bluuebunny/crossref_metadata_2025 huggingface dataset:
The MHC class-II HLA-DR receptor mediates bat influenza A-like H17N10 virus entry into mammalian cells
Authors: Giotis Efstathios S , Carnell George , Young Erik F. , Ghanny Saleena , Soteropoulos Patricia , Barclay Wendy S , Skinner Michael A , Temperton Nigel
Published: January 2019

Bats are notorious reservoirs of diverse, potentially zoonotic viruses, exemplified by the evolutionarily distinct, influenza A-like viruses H17N10 and H18N11 (BatIVs). The surface glycoproteins [haemagglutinin (H) and neuraminidase (N)] of BatIVs neither bind nor cleave sialic acid receptors, which suggests that these viruses employ cell attachment and entry mechanisms that differ from those of classical influenza A viruses (IAVs). Identifying the cellular factors that mediate entry and determine susceptibility to infection will help assess the host range of BatIVs. Here, we investigated a range of cell lines from different species for their susceptibility to infection by pseudotyped viruses (PV) bearing bat H17 and/or N10 envelope glycoproteins. We show that a number of human haematopoietic cancer cell lines and the canine kidney MDCK II (but not MDCK I) cells are susceptible to H17-pseudotypes (H17-PV). We observed with microarrays and qRT-PCR that the dog leukocyte antigen DLA-DRA mRNA is over expressed in late passaged parental MDCK and commercial MDCK II cells, compared to early passaged parental MDCK and MDCK I cells, respectively. The human orthologue HLA-DRA encodes the alpha subunit of the MHC class II HLA-DR antigen-binding heterodimer. Small interfering RNA- or neutralizing antibody-targeting HLA-DRA, drastically reduced the susceptibility of Raji B cells to H17-PV. Conversely, over expression of HLA-DRA and its paralogue HLA-DRB1 on the surface of the unsusceptible HEK293T/17 cells conferred susceptibility to H17-PV. The identification of HLA-DR as an H17N10 entry mediator will contribute to a better understanding of the tropism of the virus and will elucidate its zoonotic transmission.
Management of family relationship information for a three-generation cohort study
Authors: Shimokawa Kazuro , Ishikuro Mami , Obara Taku , Metoki Hirohito , Mizuno Satoshi , Nagaie Satoshi , Nagai Masato , Yamanaka Chizuru , Matsubara Hiroko , Kato Mayumi , Sato Yuki , Ogishima Soichi , Takai-Igarashi Takako , Kikuya Masahiro , Hozawa Atsushi , Nagami Fuji , Kuriyama Shinichi , Kinoshita Kengo , Yamamoto Masayuki , Tanaka Hiroshi
Published: January 2019

A system for inputting and storing family information, named “BirThree Enrollment,” was developed to promote a birth and three-generation cohort study (BirThree Cohort Study), and this system was operated successfully. In the study, it was necessary to satisfy many operational demands. Input information is overwritten and changed continuously. Complex kinship information must be quickly and accurately input and corrected, and information on those families not yet recruited must be retrieved. For these purposes, many devices are needed, from an input interface to the internal data structure. In the field of genetic statistics, a simple standard expressive form is used for describing family structure. This form has sufficient information for genetics; however, we developed this form further for our purposes in conducting the BirThree Cohort Study. To provide information about family roles as required in the BirThree Cohort Study, we expanded the data structure, and constructed the system that is able to be used for the daily operation. In our system, family pedigree information is stored along with initial clinical information, and enabled the input of all self-reported information to the data base. Operators are able to input this family information before the day is out. As a result, when recruitment is completed, family information will be completed concurrently. Therefore, it is possible to immediately know a certain person’s family structure. By using our system, data correction was improved dramatically, and the system was operated successfully. This study is the first report of the method for storing three generations of family data.
Systematic errors in connectivity inferred from activity in strongly coupled recurrent circuits
Authors: Das Abhranil , Fiete Ila R.
Published: January 2019

Understanding the mechanisms of neural computation and learning will require knowledge of the underlying circuitry. Because it is slow, expensive, or often infeasible to directly measure the wiring diagrams of neural microcircuits, there has long been an interest in estimating them from neural recordings. We show that even sophisticated inference algorithms, applied to large volumes of data from every node in the circuit, are biased toward inferring connections between unconnected but strongly correlated neurons, a situation that is common in strongly recurrent circuits. This e ect, representing a failure to fully “explain away” non-existent connections when correlations are strong, occurs when there is a mismatch between the true network dynamics and the generative model assumed for inference, an inevitable situation when we model the real world. Thus, effective connectivity estimates should be treated with especial caution in strongly connected networks when attempting to infer the mechanistic basis of circuit activity. Finally, we show that activity states of networks injected with strong noise or grossly perturbed away from equilibrium may be a promising way to alleviate the problems of bias error.
Influenza A virus surface proteins are organized to help penetrate host mucus
Authors: Vahey Michael D. , Fletcher Daniel A.
Published: January 2019

Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Although genetic aspects of this balance are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute. Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating an organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole. This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the virus’s conflicting needs to both penetrate mucus and stably attach to the underlying cells, and could contribute to the prevalence of the filamentous phenotype in clinical isolates of IAV.
Comparative analysis of epigenetic aging clocks from CpG characteristics to functional associations
Authors: Liu Zuyun , Leung Diana , Levine Morgan
Published: January 2019

To date, a number of epigenetic clocks have been developed using DNA methylation data, aimed at approximating biological aging in multiple tissues/cells. However, despite the assumption that these clocks are meant to capture the same phenomenon-aging, their correlations with each other are weak, and there is a lack of consistency in their associations with outcomes of aging. Therefore, the goal of this study was to compare and contrast the molecular characteristics and functional associations of 11 existing epigenetic clocks, using data from diverse human tissue and cell types. Results suggest that the CpGs comprised in the various clocks differ in regards to the consistency of their age correlations across tissues/cells. Using microarray expression data from purified CD14+ monocytes, we found that six clocks—Yang, Hannum, Lin, Levine, Horvath1, and Horvath2—has relatively similar transcriptional profiles. Network analysis revealed nine co-expression modules, most of which display robust correlations across various clocks. One significant module—turquoise is involved in mitochondrial translation, gene expression, respiratory chain complex assembly, and oxidative phosphorylation. Finally, using data from 143B cells with chronically depleted mtDNA (rho0) and 143B controls, we found that rho0 cells have more than a three-standard deviation increase in epigenetic age for Levine (p=0.006), Lin (p=0.012), and Yang (p=0.013). In summary, these results demonstrate the shared and contrasting features of existing epigenetic clocks, in regards to the CpG characteristic, tissue specificity, and co-regulatory gene network signatures, and suggesting a link between two hallmarks of aging—epigenetic alterations and mitochondrial dysfunction.
Concurrent Duties
Authors: Taylor Aaron
Published: January 2019

This paper offers an account of concurrent liability, and in particular the existence of, and interaction between, concurrent contractual and non‐contractual duties. It argues for five essential propositions: (1) a defendant can owe simultaneous private law duties towards a claimant, the content of which overlaps in whole or in part; (2) cases of concurrent liability in contract and negligence involve independent duties, which are concurrent but not coextensive; (3) the doctrine of concurrent liability is conceptually distinct from the rule that the claimant must elect between inconsistent remedies; (4) if the defendant commits a wrong in breach of more than one duty, the claimant has a prima facie choice to sue for any of those breaches; and (5) the content of one any duty might affect the content of the other. The last of these principles, it is argued, provide an explanation for the recent decisions in Wellesley Partners v Withers and AIB v Mark Redler.
Reducing Homelessness or Re‐ordering the Deckchairs?
Authors: Cowan Dave
Published: January 2019

The Homelessness Reduction Act 2017 has come into force trumpeting nothing less than the need for a ‘culture change’ among local housing authorities implementing it. Although it aims to reduce homelessness, it is more likely to hide long‐term systemic issues in the housing system. It is argued that the 2017 Act's significant alterations are likely to result in a re‐ordering of the deckchairs on the Titanic of housing policy. Following a biography and critique of the homelessness legislation as being out of time and place, as well as a discussion of the 2017 Act itself, three central points are made: the 2017 Act has ushered in a form of neo‐liberal government of the homeless; the understanding of the household seeking assistance has fundamentally altered, from passive applicant to active citizen; the private rented market provides the sole mechanism for performing the duties but remains problematic.
895. PEREZIA RECURVATA SUBSP. RECURVATA
Authors: Hind Nicholas , Babel Katarzyna
Published: January 2019

Perezia recurvata (Vahl) Less. subsp. recurvata (Compositae: Mutisieae: Nassuaviinae) is described and illustrated. Comments are provided on its cultivation, propagation and availability, although currently only available from one supplier in the United Kingdom. The problematic taxonomy of this genus is discussed. A brief comment is made on the history of the type collections of two synonyms of Perezia recurvata, and of Perdicium L. within which Vahl originally described the basionym of Perezia recurvata. The adaptive anatomy of the leaves of Perezia recurvata are commented on and likened to those found in Nassauvia falklandica, and the presence of the unique group of phytochemical compounds, the recurvatianes, is mentioned.
Agricultural Use of Reclaimed Water in Florida: Food for Thought
Authors: Parsons Lawrence R.
Published: January 2019

Florida has successfully irrigated agricultural crops with reclaimed water (RW) for more than 50 years. Florida and California are the two largest producers and users of RW in the U.S. To allay early fears about RW, Florida regulatory agencies established rules in the 1980s that prohibited direct contact of RW with crops that are not processed but eaten raw. This means that RW cannot be used for direct contact irrigation or frost protection of crops such as strawberries or blueberries. Other states do not have such limitations on RW use. Reclaimed water has an excellent safety record, and no health problems have occurred from its use. The main edible crop that uses RW in Florida is citrus. Reclaimed water contains some macro‐ and micronutrients, but can provide only a small amount of nitrogen (N) to citrus. Some RW sources can provide adequate N to turf grass. Reclaimed water production has increased dramatically in the past 20 years, and much of the increased flow has gone to public access irrigation. While still important, agricultural use of RW as a percentage of total flow may continue to decrease, but the supply of RW continues to grow as Florida’s population increases.
Water Chemistry During Baseflow Helps Inform Watershed Management: A Case Study of the Lake Wister Watershed, Oklahoma
Authors: Austin Bradley J. , Patterson Steve , Haggard Brian E.
Published: January 2019

Nonpoint source (NPS) pollution from agricultural and urban development is a primary source of nutrients and decreased water quality in aquatic systems. Installation of best management practices (BMPs) within critical source areas of the watershed can be helpful at reducing the transport of nutrients to waterbodies; however, prioritizing these areas may be difficult. The objective of this study was to develop several potential frameworks for prioritizing subwatersheds using baseflow water chemistry data in relation to a simple human development index (HDI; total percent agriculture and urban development). At a monthly interval, samples were collected at 26 sites throughout the Oklahoma portion of the Lake Wister Watershed (LWW) and analyzed for total nitrogen, total phosphorus, total suspended solids, and chlorophyll a. Changepoint analysis for each parameter found significant thresholds for each of the parameters ranging from 20 to 30% HDI. Changepoint analysis summary statistics were used to develop prioritization frameworks for the LWW that could be used to target subwatersheds where BMP installation would have the greatest effect at improving water quality. Additionally, regression models developed from the relationships between water quality parameters and HDI values serve as realistic targets for improving water quality, with the modeled line representing the target concentration for a given HDI value. After BMPs have been implemented, baseflow monitoring should continue at the subwatershed scale to track changes in water quality. Focusing monitoring efforts at the subwatershed scale will provide an earlier indication of the effectiveness of BMPs, as it may take several decades to detect improvements in water quality at the larger watershed scale.
Food Security as a Water Grand Challenge
Authors: Bangira Courage
Published: January 2019

Perhaps the biggest challenge the world faces is providing sufficient, nutritious, and safe food at the right time for its ever‐increasing population. Considering current world population growth trends, it is estimated that the global population will be about 10 billion by the year 2050. Therefore, food production should at least double in the same period if food security is to be satisfied. Water and land resources play a pivotal role in agriculture and directly connect to food security. At the same time, the capacity to produce food is constrained by global climate changes and increased pressure on land resources. These challenges are more severe in Southern Asia, Sub‐Saharan Africa, and East Asia, where conflict and lack of capacity to fund agricultural research and food production are common. Strategies that simultaneously increase food production and reduce threats to food security are therefore needed. The objectives of this paper are to review the grand challenges of global food security and to propose strategies for mitigating food insecurity, with an emphasis on the link between water resources and food production.
The Non‐Observed Economy in Portugal: The monetary model and the MIMIC model
Authors: Soares Cláudia , Afonso Óscar
Published: January 2019

This paper offers estimations for the Portuguese path of the Non‐Observed Economy (NOE), in the period 1970–2015, through two seminal approaches: monetary method and the Multiple Indicators Multiple Causes (MIMIC) model. It is observed that the tax burden and social benefits are its main causes. Then, to get a more in‐depth understanding of the phenomenon, it provides a study of the Granger causality between the NOE and the official Gross Domestic Product (GDP), emphasizing the implications of the NOE on the Portuguese economy. Evidence has been found for the existence of bidirectional causality between the NOE and the GDP, suggesting that the formal economy affects the NOE, and conversely that the NOE affects the economic growth.
Duplex nucleic acid test for the detection of chikungunya and dengue RNA viruses in blood donations
Authors: Stramer Susan L. , Stanley Jean , Nguyen Megan L. , Bertuzis Rasa , Huynh Nancy , Duncan John R. , Albrecht Patrick , Pate Lisa L. , Galel Susan A.
Published: January 2019

BACKGROUND

Chikungunya (CHIKV) and dengue (DENV) viruses are primarily mosquito‐borne, but transfusion transmission can occur (DENV) or is likely (CHIKV). In the absence of commercially available blood screening assays, a variety of strategies to ensure recipient safety in the face of expanding CHIKV and/or DENV outbreaks have been used.

STUDY DESIGN AND METHODS

Performance of cobas CHIKV/DENV, a qualitative RNA detection assay for use on the cobas 6800/8800 Systems, was evaluated at two sites (Roche Molecular Systems, Inc. [RMS], and the American Red Cross [ARC]). Analytical sensitivity, genotype inclusion, correlation with other assays, and reproducibility used clinical CHIKV‐ or DENV‐positive samples and secondary standards for DENV Types 1 to 4 and for three CHIKV genotypes (Asian; East Central South African; and West African); each secondary standard was traceable to international reference panels or reagents. Evaluation of analytic specificity assessed other microorganisms for interference and cross‐reactivity; clinical specificity was determined by individually testing 10,528 volunteer blood donations from the continental United States.

RESULTS

The 50 and 95% limit of detection (LoD) obtained by RMS for CHIKV, Asian genotype was 1.8 and 6.8 Detectable Units (DU)/mL, respectively, and 0.14 and 0.63 International Units (IU)/mL, respectively for DENV‐1. No significant differences in detection occurred by testing at a second site, the ARC (2.4 and 10.5 DU/mL for CHIKV and 0.15 and 0.60 IU/mL for DENV). Clinical specificity was 100% (95% confidence interval, 99.965%‐100%) for CHIKV and DENV.

CONCLUSIONS

The high sensitivity and specificity of the cobas CHIKV/DENV test, as demonstrated in these evaluations, indicate its suitability for blood donation screening.
Mechanics of Irradiation-Induced Structural Changes in a Lipid Vesicle
Authors: Liao Xinyu , Purohit Prashant K.
Published: January 2019

Irradiation-induced oxidation of lipid membranes is implicated in diseases and has been harnessed in medical treatments. Irradiation induces the formation of oxidative free radicals, which attack double bonds in the hydrocarbon chains of lipids. Studies of the kinetics of this reaction suggest that the result of the first stage of oxidation is a structural change in the lipid that causes an increase in the area per molecule in a vesicle. Since area changes are directly connected to membrane tension, irradiation-induced oxidation affects the mechanical behavior of a vesicle. Here, we analyze shape changes of axisymmetric vesicles that are under simultaneous influence of adhesion, micropipette aspiration, and irradiation. We study both the equilibrium and kinetics of shape changes and compare our results with experiments. The tension–area relation of a membrane, which is derived by accounting for thermal fluctuations, and the time variation of the mechanical properties due to oxidation play important roles in our analysis. Our model is an example of the coupling of mechanics and chemistry, which is ubiquitous in biology.
Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder
Authors: Winter Aaron W , Salimi Ali , Ospina Luis H , Roos Jonathan C P
Published: January 2019

Gaucher disease (GD) results from a deficiency of glucocerebrosidase activity and the subsequent accumulation of the enzyme’s metabolites, principally glucosylsphingosine and glucosylceramide. There are three principal forms: Type I, which is the most common, is usually considered non-neuronopathic. Type II, III and IIIc manifest earlier and have neurological sequelae due to markedly reduced enzyme activity. Gaucher’s can be associated with ophthalmological sequelae but these have not been systematically reviewed. We therefore performed a comprehensive literature review of all such ophthalmic abnormalities associated with the different types of Gaucher disease. We systematically searched the literature (1950 – present) for functional and structural ocular abnormalities arising in patients with Gaucher disease and found that all subtypes can be associated with ophthalmic abnormalities; these range from recently described intraocular lesions to disease involving the adnexae, peripheral nerves and brain. In summary, Gaucher can affect most parts of the eye. Rarely is it sight-threatening; some but not all manifestations are amenable to treatment, including with enzyme replacement and substrate reduction therapy. Retinal involvement is rare but patients with ocular manifestations should be monitored and treated early to reduce the risk of progression and further complications. As Gaucher disease is also associated with Parkinsons disease and may also confer an increased risk of malignancy (particularly haematological forms and melanoma), any ocular abnormalities should be fully investigated to exclude these potential underlying conditions.
Performance of injury severity measures in trauma research: a literature review and validation analysis of studies from low-income and middle-income countries
Authors: Mehmood Amber , Hung Yuen W , He Huan , Ali Shahmir , Bachani Abdul M
Published: January 2019

Introduction

Characterisation of injury severity is an important pillar of scientific research to measure and compare the outcomes. Although majority of injury severity measures were developed in high-income countries, many have been studied in low-income and middle-income countries (LMICs). We conducted this study to identify and characterise all injury severity measures, describe how widely and frequently they are used in trauma research from LMICs, and summarise the evidence on their performance based on empirical and theoretical validation​ analysis.

Methods

First, a list of injury measures was identified through PubMed search. Subsequently, a systematic search of PubMed, Global Health and EMBASE was undertaken on LMIC trauma literature published from January 2006 to June 2016, in order to assess the application and performance of injury severity measures to predict in-hospital mortality. Studies that applied one or more global injury severity measure(s) on all types of injuries were included, with the exception of war injuries and isolated organ injuries.

Results

Over a span of 40 years, more than 55 injury severity measures were developed. Out of 3862 non-duplicate citations, 597 studies from 54 LMICs were listed as eligible studies. Full-text review revealed 37 studies describing performance of injury severity measures for outcome prediction. Twenty-five articles from 13 LMICs assessed the validity of at least one injury severity measure for in-hospital mortality. Injury severity score was the most commonly validated measure in LMICs, with a wide range of performance (area under the receiver operating characteristic curve (AUROC) between 0.9 and 0.65). Trauma and Injury Severity Score validation studies reported AUROC between 0.80 and 0.98.

Conclusion

Empirical studies from LMICs frequently use injury severity measures, however, no single injury severity measure has shown a consistent result in all settings or populations and thus warrants validation studies for the diversity of LMIC population.
Effects of exercise interventions on cardiovascular health in individuals with chronic, motor complete spinal cord injury: protocol for a randomised controlled trial [Cardiovascular Health/Outcomes: Improvements Created by Exercise and education in SCI (CHOICES) Study]
Authors: Krassioukov Andrei V , Currie Katharine D , Hubli Michèle , Nightingale Tom E , Alrashidi Abdullah A , Ramer Leanne , Eng Janice J , Ginis Kathleen A Martin , MacDonald Maureen J , Hicks Audrey , Ditor Dave , Oh Paul , Verrier Molly C , Craven Beverly Catharine
Published: January 2019

Introduction

Recent studies demonstrate that cardiovascular diseases and associated complications are the leading cause of morbidity and mortality in individuals with spinal cord injury (SCI). Abnormal arterial stiffness, defined by a carotid–to-femoral pulse wave velocity (cfPWV) ≥10 m/s, is a recognised risk factor for heart disease in individuals with SCI. There is a paucity of studies assessing the efficacy of conventional training modalities on arterial stiffness and other cardiovascular outcomes in this population. Therefore, this study aims to compare the efficacy of arm cycle ergometry training (ACET) and body weight-supported treadmill training (BWSTT) on reducing arterial stiffness in individuals with chronic motor complete, high-level (above the sixth thoracic segment) SCI.

Methods and analysis

This is a multicentre, randomised, controlled, clinical trial. Eligible participants will be randomly assigned (1:1) into either ACET or BWSTT groups. Sixty participants with chronic (>1 year) SCI will be recruited from three sites in Canada (Vancouver, Toronto and Hamilton). Participants in each group will exercise three times per week up to 30 min and 60 min for ACET and BWSTT, respectively, over the period of 6 months. The primary outcome measure will be change in arterial stiffness (cfPWV) from baseline. Secondary outcome measures will include comprehensive assessments of: (1) cardiovascular parameters, (2) autonomic function, (3) body composition, (4) blood haematological and metabolic profiles, (5) cardiorespiratory fitness and (6) quality of life (QOL) and physical activity outcomes. Outcome measures will be assessed at baseline, 3 months, 6 months and 12 months (only QOL and physical activity outcomes). Statistical analyses will apply linear-mixed modelling to determine the training (time), group (ACET vs BWSTT) and interaction (time × group) effects on all outcomes.

Ethics and dissemination

Ethical approval was obtained from all three participating sites. Primary and secondary outcome data will be submitted for publication in peer-reviewed journals and widely disseminated.

Trial registration number

NCT01718977; Pre-results.

Trial status

Recruitment for this study began on January 2013 and the first participant was randomized on April 2013. Recruitment stopped on October 2018.
Predicting poorer health outcomes in older community-dwelling patients with multimorbidity: prospective cohort study assessing the accuracy of different multimorbidity definitions
Authors: Sasseville Maxime , Smith Susan M , Freyne Lisa , McDowell Ronald , Boland Fiona , Fortin Martin , Wallace Emma
Published: January 2019

Purpose

Multimorbidity is commonly defined and measured using condition counts. The UK National Institute for Health Care Excellence Guidelines for Multimorbidity suggest that a medication-orientated approach could be used to identify those in need of a multimorbidity approach to management.

Objectives

To compare the accuracy of medication-based and diagnosis-based multimorbidity measures at higher cut-points to identify older community-dwelling patients who are at risk of poorer health outcomes.

Design

A secondary analysis of a prospective cohort study with a 2-year follow-up (2010–2012).

Setting

15 general practices in Ireland.

Participants

904 older community-dwelling patients.

Exposure

Baseline multimorbidity measurements based on both medication classes count (MCC) and chronic disease count (CDC).

Outcomes

Mortality, self-reported health related quality of life, mental health and physical functioning at follow-up.

Analysis

Sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) adjusting for clustering by practice for each outcome using both definitions.

Results

Of the 904 baseline participants, 53 died during follow-up and 673 patients completed the follow-up questionnaire. At baseline, 223 patients had 3 or more chronic conditions and 89 patients were prescribed 10 or more medication classes. Sensitivity was low for both MCC and CDC measures for all outcomes. For specificity, MCC was better for all outcomes with estimates varying from 88.8% (95% CI 85.2% to 91.6%) for physical functioning to 90.9% (95% CI 86.2% to 94.1%) for self-reported health-related quality of life. There were no differences between MCC and CDC in terms of PPV and NPV for any outcomes.

Conclusions

Neither measure demonstrated high sensitivity. However, MCC using a definition of 10 or more regular medication classes to define multimorbidity had higher specificity for predicting poorer health outcomes. While having limitations, this definition could be used for proactive identification of patients who may benefit from targeted clinical care.
Acupuncture or metformin to improve insulin resistance in women with polycystic ovary syndrome: study protocol of a combined multinational cross sectional case-control study and a randomised controlled trial
Authors: Stener-Victorin Elisabet , Zhang Haolin , Li Rong , Friden Cecilia , Li Dong , Wang Wei , Wang Haining , Chang Cuiqing , Li Shi , Huo ZeJun , Zhang Hua , Ji Xiaolan , Linden-Hirschberg Angelica , Qiao Jie
Published: January 2019

Introduction

Polycystic ovary syndrome (PCOS) is linked to hyperinsulinemia and insulin resistance with dysfunctional glucose metabolism. Pilot studies suggests that acupuncture treatment with combined manual and low-frequency electrical stimulation (electroacupuncture (EA)) of the needles decrease circulating glycated haemoglobulin (HbA1c) and homeostatic model assessment-insulin resistance. Therefore, we here aim to investigate if acupuncture treatment or metformin together with lifestyle or lifestyle management alone improves insulin sensitivity and related symptoms in overweight/obese women with PCOS.

Methods and analysis

This is a two-centre multinational (Sweden and China), cross-sectional case–control study combined with an open-labelled randomised controlled trial (RCT). Participants are randomised to one of three groups: (1) EA 2–3 times/week during 4 months+lifestyle management; (2) metformin, 500 mg, three/day during 4 months+lifestyle management; or (3) lifestyle management alone. The primary outcome measure in the RCT is changes in HbA1C. A total of 123 obese overweight women with PCOS will be enrolled and randomised into one of the three groups with a target power of at least 80% and 5% significance level based on two-sided tests.

Ethics and dissemination

The study has been approved by the Regional Ethical Review Board of Stockholm and of Peking University Third Hospital, China. Primary outcome data of the RCT will be published in a relevant journal together with supporting secondary outcome measurements. Further, outcome measurements will be published in separate papers as well as case–control data.

Expected results

We anticipate that EA and metformin, both with lifestyle management, are equally effective and superior to lifestyle management alone for improvement of glycaemic control.

Trial registration numbers

NCT02647827and EudraCT2015-004250-18.
Patient-reported outcome and experience measures for diabetes: development of scale models, differences between patient groups and relationships with cardiovascular and diabetes complication risk factors, in a combined registry and survey study in Sweden
Authors: Borg Sixten , Eeg-Olofsson Katarina , Palaszewski Bo , Svedbo Engström Maria , Gerdtham Ulf-G , Gudbjörnsdottir Soffia
Published: January 2019

Purpose

The Swedish National Diabetes Register (NDR) has developed a diabetes-specific questionnaire to collect information on individuals' management of their diabetes, collaboration with healthcare providers and the disease’s impact on daily life. Our main objective was to develop measures of well-being, abilities to manage diabetes and judgements of diabetes care, and to detect and quantify differences using the NDR questionnaire.

Design, setting and participants

The questionnaire was analysed with using responses from 3689 participants with type 1 and 2 diabetes, randomly sampled from the NDR population, combined with register data on patient characteristics and cardiovascular and diabetes complication risk factors.

Methods

We used item response theory to develop scales for measuring well-being, abilities to manage diabetes and judgements of diabetes care (scores). Test–retest reliability on the scale level was analysed with intraclass correlation. Associations between scores and risk factor levels were investigated with subgroup analyses and correlations.

Results

We obtained scales with satisfactory measurement properties, covering patient reported outcome measures such as general well-being and being free of worries, and patient reported experience measure, for example, access and continuity in diabetes care. All scales had acceptable test–retest reliability and could detect differences between diabetes types, age, gender and treatment subgroups. In several aspects, for example, freedom of worries, type 1 patients report lower than type 2, and younger patients lower than older. Associations were found between some scores and glycated haemoglobin, but none with systolic blood pressure or low-density lipoprotein cholesterol. Clinicians report positive experience of using scores, visually presented, in the patient dialogue.

Conclusions

The questionnaire measures and detects differences in patient well-being, abilities and judgements of diabetes care, and identifies areas for improvement. To further improve diabetes care, we conclude that patient-reported measures are important supplements to cardiovascular and diabetes complication risk factors, reflecting patient experiences of living with diabetes and diabetes care.
MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial
Authors: Matthews Claire , Freeman Carol , Sharples Linda D , Fox-Rushby Julia , Tod Angela , Maskell Nicholas A , Edwards John G , Coonar Aman S , Sivasothy Pasupathy , Hughes Victoria , Rahman Najib M , Waller David A , Rintoul Robert Campbell
Published: January 2019

Introduction

One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand.

Methods and analysis

MesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months.

Ethics and dissemination

This study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy.

Trial registration

NCT03412357.
Effect of hyperbaric oxygen therapy and corticosteroid therapy in military personnel with acute acoustic trauma
Authors: Bayoumy A B , van der Veen E L , van Ooij P-J A M , Besseling-Hansen F S , Koch D A A , Stegeman I , de Ru J A
Published: January 2019

Introduction

Acute acoustic trauma (AAT) is a sensorineural hearing impairment due to exposure to an intense impulse noise which causes cochlear hypoxia. Hyperbaric oxygen therapy (HBO) could provide an adequate oxygen supply. The aim was to investigate the effectiveness of early treatment with combined HBO and corticosteroid therapy in patients with AAT compared with corticosteroid monotherapy.

Methods

A retrospective study was performed on military personnel diagnosed with AAT between November 2012 and December 2017. Inclusion criteria for HBO therapy were hearing loss of 30 dB or greater on at least one, 25 dB or more on at least two, or 20 dB or more on three or more frequencies as compared with the contralateral ear.

Results

Absolute hearing improvements showed significant differences (independent t-test) between patients receiving HBO and the control group at 500 Hz (p=0.014), 3000 Hz (p=0.023), 4000 Hz (p=0.001) and 6000 Hz (p=0.01) and at the mean of all frequencies (p=0.002). Relative hearing improvements were significantly different (independent t-test) at 4000 Hz (p=0.046) and 6000 Hz (p=0.013) and at all frequencies combined (p=0.005). Furthermore, the percentage of patients with recovery to the functional level required by the Dutch Armed Forces (clinical outcome score) was higher in the HBO group.

Conclusions

Early-stage combination therapy for patients with AAT was associated with better audiometric results at higher frequencies and better clinical outcome score.
Operation RUMAN and Hurricane IRMA: planning, execution and recovery
Authors: Nelstrop Andrew M
Published: January 2019

Operation RUMAN was the UK response in the Autumn of 2017 to the Category 5 Hurricane IRMA, which affected the British Overseas Territories in the Caribbean. The Joint Operations Area (JOA) spanned an archipelago of Islands over 1000 nm across, stretching logistical and medical doctrinal clinical timelines in a rapidly changing and generally high risk medical environment. Despite significant challenges and a relatively suboptimal start line position, the Operation was a success from a medical perspective, with lower than expected dNBI rates. This paper, written from the medical Operational in-Theatre HQ perspective, charts the phases of Operation RUMAN during Planning, Execution and Recovery. It examines the context and lessons that arose from the Operation RUMAN that could inform future fast-moving Humanitarian Aid and Disaster Relief Operations.
The Psychology of Cultural Dynamics: What Is It, What Do We Know, and What Is Yet to Be Known?
Authors: Kashima Yoshihisa , Bain Paul G. , Perfors Amy
Published: January 2019

The psychology of cultural dynamics is the psychological investigation of the formation, maintenance, and transformation of culture over time. This article maps out the terrain, reviews the existing literature, and points out potential future directions of this research. It is divided into three parts. The first part focuses on micro-cultural dynamics, which refers to the social and psychological processes that contribute to the dissemination and retention of cultural information. The second part, on micro–macro dynamics, investigates how micro-level processes give rise to macro-cultural dynamics. The third part focuses on macro-cultural dynamics, referring to the distribution and long-term trends involving cultural information in a population, which in turn enable and constrain the micro-level processes. We conclude the review with a consideration of future directions, suggesting behavior change research as translational research on cultural dynamics.
Liver X Receptor/Retinoid X Receptor Pathway Plays a Regulatory Role in Pacing‐Induced Cardiomyopathy
Authors: Lin Yu‐Sheng , Chang Tzu‐Hao , Shi Chung‐Sheng , Wang Yi‐Zhen , Ho Wan‐Chun , Huang Hsien‐Da , Chang Shih‐Tai , Pan Kuo‐Li , Chen Mien‐Cheng
Published: January 2019

Background

The molecular mechanisms through which high‐demand pacing induce myocardial dysfunction remain unclear.

Methods and Results

We created atrioventricular block in pigs using dependent right ventricular septal pacing for 6 months. Echocardiography was performed to evaluate dyssynchrony between pacing (n=6) and sham control (n=6) groups. Microarray and enrichment analyses were used to identify differentially expressed genes (
DEG
s) in the left ventricular (
LV
) myocardium between pacing and sham control groups. Histopathological and protein changes were also analyzed and an A cell pacing model was also performed. Pacing significantly increased mechanical dyssynchrony. Enrichment analysis using Ingenuity Pathway Analysis and the activation z‐score analysis method demonstrated that there were 5
DEG
s (
ABCA
1,
APOD
,
CLU
,
LY
96, and
SERPINF
1) in the
LV
septum (z‐score=−0.447) and 5
DEG
s (
APOD
,
CLU
,
LY
96,
MSR
1, and
SERPINF
1) in the
LV
free wall (z‐score=−1.000) inhibited the liver X receptor/retinoid X receptor (
LXR
/
RXR
) pathway, and 4
DEG
s (
ACTA
2,
MYL
1,
PPP
2R3A, and
SNAI
2) activated the integrin‐linked kinase (
ILK
) pathway in the
LV
septum (z‐score=1.000). The pacing group had a larger cell size, higher degree of myolysis and fibrosis, and increased expression of intracellular lipid, inflammatory cytokines, and apoptotic markers than the sham control group. The causal relationships between pacing and
DEG
s related to
LXR
/
RXR
and
ILK
pathways, apoptosis, fibrosis, and lipid expression after pacing were confirmed in the cell pacing model. Luciferase reporter assay in the cell pacing model also supported inhibition of the
LXR
pathway by pacing.

Conclusions

Right ventricular septal‐dependent pacing was associated with persistent
LV
dyssynchrony–induced cardiomyopathy through inhibition of the
LXR
/
RXR
pathway.
Using Photovoice to Document Living With Mental Illness on a College Campus
Authors: Skoy Elizabeth , Werremeyer Amy
Published: January 2019

Almost one-fourth of college students are living with a mental illness. Although much discussion has taken place on the mental health of today’s students, information from the students living with mental illness is lacking. The purpose of this study was to allow college students living with mental illness to document and communicate their realities with peers and university stakeholders through the participatory action research methodology, Photovoice. Seventeen college students who were prescribed at least one medication used to treat mental illness were given disposable cameras and asked to take photographs reflecting their realities of living with mental illness. Students met individually with researchers for reflection and as a focus group with other participants to discuss their photographs. All meetings were audio recorded, transcribed and qualitatively analysed. An additional meeting was held to communicate the students’ realities with campus stakeholders. Main themes identified were: insights into campus services, increasing awareness and educating others, support, and barriers to getting better. Photovoice was an effective methodology to allow college students living with mental illness to communicate with campus stakeholders to increase awareness and education. Through the sharing of photographs and reflections, policies and practices affecting students living with mental illness are being examined.
Transplantation of mesenchymal stem cells genetically engineered to overexpress interleukin-10 promotes alternative inflammatory response in rat model of traumatic brain injury
Authors: Peruzzaro S. T. , Andrews M. M. M. , Al-Gharaibeh A. , Pupiec O. , Resk M. , Story D. , Maiti P. , Rossignol J. , Dunbar G. L.
Published: January 2019

Background

Traumatic brain injury (TBI) is a major cause for long-term disability, yet the treatments available that improve outcomes after TBI limited. Neuroinflammatory responses are key contributors to determining patient outcomes after TBI. Transplantation of mesenchymal stem cells (MSCs), which release trophic and pro-repair cytokines, represents an effective strategy to reduce inflammation after TBI. One such pro-repair cytokine is interleukin-10 (IL-10), which reduces pro-inflammatory markers and trigger alternative inflammatory markers, such as CD163. In this study, we tested the therapeutic effects of MSCs that were engineered to overexpress IL-10 when transplanted into rats following TBI in the medial frontal cortex.

Methods

Thirty-six hours following TBI, rats were transplanted with MSCs and then assessed for 3 weeks on a battery of behavioral tests that measured motor and cognitive abilities. Histological evaluation was then done to measure the activation of the inflammatory response. Additionally, immunomodulatory effects were evaluated by immunohistochemistry and Western blot analyses.

Results

A significant improvement in fine motor function was observed in rats that received transplants of MSCs engineered to overexpress IL-10 (MSCs + IL-10) or MSCs alone compared to TBI + vehicle-treated rats. Although tissue spared was unchanged, anti-inflammatory effects were revealed by a reduction in the number of glial fibrillary acidic protein cells and CD86 cells in both TBI + MSCs + IL-10 and TBI + MSC groups compared to TBI + vehicle rats. Microglial activation was significantly increased in the TBI + MSC group when compared to the sham + vehicle group. Western blot data suggested a reduction in tumor necrosis factor-alpha in the TBI + MSCs + IL-10 group compared to TBI + MSC group. Immunomodulatory effects were demonstrated by a shift from classical inflammation expression (CD86) to an alternative inflammation state (CD163) in both treatments with MSCs and MSCs + IL-10. Furthermore, co-labeling of both CD86 and CD163 was detected in the same cells, suggesting a temporal change in macrophage expression.

Conclusions

Overall, our findings suggest that transplantation of MSCs that were engineered to overexpress IL-10 can improve functional outcomes by providing a beneficial perilesion environment. This improvement may be explained by the shifting of macrophage expression to a more pro-repair state, thereby providing a possible new therapy for treating TBI.
Femtosecond Laser in Cataract Surgery: What Makes it Worth it? or not?
Authors: Stonecipher Karl , Parrish Joseph , Stonecipher Megan , Maxwell Jamison , P. Maxwell Donald
Published: January 2019

This review is designed to look at a prospective evaluation of the use of the femtosecond laser and manual incision standard cataract surgery in one center with one surgeon focusing on visual outcomes and complications. Multiple studies support both benefits, risks, alternatives, and differences between manual capsulotomy combined with standard manual incision cataract surgery and cataract surgery employing the femtosecond laser in conjunction with routine phacoemulsification. The purpose of this study was to evaluate early postoperative outcomes using a prospective evaluation of cases from one surgeon over the course of two years from 2015-2017. The first group of cases involves 2134 eyes comparing phacoemulsification time in seconds (PT), ultrasound time in seconds (UT), and cumulative delivered energy (CDE). The second group of cases involves 1913 eyes that were Lens Opacification Classification III similar and without other ocular or lenticular abnormalities. Finally, a subgroup from the latter group (n=150) were evaluated over the course of two days and postoperative 3-hour examinations (visual acuity) were compared.