bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlates of advance directive treatment preferences among community‐dwelling older people with chronic diseases
Authors: Kim JinShil , Heo Seongkum , Hong Sun Woo , Shim JaeLan , Lee Jung‐Ah
Published: March 2019

Background

Concerns over the creation of advance directives (ADs) and the factors associated with treatment directive decisions among Korean community‐dwelling older people with chronic diseases have rarely been addressed.

Objectives

This study aimed to examine knowledge, attitudes and barriers/benefits regarding ADs and their associations with AD treatment preferences among chronically ill, low‐income, community‐dwelling older people.

Methods

Using a descriptive, correlational design, older people who were recipients of home visiting service for chronic disease management participated in this study. Home visiting nurses collected data on knowledge, attitudes and perceived barriers/benefits and treatment directives using questionnaires during home visits.

Results

Older people (N = 112, mean age = 74.9 years, women = 83.9%) who had chronic diseases such as hypertension (56.3%), diabetes mellitus (40.2%) and cardiovascular disease/stroke (22.3%) participated. Approximately half of the participants preferred hospice care (54.5%), while a few of them preferred aggressive treatments: cardiopulmonary resuscitation (CPR) (14.3%), ventilation support (9.8%) and haemodialysis (8.9%). Being married was associated with the likelihood of preferring CPR (odds ratio [OR] = 11.79) and ventilation support (OR = 9.99), higher education with CPR (OR = 1.23) and haemodialysis (OR = 1.16), and having a cardiovascular disease (CVD)/stroke with CPR (OR = 6.46) and hospice care (OR = 3.06). Among the modifiable factors, greater perceived barriers increased the likelihood of CPR preference (OR = 1.12) but decreased the likelihood of hospice care preference (OR = 0.96). Greater perceived benefits decreased the likelihood of CPR preference (OR = 0.81) and ventilation support (OR = 0.89), and AD knowledge decreased the likelihood of haemodialysis preference (OR = 0.23).

Conclusion

The multidimensional factors were differently associated with each of the AD treatment preferences. Modifiable factors, including perceived barriers and benefits and knowledge, should be improved to help low‐income, community‐dwelling older people select adequate AD treatment preferences.

Implications for practice

Additional information regarding AD treatments and some modifiable and non‐modifiable correlates can be integrated into primary and palliative/supportive care in public health. The current home visitation service may also benefit from incorporating AD discussions while extending the service to embrace AD issues in addition to disease management.
New Technique for Cryoneuroablation of the Proximal Greater Occipital Nerve
Authors: Stogicza Agnes , Trescot Andrea , Rabago David
Published: March 2019

Study design

Description of a new technique.

Objectives

To describe a safe ultrasound (US)‐guided cryoneuroablation technique of the proximal greater occipital nerve (GON).

Background

Cryoneuroablation is a treatment option for occipital neuralgia, providing more sustained relief when steroid injections fail. US can identify the proximal GON between the C2 spinous and C1 transverse process over the inferior oblique capitis muscle (IOCM), where the GON is clearly visualized. US‐guided GON injections are often performed with an out‐of‐plane approach; however, that approach is difficult with cryoneuroablation, because the probe has no opening (prohibiting hydrodissection), and the size and dullness of the probe hinders easy manipulation.

Setting

University‐based outpatient pain clinic.

Methods

We provide a description of the procedure based on experience in the authors’ clinic. With the patient in the prone position, the US probe is placed parallel to the IOCM. The GON is seen on top of the IOCM; a midline 2‐mm incision allows access to the bilateral GONs with a single skin entry. Using an in‐plane approach, the cryo probe is advanced to the nerve in a medial‐to‐lateral direction, with constant US visualization, staying far away from the spinal cord and vertebral artery, which increases safety.

Conclusions

Based on anecdotal evidence from the authors’ clinic, cryoneuroablation of the proximal GON can be performed safely at the level of the IOCM.

Limitations

The procedure described is based on anecdotal evidence from a small number of patients; however, the procedure is promising and formal study is warranted.
Do sensorimotor perturbations to standing balance elicit an error‐related negativity?
Authors: Payne Aiden M. , Ting Lena H. , Hajcak Greg
Published: March 2019

Detecting and correcting errors is essential to successful action. Studies on response monitoring have examined scalp ERPs following the commission of motor slips in speeded‐response tasks, focusing on a frontocentral negativity (i.e., error‐related negativity or ERN). Sensorimotor neurophysiologists investigating cortical monitoring of reactive balance recovery behavior observe a strikingly similar pattern of scalp ERPs following externally imposed postural errors, including a brief frontocentral negativity that has been referred to as the balance N1. We integrate and review relevant literature from these discrepant fields to suggest shared underlying mechanisms and potential benefits of collaboration across fields. Unlike the cognitive tasks leveraged to study the ERN, balance perturbations afford precise experimental control of postural errors to elicit balance N1s that are an order of magnitude larger than the ERN and drive robust and well‐characterized adaptation of behavior within an experimental session. Many factors that modulate the ERN, including motivation, perceived consequences, perceptual salience, expectation, development, and aging, are likewise known to modulate the balance N1. We propose that the ERN and balance N1 reflect common neural activity for detecting errors. Collaboration across fields could help clarify the functional significance of the ERN and poorly understood interactions between motor and cognitive impairments.
Twinning rate in buffaloes: A case report
Authors: Rocha Luca Godoi Santana , dos Santos Daniel Jordan Abreu , Tonhati Humberto , Costa Raphael Bermal , de Camargo Gregório Miguel Ferreira
Published: March 2019

Contents

The information of twin pregnancy frequencies in buffaloes is scarce in the literature. Evidence even indicates that twin pregnancies are not carried to term, but it does not seem to be the case. In this case report, the event of twin pregnancy in buffaloes is reported as well as its frequency. Twin birth is the presence of two or more embryos in a single gestation. Multiple births are uncommon in buffaloes since the species is uniparous. We studied a population of Murrah buffaloes in which slightly more than 13,000 births were observed. In this study, the frequency of occurrence of twin births in Murrah buffaloes was 0.14%. This low incidence impaired the estimation of genetic parameters. Twins can have advantages and disadvantages depending on the production system, which are discussed in this case report.
Mainstreamed voluntary sustainability standards and their effectiveness: Evidence from the Honduran coffee sector
Authors: Dietz Thomas , Grabs Janina , Chong Andrea Estrella
Published: March 2019

Voluntary Sustainability Standards have become a popular private governance framework for more sustainable agri‐food value chains. Yet, amid increasing concerns over the decoupling of standards and practices, it is still unclear to what extent agricultural standard requirements are implemented on the ground, and what may account for such differential implementation. This study employs a novel dataset of 659 Honduran coffee producers to examine this puzzle, focusing on the most widely used standards in the coffee sector (Common Code for the Coffee Community, Fairtrade, Fairtrade/organic, UTZ Certified, and Rainforest Alliance). It first presents results on implementation and behavioral change, based on matched groups of certified and non‐certified farmers, for eight representative social and environmental sustainability practices. Analyzing determinants of implementation success, it finds that the stringency of rules – if they are known by farmers – and the level of farm‐gate prices are significantly correlated with farmers’ performance and lower levels of decoupling across a majority of indicators. These results speak to the importance of supporting small‐scale actors’ awareness of and financial capacity to comply with proposed sustainability rules.
Transparency in transnational governance: The determinants of information disclosure of voluntary sustainability programs
Authors: Schleifer Philip , Fiorini Matteo , Auld Graeme
Published: March 2019

The rise of “new” transnational governance has intensified debates about a lack of accountability in global politics. Reviewing the mechanisms through which transparency can foster accountability beyond the state, this article explores the determinants of information disclosure in the field of transnational sustainability governance. Examining the institutional design of 113 voluntary sustainability programs, we find a positive correlation between the involvement of public actors and information disclosure. In contrast, the role of civil society is more ambiguous. There is no statistical support for arguments linking non‐governmental organization participation to increased transparency. At the same time, our analysis reveals a robust correlation between civil society‐led metagovernance and information disclosure. Moreover, we find that crowding has a negative effect on transparency, whereas normative peer pressures have no influence. At a broader level, the analysis reveals a lack of “deep transparency” among transnational sustainability governors. This limits the scope for transparency‐induced accountability in this policy domain.
Do the regulatory standards require religious literacy of U.K. health and social care professionals?
Authors: Crisp Beth R. , Dinham Adam
Published: March 2019

Health and social care professionals need sufficient religious literacy in order to handle the complexities of religious beliefs and practices, including the growing numbers who identify with other belief systems and those who claim to identify with no religion. The extent to which the need for religious literacy has been formalized was examined in an analysis of regulatory frameworks for health and social care professionals in the United Kingdom. Although all but one of the regulators make some reference to religion and beliefs, they are silent on the question as to what is meant by religion and beliefs. Some standards include a requirement not to impose one's own beliefs on others, but there is very little requirement to develop a reflective and self‐critical awareness of one's own stance. Likewise, some standards refer to knowledge and skills required, but greater specificity is required for these to be meaningful.
Outbreaks of Salmonella enterica infections linked to animal contact: Demographic and outbreak characteristics and comparison to foodborne outbreaks—United States, 2009–2014
Authors: Marus Jessica Rae , Magee Matthew James , Manikonda Karunya , Nichols Megin C.
Published: March 2019

In the United States, multistate Salmonella outbreaks are most commonly linked to a food source; however, contact with live animals can also result in outbreaks of human illness. To characterize Salmonella outbreaks linked to animal contact and examine differences compared to foodborne outbreaks, we analysed data reported to the Centers for Disease Control and Prevention through the National Outbreak Reporting System (NORS) from 2009 to 2014 with a primary mode of transmission listed as “animal contact” or “food.” Four hundred and eighty‐four outbreaks with animal contact or foodborne transmission were reported through NORS; of these outbreaks, 99 (20.5%) resulted from Salmonella transmission through animal contact and 385 (79.5%) resulted from foodborne transmission, which resulted in 3,604 (19.8%) and 13,568 (80.2%) illnesses, respectively. A higher proportion of illnesses among children aged <1 year and children aged 1–4 years were linked to animal contact outbreaks compared to foodborne outbreaks (15.2% vs. 1.4%, p < 0.01 and 24.5% vs. 5.6%, p < 0.01, respectively). Illnesses resulting in hospitalizations (OR: 1.81, 95% CI: 1.62, 2.02) were more likely to be associated with animal contact compared to food. Animal contact outbreaks reported to NORS were more likely to be multistate compared to foodborne outbreaks (OR: 5.43, 95% CI: 3.37, 8.76) and had a longer median duration (99.0 days vs. 9.0 days, p < 0.01). Characterizing the differences between outbreaks of illness linked to animal contact and outbreaks linked to food provides useful information to investigators to improve public health response.
Postural respiratory‐related cortical activation and rostral fluid shift in awake healthy humans
Authors: Launois Claire , Perger Elisa , Attali Valérie , Nierat Marie‐Cécile , Raux Mathieu , Arnulf Isabelle , Similowski Thomas , Redolfi Stefania
Published: March 2019

New Findings

What is the central question of this study?

Moving to supine induces upper airway modifications and a fluid shift to the neck, which represent inspiratory load that predisposes to upper airway collapse. Is there cortical participation in the response to the load induced by transition to a supine posture in awake healthy subjects?

What is the main finding and its importance?

Moving to supine induces transient cortical activation in awake healthy subjects, with greater fluid shift, supporting possible cortical participation in the response to upper airway load induced by transition to a supine posture. Our findings open new perspectives in the understanding of the pathogenesis of obstructive sleep apnoea.

Moving from sitting upright to lying supine causes anatomical modifications and a fluid shift to the neck, which represent inspiratory loads that predispose to upper airway collapse. The pre‐inspiratory potential (PIP) corresponds to the cortical activity observed during inspiratory load. In the sitting position during wakefulness, some obstructive sleep apnoea patients exhibit PIP, probably in relationship to upper airway abnormalities. The aim of this study was to investigate whether moving to the supine position induces respiratory‐related cortical activation (PIP) in awake healthy subjects. The ECG was analysed to detect PIP, and EMG activity of the genioglossus muscle and ventilation were measured in the sitting position, immediately after moving to the supine position, and during application of leg positive pressure in the supine position to promote fluid shift, which was measured by bioelectrical impedance. Twenty‐four subjects were included. From sitting to lying, PIP prevalence increased from 1/24 to 11/24 (P = 0.002), and ventilation decreased with no change in genioglossus activity. The fluid shift from sitting to supine was higher in the subjects exhibiting PIP while supine compared with the subjects without PIP [median (25th; 75th centiles) 440 (430; 520) versus 320 (275; 385) ml, P = 0.018], without any other differences. From before to during leg positive pressure, PIP disappeared (P = 0.006). These results indicate that moving from sitting to lying induces transient respiratory‐related cortical activity in awake healthy subjects with greater fluid shift, supporting possible cortical participation in the response to upper airway loading induced by moving from sitting upright to lying supine. This study offers new perspectives in the understanding of obstructive sleep apnoea pathogenesis.
Regular aerobic exercise‐ameliorated troponin I carbonylation to mitigate aged rat soleus muscle functional recession
Authors: Liu Wenfeng , Kuang Heyu , Xia Yan , Pope Zachary C. , Wang Zhiyuan , Tang Changfa , Yin Dazhong
Published: March 2019

New Findings

What is the central question of this study?

What is the biological role of carbonylation in muscle age‐related functional decline and how might exercise affect the carbonylation process differently compared to habitual sedentary behaviour?

What is the main finding and its importance?

The carbonylation of troponin I (TNNI1), tropomyosin α‐1 chain and α‐actinin‐1 demonstrated a relationship with muscle age‐related functional decline. Exercise attenuated the decline by slowing the rate of carbonylation and promoting antioxidant reactions within the muscle. As exercise demonstrated the greatest effect on TNNI1, quantification of protein carbonyls in TNNI1 may be used as a potential biomarker of muscle age‐related functional decline.

This study investigated the biological role of carbonylation in muscle age‐related functional decline and how regular aerobic exercise may affect the carbonylation process differently from habitual sedentary behaviour. Twenty‐four healthy male Sprague–Dawley (SD) rats (mean age: 23 months) were randomly divided into an old‐aged sedentary control group (O‐SED) and an old‐aged aerobic exercise group (O‐EX). The O‐EX group participated in regular aerobic exercise – treadmill running – with exercise intensity increased gradually from 50–55% to 65–70% of maximum oxygen consumption () over 10 weeks. Rats’ body weight, exercise behaviour index, morphology and oxidative stress were monitored. Avidin magnetic beads and electrospray ionization quadrupole time‐of‐flight mass spectrometry were used for gathering and separating carbonylated proteins while western blot tested for molecular targets. O‐SED and O‐EX rats both had 19 oxidative modification sites for protein carbonylation. In the O‐SED group, 16 specific carbonylated proteins were identified, while 16 additional specific species were also found in the O‐EX group, with all 28 species demonstrating oxidative modifications. The carbonylated proteins included troponin I (TNNI1; slow skeletal muscle), tropomyosin α1 and α‐actinin 1. In particular, TNNI1 carbonylation modifications were found only in sedentary rats. Aerobic exercise increased TNNI1 and Ca2+/calmodulin‐dependent protein kinase IIα expression significantly. Observations suggested that quantification of TNNI1 carbonylation may be a potential biomarker of muscle age‐related functional decline. Importantly, regular aerobic exercise appeared to have antioxidant effects in the muscle that reduced TNNI1 slow carbonylation and promoted Ca2+/calmodulin‐dependent protein kinase IIα (CAMK2) and TNNI1 expression for skeletal muscle contraction regulation, thus attenuating possible age‐related skeletal muscle functional decline.
Prediction of Electromigration Critical Current Density in Passivated Arbitrary-Configuration Interconnect
Authors: Kimura Yasuhiro , Saka Masumi
Published: March 2019

A critical current density, a criterion of electromigration (EM) resistance in interconnects, above which EM damages initiate has been studied to minimize EM damages of interconnects. In general, the assessment of a critical current density is confined to straight interconnect called as Blech specimen, although the critical current density is sensitive to structural characteristic. This work proposes a procedure of predicting a critical current density for any arbitrary-configuration interconnect by using the analogy between atomic density and electrical potential. In the models of straight and barrel interconnects as the typical solder bumps in modern flip-chip technology, the critical current density is predicted through calculating electrical potential by proposed formulation and simulation based on the finite element analysis (FEA). The critical current density for straight interconnect obtained by experiment leads to numerically calculate the critical electrical potential, which is independent of interconnect configuration. The critical potential corresponds to the critical atomic density, below which the accumulation of atoms allows. The calculated critical electrical potential determines a critical current density for arbitrary-configuration interconnect including current crowding effect. This finding can predict a critical current density for actual arbitrary-configuration model and provide an insight for the applying to the packaging design such as ball grid array and C4 flip-chip solder bumps.
Actuation Fatigue Life Prediction of Notched Shape Memory Alloy Members
Authors: Hasan Md Mehedi , Baxevanis Theocharis
Published: March 2019

The efficiency of the critical plane model of Smith, Watson, and Topper in estimating fatigue life for loaded notched shape memory alloy members undergoing thermal cycling is demonstrated. The field intensity approach is adopted, which characterizes fatigue damage over a critical notch root region rather than at a critical point.
Electromechanical Instability of Dielectric Elastomer Actuators With Active and Inactive Electric Regions
Authors: Sharma Atul Kumar , Kumar Pramod , Singh A. , Joglekar D. M. , Joglekar M. M.
Published: March 2019

Electrically driven dielectric elastomers (DEs) suffer from an electromechanical instability (EMI) when the applied potential difference reaches a critical value. A majority of the past investigations address the mechanics of this operational instability by restricting the kinematics to homogeneous deformations. However, a DE membrane comprising both active and inactive electric regions undergoes inhomogeneous deformation, thus necessitating the solution of a complex boundary value problem. This paper reports the numerical and experimental investigation of such DE actuators with a particular emphasis on the EMI in quasistatic mode of actuation. The numerical simulations are performed using an in-house finite element framework developed based on the field theory of deformable dielectrics. Experiments are performed on the commercially available acrylic elastomer (VHB 4910) at varying levels of prestretch and proportions of the active to inactive areas. In particular, two salient features associated with the electromechanical response are addressed: the effect of the flexible boundary constraint and the locus of the dielectric breakdown point. To highlight the influence of the flexible boundary constraint, the estimates of the threshold value of potential difference on the onset of electromechanical instability are compared with the experimental observations and with those obtained using the lumped parameter models reported previously. Additionally, a locus of localized thinning, near the boundary of the active electric region, is identified using the numerical simulations and ascertained through the experimental observations. Finally, an approach based on the Airy stress function is suggested to justify the phenomenon of localized thinning leading to the dielectric breakdown.
Numerical and Experimental Study of the Effect of Secondary Surfaces Fixed Over a Rectangular Vortex Generator
Authors: Kashyap Uddip , Das Koushik , Debnath Biplab Kumar
Published: March 2019

In order to cool a heated surface surrounded by fluid flow, vortex generator plays a significant role. The presence of a vortex generator in the flow creates both latitudinal and longitudinal vortices. The vortices energize the boundary layer over the heated surface and excel convective mode of heat transfer. Therefore, the strength of these vortices is directly proportional to the heat transferal rate. The present study considers a vortex generator attached to a heated base plate. The system is studied numerically and experimentally. The existing rectangular vortex generator is modified computationally with a goal to escalate the overall heat transferal rate. The role of secondary surfaces fixed over the primary surface of the rectangular vortex generator is discussed. Water flows over the surface of the base plate at a Reynolds number of 350. And the plate has a constant heat flux of 1 kW/m2. The results show that the secondary surfaces fixed parallel to the heated plate over the vortex generator significantly augment the heat transfer rate to about 13.4%. However, it enhances the drag by 5.7%. A linear regression analysis predicts the suitable placement of the secondary surface with an enhancement of heat transfer rate of about 7.6%, with a decrease in the drag by about 0.7%. In order to validate the obtained results, the best configuration is fabricated and tested experimentally. The experimental outcomes are found to complement the numerical results. In this experiment, the modification yields 25% enhancement in heat transfer rate.
Discussion: “Double Stratification in Flow by Curved Stretching Sheet With Thermal Radiation and Joule Heating” (Hayat, T., Qayyum, S., Imtiaz, M., and Alsaedi, A., 2018, J. Therm. Sci. Eng. Appl., 10(2), 021010)
Authors: Pantokratoras Asterios
Published: March 2019

The present discussion concerns some doubtful results included in the above paper.
Heliocentric Zoning of the Asteroid Belt by Aluminum-26 Heating
Authors: Grimm Robert E. , McSween Harry Y.
Published: March 2019

The dependence of asteroid spectral class (and inferred composition and thermal history) on heliocentric radius has been held to be the result of heating by a solar energy source, most likely electrical induction, during the formation of the planetary system. Such variations in thermal history can be more simply explained by the presence of different amounts of the radionuclide aluminum-26, whose decay products are observed in meteorites, in planetesimals. These differences occurred naturally as a function of the increasing amount of time required to aecrete objects farther from the sun, during which aluminum-26 decayed from its initial concentration in the solar nebula. Both theory and isotopic evidence suggest that increases in aecretion time across the asteroid belt are of order several half-lives of aluminum-26, which is sufficient to produce the inferred differences in thermal history.
Sweating the small things
Authors: Roberts Leslie
Published: March 2019

An eclectic group of scientists is trying to build a health system piece by piece in Madagascar, one of the poorest countries in the world.
Impacts of historical warming on marine fisheries production
Authors: Free Christopher M. , Thorson James T. , Pinsky Malin L. , Oken Kiva L. , Wiedenmann John , Jensen Olaf P.
Published: March 2019

Accounting for a warming ocean

Fisheries provide food and support livelihoods across the world. They are also under extreme pressure, with many stocks overfished and poorly managed. Climate change will add to the burden fish stocks bear, but such impacts remain largely unknown. Free
et al.
used temperature-specific models and hindcasting across fish stocks to determine the degree to which warming has, and will, affect fish species (see the Perspective by Plagányi). They found that an overall reduction in yield has occurred over the past 80 years. Furthermore, although some species are predicted to respond positively to warming waters, the majority will experience a negative impact on growth. As our world warms, responsible and active management of fisheries harvests will become even more important.

Science
, this issue p.
979
; see also p.
930
Precipitation strengthening of aluminum alloys by room-temperature cyclic plasticity
Authors: Sun Wenwen , Zhu Yuman , Marceau Ross , Wang Lingyu , Zhang Qi , Gao Xiang , Hutchinson Christopher
Published: March 2019

Pushing and pulling for high strength

High-strength aluminum alloys are important for producing lightweight cars, trains, and airplanes. The traditional strategy for doing this is through hours of high-temperature cycling to form precipitates in the alloy. Sun
et al.
developed a processing method that relies on mechanical cycling by pushing and pulling on the alloys at room temperature. This quickly creates many very fine precipitates that have the same strengthening effect as those characteristic of traditional thermal methods. This method should also work for other alloy systems.

Science
, this issue p.
972
Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos
Authors: Zuo Erwei , Sun Yidi , Wei Wu , Yuan Tanglong , Ying Wenqin , Sun Hao , Yuan Liyun , Steinmetz Lars M. , Li Yixue , Yang Hui
Published: March 2019

Spotting off-targets from gene editing

Unintended genomic modifications limit the potential therapeutic use of gene-editing tools. Available methods to find off-targets generally do not work in vivo or detect single-nucleotide changes. Three papers in this issue report new methods for monitoring gene-editing tools in vivo (see the Perspective by Kempton and Qi). Wienert
et al.
followed the recruitment of a DNA repair protein to DNA breaks induced by CRISPR-Cas9, enabling unbiased detection of off-target editing in cellular and animal models. Zuo
et al.
identified off-targets without the interference of natural genetic heterogeneity by injecting base editors into one blastomere of a two-cell mouse embryo and leaving the other genetically identical blastomere unedited. Jin
et al.
performed whole-genome sequencing on individual, genome-edited rice plants to identify unintended mutations. Cytosine, but not adenine, base editors induced numerous single-nucleotide variants in both mouse and rice.

Science
, this issue p.
286
, p.
289
, p.
292
; see also p.
234
A lipase-independent pathway of lipid release and immune modulation by adipocytes
Authors: Flaherty Stephen E. , Grijalva Ambar , Xu Xiaoyuan , Ables Eleanore , Nomani Alireza , Ferrante Anthony W.
Published: March 2019

Exosomes that fatten immune cells

Adipose tissue in mammals contains not only adipocytes (fat cells) but also a variety of immune cells—most notably, macrophages. Proper communication between these cell types is thought to be important for metabolic health. Flaherty
et al.
found that adipocytes release lipid-filled vesicles (AdExos) that serve as the primary source of lipid for adipose-resident macrophages (see the Perspective by Antonyak
et al.
). AdExos were present at low levels in the circulation of mice and were produced at twice the rate in obese versus lean animals. In vitro, AdExos induced differentiation of bone marrow precursor cells into cells resembling adipose-resident macrophages.

Science
, this issue p.
989
; see also p.
931
Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents
Authors: Rizk M. L. , Bhavnani S. M. , Drusano G. , Dane A. , Eakin A. E. , Guina T. , Jang S. H. , Tomayko J. F. , Wang J. , Zhuang L. , Lodise T. P.
Published: March 2019

In June 2017, The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled “Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens” to discuss details and critical parameters of various PK/PD methods and identify approaches for linking human pharmacokinetic (PK) data and drug efficacy analyses. The workshop participants included individuals from academia, industry, and government.
Toxoflavin Produced by
Burkholderia gladioli
from
Lycoris aurea
Is a New Broad-Spectrum Fungicide
Authors: Li Xiaodan , Li Yikui , Wang Ren , Wang Qizhi , Lu Ling
Published: March 2019

Human fungal infections are a growing problem associated with increased morbidity and mortality. Moreover, a growing number of antifungal-resistant fungal isolates have been reported over the past decade. Thus, the need for novel antifungal agents is imperative. In this study, we show that an endophytic bacterium,
Burkholderia gladioli
, isolated from the medicinal plant
Lycoris aurea
, is able to abundantly secrete a compound, toxoflavin, which has a strong fungicidal activity not only against plant fungal pathogens but also against human fungal pathogens
Aspergillus fumigatus
and
Candida albicans
,
Cryptococcus neoformans
, and the model filamentous fungus
Aspergillus nidulans
. More importantly, toxoflavin also displays an efficacious inhibitory effect against azole antifungal-resistant mutants of
A. fumigatus
. Consequently, our findings provide a promising approach to abundantly produce toxoflavin, which has novel broad-spectrum antifungal activity, especially against those currently problematic drug-resistant isolates.
Spatiotemporal Dynamics of Free-Living and Particle-Associated
Vibrio
Communities in the Northern Chinese Marginal Seas
Authors: Liang Jinchang , Liu Jiwen , Wang Xiaolei , Lin Heyu , Liu Jingli , Zhou Shun , Sun Hao , Zhang Xiao-Hua
Published: March 2019

The dynamics of
Vibrio
communities have been shown in many marine habitats that are close to land, including estuary or harbor areas. Here, we investigated the spatiotemporal dynamics of
Vibrio
populations in the northern Chinese marginal seas, spanning a wide spatial scale. We showed that the abundances of the
Vibrio
population in the present study were higher than those in most previously studied areas and that
Vibrio
species are more likely to adopt a free-living lifestyle. Moreover, our results expanded upon previous results by showing a clear shift in the dominant
Vibrio
species from summer to winter, which was mainly attributable to the reduction in the abundance of dominant species in summer. Overall, this work contributes to the understanding of the ecology of the
Vibrio
communities in the marginal seas.
Ethnic-specific mortality of infants undergoing congenital heart surgery in England and Wales
Authors: Knowles Rachel L , Ridout Deborah , Crowe Sonya , Bull Catherine , Wray Jo , Tregay Jenifer , Franklin Rodney C G , Barron David J , Parslow Roger C , Brown Katherine
Published: March 2019

Purpose

To investigate ethnic differences in mortality for infants with congenital heart defects (CHDs) undergoing cardiac surgery or interventional catheterisation.

Design

Observational study of survival to age 1 year using linked records from routine national paediatric cardiac surgery and intensive care audits. Mortality risk was investigated using multivariable Poisson models with multiple imputation. Predictors included sex, ethnicity, preterm birth, deprivation, comorbidities, prenatal diagnosis, age and weight at surgery, preprocedure deterioration and cardiac diagnosis.

Setting

All paediatric cardiac surgery centres in England and Wales.

Patients

5350 infants with CHDs born from 2006 to 2009.

Main outcome measure

Survival at age 1 year.

Results

Mortality was 83.9 (95% CI 76.3 to 92.1) per 1000 infants, with variation by ethnic group. Compared with those of white ethnicity, infants in British Asian (Indian, Pakistani and Bangladeshi) and ‘all other’ (Chinese, mixed and other) categories experienced significantly higher mortality by age 1 year (relative risk [RR] 1.52[95% CI 1.19 to 1.95]; 1.62[95% CI 1.20 to 2.20], respectively), specifically during index hospital admission (RR 1.55 [95% CI 1.07 to 2.26]; 1.64 [95% CI 1.05 to 2.57], respectively). Further predictors of mortality included non-cardiac comorbidities, prenatal diagnosis, older age at surgery, preprocedure deterioration and cardiac diagnosis. British Asian infants had higher mortality risk during elective hospital readmission (RR 1.86 [95% CI 1.02 to 3.39]).

Conclusions

Infants of British Asian and ‘all other’ non-white ethnicity experienced higher postoperative mortality risk, which was only partly explained by socioeconomic deprivation and access to care. Further investigation of case-mix and timing of risk may provide important insights into potential mechanisms underlying ethnic disparities.
‘Carpal tunnel syndrome’ and ‘tennis elbow’ as prodromes for granulomatosis with polyangiitis (formerly Wegener’s granulomatosis)
Authors: Geier Christian , Steed Kelly
Published: March 2019

A 62-year-old man presented with excruciating joint pains, back stiffness and numbness of his hands and feet. Over the past 18 months, he had experienced similar episodes for which the diagnoses of bilateral carpal tunnel syndrome and lateral epicondylitis had been made. Physical examination revealed polyarticular arthritis affecting the shoulders, wrists and right knee. Palpable purpura overlying the calves and ankles was present. Laboratory tests showed markedly elevated erythrocyte sedimentation rate and C-reactive protein in the setting of negative blood and urine cultures. Rheumatoid factor and antinuclear antibodies were negative. Chest CT demonstrated bilateral pulmonary infiltrates. A punch biopsy of the rash showed leukocytoclastic vasculitis. Anti-proteinase-3 titers returned strongly positive. A diagnosis of granulomatosis with polyangiitis was made. Treatment with high-dose steroids, followed by rituximab resulted in normalisation of inflammatory markers with subsequent resolution of joint pains, rash and pulmonary infiltrates and improvement of neuropathic symptoms.
Erosive rheumatoid arthritis in a young patient with mirror hand
Authors: Sheikh Ali Sibtain Farooq , Wong Ernest
Published: March 2019

Mirror hand is a congenital anomaly characterised by duplication of the ulnar ray, resulting in polydactyly and functional disability of the hand. It can cause arthralgias and weakness in intrinsic muscles of the hand. We present a young woman who had a surgically corrected mirror hand and subsequently developed aggressive rheumatoid arthritis, which increased her limitations to a significant degree. Early diagnosis and treatment in such cases is very important to prevent long-term disability.
Mandibular resorption and vocal cord paralysis: a catastrophic form of systemic sclerosis
Authors: Mendonça Pedro , Taulaigo Anna Viola , Caetano Antonio , Moraes-Fontes Maria Francisca
Published: March 2019

Sudden respiratory distress in association with severe weight loss are unusual features of systemic sclerosis (SSc). We report the case of a 56-year-old Caucasian woman with a 9-year history of a diffuse form of SSc who presented with acute stridor due to vocal cord paralysis and required an emergency tracheostomy. She had sought medical attention only after 4 years of disease onset, presenting with a mask-like face, diffuse skin thickening, acro-osteolysis and severe interstitial lung disease. Even though skin tightness improved after immunosuppressive treatment, several spontaneous facial fractures and episodes of dysphagia and choking occurred in the years that followed. At the time of stridor, she was severely malnourished and a percutaneous endoscopic gastrostomy was required for feeding. Permanent vocal cord damage in combination with severe loco-regional bone resorption resulted in severe disability and impaired nutrition. We hereby highlight the features of SSc for which therapy remains challenging.
Do multi-ingredient protein supplements augment resistance training-induced gains in skeletal muscle mass and strength? A systematic review and meta-analysis of 35 trials
Authors: O’Bryan Kerry R , Doering Thomas M , Morton Robert W , Coffey Vernon G , Phillips Stuart M , Cox Gregory R
Published: March 2019

Objective

To determine the effects of multi-ingredient protein (MIP) supplements on resistance exercise training (RT)-induced gains in muscle mass and strength compared with protein-only (PRO) or placebo supplementation.

Data sources

Systematic search of MEDLINE, Embase, CINAHL and SPORTDiscus.

Eligibility criteria

Randomised controlled trials with interventions including RT ≥6 weeks in duration and a MIP supplement.

Design

Random effects meta-analyses were conducted to determine the effect of supplementation on fat-free mass (FFM), fat mass, one-repetition maximum (1RM) upper body and 1RM lower body muscular strength. Subgroup analyses compared the efficacy of MIP supplementation relative to training status and chronological age.

Results

The most common MIP supplements included protein with creatine (n=17) or vitamin D (n=10). Data from 35 trials with 1387 participants showed significant (p<0.05) increases in FFM (0.80 kg (95% CI 0.44 to 1.15)), 1RM lower body (4.22 kg (95% CI 0.79 to 7.64)) and 1RM upper body (2.56 kg (95% CI 0.79 to 4.33)) where a supplement was compared with all non-MIP supplemented conditions (means (95% CI)). Subgroup analyses indicated a greater effect of MIP supplements compared with all non-MIP supplements on FFM in untrained (0.95 kg (95% CI 0.51 to 1.39), p<0.0001) and older participants (0.77 kg (95% CI 0.11 to 1.43), p=0.02); taking MIP supplements was also associated with gains in 1RM upper body (1.56 kg (95% CI 0.80 to 2.33), p=0.01) in older adults.

Summary/conclusions

When MIP supplements were combined with resistance exercise training, there were greater gains in FFM and strength in healthy adults than in counterparts who were supplemented with non-MIP. MIP supplements were not superior when directly compared with PRO supplements. The magnitude of effect of MIP supplements was greater (in absolute values) in untrained and elderly individuals undertaking RT than it was in trained individuals and in younger people.

Trial registration number

CRD42017081970.
How cold is too cold? Establishing the minimum water temperature limits for marathon swim racing
Authors: Saycell Jane , Lomax Mitch , Massey Heather , Tipton Mike
Published: March 2019

Objectives

To provide a rationale for minimum water temperature rules for elite and subelite marathon swim racing and highlight factors that make individuals vulnerable to excessive cooling during open water swimming.

Methods

12 lean competitive swimmers swam for up to 2 hours, three times in different water temperatures between 14°C and 20°C, wearing standard swimming costumes and hats. Rectal temperature (Tre), oxygen consumption, perception of cold and performance were measured.

Results

In 16°C, half the swimmers did not complete a 2-hour swim; four became (or were predicted to become) hypothermic within 2 hours. In 18°C, three-quarters completed the swim; three became (or were predicted to become) hypothermic. In 20°C, one swimmer was predicted to become hypothermic in under 2 hours. The mean linear rate of fall of Trewas greater in 16°C (−1.57°C/hour) than 18°C (−1.07°C/hour) (p=0.03). There was no change in swimming performance during the swims or between conditions. Most of the cooling rate could be explained by metabolic heat production and morphology for both 16°C (R2=0.94, p<0.01) and 18°C (R2=0.82, p<0.01) conditions. No relationship was observed between Treand perception of thermal sensation (r=0.25, p=0.13), and there was a weak correlation between Treand thermal comfort (r=0.32, p=0.04).

Conclusion

We recommend that 16°C and 18°C water are too cold for elite marathon swim racing. FédérationInternationale de Natation rules were changed in 2017 to make wetsuits compulsory below 18°C and optional below 20°C.
Factors associated with and long-term outcome of benign multiple sclerosis: a nationwide cohort study
Authors: Crielaard Loes , Kavaliunas Andrius , Ramanujam Ryan , Olsson Tomas , Hillert Jan , Stridh Pernilla , Kockum Ingrid , Manouchehrinia Ali
Published: March 2019

Objective

Benign multiple sclerosis (BMS) is often defined by the Expanded Disability Status Scale (EDSS) score of ≤3.0 after ≥15 years of disease duration. This classification’s clinical relevance remains unclear as benign patients may suffer other impairments and advance towards a progressive course, prompting our objective to holistically investigate factors associated with BMS and its long-term prognosis.

Methods

Benign cases were identified in the Swedish Multiple Sclerosis registry. Baseline clinical data, demographic features and influence of multiple sclerosis (MS) major risk alleles on likelihood of benign course were investigated. Physical disability (EDSS), cognitive function (Symbol Digit Modalities Test; SDMT) and self-reported and socioeconomic differences between benign and non-benign patients were evaluated using generalised estimation equations models.

Results

11222 patients (2420 benign/8802 non-benign) were included. Benign patients were more likely to be female and younger at MS onset, have fewer relapses within the first two and 5 years from onset and fully recover from the first relapse (p<0.001). No association between human leucocyte antigen (HLA)DRB1*15:01carriership (OR: 0.97, 95% CI: 0.86 to 1.09) orHLA-A*02:01lacking (OR: 0.99, 95% CI: 0.87 to 1.11) and benign/non-benign was found. Non-benign patients accumulated an extra 0.04 (95% CI 0.03 to 0.04, p<0.001) EDSS score/year, lost an extra 0.3 (95% CI − 0.39 to − 0.18, p<0.001) SDMT score/year and deteriorated faster in self-reported impact and socioeconomic measures (p<0.001).

Conclusion

Patients with BMS have a better disease course as they progress more slowly at the group level in all respects. Lack of an association with major genetic risk factors indicates that MS course is most likely influenced by either environmental factor(s) or genetic factors outside theHLAregion.
Should the deceased be listed as authors?
Authors: Helgesson Gert , Bülow William , Eriksson Stefan , Godskesen Tove E
Published: March 2019

Sometimes participants in research collaboration die before the paper is accepted for publication. The question we raise in this paper is how authorship should be handled in such situations. First, the outcome of a literature survey is presented. Taking this as our starting point, we then go on to discuss authorship of the dead in relation to the requirements of the Vancouver rules. We argue that in principle the deceased can meet the requirements laid down in these authorship guidelines. However, to include a deceased researcher as author requires a strong justification. The more the person has been involved in the research and writing process before he or she passes away, the stronger the justification for inclusion.
Thermal effects on mechanical behaviour of soil–structure interface
Authors: Maghsoodi Soheib , Cuisinier Olivier , Masrouri Farimah
Published: March 2019

Mechanical behaviour of the soil–structure interface plays a major role in the shear characteristics and bearing capacity of foundations. In thermoactive structures, due to nonisothermal conditions, the interface behaviour becomes more complex. The objective of this study is to investigate the effects of temperature variations on the mechanical behaviour of soils and the soil–structure interface. Constant normal load (CNL) and constant normal stiffness (CNS) tests were performed on the soil and soil–structure interface in a direct shear device at temperatures of 5, 22, and 60 °C. Fontainebleau sand and kaolin clay were used as proxies for sandy and clayey soils. The sandy soil was prepared in a dense state and the clayey soil was prepared in a normally consolidated state. Results show that the applied thermal variations have a negligible effect on the shear strength of the sand and sand–structure interface under CNL and CNS conditions, and the soil and soil–structure interface behaviour could be considered thermally independent. In clay samples, an increase in the temperature increased the cohesion and consequently the shear strength, due to thermal contraction during heating. The temperature rise had less impact on the shear strength in the case of the clay–structure interface than in the clay samples. The adhesion of the clay–structure interface is less than the cohesion of the clay samples.