6 (HDAC6) in normal and PCO patient samples were measured by qPCR. Human lens epithelial explants were treated with TGF‐β2 in the presence or absence of miR‐22‐3p mimics or inhibitor. Cell proliferation was determined by MTS assay, and migration was tested by transwell assay. Expression of HDAC6 and EMT‐related molecules were analysed by Western blot, qPCR and immunocytochemical experiments.

Results

We identify miR‐22‐3p as a downregulated miRNA targeting HDAC6 in LECs during lens fibrosis and TGF‐β2 treatment. Mechanistically, gain‐ and loss‐of‐function experiments in human LECs and lens epithelial explants reveal that miR‐22‐3p prevents proliferation, migration and TGF‐β2 induced EMT of LECs via targeting HDAC6 and thereby promoting α‐tubulin acetylation. Moreover, pharmacological targeting of HDAC6 deacetylase with Tubacin prevents fibrotic opaque formation through increasing α‐tubulin acetylation under TGF‐β2 stimulated conditions in both human lens epithelial explants and the whole rat lenses.

Conclusions

These findings suggest that miR‐22‐3p prevents lens fibrotic progression by targeting HDAC6 thereby promoting α‐tubulin acetylation. The ‘miR‐22‐HDAC6‐α‐tubulin (de)acetylation’ signalling axis may be therapeutic targets for the treatment of fibrotic cataract.
Uniqueness of laryngeal nerve injury following heart transplantation
Authors: de la Rosa Angelo , Aguilar Jack , Barbu Anca M. , Chang David , Kobashigawa Jon
Published: September 2020

Background

The incidence of recurrent laryngeal nerve injury (RLNI) after heart transplantation has not been well studied. This can manifest as vocal cord dysfunction causing dysphonia. Previous research is limited to aortic, coronary bypass, and valvular surgery. Identifying RLNI after heart transplantation is important in order to more accurately detail complications associated with this major surgery.

Methods

This is a retrospective study assessing 972 adult patients who underwent orthotopic heart transplantation between 2010‐2019. Primary outcome was incidence of RLNI. Secondary outcomes were 1‐year mortality and length of stay. Cardiology and otolaryngology notes were examined. Key word searches were used to identify possible RLNI in patients' health care record.

Results

2.9% (29/972) of patients developed new RLNI confirmed by laryngoscopy during hospitalization. Patients with RLNI had a significantly increased risk of 1‐year mortality (P = .015) and length of stay (P = .006) compared to those without RLNI. 68.9% (20/29) of RLNI was left‐sided (68.9%).

Conclusions

Recurrent laryngeal nerve injury is a recognizable adverse outcome following heart transplantation. This study supports that RLNI is associated with increased 1‐year mortality and length of stay. Early otolaryngology evaluation may be warranted to evaluate vocal cord mobility and address potential management.
Insights on the Evidence of Cardiotoxicity of Hydroxychloroquine Prior and During COVID‐19 Epidemic
Authors: Romani Serena , Gérard Alexandre , Fresse Audrey , Viard Delphine , Van‐Obberghen Élise , Micallef Joëlle , Rocher Fanny , Drici Milou‐Daniel ,   the French Pharmacovigilance Network
Published: September 2020

The recent empirical use of hydroxychloroquine (HCQ) in coronavirus disease 2019 (COVID‐19) revived the interest in its cardiac toxicity, increasingly sidelined over time. We aimed to assess and compare the profile of cardiac adverse drug reactions (CADRs) associated with HCQ before and during COVID‐19. We performed a retrospective comparative observational study using the French Pharmacovigilance network database between 1985 and May 2020 to assess all postmarketing CADRs associated with HCQ notified before COVID‐19 in its approved indications for lupus and rheumatoid arthritis (preCOV), and those concerning its empirical use in COVID‐19 (COV). Eighty‐five CADR in preCOV were compared with 141 CADRs in COV. The most common CADR of preCOV were cardiomyopathies (42.4%) and conduction disorders (28.2%), both statistically more frequent than in COV (P < 0.001). COV notifications significantly highlighted repolarization and ventricular rhythm disorders (78.0%, P < 0.001) as well as sinus bradycardias (14.9%, P = 0.01) as compared with preCOV. Estimated incidence of CADR was significantly higher among patients exposed to off‐label use of HCQ in COVID‐19 (2.9%) than before COVID‐19 in its approved indications (0.01%, P < 0.001). The use of HCQ in COVID‐19 sheds a new light on the spectrum of its cardiac toxicity. This fosters the value of a closer monitoring of all patients treated with HCQ, regardless of its indication, and the importance of an update of its summary of product characteristics.
Seeking an ethical theory for the COVID‐19 pandemic outbreak with special reference to Bangladesh’s law and policy
Authors: Bhuiyan A S M Anwarullah
Published: September 2020

Globally, a traditional management model has generally been used to manage disaster situations, including in Bangladesh. In Bangladesh, the government mostly uses the preparedness policy for pandemic outbreak case management. With regard to the limitations arising from the pandemic outbreak the current research will investigate the following questions: when facing a devastating situation, what exactly is the nature of the pandemic outbreak management model incorporated at the governmental level? Keeping these questions in mind, the intention of the existing model is to provide smooth and appropriate assistance to recover from a pandemic outbreak, and to implement effective governance of the situation. This research will identify deficiencies in the current epidemic management policy in Bangladesh, and will assist in forming a new model and developing a systematic procedure for managing future pandemic outbreak situations. The main deficiency in Bangladesh’s pandemic management is that the policy paper has failed to identify all hazardous events that may occur in a pandemic outbreak. In most cases, it has underestimated the issues of bioethical responsibility toward the different stakeholders affected during the devastating situation of a pandemic outbreak. The policy does not emphasize the bioethical model; therefore, it fails to encourage support for either public protection or an ethically friendly management system. The model proposed in this article demonstrates an appropriate way to reduce or, if possible, avoid potential damages and losses from a pandemic outbreak. The model aims to prioritize the problems that need assistance to recover from the outbreak.
Circling the wagons or opening the circle
Authors: Pally Marcia
Published: September 2020

“To approach eudaimonia or human flourishing,” Darcia Narvaez writes, “one must have a concept of human nature… a normal baseline.” This article asks: what is the human baseline so that we may develop public policy to suit and advance human and planetary flourishing? It proposes that our “baseline” is relational, where each person becomes her singular self through networks of relations with others and planet. Relationality is explored through Trinity, covenant, evolutionary biology, and psychology. The article concludes that public policy must be grounded not in “us‐them” thinking but in relationality as this is how we are created.
Effect of fully automated closed‐loop insulin delivery using faster aspart versus standard aspart on gluco‐regulatory hormones in type 2 diabetes
Authors: Herzig David , Studer David , Nakas Christos T , Kuenzli Christina , Stauffer Thomas P , Hovorka Roman , Bally Lia
Published: September 2020

We retrospectively assessed gluco‐regulatory hormones over 10 h (including two meals) of fully automated closed‐loop insulin delivery using faster (FA) versus standard insulin aspart (IAsp) in adults with type 2 diabetes [n = 15, age 59 ± 10 years, body mass index 34.5 ± 9.1 kg/m2, glycated haemoglobin 7.7 ± 1.2% (60 ± 13 mmol/mol)]. Plasma concentration of human insulin, IAsp, C‐peptide, glucagon, glucagon‐like peptide 1, glucose‐dependent insulinotropic peptide and peptide tyrosine tyrosine were measured every 15‐30 min. Endogenous insulin secretion was calculated using C‐peptide deconvolution and exposures to hormones were compared using their mean plasma concentrations. Ten‐hour exposure of IAsp was higher with FA versus IAsp (P = .037) in line with the 10% higher insulin requirements to achieve similar glucose control. No significant difference was found for total insulin exposure and endogenous insulin secretion. Similarly, other gluco‐regulatory hormones did not significantly differ. In conclusion, the faster pharmacokinetic profile and slightly higher aspart exposure of FA versus IAsp remained without significant effects on endogenous insulin secretion or other gluco‐regulatory hormones. Further studies are warranted to explore the metabolic and endocrine effects of novel insulins with accelerated pharmacokinetic properties.
Evidence‐based weight loss interventions: Individualized treatment options to maximize patient outcomes
Authors: Bray George A. , Ryan Donna H.
Published: September 2020

Against the backdrop of obesity as a major public health problem, we examined three questions: How much weight loss is needed to benefit patients with obesity? How well do current therapies do in producing weight loss? What strategies can be used to improve patient outcomes using evidence‐based studies. This paper reviews literature on the outcomes of lifestyle, diet, medications and surgical treatments for obesity using literature searches for obesity treatments. Current treatments, including lifestyle, diet and exercise, produce a weight loss of 5% to 7% on average. Despite continued attempts to identify superior dietary approaches, most careful comparisons find that low carbohydrate diets are not significantly better than low fat diets for weight loss. The four medications currently approved by the US Food and Drug Administration for long‐term management of obesity are not as effective as surgery, adding about 5% on average to lifestyle approaches to weight loss. Two new medications that are under investigation, semaglutide and tirzepatide, significantly improve on this. For all treatments for weight loss, including lifestyle, medications and surgery, there is enormous variability in the amount of weight lost. Examination of this literature has yielded evidence supporting baseline and process predictors, but the effect sizes associated with these predictors are small and there are no prospective studies showing that a personalized approach based on genotype or phenotype will yield uniform success. Because obesity is a chronic disease it requires a ‘continuous treatment model’ across the lifespan.
Dimensionless index of the mitral valve for evaluation of degenerative mitral stenosis
Authors: Oktay Ahmet Afşin , Riehl Russell , Kachur Sergey , Khan Zahoor , Tutor Austin , Chainani Vinod , Cash Michael E. , Shah Sangeeta , Lavie Carl J. , Morin Daniel P. , Gilliland Yvonne E. , Qamruddin Salima
Published: September 2020

Purpose

Degenerative mitral stenosis (DMS) is an increasingly recognized cause of mitral stenosis. The goal of this study was to compare echocardiographic differences between DMS and rheumatic mitral stenosis (RMS), identify echocardiographic variables reflective of DMS severity, and propose a dimensionless mitral stenosis index (DMSI) for assessment of DMS severity.

Methods

This is a single‐center, retrospective cohort study. We included patients with at least mild MS and a mean transmitral pressure gradient (TMPG) ≥4 mm Hg. Mitral valve area by the continuity equation (MVACEQ) was used as an independent reference. The DMSI was calculated as follows: DMSI = VTILVOT/ VTIMV. All‐cause mortality data were collected retrospectively.

Results

A total of 64 patients with DMS and 24 patients with RMS were identified. MVACEQ was larger in patients with DMS (1.43 ± 0.4 cm2) than RMS (0.9 ± 0.3 cm2) by ~0.5 cm2 (P = <.001), and mean TMPG was lower in the DMS group (6.0 ± 2 vs 7.9 ± 3 mm Hg, P = .003). A DMSI of ≤0.50 and ≤0.351 was associated with MVACEQ ≤1.5 and MVACEQ ≤1.0 cm2 (P < .001), respectively. With the progression of DMS from severe to very severe, there was a significant drop in DMSI. There was a nonsignificant trend toward worse survival in patients with MVACEQ ≤1.0 cm2 and DMSI ≤0.35, suggesting severe stenosis severity.

Conclusion

Our results show that TMPG correlates poorly with MVA in patients with DMS. Proposed DMSI may serve as a simple echocardiographic indicator of hemodynamically significant DMS.
DO TAXES ON SODA AND SUGARY DRINKS WORK? SCANNER DATA EVIDENCE FROM BERKELEY AND WASHINGTON STATE
Authors: Rojas Christian , Wang Emily
Published: September 2020

We study two beverage taxes: the SSB tax of 1¢/oz in the city of Berkeley (in effect since 2015) and the temporary 2010 soda tax of 0.166¢/oz in Washington State. Using detailed scanner data, we find that prices in Washington reacted sharply and promptly (often by a larger magnitude than the tax), whereas retail prices in Berkeley reacted marginally (by less than 30% the magnitude of the tax). Further, we find a 5% volume reduction in Washington but fail to detect an effect in Berkeley. We discuss the possible causes for the discrepancy in effectiveness, in particular cross‐border shopping. (JEL H22, L66, I18)
Monitoring and predictive mapping of floristic biodiversity along a climatic gradient in ENSO's terrestrial core region, NW Peru
Authors: Muenchow Jannes , Dieker Petra , Böttcher Thea , Brock Jonas , Didenko Gregor , Fremout Tobias , Jakubka Desiree , Jentsch Anke , Nüst Daniel , Richter Michael , Rodríguez Eric Frank , Rodríguez Rodolfo Arismendiz , Rollenbeck Rütger , Salazar Zarsosa Pablo , Schratz Patrick , Brenning Alexander
Published: September 2020

The tropical dry forests of NW Peru are heavily shaped by the El Niño Southern Oscillation (ENSO), where especially El Niño brings rain to arid to semi‐arid areas. However, the resulting effects on biodiversity patterns remain largely unknown as well as the effect of environmental variables on the floristic composition under varying rainfall patterns. Therefore, we studied the spatio‐temporal effects of different ENSO episodes on floristic biodiversity along a climatic gradient ranging from the coastal desert to the Andean foothills. We sampled 50 vegetation plots in four years representing different ENSO episodes. To highlight the spatio‐temporal changes in floristic composition and beta diversity across ENSO episodes, we predicted ordination scores with a Generalized Additive Model. We applied variation partitioning to test if topographic or edaphic variables gained in importance during more humid ENSO episodes. Additionally, we executed an irrigation–fertilization experiment to quantify the beneficial effects of the water–nutrient interaction under different simulated ENSO rainfall scenarios. Plant species richness increased under humid conditions during the humid La Niña (2012) and the moderate El Niño (2016), and slightly decreased under the very humid conditions during the coastal El Niño (2017). The spatial prediction revealed that specific vegetation formations became more pronounced with increasing water input, but that a large water surplus led to the disruption of the strict order along the climatic gradient. Edaphic and topographic variables gained in importance with increased water availability (2012 and 2016), however, this effect was not further amplified under very wet conditions (2017). The experiment showed that plant cover under Super Niño conditions was three times higher when fertilized. Overall, our spatial predictions concede detailed insights into spatio‐temporal ecosystem dynamics in response to varying rainfall caused by different ENSO episodes while the results of the experiment can support farmers regarding a sustainable agrarian management.
Opioid analgesic use and its sequelae: Opioid and other substance use disorders
Authors: Rhee Taeho Greg , Rosenheck Robert A.
Published: September 2020

Objectives

While use of opioids is a well‐established risk factor for opioid use disorder (OUD), its association with lifetime use of other addictive substances and the emergence of other lifetime substance use disorders (SUDs) has not been studied.

Methods

We used data from 36 309 US adults in the 2012‐2013 National Epidemiologic Survey on Alcohol and Related Conditions III to identify those with lifetime opioid use (n = 4090; 11.3%). Of these individuals, we quantified use of other addictive substances; development of OUD and other SUDs; and whether use of opioids and development of OUD came before or after use of other substances and the emergence of other SUDs.

Results

Of the 11.3% of adults who reported any opioid use, 98.2% of such users reported use of other addictive substances. Of these opioid users, 18.1% met criteria for lifetime OUD but only 3.5% had OUD alone; 47.6% had SUDs other than OUD and 14.6% had OUD plus another SUD. In most instances, opioid use followed use of other substances and OUD followed development of other SUDs.

Conclusion

Opioid use is typically linked to use of multiple substances and while less than 20% developed OUD, more than half developed either OUD or another SUD. Opioid use and OUD most often followed other substance use and the emergence of other SUDs. Early intervention in OUD should consider potential complications of other present or past SUDs, and both prevention and treatment development efforts should focus on the multi‐morbid dimensions of the current opioid epidemic.
Does Special Educator Effectiveness Vary Depending on the Observation Instrument Used?
Authors: Johnson Evelyn S. , Crawford Angela R. , Zheng Yuzhu , Moylan Laura A.
Published: September 2020

In this study, we compared the results of 27 special education teachers’ evaluations using two different observation instruments, the Framework for Teaching (FFT), and the Explicit Instruction observation protocol of the Recognizing Effective Special Education Teachers (RESET) observation system. Results indicate differences in the rank‐ordering of teachers depending on which instrument was used. Overall scores on RESET were higher on average than those on FFT. Item‐level analyses showed that across 125 correlations, 73 were significant, low‐moderate, and 52 were nonsignificant. Implications for research and practice are discussed.
Late‐onset presentation and phenotypic heterogeneity of the rare R377W PSEN1 mutation
Authors: Scarioni M. , Arighi A. , Fenoglio C. , Sorrentino F. , Serpente M. , Rotondo E. , Mercurio M. , Marotta G. , Dijkstra A. A. , Pijnenburg Y. A. L. , Scarpini E. , Galimberti D.
Published: September 2020

Background and purpose

Mutations in the PSEN1 gene are the most common cause of autosomal‐dominant Alzheimer’s disease and have been associated with the earliest disease onset. We describe an unusual presentation of the rare R377W PSEN1 mutation with a late age of onset, and we provide for the first time in vivo pathological evidence for this mutation.

Methods

A 71‐year‐old female patient with progressive cognitive decline in the past 3 years and positive family history for dementia underwent neurological evaluation, neuropsychological testing, lumbar puncture, conventional brain imaging, amyloid‐positron emission tomography (PET) and extensive genetic screening with a next‐generation sequencing technique.

Results

The diagnostic workup revealed mixed behavioural and amnestic disease features on neuropsychological tests, magnetic resonance imaging, and 18‐fluorodeoxyglucose (FDG)‐PET. Amyloid‐PET detected amyloid deposition in the frontal areas, in the parietal lobes and the precunei. The genetic screening revealed the presence of the rare R377W mutation in the PSEN1 gene.

Conclusions

Extensive genetic screening is also advisable for late‐onset presentations of Alzheimer’s disease, especially in the presence of a positive family history or atypical clinical features.
Predictive factors of functional independence after optimal reperfusion in anterior circulation ischaemic stroke with indication for intravenous thrombolysis plus mechanical thrombectomy
Authors: Riou‐Comte N. , Guillemin F. , Gory B. , Lapergue B. , Zhu F. , Soudant M. , Piotin M. , Humbertjean L. , Mione G. , Lacour J.‐C. , Anxionnat R. , Hossu G. , Bracard S. , Richard S. ,   the THRACE, ASTER investigators
Published: September 2020

Background and purpose

Intravenous thrombolysis plus mechanical thrombectomy (IVT + MT) is the best current management of acute stroke due to large‐vessel occlusion and results in optimal reperfusion for most patients. Nevertheless, some of these patients do not subsequently achieve functional independence. The aim was to identify baseline factors associated with 3‐month independence after optimal reperfusion and to validate a prediction model.

Methods

All consecutive patients with intracranial anterior large‐vessel occlusion, with indication for IVT + MT and achieving optimal reperfusion (defined as modified Treatment in Cerebral Ischaemia score 2b–3), from the THRACE trial and the ETIS registry, were included in order to identify a prediction model. The primary outcome was 3‐month independence [modified Rankin Scale (mRS) score ≤ 2]. Multivariate inferences invoked forward logistic regression, multiple imputation and bootstrap resampling. Predictive performance was assessed by c‐statistic. Model validation was conducted on patients from the ASTER trial.

Results

Amongst 139 patients (mean age 65.5 years; 54.3% female), predictors of 3‐month mRS ≤ 2 (n = 82) were younger age [odds ratio 0.62 per 10‐year increase; 95% confidence interval (CI) 0.53–0.72] and higher Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (odds ratio 1.65 per 1‐point increase; 95% CI 1.47–1.86) with c‐statistic 0.77. Model validation (n = 104/181 patients with 3‐month mRS ≤ 2) demonstrated a moderate discrimination (c‐statistic 0.74; 95% CI 0.66–0.81) combining age and ASPECTS. The validation model was improved by the adjunction of three candidate variables that were found to be predictors. Addition of baseline National Institutes of Health Stroke Scale (NIHSS) score, history of vascular risk factor and onset‐to‐reperfusion time significantly improved discrimination (c‐statistic 0.85; 95% CI 0.83–0.87).

Conclusions

After optimal reperfusion, younger age, higher ASPECTS, lower NIHSS score, shorter onset‐to‐reperfusion time and absence of vascular risk factor were predictive of independence and could help to guide patient management.