bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonreciprocal complementation of KNOX gene function in land plants
Authors: Frangedakis Eftychios , Saint‐Marcoux Denis , Moody Laura A. , Rabbinowitsch Ester , Langdale Jane A.
Published: November 2016

Class I KNOTTED‐LIKE HOMEOBOX (KNOX) proteins regulate development of the multicellular diploid sporophyte in both mosses and flowering plants; however, the morphological context in which they function differs.

In order to determine how Class I KNOX function was modified as land plants evolved, phylogenetic analyses and cross‐species complementation assays were performed.

Our data reveal that a duplication within the charophyte sister group to land plants led to distinct Class I and Class II KNOX gene families. Subsequently, Class I sequences diverged substantially in the nonvascular bryophyte groups (liverworts, mosses and hornworts), with moss sequences being most similar to those in vascular plants. Despite this similarity, moss mutants were not complemented by vascular plant KNOX genes. Conversely, the Arabidopsis brevipedicellus (bp‐9) mutant was complemented by the PpMKN2 gene from the moss Physcomitrella patens. Lycophyte KNOX genes also complemented bp‐9 whereas fern genes only partially complemented the mutant. This lycophyte/fern distinction is mirrored in the phylogeny of KNOX‐interacting BELL proteins, in that a gene duplication occurred after divergence of the two groups.

Together, our results imply that the moss MKN2 protein can function in a broader developmental context than vascular plant KNOX proteins, the narrower scope having evolved progressively as lycophytes, ferns and flowering plants diverged.
Immune reactivity after adenoviral‐mediated aquaporin‐1 cDNA transfer to human parotid glands
Authors: Alevizos I , Zheng C , Cotrim AP , Goldsmith CM , McCullagh L , Berkowitz T , Strobl SL , Malyguine A , Kopp WC , Chiorini JA , Nikolov NP , Neely M , Illei GG , Baum BJ
Published: November 2016

Objectives

The purpose of this study was to examine the humoral and cellular immune reactivity to adenoviral vector (AdhAQP1) administration in the human parotid gland over the first 42 days of a clinical gene therapy trial.

Methods

Of eleven treated subjects, five were considered as positive responders (Baum et al, 2012). Herein, we measured serum neutralizing antibody titers, circulating cytotoxic lymphocytes, and lymphocyte proliferation in peripheral blood mononuclear cells. Additionally, after adenoviral vector stimulation of lymphocyte proliferation, we quantified secreted cytokine levels.

Results

Responders showed little to modest immune reactivity during the first 42 days following gene transfer. Additionally, baseline serum neutralizing antibody titers to serotype 5‐adenovirus generally were not predictive of a subject's response to parotid gland administration of AdhAQP1. Cytokine profiling from activated peripheral blood mononuclear cells could not distinguish responders and non‐responders.

Conclusions

The data are the first to describe immune responses after adenoviral vector administration in a human parotid gland. Importantly, we found that modest (2–3 fold) changes in systemic cell‐mediated immune reactivity did not preclude positive subject responses to gene transfer. However, changes beyond that level likely impeded the efficacy of gene transfer.
Selective gene dosage by CRISPR‐Cas9 genome editing in hexaploid Camelina sativa
Authors: Morineau Céline , Bellec Yannick , Tellier Frédérique , Gissot Lionel , Kelemen Zsolt , Nogué Fabien , Faure Jean‐Denis
Published: November 2016

In many plant species, gene dosage is an important cause of phenotype variation. Engineering gene dosage, particularly in polyploid genomes, would provide an efficient tool for plant breeding. The hexaploid oilseed crop Camelina sativa, which has three closely related expressed subgenomes, is an ideal species for investigation of the possibility of creating a large collection of combinatorial mutants. Selective, targeted mutagenesis of the three delta‐12‐desaturase (FAD2) genes was achieved by CRISPR‐Cas9 gene editing, leading to reduced levels of polyunsaturated fatty acids and increased accumulation of oleic acid in the oil. Analysis of mutations over four generations demonstrated the presence of a large variety of heritable mutations in the three isologous CsFAD2 genes. The different combinations of single, double and triple mutants in the T3 generation were isolated, and the complete loss‐of‐function mutants revealed the importance of delta‐12‐desaturation for Camelina development. Combinatorial association of different alleles for the three FAD2 loci provided a large diversity of Camelina lines with various lipid profiles, ranging from 10% to 62% oleic acid accumulation in the oil. The different allelic combinations allowed an unbiased analysis of gene dosage and function in this hexaploid species, but also provided a unique source of genetic variability for plant breeding.
Everyday emotion word and personal pronoun use reflects dyadic adjustment among couples coping with breast cancer
Authors: KARAN ALEXANDER , WRIGHT ROBERT C. , ROBBINS MEGAN L.
Published: November 2016

Dyadic adjustment is integral for couples facing breast cancer; therefore, it is important to identify its everyday indicators. A total of 52 couples coping with breast cancer wore the Electronically Activated Recorder (EAR) for one weekend and completed the Dyadic Adjustment Scale to investigate how dyadic adjustment manifests in noncancer‐related word use. Multilevel models revealed that partners', rather than one's own, positive emotion words positively related to dyadic adjustment. Conversely, spouses' negative emotion words and patients' anger words were negatively related to dyadic adjustment. Furthermore, focus on spouses rather than patients (spouses “I” and patients “you”) positively related to dyadic adjustment. Results revealed that dyadic adjustment can be reflected in couples' everyday word use, serving as an objective indicator of marital quality.
A Case of Solitary Well‐Differentiated Papillary Mesothelioma with Invasive Foci in the Pleura
Authors: Shimizu Shigeki , Yoon Hyung‐Eun , Ito Norimasa , Tsuji Taisuke , Funakoshi Yasunobu , Utsumi Tomoki , Sakaguchi Masahiro , Tsujimura Toru , Kasai Takahiko , Hiroshima Kenzo , Matsumura Akihide
Published: November 2016

Well‐differentiated papillary mesothelioma (WDPM) is a rare, distinct tumor consisting of mesothelial cells with a papillary architecture, bland cytological features, and a tendency toward superficial spread without invasion. Rare cases with superficial invasion are termed WDPM with invasive foci. We report a case of solitary WDPM with invasive foci in the pleura. A 61‐year‐old woman presented with a lung adenocarcinoma. A small papillary lesion measuring 29 × 10 × 8 mm was incidentally found in the parietal pleura during a lobectomy for the lung adenocarcinoma. The fibrovascular core of the small papillary lesion was surrounded by a single layer of cuboidal cells with mild to moderate atypia and large nucleoli. Atypical mesothelial cells focally invaded the submesothelial layer. The cells of the papillary lesion were positive for cytokeratins and mesothelial markers. The Ki67 index was <1 %. The lesion did not show p16 loss on fluorescence in situ hybridization. We could not detect atypical mesothelial cells in the specimen from an extrapleural pneumonectomy. WDPM with invasive foci is prone to multifocality; however, our case represents a solitary case in the pleura.
Research on Idea Generation and Selection: Implications for Management of Technology
Authors: Kornish Laura J. , Hutchison‐Krupat Jeremy
Published: November 2016

Idea generation and selection are fundamental activities in innovation. Scholars in many disciplines have written about these activities, addressing diverse perspectives. In this study, we synthesize the research findings most applicable to the management of technology. First, we present findings on the process of idea generation: the importance of problem recognition and the many decisions made in organizing the effort. Second, we present findings about the process of idea selection, focusing on the different types of information that can be used in that decision. Third, we turn our attention to the organizational context in which both idea generation and selection occur: the corporate culture, use of incentives, organizational structure, and use of teams. Finally, we conclude, emphasizing that although idea generation and selection are as old as human decision making, changes in technology still affect these fundamental processes.
Phenotypic and genetic characterization of Pseudomonas syringae strains associated with the recent citrus bacterial blast and bacterial black pit epidemics in Tunisia
Authors: Abdellatif E. , Kałużna M. , Janse J. D. , Sobiczewski P. , Helali F. , Lamichhane J. R. , Rhouma A.
Published: November 2016

In the spring of 2012, symptoms of a disease resembling citrus blast and citrus black pit were observed in some orchards in Tunisia. The epidemic spread rapidly in the following years. Twenty‐four commercial citrus orchards from four Tunisian regions showing characteristic symptoms of bacterial diseases were surveyed during a 3‐year study. Eighty‐eight Pseudomonas‐like bacterial isolates were successfully obtained from the northeast and west of Tunisia. No isolates were recovered from the central region. Overall, 46 isolates were identified as Pseudomonas syringae pv. syringae and most of them showed similar phenotypic and genetic profiles. The virulence of three selected isolates differed from one plant cultivar to another as well as from the type of plant organ used for the inoculation. In a bioassay test, all isolates produced syringomycin, which was confirmed by molecular detection based on the syrB and syrD genes. Only EC122 possessed syrD but not syrB. DNA fingerprints, based on repetitive sequence‐based polymerase chain reaction (rep‐PCR) and PCR melting profile (PCR MP), were used to determine the potential genetic diversity among strains. Clustering of PCR MP fingerprinting data matched with rep‐PCR fingerprinting data. The generated distribution tree showed that Tunisian isolates were closely related to the citrus reference strain LMG5496. In contrast, EC112, isolated from citrus, and the almond isolate EC122 were distantly related to the type strain LMG1247T isolated from lilac. Such studies have not been reported until now for P. syringae from citrus.
Cryopreservation of feline oocytes by vitrification using commercial kits and slush nitrogen technique
Authors: Fernandez‐Gonzalez L , Jewgenow K
Published: November 2016

Contents

Assisted reproductive techniques are a valuable tool for conservation breeding of endangered species. Cryopreservation methods are the basis of gamete banks, supporting genetic diversity preservation. Unfortunately, cryopreservation of feline oocytes is still considered an experimental technique. The aim of this study was to compare two commercial kits, with our protocol for vitrification of cat oocytes (IZW), which comprises a three‐step method with ethylene glycol, DMSO, fetal calf serum, trehalose and Ficoll PM‐70. Furthermore, we applied slush nitrogen (SN2) for ultra‐rapid freezing to improve survival rates. Cumulus–oocyte complexes were collected from domestic cat ovaries by slicing and vitrified at immature stage using Cryotop as storage device. Vit Kit® Freeze/Thaw (n = 89) showed the lowest maturation percentage obtained after warming (10.1%). A significant difference in maturation percentage of oocytes was found between Kitazato® kit (38.7%, n = 137) and IZW protocol (24.5%, n = 143). The cleavage after ICSI of warmed and matured oocytes (20.7% and 28.6%, respectively) and the morula percentage (18. 2% and 22.5%, respectively), however, did not reveal any significant difference between the two methods. Application of SN2 did not result in any improvement of oocytes’ cryopreservation. Maturation percentage of the oocytes vitrified by IZW method with SN2 (n = 144) decreased until 6.1%, without any cleavage after fertilization. For Kitazato® (n = 62), only 17.7% were able to undergo maturation and cleavage percentage dropped to 18.2%, not reaching morula stage. These data demonstrate that feline oocytes can be vitrified either by our IZW method or by commercial Kitazato® kit, but the use of SN2 is improving neither maturation nor cleavage percentages when combined with these procedures.
Center‐Periphery Bargaining in the Age of Democracy
Authors: Siroky David S. , Mueller Sean , Hechter Michael
Published: November 2016

This paper introduces the key concepts used in this special issue – center, periphery, and vertical bargaining – and inquires why some national groups within democratic states demand outright independence, while others mobilize for regional autonomy and still others settle for even less. It then specifies a theoretical framework that tries to explain cross‐sectional differences and temporal changes in both peripheral demands and central responses. The building blocks of that framework include cultural distinctiveness, credibility of the exit threat and central dependence on the periphery. As an empirical illustration, the paper discusses the case of the Bernese Jura in Switzerland, and then briefly introduces the contributions to this special issue.
Identification of the novel HLA‐DRB1*08:69 allele by polymerase chain reaction sequence‐based typing in a Chinese cord blood donor
Authors: Dong L.‐N. , Han Z.‐D. , Zhang W. , He J. , Zhu F.‐M.
Published: November 2016

HLA‐DRB1*08:69 has one nucleotide change from HLA‐DRB1*08:03:02 at position 262 G>A.
ANALYSIS OF FACTORS AFFECTING OUTCOME OF ULTRASOUND‐GUIDED RADIOFREQUENCY HEAT ABLATION FOR TREATMENT OF PRIMARY HYPERPARATHYROIDISM IN DOGS
Authors: Bucy Daniel , Pollard Rachel , Nelson Richard
Published: November 2016

Radiofrequency (RF) parathyroid ablation is a noninvasive treatment for hyperparathyroidism in dogs. There are no published data assessing factors associated with RF parathyroid ablation success or failure in order to guide patient selection and improve outcome. The purpose of this retrospective analytical study was to determine whether imaging findings, biochemical data, or concurrent diseases were associated with RF heat ablation treatment failure. For inclusion in the study, dogs must have had a clinical diagnosis of primary hyperparathyroidism, undergone cervical ultrasound and RF ablation of abnormal parathyroid tissue, and must have had at least 3 months of follow‐up information available following the date of ultrasound‐guided parathyroid ablation. Dogs were grouped based on those with recurrent or persistent hypercalcemia and those without recurrent or persistent hypercalcemia following therapy. Parathyroid nodule size, thyroid lobe size, nodule location, and presence of concurrent disease were recorded. Recurrence of hypercalcemia occurred in 9/32 dogs that had ablation of abnormal parathyroid tissue (28%) and one patient had persistent hypercalcemia (3%) following parathyroid ablation. Nodule width (P= 0.036), height (P= 0.028), and largest cross‐sectional area (P= 0.023) were larger in dogs that had recurrent or persistent hypercalcemia following ablation. Hypothyroidism was more common in dogs with recurrent disease (P= 0.044). Radiofrequency ablation was successful in 22/32 (69%) dogs. Larger parathyroid nodule size and/or concurrent hypothyroidism were associated with treatment failure in dogs that underwent ultrasound‐guided RF parathyroid nodule ablation.
Ecological speciation of bacteriophage lambda in allopatry and sympatry
Authors: Meyer Justin R. , Dobias Devin T. , Medina Sarah J. , Servilio Lisa , Gupta Animesh , Lenski Richard E.
Published: November 2016

A laboratory model of viral speciation

New species arise through the evolution of barriers to reproduction. This process is well understood where the emerging species are spatially isolated from one another. But the process of sympatric speciation—where the diverging species co-occur—is more enigmatic. Bacterial viruses make good models for addressing such questions because of their rapid generation times. Meyer
et al.
took bacteriophage λ and grew it on a mix of two strains of
Escherichia coli.
The virus duly split its host preferences into lineages with differing affinity for their respective
E. coli
hosts. In some experiments, the phages diverged to the extent that they became reproductively restricted to one strain of
E. coli
, even when the other was present.

Science
, this issue p.
1301
Long-term intestinal bleeding in a child: a rare case of heterotopic gastric mucosa in the jejunum
Authors: Leng Stella , Ghionzoli Marco , Caporalini Chiara , Buccoliero Anna Maria
Published: November 2016

We report a rare case of heterotopic gastric mucosa presenting in a jejunal polyp of a 9-year-old girl, diagnosed with capsule endoscopy and laparoscopic exploration, after a 15-month history of lower gastrointestinal bleeding and anaemia. During surgery, the jejunal segment containing the polyp was resected and pathological examination revealed a polyp with gastric heterotopia. Heterotopic gastric mucosa is a rare pathology characterised by the presence of gastric mucosa outside of the stomach. Heterotopic gastric mucosa usually occurs in the oesophagus, duodenum, Meckel's diverticulum and enteric duplication cysts. It can be either congenital (heterotopic) or acquired (metaplastic). Symptoms vary from mild dyspepsia to massive gastrointestinal bleeding.
Severe endocarditis and open-heart surgery during pregnancy
Authors: Kastelein Arnoud W , Oldenburger Nanne Y , van Pampus Mariëlle G , Janszen Erica W M
Published: November 2016

A woman aged 36 years G2P1 presented at our outpatient clinic with symptoms of discomfort, dyspnoea and fever at a gestational age of 17 weeks. She was subsequently diagnosed with severe endocarditis with a large vegetation on the mitral valve. She underwent open chest mitral valve surgery while on cardiopulmonary bypass (CPB) within a few days. Such surgical intervention is not only associated with increased maternal risks, but also with severe fetal morbidity and mortality. In such patients, certain perioperative measures can diminish these risks. In this case, mitral valve plasty was successfully performed and no maternal complications occurred. 22 weeks later, she had an at term vaginal delivery of a healthy son.
The importance of an integrating framework for achieving the Sustainable Development Goals: the example of health and well-being
Authors: Nunes Ana Raquel , Lee Kelley , O'Riordan Tim
Published: November 2016

The 2030 Agenda for Sustainable Development came into force in January 2016 as the central United Nations (UN) platform for achieving ‘integrated and indivisible’ goals and targets across the three characteristic dimensions of sustainable development: the social, environmental and economic. We argue that, despite the UN adoption of the Sustainable Development Goals (SDGs), a framework for operationalising them in an integrated fashion is lacking. This article puts forth a framework for integrating health and well-being across the SDGs as both preconditions and outcomes of sustainable development. We present a rationale for this approach, and identify the challenges and opportunities for implementing and monitoring such a framework through a series of examples. We encourage other sectors to develop similar integrating frameworks for supporting a more coordinated approach for operationalising the 2030 Agenda for Sustainable Development.
Responding to ever-changing epidemiological dynamics of Ebola virus disease
Authors: Maehira Yuki , Kurosaki Yohei , Saito Tomoya , Yasuda Jiro , Tarui Masayoshi , Malvy Denis J M , Takeuchi Tsutomu
Published: November 2016

With the incidence and mortality rates of Ebola virus disease (EVD) in Guinea, Liberia and Sierra Leone now at zero and reports of the largest and most complex EVD outbreak in history no longer on the front pages of newspapers worldwide, the urgency of that crisis seems to have subsided. During this lull after the storm and before the next one, the international community needs to engage in a ‘lessons-learned’ exercise with respect to our collective scientific, clinical and public health preparedness. This engagement must identify pragmatic, innovative mechanisms at multinational, national and community levels that allow research and development of next generation diagnostics and therapeutics, the safe and effective practice of medicine, and the maintenance of public health to keep pace with the rapid epidemiological dynamics of EVD and other deadly infectious diseases.
Herbal medicines for the treatment of otitis media with effusion: a systematic review of randomised controlled trials
Authors: Son Mi Ju , Choi Songie , Kim Young-Eun , Kim Yun Hee
Published: November 2016

Objectives

This systematic review aimed to assess the clinical evidence supporting the use of herbal medicines (HMs) for the treatment of otitis media with effusion (OME).

Design

Systematic review and meta-analysis.

Data sources

MEDLINE, EMBASE, Cochrane Library, AMED, CINAHL and three trial registries were searched up to January 2015. We also searched five Korean medical databases (KoreaMed, RISS, OASIS, DBPIA and KISS) and three Chinese databases (CNKI, Wanfang and VIP).

Study eligibility criteria

This study included randomised clinical trials that reported the effects of HM for OME. The primary outcome was the complete resolution of OME at 2 or 3 months post randomisation. Secondary outcomes included the partial or complete resolution at all possible time points and hearing test. Three authors independently screened the titles and abstracts, selected studies and extracted the data relating to trial quality, characteristics and results.

Results

A total of 2141 potentially relevant studies were identified, of which 17 randomised clinical trials met our inclusion criteria. Most were evaluated as having a high or unclear risk of bias. Tongqiao tablets, Tongqiao huoxue decoctions and Tsumura-Saireito were associated with a lower complete or partial resolution rate when compared with conventional medicines (CMs) (p=0.02, p=0.0001, and p=0.04, respectively), and similar outcomes were observed with Huanglong tonger pills, Erzhang decoctions and Shenling baizhu powder when combined with CM versus CM alone (p<0.00001, p=0.02, and p=0.05, respectively). Tongqiao huoxue decoction plus CM appeared to be more effective than CM in terms of improving the pure tone threshold levels (p=0.0007). Tsumura-Saireito was found to affect the proportion of patients with normalised tympanometry (p=0.03).

Conclusions

Despite some indications of potential symptom improvement, the evidence regarding the effectiveness and efficacy of HMs for OME is of poor quality and therefore inconclusive.

Protocol registration number

CRD42013005430.
Traumatic brain injury in England and Wales: prospective audit of epidemiology, complications and standardised mortality
Authors: Lawrence T , Helmy A , Bouamra O , Woodford M , Lecky F , Hutchinson P J
Published: November 2016

Objectives

To provide a comprehensive assessment of the management of traumatic brain injury (TBI) relating to epidemiology, complications and standardised mortality across specialist units.

Design

The Trauma Audit and Research Network collects data prospectively on patients suffering trauma across England and Wales. We analysed all data collected on patients with TBI between April 2014 and June 2015.

Setting

Data were collected on patients presenting to emergency departments across 187 hospitals including 26 with specialist neurosurgical services, incorporating factors previously identified in the Ps14 multivariate logistic regression (Ps14n) model multivariate TBI outcome prediction model. The frequency and timing of secondary transfer to neurosurgical centres was assessed.

Results

We identified 15 820 patients with TBI presenting to neurosurgical centres directly (6258), transferred from a district hospital to a neurosurgical centre (3682) and remaining in a district general hospital (5880). The commonest mechanisms of injury were falls in the elderly and road traffic collisions in the young, which were more likely to present in coma. In severe TBI (Glasgow Coma Score (GCS) ≤8), the median time from admission to imaging with CT scan is 0.5 hours. Median time to craniotomy from admission is 2.6 hours and median time to intracranial pressure monitoring is 3 hours. The most frequently documented complication of severe TBI is bronchopneumonia in 5% of patients. Risk-adjusted W scores derived from the Ps14nmodel indicate that no neurosurgical unit fell outside the 3 SD limits on a funnel plot.

Conclusions

We provide the first comprehensive report of the management of TBI in England and Wales, including data from all neurosurgical units. These data provide transparency and suggests equity of access to high-quality TBI management provided in England and Wales.
Prevalence and determinants of carotid plaque in the cross-sectional REFINE-Reykjavik study
Authors: Sturlaugsdottir Ran , Aspelund Thor , Bjornsdottir Gudlaug , Sigurdsson Sigurdur , Thorsson Bolli , Eiriksdottir Gudny , Gudnason Vilmundur
Published: November 2016

Objective

Carotid plaque and intima-media thickness are non-invasive arterial markers that are used as surrogate end points for cardiovascular disease. The aim was to assess the prevalence and severity of carotid plaque, and examine its determinant risk factors and their association to the common carotid artery intima-media thickness (CCA-IMT) in a general population.

Methods

We examined 6524 participants aged 25–69 years in the population-based REFINE (Risk Evaluation For INfarct Estimates)-Reykjavik study. Plaques at the bifurcation and internal carotid arteries were evaluated. Mean CCA-IMT was measured in the near and far walls of the common carotid arteries.

Results

The prevalence of minimal, moderate and severe plaque was 35.0%, 8.9% and 1.1%, respectively, and the mean CCA-IMT was 0.73 (SD 0.14) mm. Age, sex, smoking and type 2 diabetes mellitus (T2DM) were the strongest risk factors associated with plaque, followed by systolic blood pressure, total cholesterol, body mass index and family history of myocardial infarct. Low educational level was also strongly and independently associated with plaque. CCA-IMT shared the same risk factors except for a non-significant association with T2DM and family history of myocardial infarction (MI). Participants with T2DM had greater plaque prevalence, 2-fold higher in those <50 years and 17–30% greater in age groups 50–54 to 60–64, and more significant plaques (moderate or severe) were the difference in prevalence was 24% in age group 50–54 and ≥60% in older age groups, compared with non-T2DM.

Conclusions

Carotid plaque and CCA-IMT have mostly common determinants. However, T2DM and family history of MI were associated with plaque but not with CCA-IMT. Greater prevalence and more severe plaques in individuals with T2DM raise the concern that with increasing prevalence of T2DM we may expect an increase in atherosclerosis and its consequences.
Are differences in travel time or distance to healthcare for adults in global north countries associated with an impact on health outcomes? A systematic review
Authors: Kelly Charlotte , Hulme Claire , Farragher Tracey , Clarke Graham
Published: November 2016

Objectives

To investigate whether there is an association between differences in travel time/travel distance to healthcare services and patients' health outcomes and assimilate the methodologies used to measure this.

Design

Systematic Review. We searched MEDLINE, Embase, Web of Science, Transport database, HMIC and EBM Reviews for studies up to 7 September 2016. Studies were excluded that included children (including maternity), emergency medical travel or countries classed as being in the global south.

Settings

A wide range of settings within primary and secondary care (these were not restricted in the search).

Results

108 studies met the inclusion criteria. The results were mixed. 77% of the included studies identified evidence of a distance decay association, whereby patients living further away from healthcare facilities they needed to attend had worse health outcomes (eg, survival rates, length of stay in hospital and non-attendance at follow-up) than those who lived closer. 6 of the studies identified the reverse (a distance bias effect) whereby patients living at a greater distance had better health outcomes. The remaining 19 studies found no relationship. There was a large variation in the data available to the studies on the patients' geographical locations and the healthcare facilities attended, and the methods used to calculate travel times and distances were not consistent across studies.

Conclusions

The review observed that a relationship between travelling further and having worse health outcomes cannot be ruled out and should be considered within the healthcare services location debate.
Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study
Authors: Tsim Selina , Kelly Caroline , Alexander Laura , McCormick Carol , Thomson Fiona , Woodward Rosie , Foster John E , Stobo David B , Paul Jim , Maskell Nick A , Chalmers Anthony , Blyth Kevin G
Published: November 2016

Introduction

Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.

Methods and analysis

Serum and plasma (for SOMAscan and fibulin-3, respectively) will be collected at presentation, prior to pleural biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of MPM/non-MPM cases will depend on the incidence of MPM in the study population (estimated at 13–20%). Identical sampling and storage protocols will be used in 22 recruiting centres and histological confirmation sought in all cases. Markers will be measured using the SOMAscan proteomic assay (SomaLogic) and a commercially available fibulin-3 ELISA (USCN Life Science). The SE in the estimated sensitivity and specificity will be <5% for each marker and their performance will be compared with serum mesothelin. Blood levels will be compared with paired pleural fluid levels and MPM tumour volume (using MRI) in a nested substudy. The prognostic value of each marker will be assessed and a large bioresource created.

Ethics and dissemination

The study has been approved by the West of Scotland Research Ethics Committee (Ref: 13/WS/0240). A Trial Management Group meets on a monthly basis. Results will be published in peer-reviewed journals, presented at international meetings and disseminated to patient groups.

Trial registration number

ISRCTN10079972, Pre-results.
Gyejibongneyong-hwan, a herbal medicine for the treatment of dysmenorrhoea with uterine fibroids: a protocol for a randomised controlled trial
Authors: Jung Jeeyoun , Lee Ju Ah , Ko Mi Mi , You Sooseong , Lee Eunhee , Choi Jiae , Kang Byoung-Kab , Lee Myeong Soo
Published: November 2016

Introduction

Gyejibongneyong-hwan (GBH), or the Guizhi Fuling Formula in Chinese, is widely used to treat uterine fibroids in East Asian countries including Korea, China and Japan. This study will assess the efficacy and safety of the GBH formula for the treatment of dysmenorrhoea.

Methods and analysis

This study will be a randomised double-blind controlled trial with two parallel arms: the GBH group and the placebo group. This trial will recruit 38 women between 18 and 45 years of age with secondary dysmenorrhoea with uterine fibroids. The investigational drugs, either GBH or placebo, will be administered to the participants three times per day for two menstrual periods (8 weeks). The participants will be followed up for three menstrual cycles after administration of the drugs. The primary outcome will be the Numeric Rating Scale score of average menstrual pain. All analyses will be performed with SAS (V.9.1.3; SAS Institute, Cary, North Carolina, USA) by a statistician blinded to the allocation of the groups. Statistical analysis will be undertaken on the intent-to-treat (ITT) basis with a 95% CI using the last observation carried forward for missing values. The ITT analysis will include all randomised patients.

Ethics and dissemination

This research protocol has been reviewed and approved by the institutional review boards of the trial centre (number WSOH IRB 1606-03). Written informed consent will be obtained from all study participants prior to enrolment in the study. The results will be published in a peer-reviewed journal and will be disseminated electronically and in print.

Trial registration number

KCT0001967.
Cross-sectional assessment of patient attitudes towards participation in clinical trials: does making results publicly available matter?
Authors: Jones Christopher W , Braz Valerie A , McBride Stephen M , Roberts Brian W , Platts-Mills Timothy F
Published: November 2016

Objectives

Previous studies have shown that a majority of patients cite altruistic motives, such as contributing to generalisable medical knowledge, as factors motivating clinical trial participation. We sought to examine the impact of making trial results publicly available on patients' willingness to participate in clinical research.

Design

Cross-sectional analysis using a questionnaire developed by a panel with expertise in publication bias, informed consent and survey design.

Setting

A single urban, academic emergency department (ED) in the Northeastern USA.

Participants

799 ED patients.

Outcome Measures

We assessed (1) participants' attitudes towards clinical trial participation, and (2) the impact of whether study results would eventually be made publicly available or not on willingness to participate in a trial.

Results

Of 799 patients surveyed, 36% (95% CI 32% to 39%) reported that they would generally like to participate in a trial, and another 50% (95% CI 47% to 54%) reported that they would consider participation depending on study details. For the majority of participants, the publication of trial results was either important (36%; 95% CI 33% to 40%) or very important (48%; 95% CI 44% to 51%). Most (63%; 95% CI 59% to 66%) reported they would be less likely to participate in a trial if investigators had not publicly released results from a prior study. Additionally, 85% (95% CI 82% to 87%) felt that it was important or very important to receive information about the publication track record of sponsors and investigators during the informed consent process.

Conclusions

The majority of patients in this sample would consider participation in a clinical trial. Patients value the public release of trial results, and believe that the informed consent process should address the possibility of non-publication.
Effectiveness of trauma-focused psychological therapies compared to usual postnatal care for treating post-traumatic stress symptoms in women following traumatic birth: a systematic review protocol
Authors: Furuta Marie , Spain Debbie , Bick Debra , Ng Edmond S W , Sin Jacqueline
Published: November 2016

Introduction

Maternal mental health has been largely neglected in the literature. Women, however, may be vulnerable to developing post-traumatic stress symptoms or post-traumatic stress disorder (PTSD), following traumatic birth. In turn, this may affect their capacity for child rearing and ability to form a secure bond with their baby and impact on the wider family. Trauma-focused psychological therapies (TFPT) are widely regarded as effective and acceptable interventions for PTSD in general and clinical populations. Relatively little is known about the effectiveness of TFPT for women postpartum who have post-traumatic stress symptoms.

Methods and analysis

We will conduct a review to assess the effectiveness of TFPT, compared with usual postpartum care, as a treatment for post-traumatic stress symptoms or PTSD for women following traumatic birth. Using a priori search criteria, we will search for randomised controlled trials (RCT) in four databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO and OpenGrey. We will use search terms that relate to the population, TFPT and comparators. Screening of search results and data extraction will be undertaken by two reviewers, independently. Risk of bias will be assessed in RCTs which meet the review criteria. Data will be analysed using the following methods, as appropriate: narrative synthesis; meta-analysis; subgroup analysis and meta-regression.

Dissemination and ethics

As this work comprises a synthesis of existing studies, ethical approvals are not required. Results will be disseminated at conferences and in publications.
Implementing shared decision-making in interprofessional home care teams (the IPSDM-SW study): protocol for a stepped wedge cluster randomised trial
Authors: Légaré France , Brière Nathalie , Stacey Dawn , Lacroix Guy , Desroches Sophie , Dumont Serge , Fraser Kimberly D , Rivest Louis-Paul , Durand Pierre J , Turcotte Stéphane , Taljaard Monica , Bourassa Henriette , Roy Lise , Painchaud Guérard Geneviève
Published: November 2016

Introduction

The frail elderly in Canada face a tough decision when they start to lose autonomy: whether to stay at home or move to another location. This study seeks to scale up and evaluate the implementation of shared decision-making (SDM) in interprofessional (IP) home care teams caring for elderly clients or their caregivers facing a decision about staying at home or moving elsewhere.

Methods

A stepped wedge cluster randomised trial involving 8 Health and Social Service Centers (HSSCs) will be conducted with IP home care teams. HSSCs are the unit of randomisation. A decision guide will be passively distributed to all of the participating HSSCs at the beginning of the project. The participating HSSCs will then be randomised to 1 of 4 intervention start times, separated by 7-month intervals. The primary outcome is whether or not clients and caregivers assumed an active role in decision-making, assessed with a modified version of the Control Preferences Scale. The intervention, targeted at IP home care teams, consists of a 1.5 hour online tutorial and a 3.5 hour skills building workshop in IP SDM. Clients will be eligible for outcome assessment if they (1) are aged ≥65; (2) are receiving care from the IP home care team of the enrolled HSSCs; (3) have made a decision about whether to stay at home or move to another location during the recruitment periods; (4) are able to read, understand and write French or English; (5) can give informed consent. If clients are not able to provide informed consent, their primary caregiver will become the eligible participant.

Ethics and dissemination

Ethics committee review approval has been obtained from the Multicenter Ethics Committee of CISSS-Laval. Results will be disseminated at conferences, on websites of team members and in peer-reviewed and professional journals intended for policymakers and managers.

Trial registration number

NCT02592525, Pre-results.
Low-acuity presentations to the emergency department in Canada: exploring the alternative attempts to avoid presentation
Authors: Krebs Lynette D , Kirkland Scott W , Chetram Rajiv , Nikel Taylor , Voaklander Britt , Davidson Alan , Holroyd Bryn , Villa-Roel Cristina , Crick Katelynn , Couperthwaite Stephanie , Alexiu Chris , Cummings Garnet , Rowe Brian H
Published: November 2016

Objective

ED visits have been rising year on year worldwide. It has been suggested that some of these visits could be avoided if low-acuity patients had better primary care access. This study explored patients' efforts to avoid ED presentation and alternative care sought prior to presentation.

Methods

Consecutive adult patients presenting to three urban EDs in Edmonton, Canada, completed a questionnaire collecting demographics, actions attempted to avoid presentation and reasons for presentation. Survey data were cross-referenced to a minimal patient dataset containing ED and demographic information.

Results

A total of 1402 patients (66.5%) completed the survey. Although 89.3% of the patients felt that the ED was their best care option, the majority of patients (60.1%) sought alternative care or advice prior to presentation. Men, individuals who presented with injury only, and individuals with less than a high school education were all less likely to seek alternative care. Alternative care actions included visiting a physician (54.1%) or an alternative healthcare professional (eg, chiropractor, physiotherapist, etc; 21.2%), calling physician offices (47%) or the regional health information line (13%). Of those who called their physicians, the majority received advice to present to the ED (67.5%).

Conclusions

Most low-acuity patients attempt to avoid ED presentation by seeking alternative care. This analysis identifies groups of individuals in the study region who are less likely to seek alternative care first and may benefit from targeted interventions/education. Other regions may wish to complete a similar profile to determine which patients are less likely to seek alternative care first.
Residential segregation and mental health among Latinos in a nationally representative survey
Authors: Nobles Carrie J , Valentine Sarah E , Zepeda E David , Wang Ye , Ahles Emily M , Shtasel Derri L , Marques Luana
Published: November 2016

Background

Among Latinos, living in a locality with greater Latino ethnic density may be protective for mental health, although findings vary by Latino subgroup, gender and birthplace. Although little studied, Latino residential segregation may capture different pathways linking risk and protective environmental factors to mental health than local ethnic density.

Methods

This study evaluated the association between residential segregation and mental distress as measured by the Kessler-10 (K10) among Latino participants in the National Latino and Asian American Study (NLAAS). Census data from 2000 was used to calculate metropolitan statistical area (MSA) residential segregation using the dissimilarity and isolation indices, as well as census tract ethnicity density and poverty. Latino subgroup (Puerto Rican, Mexican American, Cuban American and other Latino subgroup), gender and generation status were evaluated as moderators.

Results

Among 2554 Latino participants in NLAAS, residential segregation as measured by the isolation index was associated with less mental distress (β −0.14, 95% CI −0.26 to −0.03 log(K10)) among Latinos overall after adjustment for ethnic density, poverty and individual covariates. Residential segregation as measured by the dissimilarity index was significantly associated with less mental distress among men (β −0.56, 95% CI −1.04 to −0.08) but not among women (β −0.20, 95% CI −0.45 to 0.04, p-interaction=0.019). No modification was observed by Latino subgroup or generation.

Conclusions

Among Latinos, increasing residential segregation was associated with less mental distress, and this association was moderated by gender. Findings suggest that MSA-level segregation measures may capture protective effects associated with living in Latino communities for mental health.
Trends in educational inequalities in premature mortality in Belgium between the 1990s and the 2000s: the contribution of specific causes of deaths
Authors: Renard Françoise , Gadeyne Sylvie , Devleesschauwer Brecht , Tafforeau Jean , Deboosere Patrick
Published: November 2016

Background

Reducing socioeconomic inequalities in mortality, a key public health objective may be supported by a careful monitoring and assessment of the contributions of specific causes of death to the global inequality.

Methods

The 1991 and 2001 Belgian censuses were linked with cause-of-death data, each yielding a study population of over 5 million individuals aged 25–64, followed up for 5 years. Age-standardised mortality rates (ASMR) were computed by educational level (EL) and cause. Inequalities were measured through rate differences (RDs), rate ratios (RRs) and population attributable fractions (PAFs). We analysed changes in educational inequalities between the 1990s and the 2000s, and decomposed the PAF into the main causes of death.

Results

All-cause and avoidable ASMR decreased in all ELs and both sexes. Lung cancer, ischaemic heart disease (IHD), chronic obstructive pulmonary disease (COPD) and suicide in men, and IHD, stroke, lung cancer and COPD in women had the highest impact on population mortality. RDs decreased in men but increased in women. RRs and PAFs increased in both sexes, albeit more in women. In men, the impact of lung cancer and COPD inequalities on population mortality decreased while that of suicide and IHD increased. In women, the impact of all causes except IHD increased.

Conclusion

Absolute inequalities decreased in men while increasing in women; relative inequalities increased in both sexes. The PAFs decomposition revealed that targeting mortality inequalities from lung cancer, IHD, COPD in both sexes, suicide in men and stroke in women would have the largest impact at population level.
MACRA 2.0: are you ready for MIPS?
Authors: Hirsch Joshua A , Rosenkrantz Andrew B , Ansari Sameer A , Manchikanti Laxmaiah , Nicola Gregory N
Published: November 2016

The annual cost of healthcare delivery in the USA now exceeds US$3 trillion. Fee for service methodology is often implicated as a cause of this exceedingly high figure. The Affordable Care Act created the Center for Medicare and Medicaid Innovation (CMMI) to pilot test value based alternative payments for reimbursing physician services. In 2015, the Medicare Access and CHIP Reauthorization Act (MACRA) was passed into law. MACRA has dramatic implications for all US based healthcare providers. MACRA permanently repealed the Medicare Sustainable Growth Rate so as to stabilize physician part B Medicare payments, consolidated pre-existing federal performance programs into the Merit based Incentive Payments System (MIPS), and legislatively mandated new approaches to paying clinicians. Neurointerventionalists will predominantly participate in MIPS. MIPS unifies, updates, and streamlines previously existing federal performance programs, thereby reducing onerous redundancies and overall administrative burden, while consolidating performance based payment adjustments. While MIPS may be perceived as a straightforward continuation of fee for service methodology with performance modifiers, MIPS is better viewed as a stepping stone toward eventually adopting alternative payment models in later years. In October 2016, the Centers for Medicare and Medicaid Services (CMS) released a final rule for MACRA implementation, providing greater clarity regarding 2017 requirements. The final rule provides a range of options for easing MIPS reporting requirements in the first performance year. Nonetheless, taking the newly offered ‘minimum possible’ approach toward meeting the requirements will still have negative consequences for providers.