bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of guide wire removal on tip location in peripherally inserted central catheters (PICCs): a retrospective cross-sectional study
Authors: Wang Dan , Niu Fangfang , Gao Huining , Yu Mingkai , Li Yuhang , Xu Liqun , Cao Huizhi , Wang Lili , Liu Jinhua , Ding Xue , Wang Ying , Yu Chen , Li Huiyan , Yu Kaijiang , Wang Changsong
Published: November 2019

Objectives

The aim of this study was to identify the prevalence of peripherally inserted central catheter (PICC) malposition and the influence of guide wire removal on tip location in PICCs and determine whether related factors, including age, sex, side of insertion and brand of catheter, influence the PICC tip location.

Setting

Single-centre research institute in China recruiting patients from the hospital.

Participants

A total of 837 adult patients with inserted PICCs were recruited from October 2016 to May 2017.

Interventions

This was a cross-sectional study aiming to identify the prevalence of PICC malposition and the influence of guide wire removal on tip location in PICCs. A linear regression model and a variance of factorial design analysis were performed. The PICC tip location was documented on a postinsertion chest X-ray. Multivariable analyses were performed based on the following related factors: age, sex, side of insertion and brand of catheter.

Results

The tip location moved a mean of 17.4 mm among the 837 included patients. The prevalence of PICC malposition was 83.6% (700/837), while 16.4% (137/837) of PICCs remained in correct location. The mean movement caused by guide wire removal without an adjusted tail end was (−1.95±26.90) mm. The difference between tail end adjustment movement and actual tip position movement in each PICC was (33.0±17.1) mm in type C, which was significantly higher than the findings for type A (12.8±13.3) mm and type B (12.9±12.7) mm.

Conclusions

PICC malposition is a frequent event. Different catheter brands were associated with different ranges of movement in tip location after guide wire removal. The age and sex of the patients and the insertion side did not influence the extent of movement.
Prototyping for public health in a local context: a streamlined evaluation of a community-based weight management programme (Momenta), Northumberland, UK
Authors: Dodd-Reynolds Caroline J , Nevens Lisa , Oliver Emily J , Finch Tracy , Lake Amelia A , Hanson Coral L
Published: November 2019

Objectives

Stakeholder co-production in design of public health programmes may reduce the ‘implementation gap’ but can be time-consuming and costly. Prototyping, iterative refining relevant to delivery context, offers a potential solution. This evaluation explored implementation and lessons learnt for a 12-week referral-based weight-management programme, ‘Momenta’, along with feasibility of an iterative prototyping evaluation framework.

Design

Mixed methods evaluation: Qualitative implementation exploration with referrers and service users; preliminary analysis of anonymised quantitative service data (12 and 52 weeks).

Setting

Two leisure centres in Northumberland, North East England.

Participants

Individual interviews with referring professionals (n=5) and focus groups with service users (n=13). Individuals (n=182) referred by healthcare professionals (quantitative data).

Interventions

Three 12-week programme iterations: Momenta (n=59), Momenta-Fitness membership (n=58) and Fitness membership only (n=65).

Primary and secondary outcome measures

Primary outcome: Qualitative themes developed through stakeholder-engagement. Secondary outcomes included preliminary exploration of recruitment, uptake, retention, and changes in weight, body mass index, waist circumference and psychological well-being.

Results

Service users reported positive experiences of Momenta. Implementation gaps were revealed around the referral process and practitioner knowledge. Prototyping enabled iterative refinements such as broadening inclusion criteria. Uptake and 12-week retention were higher for Momenta (84.7%, 45.8%) and Momenta-Fitness (93.1%, 60.3%) versus Fitness only (75.4%, 24.6%). Exploration of other preliminary outcomes (completers only) suggested potential for within-group weight loss and increased psychological well-being for Momenta and Momenta-Fitness at 12 weeks. 52 week follow-up data were limited (32%, 33% and 6% retention for those who started Momenta, Momenta-Fitness and Fitness, respectively) but suggested potential weight loss maintenance for Momenta-Fitness.

Conclusions

Identification of issues within the referral process enabled real-time iterative refinement, while lessons learnt may be of value for local implementation of ‘off-the-shelf’ weight management packages more generally. Our preliminary data for completers suggest Momenta may have potential for weight loss, particularly when offered with a fitness membership.
Axial length elongation in primary school-age children: a 3-year cohort study in Shanghai
Authors: Li Tao , Jiang Bo , Zhou Xiaodong
Published: November 2019

Objective

To investigate the axial length (AL) elongation in primary school-age children during 3-year follow-up period and evaluate the associations of AL elongation with spherical equivalent (SE), AL at baseline, body height and weight.

Design

A 3-year observational cohort study from 2014 to 2017.

Setting

Jinshan Hospital of Fudan University in Shanghai.

Methods

A total of 452 children successfully completed their measurements in the 3-year follow-up period. The mean age of those children was 6.9±0.7 years, ranging from 6 to 8 years, and 217 (42.7%) were boys. AL was measured with an ocular biometry system. Refractive error was measured using an auto-refractor without cycloplegia.

Results

The mean changes of ALs were 0.27±0.28 mm, 0.52±0.40 mm and 0.89±0.51 mm over 1, 2 and 3 years, respectively. The mean changes of SEs were −0.27±0.80 D, −0.56±1.00 D and −0.95±1.41 D over 1, 2 and 3 years, respectively. Multivariate linear regression analysis revealed that mean change of AL was associated with mean change of SE at all points (all p<0.001). In addition, linear regression analysis revealed that AL elongation in the 3year follow-up period was associated with AL at baseline (R2=0.009, p=0.045).

Conclusions

AL elongation is relatively high in the primary school-age children in Jinshan District, Shanghai. Effect strategies are needed to control AL elongation.
Prevalence of undiagnosed diabetes mellitus and associated factors among adult residents of Bahir Dar city, northwest Ethiopia: a community-based cross-sectional study
Authors: Bantie Getasew Mulat , Wondaye Achenef Almaw , Arike Efrem Beru , Melaku Mesfin Tenagne , Ejigu Simegnew Tilaneh , Lule Abel , Lingerew Wondemagegn Mulu , Tamirat Koku Sisay
Published: November 2019

Objective

To assess the prevalence of undiagnosed diabetes mellitus (DM) and associated factors among adult inhabitants of Bahir Dar city, northwest Ethiopia.

Design

A community-based cross-sectional study was conducted on adults (n=607) of Bahir Dar city from 10 March to 20 May 2018.

Measurements

Data were collected using structured interviewer-administered questionnaire, and anthropometric measurements were taken from each participant. Fasting blood sugar (FBS) level was determined by samples taken early in the morning and readings of FBS≥126 mg/dL were classified as diabetes. The multivariate logistic regression model was fitted to identify the predictors of undiagnosed DM; adjusted OR (AOR) with a 95% CI was computed to assess the strength of associations.

Result

The study revealed that the prevalence of undiagnosed DM was 10.2% with 95% CI 7.9 to 12.9. Ever checked blood glucose level (AOR=1.91, 95% CI 1.03 to 3.51), don’t know the symptoms of diabetes (AOR=2.06, 95% CI 1.08 to 3.89), family history of DM (AOR=2.5, 95% CI 1.21 to 5.18) and body mass index (BMI) ≥25 kg/m2(AOR=1.98, 95% CI 1.09 to 3.60) were factors associated with undiagnosed DM.

Conclusion

The magnitude of undiagnosed diabetes was high. Family history of DM, ever checked blood glucose level, don’t know about the symptoms of diabetes and overweight BMI were predictors of undiagnosed DM. Hence, screening and treatment are mandatory for high-risk groups. In addition, this study suggests frequent screening for those with family history and awareness creating about the disease for early detection and treatment.
Can the Healthy Primary School of the Future offer perspective in the ongoing obesity epidemic in young children? A Dutch quasi-experimental study
Authors: Bartelink Nina H M , van Assema Patricia , Kremers Stef P J , Savelberg Hans H C M , Oosterhoff Marije , Willeboordse Maartje , van Schayck Onno C P , Winkens Bjorn , Jansen Maria W J
Published: November 2019

Objectives

Schools play an important role in promoting healthy behaviours in children and can offer perspective in the ongoing obesity epidemic. The ‘Healthy Primary School of the Future’ (HPSF) aims to improve children’s health and well-being by enhancing school health promotion. The current study aims to assess the effect of HPSF on children’s body mass index (BMI) z-score after 1 and 2 years follow-up and to investigate whether HPSF has different effects within specific subgroups of children.

Design

A longitudinal quasi-experimental design.

Setting

Four intervention and four control schools participated; located in a low socioeconomic status region in the Netherlands.

Participants

1676 children (aged 4–12 years).

Interventions

HPSF uses a contextual systems approach and includes health-promoting changes in the school. Central to HPSF is the provision of a daily healthy lunch and structured physical activity sessions each day. Two intervention schools implemented both changes (full HPSF), two intervention schools implemented only the physical activity change (partial HPSF).

Main outcome measures

BMI z-score, determined by measurements of children’s height and weight at baseline, after 1 and 2 years follow-up.

Results

The intervention effect was significant after 1-year follow-up in the partial HPSF (standardised effect size (ES)=−0.05), not significant in the full HPSF (ES=−0.04). After 2 years follow-up, BMI z-score had significantly decreased in children of both the full HPSF (ES=−0.08) and the partial HPSF (ES=−0.07) compared with children of the control schools, whose mean BMI z-score increased from baseline to 2 years. None of the potential effect modifiers (gender, baseline study year, socioeconomic status and baseline weight status) were significant.

Conclusions

HPSF was effective after 1 and 2 years follow-up in lowering children’s BMI z-scores. No specific subgroups of children could be identified who benefitted more from the intervention.

Trial registration number

NCT02800616.
Cannabinoids versus placebo or no intervention for pain: protocol for a systematic review with meta-analysis and trial sequential analysis
Authors: Barakji Jehad Ahmad , Korang Steven Kwasi , Feinberg Joshua , Maagard Mathias , Gluud Christian , Mathiesen Ole , Jakobsen Janus Christian
Published: November 2019

Introduction

Pain is a frequent clinical symptom with significant impact on the patient’s well-being. Therefore, adequate pain management is of utmost importance. While cannabinoids have become a more popular alternative to traditional types of pain medication among patients, the quality of evidence supporting the use of cannabinoids has been questioned. The beneficial and harmful effects of cannabinoids in patients with pain is unknown. Accordingly, we aim to assess the efﬁcacy, tolerability and safety of cannabinoids (herbal, plant-derived extracts and synthetic) compared with placebo or no intervention for any type of pain.

Methods and analyses

We will conduct a systematic review of randomised clinical trials with meta-analysis and Trial Sequential Analysis to assess the beneficial and harmful effects of cannabinoids in any dose, formulation and duration. We will accept placebo or no treatment as control interventions. We will include participants with any type of pain (acute and chronic pain, cancer-related pain, headache, neuropathic pain or any other types of pain). We will systematically search The Cochrane Library, MEDLINE, Embase, Science Citation Index and BIOSIS for relevant literature. We will follow the recommendations by Cochrane and the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. The risk of systematic errors (bias) and random errors (play of chance) will be assessed. The overall certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethics and dissemination

Ethical approval is not a requirement since no primary data will be collected. The findings of this systematic review will be submitted for peer-reviewed publication and disseminated in national and international conferences.

Discussion

Although cannabinoids are now being used to manage different pain conditions, the evidence for the clinical effects are unclear. The present review will systematically assess the current evidence for the benefits and harms of cannabinoids to inform practice and future research.
Behavioural activation in nursing homes to treat depression (BAN-Dep): study protocol for a pragmatic randomised controlled trial
Authors: Velasquez Reyes Diana , Patel Hema , Lautenschlager Nicola , Ford Andrew H , Curran Eleanor , Kelly Rachael , Lai Rhoda , Chong Terence , Flicker Leon , Ekers David , Gilbody Simon , Etherton-Beer Christopher , Lo Giudice Dina , Ellis Kathryn A , Martini Angelita , Almeida Osvaldo P
Published: November 2019

Introduction

Depression is a common disorder among older people living in residential aged care facilities. Several trials have demonstrated the effectiveness of behavioural therapies in treating depressive symptoms in older adults living in the community and in residential aged care. Behavioural Activation is demonstrably effective even when delivered by non-specialists (staff without formal psychological training), although strategies for adapting its use in residential aged care facilities are yet to be explored. This study will determine whether training residential care staff in the use of a structured Behavioural Activation programme is more effective at decreasing depressive symptoms among older residents than internet-based training about depression recognition and management alone.

Method and analysis

The behavioural activation in nursing homes to treat depression (BAN-Dep) trial is a pragmatic two-arm parallel clustered randomised controlled trial. It will recruit 666 residents aged 60 or older from 100 residential aged care facilities, which will be randomly assigned to the Behavioural Activation or control intervention. Staff in both treatment groups will be encouraged to complete theBeyondblueProfessional Education to Aged Care e-learning programme to improve their recognition of and ability to respond to depression in older adults. Selected staff from intervention facilities will undergo additional training to deliver an 8-module Behavioural Activation programme to residents with subthreshold symptoms of depression-they will receive ongoing Mental support from trained Behavioural Activation therapists. Outcome measures will be collected by blind research officer at baseline and after 3, 6 and 12 months. The Patient Health Questionnaire-9 is the primary outcome measure of the study.

Ethics and dissemination

The trial will comply with the principles of the Declaration of Helsinki for Human Rights and is overseen by the University of Western Australia (reference RA/4/20/4234) and Melbourne Health (reference number HREC/18/MH/47) Ethics Committees. The results of this research project will be disseminated through publications and/or presentations in a variety of media to health professionals, academics, clinicians and the public. Only de-identified group data will be presented.

Trial registration

ACTRN12618000634279.
Successful reperfusion, rather than number of passes, predicts clinical outcome after mechanical thrombectomy
Authors: Tonetti Daniel A , Desai Shashvat M , Casillo Stephanie , Stone Jeremy , Brown Merritt , Jankowitz Brian , Jovin Tudor G , Gross Bradley A , Jadhav Ashutosh
Published: November 2019

Introduction

For patients undergoing mechanical thrombectomy, numerous (>3) thrombectomy passes may be harmful. However, non-recanalization leads to poor outcomes. For patients requiring multiple thrombectomy passes to achieve reperfusion, it remains unclear if the risk/benefit ratio favors recanalization.

Objective

To test the hypothesis that the benefits afforded by successful reperfusion outweigh the risk conveyed by the numerous passes required.

Methods

We retrospectively reviewed prospectively collected data for patients presenting to a comprehensive stroke center with anterior circulation large vessel occlusion (ACLVO) and undergoing thrombectomy requiring more than one pass over 24 months. We stratified patients into three groups: group 1 (successful reperfusion in 2–3 passes), group 2 (successful reperfusion in ≥4 passes), and group 3 (unsuccessful reperfusion).

Results

250 patients with ACLVO constituted the study cohort. Despite similar demographics, group 2 patients had better clinical outcomes than those in group 3 at 24 hours (National Institutes of Health Stroke Scale (NIHSS) score 13.5 vs 19.1, p<0.001) and at 90 days (modified Rankin Scale score 0–2 rates of 31.1% vs 0.0%, p=0.006) On multivariate logistic regression analysis, age (p=0.034), Alberta Stroke Program Early CT Score (p<0.01), NIHSS score (p=0.02), and parenchymal hematoma type 2 (p=0.015) were significant predictors of functional independence among those who achieved successful reperfusion, but the number of passes required did not predict outcome for these patients (p=0.74).

Conclusion

Patients who achieve successful reperfusion after many passes have better clinical outcomes than those who do not, despite the number of passes and procedural time required. The number of passes required to achieve successful reperfusion beyond the first pass is not a predictor of functional independence.
Inhibitory tendon-evoked reflex is attenuated in the torque-depressed isometric steady-state following active shortening
Authors: Sypkes Caleb T. , Dalton Brian H. , Stuart Joanna , Power Geoffrey A.
Published: November 2019

Residual torque depression (rTD) is the reduction in steady-state isometric torque following an active shortening contraction when compared with an isometric contraction at the same muscle length and activation level. We have shown that spinal excitability increases in the rTD state, yet the mechanisms remains unknown. Percutaneous electrical tendon stimulation was used to induce tendon-evoked inhibitory reflexes. We demonstrated that in the rTD state, reduced torque contributes to a reduction in inhibitory afferent feedback, which indicates that the history-dependent properties of muscle can alter spinal excitability and the voluntary control of submaximal contractions through changes in peripheral afferent feedback.

Novelty Residual force depression is a basic property of skeletal muscle, which can influence spinal and supraspinal excitability via inhibitory reflex activity. Residual force depression alters the voluntary control of force.
Dynamics of ground-nest egg depredation by rodents in a mixed-wood forest
Authors: Bouffard Jeremie , Garant Dany , Bergeron Patrick
Published: November 2019

Predation is a leading cause of nest failure in birds, which has significant consequences on their population dynamics. Rodents commonly prey on nests in deciduous forest habitats. This has important implications considering how rodent populations fluctuate with changes in resource availability, such as synchronized but intermittent tree-seed production (mast). In this study, we investigated ground-nest egg predation by rodents over 2 years characterized by high and low beech (Fagus grandifolia Ehrh.) seed availability (mast vs. no-mast years). We used artificial nests monitored by motion-sensing cameras on a study site where eastern chipmunk (Tamias striatus (Linnaeus, 1758)) local abundance was known. We placed the artificial nests in areas of high and low chipmunk abundance as proxy of predation risk. Blue Jays (Cyanocitta cristata (Linnaeus, 1758)) depredated the most eggs overall, but rodent population and egg depredation increased in 2018 following the 2017 mast. However, chipmunks were minor predators and their local abundance did not reflect predation risk. Our results highlight the complexity of predation dynamics on ground-nesting birds and the importance of studying them locally and over multiple years.
Optimal power tracking control of a hydraulic wind turbine based on active disturbance rejection control methodology
Authors: Ai Chao , Wu Chao , Zhao Fan , Kong Xiangdong
Published: November 2019

Power point tracking (PPT) is one of the necessary functions of the wind turbine to optimize the use of wind energy. PPT is a condition that needs to be completed after the grid is connected, which can be achieved by tracking the optimal rotation speed of the output of the wind turbine and the optimum torque and power output of the hydraulic system. Based on a fixed displacement pump speed control, an optimal PPT strategy with the active disturbance rejection control (ADRC) method is proposed, and the control objective is to maximize the energy conversion of the system. This paper sets out to (i) establish a hydraulic wind turbine grid-connected affine nonlinear mathematical model, based on the ADRC method and a fixed displacement pump speed output control, (ii) design a nonlinear tracking differentiator and extended state observer and nonlinear state error feedback control law, and (iii) achieve optimal PPT under different wind speeds. Simulations were model by MATLAB/Simulink, where the system inputs signals of different wind speeds and analyses control system stability and robustness. Simulation results show that the input power was greater with a fixed displacement pump speed .
Synthesis and luminescence properties of CaLaMgNbO6:Mn4+ red phosphor for UV-based w-LEDs
Authors: Shi Lei , Han Ya-Jie , Wang Shuang , Ji Zhi-Xin , Sun Meng , Li Zi-Han , Wang Wei , Zhang Zhi-Wei
Published: November 2019

A series of [Formula: see text] ([Formula: see text] = 0.0005, 0.001, 0.003, 0.005, 0.007, 0.009) phosphors were prepared by traditional solid-state method at high temperature. The structure and morphology of the samples were analyzed. The results showed that the prepared [Formula: see text] [Formula: see text] phosphors were uniformly dispersed and the particle size was less than 5 [Formula: see text]m. [Formula: see text] phosphors have the strongest excitation peak at 351 nm, which is caused by the [Formula: see text] transition of [Formula: see text] ions. The strongest emission peak is at 697 nm, which is due to the [Formula: see text] level transition of [Formula: see text]. The optimum doping concentration is 0.5 mol.% and the mechanism of concentration quenching is the dipole–dipole interaction between [Formula: see text] ions. Importantly, [Formula: see text] sample has good thermal stability ([Formula: see text]/[Formula: see text] = 48.3%). In addition, the color coordinates of all samples were concentrated in the far-red region (0.733, 0.267). The above results indicate that [Formula: see text] sample has potential application value in the field of white light-emitting diodes ([Formula: see text]-LEDs).
A Privacy Awareness System for Software Design
Authors: Omoronyia Inah , Etuk Ubong , Inglis Peter
Published: November 2019

There have been concerting policy and legal initiatives to mitigate the privacy harm resulting from badly designed software technology. But one main challenge to realizing these initiatives is the difficulty in translating proposed principles and regulations into concrete and verifiable evidence in technology. This is partly due to the lack of systematic techniques and tools to address privacy in the software design, hence making it difficult for the designer to measure disclosure risk in a more intuitive way, taking into account the privacy objective that matters to each end user. To bridge this gap, we propose a framework for verifying the satisfaction of user privacy objectives in software design. Our approach is based on the (un)awareness that users acquire when information is disclosed, as it relates to the communication properties of objects in a design. This property is used to determine the expected privacy utility that users will derive from the design for a specified privacy objective. We demonstrate through case studies how this approach can help designers determine which design decision undermines users’ privacy expectations and better design alternatives.
Strategies to Regulate the Degradability of Mesoporous Silica-based Nanoparticles for Biomedical Applications
Authors: Li Xiangye , Gao Feixue , Dong Yunhui , Li Xinjin
Published: November 2019

Cancer is the second major threat to human health, and more effective cancer therapy strategies are imperative. With the development of nanotechnology, mesoporous silica-based nanoparticles (MSNs) have seen unprecedented development in cancer treatment, such as drug delivery, bioimaging and biosensing. They have received extensive attention because of their easy preparation, adjustable morphology, homogeneous pore structure, high surface areas and good biocompatibility. However, cumulative toxicity for organism caused by the low degradability of MSNs heavily hinders their translation from bench to beside. Enhancing the degradability of MSNs has provided an effective solution to solve this problem. This review aims at summarizing the effective strategies utilized to regulate the degradability of MSNs during the last few years, giving a complete overview on the recent progress and remaining challenges of degradable MSNs.
Layer-Wise De-Training and Re-Training for ConvS2S Machine Translation
Authors: Yu Hongfei , Zhou Xiaoqing , Duan Xiangyu , Zhang Min
Published: November 2019

The convolutional sequence-to-sequence (ConvS2S) machine translation system is one of the typical neural machine translation (NMT) systems. Training the ConvS2S model tends to get stuck in a local optimum in our pre-studies. To overcome this inferior behavior, we propose to de-train a trained ConvS2S model in a mild way and retrain to find a better solution globally. In particular, the trained parameters of one layer of the NMT network are abandoned by re-initialization while other layers’ parameters are kept at the same time to kick off re-optimization from a new start point and safeguard the new start point not too far from the previous optimum. This procedure is executed layer by layer until all layers of the ConvS2S model are explored. Experiments show that when compared to various measures for escaping from the local optimum, including initialization with random seeds, adding perturbations to the baseline parameters, and continuing training (con-training) with the baseline models, our method consistently improves the ConvS2S translation quality across various language pairs and achieves better performance.
The Grammar of Degree: Gradability Across Languages
Authors: Hohaus Vera , Bochnak M. Ryan
Published: November 2019

In this review, we discuss the empirical landscape of degree constructions cross-linguistically as well as the major analytical avenues that have been pursued to account for individual languages and cross-linguistic variation. We first focus on comparatives and outline various compositional strategies for different types of comparative sentences as well as points of cross-linguistic variation in the lexicalization of comparative operators and gradable predicates. We then expand the discussion to superlatives, equatives, and other degree constructions. Finally, we turn to constructions beyond the prototypical degree constructions but where degree-based analyses have been pursued; we focus on change-of-state verbs and exclamatives. This is an area that is especially ripe for future cross-linguistic research. We conclude by mentioning connections to other subfields of linguistics, such as language acquisition, historical linguistics, and language processing.
Studying Leaders and Elites: The Personal Biography Approach
Authors: Krcmaric Daniel , Nelson Stephen C. , Roberts Andrew
Published: November 2019

The last two decades have seen a revival in work that takes the role of individual leaders and elites seriously. This article surveys new research that explores how biographical factors influence their behavior. We call this literature the personal biography approach to political leadership. Our survey first lays out four mechanisms through which biographical characteristics might affect leader behavior. We then discuss the main findings, grouping them according to socializing experiences (e.g., education, military service, and prior occupation) and ascriptive traits (e.g., gender, race, and ethnicity). We also consider the methodological problems, especially endogeneity and selection effects, that pose challenges to this style of research. We conclude with an assessment of gaps in the literature and provide suggestions for future work in the biographical vein.
Sympathetic baroreflex sensitivity is inversely related to vascular transduction in men but not women
Authors: Hissen Sarah L. , Macefield Vaughan G. , Brown Rachael , Taylor Chloe E.
Published: November 2019

Sympathetic baroreflex sensitivity (BRS) is a measure of how effectively the baroreflex buffers beat-to-beat changes in blood pressure through the modulation of muscle sympathetic nerve activity (MSNA). However, current methods of assessment do not take into account the transduction of sympathetic nerve activity at the level of the vasculature, which is known to vary between individuals. In this study we tested the hypothesis that there is an inverse relationship between sympathetic BRS and vascular transduction. In 38 (18 men) healthy adults, continuous measurements of blood pressure, MSNA and superficial femoral artery diameter and blood flow (Doppler ultrasound) were recorded during 10 min of rest. Spontaneous sympathetic BRS was quantified as the relationship between diastolic pressure and MSNA burst incidence. Vascular transduction was quantified by plotting the changes in leg vascular conductance for 10 cardiac cycles following each burst of MSNA, and taking the nadir. In men, sympathetic BRS was inversely related to vascular transduction ( r = −0.49; P = 0.04). However, this relationship was not present in women ( r = −0.17; P = 0.47). To conclude, an interaction exists between sympathetic BRS and vascular transduction in healthy men, such that men with high sympathetic BRS have low vascular transduction and vice versa. This may be to ensure that blood pressure is regulated effectively, although further research is needed to explore what mechanisms are involved and examine why this relationship was not apparent in women.

NEW & NOTEWORTHY Evidence suggests that compensatory interactions exist between factors involved in cardiovascular control. This study was the first to demonstrate an inverse relationship between sympathetic BRS and beat-to-beat vascular transduction. Those with low sympathetic BRS had high vascular transduction and vice versa. However, this interaction was present in young men but not women.
Genetics Helps to Find Synergy for Immune Checkpoint and Targeted Combination Therapies
Authors: Prokunina-Olsson Ludmila
Published: November 2019

Checkpoint inhibitors, including anti-PD-L1 therapy, emerged as a treatment option for many cancer types, albeit with limited response rates. Combinations of immune-based and -targeted therapies are needed to achieve synergistic antitumor effects and provide much needed treatment personalization and improved response. Genetic alterations can be used as molecular drug targets and as biomarkers to select patients for specific therapies and their combinations. Fukumoto and colleagues present a promising example of this approach for the treatment of ovarian cancer with inactivating ARID1A mutations using a combination of the checkpoint and histone deacetylase inhibitors.

See related article by Fukumoto et al., p. 5482
Targeting the EGFR and Immune Pathways in Squamous Cell Carcinoma of the Head and Neck (SCCHN): Forging a New Alliance
Authors: Saba Nabil F. , Chen Zhuo Gerogia , Haigentz Missak , Bossi Paolo , Rinaldo Alessandra , Rodrigo Juan P. , Mäkitie Antti A. , Takes Robert P. , Strojan Primoz , Vermorken Jan B. , Ferlito Alfio
Published: November 2019

Despite the recent approval of immune-modulatory agents, EGFR inhibition continues to be a cornerstone in the management of squamous cell carcinoma of the head and neck (SCCHN) namely in combination with radiotherapy in the treatment of locoregionally advanced disease as well as in platinum-sensitive recurrent or metastatic disease in the first-line setting. Importantly, recent evidence has emerged supporting also an immune-modulatory effect of EGFR inhibition, and interest has now focused on utilizing these effects in the current treatment approaches for SCCHN. In this report, we review the rationale and evidence supporting the forging of this new alliance in optimizing the treatment of SCCHN.
Dominant-Negative ATF5 Compromises Cancer Cell Survival by Targeting CEBPB and CEBPD
Authors: Sun Xiaotian , Jefferson Parvaneh , Zhou Qing , Angelastro James M. , Greene Lloyd A.
Published: November 2019

The basic leucine zipper transcription factor ATF5 is overexpressed in many tumor types and interference with its expression or function inhibits cancer cell survival. As a potential therapeutic approach to exploit these findings, we created dominant-negative (DN) ATF5 forms lacking DNA-binding ability that retain the ATF5 leucine zipper, and thus associate with and sequester ATF5's requisite leucine zipper–binding partners. Preclinical studies with DN-ATF5, including a cell-penetrating form, show in vitro and in vivo efficacy in compromising cancer cell survival. However, DN-ATF5's targets, and particularly those required for tumor cell survival, have been unknown. We report that cells lacking ATF5 succumb to DN-ATF5, indicating that ATF5 itself is not DN-ATF5's obligate target. Unbiased pull-down assays coupled with mass spectrometry and immunoblotting revealed that DN-ATF5 associates in cells with the basic leucine zipper proteins CEBPB and CEBPD and coiled-coil protein CCDC6. Consistent with DN-ATF5 affecting tumor cell survival by suppressing CEBPB and CEBPD function, DN-ATF5 interferes with CEBPB and CEBPD transcriptional activity, while CEBPB or CEBPD knockdown promotes apoptotic death of multiple cancer cells lines, but not of normal astrocytes. We propose a two-pronged mechanism by which DN-ATF5 kills tumor cells. One is by inhibiting heterodimer formation between ATF5 and CEBPB and CDBPD, thus suppressing ATF5-dependent transcription. The other is by blocking the formation of transcriptionally active CEBPB and CEBPD homodimers as well as heterodimers with partners in addition to ATF5.

Implications:

This study indicates that the potential cancer therapeutic DN-ATF5 acts by associating with and blocking the transcriptional activities of CEBPB and CEBPD.
Mesothelin Enhances Tumor Vascularity in Newly Forming Pancreatic Peritoneal Metastases
Authors: Avula Leela Rani , Rudloff Michael , El-Behaedi Salma , Arons Danielle , Albalawy Rakan , Chen Xiongfong , Zhang Xianyu , Alewine Christine
Published: November 2019

Over 90% of pancreatic ductal adenocarcinomas (PDAC) express mesothelin (MSLN). Overexpression or knockdown of MSLN has been implicated in PDAC aggressiveness. This activity has been ascribed to MSLN-induced activation of MAPK or NF-κB signaling pathways and to interaction of MSLN with its only known binding partner, MUC16. Here, we used CRISPR/Cas9 gene editing to delete MSLN from PDAC, then restored expression of wild-type (WT) or Y318A mutant MSLN by viral transduction. We found that MSLN KO cells grew in culture and as subcutaneous tumors in mouse xenografts at the same rate as WT cells but formed intraperitoneal metastases poorly. Complementation with WT MSLN restored intraperitoneal growth, whereas complementation with Y318A mutant MSLN, which does not bind MUC16, was ineffective at enhancing growth in both MUC16(+) and MUC16(−) models. Restoration of WT MSLN did enhance growth but did not affect cell-to-cell binding, cell viability in suspension or signaling pathways previously identified as contributing to the protumorigenic effect of MSLN. RNA deep sequencing of tumor cells identified no changes in transcriptional profile that could explain the observed phenotype. Furthermore, no histologic changes in tumor cell proliferation or morphology were observed in mature tumors. Examination of nascent MSLN KO tumors revealed decreased microvascular density as intraperitoneal tumors were forming, followed by decreased proliferation, which resolved by 2 weeks postimplantation. These data support a model whereby MSLN expression by tumor cells contributes to metastatic colonization.

Implications:

MSLN confers a growth advantage to tumor cells during colonization of peritoneal metastasis. Therapeutic blockade of MSLN might limit peritoneal spread.
BalanCI: Head-Referenced Cochlear Implant Stimulation Improves Balance in Children with Bilateral Cochleovestibular Loss
Authors: Wolter Nikolaus E. , Gordon Karen A. , Campos Jennifer L. , Vilchez Madrigal Luis D. , Pothier David D. , Hughes Cían O. , Papsin Blake C. , Cushing Sharon L.
Published: November 2019

Introduction: To determine the impact of a head-referenced cochlear implant (CI) stimulation system, BalanCI, on balance and postural control in children with bilateral cochleovestibular loss (BCVL) who use bilateral CI. Methods: Prospective, blinded case-control study. Balance and postural control testing occurred in two settings: (1) quiet clinical setting and (2) immersive realistic virtual environment (Challenging Environment Assessment Laboratory [CEAL], Toronto Rehabilitation Institute). Postural control was assessed in 16 and balance in 10 children with BCVL who use bilateral CI, along with 10 typically developing children. Children with neuromotor, cognitive, or visual deficits that would prevent them from performing the tests were excluded. Children wore the BalanCI, which is a head-mounted device that couples with their CIs through the audio port and provides head-referenced spatial information delivered via the intracochlear electrode array. Postural control was measured by center of pressure (COP) and time to fall using the WiiTM (Nintendo, WA, USA) Balance Board for feet and the BalanCI for head, during the administration of the Modified Clinical Test of Sensory Interaction in Balance (CTSIB-M). The COP of the head and feet were assessed for change by deviation, measured as root mean square around the COP (COP-RMS), rate of deviation (COP-RMS/duration), and rate of path length change from center (COP-velocity). Balance was assessed by the Bruininks-Oseretsky Test of Motor Proficiency 2, balance subtest (BOT-2), specifically, BOT-2 score as well as time to fall/fault. Results: In the virtual environment, children demonstrated more stable balance when using BalanCI as measured by an improvement in BOT-2 scores. In a quiet clinical setting, the use of BalanCI led to improved postural control as demonstrated by significant reductions in COP-RMS and COP-velocity. With the use of BalanCI, the number of falls/faults was significantly reduced and time to fall increased. Conclusions: BalanCI is a simple and effective means of improving postural control and balance in children with BCVL who use bilateral CI. BalanCI could potentially improve the safety of these children, reduce the effort they expend maintaining balance and allow them to take part in more complex balance tasks where sensory information may be limited and/or noisy.
Case Report of Exercise to Attenuate Side Effects of Treatment for Pancreatic Cancer
Authors: McLaughlin Marie , Christie Alan , Campbell Anna
Published: November 2019

Treatments for pancreatic cancer can have debilitating side effects including fatigue, weight loss, and cardiac toxicity, resulting in functional loss and psychological distress. Exercise has been proposed as a therapy to counteract physical and psychological detriments. The case: A 47-year-old male undergoing chemotherapy for stage 3 locally advanced pancreatic cancer. He was cycling during hospital chemotherapy infusions (6 fortnightly cycles of FOLFIRINOX: 5-FU 2, 400 mg/m2, over 48 h: irinotecan 180 mg/m2, oxaliplatin 85 mg/m2, no 5-FU bolus) plus 12 weeks of twice weekly aerobic and resistance exercise. Over 12 weeks, body composition was maintained, and physical function improved, with specific increases in muscular strength of up to 50% and aerobic capacity improving by 9%. Moreover, quality of life, fatigue, psychological distress, and sleep quality improved by 38, 113, 50, and 9%, respectively. Additionally, the participant experienced more severe side effects in week 6, when he did not cycle to a high intensity during hospital infusion and had less total weekly exercise. After cycle 6 (week 11), chemotherapy was halted, and a Whipple resection procedure was successfully performed. It can be concluded that regular aerobic and resistance exercise plus exercise during infusion can attenuate expected decline in physical and mental health with pancreatic cancer treatment and may reduce treatment side effects and have favourable effects on prognosis.
Aberrant Expression of Peroxisome Proliferator-Activated Receptors in Colorectal Cancer and Their Association with Cancer Progression and Prognosis
Authors: Yaghoubizadeh Musa , Pishkar Leila , Basati Gholam
Published: November 2019

Introduction: Peroxisome proliferator-activated receptors (PPARs), PPARα, PPARγ, and PPARδ, are nuclear ligand-activated transcription factors which presumably contribute to a broad range of pathophysiological processes, such as tumorigenesis. Nevertheless, their exact role as tumor suppressors or promoters is not straightforward in colorectal cancer (CRC). Therefore, expression values of these PPARs and their relation with tumor progression and prognosis were examined in CRC patients. Methods: In this work, the relative expression values of the PPARs were measured by real-time polymerase chain reaction in 100 CRC tumor tissues paired with adjacent normal tissues. After that, the association between relative expression values of the PPARs in tumor tissues and the cancer progression-related clinicopathological characteristics as well as overall survival of patients were assessed. Results: While PPARα and PPARδ seemed to be overexpressed, PPARγ was suppressed in CRC tumor tissues compared with paired adjacent normal tissues (p = 0.0001). The relative expressions of PPARα and PPARδ were negatively associated with tumor size, tumor grade, TNM stage, metastasis, lymphatic invasion, and decreased overall survival time (p < 0.05). The same associations, but in reverse direction, were found for PPARγ. Conclusions: It was found that PPARα and PPARδ were overexpressed while PPARγ was suppressed in CRC tumor tissues, and these deregulations are associated with cancer progression and poor prognosis.
Successful Eradication of Helicobacter pylori Could Prevent Metachronous Gastric Cancer: A Propensity Matching Analysis
Authors: Nakata Rieko , Nagami Yasuaki , Hashimoto Atsushi , Sakai Taishi , Ominami Masaki , Fukunaga Shusei , Otani Koji , Hosomi Shuhei , Tanaka Fumio , Ohira Mizuki , Taira Koichi , Yamagami Hirokazu , Tanigawa Tetsuya , Watanabe Toshio , Fujiwara Yasuhiro
Published: November 2019

Background and Aim: Helicobacter pylori is the leading cause of gastric cancer, but it is still uncertain whether eradicating H. pylori in early gastric cancer (EGC) patients who underwent endoscopic resection can prevent metachronous gastric cancer (MGC). This study aimed to investigate the effect of H. pylori eradication to prevent MGC after endoscopic submucosal dissection (ESD). Methods: In this propensity-matched retrospective observational study, 770 patients with EGC who received ESD were enrolled. The outcome was the incidence of MGC; this was compared between the persistent and eradicated groups. Results: MGC was detected in 27 patients (7.8%) during a median period of 39.0 months (range 26.0–64.0). After propensity matching, 126 pairs of patients in each group were analyzed. The 5-year cumulative incidence rates of MGC were 13.2 and 3.9% in the persistent and eradicated groups, respectively (p= 0.021, log-rank test). On multivariate analysis, H. pylori eradication prevented MGC significantly (hazard ratio [HR] 0.32; p = 0.029). The results remained robust after inverse probability of treatment weighting analysis (HR 0.30; p = 0.020). Conclusions: Successful H. pylori eradication could prevent MGC after ESD for EGC.
Conflito de terras nos sertões de Angola
Authors: Gloss Marão Alfagali Crislayne
Published: November 2019

Este artigo analisa os conflitos de terra que decorreram da instalação de uma fábrica de ferro na região da Ilamba, no interior de Angola, na segunda metade do século XVIII. A desapropriação das terras africanas, na África Centro-Ocidental, em períodos anteriores ao século XIX, é uma temática pouco abordada pela historiografia. Este estudo de caso contribui para pensar a questão à medida que analisa os mecanismos coloniais de espoliação das terras e recursos naturais das lideranças africanas locais, considerando também as estratégias dos sobas para manter seu poder político ao longo do tempo.
D. Francisco de Lemos de Faria Pereira Coutinho, uma biografia (1735-1822)
Authors: Alves Carlos F. T.
Published: November 2019

Francisco de Lemos, nascido no Rio de Janeiro, tornou-se uma das personalidades mais importantes da realidade setecentista portuguesa, principalmente na área do ensino e da administração civil e eclesiástica. Próximo de Pombal, acaba por ter uma enorme projeção alcançando posições de destaque, principalmente reitor da Universidade de Coimbra e bispo. Mas sua capacidade de adaptação acaba por permitir que sua carreira se mantenha na ribalta com alguma regularidade. Neste trabalho pretendo fazer uma análise detalhada sobre Francisco de Lemos, desde a sua vinda para Coimbra até o ano da sua morte, 1822, focando-me principalmente nos pontos chave de sua carreira e rede de influências.
Estado, transportes e mercado de trabalho
Authors: Cravo Télio Anísio , Godoy Marcelo Magalhães
Published: November 2019

Durante as décadas de 1830 e 1840, o Governo Provincial de Minas Gerais investiu diretamente na construção da Estrada do Paraibuna. A intervenção viária exigiu a contratação de trabalhadores braçais e qualificados. Pretende-se neste estudo explorar o ajustamento de trabalhadores livres e libertos e o sistema de aluguel de escravos. Enfatiza-se a participação de artífices forros no sistema de aluguel e a negociação para o ajustamento contratual de trabalho de um mestre carpinteiro livre. Valendo-se do cruzamento de fontes primárias, analisa-se a mobilidade social ascendente de um mestre pedreiro livre. A pesquisa identifica três resultados: (I) organização social laboral caracterizada pelo trabalho intermitente; (II) elevada taxa bruta de retorno obtida pelos donos de escravos alugados; (III) acumulação de capital-dinheiro e a inversão na importação de escravos do tráfico negreiro transatlântico.
Plínio Salgado
Authors: Martinho Francisco Carlos Palomanes
Published: November 2019

Resenha do livro Plínio Salgado: um católico integralista entre Portugal e o Brasil (1895-1975), de Leandro Pereira Gonçalves.