bluuebunny/crossref_metadata_2025 huggingface dataset:
Ten‐year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection
Authors: Marcellin Patrick , Wong David K , Sievert William , Buggisch Peter , Petersen Jörg , Flisiak Robert , Manns Michael , Kaita Kelly , Krastev Zahari , Lee Samuel S , Cathcart Andrea L , Crans Gerald , Op den Brouw Marjoleine , Jump Belinda , Gaggar Anuj , Flaherty John , Buti Maria
Published: May 2019

Background & Aims

Tenofovir disoproxil fumarate (TDF) is a first‐line treatment for chronic hepatitis B (CHB). We aimed to describe the efficacy and safety profiles of TDF treatment for up to 10 years in a well‐described cohort of CHB patients.

Methods

Hepatitis B e antigen (HBeAg)‐negative and HBeAg‐positive patients from two randomised, double‐blind trials (ClinicalTrials.gov: NCT00117676 and NCT00116805) completed 48 weeks of randomised treatment with TDF or adefovir dipivoxil. A subset of these patients was then eligible to receive open‐label TDF treatment for up to 10 years. At Year 10, patients were assessed for virological suppression, alanine aminotransferase (ALT) normalisation, serological response, safety and tolerability.

Results

Of 641 randomised and treated patients, 585 (91%) entered the open‐label extension phase with 203 (32%) patients completing Year 10 of the study. At Year 10, 118/118 (100%) of HBeAg‐negative patients and 78/80 (98%) of HBeAg‐positive patients with available data achieved hepatitis B virus (HBV) DNA < 69 IU/mL, while 88/106 (83%) and 60/77 (78%) patients achieved ALT normalisation, respectively. Of the 23 patients with HBeAg status available at Year 10, 12 (52%) and six (27%) experienced HBeAg loss and seroconversion, respectively. No resistance to TDF was documented up to Year 10. In the period between Year 8 and Year 10, the safety profile of TDF was similar to previous reports, with few patients experiencing renal‐ or bone‐related adverse events.

Conclusions

Over 10 years, TDF had a favourable safety profile, was well tolerated, and resulted in continued maintenance of virological suppression with no documented resistance.
Pregnancy rate and biomarker validations from the blubber of eastern North Pacific blue whales
Authors: Atkinson Shannon , Gendron Diane , Branch Trevor A. , Mashburn Kendall L. , Melica Valentina , Enriquez‐Paredes Luis E. , Brownell Robert L.
Published: May 2019

Hormonal biomarkers are useful indicators of mammalian reproductive and metabolic states. The present study validated and applied the use of progesterone and cortisol blubber assays for studies of blue whales from the Gulf of California, Mexico. In a validation study for pregnancy detection, blubber progesterone concentrations were correlated with pregnancy status for four female blue whales: three resighted with a calf the year following sampling and the fourth stranded with a fetus. The progesterone concentrations were significantly higher than those measured in juvenile whales (n = 3). In the application study, blubber samples from blue whales (51 noncalf females, 2 female calves, 48 noncalf males, and 1 male calf) with known sighting histories were analyzed. Putative pregnant females had elevated progesterone concentrations. Cortisol concentrations did not differ between male and female blue whales, or among females in different reproductive classes. After correcting for uncertain ages, hence maturity status, the pregnancy rate of noncalf females was 33.4% (95% CI 32.2%–34.3%). Although interpretation of hormone biomarkers must consider all physiological states that may influence progesterone concentrations, these results demonstrate the utility of pairing hormone biomarkers with sighting histories to help assess environmental or anthropogenic impacts on reproduction in blue whales.
Volatiles from Merino fleece evoke antennal and behavioural responses in the Australian sheep blow fly Lucilia cuprina
Authors: Yan G. , Liu S. , Schlink A. C. , Flematti G. R. , Brodie B. S. , Bohman B. , Greeff J. C. , Vercoe P. E. , Hu J. , Martin G. B.
Published: May 2019

To identify flystrike‐related volatile compounds in wool from Merino sheep, the attractiveness of wool to Lucilia cuprina Wiedmann (Diptera: Calliphoridae) was examined. First, a selection of wool samples guided by previous knowledge of sheep lines, predicted to be more susceptible or more resistant to flystrike, was tested. The attractiveness of the 10 samples selected was not associated with field susceptibility: two samples from the more resistant line were identified as most attractive and two samples from the more susceptible line were identified as least attractive, based on the behavioural assays with gravid flies. Comparison of the headspace volatiles of these samples, using solid phase microextraction and gas chromatography‐mass spectrometry‐electroantennographic detection, revealed octanal and nonanal to be present in the attractive wool samples that elicited responses from the fly antenna. Furthermore, the two compounds were not present in wool that was least attractive to L. cuprina. In laboratory bioassays, octanal and nonanal evoked antennal and behavioural responses in gravid L. cuprina, thus confirming their potential role as semiochemicals responsible for attracting L. cuprina to Merino sheep.
Rapid evolution in plant–microbe interactions – a molecular genomics perspective
Authors: Frantzeskakis Lamprinos , Di Pietro Antonio , Rep Martijn , Schirawski Jan , Wu Chih‐Hang , Panstruga Ralph
Published: May 2019

Rapid (co‐)evolution at multiple timescales is a hallmark of plant–microbe interactions. The mechanistic basis for the rapid evolution largely rests on the features of the genomes of the interacting partners involved. Here, we review recent insights into genomic characteristics and mechanisms that enable rapid evolution of both plants and phytopathogens. These comprise fresh insights in allelic series of matching pairs of resistance and avirulence genes, the generation of novel pathogen effectors, the recently recognised small RNA warfare, and genomic aspects of secondary metabolite biosynthesis. In addition, we discuss the putative contributions of permissive host environments, transcriptional plasticity and the role of ploidy on the interactions. We conclude that the means underlying the rapid evolution of plant–microbe interactions are multifaceted and depend on the particular nature of each interaction.
Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low‐ and middle‐income countries
Authors: Bourassa Megan W. , Osendarp Saskia J.M. , Adu‐Afarwuah Seth , Ahmed Saima , Ajello Clayton , Bergeron Gilles , Black Robert , Christian Parul , Cousens Simon , de Pee Saskia , Dewey Kathryn G. , Arifeen Shams El , Engle‐Stone Reina , Fleet Alison , Gernand Alison D. , Hoddinott John , Klemm Rolf , Kraemer Klaus , Kupka Roland , McLean Erin , Moore Sophie E. , Neufeld Lynnette M. , Persson Lars‐Åke , Rasmussen Kathleen M. , Shankar Anuraj H. , Smith Emily , Sudfeld Christopher R. , Udomkesmalee Emorn , Vosti Stephen A.
Published: May 2019

Inadequate micronutrient intakes are relatively common in low‐ and middle‐income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost‐effectiveness of MMS compared with IFA. Recent meta‐analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual‐participant data meta‐analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost‐effective method to reduce the risk of adverse birth outcomes.
Enterovirus D68 respiratory infection in a children's hospital in Japan in 2015
Authors: Funakoshi Yu , Ito Kenta , Morino Saeko , Kinoshita Kazue , Morikawa Yoshihiko , Kono Tatsuo , Doan Yen Hai , Shimizu Hiroyuki , Hanaoka Nozomu , Konagaya Masami , Fujimoto Tsuguto , Suzuki Ai , Chiba Takashi , Akiba Tetsuya , Tomaru Yasuhiro , Watanabe Ken , Shimizu Norio , Horikoshi Yuho
Published: May 2019

Background

Outbreaks of enterovirus D68 (EV‐D68) respiratory infections in children were reported globally in 2014. In Japan, there was an EV‐D68 outbreak in the autumn of 2015 (September–October). The aim of this study was to compare EV‐D68‐specific polymerase chain reaction (PCR)‐positive and EV‐D68‐specific PCR‐negative patients.

Methods

Pediatric patients admitted for any respiratory symptoms between September and October 2015 were enrolled. Nasopharyngeal swabs were tested for multiplex respiratory virus PCR and EV‐D68‐specific reverse transcription‐PCR. EV‐D68‐specific PCR‐positive and ‐negative patients were compared regarding demographic data and clinical information.

Results

A nasopharyngeal swab was obtained from 76 of 165 patients admitted with respiratory symptoms during the study period. EV‐D68 was detected in 40 samples (52.6%). Median age in the EV‐D68‐specific PCR‐positive and ‐negative groups was 3.0 years (IQR, 5.5 years) and 3.0 years (IQR, 4.0 years), respectively. The rates of coinfection in the two groups were 32.5% and 47.2%, respectively. There was no significant difference in the history of asthma or recurrent wheezing, length of hospitalization, or pediatric intensive care unit admission rate between the groups. The median days between symptom onset and admission was significantly lower for the EV‐D68‐positive group (3.0 days vs 5.0 days, P = 0.001). EV‐D68 was identified as clade B on phylogenetic analysis. No cases of acute flaccid myelitis were encountered.

Conclusions

More than half of the samples from the children admitted with respiratory symptoms were positive for EV‐D68‐specific PCR during the outbreak. Asthma history was not associated with the risk of developing severe respiratory infection.
Electrophysiological indexes of option characteristic processing
Authors: Lin Yongling , Duan Lian , Xu Pengfei , Li Xinying , Gu Ruolei , Luo Yuejia
Published: May 2019

Decision making is vital to human behavior and can be divided into multiple stages including option assessment, behavioral output, and feedback evaluation. Studying how people evaluate option characteristics in the option assessment stage would provide important knowledge on human decision making. Using the event‐related potential (ERP) method, the present study investigated the neural mechanism of evaluating two types of option characteristics (i.e., reward magnitude and degree of uncertainty) in the temporal dimension. Thirty‐five volunteers participated in a monetary gambling task, where they either accepted or rejected gambles. The ERP results showed a double dissociation pattern, with the early P1 component being sensitive to magnitude but insensitive to degree of uncertainty, while both the N2 and P3 components showed the opposite pattern. The results suggest that these two fundamental option features are assessed rapidly and separately in the human brain. Specifically, small magnitude elicited a larger P1 than did large magnitude, indicating that the perceptual and attentional processing of options is modulated by magnitude. Both the N2 and P3 amplitudes evoked by the risky context were larger than those evoked by the ambiguous one, reflecting that more cognitive conflicts and resources are involved in the former condition. Furthermore, the P1, but not the N2 or P3, amplitude was sensitive to decisions, suggesting that early attentional processes may contribute to human decision making. These findings may provide insight into the temporal mechanisms of option characteristic processing.
A novel strategy for resynchronization of ovulation in Nelore cows using injectable progesterone (P4) and P4 releasing devices to perform two timed inseminations within 22 days
Authors: Pugliesi Guilherme , Bisinotto Danilo Zago , Mello Barbara Piffero , Lahr Fábio C. , Ferreira Catia A. , Melo Gabriela Dalmaso , Bastos Michele Ricieri , Madureira Ed Hoffmann
Published: May 2019

We aimed to evaluate the reproductive performance of Nelore lactating cows submitted to a resynchronization 12 days after timed artificial insemination (TAI) with or without a long‐acting progesterone (P4‐LA) treatment. Nelore cows were submitted to a P4/oestradiol‐based TAI protocol (D0 = insemination). On D12, cows in the control group (n = 184) received a new P4 intravaginal device (0.96 g), whereas cows in the P4‐LA group (n = 192) received the P4 device and 75 mg P4‐LA. Cows identified as non‐pregnant (n = 120) by regression of corpus luteum using colour Doppler ultrasonography on D20 had the P4 device removed and received 500ug of sodium cloprostenol, 1 mg of oestradiol cypionate and 300 IU of eCG and were re‐inseminated on D22. There was no difference (p > 0.10) in the pregnancy rate at D20, D30 and D60 after first TAI between the control (69%, 59.7% and 57%, respectively) and P4‐LA (67%, 55.7%, and 55.2%, respectively) groups. Pregnancy losses were similar between both groups (p > 0.1). For cows submitted to the second TAI, the pre‐ovulatory follicle size did not differ (p > 0.1), but the oestrous detection and pregnancy rates were greater (p < 0.05) in the P4‐LA group (92.2% [59/64] and 60.9% [39/64], respectively) than in controls (75% [42/56] and 44.6% [25/56]). The cumulative pregnancy rate after two TAIs did not differ (p > 0.1) between control (73.3% [135/184]) and P4‐LA (76% [146/192]) groups. The use of P4‐LA at 12 days after TAI potentially increases the pregnancy rates for a new early resynchronization strategy associated with the Doppler imaging for pregnancy diagnosis and results in an alternative to perform two TAIs in 22 days in beef cows.
Illustration of a Method to Incorporate Preference Uncertainty in Benefit–Cost Analysis
Authors: Baik Sunhee , Davis Alexander L. , Morgan M. Granger
Published: May 2019

Benefit–cost analysis is widely used to evaluate alternative courses of action that are designed to achieve policy objectives. Although many analyses take uncertainty into account, they typically only consider uncertainty about cost estimates and physical states of the world, whereas uncertainty about individual preferences, thus the benefit of policy intervention, is ignored. Here, we propose a strategy to integrate individual uncertainty about preferences into benefit–cost analysis using societal preference intervals, which are ranges of values over which it is unclear whether society as a whole should accept or reject an option. To illustrate the method, we use preferences for implementing a smart grid technology to sustain critical electricity demand during a 24‐hour regional power blackout on a hot summer weekend. Preferences were elicited from a convenience sample of residents in Allegheny County, Pennsylvania. This illustrative example shows that uncertainty in individual preferences, when aggregated to form societal preference intervals, can substantially change society's decision. We conclude with a discussion of where preference uncertainty comes from, how it might be reduced, and why incorporating unresolved preference uncertainty into benefit–cost analyses can be important.
The chosen fortunate in the urbanization process in China? Evidence from a geographic regression discontinuity study
Authors: Liu Xiuyan , Zeng Jiangnan , Zhou Qiyao
Published: May 2019

After decades of delayed urbanization, since 1998, China has implemented the “county‐to‐district” policy to promote urbanization and stimulate regional economic development. This policy was designed to expand the urban area of large cities by merging counties (rural areas) with nearby cities (urban areas). Intuitively, these regions are the “chosen fortunate” since they are the privileged beneficiaries of this policy experiment. However, at the time of writing (2018), recent studies have been inconsistent regarding this issue, and several studies have revealed that this policy has impeded regional growth. Therefore, the true effect of this policy must be carefully examined. Using grid‐level nighttime light data and a border‐based regression discontinuity design framework, we find that the average effect of the “county‐to‐district” policy on nighttime light growth is significant and positive, and this result also coincides with the increase of entry and decrease of exit of manufacturing enterprises, and the increase of the county‐level manufacturing employment. However, the policy effect on nighttime light turns to be negative in the long run, implying that short‐term economic growth may outweigh the long‐term economic growth potential. A further investigation of the underlying mechanism indicates that industrial enterprises in the experimental policy area do not perform better in terms of total factor productivity (TFP) and profit margin than their counterparts. Moreover, this policy aggravates the polarization between central and border areas.
Social Enterprise: A Study of Its Prevalence, Role and Characteristics in Swedish‐Speaking Regions of Finland
Authors: Melkas Helinä
Published: May 2019

An increasing literature has emerged to examine development of social enterprises (SEs) in varying national or regional contexts. This paper presents empirical research on SEs in Finland’s Swedish‐speaking regions. Differences between Finnish speakers and Swedish speakers have been identified in studies on, for instance, social capital and communality. Both groups have equal constitutional status. This study focuses on the prevalence, role and characteristics of SEs in Swedish‐speaking regions. The research data consist of statistical and other background data, a survey and strategy documents. The study shows that SEs do not appear to be more common in the Swedish‐speaking regions, despite positive preconditions for SEs and their operations in those regions. At the same time, Finnish SEs still appear to face similar challenges in, for instance, their funding and management, and general prejudice and ignorance about SEs.
Ascending chain condition for -pure thresholds on a fixed strongly -regular germ
Authors: Sato Kenta
Published: May 2019

In this paper, we prove that the set of all $F$-pure thresholds on a fixed germ of a strongly $F$-regular pair satisfies the ascending chain condition. As a corollary, we verify the ascending chain condition for the set of all $F$-pure thresholds on smooth varieties or, more generally, on varieties with tame quotient singularities, which is an affirmative answer to a conjecture given by Blickle, Mustaţǎ and Smith.
The AGC Kinase SsAgc1 Regulates
Sporisorium scitamineum
Mating/Filamentation and Pathogenicity
Authors: Wang Yixu , Deng Yi Zhen , Cui Guobing , Huang Chengwei , Zhang Bin , Chang Changqing , Jiang Zide , Zhang Lian-Hui
Published: May 2019

The AGC signaling pathway represents a conserved distinct signaling pathway in regulation of fungal differentiation and virulence, while it has not been identified or characterized in the sugarcane smut fungus
Sporisorium scitamineum
. In this study, we identified a PAS domain-containing AGC kinase, SsAgc1, in
S. scitamineum
. Functional analysis revealed that SsAgc1 plays a regulatory role on the fungal dimorphic switch.
Rare cause of bilateral foot gangrene: coexisting essential cryofibrogenaemia and cryoglobulinaemic vasculitis
Authors: Belfeki Nabil , Abroug Sarra , Strazzulla Alessio , Diamantis Sylvain
Published: May 2019

Cryofibrinogenaemia is a rare haematological disorder characterised by cold temperature-induced precipitation of plasma proteins causing small-vessel occlusive vascular disorder with a hallmark of skin ulceration. It remains an underdiagnosed entity because of a lack of diagnostic criteria. Cryoglobulinaemia vasculitis is a small-vessel vasculitis involving the skin, the joints, the peripheral nerve system and the kidneys. Its association with cryofibrinogenaemia causes more severe phenotype with poor prognosis. We describe the case of a 59-year-old woman presenting with cold-induced extensive bilateral foot gangrene due to coexisting cryofibrinogenaemia and cryoglobulinaemic vasculitis that required bilateral amputation and rituximab perfusions as maintenance therapy.
Acute retinal necrosis in a patient with remote severe herpes simplex encephalitis
Authors: Kobayashi Takaaki , Sekar Poorani , Meier Jeffery , Streit Judy
Published: May 2019

A 60-year-old man with a history of severe herpes simplex virus type 1 (HSV-1) encephalitis 2 years prior presented with acute onset of visual loss in the left eye. Dilated funduscopic examination showed retinitis and occlusive vasculitis with retinal necrosis. PCR of the vitreous fluid was positive for HSV-1, and he was diagnosed with acute retinal necrosis (ARN) due to HSV-1. The patient was treated with intravenous acyclovir and intravitreous foscarnet for 2 weeks, followed by high dose oral valacyclovir for 2 weeks. He was subsequently placed on planned life-long suppressive valacyclovir. His case demonstrates that acute visual loss concomitant with or subsequent to HSV-1 encephalitis warrants suspicion of ARN. Prompt therapy with effective antiviral medication is necessary to reduce the risk of sight-threatening complications. Chronic suppression with oral antiviral therapy after ARN is recommended to prevent involvement of the contralateral eye, though there is no consensus on the duration and dosage of antivirals.
New directions in incidence and prevalence of diagnosed diabetes in the USA
Authors: Benoit Stephen R , Hora Israel , Albright Ann L , Gregg Edward W
Published: May 2019

Objective

To determine whether diabetes prevalence and incidence has remained flat or changed direction during the past 5 years.

Research design and methods

We calculated annual prevalence and incidence of diagnosed diabetes (type 1 and type 2 combined) for civilian, non-institutionalized adults aged 18–79 years using annual, nationally representative cross-sectional survey data from the National Health Interview Survey from 1980 to 2017. Trends in rates by age group, sex, race/ethnicity, and education were calculated using annual percentage change (APC).

Results

Overall, the prevalence of age-adjusted, diagnosed diabetes did not change significantly from 1980 to 1990, but increased significantly (APC 4.4%) from 1990 to 2009 to a peak of 8.2 per 100 adults (95% CI 7.8 to 8.6), and then plateaued through 2017. The incidence of age-adjusted, diagnosed diabetes did not change significantly from 1980 to 1990, but increased significantly (APC 4.8%) from 1990 to 2007 to 7.8 per 1000 adults (95% CI 6.7 to 9.0), and then decreased significantly (APC −3.1%) to 6.0 (95% CI 4.9 to 7.3) in 2017. The decrease in incidence appears to be driven by non-Hispanic whites with an APC of −5.1% (p=0.002) after 2008.

Conclusions

After an almost 20-year increase in the national prevalence and incidence of diagnosed diabetes, an 8-year period of stable prevalence and a decrease in incidence has occurred. Causes of the plateauing and decrease are unclear but the overall burden of diabetes remains high and deserves continued monitoring and intervention.
Dog ownership, the natural outdoor environment and health: a cross-sectional study
Authors: Zijlema Wilma L , Christian Hayley , Triguero-Mas Margarita , Cirach Marta , van den Berg Magdalena , Maas Jolanda , Gidlow Christopher J , Kruize Hanneke , Wendel-Vos Wanda , Andrušaitytė Sandra , Grazuleviciene Regina , Litt Jill , Nieuwenhuijsen Mark J
Published: May 2019

Objectives

Dog owners walking their dog in natural outdoor environments (NOE) may benefit from the physical activity facilitated by dog walking and from time spent in nature. However, it is unclear whether dog owners receive additional health benefits associated with having access to NOE above the physical activity benefit of walking with their dog. We investigated associations between dog ownership, walking, time spent in NOE and health and whether these associations differed among those with good and poor access to NOE and those living in green and less green areas.

Design

Cross-sectional study.

Setting

The Positive Health Effects of the Natural Outdoor Environment in Typical Populations in Different Regions in Europe project.

Participants

n=3586 adults from Barcelona (Spain), Doetinchem (the Netherlands), Kaunas (Lithuania) and Stoke-on-Trent (UK).

Data collection and analysis

We calculated access to NOE with land maps and residential surrounding greenness with satellite data. Leisure time walking, time spent in NOE and general and mental health status were measured using validated questionnaires. Associations were estimated using multilevel analysis with a random intercept defined at the neighbourhood level.

Results

Dog ownership was associated with higher rates of leisure time walking and time spending in NOE (OR 2.17, 95% CI 1.86 to 2.54 and 2.37, 95% CI 2.02 to 2.79, respectively). These associations were stronger in those living within 300 m of a NOE and in greener areas. No consistent associations were found between dog ownership and perceived general or mental health status.

Conclusions

Compared with non-dog owners, dog owners walked more and spent more time in NOE, especially those living within 300 m of a NOE and in greener areas. The health implications of these relationships should be further investigated. In a largely physically inactive society, dog walking in NOE may be a simple way of promoting physical activity and health.
What is the prevalence, and what are the clinical correlates, of insulin resistance in young people presenting for mental health care? A cross-sectional study
Authors: Scott Elizabeth M , Carpenter Joanne S , Iorfino Frank , Cross Shane P M , Hermens Daniel F , Gehue Jeanne , Wilson Chloe , White Django , Naismith Sharon L , Guastella Adam J , Hickie Ian B
Published: May 2019

Objectives

To report the distribution and predictors of insulin resistance (IR) in young people presenting to primary care-based mental health services.

Design

Cross-sectional.

Setting

Headspace-linked clinics operated by the Brain and Mind Centre of the University of Sydney.

Participants

768 young people (66% female, mean age 19.7±3.5, range 12–30 years).

Main outcome measures

IR was estimated using the updated homeostatic model assessment (HOMA2-IR). Height and weight were collected from direct measurement or self-report for body mass index (BMI).

Results

For BMI, 20.6% of the cohort were overweight and 10.2% were obese. However, <1% had an abnormally high fasting blood glucose (>6.9 mmol/L). By contrast, 9.9% had a HOMA2-IR score >2.0 (suggesting development of IR) and 11.7% (n=90) had a score between 1.5 and 2. Further, there was a positive correlation between BMI and HOMA2-IR (r=0.44, p<0.001). Participants in the upper third of HOMA2-IR scores are characterised by younger age, higher BMIs and depression as a primary diagnosis. HOMA2-IR was predicted by younger age (β=0.19, p<0.001) and higher BMI (β=0.49, p<0.001), together explaining 22% of the variance (F(2,361)=52.1, p<0.001).

Conclusions

Emerging IR is evident in a significant subgroup of young people presenting to primary care-based mental health services. While the major modifiable risk factor is BMI, a large proportion of the variance is not accounted for by other demographic, clinical or treatment factors. Given the early emergence of IR, secondary prevention interventions may need to commence prior to the development of full-threshold or major mood or psychotic disorders.
Western Australian pregnancy cohort (Raine) Study: Generation 1
Authors: Dontje Manon L , Eastwood Peter , Straker Leon
Published: May 2019

Purpose

The purpose of the Raine Study is to improve human health and well-being by studying the life-course of a cohort of Western Australians, based on a life-course conceptual framework that considers interactions between genetics, phenotypes, behaviours, the environment and developmental and social outcomes.

Participants

Between May 1989 and November 1991, 2900 pregnant women were enrolled in the Raine Study in Perth, Western Australia. In total, 2730 women gave birth to 2868 children (Generation 2) between August 1989 and April 1992. The mothers and fathers of Generation 2 are referred to as Generation 1 of the Raine Study. In the most recent Generation 1 follow-up, 636 mothers and 462 fathers participated.

Findings to date

Until the 26-year follow-up of Generation 1 the focus of research within the Raine Study was on outcomes in Generation 2, with information on the parents mainly being used to examine its influence on their children’s outcomes. For example, recent findings showed that several characteristics of mothers, such as obesity, early mid-gestational weight gain and socioeconomic status were associated with non-alcoholic fatty liver disease, adiposity and cardiometabolic characteristics in offspring. Other findings showed that parents with back pain were more likely to have offspring who experienced back pain. Also, non-linear and dynamic relationships were found between maternal working hours and offspring overweight or obesity.

Future plans

The Raine Study will continue to provide access to its dense longitudinal genetic, phenotypic, behavioural, environmental, developmental and social data to undertake studies with the ultimate goal of improving human health and well-being. Analyses of data from the recent Generation 1 year 26 follow-up are underway.

Trial registration number

ACTRN12617001599369
Using a period incidence survey to compare antibiotic use in children between a university hospital and a district hospital in a country with low antimicrobial resistance: a prospective observational study
Authors: Thaulow Christian Magnus , Blix Hege Salvesen , Eriksen Beate Horsberg , Ask Ingvild , Myklebust Tor Åge , Berild Dag
Published: May 2019

Objectives

To describe and compare antibiotic use in relation to indications, doses, adherence rate to guidelines and rates of broad-spectrum antibiotics (BSA) in two different paediatric departments with different academic cultures, and identify areas with room for improvement.

Design

Prospective observational survey of antibiotic use.

Setting

Paediatric departments in a university hospital (UH) and a district hospital (DH) in Norway, 2017. The registration period was 1 year at the DH and 4 months at the UH.

Participants

201 children at the DH (mean age 3.8: SD 5.1) and 137 children at the UH (mean age 2.0: SD 5.9) were treated with systemic antibiotics by a paediatrician in the study period and included in the study.

Outcome measures

Main outcome variables were prescriptions of antibiotics, treatments with antibiotics, rates of BSA, median doses and adherence rate to national guidelines.

Results

In total, 744 prescriptions of antibiotics were given at the UH and 638 at the DH. Total adherence rate to guidelines was 75% at the UH and 69% at the DH (p=0.244). The rate of treatments involving BSA did not differ significantly between the hospitals (p=0.263). Use of BSA was related to treatment of central nervous system (CNS) infections, patients with underlying medical conditions or targeted microbiological treatment in 92% and 86% of the treatments, at the UH and DH, respectively (p=0.217). A larger proportion of the children at the DH were treated for respiratory tract infections (p<0.01) compared with the UH. Children at the UH were treated with higher doses of ampicillin and cefotaxime (p<0.05) compared with the DH.

Conclusion

Our results indicate that Norwegian paediatricians have a common understanding of main aspects in rational antibiotic use independently of working in a UH or DH. Variations in treatment of respiratory tract infections and in doses of antibiotics should be further studied.
Associations of theNOS3rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis
Authors: Luo Zhi , Jia Aimei , Lu Zhan , Muhammad Irfan , Adenrele Adebayo , Song Yongyan
Published: May 2019

Background

Circulating nitric oxide (NO) and lipid levels are closely associated with coronary artery disease (CAD). It is unclear whether the rs1799983 polymorphism in endothelial nitric oxide synthase (NOS3) gene is associated with plasma levels of NO and lipids. This systematic review and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) aimed to clarify the relationships between the rs1799983 polymorphism and plasma levels of NO and lipids.

Methods

Sixteen studies (2702 subjects) and 59 studies (14 148 subjects) were identified for the association analyses for NO and lipids, respectively. Mean difference (MD) and 95% CI were used to estimate the effects of the rs1799983 polymorphism on plasma NO and lipid levels. The primary outcome variable was NO, and the secondary outcomes included triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C).

Results

Carriers of the T allele had lower levels of NO (MD −0.27 μmol/L, 95% CI −0.42 to −0.12 μmol/L, p<0.001) and HDL-C (MD −0.07 mmol/L, 95% CI −0.14 to −0.00 mmol/L, p=0.04), and higher levels of TC (MD 0.13 mmol/L, 95% CI 0.06 to 0.20 mmol/L, p<0.001) and LDL-C (MD 0.14 mmol/L, 95% CI 0.05 to 0.22 mmol/L, p=0.002) than the non-carriers. Triglyceride levels were comparable between the genotypes.

Conclusion

The association between the NOS3 rs1799983 polymorphism and CAD may be partly mediated by abnormal NO and lipid levels caused by the T allele.
Comparison of hypoxic effects induced by chemical and physical hypoxia on cardiomyocytes
Authors: Zhao Ru-Zhou , Jiang Shuai , Ru Ning-Yu , Jiao Bo , Yu Zhi-Bin
Published: May 2019

The degree and duration of chemical hypoxia induced by sodium dithionite (Na2S2O4) have not been reported. It is not yet clear how much reduction in the O2 concentration (physical hypoxia) can lead to hypoxia in cultured cardiomyocytes. In this study, oxygen microelectrodes were used to measure changes in the O2 concentration in media containing different concentrations of Na2S2O4. Then, hypoxic effects of 0.8, 1.0, and 2.0 mM Na2S2O4 or 1%, 3%, and 5% O2 in cultured cardiomyocytes from neonatal rats were observed and compared. The results showed that the O2 concentration failed to remain constant by Na2S2O4 treatment during the 180-minute observation period. Only the 2.0 mM Na2S2O4 group significantly increased the expression of hypoxia-inducible factor 1α (HIF-1α) and hypoxic responses. Notably, 3% O2 only significantly increased the expression of HIF-1α in cardiomyocytes, while 1% O2 not only increased the expression of HIF-1α but also increased the apoptotic rate in cardiomyocytes. These results suggest that Na2S2O4 is not suitable for establishing a hypoxic model in cultured neonatal rat cardiomyocytes, and neonatal rat cardiomyocytes cultured at or below 1% O2 induced significant hypoxic effects, which can be used as a starting O2 concentration for establishing a hypoxic cell model.
New physics implication of Higgs precision measurements
Authors: Chen Ning , Gu Jiayin , Han Tao , Li Honglei , Liu Zhen , Song Huayang , Su Shufang , Su Wei , Wu Yongcheng , Yang Jin Min
Published: May 2019

Studying the properties of the Higgs boson can be an important window to explore the physics beyond the Standard Model (SM). In this work, we present studies on the implications of the Higgs precision measurements at future Higgs Factories. We perform a global fit to various Higgs search channels to obtain the 95% C.L. constraints on the model parameter spaces of two-Higgs Doublet Model (2HDM) and Minimal Supersymmetric Standard Model (MSSM). In the 2HDM, we analyze tree-level effects as well as one-loop contributions from the heavy Higgs bosons. The strong constraints on [Formula: see text], heavy Higgs masses and their mass splitting are complementary to direct search of the LHC as well as possible future [Formula: see text] pole precision measurements. For the MSSM, we study both the Higgs couplings and mass precisions. The constraints on the CP-odd Higgs mass [Formula: see text] and stop mass scale [Formula: see text] can be complementary to the direct search of HL-LHC. We also compare the sensitivity of various future Higgs factories, namely, Circular Electron Positron Collider (CEPC), Future Circular Collider (FCC)-ee and International Linear Collider (ILC).
The Anthropology of Populism: Beyond the Liberal Settlement
Authors: Mazzarella William
Published: May 2019

This article suggests that although there is not much of an explicitly defined anthropology of populism, anthropologists have nevertheless been working for many years on the things we talk about when we talk about populism. Anthropologists should thus be exceptionally well situated to divert the debate on populism in creative ways. In particular, I argue that the term populism registers an intensified insistence of collective forces that are no longer adequately organized by formerly hegemonic social forms: a mattering-forth of the collective flesh. The article also shows why populism is such an awkward topic for anthropologists. In part, this discomfort has to do with a tension between anthropologists’ effectively populist commitments to the common sense of common people at a time when that common sense can often look ugly. In part, it has to do with how the populist challenge to liberalism both aligns populist politics with anthropological critiques of liberal norms and puts pressure on anthropology's continued dependence on liberal categories for its own relevance to broader public debates.
Production Networks: A Primer
Authors: Carvalho Vasco M. , Tahbaz-Salehi Alireza
Published: May 2019

This article reviews the literature on production networks in macroeconomics. It presents the theoretical foundations for the role of input–output linkages as a shock propagation channel and as a mechanism for transforming microeconomic shocks into macroeconomic fluctuations. The article also provides a brief guide to the growing literature that explores these themes empirically and quantitatively.
Functional Regulators of Bacterial Flagella
Authors: Subramanian Sundharraman , Kearns Daniel B.
Published: May 2019

Bacteria move by a variety of mechanisms, but the best understood types of motility are powered by flagella ( 72 ). Flagella are complex machines embedded in the cell envelope that rotate a long extracellular helical filament like a propeller to push cells through the environment. The flagellum is one of relatively few biological machines that experience continuous 360° rotation, and it is driven by one of the most powerful motors, relative to its size, on earth. The rotational force (torque) generated at the base of the flagellum is essential for motility, niche colonization, and pathogenesis. This review describes regulatory proteins that control motility at the level of torque generation.
Merger and Mass Ejection of Neutron Star Binaries
Authors: Shibata Masaru , Hotokezaka Kenta
Published: May 2019

Mergers of binary neutron stars and black hole–neutron star binaries are among the most promising sources for ground-based gravitational-wave (GW) detectors and are also high-energy astrophysical phenomena, as illustrated by the observations of GWs and electromagnetic (EM) waves in the event of GW170817. Mergers of these neutron star binaries are also the most promising sites for r-process nucleosynthesis. Numerical simulation in full general relativity (numerical relativity) is a unique approach to the theoretical prediction of the merger process, GWs emitted, mass ejection process, and resulting EM emission. We summarize the current understanding of the processes of neutron star mergers and subsequent mass ejection based on the results of the latest numerical-relativity simulations. We emphasize that the predictions of the numerical-relativity simulations agree broadly with the optical and IR observations of GW170817.
Heat therapy improves glucose tolerance and adipose tissue insulin signaling in polycystic ovary syndrome
Authors: Ely Brett R. , Clayton Zachary S. , McCurdy Carrie E. , Pfeiffer Joshua , Needham Karen Wiedenfeld , Comrada Lindan N. , Minson Christopher T.
Published: May 2019

Polycystic ovary syndrome (PCOS) is associated with high rates of obesity and metabolic dysfunction. Repeated passive heat exposure (termed heat therapy) is a novel lifestyle intervention for improving health in obese women with PCOS. The purpose of this study was to examine changes in metabolic function in obese women with PCOS following heat therapy. Eighteen age- and BMI-matched obese women with PCOS (age: 27 ± 1 yr, BMI: 41.3 ± 1.1 kg/m−2) were assigned to heat therapy (HT) or time control (CON). HT participants underwent 30 one-hour hot tub sessions over 8–10 wk, while CON participants completed all testing but did not undergo heat therapy. Before (Pre), at the mid-point (Mid), and following (Post) 8–10 wk of heat therapy, metabolic health was assessed using a 2-h oral glucose tolerance test, a subcutaneous abdominal fat biopsy (Pre-Post only), and other blood markers relating to metabolic function. HT participants exhibited improved fasting glucose (Pre: 105 ± 3, Post: 89 ± 5mg/dl; P = 0.001), glucose area under the curve (AUC) (Pre: 18,698 ± 1,045, Post: 16,987 ± 1,017 mg·dl−1·min−1; P = 0.028) and insulin AUC (Pre: 126,924 ± 11,730, Post: 91,233 ± 14,429 IU l−1·min−1; P = 0.012). Adipocyte insulin signaling (p-AKT at Ser-473 with 1.2 nM insulin) increased in HT (Pre: 0.29 ± 0.14, Post: 0.93 ± 0.29 AU; P = 0.021). Additionally, serum testosterone declined in HT participants (Pre: 51 ± 7, Post: 34 ± 4 ng/dl; P = 0.033). No parameters changed over time in CON, and no change in BMI was observed in either group. HT substantially improved metabolic risk profile in obese women with PCOS. HT also reduced androgen excess and may improve PCOS symptomology.
Evolution Characteristics of the Cracks in the Completely Disintegrated Carbonaceous Mudstone Subjected to Cyclic Wetting and Drying
Authors: Zeng Ling , Liu Jie , Gao Qian-Feng , Bian Hanbing
Published: May 2019

Completely disintegrated carbonaceous mudstone, a common embankment material, has significant swelling‐shrinkage behavior under cyclic wetting and drying, which often causes the instability of embankments. In this paper, the evolution of the cracks in the completely disintegrated carbonaceous mudstone subjected to cyclic wetting and drying was studied by laboratory tests. The vacuum saturation method and the drying method based on heat lamps and a fan were employed to simulate the wetting and drying processes, respectively. The image processing technique was used to treat the images of the sample surface. Afterward, various geometric parameters of the cracks appeared on the sample surface were measured, and the evolution characteristics of the cracks were analyzed. The results show that with the increase in the number of wetting and drying cycles, the number of cracks on the sample surface gradually increases. After four wetting and drying cycles, the existing cracks produce a large number of small branches, which are connected to form irregular polygonal grids. The development of the cracks in the completely disintegrated carbonaceous mudstone sample can be divided into three stages, i.e., slow development, rapid development, and stable development. Both the surface density of crack and the crack rate first increase and then tend to be stable with the increasing number of wetting and drying cycles. New cracks are mainly generated on the basis of the existing cracks, and some cracks appear to heal under cyclic wetting and drying. The early cracks are mainly developed in the directions of 0°–90° and 300°–360°, and the development rate of the cracks in the directions of 30°, 90°, 140°–150°, and 180°–270° is significantly higher than that of the cracks in other directions.
Handling Parameter Variations during the Treatment of Type 1 Diabetes Mellitus: In Silico Results
Authors: Villa Tamayo María F. , Caicedo Alvarez Michelle A. , Rivadeneira Pablo S.
Published: May 2019

Type 1 diabetic patients need a strict treatment to regulate blood glucose concentration in a target range. Despite the development of different control strategies, the model parameter variations, given by physiological changes, can generate an inaccurate treatment and in consequence hyperglycemia and hypoglycemia episodes. Therefore, it is necessary to use control techniques that compensate such effects and maintain the control goals. Here, the effect of parametric variations is examined by the sensitivity analysis from which the most influential parameters in glycemia dynamics are detected. Based on that, an offset‐free MPC strategy for impulsive systems is given for the first time in literature and simulated for type 1 diabetes treatment. This scheme along with the impulsive zone MPC with artificial variables reestablishes the normoglycemia behavior since the parameter variations are adequately rejected. However, only parametric variations up to 50% from their nominal values are well compensated, which suggests that more robust formulations are needed to ensure a greater rejection of physiological variations.
Permanganate Oxidation of Microcystin-LA: Kinetics, Quantification, and Implications for Effective Drinking Water Treatment
Authors: Szlag David C. , Spies Brian , Szlag Regina G. , Westrick Judy A.
Published: May 2019

Permanganate pretreatment of drinking water is effective in transforming dissolved, noxious contaminants and in reducing halogenated by-products. Permanganate targets specific compounds such as taste and odor compounds, disinfection precursors, manganese, and natural organic contaminants that are not removed readily by conventional treatment alone. Cyanobacterial blooms (cHABs) can increase disinfection by-product precursors as well as the cyanotoxin, microcystin (MC), a potent liver toxin. MC toxicity is conferred by a unique, conserved amino acid, Adda, that inhibits protein phosphatase 1 and 2A. Although over 150 MC congeners have been reported, thousands of MCs are statistically possible. Over the last ten years, one congener, MC-LA, has been reported with increasing frequency, making it one of the most common cyanotoxins identified in North American freshwater systems; yet its oxidation has not been widely studied. Frequently, Adda specific enzyme-linked immunosorbent assay (ELISA) and protein phosphatase inhibition assay (PPIA) are used to quantitate total MCs to evaluate treatment efficiency and exposure. Anecdotal reports suggest that MC degradation products can cause interference with the Adda-ELISA. MC-LA was used as the model MC compound in this study. PPIA quantitation of MC-LA in water agreed with liquid chromatography high resolution mass spectrometry (LC/HRMS), whereas the ELISA quantitation did not agree with LC/HRMS quantitation. We determined the second order rate constant for MC-LA as 118 ± 9 M−1s−1, the activation energy to be 21.2 kJ mol−1, and the rate to be independent of pH between pH 6 and 9. Ten oxidation products (OPs) were observed by LC/HRMS and three primary reaction pathways are proposed. The reaction pathways were used to explain differences in the quantification by Adda-ELISA, HRMS, and PPIA. The oxohydroxylation of MC-LA produced two major OPs, C46H67N7O14[M+H]+= 942.4819 and C46H69N7O15[M+H]+=960.4925. Major OPs may contain an unmodified Adda and are the likely cause of interference with the Adda-ELISA. Several governmental agencies recommend the use of the Adda-ELISA to determine the MC quantitation for treatment efficiency and customer exposure; yet our results suggest that these or other OPs interfere with the Adda-ELISA causing artificially high values for total MCs.