bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of the combination of reduced duration prophylaxis followed by immuno-guided prophylaxis to prevent cytomegalovirus disease in lung transplant recipients (CYTOCOR STUDY): an open-label, randomised, non-inferiority clinical trial
Authors: Paez-Vega Aurora , Cantisan Sara , Vaquero José Manuel , Vidal Elisa , Luque-Pineda Antonio , Lobo-Acosta María Ángeles , Pérez Ana Belén , Alonso-Moralejo Rodrigo , Iturbe David , Monforte Victor , Otero-Gonzalez Isabel , Pastor Amparo , Ussetti Piedad , Torre-Cisneros Julian
Published: August 2019

Introduction

Prolonged use of antivirals to prevent the development of cytomegalovirus (CMV) disease in lung transplant patients has been shown to have significant side effects, for which alternatives are being sought to reduce their use. The monitoring of cell immunity against CMV could be an alternative as it has shown to be useful in identifying transplant patients at low risk of infection, who could benefit from shorter prophylaxis. Theaimof the CYTOCOR study is to demonstrate that the combination of a reduced prophylaxis strategy with subsequent CMV-specific immunological monitoring would allow CMV infection to be controlled in lung transplant patients as effectively as the usual strategy (prophylaxis followed by pre-emptive therapy), while reducing the side effects of antivirals due to the shorter duration of prophylaxis.

Methods and analysis

Phase III randomised, open, multicentre, parallel, non-inferiority clinical trial to study the efficacy and safety of the combination of a prophylaxis strategy up to month +3 post-transplant followed by immuno-guided prophylaxis using the QuantiFERON-CMV technique up to month +12 post-transplant to prevent CMV disease in CMV-seropositive lung transplant recipients. This strategy will be compared with a combination of a usual prophylaxis strategy up to month +6 post-transplant followed by pre-emptive therapy up to month +12. To study the incidence of CMV disease, patients will be followed up to 18 months post-transplantation. A total of 150 patients are expected to be recruited for the study.

Ethics and public dissemination

The clinical trial has been approved by the Research Ethics Committees and authorised by the Spanish Agency of Medicines and Medical Devices (AEMPS).

If the hypothesis of this clinical trial is verified, the dissemination of the results could change clinical practice by increasing knowledge about the safety and efficacy of discontinuing valganciclovir prophylaxis in lung transplant recipients.

Trial registration number

NCT03699254.
Hypertension management: experiences, wishes and concerns among older people—a qualitative study
Authors: van Bussel Emma , Reurich Leony , Pols Jeannette , Richard Edo , Moll van Charante Eric , Ligthart Suzanne
Published: August 2019

Objectives

Sixty-five per cent of older people have hypertension, but little is known about their preferences and concerns regarding hypertension management. Guidelines on hypertension lack consensus on how to treat older people without previous cardiovascular disease (CVD). This asks for explicit consideration of patient preferences in decision making. Therefore, the aim of this study was to explore older peoples’ experiences, preferences, concerns and perceived involvement regarding hypertension management.

Design

Qualitative interview study.

Setting

Participants were selected from 11 general practitioner (GP) practices in the Netherlands and purposively sampled until data saturation was achieved. Semistructured interviews were conducted, audio recorded and analysed by two researchers using thematic analysis.

Participants

Fifteen community dwelling older people aged 74–93 years with hypertension and without previous CVD participated.

Results

Interviewees rarely started the conversation about hypertension management with their GP, although they did have concerns. Reasons for not discussing the subject included low priority of hypertension concerns, reliance on GPs or trust in GPs to make the right decision on their behalf. Also, interviewees anticipated regret of reducing medication, fearing vascular incidents. Interviewees would like to discuss tailoring treatment to their needs, deprescription of medication and ways to reduce side effects. They expected GPs to be more transparent on treatment effects.

Conclusion

Older people describe having little involvement in hypertension management, although they have several concerns. Since GPs are also known to be hesitant to bring up this subject, we signal a conspiracy of silence about antihypertensive medication. Through breaking this silence, GPs can facilitate shared decision-making on hypertension management and better tailored care.
Effects of adenotonsillectomy on the growth of children with obstructive sleep apnoea-hypopnea syndrome (OSAHS): protocol for a systematic review
Authors: Hua Fang , Zhao Tingting , Walsh Tanya , Sun Qiao , Chen Xiong , Worthington Helen , Jiang Fan , He Hong
Published: August 2019

Introduction

Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is characterised by recurring episodes of complete or partial upper airway collapse during sleep. Persistent OSAHS is associated with long-term consequences, such as growth failure, cardiovascular and neurocognitive problems in children. Different from the aetiology of OSAHS in adults, the most common cause of paediatric OSAHS is adenotonsillar hypertrophy. Adenotonsillectomy (AT) has been recommended as the first-line treatment of paediatric OSAHS. Several studies have suggested that retarded growth caused by OSAHS can improve after AT during the prepubertal period. This review will systematically search and summarise the available evidence on the effects of AT on children’s growth.

Methods and analysis

We will conduct electronic searches in MEDLINE (via PubMed), Embase, Google Scholar and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) or cohort studies that included a control group. Additional records will be searched by checking the references included in the selected studies and relevant reviews. At least two authors will undertake selection of studies and data extraction independently and in duplicate. The Cochrane Risk of Bias tool and Risk Of Bias In Non-randomised Studies—of Interventions will be used to assess the risk of bias of RCT and cohort studies, respectively. A random-effects model will be used for meta-analyses. Data synthesis and other analyses will be carried out using the RevMan V.5.3 software. The Grades of Recommendation, Assessment, Development and Evaluation will be used to assess the quality of the supporting evidence behind each main comparison.

Ethics and dissemination

There is no ethical issue in this systematic review given that we will only include published studies. The results will be disseminated via peer-reviewed publications and social networks.

PROSPERO registration number

CRD42019125882
RESTORE—Cognitive functional therapy with or without movement sensor biofeedback versus usual care for chronic, disabling low back pain: study protocol for a randomised controlled trial
Authors: Kent Peter , O'Sullivan P , Smith Anne , Haines Terry , Campbell Amity , McGregor Alison H , Hartvigsen Jan , O'Sullivan Kieran , Vickery Alistair , Caneiro JP , Schütze Robert , Laird Robert A , Attwell Stephanie , Hancock Mark
Published: August 2019

Introduction

Low back pain (LBP) is the leading cause of disability globally and its costs exceed those of cancer and diabetes combined. Recent evidence suggests that individualised cognitive and movement rehabilitation combined with lifestyle advice (cognitive functional therapy (CFT)) may produce larger and more sustained effects than traditional approaches, and movement sensor biofeedback may enhance outcomes. Therefore, this three-arm randomised controlled trial (RCT) aims to compare the clinical effectiveness and economic efficiency of individualised CFT delivered with or without movement sensor biofeedback, with usual care for patients with chronic, disabling LBP.

Methods and analysis

Pragmatic, three-arm, randomised, parallel group, superiority RCT comparing usual care (n=164) with CFT (n=164) and CFT-plus-movement-sensor-biofeedback (n=164). Inclusion criteria include: adults with a current episode of LBP >3 months; sought primary care ≥6 weeks ago for this episode of LBP; average LBP intensity of ≥4 (0–10 scale); at least moderate pain-related interference with work or daily activities. The CFT-only and CFT-plus-movement-sensor-biofeedback participants will receive seven treatment sessions over 12 weeks plus a ‘booster’ session at 26 weeks. All participants will be assessed at baseline, 3, 6, 13, 26, 40 and 52 weeks. The primary outcome is pain-related physical activity limitation (Roland Morris Disability Questionnaire). Linear mixed models will be used to assess the effect of treatment on physical activity limitation across all time points, with the primary comparison being a formal test of adjusted mean differences between groups at 13 weeks. For the economic (cost-utility) analysis, the primary outcome of clinical effect will be quality-adjusted life years measured across the 12-month follow-up using the EuroQol EQ-5D-5L .

Ethics and dissemination

Approved by Curtin University Human Research Ethics Committee (HRE2018-0062, 6 Feb 2018). Study findings will be disseminated through publication in peer-reviewed journals and conference presentations.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12618001396213).
Southampton Arm Fracture Frailty and Sarcopenia Study (SAFFSS): a study protocol for the feasibility of assessing frailty and sarcopenia among older patients with an upper limb fracture
Authors: Ibrahim Kinda , Mullee Mark , Yao Guiqing Lily , Zhu Shihua , Baxter Mark , Tilly Simon , Russell Cynthia , Roberts Helen C
Published: August 2019

Introduction

Falls are a major health problem for older people; 35% of people aged 65+ years fall every year, leading to fractures in 10%–15%. Upper limb fractures are often the first sign of osteoporosis and routine screening for osteoporosis is recommended by the National Institute for Health and Care Excellence to prevent subsequent hip fractures. However, both frailty and sarcopenia (muscle weakness) are associated with increased risk of falling and fracture but are not routinely identified in this group. The aim of this study is to evaluate the feasibility of assessing and managing frailty and sarcopenia among people aged 65+ years with an upper limb fracture.

Methods and analysis

This study will be conducted in three fracture clinics in one acute trust in England. 100 people aged 65+ years with an upper arm fracture will be recruited and assessed using six validated frailty measures and two sarcopenia tools. The prevalence of the two conditions and the best tools to use will be determined. Those with either condition will be referred to geriatric clinical teams for comprehensive geriatric assessment (CGA). We will document the proportion who are referred for CGA and those who receive CGA. Other outcome measures including falls, fractures and healthcare resource use over 6 months will be collected. In-depth interviews with a purposive sample of patients who undergo the frailty and sarcopenia assessments and healthcare professionals in fracture clinics and geriatric services will be carried out to their acceptability of assessing frailty and sarcopenia in a busy environment.

Ethics and dissemination

The study was given the relevant ethical approvals from NHS Research Ethics Committee (REC No: 18/NE/0377), the University Hospital Southampton NHS Foundation Trust, and the University of Southampton, Faculty of Medicine Ethics Committee and Research Governance Office. Findings will be published in scientific journals and presented to local, national and international conferences.

Trial registration number

ISRCTN13848445
Subcutaneous sumatriptan for the treatment of postcraniotomy pain (SUPS trial): protocol for a randomised double-blinded placebo controlled trial
Authors: Licina Ana , Russell Jeremy , Silvers Andrew , Jin Xin , Denny Jason
Published: August 2019

Introduction

Postcraniotomy pain protocols use opioids, which are considered suboptimal analgesia following this procedure. Multimodal analgesia components are sparse. Our null hypothesis states that sumatriptan is not different to placebo in addition to usual intravenous opioids, for the treatment of acute postcraniotomy pain.

Methods and analysis

This is a prospective single-centre randomised double-blinded placebo-controlled phase III clinical trial comparing subcutaneous sumatriptan injection in the recovery area with placebo for the treatment of postcraniotomy pain. Eligible adult patients (18 years and older) undergoing craniotomy will be identified preoperatively. Both patient groups will receive a subcutaneous injection at a point where recovery-nursing staff would initiate the usual intravenous opioid analgesia as per standardised pain management protocol. In both groups, further pain management will be followed by the usual intravenous opioid administration. Primary outcome will consist of the difference in pain experienced by the two groups of patients in recovery area 60 min after the study drug administration. Postcraniotomy pain will be measured at regular intervals using the Visual Analogue Scale (VAS) in recovery area. The minimal clinically important difference of 10 mm on the VAS between the two groups will be considered as statistically significant. We will include selected clinical and patient-reported outcomes as secondary endpoints. Univariate regression will be conducted on each one of the clinically plausible potential confounders. We will enrol a total 136 patients, with the study duration of 2 years. This trial will commence recruitment on the 1 July 2019.

Ethics and dissemination

This trial protocol has achieved approval by the Austin Health Research Committee, HREC/17/Austin/596. This trial was prospectively registered with Australian New Zealand Clinical Trials Registry on the 10/05/2018 with a unique trial identifier U1111-1209-9072 and registration Number ACTRN12618000793213P. Findings of this study will be disseminated in peer-reviewed academic journals.

Trial registration number

U1111-1209-9072, ACTRN12618000793213P
Mental well-being, job satisfaction and self-rated workability in general practitioners and hospitalisations for ambulatory care sensitive conditions among listed patients: a cohort study combining survey data on GPs and register data on patients
Authors: Nørøxe Karen Busk , Pedersen Anette Fischer , Carlsen Anders Helles , Bro Flemming , Vedsted Peter
Published: August 2019

Background

Physicians’ work conditions and mental well-being may affect healthcare quality and efficacy. Yet the effects on objective measures of healthcare performance remain understudied. This study examined mental well-being, job satisfaction and self-rated workability in general practitioners (GPs) in relation to hospitalisations for ambulatory care sensitive conditions (ACSC-Hs), a register-based quality indicator affected by referral threshold and prevention efforts in primary care.

Methods

This is an observational study combining data from national registers and a nationwide questionnaire survey among Danish GPs. To ensure precise linkage of each patient with a specific GP, partnership practices were not included. Study cases were 461 376 adult patients listed with 392 GPs. Associations between hospitalisations in the 6-month study period and selected well-being indicators were estimated at the individual patient level and adjusted for GP gender and seniority, list size, and patient factors (comorbidity, sociodemographic characteristics).

Results

The median number of ACSC-Hs per 1000 listed patients was 10.2 (interquartile interval: 7.0–13.7). All well-being indicators were inversely associated with ACSC-Hs, except for perceived stress (not associated). The adjusted incidence rate ratio was 1.26 (95% CI 1.13 to 1.42) for patients listed with GPs in the least favourable category of self-rated workability, and 1.19 (95% CI 1.05 to 1.35), 1.15 (95% CI 1.04 to 1.27) and 1.14 (95% CI 1.03 to 1.27) for patients listed with GPs in the least favourable categories of burn-out, job satisfaction and general well-being (the most favourable categories used as reference). Hospitalisations for conditions not classified as ambulatory care sensitive were not equally associated.

Conclusions

ACSC-H frequency increased with decreasing levels of GP mental well-being, job satisfaction and self-rated workability. These findings imply that GPs’ work conditions and mental well-being may have important implications for individual patients and for healthcare expenditures.
Managing psychological safety in debriefings: a dynamic balancing act
Authors: Kolbe Michaela , Eppich Walter , Rudolph Jenny , Meguerdichian Michael , Catena Helen , Cripps Amy , Grant Vincent , Cheng Adam
Published: August 2019

Debriefings should promote reflection and help learners make sense of events. Threats to psychological safety can undermine reflective learning conversations and may inhibit transfer of key lessons from simulated cases to the general patient care context. Therefore, effective debriefings require high degrees of psychological safety—the perception that it is safe to take interpersonal risks and that one will not be embarrassed, rejected or otherwise punished for speaking their mind, not knowing or asking questions. The role of introductions, learning contracts and prebriefing in establishing psychological safety is well described in the literature. How to maintain psychological safety, while also being able to identify and restore psychological safety during debriefings, is less well understood. This review has several aims. First, we provide a detailed definition of psychological safety and justify its importance for debriefings. Second, we recommend specific strategies debriefers can use throughout the debriefing to build and maintain psychological safety. We base these recommendations on a literature review and on our own experiences as simulation educators. Third, we examine how debriefers might actively address perceived breaches to restore psychological safety. Re-establishing psychological safety after temporary threats or breaches can seem particularly daunting. To demystify this process, we invoke the metaphor of a ‘safe container’ for learning; a space where learners can feel secure enough to work at the edge of expertise without threat of humiliation. We conclude with a discussion of limitations and implications, particularly with respect to faculty development.
Congenital chloride-losing diarrhoea and Crohn’s disease: a diagnostic and therapeutic challenge
Authors: Harris Rachel Elizabeth , Tayler Rachel , Russell Richard K
Published: August 2019

We describe the case of a patient with congenital chloride-losing diarrhoea (CCLD), global developmental delay and intermittent transaminitis who was diagnosed with Crohn’s disease after persistent anaemia and onset of rectal bleeding. CCLD is a rare autosomal recessive condition causing large-volume chloride-rich diarrhoea, metabolic alkalosis and potentially life-threatening electrolyte disturbance. A possible association between CCLD and inflammatory bowel disease (IBD) has recently become apparent; however, the underlying mechanism has not been identified, with the role of increased expression of tumour necrosis factor-alpha hypothesised. Early diagnosis and management are key for favourable outcomes within both CCLD and IBD, and understanding a potential link between the two conditions may lead to development of novel therapies and management strategies. We aim to highlight the pathophysiology, diagnosis and management of CCLD; its potential association with IBD; and the potential therapeutic difficulties within the management of patients with comorbid CCLD and IBD.
Epilepsy surgery
Authors: Rugg-Gunn Fergus , Miserocchi Anna , McEvoy Andrew
Published: August 2019

Epilepsy surgery offers the chance of seizure remission for the 30%–40% of patients with focal epilepsy whose seizures continue despite anti-epileptic medications. Epilepsy surgery encompasses curative resective procedures, palliative techniques such as corpus callosotomy and implantation of stimulation devices. Pre-surgical evaluation aims to identify the epileptogenic zone and to prevent post-operative neurological and cognitive deficits. This entails optimal imaging, prolonged video-electroencephalogram (EEG) recordings, and neuropsychological and psychiatric assessments; some patients may then require nuclear medicine imaging and intracranial EEG recording. The best outcomes are in those with an electro-clinically concordant structural lesion on MRI (60%–70% seizure freedom). Lower rates of seizure freedom are expected in people with extra-temporal lobe foci, focal-to-bilateral tonic-clonic seizures, normal structural imaging, psychiatric co-morbidity and learning disability. Nevertheless, surgery for epilepsy is under-used and should be considered for all patients with refractory focal epilepsy in whom two or three anti-epileptic medications have been ineffective.
Attitudes of dog owners in Edinburgh towards canine blood donation
Authors: Wang Linda , Murison Pamela J
Published: August 2019

The establishment of animal blood banks following legislative changes in the UK in 2005 has led to increasing accessibility and use of animal blood products. However, the supply of animal blood is currently not meeting demand. This study aims to identify potential methods of increasing donor recruitment to meet this demand. A questionnaire was constructed, consisting of three sections designed to evaluate owner perceptions, identify incentives for donation and to obtain demographic data. Seventy‐nine responses were included, 76 of which were previous non‐donors. The top three reasons for not donating in this group were uncertainty over where to donate, veterinarians not expressing the need for donors and lack of awareness. Considering these results, one method of potentially increasing donor recruitment is encouraging more veterinarians to actively advertise local donor programmes. Emphasising the mandatory inclusion of a free annual health check in the donor process may also be helpful as many respondents rated this highly. It is the authors’ hope that this preliminary data may lead to increased willingness of owners to nominate their dogs for donation by guiding the provision of appropriate incentives and education to quell owner concerns as highlighted by this study.
Clinical signs and mortality of non‐released stranded California sea lions housed in display facilities: the suspected role of prior exposure to algal toxins
Authors: Simeone Claire , Fauquier Deborah , Skidmore Jennifer , Cook Peter , Colegrove Kathleen , Gulland Frances , Dennison Sophie , Rowles Teresa K
Published: August 2019

Stranded California sea lions considered unable to survive in the wild are often placed in public display facilities. Exposure to the biotoxin domoic acid (DA) is a common cause of stranding, and chronic effects are observed long after initial exposure. Medical records for 171 sea lions placed in US institutions between 2000 and 2016 were reviewed, including results from clinical examinations, histopathology, behavioural testing and advanced imaging. There was a statistically significant increase in neurological disease detected in neonates (24%) compared with other age classes (11%). Sixty per cent of all neurological cases died during the study period. In the 11 neurological neonate cases, six died (55%) and five are still alive with three of five developing epilepsy during placement. Of the six neurological neonate cases that died, one was attributed to DA toxicosis, one to seizures and four to acute unexplained neurological disease. This survey suggests delayed neurological disease can develop in sea lions after stranding as neonates. These data coupled with stranding records and epidemiological data on DA‐producing algal blooms suggest further research into effects of neonatal exposure to DA on risk of neurological disease in later life is warranted. California sea lions offer a natural model of DA exposure to study such effects.
Binding of muonated hydrogen molecules and Born–Oppenheimer approximation revisited
Authors: Varandas A.J.C. , da Providência J. , da Providência J.P.
Published: August 2019

The stability of four fermionic particles with unit charge, of which two are positively and two negatively charged, is discussed. Except for using the simplest approximation of a single Gaussian orbital per particle, the problem is exactly solved variationally by varying the masses to simulate molecular di-hydrogen, mono-muonated di-hydrogen, and di-muonated di-hydrogen. We illustrate the celebrated Born–Oppenheimer approximation 2 years after the occasion of its 90th anniversary. It is suggested that this method is valid only for di-hydrogen.
A Study on the Evaluation of Ventilation Performance According to the Location of the Return Diffusers of an Upward Displacement Ventilation System in a Dome-Shaped Small Concert Hall
Authors: Kwon Yong-Il
Published: August 2019

The modern people are active in various cultural facilities and enjoy the leisure life. The spectators and performers using a small concert hall generally use this space for about 2[Formula: see text]h in an enclosed state, and so the space should maintain a comfortable thermal environment and indoor air quality. The ventilation systems that can be applied to small concert hall are generally classified as the mixing ventilation system and the displacement ventilation system, but the upward displacement ventilation system is known to be able to maintain the clean indoor air quality with high energy efficiency. The upward displacement ventilation system installed in a dome-shaped small concert hall is not limited in the height of the vertical wall. Therefore, it is necessary to evaluate the optimal height of the return diffuser by utilizing the ventilation performance and the air diffusion performance index (ADPI). This study was carried out to evaluate the effect of the return diffuser position on the ventilation performance of an upward displacement ventilation system installed in a dome-shaped small concert hall. It was confirmed that as the height at which the return diffuser is installed on the vertical wall increases, the ventilation efficiency increases and the thermal stratification formed in the upper area is significantly reduced.
Incomplete SMT Techniques for Solving Non-Linear Formulas over the Integers
Authors: Borralleras Cristina , Larraz Daniel , Rodríguez-Carbonell Enric , Oliveras Albert , Rubio Albert
Published: August 2019

We present new methods for solving the Satisfiability Modulo Theories problem over the theory of Quantifier-Free Non-linear Integer Arithmetic, SMT(QF-NIA), which consists of deciding the satisfiability of ground formulas with integer polynomial constraints. Following previous work, we propose to solve SMT(QF-NIA) instances by reducing them to linear arithmetic: non-linear monomials are linearized by abstracting them with fresh variables and by performing case splitting on integer variables with finite domain. For variables that do not have a finite domain, we can artificially introduce one by imposing a lower and an upper bound and iteratively enlarge it until a solution is found (or the procedure times out).

The key for the success of the approach is to determine, at each iteration, which domains have to be enlarged. Previously, unsatisfiable cores were used to identify the domains to be changed, but no clue was obtained as to how large the new domains should be. Here, we explain two novel ways to guide this process by analyzing solutions to optimization problems: (i) to minimize the number of violated artificial domain bounds, solved via a Max-SMT solver, and (ii) to minimize the distance with respect to the artificial domains, solved via an Optimization Modulo Theories (OMT) solver. Using this SMT-based optimization technology allows smoothly extending the method to also solve Max-SMT problems over non-linear integer arithmetic. Finally, we leverage the resulting Max-SMT(QF-NIA) techniques to solve ∃ ∀ formulas in a fragment of quantified non-linear arithmetic that appears commonly in verification and synthesis applications.
Living with Two Genomes: Grafting and Its Implications for Plant Genome-to-Genome Interactions, Phenotypic Variation, and Evolution
Authors: Gaut Brandon S. , Miller Allison J. , Seymour Danelle K.
Published: August 2019

Plant genomes interact when genetically distinct individuals join, or are joined, together. Individuals can fuse in three contexts: artificial grafts, natural grafts, and host–parasite interactions. Artificial grafts have been studied for decades and are important platforms for studying the movement of RNA, DNA, and protein. Yet several mysteries about artificial grafts remain, including the factors that contribute to graft incompatibility, the prevalence of genetic and epigenetic modifications caused by exchanges between graft partners, and the long-term effects of these modifications on phenotype. Host–parasite interactions also lead to the exchange of materials, and RNA exchange actively contributes to an ongoing arms race between parasite virulence and host resistance. Little is known about natural grafts except that they can be frequent and may provide opportunities for evolutionary innovation through genome exchange. In this review, we survey our current understanding about these three mechanisms of contact, the genomic interactions that result, and the potential evolutionary implications.
Prospects for Diminishing the Impact of Nonamyloid Small-Vessel Diseases of the Brain
Authors: Joutel Anne
Published: August 2019

Small-vessel diseases (SVDs) of the brain are involved in about one-fourth of ischemic strokes and a vast majority of intracerebral hemorrhages and are responsible for nearly half of dementia cases in the elderly. SVDs are a heavy burden for society, a burden that is expected to increase further in the absence of significant therapeutic advances, given the aging population. Here, we provide a critical appraisal of currently available therapeutic approaches for nonamyloid sporadic SVDs that are largely based on targeting modifiable risk factors. We review what is known about the pathogenic mechanisms of vascular risk factor–related SVDs and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most frequent hereditary SVD, and elaborate on two mechanism-based therapeutic approaches worth exploring in sporadic SVD and CADASIL. We conclude by discussing opportunities and challenges that need to be tackled if efforts to achieve significant therapeutic advances for these diseases are to be successful.
AVE 0991 Attenuates Pyroptosis and Liver Damage after Heatstroke by Inhibiting the ROS-NLRP3 Inflammatory Signalling Pathway
Authors: Zhang Ming , Zhu Xintao , Tong Huasheng , Lou Anni , Li Yue , Li Yang , Su Lei , Li Xu
Published: August 2019

We previously demonstrated that angiotensin-(1-7) (Ang-(1-7)), an essential endocrine factor, inhibits the NLRP3 inflammasome by regulating reactive oxygen species (ROS) in fibrotic livers. We also demonstrated that the NLRP3 inflammasome contributes to the liver damage induced by pyroptosis after heatstroke. However, the role of Ang-(1-7) in the hepatocytes under heat stress remains uncertain. We aimed to examine the change in angiotensin peptides in the livers affected by heatstroke and the effect on the ROS-NLRP3 inflammatory signalling pathway. In vivo, increased angiotensin II (Ang II) and decreased Ang-(1-7) in the serum of heatstroke patients suffering from hepatic dysfunction were observed. The change in angiotensin peptides was considered a potential biomarker that could be used to predict hepatic dysfunction. Enhanced Ang II and attenuated Ang-(1-7) levels were also observed in the liver tissue of heatstroke rats, which were consistent with their receptors and converting enzymes. Hepatic damage associated with increased ROS and protein expression levels of NOX4, NLRP3, caspase-1, and IL-1β was attenuated by AVE 0991, an analogue of Ang-(1-7). In vitro, pyroptosis, characterized by activated caspase-1 and IL-1β, was observed in hepatocytes under heat stress, which was enhanced by Ang II and attenuated by antioxidants, NOX4 siRNA, and AVE 0991. In summary, AVE 0991 attenuates pyroptosis and liver damage induced by heat stress by inhibiting the ROS-NLRP3 inflammatory signalling pathway.
Commercial Vehicle Ride Comfort Optimization Based on Intelligent Algorithms and Nonlinear Damping
Authors: He Shuilong , Chen Keren , Xu Enyong , Wang Wei , Jiang Zhansi
Published: August 2019

The method chosen to conduct vehicle dynamic modeling has a significant impact on the evaluation and optimization of ride comfort. This paper summarizes the current modeling methods of ride comfort and their limitations. Then, models based on nonlinear damping and equivalent damping and the multibody dynamic model are developed and simulated in Matlab/Simulink and Adams/Car. The driver seat responses from these models are compared, showing that the accuracy of the ride comfort model based on nonlinear damping is higher than the one based on equivalent damping. To improve the reliability of ride comfort optimization and analysis, a ride comfort optimization method based on nonlinear damping and intelligent algorithms is proposed. The sum of the frequency‐weighted RMS of the driver seat acceleration, the RMS of dynamic tyre load, and suspension working space is taken as the objective function in this article, using nonlinear damping coefficients and stiffness of suspension as design variables. By applying the particle swarm optimization (PSO), cuckoo search (CS), dividing rectangles (DIRECT), and genetic algorithm (GA), a set of optimal solutions are obtained. The method efficiency is verified through a comparison between frequency‐weighted RMS before and after optimization. Results show that the frequency‐weighted RMS of driver seat acceleration, RMS values of the suspension working space of the front and rear axles, and RMS values of the dynamic tyre load of front and rear wheels are decreased by an average of 27.4%, 21.6%, 25.0%, 19.3%, and 22.3%, respectively. The developed model is studied in a pilot commercial vehicle, and the results show that the optimization method proposed in this paper is more practical and features improvement over previous models.
Heating Characteristics of Films Prepared with Polymer-Graphite Composites
Authors: Kim Seojin , Oh Weontae , Bae Jong-Seong , Yang Seong Baek , Yeum Jeong Hyun , Park Jaehyeung , Sung Choonghyun , Kim Jungsoo , Shin Jae-Cheon
Published: August 2019

Heating films were prepared by using poly(methyl methacrylate) and polybutadiene composites containing graphite. The heating film was prepared by casting the as-made polymer composite on the PET film. Copper electrodes were attached to both ends of the as-prepared film, and the heating characteristics of the film were analyzed while applying the DC voltage. The electrical conductivity and the heating temperature of the heating films depended on the size, the structure, the content, and the dispersion characteristics of the graphite in the composite. The electrical resistance of the heating film was controlled to adjust the heating temperature of the film. The relationship between the physical/chemical structure and the heating characteristics of the composite film was studied by measuring the heating temperature as functions of film thickness and resistance by using an infrared thermal imaging camera. The lower the film resistance, the higher the heating temperature of the film. The surface temperature was uniform throughout the film.
Management of Locally Advanced Esthesioneuroblastoma in a Pregnant Woman
Authors: Guerreiro Inês Maria , Vieira Cláudia , Soares André , Braga António , Jácome Manuel , Dinis José
Published: August 2019

Esthesioneuroblastoma (ENB) is a rare malignant tumor that commonly develops in the upper nasal cavity. Standard treatment is not established, especially in locally advanced disease which portends the worse prognosis. Hereby, we report a case of a 27-year-old, 23-week pregnant woman, with a 2-month history of progressively growing right cervical lymphadenopathy, nasal obstruction, anosmia, frequent episodes of epistaxis, and right frontal headache. Imagiological evaluation revealed a lesion with 7×5,2×3,2 cm in the nasal fossae with extension to the ethmoidal complex and right olfactive fend and invasion of the endocranial compartment associated with lymphadenopathy. The biopsy revealed a high-grade EBN. Neoadjuvant chemotherapy with cisplatin and etoposide was administrated during pregnancy and continued after delivery up to 6 cycles of treatment with partial response. Radiotherapy followed, with complete response. This case report is intended to highlight that a high grade of suspicion should be kept in the presence of nonspecific symptoms of nasal obstruction, anosmia, facial pain, and/or headache and focus that chemotherapy is an important component of a combined-treatment modality for locally advanced ENB that can be used during pregnancy in a lifesaving situation.
Development of Potentiometric Phenol Sensors by Nata de Coco Membrane on Screen-Printed Carbon Electrode
Authors: Mulyasuryani Ani , Mustaghfiroh Afifah Muhimmatul
Published: August 2019

Nata de coco, a bacterial cellulose as a result of coconut water fermentation, is a conductive polymer with a electrical conductivity of 553 μS/cm and has high mechanical stability. In this study, nata de coco was used as a supporting membrane for the development of phenol sensors in potentiometry. Nata de coco membrane containing phenol is coated on the surface of the printed carbon electrode (screen-printed carbon electrode). The cross-sectional area of the carbon electrode coated with the membrane is 1.5 × 3 mm2, while the reference electrode is Ag/AgCl. The thickness of the electrode membrane affects the Nernstian factor. The optimum Nernstian factor is produced by 100 μm membrane thickness containing 117.5 μg of phenol. Measurement of phenol solution was carried out at pH 11, in the concentration range of 10−8 to 10−2 mol/L, resulting in a Nernstian factor of 41.8 ± 1.3 mV/decade. The Nernstian factor increased to 55.7 ± 0.4 mV/decade if the membrane of the electrode contained 0.1% Fe3O4 nanoparticles. This sensor has been applied in the real sample of river water, resulting in good accuracy and precision.
Simulation and Optimization of Short Fiber Circumferential Orientation in Short-Fiber-Reinforced Composites Overflow Water-Assisted Injection Molded Tube
Authors: Zhou Haiying , Liu Hesheng , Kuang Tangqing , Jiang Qingsong , Chen Zhixin , Li Weiping
Published: August 2019

The mechanical properties of the water-assisted injection molded tube can be enhanced by the increase in the short fiber circumferential orientation (SFCO). Thus, the numerical method verified by experiments is used to simulate the SFCO distribution in the overflow water-assisted injection molding (OWAIM), with the mechanism of short fiber orientation analyzed as well. The effect of parameters (filling time, melt temperature, mold temperature, delay time, water pressure, and water temperature) on the SFCO is explored by range analysis and variance analysis of the orthogonal experimental scheme. Moreover, both of artificial neural network (ANN) and genetic algorithm (GA) are used to model and optimize process parameters. Results show that the melt temperature, delay time, and water pressure are predominant parameters. The evolution of SFCO increases with the increase of melt temperature and water pressure, whereas the changes in delay time reverse. The value of the maximum SFCO tensor obtained by GA optimization is found to be 0.234.
Mathematical Modeling to Study Multistage Stem Cell Transplantation in HIV-1 Patients
Authors: Qudah Manar A. Al , Zarea Sana’a A. , Kallel-Jallouli Saoussan A.
Published: August 2019

Stem cells as a therapeutic measure for the treatment of different diseases have a great potential to give rise to different mature cells as they could be used to treat HIV-1 patients when provided with the convenient factors. Thus, this paper proposes a new mathematical model, represented by a system of ODEs, to study the effect of stem cell transplantation for HIV-1 patients. Since stem cells lineage passes through many stages to become more specialized cell types, investigating (theorizing) the best stage for these cells to be engrafted was needed. The proposed system of ODEs can help medicine make the right decision about the proposed therapy.
Outsourcing Computing of Large Matrix Jordan Decomposition
Authors: Wu Hongfeng , Yan Jingjing
Published: August 2019

The Jordan decomposition of matrix is a typical scientific and engineering computational task, but such computation involves enormous computing resources for large matrices, which is burdensome for the resource‐limited clients. Cloud computing enables computational resource‐limited clients to economically outsource such problems to the cloud server. However, outsourcing Jordan decomposition of large‐scale matrix to the cloud brings great security concerns and challenges since the matrices usually contain sensitive information. In this paper, we present a secure, verifiable, efficient, and privacy preserving algorithm for outsourcing Jordan decomposition of large‐scale matrix. Security analysis shows that our algorithm is practically secure. Efficient verification algorithm is used to verify the results returned from the cloud.
Hypergraph Regularized Discriminative Nonnegative Matrix Factorization on Sample Classification and Co‐Differentially Expressed Gene Selection
Authors: Hao Yong-Jing , Gao Ying-Lian , Hou Mi-Xiao , Dai Ling-Yun , Liu Jin-Xing
Published: August 2019

Nonnegative Matrix Factorization (NMF) is a significant big data analysis technique. However, standard NMF regularized by simple graph does not have discriminative function, and traditional graph models cannot accurately reflect the problem of multigeometry information between data. To solve the above problem, this paper proposed a new method called Hypergraph Regularized Discriminative Nonnegative Matrix Factorization (HDNMF), which captures intrinsic geometry by constructing hypergraphs rather than simple graphs. The introduction of the hypergraph method allows high‐order relationships between samples to be considered, and the introduction of label information enables the method to have discriminative effect. Both the hypergraph Laplace and the discriminative label information are utilized together to learn the projection matrix in the standard method. In addition, we offered a corresponding multiplication update solution for the optimization. Experiments indicate that the method proposed is more effective by comparing with the earlier methods.
Implementation of HPV-based Cervical Cancer Screening Combined with Self-sampling Using a Midwifery Network Across Rural Greece: The GRECOSELF Study
Authors: Agorastos Theodoros , Chatzistamatiou Kimon , Tsertanidou Athena , Mouchtaropoulou Evangelia , Pasentsis Konstantinos , Kitsou Anastasia , Moysiadis Theodoros , Moschaki Viktoria , Skenderi Alkmini , Katsiki Evangelia , Aggelidou Stamatia , Venizelos Ioannis , Ntoula Maria , Daponte Alexandros , Vanakara Polyxeni , Garas Antonios , Stefos Theodoros , Vrekoussis Thomas , Lymberis Vasilis , Kontomanolis Emmanuel N. , Makrigiannakis Antonis , Manidakis George , Deligeoroglou Efthimios , Panoskaltsis Theodoros , Decavalas George O. , Michail George , Kalogiannidis Ioannis , Koukoulis George , Zempili Paraskevi , Halatsi Despina , Truva Theoni , Piha Vaia , Agelena Georgia , Chronopoulou Athanasia , Vaitsi Violetta , Chatzaki Ekaterini , Paschopoulos Minas , Adonakis George , Kaufmann Andreas M. , Hadzidimitriou Anastasia , Stamatopoulos Kostas
Published: August 2019

Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25–29 years to 5.1% for women aged 50–60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25–29) to 76.3% (for women 40–49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.
Pegadas dos alimentos e das preparações culinárias consumidos no Brasil
Authors:   Universidade de São Paulo. Faculdade de Saúde Pública, Garzillo Josefa Maria Fellegger , Machado Priscila Pereira ,   Universidade de São Paulo. Faculdade de Saúde Pública, Louzada Maria Laura da Costa ,   Universidade Federal de São Paulo, Levy Renata Bertazzi ,   Universidade de São Paulo. Faculdade de Medicina, Monteiro Carlos Augusto ,   Universidade de São Paulo. Faculdade de Saúde Pública
Published: August 2019

Os vestígios ou rastros de degradação ambiental mensuráveis que marcam a passagem descuidada do ser humano pela Terra são chamados de pegadas. Este livro traz a tabela com as pegadas de carbono, hídrica e ecológica dos alimentos e preparações culinárias consumidos no Brasil, ferramenta desenvolvida para viabilizar os estudos da tese “A alimentação e seus impactos ambientais: abordagens dos guias alimentares nacionais e estudo da dieta dos brasileiros”. O livro se diferencia da tese pela inclusão de um indicador a mais (pegada ecológica), pelo formato em que as tabelas são apresentadas e a descrição de conceitos básicos e dos processos metodológicos, incentivando os pesquisadores que ingressarão no campo das avaliações dos impactos ambientais da alimentação com base na Pesquisa de Orçamentos Familiares do IBGE. Procurou-se explicar, de modo simples e objetivo, os temas de nutrição para quem é atuante na área ambiental e os temas ambientais para os pesquisadores da nutrição, facilitando a comunicação e os arranjos em trabalhos interdisciplinares.