bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum emitters in two dimensions
Authors: Aharonovich Igor , Toth Milos
Published: October 2017

Two-dimensional materials offer potential for developing integrated quantum technologies
Rebuilding Caribbean science
Authors: Ramírez Lugo Juan S. , Torres-Ramos Carlos A.
Published: October 2017

Much of the Caribbean has been devastated by two major hurricanes that struck last month. Hurricane Irma first rampaged through the eastern Caribbean, British and the U.S. Virgin Islands, Puerto Rico, and Cuba, leaving islands such as Barbuda and St. Martin nearly uninhabitable. Less than 2 weeks later, Hurricane Maria tore through Dominica and pummeled the Puerto Rican archipelago with great fury.
A robotic device using gecko-inspired adhesives can grasp and manipulate large objects in microgravity
Authors: Jiang Hao , Hawkes Elliot. W. , Fuller Christine , Estrada Matthew A. , Suresh Srinivasan A. , Abcouwer Neil , Han Amy K. , Wang Shiquan , Ploch Christopher J. , Parness Aaron , Cutkosky Mark R.
Published: October 2017

A load-sharing robotic device can grasp, manipulate, and release objects in microgravity using space-qualified dry adhesives.
Papers of note in
Science Translational Medicine
9
(393)
Authors: Ferrarelli Leslie K.
Published: October 2017

This week’s articles describe a new combination therapy for BRCA1-mutant breast cancer and a new therapeutic target in patients with the ectopic calcification disease PXE.
Detecting and treating brain cancer
Authors: Ferrarelli Leslie K.
Published: October 2017

A systems biology approach identifies plasma biomarkers and potential therapeutic targets for patients with glioblastoma.
Papers of note in
Nature
546
(7658)
Authors: VanHook Annalisa M.
Published: October 2017

This week’s articles highlight a compound that may be useful for treating cryptosporidiosis and a kinase complex that links cell division to cellular metabolism.
Dazed and confused from infection
Authors: Wong Wei
Published: October 2017

TNF-α produced by circulating CX
3
CR1
high
monocytes causes the problems that infected individuals have with learning and remembering.
Glucose-regulated protein 78 autoantibody associates with blood-brain barrier disruption in neuromyelitis optica
Authors: Shimizu Fumitaka , Schaller Kristin L. , Owens Gregory P. , Cotleur Anne C. , Kellner Debra , Takeshita Yukio , Obermeier Birgit , Kryzer Thomas J. , Sano Yasuteru , Kanda Takashi , Lennon Vanda A. , Ransohoff Richard M. , Bennett Jeffrey L.
Published: October 2017

An autoantibody target on brain microvascular endothelial cells in patients with neuromyelitis optica may be exploited to manipulate blood-brain barrier permeability.
Recent Approaches To Optimize Laboratory Assessment of Antinuclear Antibodies
Authors: Tebo Anne E.
Published: October 2017

The presence of antinuclear antibodies (ANAs) is a hallmark of a number of systemic autoimmune rheumatic diseases, and testing is usually performed as part of the initial diagnostic workup when suspicion of an underlying autoimmune disorder is high. The indirect immunofluorescence antibody (IFA) technique is the preferred method for detecting ANAs, as it demonstrates binding to specific intracellular structures within the cells, resulting in a number of staining patterns that are usually categorized based on the cellular components recognized and the degree of binding, as reflected by the fluorescence intensity or titer. As a screening tool, the ANA patterns can guide confirmatory testing useful in elucidating a specific clinical diagnosis or prognosis. However, routine use of ANA IFA testing as a global screening test is hampered by its labor-intensiveness, subjectivity, and limited diagnostic specificity, among other factors. This review focuses on current efforts to standardize the nomenclature of ANA patterns and on alternative methods for ANA determination, as well as on recent advances in image-based computer algorithms to automate IFA testing in clinical laboratories.
Safety and Accuracy of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Identification of Highly Pathogenic Organisms
Authors: Rudrik James T. , Soehnlen Marty K. , Perry Michael J. , Sullivan Maureen M. , Reiter-Kintz Wanda , Lee Philip A. , Pettit Denise , Tran Anthony , Swaney Erin
Published: October 2017

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) sample preparation methods, including the direct, on-plate formic acid, and ethanol/formic acid tube extraction methods, were evaluated for their ability to render highly pathogenic organisms nonviable and safe for handling in a biosafety level 2 laboratory. Of these, the tube extraction procedure was the most successful, with none of the tested strains surviving this sample preparation method. Tube extracts from several agents of bioterrorism and their near neighbors were analyzed in an eight-laboratory study to examine the utility of the Bruker Biotyper and Vitek MS MALDI-TOF MS systems and their
in vitro
diagnostic (IVD), research-use-only, and Security-Relevant databases, as applicable, to accurately identify these agents. Forty-six distinct strains of
Bacillus anthracis
,
Yersinia pestis
,
Francisella tularensis
,
Burkholderia mallei
,
Burkholderia pseudomallei
,
Clostridium botulinum
,
Brucella melitensis
,
Brucella abortus
,
Brucella suis
, and
Brucella canis
were extracted and distributed to participating laboratories for analysis. A total of 35 near-neighbor isolates were also analyzed.
Human Parvovirus Infection of Human Airway Epithelia Induces Pyroptotic Cell Death by Inhibiting Apoptosis
Authors: Deng Xuefeng , Zou Wei , Xiong Min , Wang Zekun , Engelhardt John F. , Ye Shui Qing , Yan Ziying , Qiu Jianming
Published: October 2017

Human bocavirus 1 (HBoV1) is a human parvovirus that causes acute respiratory tract infections in young children. In this study, we confirmed that, when polarized/well-differentiated human airway epithelia are infected with HBoV1
in vitro
, they develop damage characterized by barrier function disruption and cell hypotrophy. Cell death mechanism analyses indicated that the infection induced pyroptotic cell death characterized by caspase-1 activation. Unlike infections with other parvoviruses, HBoV1 infection did not activate the apoptotic or necroptotic cell death pathway. When the NLRP3-ASC-caspase-1 inflammasome-induced pathway was inhibited by short hairpin RNA (shRNA), HBoV1-induced cell death dropped significantly; thus, NLRP3 mediated by ASC appears to be the pattern recognition receptor driving HBoV1 infection-induced pyroptosis. HBoV1 infection induced steady increases in the expression of interleukin 1α (IL-1α) and IL-18. HBoV1 infection was also associated with the marked expression of the antiapoptotic genes
BIRC5
and
IFI6
. When the expression of
BIRC5
and/or
IFI6
was inhibited by shRNA, the infected cells underwent apoptosis rather than pyroptosis, as indicated by increased cleaved caspase-3 levels and the absence of caspase-1.
BIRC5
and/or
IFI6
gene inhibition also significantly reduced HBoV1 replication. Thus, HBoV1 infection of human airway epithelial cells activates antiapoptotic proteins that suppress apoptosis and promote pyroptosis. This response may have evolved to confer a replicative advantage, thus allowing HBoV1 to establish a persistent airway epithelial infection. This is the first report of pyroptosis in airway epithelia infected by a respiratory virus.

IMPORTANCE
Microbial infection of immune cells often induces pyroptosis, which is mediated by a cytosolic protein complex called the inflammasome that senses microbial pathogens and then activates the proinflammatory cytokines IL-1 and IL-18. While virus-infected airway epithelia often activate NLRP3 inflammasomes, studies to date suggest that these viruses kill the airway epithelial cells via the apoptotic or necrotic pathway; involvement of the pyroptosis pathway has not been reported previously. Here, we show for the first time that virus infection of human airway epithelia can also induce pyroptosis. Human bocavirus 1 (HBoV1), a human parvovirus, causes lower respiratory tract infections in young children. This study indicates that HBoV1 kills airway epithelial cells by activating genes that suppress apoptosis and thereby promote pyroptosis. This strategy appears to promote HBoV1 replication and may have evolved to allow HBoV1 to establish persistent infection of human airway epithelia.
Tackling concussion in professional rugby union: a case–control study of tackle-based risk factors and recommendations for primary prevention
Authors: Cross Matthew J , Tucker Ross , Raftery Martin , Hester Ben , Williams Sean , Stokes Keith A , Ranson Craig , Mathema Prav , Kemp Simon
Published: October 2017

Background/aim

Concussion, the most common injury in professional rugby union, occurs most commonly during the tackle. Thus, we investigated the association between tackle characteristics and concussion.

Methods

182 video clips of tackles leading to clinically diagnosed concussion and 4619 tackles that did not were coded across three professional rugby union competitions. A variable selection process was undertaken to identify the most important variables for interpretation. A multivariate generalised linear model was used to model the association between retained variables and concussion risk. Magnitude-based inferences provided an interpretation of the real-world relevance of the outcomes.

Results

The four retained variables were: accelerating player, tackler speed, head contact type and tackle type. Overall, 70% of concussions occurred to the tackler and 30% to the ball carrier. There was a higher risk of concussion if the tackler accelerated into the tackle (OR: 2.49, 95% CI 1.70 to 3.64) or the tackler was moving at high speed (OR: 2.64, 95% CI 1.92 to 3.63). Head contact with the opposing player’s head (OR: 39.9, 95% CI 22.2 to 71.1) resulted in a substantially greater risk of concussion compared with all other head contact locations.

Conclusions

Interventions that reduce the speed and acceleration of the tackler and reduce exposure to head-to-head contact would likely reduce concussion risk in professional rugby union.
Comparison of the cerebroprotective effect of inhalation anaesthesia and total intravenous anaesthesia in patients undergoing cardiac surgery with cardiopulmonary bypass: a systematic review and meta-analysis
Authors: Chen Feng , Duan Guangyou , Wu Zhuoxi , Zuo Zhiyi , Li Hong
Published: October 2017

Objective

Neurological dysfunction remains a devastating postoperative complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), and previous studies have shown that inhalation anaesthesia and total intravenous anaesthesia (TIVA) may produce different degrees of cerebral protection in these patients. Therefore, we conducted a systematic literature review and meta-analysis to compare the neuroprotective effects of inhalation anaesthesia and TIVA.

Design

Searching in PubMed, EMBASE, Science Direct/Elsevier, China National Knowledge Infrastructure and Cochrane Library up to August 2016, we selected related randomised controlled trials for this meta-analysis.

Results

A total of 1485 studies were identified. After eliminating duplicate articles and screening titles and abstracts, 445 studies were potentially eligible. After applying exclusion criteria (full texts reported as abstracts, review article, no control case, lack of outcome data and so on), 13 studies were selected for review. Our results demonstrated that the primary outcome related to S100B level in the inhalation anaesthesia group was significantly lower than in the TIVA group after CPB and 24 hours postoperatively (weighted mean difference (WMD); 95% CI (CI): −0.41(–0.81 to –0.01), −0.32 (−0.59 to −0.05), respectively). Among secondary outcome variables, mini-mental state examination scores of the inhalation anaesthesia group were significantly higher than those of the TIVA group 24 hours after operation (WMD (95% CI): 1.87 (0.82 to 2.92)), but no significant difference was found in arteriovenous oxygen content difference, cerebral oxygen extraction ratio and jugular bulb venous oxygen saturation, which were assessed at cooling and rewarming during CPB.

Conclusion

This study demonstrates that anaesthesia with volatile agents appears to provide better cerebral protection than TIVA for patients undergoing cardiac surgery with CPB, suggesting that inhalation anaesthesia may be more suitable for patients undergoing cardiac surgery.
Influence of social deprivation on provision of bariatric surgery: 10-year comparative ecological study between two UK specialist centres
Authors: Bhanderi Shivam , Alam Mushfique , Matthews Jacob Henry , Rudge Gavin , Noble Hamish , Mahon David , Richardson Martin , Welbourn Richard , Super Paul , Singhal Rishi
Published: October 2017

Objective

To investigate the effect of residential location and socioeconomic deprivation on the provision of bariatric surgery.

Design

Retrospective cross-sectional ecological study.

Setting

Patients resident local to one of two specialist bariatric units, in different regions of the UK, who received obesity surgery between 2003 and 2013.

Methods

Demographic data were collected from prospectively collected databases. Index of Multiple Deprivation (IMD 2010) was used as a measure of socioeconomic status. Obesity prevalences were obtained from Public Health England (2006). Patients were split into three IMD tertiles (high, median, low) and also tertiles of time. A generalised linear model was generated for each time period to investigate the effect of socioeconomic deprivation on the relationship between bariatric case count and prevalence of obesity. We used these to estimate surgical intervention provided in each population in each period at differing levels of deprivation.

Results

Data were included from 1163 bariatric cases (centre 1–414, centre 2–749). Incidence rate ratios (IRRs) were calculated to measure the associations between predictor and response variables. Associations were highly non-linear and changed over the 10-year study period. In general, the relationship between surgical case volume and obesity prevalence has weakened over time, with high volumes becoming less associated with prevalence of obesity.

Discussion

As bariatric services have matured, the associations between demand and supply factors have changed. Socioeconomic deprivation is not apparently a barrier to service provision more recently, but the positive relationships between obesity and surgical volume we would expect to find are absent. This suggests that interventions are not being taken up in the areas of need. We recommend a more detailed national analysis of the relationship between supply side and demand side factors in the provision of bariatric surgery.
Neighbourhood characteristics and mental disorders in three Chinese cities: multilevel models from the World Mental Health Surveys
Authors: Chiavegatto Filho Alexandre Dias Porto , Sampson Laura , Martins Silvia S , Yu Shui , Huang Yueqin , He Yanling , Lee Sing , Hu Chiyi , Zaslavsky Alan , Kessler Ronald C , Galea Sandro
Published: October 2017

Objectives

The rapid growth of urban areas in China in the past few decades has introduced profound changes in family structure and income distribution that could plausibly affect mental health. Although multilevel studies of the influence of area-level socioeconomic factors on mental health have become more common in other parts of the world, a study of this sort has not been carried out in Chinese cities. Our objectives were to examine the associations of two key neighbourhood-level variables—median income and percentage of married individuals living in the neighbourhood—with mental disorders net of individual-level income and marital status in three Chinese cities.

Setting

Household interviews in Beijing, Shanghai and Shenzhen, PRC, as part of the cross-sectional World Mental Health Surveys.

Participants

4072 men and women aged 18–88 years.

Primary and secondary outcome measures

Lifetime and past-year internalising and externalising mental disorders.

Results

Each one-point increase in neighbourhood-level percentage of married residents was associated with a 1% lower odds of lifetime (p=0.024) and 2% lower odds of past-year (p=0.008) individual-level externalising disorder, net of individual-level marital status. When split into tertiles, individuals living in neighbourhoods in the top tertile of percentage of married residents had 54% lower odds of a past-year externalising disorder (OR=0.46, 95% CI: 0.24 to 0.87) compared with those in the bottom tertile. Neighbourhood-level marital status was not statistically associated with either lifetime or past-year internalising disorders. Neighbourhood-level income was not statistically associated with odds of either internalising or externalising disorders.

Conclusions

The proportion of married residents in respondents’ neighbourhoods was significantly inversely associated with having externalising mental disorders in this sample of Chinese cities. Possible mechanisms for this finding are discussed and related to social causation, social selection and social control theories. Future work should examine these relationships longitudinally.
Cohort profile for the MASTERMIND study: using the Clinical Practice Research Datalink (CPRD) to investigate stratification of response to treatment in patients with type 2 diabetes
Authors: Rodgers Lauren R , Weedon Michael N , Henley William E , Hattersley Andrew T , Shields Beverley M
Published: October 2017

Purpose

This is a retrospective cohort study using observational data from anonymised primary care records. We identify and extract all patients with type 2 diabetes and associated clinical data from the Clinical Practice Research Datalink (CPRD) to inform models of disease progression and stratification of treatment.

Participants

Data were extracted from CPRD on 8 August 2016. The initial data set contained all patients (n=313 485) in the database who had received a type 2 diabetes medication. Criteria were applied to identify and exclude those with type 1 diabetes, polycystic ovarian syndrome or other forms of diabetes (n=40 204), and for data quality control (n=12). We identified 251 338 patients for inclusion in future analyses of diabetes progression and treatment response.

Findings to date

For 6-month response to treatment, measured by change in glycated haemoglobin (HbA1c), we have 91 765 patients with 119 785 treatment response episodes. The greatest impact on reduction of HbA1c occurs with first-line and second-line treatments, metformin and sulfonylurea. Patients moving to third-line treatments tend to have greater weights and higher body mass index. We have investigated the impact of non-adherence to commonly used glucose-lowering medications on HbA1c. For baseline-adjusted HbA1c change over 1 year, non-adherent patients had lower HbA1c reductions than adherent patients, with mean and 95% CI of −4.4 (−4.7 to −4.0) mmol/mol (−0.40 (−0.43 to −0.37) %).

Future plans

Findings from studies using these data will help inform future treatment plans and guidelines. Additional data are added with updates from CPRD. This will increase the numbers of patients on newer medications and add more data on those already receiving treatment. There are several ongoing studies investigating different hypotheses regarding differential response to treatment and progression of diabetes. For side effects, links to Hospital Episode Statistics data, where severe events such as hypoglycaemia will be recorded, will also be explored.
Exploring the role of the nurse manager in supporting point-of-care nurses’ adoption of electronic health records: protocol for a qualitative research study
Authors: Strudwick Gillian , Booth Richard G , Bjarnadottir Ragnhildur I , Collins Sarah , Srivastava Rani
Published: October 2017

Introduction

An increasing number of electronic health record (EHR) systems have been implemented in clinical practice environments where nurses work. Findings from previous studies have found that a number of intended benefits of the technology have not yet been realised to date, partially due to poor system adoption among health professionals such as nurses. Previous studies have suggested that nurse managers can support the effective adoption and use of the technology by nurses. However, no known studies have identified what role nurse managers have in supporting technology adoption, nor the specific strategies that managers can employ to support their staff. Therefore, the purpose of this research is to better understand the role of the nurse manager in point-of-care nurses’ use of EHRs, and to identify strategies that may be effective in supporting clinical adoption.

Methods and analysis

This study will use a qualitative descriptive design. Interviews with both nurse managers and point-of-care nursing staff will be conducted in a Canadian mental health and addiction healthcare organisation where an EHR has been implemented. A semistructured interview guide will be used, and interviews will be audio recorded. Transcripts will be analysed using a directed content analysis technique. Strategies to ensure the trustworthiness of the data analysis procedure and findings will be employed.

Ethics and dissemination

Ethical approval for this study has been obtained. Dissemination strategies may include a paper submission to a peer-reviewed journal, a conference submission and meetings to share findings with the study site leadership team. Findings from this research will be used to inform a future study which aims to assess levels of competencies and perform a psychometric analysis of the Nursing Informatics Competency Assessment for the Nurse Leader instrument in a Canadian context.
The association between adverse childhood experiences and traumatic brain injury/concussion in adulthood: A scoping review protocol
Authors: Ma Zechen , Bayley Mark T , Perrier Laure , Dhir Priya , Dépatie Lana , Comper Paul , Ruttan Lesley , Munce Sarah EP
Published: October 2017

Introduction

Exposure to adverse childhood experiences (ACEs) is a significant risk factor for physical and mental illnesses later in life. Concussion or traumatic brain injury is a challenging condition where preinjury factors may interact to affect recovery. The association between ACEs and traumatic brain injury/concussion is not well mapped in any previous reviews of the literature. Using a scoping review methodology, the research question that will be addressed is: what is known from the existing literature about the association between ACEs and traumatic brain injury/concussion in adults?

Methods and analysis

The methodological frameworks outlined by Arksey and O’Malley and Levacet alwill be used. All original studies in English published since 2007 investigating ACEs and traumatic brain injury/concussion outcomes will be included with no limitations on study type. Literature search strategies will be developed using medical subject headings and text words related to ACEs and traumatic brain injury/concussions. Multiple electronic databases will be searched. Two independent reviewers will screen titles and abstracts for full-text review and full texts for final inclusion. Two independent reviewers will extract data on study characteristics for ACE exposure and traumatic brain injury/concussion outcomes. Extracted data will be summarised quantitatively using numerical counts and qualitatively using thematic analysis.

Dissemination

This review will identify knowledge gaps on the associations between ACEs and traumatic brain injury/concussion and promote further research. Knowledge translation will occur throughout the review process with dissemination of project findings to stakeholders at the local, national and international levels.
Attitudes towards protective headgear in UK rugby union players
Authors: Barnes Andrew , Rumbold James L , Olusoga Peter
Published: October 2017

Background/aim

Concussions in rugby union pose a major threat to player welfare. Research has found protective headgear offers no significant protection against concussions but suggests a large proportion of players perceive headgear to be effective in preventing concussions. This study aimed to explore UK rugby union players’ attitudes towards wearing protective headgear.

Methods

545 rugby union players (85% male) from a range of playing standards completed an online survey. Quantitative and qualitative data were collected on player attitudes towards protective headgear use. Descriptive statistics, multiple regressions and content analysis were used to analyse the responses.

Results

37% of players believed that headgear was effective in preventing head injuries. Playing group was found to be inversely associated with headgear effectiveness (∆R2=0.01,B=−0.13, p=0.02), with youth players holding stronger beliefs that headgear is effective at preventing head injuries compared with all senior groups. The main reasons cited for wearing headgear related to protection from minor injuries (55%) with only 10% of responses related to concussion prevention.

Conclusions

There appears to be a good awareness in UK players that protective headgear is not effective at preventing concussions. Continued education is vital to ensure players are fully aware of the limitations of headgear, and players who wear it do not engage in overly reckless behaviours as a result.
Acceptability and perceptions of end-users towards an online sports-health surveillance system
Authors: Barboza Saulo Delfino , Bolling Caroline Silveira , Nauta Joske , Mechelen Willem van , Verhagen Evert
Published: October 2017

Aim

To describe the acceptability and the perceptions of athletes and staff members (ie, end-users) towards an online sports-health surveillance system.

Methods

A pilot study with a mixed-methods approach was pursued. Descriptive analysis was conducted to present the adherence of judo (n=34), swimming (n=21) and volleyball (n=14) athletes to an online registration of their sport exposure and any health complaints between April 2014 and January 2015. End-users’ perceptions towards the system were investigated qualitatively with semistructured interviews (n=21). Qualitative analysis was based on the constant comparative method using principles of the grounded theory.

Results

The response rates of judo, swimming and volleyball athletes were 50% (SD 23), 61% (SD 27) and 56% (SD 25), respectively. Most athletes found it simple to register their sport exposure and health complaints online; however, personal communication was still preferred for this purpose. The system facilitated the communication between medical and trainer staff, who were able to identify in the system reports health complaints from athletes that were not necessarily communicated face-to-face. Therefore, staff members reported that they were able to intervene earlier to prevent minor health complaints from becoming severe health problems. However, staff members expected higher adherence of athletes to the online follow-ups, and athletes expected to receive feedback on their inputs to the system.

Conclusion

An online system can be used in sporting settings complementary to regular strategies for monitoring athletes’ health. However, providing feedback on athletes’ inputs is important to maintain their adherence to such an online system.
Feasibility of a real-time self-monitoring device for sitting less and moving more: a randomised controlled trial
Authors: Martin Anne , Adams Jacob M , Bunn Christopher , Gill Jason M R , Gray Cindy M , Hunt Kate , Maxwell Douglas J , van der Ploeg Hidde P , Wyke Sally , Mutrie Nanette
Published: October 2017

Objectives

Time spent inactive and sedentary are both associated with poor health. Self-monitoring of walking, using pedometers for real-time feedback, is effective at increasing physical activity. This study evaluated the feasibility of a new pocket-worn sedentary time and physical activity real-time self-monitoring device (SitFIT).

Methods

Forty sedentary men were equally randomised into two intervention groups. For 4 weeks, one group received a SitFIT providing feedback on steps and time spent sedentary (lying/sitting); the other group received a SitFIT providing feedback on steps and time spent upright (standing/stepping). Change in sedentary time, standing time, stepping time and step count was assessed using activPAL monitors at baseline, 4-week follow-up (T1) and 12-week (T2) follow-up. Semistructured interviews were conducted after 4 and 12 weeks.

Results

The SitFIT was reported as acceptable and usable and seen as a motivating tool to reduce sedentary time by both groups. On average, participants reduced their sedentary time by 7.8 minutes/day (95% CI −55.4 to 39.7) (T1) and by 8.2 minutes/day (95% CI −60.1 to 44.3) (T2). They increased standing time by 23.2 minutes/day (95% CI 4.0 to 42.5) (T1) and 16.2 minutes/day (95% CI −13.9 to 46.2) (T2). Stepping time was increased by 8.5 minutes/day (95% CI 0.9 to 16.0) (T1) and 9.0 minutes/day (95% CI 0.5 to 17.5) (T2). There were no between-group differences at either follow-up time points.

Conclusion

The SitFIT was perceived as a useful tool for self-monitoring of sedentary time. It has potential as a real-time self-monitoring device to reduce sedentary and increase upright time.
Atypical haematological presentation in a case of polycythaemia vera with a new variant mutation detected in exon 12: c.1605G>T (p.Met535Ile)
Authors: Pita Amélia Soraia Andrade , Azevedo Ana Paula da Silva , Reichert Alice , Silva Cândido José Pimenta da , Henriques Vanessa , Mendes Diana Sousa , Reis Ana Maria Batalha , Cerqueira Rita , Torres Fátima , Viana João Faro
Published: October 2017

One of the major genetic insights into the pathogenesis of polycythaemia vera included the identification of the somatic point gain-of-function mutations in Janus kinase 2 gene—firstJAK2V617Fon exon 14, present in 95%–97% of the cases, and later on exon 12. In the literature, we can find some reported studies where different exon 12 mutations are identified. Unlike patients withJAK2V617Fmutation in exon 14, the mutation at exon 12 is not usually associated with an increase in the three haematopoietic series (erythrocytosis, leucocytosis and thrombocytosis). It appears to be associated with a distinct syndrome, mostly characterised by isolated and more marked erythrocytosis, independently of the mutational variant. We report here the case of a patient who isJAK2exon 12 positive, presenting a novel mutation—c.1605G>T (p.Met535Ile)—associated with c.1612C>T (p.His538Tyr) mutation previously described, evidencing an atypical clinical phenotype.
Embolization of palpebral and orbito-frontal fistulas: technical and anatomical considerations in treating high-flow superficial skin lesions with liquid embolics
Authors: Samaniego Edgar A , Fisher Mark , Hasan David , Guerrero Waldo R , Fifi Johanna T , Bottani Laura , Ortega-Gutierrez Santiago
Published: October 2017

The treatment of palpebral and periorbital fistulas may be challenging due to the presence of multiple anastomosis with eloquent ophthalmic and intracranial vascular territories. Moreover, cosmetic and functional characteristics of this area pose unique challenges to open surgical approaches and endovascular therapy. We review the advantages and disadvantages of different liquid embolics in treating palpebral and periorbital fistulas as we describe three successfully treated cases. Moreover, we describe important anatomical landmarks that should be considered at the time of treatment of these lesions.
Acute ischemic stroke with tandem lesions: technical endovascular management and clinical outcomes from the ESCAPE trial
Authors: Assis Zarina , Menon Bijoy K , Goyal Mayank , Demchuk Andrew M , Shankar Jai , Rempel Jeremy L , Roy Daniel , Poppe Alexander Y , Yang Victor , Lum Cheemun , Dowlatshahi Dar , Thornton John , Choe Hana , Burns Paul A , Frei Donald F , Baxter Blaise W , Hill Michael D
Published: October 2017

Background

Tandem occlusions of the extracranial carotid and intracranial carotid or middle cerebral artery have a particularly poor prognosis without treatment. Several management strategies have been used with no clear consensus recommendations. We examined subjects with tandem occlusions enrolled in the ESCAPE trial and their outcomes.

Methods

Data are from the ESCAPE trial. Additional data were sought on interventions for each subject.

Results

There were 54 (17%) subjects with tandem extracranial and intracranial occlusions. Patients in the endovascular treatment arm (n=30) were more likely to be younger (median age 66 years, p<0.01), male (66.7%, p=0.03), diabetic, and without atrial fibrillation. Subjects with tandem occlusions were more likely to have intracranial internal carotid artery occlusions than M1 occlusions (p<0.01). Of the 30 intervention-arm subjects, 17 (57%) underwent emergency endovascular treatment of the extracranial disease, 10 subjects before and seven subjects after intracranial thrombectomy. Of the remaining 13 subjects, only four required staged carotid revascularization due to persistent severe carotid stenosis; four had cervical pseudo-occlusions with no residual stenosis after large distal carotid thrombus burden aspiration/retrieval. Outcomes were similar between subjects with and without tandem lesions. The use of antithrombotic agents after acute carotid artery stenting was variable but no symptomatic intracerebral hemorrhage was seen in subjects who underwent emergency endovascular treatment of extracranial carotid artery.

Conclusions

Tandem occlusions occurred in one-sixth of patients and were treated highly variably within the ESCAPE trial. While outcomes were similar, the best method to treat the carotid artery in patients with tandem occlusion awaits further randomized data.

Trial registration number

NCT01778335.
Infection rates in patients from five rheumatoid arthritis (RA) registries: contextualising an RA clinical trial programme
Authors: Yamanaka Hisashi , Askling Johan , Berglind Niklas , Franzen Stefan , Frisell Thomas , Garwood Christopher , Greenberg Jeffrey D , Ho Meilien , Holmqvist Marie , Novelli Horne Laura , Inoue Eisuke , Michaud Kaleb , Pappas Dimitrios A , Reed George , Symmons Deborah , Tanaka Eiichi , Tran Trung N , Verstappen Suzanne M M , Wesby-van Swaay Eveline , Nyberg Fredrik
Published: October 2017

Objective

Patients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study methodology. We measured infection rates from five RA registries globally, with the aim to contextualise infection rates from an RA clinical trials population.

Methods

We used data from Consortium of Rheumatology Research of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (Sweden), Norfolk Arthritis Register (UK), CORRONA International (multiple countries) and Institute of Rheumatology Rheumatoid Arthritis (Japan) and an RA clinical trial programme (fostamatinib). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data. Infection definitions were harmonised across registries. Sensitivity analyses to address potential confounding explored subcohorts defined by disease activity, treatment change and/or prior comorbidities and restriction by calendar time or follow-up. Rates of infections were estimated and standardised to the trial population for age/sex and, in one sensitivity analysis also, for Health Assessment Questionnaire (HAQ) score.

Results

Overall, age/sex-standardised rates of hospitalised infection were quite consistent across registries (range 1.14–1.62 per 100 patient-years). Higher and more consistent rates across registries and with the trial programme overall were seen when adding standardisation for HAQ score (registry range 1.86–2.18, trials rate 2.92) or restricting to a treatment initiation subcohort followed for 18 months (registry range 0.99–2.84, trials rate 2.74).

Conclusion

This prospective, coordinated analysis of RA registries provided incidence rate estimates for infection events to contextualise infection rates from an RA clinical trial programme and demonstrated relative comparability of hospitalised infection rates across registries.
Repeat syphilis has a different immune response compared with initial syphilis: an analysis of biomarker kinetics in two cohorts
Authors: Kenyon Chris , Tsoumanis Achilleas , Osbak Kara , Van Esbroeck Marjan , Florence Eric , Crucitti Tania , Kestens Luc
Published: October 2017

Objective

We aimed to asses if there are differences in the clinical presentation and immune response of repeat as compared with initial syphilis.

Methods

Prospective study: we prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for a range of cytochemokines and rapid plasma reagin (RPR) at baseline pretreatment and 6 months following therapy. Retrospective study: we compared RPR assay response kinetics between initial and repeat syphilis in persons attending our HIV/STI clinic from 1993 to 2016.

Results

Prospective study: a total of 91 individuals, 36 with initial syphilis and 55 with repeat syphilis, were included in the study. At baseline visit, those with initial syphilis were more likely to be symptomatic and have higher levels of interleukin-10 than repeaters. At baseline, median RPR titres were higher in the repeat than the initial infection groups. Repeaters were less likely than those with initial infections to serorevert to a negative RPR and be serofast (<4-fold RPR titre decline) at 6 months.

Retrospective study: syphilis was diagnosed in 1027/43 870 individuals tested. At diagnosis, repeaters had higher RPR titres and a stepwise increase in RPR titre with number of syphilis episodes. They had a different RPR test response kinetic: they were less likely to be serofast and to serorevert than initial syphilis at 6 and 12 months. No individuals with four or more previous episodes of syphilis seroreverted.

Conclusion

Repeat syphilis has a different clinical presentation and immunological response to initial infection.
Exercise tolerance during muscle contractions below and above the critical torque in different muscle groups
Authors: Abdalla Leonardo Henrique Perinotto , Denadai Benedito Sérgio , Bassan Natália Menezes , Greco Camila Coelho
Published: October 2017

The objective of this study was to test the hypotheses that end-test torque (ET) (expressed as % maximal voluntary contraction; MVC) is higher for plantar flexors (PF) than knee extensors (KE) muscles, whereas impulse above ET (IET) is higher for KE than PF. Thus, we expected that exercise tolerance would be longer for KE than PF only during the exercise performed above ET. After the determination of MVC, 40 men performed two 5-min all-out tests to determine ET and IET. Eleven participants performed a further 4 intermittent isometric tests, to exhaustion, at ET + 5% and ET – 5%, and 1 test for KE at the exercise intensity (%MVC) corresponding to ET + 5% of PF. The IET (7243.2 ± 1942.9 vs. 3357.4 ± 1132.3 N·m·s) and ET (84.4 ± 24.8 vs. 73.9 ± 19.5 N·m) were significantly lower in PF compared with KE. The exercise tolerance was significantly longer for PF (300.7 ± 156.7 s) than KE (156.7 ± 104.3 s) at similar %MVC (∼60%), and significantly shorter for PF (300.7 ± 156.7 s) than KE (697.0 ± 243.7 s) at ET + 5% condition. However, no significant difference was observed for ET – 5% condition (KE = 1030.2 ± 495.4 s vs. PF = 1028.3 ± 514.4 s). Thus, the limit of tolerance during submaximal isometric contractions is influenced by absolute MVC only during exercise performed above ET, which seems to be explained by differences on both ET (expressed as %MVC) and IET values.
Role of the TSLP–DC–OX40L pathway in asthma pathogenesis and airway inflammation in mice
Authors: Feng Shuang , Zhang Li , Bian Xu-Hua , Luo Ying , Qin Guang-Hui , Shi Rui-Ming
Published: October 2017

This study aimed to explore the effect of the TSLP–DC–OX40L pathway in asthma pathogenesis and airway inflammation in mice. For this, 65 male BALF/c mice were distributed among the control, asthma, immunoglobulin G (IgG) + asthma (IgG, 500 μg/500 μL, intratracheal injection of 50 μL each time), LY294002 (OX40L inhibitor) + asthma (intratracheal injection of 2 mg/kg LY294002), and anti-TSLP + asthma (intratracheal injection of 500 μg/500 μL TSLP antibody, 50 μL each time) groups. ELISA was applied to measure the serum levels of immunoglobulin E (IgE), ovalbumin (OVA)-sIgE, interleukin-4 (IL-4), IL-5, IL-13, and interferon-γ (IFN-γ); flow cytometry was employed to detect Treg cells and dendritic cell (DC) and lymphopoiesis. RT–qPCR and Western blot assays were used to measure the levels of TSLP, OX40L, T-bet, GATA-3, NF-κB, p38, and ERK. Treatment with LY294002 and anti-TSLP resulted in increases in the numbers of total cells, eosinophils, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid; total serum levels of IgE, OVA-sIgE, IL-4, IL-5, and IL-13; levels of DC cells; lymphopoiesis; and levels of TSLP, OX40L, GATA-3, NF-κB, p38, and ERK, whereas there were decreases in the levels of IFN-γ and CD4+CD25+Treg cells; CD4+Foxp3+Treg cells; and T-bet. The TSLP–DC–OX40L pathway may contribute to asthma pathogenesis and airway inflammation by modulating the levels of CD4+CD25+Treg cells and inflammatory cytokines.
Knockdown of CEMIP suppresses proliferation and induces apoptosis in colorectal cancer cells: downregulation of GRP78 and attenuation of unfolded protein response
Authors: Liang Guodong , Fang Xuedong , Yang Yubo , Song Yan
Published: October 2017

It has been suggested that cell migration inducing hyaluronan binding protein (CEMIP) contributes to the carcinogenesis of colorectal cancer (CRC). Cancer cells can adapt to endoplasmic reticulum (ER) stress by initiating an unfolded protein response (UPR). This study aimed to investigate whether CEMIP affects the UPR of CRC cells, with a focus on 78 kDa glucose-regulated protein (GRP78, a major ER chaperone). We found that knockdown of CEMIP inhibited cell proliferation and induced a G1 arrest in SW480 CRC cells. The levels of cyclin D1 and cyclin E1 and phospho-retinoblastoma, which are known to promote the cell cycle progression from G0 or G1 into S phase, were decreased in CEMIP-silenced cells. CEMIP shRNA induced apoptosis and inhibited GRP78 expression in SW480 and Colo205 cells. The basal UPR of cancer cells was attenuated by CEMIP shRNA, as evidenced by the decreased expression of UPR sensors, protein kinase R-like endoplasmic reticulum kinase (PERK), inositol requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). Furthermore, CEMIP silencing sensitized CRC cells to thapsigargin-induced apoptosis. Our study demonstrates that the in-vitro anti-proliferative and pro-apoptotic effects in CRC cells that were induced by silencing CEMIP may be associated with GRP78 repression and UPR attenuation.
Plastic adaptations of foraging strategies to variation in forage quality in Alpine chamois (Rupicapra rupicapra)
Authors: Puorger Arno , Rossi Christian , Haller Rudolf M. , Anderwald Pia
Published: October 2017

Foraging efficiency strongly affects individual fitness and is influenced by diverse factors such as food quality and quantity, as well as intra- and inter-specific interactions. We investigated whether Alpine chamois (Rupicapra rupicapra (Linnaeus, 1758)) in a protected area in the Swiss Alps adapted their foraging behaviour to forage availability and quality by modeling the bite and step rates of individuals on vegetation nitrogen content, relative plant cover, sex, daytime, air temperature, and slope. Vegetation characteristics were derived using remote sensing data from airborne imaging spectroscopy data sets and feeding locations determined using a theodolite. Chamois increased their bite rates with decreasing forage nitrogen content, decreasing slope, and increasing temperature. Step rates were higher at high temperatures and decreased with increasing relative plant cover. Males showed higher bite rates and lower step rates than females. Daytime had no influence on either bite or step rates. An increase in bite rate may represent a plastic adaptation of foraging behaviour to compensate for lower nutritional quality of the available vegetation. Our results show variability in foraging behaviour according to both vegetation characteristics and physical environment and emphasize the use of remote sensing data to investigate relationships between habitat and subtle behavioural adaptations in ungulates.
On the Inverse Problem of Competitive Modes and the Search for Chaotic Dynamics
Authors: Ruks Lewis , Van Gorder Robert A.
Published: October 2017

Generalized competitive modes (GCM) have been used as a diagnostic tool in order to analytically identify parameter regimes which may lead to chaotic trajectories in a given first order nonlinear dynamical system. The approach involves recasting the first order system as a second order nonlinear oscillator system, and then checking to see if certain conditions on the modes of these oscillators are satisfied. In the present paper, we will consider the inverse problem of GCM: If a system of second order oscillator equations satisfy the GCM conditions, can we then construct a first order dynamical system from it which admits chaotic trajectories? Solving the direct inverse problem is equivalent to finding solutions to an inhomogeneous form of the Euler equations. As there are no general solutions to this PDE system, we instead consider the problem for restricted classes of functions for autonomous systems which, upon obtaining the nonlinear oscillatory representation, we are able to extract at least two of the modes explicitly. We find that these methods often make finding chaotic regimes a much simpler task; many classes of parameter-function regimes that lead to nonchaos are excluded by the competitive mode conditions, and classical knowledge of dynamical systems then allows us to tune the free parameters or functions appropriately in order to obtain chaos. To find new hyperchaotic systems, a similar approach is used, but more effort and additional considerations are needed. These results demonstrate one method for constructing new chaotic or hyperchaotic systems.
Research on Bifurcation and Chaos in a Dynamic Mixed Game System with Oligopolies Under Carbon Emission Constraint
Authors: Ma Junhai , Yang Wenhui , Lou Wandong
Published: October 2017

This paper establishes an oligopolistic game model under the carbon emission reduction constraint and investigates its complex characteristics like bifurcation and chaos. Two oligopolistic manufacturers comprise three mixed game models, aiming to explore the variation in the status of operating system as per the upgrading of benchmark reward-penalty mechanism. Firstly, we set up these basic models that are respectively distinguished with carbon emission quantity and study these models using different game methods. Then, we concentrate on one typical game model to further study the dynamic complexity of variations in the system status, through 2D bifurcation diagrams and 4D parameter adjustment features based on the bounded rationality scheme for price, and the adaptive scheme for carbon emission. The results show that the carbon emission constraint has significant influence on the status variation of two-oligopolistic game operating systems no matter whether it is stable or chaotic. Besides, the new carbon emission regulation meets government supervision target and achieves the goal of being environment friendly by motivating the system to operate with lower carbon emission.