bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetostatic and Dynamic Modeling of Flexure-Based Compliant Mechanisms: A Survey
Authors: Ling Mingxiang , Howell Larry L. , Cao Junyi , Chen Guimin 
Published: December 2019

Abstract
Flexure-based compliant mechanisms are becoming increasingly promising in precision engineering, robotics, and other applications due to the excellent advantages of no friction, no backlash, no wear, and minimal requirement of assembly. Because compliant mechanisms have inherent coupling of kinematic-mechanical behaviors with large deflections and/or complex serial-parallel configurations, the kinetostatic and dynamic analyses are challenging in comparison to their rigid-body counterparts. To address these challenges, a variety of techniques have been reported in a growing stream of publications. This paper surveys and compares the conceptual ideas, key advances, and applicable scopes, and open problems of the state-of-the-art kinetostatic and dynamic modeling methods for compliant mechanisms in terms of small and large deflections. Future challenges are discussed and new opportunities for extended study are highlighted as well. The presented review provides a guide on how to select suitable modeling approaches for those engaged in the field of compliant mechanisms.
Buckling and Post-Buckling of Thin-Walled Composite Laminated Beams—A Review of Engineering Analysis Methods
Authors: Mittelstedt Christian 
Published: December 2019

AbstractThin-walled beams made of laminated composite materials are increasingly used in any engineering branch where structural weight is one of the major aspects in the design process of load bearing structures. Quite naturally, when composite materials are being employed, analysis methods are required that adequately take effects such as material anisotropy, coupling effects, and shear deformations into account which are inherent to this class of materials. This paper aims to provide an overview of engineering analysis methods concerning the buckling and post-buckling behavior of thin-walled composite laminated beams, covering topics such as exact and closed-form analytical approximate solutions as well as semi-analytical and numerical methods wherein a distinction is made between local and global buckling of beam structures, and the interaction of global and local buckling modes. This paper also covers an overview of experimental investigations as well as of design optimization studies and closes with an outlook on future investigations.
The Physiological, Physical, and Biomechanical Demands of Walking Football: Implications for Exercise Prescription and Future Research in Older Adults
Authors: Harper Liam D. , Field Adam , Corr Liam D. , Naughton Robert J. 
Published: December 2019

The aim of this investigation was to profile the physiological, physical, and biomechanical responses during walking football. A total of 17 male participants (aged 66 ± 6 years) participated. Heart rate; blood lactate; accelerometer variables (biomechanical load [PlayerLoad™], changes of direction); and rating of perceived exertion were measured. Participants mean percentage of maximum heart rate was 76 ± 6% during the sessions, with rating of perceived exertion across all sessions at 13 ± 2. Blood lactate increased by ∼157% from presession (1.24 ± 0.4 mmol/L) to postsession (3.19 ± 1.7 mmol/L; p ≤ .0005). PlayerLoad™ values of 353 ± 67 arbitrary units were observed, as well as ∼100 changes of direction per session. In conclusion, walking football is a moderate- to vigorous-intensity activity. The longitudinal health benefits of walking football remain to be elucidated, particularly on bone health, cardiovascular fitness, and social and mental well-being.
Changes in neovascular activity following fixed dosing with an anti-vascular endothelial growth factor agent over 52 weeks in the phase III VIEW 1 and VIEW 2 studies
Authors: Moshfeghi Darius M , Thompson Desmond , Saroj Namrata 
Published: December 2019

Background/aims
To understand changes in disease activity as assessed by leakage and retinal fluid status in patients with neovascular age-related macular degeneration (nAMD) receiving fixed dosing with an anti-vascular endothelial growth factor (anti-VEGF) agent.

Methods

In the phase III VIEW 1 (
NCT00509795
) and VIEW 2 (
NCT00637377
) studies, eyes with nAMD were treated with intravitreal aflibercept or ranibizumab. Independent, masked reading centres determined the presence/absence of leakage (fluorescein angiography) and retinal fluid (optical coherence tomography) at baseline, week 24 and week 52. In this integrated, post hoc analysis of the VIEW studies, the relationship between leakage/fluid status and best-corrected visual acuity (BCVA) was assessed. The impact of baseline lesion type (predominantly classic (PC), minimally classic (MC), occult) was also evaluated. Data from all treatment groups were pooled.

Results
2373 eyes were included in this analysis. At baseline, 95.4% of eyes presented with both leakage and fluid. By week 52, leakage and fluid were present in 16.0% of eyes. Mean BCVA gains at week 52 were numerically greater in eyes without leakage and fluid versus eyes with both leakage and fluid (10.3 vs 9.2 letters). At week 52, 11.6%, 15.3% and 20.1% of eyes with PC, MC and occult lesions, respectively, had both leakage and fluid present.

Conclusion
In this post hoc analysis, fixed dosing with an anti-VEGF agent over 52 weeks eliminated disease activity (absence of both leakage and fluid) in most eyes. The effect of anti-VEGF treatment on leakage/fluid status favoured PC versus occult lesions.
How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study
Authors: Challenger Joseph D , Gonçalves Bronner P , Bradley John , Bruxvoort Katia , Tiono Alfred B , Drakeley Chris , Bousema Teun , Ghani Azra C , Okell Lucy C 
Published: December 2019

IntroductionArtemether-lumefantrine (AL) is the most widely-recommended treatment for uncomplicatedPlasmodium falciparummalaria. Its efficacy has been extensively assessed in clinical trials. In routine healthcare settings, however, its effectiveness can be diminished by delayed access to treatment and poor adherence. As well as affecting clinical outcomes, these factors can lead to increased transmission, which is the focus of this study.MethodsWe extend a within-host model ofP. falciparumto include gametocytes, the parasite forms responsible for onward transmission. The model includes a pharmacokinetic–pharmacodynamic model of AL, calibrated against both immature and mature gametocytes using individual-level patient data, to estimate the impact that delayed access and imperfect adherence to treatment can have on onward transmission of the parasite to mosquitoes.ResultsUsing survey data from seven African countries to determine the time taken to acquire antimalarials following fever increased our estimates of mean total infectivity of a malaria episode by up to 1.5-fold, compared with patients treated after 24 hours. Realistic adherence behaviour, based on data from a monitored cohort in Tanzania, increased the contribution to transmission by 2.2 to 2.4-fold, compared with a perfectly-adherent cohort. This was driven largely by increased rates of treatment failure leading to chronic infection, rather than prolonged gametocytaemia in patients who have slower, but still successful, clearance of parasites after imperfect adherence to treatment. Our model estimated that the mean infectivity of untreated infections was 29–51 times higher than that of treated infections (assuming perfect drug adherence), underlining the importance of improving treatment coverage.ConclusionUsing mathematical modelling, we quantify how delayed treatment and non-adherent treatment can increase transmission compared with prompt effective treatment. We also highlight that transmission from the large proportion of infections which never receive treatment is substantially higher than those treated.
Association between neck circumference and cardiometabolic disease in Chinese adults: a community-based cross-sectional study
Authors: Fu Wenning , Zou Li , Yin Xiaoxu , Wu Jiang , Zhang Shengchao , Mao Jing , Cao Shiyi , Li Wenzhen , Gan Yong , Yan Shijiao , Gong Yanhong , Lu Zuxun 
Published: December 2019

ObjectivesSeveral studies have indicated that neck circumference (NC) was associated with cardiometabolic disease in some Western countries. However, there are limited data regarding this association among Chinese adults.DesignA community-based cross-sectional study.SettingA multistage-stratified random cluster survey was conducted in Xixiang Street, Bao’an District of Shenzhen in southeast China.ParticipantsThis study included 4000 participants (1605 men and 2395 women) with a mean age of 56.0±9.8 years.Main outcome measuresCategorical data were reported as percentage and continuous data were reported as mean±SD. Receiver operating characteristic analysis and logistic regression analysis were used to evaluate the association of NC with cardiometabolic disease.ResultsThe mean NC values were 35.50±4.23 cm for men and 32.32±3.59 cm for women. After adjusting for body mass index and waist circumference, NC was significantly associated with the risk of hypertension (OR: 1.42 in women), decreased high-density lipoprotein (HDL) levels (OR: 1.27 in men; OR: 1.12 in women), high triglyceride (TG) levels (OR: 1.54 in women) and diabetes (OR: 1.41 in men; OR: 1.37 in women). Among men, the optimal NC cut-off values were 38.10 cm for identifying hypertension, 32.32 cm for decreased HDL levels, 36.6 cm for high TG levels and 36.6 cm for diabetes. Among women, the optimal NC cut-off values were 32.35 cm for identifying hypertension, 33.40 cm for decreased HDL levels, 32.90 cm for high TG levels and 33.40 cm for diabetes.ConclusionsNC was significantly associated with cardiometabolic disease in Chinese population. Although further studies are needed to confirm the optimal cut-off values, evaluating NC may be useful for predicting cardiometabolic disease risk during clinical assessments.
Associations between socioeconomic position and changes in children’s screen-viewing between ages 6 and 9: a longitudinal study
Authors: Salway Ruth E , Emm-Collison Lydia , Sebire Simon , Thompson Janice L , Jago Russ 
Published: December 2019

ObjectivesTo explore socioeconomic differences in screen-viewing at ages 6 and 9, and how these are related to different media uses.DesignLongitudinal cohort study.SettingChildren recruited from 57 state-funded primary schools in Southwest England, UK.Participants1299 children at ages 5–6, 1223 children at ages 8–9, including 685 children at both time points.Outcome measuresChildren’s total screen-viewing time (parent-reported) and time spent using multiple screen devices simultaneously (multiscreen viewing), for weekdays and weekends.MethodsNegative binomial regression was used to model associations between socioeconomic variables (highest household education and area deprivation) and total screen-viewing at age 6 and the change from age 6 to 9. We additionally adjusted for child characteristics, parental influences and media devices in the home. Multiscreen viewing was analysed separately.ResultsHousehold education was associated with children’s screen-viewing at age 6 with lower screen-viewing in higher socioeconomic groups (21%–27% less in households with a Degree or Higher Degree, compared with General Certificate of Secondary Education: GCSE). These differences were explained by the presence of games consoles, parental limits on screen-viewing and average parent screen-viewing. Between ages 6 and 9, there were larger increases in screen-viewing for children from A level and Degree households (13% and 6%, respectively, in the week) and a decrease in Higher Degree households (16%), compared with GCSE households. Differences by household education remained when adjusting for media devices and parental factors.ConclusionsChildren’s screen-viewing patterns differ by parental education with higher levels of viewing among children living in households with lower educational qualifications. These differences are already present at age 6, and continue at age 9. Strategies to manage child sedentary time, and particularly screen-viewing, may need to take account of the socioeconomic differences and target strategies to specific groups.
A prospective, open-label, interventional study protocol to evaluate treatment efficacy of nivolumab based on serum-soluble PD-L1 concentration for patients with metastatic and unresectable renal cell carcinoma
Authors: Bando Yukari , Hinata Nobuyuki , Omori Takashi , Fujisawa Masato 
Published: December 2019

IntroductionNivolumab has been proven to prolong overall survival as a second-line therapy for patients with advanced renal cell carcinoma (RCC) in a phase III clinical trial. However, versatile biomarkers have not been established to predict the efficacy of nivolumab against target disease.Methods and analysisAfter registration, screening test and serum-soluble programmed cell death 1-ligand 1 (sPD-L1) measurement will be performed by using the ELISA; patients will be grouped into high sPD-L1 or low sPD-L1 groups. Nivolumab (240 mg every 2 weeks by intravenous drip infusion) will be administered to each participant. For this prospective study, statistical power calculation indicated that 48 participants with metastatic or unresectable RCC are needed to assess the efficacy of this method. The participants must be at the age of at least 20 years at the time of informed consent and require second-line therapy after failure of first-line therapy or discontinuation due to adverse effects. All data will be collected in our institution. The primary endpoint is progression-free survival, and secondary endpoints are overall survival and objective response rate. In this protocol, we will examine sPD-L1 as a promising predictive marker.Ethics and disseminationThis protocol was approved by the Kobe University Clinical Research Ethical Committee (C180067). Findings of this study will be widely disseminated through conference presentations, reports, factsheets and academic publications; further generalisation will also be discussed.Trial registration numberUMIN000027873.
Anticancer drug prices and clinical outcomes: a cross-sectional study in Italy
Authors: Trotta Francesco , Mayer Flavia , Barone-Adesi Francesco , Esposito Immacolata , Punreddy Ranadhir , Da Cas Roberto , Traversa Giuseppe , Perrone Francesco , Martini Nello , Gyawali Bishal , Addis Antonio 
Published: December 2019

ObjectiveTo investigate whether the prices of new anticancer drugs correlated with their relative benefit despite negotiation.DesignRetrospective cross-sectional study correlating new anticancer drugs prices with clinical outcomes.SettingWe did a retrospective cross-sectional study including all new anticancer drugs approved by the European Medicines Agency (EMA) (2010–2016) and reimbursed in Italy.Main outcome(s) and measure(s)Information on clinical outcomes—in terms of median overall survival (OS), median progression-free survival (PFS) and objective response rate (ORR)—was extracted from pivotal trials as reported in the European Public Assessment Reports available on the EMA website. Cost of a full course treatment was estimated on negotiated official and discounted prices. Regression coefficients β, their levels of significance p and the coefficients of determination R2 were estimated adjusting by tumour type.ResultsOverall, 30 new anticancer drugs (with 35 indications) were available for analysis. Where data on OS were available, we observed no correlation between the improvement in median OS (in weeks) and negotiated price (R2=0.067, n=16 drugs for 17 indications). When the clinical outcomes were expressed as improvements in the median PFS or ORR, 25 drugs (29 indications) were available for the analysis, and again, there was no correlation with prices (R2=0.004 and 0.006, respectively).Conclusions and relevanceOur results suggest that the prices of anticancer drugs in Italy do not reflect their therapeutic benefit. Drug price negotiations, which is mandatory by law in Italy, do not seem to ensure that prices correlate with clinical benefits provided by the cancer drugs. These results call for further efforts to establish the standard determinants of drug prices available at the time of negotiation. These findings need to be confirmed in other countries where price negotiations are in place. Moreover, further investigations may verify whether outcome data obtained after drug marketing would improve the correlation between prices and therapeutic benefit.
Logic model framework for considering the inputs, processes and outcomes of a healthcare organisation–research partnership
Authors: Tabriz Amir Alishahi , Flocke Susan A , Shires Deirdre , Dyer Karen E , Schreiber Michelle , Elston Lafata Jennifer 
Published: December 2019

BackgroundThe published literature provides few insights regarding how to develop or consider the effects of knowledge co-production partnerships in the context of delivery system science.ObjectiveTo describe how a healthcare organisation–university-based research partnership was developed and used to design, develop and implement a practice-integrated decision support tool for patients with a physician recommendation for colorectal cancer screening.DesignInstrumental case study.ParticipantsData were ascertained from project documentation records and semistructured questionnaires sent to 16 healthcare organisation leaders and staff, research investigators and research staff members.ResultsUsing a logic model framework, we organised the key inputs, processes and outcomes of a healthcare organisation–university-based research partnership. In addition to pragmatic researchers, partnership inputs included a healthcare organisation with a supportive practice environment and an executive-level project sponsor, a mid-level manager to serve as the organisational champion and continual access to organisational employees with relevant technical, policy and system/process knowledge. During programme design and implementation, partnership processes included using project team meetings, standing organisational meetings and one-on-one consultancies to provide platforms for shared learning and problem solving. Decision-making responsibility was shared between the healthcare organisation and research team. We discuss the short-term outcomes of the partnership, including how the partnership affected the current research team’s knowledge and health system initiatives.ConclusionUsing a logic model framework, we have described how a healthcare organisation–university-based research team partnership was developed. Others interested in developing, implementing and evaluating knowledge co-production partnerships in the context of delivery system science projects can use the experiences to consider ways to develop, implement and evaluate similar co-production partnerships.
Virtual patient technology to educate pharmacists and pharmacy students on patient communication: a systematic review
Authors: Richardson Charlotte Lucy , White Simon , Chapman Stephen 
Published: December 2019

BackgroundVirtual patients (VPs) are a sub-type of healthcare simulation that have been underutilised in health education. Their use is increasing, but applications are varied, as are designs, definitions and evaluations. Previous reviews have been broad, spanning multiple professions not accounting for design differences.ObjectivesThe objective was to undertake a systematic narrative review to establish and evaluate VP use in pharmacy. This included VPs that were used to develop or contribute to communication or counselling skills in pharmacy undergraduates, pre-registration pharmacists and qualified pharmacists.Study selectionEight studies were identified using EBSCO and were quality assessed. The eligibility criteria did not discriminate between study design or outcomes but focused on the design and purpose of the VP. All the included studies used different VP applications and outcomes.FindingsFour themes were identified from the studies: knowledge and skills, confidence, engagement with learning, and satisfaction. Results favoured the VPs but not all studies demonstrated this statistically due to the methods. VP potential and usability are advantageous, but technological problems can limit use. VPs can help transition knowledge to practice.ConclusionsVPs are an additional valuable resource to develop communication and counselling skills for pharmacy students; use in other pharmacy populations could not be established. Individual applications require evaluation to demonstrate value due to different designs and technologies; quality standards may help to contribute to standardised development and implementation in varied professions. Many studies are small scale without robust findings; consequently, further quality research is required. This should focus on implementation and user perspectives.
Fragility Index in Cardiovascular Randomized Controlled Trials
Authors: Khan Muhammad Shahzeb , Ochani Rohan Kumar , Shaikh Asim , Usman Muhammad Shariq , Yamani Naser , Khan Safi U. , Murad M. Hassan , Mandrola John , Doukky Rami , Krasuski Richard A. 
Published: December 2019

Background:

Efficacy of an intervention is commonly evaluated using
P
values, in addition to effect size measures such as absolute risk reduction, relative risk reduction, and numbers needed to treat. However, these measures are not always intuitive to clinicians. The fragility index (FI) is a more intuitive number that can facilitate interpretation but can only be used with binary outcomes. FI is the minimum number of patients who must be moved from the nonevent group to the event group to turn a significant result nonsignificant. In this retrospective analysis, we assessed the robustness of cardiovascular randomized controlled trials (RCTs), which report a positive (statistically significant) primary outcome by using the FI.

Methods and Results:

We searched Medline from 2007 to 2017 to identify cardiovascular RCTs published in 6 high impact journals (
The Lancet
,
New England Journal of Medicine
,
Journal of the American Medical Association
,
Circulation
,
Journal of the American College of Cardiology
and
European Heart Journal
). Only RCTs with sample sizes >500 and a 2-by-2 factorial design or dichotomous primary outcomes were selected. FI was calculated using a defined approach. Among the cohort of 123 RCTs that met inclusion criteria, median FI was 13 (interquartile range, 5–26). In 28 trials (22.8%), FI ranged between 1 and 4. In 37 trials (30.1%), number of patients lost to follow-up was higher than the FI. Pharmaceutical interventions had higher FI compared with other interventions, FI=19 (7–52;
P
=0.002). Median FI varied according to subspecialty (electrophysiology=2; heart failure=11; interventional cardiology=8;
P
=0.020) and multiregional RCTs had higher FI=22 (12–53.25;
P
=0.023). FI did not differ based on risk of bias indicators, funding, or publication year.

Conclusions:
Considerable variations in FI were observed among cardiovascular trials, suggesting the need for careful interpretation of results, particularly when number of patients lost to follow-up exceeds FI.