bluuebunny/crossref_metadata_2025 huggingface dataset:
From Professional Development to Implementation: A District's Experience Implementing Mathematics Tiered Systems of Support
Authors: Mason Erica N. , Benz Sarah A. , Lembke Erica S. , Burns Matthew K. , Powell Sarah R.
Published: September 2019

This article is about a school‐district‐initiated partnership with university faculty and their effort to implement a mathematics multi‐tiered system of support (MTSS). In addition to reporting research about MTSS implementation, we describe how this district translated research into practice. We also share the perceptions of key stakeholders about implementing mathematics MTSS in their district. We found that stakeholders identified time and human capacity as barriers to implementation, while the primary facilitator to implementation was identified as the acquisition of concrete strategies and tools supporting instruction. These stakeholder perceptions have implications for other districts with limited resources attempting to implement mathematics MTSS in their buildings through professional development and coaching.
Suicide—turning the tide
Authors: Nordentoft Merete , Erlangsen Annette
Published: September 2019

Suicide is a devastating public health problem, afflicting individuals, families, and societies. Fortunately, continuous striving by the World Health Organization to strengthen suicide prevention efforts is paying off. The annual number of suicide deaths decreased from 1 million to 800,000 worldwide during recent decades. A gloomy exception to this trend is the increasing rate of suicide in the United States (14.0 per 100,000 in 2017). But Denmark's experience offers some hope that prevention of suicide is possible. Why has its decline in suicide been steeper than in most other countries?
Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study
Authors: Thayakaran Rasiah , Adderley Nicola J , Sainsbury Christopher , Torlinska Barbara , Boelaert Kristien , Šumilo Dana , Price Malcolm , Thomas G Neil , Toulis Konstantinos A , Nirantharakumar Krishnarajah
Published: September 2019

Objective

To explore whether thyroid stimulating hormone (TSH) concentration in patients with a diagnosis of hypothyroidism is associated with increased all cause mortality and a higher risk of cardiovascular disease and fractures.

Design

Retrospective cohort study.

Setting

The Health Improvement Network (THIN), a database of electronic patient records from UK primary care.

Participants

Adult patients with incident hypothyroidism from 1 January 1995 to 31 December 2017.

Exposure

TSH concentration in patients with hypothyroidism.

Main outcome measures

Ischaemic heart disease, heart failure, stroke/transient ischaemic attack, atrial fibrillation, any fractures, fragility fractures, and mortality. Longitudinal TSH measurements from diagnosis to outcomes, study end, or loss to follow-up were collected. An extended Cox proportional hazards model with TSH considered as a time varying covariate was fitted for each outcome.

Results

162 369 patients with hypothyroidism and 863 072 TSH measurements were included in the analysis. Compared with the reference TSH category (2-2.5 mIU/L), risk of ischaemic heart disease and heart failure increased at high TSH concentrations (>10 mIU/L) (hazard ratio 1.18 (95% confidence interval 1.02 to 1.38; P=0.03) and 1.42 (1.21 to 1.67; P<0.001), respectively). A protective effect for heart failure was seen at low TSH concentrations (hazard ratio 0.79 (0.64 to 0.99; P=0.04) for TSH <0.1 mIU/L and 0.76 (0.62 to 0.92; P=0.006) for 0.1-0.4 mIU/L). Increased mortality was observed in both the lowest and highest TSH categories (hazard ratio 1.18 (1.08 to 1.28; P<0.001), 1.29 (1.22 to 1.36; P<0.001), and 2.21 (2.07 to 2.36; P<0.001) for TSH <0.1 mIU/L, 4-10 mIU/L, and >10 mIU/L. An increase in the risk of fragility fractures was observed in patients in the highest TSH category (>10 mIU/L) (hazard ratio 1.15 (1.01 to 1.31; P=0.03)).

Conclusions

In patients with a diagnosis of hypothyroidism, no evidence was found to suggest a clinically meaningful difference in the pattern of long term health outcomes (all cause mortality, atrial fibrillation, ischaemic heart disease, heart failure, stroke/transient ischaemic attack, fractures) when TSH concentrations were within recommended normal limits. Evidence was found for adverse health outcomes when TSH concentration is outside this range, particularly above the upper reference value.
Sitagliptin for the prevention of stress hyperglycemia in patients without diabetes undergoing coronary artery bypass graft (CABG) surgery
Authors: Cardona Saumeth , Tsegka Katerina , Pasquel Francisco J , Fayfman Maya , Peng Limin , Jacobs Sol , Vellanki Priyathama , Halkos Michael , Guyton Robert A , Thourani Vinod H , Galindo Rodolfo J , Umpierrez Guillermo
Published: September 2019

Aims

To determine if treatment with sitagliptin, a dipeptidyl peptidase-4 inhibitor, can prevent stress hyperglycemia in patients without diabetes undergoing coronary artery bypass graft (CABG) surgery.

Methods

We conducted a pilot, double-blinded, placebo-controlled randomized trial in adults (18–80 years) without history of diabetes. Participants received sitagliptin or placebo once daily, starting the day prior to surgery and continued for up to 10 days. Primary outcome was differences in the frequency of stress hyperglycemia (blood glucose (BG) >180 mg/dL) after surgery among groups.

Results

We randomized 32 participants to receive sitagliptin and 28 to placebo (mean age 64±10 years and HbA1c: 5.6%±0.5%). Treatment with sitagliptin resulted in lower BG levels prior to surgery (101±mg/dL vs 107±13 mg/dL, p=0.01); however, there were no differences in the mean BG concentration, proportion of patients who developed stress hyperglycemia (21% vs 22%, p>0.99), length of hospital stay, rate of perioperative complications and need for insulin therapy in the intensive care unit or during the hospital stay.

Conclusion

The use of sitagliptin during the perioperative period did not prevent the development of stress hyperglycemia or need for insulin therapy in patients without diabetes undergoing CABG surgery.
In-depth examination of issues surrounding the reasons for child marriage in Kelantan, Malaysia: a qualitative study
Authors: Kohno Ayako , Dahlui Maznah , Nik Farid Nik Daliana , Ali Siti Hawa , Nakayama Takeo
Published: September 2019

Objective

To examine individual, familial, community and societal issues surrounding the reasons for child marriage in Kelantan, Malaysia.

Design

Qualitative study by means of semistructured interviews with women and key informants, using social-ecological model as a conceptual framework.

Setting

Interviews were conducted in Kota Bharu district, Kelantan, a northeast state in Peninsular Malaysia.

Participants

Eighteen women of reproductive age (18 to 44 years old) that experienced their first marriage below the age of 18, as well as five key informants, consisting of a government officer, a community leader, an officer from religious department and two mothers. The women were recruited from a reproductive health clinic. The key informants who had specialised knowledge related to child marriage were selectively chosen.

Results

Three themes emerged that aligned with the social-ecological model: immaturity in decision-making, family poverty and religious and cultural norms.

Conclusions

The findings imply that sex education and awareness-building activities regarding the consequences of child marriage must be implemented to eradicate child marriage in Malaysia. Such implementation must be coordinated as a team-based approach involving experts in such fields as law, religion, psychology, social-welfare and public health. In order to increase the awareness of child marriage consequences, the target for awareness must extend not only to the adolescent girls and their families, but also to the community and society at large by clearly communicating the negative consequences of and addressing the drivers for child marriage.
Healthy Lifestyle Program (HeLP) for low back pain: protocol for a randomised controlled trial
Authors: Robson Emma K , Kamper Steven J , Davidson Simon , Viana da Silva Priscilla , Williams Amanda , Hodder Rebecca K , Lee Hopin , Hall Alix , Gleadhill Connor , Williams Christopher M
Published: September 2019

Introduction

Low back pain is one of the most common and burdensome chronic conditions worldwide. Lifestyle factors, such as excess weight, physical inactivity, poor diet and smoking, are linked to low back pain chronicity and disability. There are few high-quality randomised controlled trials that investigate the effects of targeting lifestyle risk factors in people with chronic low back pain.

Methods and analysis

The aim of this study is to determine the effectiveness of a Healthy Lifestyle Program (HeLP) for low back pain targeting weight, physical activity, diet and smoking to reduce disability in patients with chronic low back pain compared with usual care. This is a randomised controlled trial, with participants stratified by body mass index, allocated 1:1 to the HeLP intervention or usual physiotherapy care. HeLP involves three main components: (1) clinical consultations with a physiotherapist and dietitian; (2) educational resources; and (3) telephone-based health coaching support for lifestyle risk factors. The primary outcome is disability (Roland Morris Disability Questionnaire) at 26 weeks. Secondary outcomes include pain intensity, weight, quality of life and smoking status. Data will be collected at baseline, and at weeks 6, 12, 26 and 52. Patients with chronic low back pain who have at least one health risk factor (are overweight or obese, are smokers and have inadequate physical activity or fruit and vegetable consumption) will be recruited from primary or secondary care, or the community. Primary outcome data will be analysed by intention to treat using linear mixed-effects regression models. We will conduct three supplementary analyses: causal mediation analysis, complier average causal effects analysis and economic analysis.

Ethics and dissemination

This study was approved by the Hunter New England Research Ethics Committee (Approval No 17/02/15/4.05), and the University of Newcastle Human Research Ethics Committee (Ref No H-2017-0222). Outcomes of this trial and supplementary analyses will be disseminated through publications in peer-reviewed journals and conference presentations.

Trial registration number

ACTRN12617001288314.
The prevalence and influencing factors of physical activity and sedentary behaviour in the rural population in China: the Henan Rural Cohort Study
Authors: Tu Runqi , Li Yuqian , Shen Lijun , Yuan HuiJuan , Mao Zhenxing , Liu Xiaotian , Zhang Haiqing , Zhang Liying , Li Ruiying , Wang Yikang , Wang Yuming , Wang Chongjian
Published: September 2019

Objectives

To estimate the prevalence and influencing factors of physical activity (PA) and sedentary behaviour (SB) in rural areas of China.

Design

Cross-sectional study.

Setting

A multistage, stratified cluster sampling method was used to obtain samples in the general population of Henan province in China.

Participants

38 515 participants aged 18–79 years were enrolled from the Henan Rural Cohort Study for the cross-sectional study.

Main outcome measures

The International Physical Activity Questionnaire was used to assess the levels of PA and SB. Multiple logistic regression analysis was used to calculate ORs and 95% CIs of potential influencing factors with physical inactivity.

Results

The age-standardised prevalence of light PA and sitting >7.5 hours per day were 32.74% and 26.88% in the general Chinese rural adults, respectively. Gender differences were: 34.91%, 29.76% for men and 31.75%, 25.16% for women, respectively. The prevalence of participants with both light PA and sitting >7.5 hours per day was 13.95%. Education at least junior middle school, divorced/widowed/unmarried, RMB1000> per capita monthly income ≥RMB500, sitting >7.5 hours per day were negatively associated with light PA. For sitting >7.5 hours per day, the negative factors were being men, divorced/widowed/unmarried, heavy smoking, Fishery products, vegetable and fruits intake .

Conclusion

Physical inactivity and SB were high in rural China. There is an increased need to promote a healthy lifestyle to the rural population.

Clinical trial registration

The Henan Rural Cohort Study has been registered with the Chinese Clinical Trial Register.

Registration number: ChiCTR-OOC-15006699.http://www.chictr.org.cn/showproj.aspx?proj=11375
Developing a training programme in physical activity counselling for undergraduate medical curricula: a nationwide Delphi study
Authors: Wattanapisit Apichai , Petchuay Prachyapan , Wattanapisit Sanhapan , Tuangratananon Titiporn
Published: September 2019

Objectives

To identify the essential content and approaches for developing a training programme in physical activity (PA) counselling for undergraduate medical curricula.

Design

A three-round Delphi survey was conducted to investigate four key topics: (1) contents of PA counselling in medical education; (2) teaching and learning methods; (3) medical school collaboration and (4) educational policy implementation. Round 1 collected opinions from the participants. Round 2 focused on scoring the opinions. Round 3 summarised the expert opinions. A mean score of 4 or above identified as an important item.

Setting

All 23 medical schools in Thailand.

Participants

Academic staff who were experts or in charge of medical schools in the fields of PA, health promotion or medical education.

Results

A total of 20 representatives from 18 of the 23 Thai medical schools participated in the study (for a response rate of 78.2%). The top three most important indicators of knowledge were (1) the definition and types of PA (4.75±0.55), (2) the FITT principle (frequency, intensity, time and type) (4.75±0.55) and (3) the benefits of PA (4.65±0.67). The most important component of the training involved general communication skills (4.55±0.60). An extracurricular module (4.05±0.76) was preferable to an intracurricular module (3.95±0.94). Collaborations with medical education centres and teaching hospitals (4.45±0.78) and supporting policies to increase medical students’ PA (4.40±0.73) were considered to be important.

Conclusion

Knowledge and counselling skills are important for PA counselling. Building collaborations between medical education and health institutions, as well as implementing effective educational policies, are key approaches to the integration of PA counselling into medical education. Future research should focus on investigating the effects of training in PA counselling on the learning outcomes of medical students and the clinical outcomes of patients.
Economic burden of paediatric-onset disabilities among young and middle-aged adults in the USA: a cohort study of privately insured beneficiaries
Authors: Whitney Daniel , Kamdar Neil , Hirth Richard A , Hurvitz Edward A , Peterson Mark D
Published: September 2019

Objective

Individuals with paediatric-onset disabilities (PoDs) have complex healthcare needs and are susceptible to adverse health outcomes, which may impose a higher strain on healthcare resources. The burden of healthcare resource utilisation and costs attributed to the population of adults with PoDs is not clearly established. The objective here was to compare healthcare resource utilisation and costs between adults with versus without PoDs.

Design

Cohort.

Setting

Data were from the 2016 Optum Clinformatics Data Mart, a de-identified nationwide claims database of beneficiaries from a single private payer in the USA.

Participants

International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes were used to identify beneficiaries with PoDs that were between 18 and 64 years of age.

Primary and secondary outcome measures

Annual all-cause healthcare resource utilisation and total healthcare costs were compared between adults with and without PoDs before and after adjusting for sociodemographics and several costly non-communicable diseases.

Results

Adults with PoDs (n=121 446) had greater annual mean counts of service utilisation for all service types (eg, inpatient, outpatient, emergency visits) compared with adults without PoDs (n=5 415 475) before and after adjustments (all p<0.001). Adults with PoDs had greater unadjusted total standardised reimbursement costs (US$26 702 vs US$8464; mean difference=US$18 238; cost ratio (CR)=3.16; 95% CI=3.13 to 3.18) and total patient out-of-pocket costs (US$2226 vs US$1157; mean difference=US$1069; CR=1.88; 95%CI=1.86 to 1.89). After adjustments, total standardised reimbursement costs were 2.32 times higher (95% CI=2.30 to 2.34) and total patient out-of-pocket costs were 1.65 times higher (95% CI=1.64 to 1.66) compared with adults without PoDs.

Conclusion

Adults with PoDs had greater healthcare utilisation and costs, even after accounting for costly diseases. Future research is needed to identify the cost drivers for adults with PoDs.
Assessing the effectiveness of perioperative s-ketamine on new-onset headache after resective epilepsy surgery (ESPAIN-trial): protocol for a randomised, double-blind, placebo-controlled trial
Authors: Sloekers Jiske Cornelia Theresa , Bos Michael , Hoogland Govert , Bastiaenen Caroline , van Kuijk Sander , Theunissen Maurice , Rijkers Kim , Dings Jim , Colon Albert , Rouhl Rob P W , Schijns Olaf Elisabeth Maria Ghislaine
Published: September 2019

Introduction

Effective treatment of new-onset headache after craniotomy, especially anterior temporal lobectomy (ATL) and amygdalohippocampectomy for drug-resistant temporal lobe epilepsy, is a challenge. The current practice, acetaminophen combined with opioids is often reported by patients as insufficient and sometimes accompanied by opioid-related adverse effects. Based on expert opinion, anaesthesiologists therefore frequently consider s-ketamine as add-on therapy. This randomised parallel group design trial compares s-ketamine with a placebo as add on medication to a multimodal pain approach.

Methods and analysis

In total 62 adult participants, undergoing ATL for drug resistant epilepsy under general anaesthesia, will be randomised to either receive a 0.25 mg/kg bolus followed by a continuous infusion of 0.1 mg/kg/hour of s-ketamine or placebo (0.9% NaCl) starting before incision and continued for 48 hours as an addition to acetaminophen and opioids administered in a patient-controlled analgesia pump. The primary outcome measure is the cumulative postoperative opioid consumption. Patient recruitment started August 2018 and will end in 2021. Secondary outcome measures are postoperative pain intensity scores, psychological parameters, length of hospital stay and adverse events and will be reassessed at 3 and 6 months after surgery, with a baseline measurement preoperatively. All data are collected by researchers who are blinded to the treatment. The data will be analysed by multivariable linear mixed-effects regression.

Ethics and dissemination

Ethical approval has been given by the local medical ethical committee (NL61666.068.17). This study will be conducted in accordance with the Dutch Medical Research Involving Human Subjects Act and the Declaration of Helsinki. The results of this trial will be publicly disclosed and submitted for publication in an international peer-reviewed scientific journal.

Trial registration number

NTR6480.
Efficacy and safety of 1C class antiarrhythmic agent (propafenone) for supraventricular arrhythmias in septic shock compared to amiodarone: protocol of a prospective randomised double-blind study
Authors: Balik Martin , Waldauf Petr , Maly Michal , Matousek Vojtech , Brozek Tomas , Rulisek Jan , Porizka Michal , Sachl Robert , Otahal Michal , Brestovansky Petr , Svobodova Eva , Flaksa Marek , Stach Zdenek , Pazout Jaroslav , Duska Frantisek , Smid Ondrej , Stritesky Martin
Published: September 2019

Introduction

Supraventricular arrhythmias contribute to haemodynamic compromise in septic shock. A retrospective study generated the hypothesis that propafenone could be more effective than amiodarone in achieving and maintaining sinus rhythm (SR). Certain echocardiographic parameters may predict a successful cardioversion and help in the decision on rhythm or rate control strategy.

Methods and analysis

The trial includes septic shock patients with new-onset arrhythmia, but without severe impairment of the left ventricular ejection fraction. After baseline echocardiography, the patient is randomised to receive a bolus and maintenance dose of either amiodarone or propafenone. The primary outcome is the proportion of patients that have achieved rhythm control at 24 hours after the start of the infusion. The secondary outcomes are the percentages of patients that needed rescue treatments (DC cardioversion or unblinding and crossover of the antiarrhythmics), the recurrence of arrhythmias, intensive care unit mortality, 28-day and 1-year mortality. In the posthoc analysis, we separately assess subgroups of patients with pulmonary hypertension and right ventricular dysfunction. In the exploratory part of the study, we assess whether the presence of a transmitral diastolic A wave and its higher velocity-time integral is predictive for the sustainability of mechanical SR and whether the indexed left atrial endsystolic volume is predictive of recurrent arrhythmia. Considering that the restoration of SR within 24 hours occurred in 74% of the amiodarone-treated patients and in 89% of the patients treated with propafenone, we plan to include 200 patients to have an 80% chance to demonstrate the superiority of propafenone at p=0.05.

Ethics and dissemination

The trial is recruiting patients according to its second protocol version approved by the University Hospital Ethical Board on the 6 October 2017 (No. 1691/16S-IV). The results will be disseminated through peer reviewed publications and conference presentations.

Trial registration number

NCT03029169.
Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study
Authors: Boman Antonia , Brink Mikael , Lundquist Anders , Hansson Monica , Mathsson-Alm Linda , Rönnelid Johan , Berglin Ewa , Holmdahl Rikard , Skriner Karl , Serre Guy , Klareskog Lars , Rantapää-Dahlqvist Solbritt
Published: September 2019

Introduction

Anticitrullinated peptide antibody (ACPA) responses for 22 citrullinated peptides in patients with early rheumatoid arthritis (RA) were analysed and related to radiological and clinical outcome during the first 2 years in a prospective inception cohort.

Methods

The ACPA reactivities were assessed in 1022 patients with early RA (symptoms <12 months) using the custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden) in a prospective longitudinal study of observational assessments of Disease Activity Score (DAS28 and its components) and radiology during the first 24 months, accounting for the treatment.

Results

Frequency of ACPA reactivities varied between 13.3% and 63.1%. Of the anticyclic citrullinated peptide-2 (anti-CCP2) antibody-negative patients, ACPA reactivities were positive in 32.6%. Smoking, human leucocyte antigen-shared epitope (HLA-SE), anti-CCP2/rheumatoid factor, protein tyrosine phosphatase non-receptor type 22 (1858C/T) and DAS28 were significantly associated with number of ACPA reactivities. The ACPA reactivities modified differently the development of DAS28 over 24 months (identified using trajectories). Anti-Filaggrin307-324, anti-hnRNP (Peptide)-Z1 and anti-F4-CIT-R antibodies anticipated lower DAS28 values (p<0.01–0.05), while positivity for anti-Fibrinogen(Fib)β62-78(74), and anti-Fibα563-583 predicted higher DAS28 (p<0.01 both). Interaction between anti-Fibß36-52, anti-Pept-5 and anti-Bla-26 antibodies, respectively, and DAS28 during 24 months decreased significantly the DAS28 values (p<0.01–0.05). Corticosteroids and biologicals were related to DAS28-area under the curve and Larsen score 24 months. Anti-vimentin2-17 antibodies remained significantly associated with Larsen score at baseline and 24 months, respectively, and radiological progression, besides biologicals at 24 months adjusted for sex and age.

Conclusions

Several ACPA reactivities modified significantly the DAS28 development during the first 24 months and were significantly associated with Larsen score at baseline, 24 months and radiological progression.
Accounting for Reliability in Unacknowledged Time-Constrained WSNs
Authors: Parsch Philip , Masrur Alejandro
Published: September 2019

Wireless sensor networks typically consist of nodes that collect and transmit data periodically. In this context, we are concerned with unacknowledged communication, such as where data packets are not confirmed upon successful reception. This allows reducing traffic on the communication channel—neither acknowledgments nor retransmissions are sent—and results in less overhead and less energy consumption, which are meaningful goals in the era of the Internet of Things. However, packets can be lost, and hence we do not know how long it takes to convey data from one node to another, which hinders any form of real-time operation and/or quality of service. To overcome this problem, we propose a medium access control protocol, which consists of transmitting each packet at a random instant but within a specified time interval from the last transmission. In contrast to existing approaches from the literature, the proposed medium access control can be configured to meet reliability requirements—given by the probability that at least one data packet reaches its destination within a specified deadline—in the absence of acknowledgments. We illustrate this and other benefits of the proposed approach based on detailed OMNeT++ simulations.
Improving the Security of Visual Challenges
Authors: Valente Junia , Bahirat Kanchan , Venechanos Kelly , Cardenas Alvaro A. , Balakrishnan Prabhakaran
Published: September 2019

This article proposes new tools to detect the tampering of video feeds from surveillance cameras. Our proposal illustrates the unique
cyber-physical
properties that sensor devices can leverage for their cyber-security. While traditional attestation algorithms exchange
digital
challenges between devices authenticating each other, our work instead proposes challenges that manifest physically in the field of view of the camera (e.g., a QR code in a display). This physical (challenge) and cyber (verification) attestation mechanism can help protect systems even when the sensors (cameras) and actuators (a display, infrared LEDs, color light bulbs) are compromised. In this article, we consider skillful adversaries that can capture the correct challenges (our system is sending) and can re-create them in the response to try fooling our verification system, and we propose new algorithms to detect these powerful attackers. Also, we introduce new visual challenges that make harder for anti-forensics attackers to succeed, and we present experimental results showing how our system is robust against a variety of attacks ranging from naive attacks to more sophisticated anti-forensics attackers.
Automated Reuse of Model Transformations through Typing Requirements Models
Authors: Lara Juan De , Guerra Esther , Ruscio Davide Di , Rocco Juri Di , Cuadrado Jesús Sánchez , Iovino Ludovico , Pierantonio Alfonso
Published: September 2019

Model transformations are key elements of model-driven engineering, where they are used to automate the manipulation of models. However, they are typed with respect to concrete source and target meta-models, making their reuse for other (even similar) meta-models challenging.

To improve this situation, we propose capturing the typing requirements for reusing a transformation with other meta-models by the notion of a
typing requirements model
(TRM). A TRM describes the prerequisites that a model transformation imposes on the source and target meta-models to obtain a correct typing. The key observation is that any meta-model pair that satisfies the TRM is a valid reuse context for the transformation at hand.

A TRM is made of two
domain requirement models
(DRMs) describing the requirements for the source and target meta-models, and a compatibility model expressing dependencies between them. We define a notion of refinement between DRMs and see meta-models as a special case of DRM. We provide a catalogue of valid refinements and describe how to automatically extract a TRM from an ATL transformation. The approach is supported by our tool TOTEM. We report on two experiments—based on transformations developed by third parties and meta-model mutation techniques—validating the correctness and completeness of our TRM extraction procedure and confirming the power of TRMs to encode variability and support flexible reuse.
NavCog3 in the Wild
Authors: Sato Daisuke , Oh Uran , Guerreiro João , Ahmetovic Dragan , Naito Kakuya , Takagi Hironobu , Kitani Kris M. , Asakawa Chieko
Published: September 2019

NavCog3 is a smartphone turn-by-turn navigation assistant system we developed specifically designed to enable independent navigation for people with visual impairments. Using off-the-shelf Bluetooth beacons installed in the surrounding environment and a commodity smartphone carried by the user, NavCog3 achieves unparalleled localization accuracy in real-world large-scale scenarios. By leveraging its accurate localization capabilities, NavCog3 guides the user through the environment and signals the presence of semantic features and points of interest in the vicinity (e.g., doorways, shops).

To assess the capability of NavCog3 to promote independent mobility of individuals with visual impairments, we deployed and evaluated the system in two challenging real-world scenarios. The first scenario demonstrated the scalability of the system, which was permanently installed in a five-story shopping mall spanning three buildings and a public underground area. During the study, 10 participants traversed three fixed routes, and 43 participants traversed free-choice routes across the environment. The second scenario validated the system’s usability in the wild in a hotel complex temporarily equipped with NavCog3 during a conference for individuals with visual impairments. In the hotel, almost 14.2h of system usage data were collected from 37 unique users who performed 280 travels across the environment, for a total of 30,200m traversed.
Find and Seek
Authors: Williams Kristin , Clarke Taylor , Gardiner Steve , Zimmerman John , Tomasic Anthony
Published: September 2019

Web designers use visual cues such as layout and typography to make pages easier to navigate and understand. Yet, screen readers generally ignore these features and present page information in a linear audio stream. We investigate whether transcoding the visual semantics of grid-based layouts to tables supports better navigation. In a controlled experiment, participants navigated re-written pages significantly faster when doing data synthesis tasks and more accurately when looking up information meeting multiple criteria. Participants rated their table navigation experience better in terms of effort, memorization, ease of navigation, understanding of page information, and confidence in submitted answers. Participants attributed these gains to the table structure’s support for (1) predictable audio presentation, (2) adopting an appropriate search strategy, and (3) making sense of page content. Contrary to the established belief that tables are inaccessible, our results show that tables can facilitate navigation when users need to synthesize across page content.
Loss of mitochondrial energetics is associated with poor recovery of muscle function but not mass following disuse atrophy
Authors: Trevino Michelle B. , Zhang Xiaolei , Standley Robert A. , Wang Miao , Han Xianlin , Reis Felipe C. G. , Periasamy Muthu , Yu Gongxin , Kelly Daniel P. , Goodpaster Bret H. , Vega Rick B. , Coen Paul M.
Published: September 2019

Skeletal muscle atrophy is a clinically important outcome of disuse because of injury, immobilization, or bed rest. Disuse atrophy is accompanied by mitochondrial dysfunction, which likely contributes to activation of the muscle atrophy program. However, the linkage of muscle mass and mitochondrial energetics during disuse atrophy and its recovery is incompletely understood. Transcriptomic analysis of muscle biopsies from healthy older adults subject to complete bed rest revealed marked inhibition of mitochondrial energy metabolic pathways. To determine the temporal sequence of muscle atrophy and changes in intramyocellular lipid and mitochondrial energetics, we conducted a time course of hind limb unloading-induced atrophy in adult mice. Mitochondrial respiration and calcium retention capacity were diminished, whereas H2O2 emission was increased within 3 days of unloading before significant muscle atrophy. These changes were associated with a decrease in total cardiolipin and profound changes in remodeled cardiolipin species. Hind limb unloading performed in muscle-specific peroxisome proliferator-activated receptor-γ coactivator-1α/β knockout mice, a model of mitochondrial dysfunction, did not affect muscle atrophy but impacted muscle function. These data suggest early mitochondrial remodeling affects muscle function but not mass during disuse atrophy. Early alterations in mitochondrial energetics and lipid remodeling may represent novel targets to prevent muscle functional impairment caused by disuse and to enhance recovery from periods of muscle atrophy.
Modification of Peak Plasticity Induced by Brief Dark Exposure
Authors: Lingley Alexander J. , Mitchell Donald E. , Crowder Nathan A. , Duffy Kevin R.
Published: September 2019

The capacity for neural plasticity in the mammalian central visual system adheres to a temporal profile in which plasticity peaks early in postnatal development and then declines to reach enduring negligible levels. Early studies to delineate the critical period in cats employed a fixed duration of monocular deprivation to measure the extent of ocular dominance changes induced at different ages. The largest deprivation effects were observed at about 4 weeks postnatal, with a steady decline in plasticity thereafter so that by about 16 weeks only small changes were measured. The capacity for plasticity is regulated by a changing landscape of molecules in the visual system across the lifespan. Studies in rodents and cats have demonstrated that the critical period can be altered by environmental or pharmacological manipulations that enhance plasticity at ages when it would normally be low. Immersion in complete darkness for long durations (dark rearing) has long been known to alter plasticity capacity by modifying plasticity-related molecules and slowing progress of the critical period. In this study, we investigated the possibility that brief darkness (dark exposure) imposed just prior to the critical period peak can enhance the level of plasticity beyond that observed naturally. We examined the level of plasticity by measuring two sensitive markers of monocular deprivation, namely, soma size of neurons and neurofilament labeling within the dorsal lateral geniculate nucleus. Significantly larger modification of soma size, but not neurofilament labeling, was observed at the critical period peak when dark exposure preceded monocular deprivation. This indicated that the natural plasticity ceiling is modifiable and also that brief darkness does not simply slow progress of the critical period. As an antecedent to traditional amblyopia treatment, darkness may increase treatment efficacy even at ages when plasticity is at its highest.
Molecular Detection ofBartonellaspp. in China and St. Kitts
Authors: Huang Ke , Kelly Patrick John , Zhang Jilei , Yang Yi , Liu Weiguo , Kalalah Anwar , Wang Chengming
Published: September 2019

Bartonellaare vector-borne hemotropic bacteria that infect a wide variety of hosts, including people. While there are PCR assays that can identify individual or groups ofBartonella, there is no reliable molecular method to simultaneously detect all species while maintaining genus specificity and sensitivity. By comparing highly conserved16S rRNAsequences of the better-recognizedBartonellaspp. on GenBank, we selected primers and probes for a genus-specific pan-BartonellaFRET-qPCR. Then, agltA-basedBartonellaPCR was established by selecting primers for a highly variable region ofgltA, of which the sequenced amplicons could identify individualBartonellaspp. The pan-BartonellaFRET-qPCR did not detect negative controls (Brucellaspp.,Anaplasmaspp.,Rickettsiaspp.,Coxiella burnetii, andWolbachia) but reliably detected as few as two copies of the positive control (Bartonella henselae) per reaction. There was complete agreement between the pan-BartonellaFRET-qPCR and thegltA-basedBartonellaPCR in detectingBartonellain convenience test samples from China and St. Kitts: cats (26%; 81/310),Ctenocephalides felis(20%; 12/60), cattle (24%; 23/98), and donkeys (4%; 1/20). Sequencing of thegltA-basedBartonellaPCR products revealedB. henselae(70%; 57/81) andB. clarridgeiae(30%; 24/81) in cats andC. felis(67%; 8/12, and 33%; 4/12, respectively) andB. bovisin cattle (23.5%; 23/98) and donkeys (4.0%; 1/24). The pan-BartonellaFRET-qPCR andgltA-basedBartonellaPCR we developed are highly sensitive and specific in detecting recognizedBartonellaspp. in a single reaction. The pan-BartonellaFRET-qPCR is convenient requiring no gel electrophoresis and providing copy numbers, while thegltA-basedBartonellaPCR reliably differentiates individualBartonellaspecies. The use of these PCRs should greatly facilitate large-scale surveillance studies and the diagnosis of infections in clinical samples.
Effect of Fiber Laser Irradiation on the Shear Bond Strength between Acrylic Resin and Titanium
Authors: Korkmaz Fatih Mehmet , Aycan Selin
Published: September 2019

Objectives. The aim of this study is to investigate the shear bond strength of an acrylic resin to titanium after different surface treatment methods. Material and Methods. A total of seventy-two disc-shaped specimens (10 mm×10 mm×2 mm) were prepared from titanium alloy. The specimens were randomly allocated to six equal groups: Group S (sandblasting), Group MP (metal primer), Group 10W (fiber laser 10 W), Group 20W (fiber laser 20 W), Group 10WMP (fiber laser 10 W+metal primer), and Group 20WMP (fiber laser 20 W+metal primer). All of the specimens were thermocycled up to 5000 cycles. After thermal cycling, a shear bond strength test was conducted. The shear bond strength data were analyzed with one-way ANOVA and Tukey’s post hoc pairwise comparisons (p<0.05). Results. While the highest values were determined in Group MP, the lowest values were observed in Group S. Additionally, Group MP exhibited significantly higher shear bond strength values than any of the other groups (p<0.05) except Group 10WMP. Similar results were observed between Group MP and Group 10WMP (p>0.05). The groups in which a metal primer was applied (Group MP, 10WMP, and 20WMP) showed significantly higher values than Group S. The shear bond strength values of Group 10W and Group 20W were similar. Conclusions. The application of a metal primer significantly improved the bond strength of acrylic resin to titanium. Fiber laser application may be an alternative method to sandblasting for improving the bond strength of acrylic resin to titanium.
Analytically Simple and Computationally Efficient Results for the GIX/Geo/c Queues
Authors: Chaudhry Mohan L. , Kim James J. , Banik Abhijit D.
Published: September 2019

A simple solution to determine the distributions of queue-lengths at different observation epochs for the model GIX/Geo/c is presented. In the past, various discrete-time queueing models, particularly the multiserver bulk-arrival queues, have been solved using complicated methods that lead to incomplete results. The purpose of this paper is to use the roots method to solve the model GIX/Geo/c that leads to a result that is analytically elegant and computationally efficient. This method works well even for the case when the inter-batch-arrival times follow heavy-tailed distributions. The roots of the underlying characteristic equation form the basis for all distributions of queue-lengths at different time epochs.
Reclamation of Astragalus By-Product through Dietary Inclusion in Ruminant Diets: Effects on Growth Performance, Nutrient Digestibility, Rumen Fermentation, Blood Biochemical Parameters, and Humoral Immune Response in Sheep
Authors: Abdallah Abedin , Zhang Pei , Abubakari Abdul-Halim , Elemba Evera , Zhong Qingzhen , Sun Zewei
Published: September 2019

This study was conducted to investigate the effects of Astragalus by-product (ABP) through dietary supplementation at different levels on performance, nutrient digestibility, rumen fermentation, blood metabolites, and immune response in sheep. Twenty-four Doper × Small Tail Han ewes (6-7 months of age; 29.07 ± 2.28 kg initial body weight) were randomly assigned to one of three treatments for a 47 d feeding period. Treatments consisted of the sheep diet supplemented with 0% ABP-control, 10% ABP, or 15% ABP of the diet (dry matter basis). Blood samples were collected on days 0, 15, 30, and 45 of the feeding period. APB supplementation did not affect growth performance and apparent digestibility of organic matter, crude protein, and acid detergent fibre (P>0.05). However, ether extract digestibility was decreased in the 10% ABP group and increased in the 15% ABP group (P<0.001), and both 10% ABP and 15% ABP decreased the neutral detergent fibre digestibility (P=0.005). Feeding ABP increased rumen pH (P<0.001) and ammonia N (P<0.001) and decreased concentrations of acetate (P=0.007) and propionate (P=0.001) which resultantly increased the acetate-to-propionate ratio (P<0.001) in ruminal fluid. There were no interaction effects between treatment and sampling time for plasma metabolites and immunity (P>0.05). However, inclusion of dietary 10% ABP decreased concentrations of plasma cholesterol (P=0.043). Also, plasma concentrations of low-density lipoprotein decreased on days 30 and 45 (P=0.017) of the feeding period. Metabolite concentrations of total protein, albumin, globulin, blood urea N, glucose, triglyceride, and high-density lipoprotein cholesterol and humoral immune indicators were not affected (P>0.05) by dietary ABP supplementation. The results suggest that ABP could be reclaimed through dietary inclusion in animal feed since it had beneficial effects on rumen fermentation patterns and lipid metabolism and had no adverse effects on performance and humoral immunity in sheep.
An “EZ” Epigenetic Road to Leukemia Stem Cell Metabolic Reprogramming?
Authors: Li Meng , Melnick Ari M.
Published: September 2019

In this issue of Cancer Discovery, Gu and colleagues developed a mouse model of myeloproliferative neoplasm driven by NrasG12D and Ezh2−/−, which cooperated to induce malignant transformation and metabolic reprogramming of leukemic stem cells at least in part through loss of normal epigenetic regulation of gene expression. Furthermore, their findings point to Ezh1 and branched chain amino acid metabolism as biological dependencies and potential therapeutic targets in myeloid neoplasms.

See related article by Gu et al., p. 1228.
Gamma Knife Radiosurgery for Uveal Melanoma: A Retrospective Review of Clinical Complications in a Tertiary Referral Center
Authors: Modorati Giulio Maria , Dagan Roi , Mikkelsen Lauge Hjorth , Andreasen Simon , Ferlito Alfio , Bandello Francesco
Published: September 2019

Introduction: Gamma knife radiosurgery (GKR) has shown promising results in the treatment of intraocular uveal melanoma (UM) in terms of local tumor control. However, GKR is not free from potentially sight-threatening side effects, including cataract, dry eye disease, vitreous hemorrhage, radiation retinopathy (RR), radiation maculopathy (RM), optic neuropathy, and neovascular glaucoma. The aim of this paper is to report our 20-year experience in UM management with GKR focusing on the rate of clinical treatment-induced complications. Methods: Single-center, retrospective, observational study, including all patients with UM treated at the Ocular Oncology and Uveitis Service, in the Department of Ophthalmology of the San Raffaele Scientific Institute, Milan from September 1993 to September 2018. Clinical charts comprised complete ophthalmological examination with measurement of best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure measurement, gonioscopy, and indirect ophthalmoscopy at each visit. B-scan ultrasound (Aviso S, 10 MHz probe; Paris, France), optical coherence tomography (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany), retinography, and fundus fluorescein angiography (standard or ultra-widefield [UWF; California, Optos, Dunfermline, Scotland, UK]) were performed aiding in the diagnosis of complications. Results: Overall, 194 patients (100 males, 51.6%) were reviewed. The median age at the time of the treatment was 65 years (range 27–89) and all participants were Caucasian. In 185 eyes (95.4%), the tumor was primarily located at the choroid. The median follow-up was 57.6 months; radiation-induced complications were found in 145 eyes (74.7%). Radiation-induced cataract and RR were the most frequent events, with a relative incidence of 41.2 and 34.5%, respectively, followed by neovascular glaucoma (27.3%), optic neuropathy (18.6%), RM (11.4%), vitreous hemorrhage (14.4%), phthisis bulbi (7.7%), hyphema (0.5%), and corneal melting (0.5%). The shorter onset of side effects involved the optic nerve (median 14.9 months) and the macula (median 13.7 months). Conclusion: Despite modern and advanced strategies introduced to limit GKR side effects, cataract and RR still represent a serious limitation of this treatment. Incidence of RR was higher in our cohort compared to other reports, probably due to increased diagnosis rate permitted by UWF retinal imaging.
Wogonoside Inhibits Prostate Cancer Cell Growth and Metastasis via Regulating Wnt/β-Catenin Pathway and Epithelial-Mesenchymal Transition
Authors: Wei Can , Jing Junfeng , Zhang Yanbin , Fang Ling
Published: September 2019

Background: Wogonoside, an effective component of Scutellaria baicalensis extract, has recently become a hot topic for its newly discovered anticancer efficacy, but the underlying pharmacological mechanism is still unclear. In this study, we tested the inhibitory effects of wogonoside in human prostate cancer PC3 cells in vitro and vivo. Methods: The effects of wogonoside on cell viability, cycle progression, invasion, migration, and apoptosis were assessed in vitro. The levels of proteins in related signaling pathways were detected by western blotting assay. Finally, nude mouse tumorigenicity assay was conducted to detect the anticancer effect of wogonoside in vivo. Results: Wogonoside inhibited cell viability, invasive and migratory ability in a time- and dose-dependent manner. Flow cytometry indicated that wogonoside could induce cell apoptosis and S phase cell-cycle arrest. Mechanically, wogonoside suppressed the Wnt/β-catenin signaling pathway, and the level of p-glycogen synthase kinase-3β (GSK-3β; Ser9) was inhibited by wogonoside. The epithelial-mesenchymal transition (EMT) process was also reversed in PC3 cell line after wogonoside treatment. In vivo experiments showed that wogonoside inhibited tumor growth in xenograft mouse models. Conclusion: These findings revealed that wogonoside could suppress Wnt/β-catenin pathway and reversing the EMT process in PC3 cells. GSK-3β acts as a tumor suppressor in prostate cancer. Wogonoside may serve as an effective agent for treating prostate cancer.