bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring and understanding the scope and value of the Parkinson’s nurse in the UK (The USP Project): a realist economic evaluation protocol
Authors: Brown Sarah , Dalkin Sonia Michelle , Bate Angela , Bradford Russ , Allen Charlotte , Brittain Katie , Clarke Amanda , Hand Annette
Published: October 2020

Introduction

There are multiple configurations of specialist nurses working in the field of Parkinson’s. Parkinson’s Nurse Specialists (PNSs) are recognised as playing a pivotal role; however, there is little published evidence to demonstrate their effectiveness. Further evidence is needed to establish which aspects of the PNSs provide the greatest benefit to people with Parkinson’s and their families, and the cost-effectiveness of different models of care.

Methods and analysis

Realist approaches explain how and why programmes work (or not) through striving to answer the question: what works, for whom and under what circumstances. This research uses a realist evaluation and aims to integrate an economic analysis within the realist framework. We refer to this as ‘realist economic evaluation’. It comprises four phases: (1) developing resource-sensitive initial programme theories (IPTs) using surveys to gain a better understanding of the role and impact (costs and benefits) of the PNSs; (2) testing the IPTs through qualitative interviews and quantitative data analysis; (3) evaluating the cost and resource use implications alongside the benefits associated with the role of the PNSs and (4) iteratively refining the IPTs throughout the project. The IPTs will draw on both quantitative and qualitative data. The result of the study will be a series of refined programme theories, which will explain how specialist nurses work in the field of Parkinson’s in the UK, what impact they have on people with Parkinson’s and their families and carers, and at what cost.

Ethics and dissemination

Northumbria University, the Health Research Authority and Health and Care Research Wales have approved this study. Key findings will be disseminated throughout the duration of the project online and through social media, and via annual and regional Parkinson’s meetings and the Parkinson’s UK Excellence Network. Academic dissemination will occur through publication and conference presentations.
Factors associated with non-initiation of mental healthcare after detection of poor mental health at a scheduled health check: a cohort study
Authors: Geyti Christine , Christensen Kaj Sparle , Dalsgaard Else-Marie , Bech Bodil Hammer , Gunn Jane , Maindal Helle Terkildsen , Sandbaek Annelli
Published: October 2020

Introduction

Poor mental health is an important public health concern, but mental health problems are often under-recognised. Providing feedback to general practitioners (GPs) on their patients’ mental health status may improve the identification of cases in need of mental healthcare.

Objectives

To investigate the extent of initiation of mental healthcare after identification of poor mental health and to identify factors associated with non-initiation.

Design

Prospective cohort study with 1-year follow-up.

Setting

In a population-based health preventive programme, Check Your Health, we conducted a combined mental and physical health check in Randers Municipality, Denmark, in 2012–2015 in collaboration with local GPs.

Participants

Participants were 350 individuals aged 30–49 years old with screen-detected poor mental health who had not received mental healthcare within the past year. The cohort was derived from 14 167 randomly selected individuals of whom 52% (n=7348) participated. Mental health was assessed by the mental component summary score of the 12-item Short-Form Health Survey.

Outcome

The outcome was initiation of mental healthcare. Mental healthcare included psychometric testing by GP, talk therapy by GP, contact with a psychologist, contact with a psychiatrist and psychotropic medication.

Results

Within 1 year, 22% (95% CI 18 to 27) of individuals with screen-detected poor mental health initiated mental healthcare. Among individuals who initiated mental healthcare within follow-up, one in six had visited their GP once or less in the preceding year. Male sex (OR: 0.49 (95% CI 0.28 to 0.86)) and less impaired mental health (OR: 0.93 (95% CI 0.89 to 0.98)) were associated with non-initiation of mental healthcare. We found no overall association between socioeconomic factors and initiating mental healthcare.

Conclusion

Systematic provision of mental health test results to GPs may improve the identification of cases in need of mental healthcare, but does not translate into initiation of mental healthcare. Further research should focus on methods to improve initiation of mental healthcare, especially among men.

Trial registration number

NCT02028195.
Uptake and effectiveness of a tailor-made online lifestyle programme targeting modifiable risk factors for dementia among middle-aged descendants of people with recently diagnosed dementia: study protocol of a cluster randomised controlled trial (Demin study)
Authors: Vrijsen Joyce , Abu-Hanna Ameen , Maeckelberghe Els LM , De Deyn Peter Paul , de Winter Andrea F , Reesink Fransje E , Oude Voshaar Richard C , Buskens Erik , de Rooij Sophia E , Smidt Nynke
Published: October 2020

Introduction

Descendants of patients with dementia have a higher risk to develop dementia. This study aims to investigate the uptake and effectiveness of an online tailor-made lifestyle programme for dementia risk reduction (DRR) among middle-aged descendants of people with recently diagnosed late-onset dementia.

Methods and analysis

Demin is a cluster randomised controlled trial, aiming to include 21 memory clinics of which 13 will be randomly allocated to the passive (poster and flyer in a waiting room) and 8 to the active recruitment strategy (additional personal invitation by members of the team of the memory clinic). We aim to recruit 378 participants (40–60 years) with a parent who is recently diagnosed with Alzheimer’s disease or vascular dementia at one of the participating memory clinics. All participants receive a dementia risk assessment (online questionnaire, physical examination and blood sample) and subsequently an online tailor-made lifestyle advice regarding protective (Mediterranean diet, low/moderate alcohol consumption and high cognitive activity) and risk factors (physical inactivity, smoking, loneliness, cardiovascular diseases (CVD), hypertension, high cholesterol, diabetes, obesity, renal dysfunction and depression) for dementia. The primary outcome is the difference in uptake between the two recruitment strategies. Secondary outcomes are change(s) in (1) the Lifestyle for Brain Health score, (2) individual health behaviours, (3) health beliefs and attitudes towards DRR and (4) compliance to the tailor-made lifestyle advice. Outcomes will be measured at 3, 6, 9 and 12 months after baseline. The effectiveness of this online tailor-made lifestyle programme will be evaluated by comparing Demin participants to a matched control group (lifelines cohort).

Ethics and dissemination

This study has been approved by the Dutch Ministry of Health, Welfare and Sport according to the Population Screening Act. All participants have to give online informed consent using SMS-tan (transaction authentication number delivered via text message). Findings will be disseminated through peer-reviewed journals and (inter)national conferences.

Trial registration number

NTR7434.
Perceived barriers and facilitators to chronic kidney disease care among patients in Singapore: a qualitative study
Authors: Hwang Sun Joon , Tan Ngiap Chuan , Yoon Sungwon , Ramakrishnan Chandrika , Paulpandi Muthulakshmi , Gun Shihying , Lee Jia Ying , Chang Zi Ying , Jafar Tazeen H
Published: October 2020

Objective

To outline the facilitators and barriers to patients’ self-management of predialysis chronic kidney disease (CKD).

Design

Qualitative.

Setting

Three polyclinics in a public primary care institution in Singapore.

Participants

20 patients entered and completed the study. Inclusion criteria were: (1) English speaking, (2) aged 40 years and above, (3) identified by clinical coding as ‘DM (diabetes mellitus) nephropathy-overt’ and ‘DM nephropathy-incipient’, by their physicians in the polyclinic, with an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 (based on electronic health records) and (4) aware of their CKD illness. Exclusion criteria were: (1) receiving dialysis or had received a kidney transplant, (2) suffered from any visual, auditory or cognitive impairment which could hinder their ability to participate in the study or (3) pregnant.

Results

We found that the major barriers to CKD management were a lack of knowledge and awareness of CKD, a passive attitude toward self-management and insufficient patient-physician communication. Major facilitators included patient trust and satisfaction with the physician and family support. Many patients reported that there was an overload of information and too little guidance on how to manage their condition, especially regarding dietary recommendations.

Conclusion

We identified several barriers and facilitators to the management of predialysis CKD among patients. A multi-pronged approach for raising CKD awareness is required: improving patient-physician communication, implementing CKD workshops and home-visits and disseminating accurate online information about CKD. Strategies should also focus on increasing patient engagement and optimising family support by involving family members in patients’ care. Furthermore, clear dietary recommendations and patient-specific advice are needed to empower patients to manage their own condition.
Inflammatory bowel disease and Parkinson’s disease: common pathophysiological links
Authors: Lee Ho-Su , Lobbestael Evy , Vermeire Séverine , Sabino João , Cleynen Isabelle
Published: October 2020

Inflammatory bowel disease and Parkinson’s disease are chronic progressive disorders that mainly affect different organs: the gut and brain, respectively. Accumulating evidence has suggested a bidirectional link between gastrointestinal inflammation and neurodegeneration, in accordance with the concept of the ‘gut–brain axis’. Moreover, recent population-based studies have shown that inflammatory bowel disease might increase the risk of Parkinson's disease. Although the precise mechanisms underlying gut–brain interactions remain elusive, some of the latest findings have begun to explain the link. Several genetic loci are shared between both disorders with a similar direction of effect on the risk of both diseases. The most interesting example is LRRK2 (leucine-rich repeat kinase 2), initially identified as a causal gene in Parkinson's disease, and recently also implicated in Crohn’s disease. In this review, we highlight recent findings on the link between these seemingly unrelated diseases with shared genetic susceptibility. We discuss supporting and conflicting data obtained from epidemiological and genetic studies along with remaining questions and concerns. In addition, we discuss possible biological links including the gut–brain axis, microbiota, autoimmunity, mitochondrial function and autophagy.
Socioeconomic characteristics of patients with coronary heart disease in relation to their cardiovascular risk profile
Authors: De Bacquer Dirk , van de Luitgaarden Inge A T , De Smedt Delphine , Vynckier Pieter , Bruthans Jan , Fras Zlatko , Jankowski Piotr , Dolzhenko Marina , Kotseva Kornelia , Wood David , De Backer Guy
Published: October 2020

Objective

People’s socioeconomic status (SES) has a major impact on the risk of atherosclerotic cardiovascular disease (ASCVD) in primary prevention. In patients with existing ASCVD these associations are less documented. Here, we evaluate to what extent SES is still associated with patients’ risk profile in secondary prevention.

Methods

Based on results from a large sample of patients with coronary heart disease from the European Action on Secondary and Primary Prevention through Intervention to Reduce Events study, the relationship between SES and cardiovascular risk was examined. A SES summary score was empirically constructed from the patients’ educational level, self-perceived income, living situation and perception of loneliness.

Results

Analyses are based on observations in 8261 patients with coronary heart disease from 27 countries. Multivariate logistic regression analyses demonstrate that a low SES is associated (OR, 95% CI) with lifestyles such as smoking in men (1.63, 1.37 to 1.95), physical activity in men (1.51, 1.28 to 1.78) and women (1.77, 1.32 to 2.37) and obesity in men 1.28 (1.11 to 1.49) and women 1.65 (1.30 to 2.10). Patients with a low SES have more raised blood pressure in men (1.24, 1.07 to 1.43) and women (1.31, 1.03 to 1.67), used less statins and were less adherent to them. Cardiac rehabilitation programmes were less advised and attended by patients with a low SES. Access to statins in middle-income countries was suboptimal leaving about 80% of patients not reaching the low-density lipoprotein cholesterol target of <1.8 mmol/L. Patients’ socioeconomic level was also strongly associated with markers of well-being.

Conclusion

These results illustrate the complexity of the associations between SES, well-being and secondary prevention in patients with ASCVD. They emphasise the need for integrating innovative policies in programmes of cardiac rehabilitation and secondary prevention.
Shift in racial communities impacted by COVID-19 in California
Authors: Cuomo Raphael E
Published: October 2020

Introduction

Since the first case of COVID-19 was recorded in California, the geospatial distribution of disease cases has fluctuated over time. Given documented racial disparities in other parts of the country, longitudinal convergence of COVID-19 rates around race groups warrants assessment.

Methods

County-level cases for COVID-19 were collected from the Johns Hopkins University, and racial distributions were collected from the American Community Survey. Pearson’s correlation coefficients were computed for each day since COVID-19 was first reported in California, and the longitudinal distribution of each race-specific set of correlation coefficients was assessed for stationarity, linear trend and exponential trend.

Results

Earlier in the outbreak, the distribution of COVID-19 was most highly correlated with Asian American communities; after approximately 100 days, the distribution of COVID-19 most closely resembled that of African American communities. For every day in this dataset, the county-level distribution of COVID-19 was negatively correlated with the distribution of White American communities in California.

Discussion

The geospatial distribution of COVID-19 in California has increasingly resembled that of African American communities within the state. Further study should be conducted to characterise potentially disproportionate impacts of the COVID-19 pandemic across race groups.
Stay at home: implementation and impact of virtualising cancer genetic services during COVID-19
Authors: Norman Maia Leigh , Malcolmson Janet , Randall Armel Susan , Gillies Brittany , Ou Brian , Thain Emily , McCuaig Jeanna Marie , Kim Raymond H
Published: October 2020

The COVID-19 pandemic has led to the rapid adoption of virtual clinic processes and healthcare delivery. Herein, we examine the impact of virtualising genetics services at Canada’s largest cancer centre. A retrospective review was conducted to evaluate relevant metrics during the 12 weeks prior to and during virtual care, including referral and clinic volumes, patient wait times and genetic testing uptake. The number of appointments and new patients seen were maintained during virtual care. Likewise, there was a significant increase in the number of patients offered testing during virtual care who did not provide a blood sample (176/180 (97.7%) vs 180/243 (74.1%); p<0.001), and a longer median time from the date of pretest genetic counselling to the date a sample was given (0 vs 11 days; p<0.001). Referral volumes significantly decreased during virtual care (35 vs 22; p<0.001), which was accompanied by a decreased median wait time for first appointment (55 days vs 30 days; p<0.001). The rapid virtualisation of cancer genetic services allowed the genetics clinic to navigate the COVID-19 pandemic without compromising clinical volumes or access to genetic testing. There was a decrease in referral volumes and uptake of genetic testing, which may be attributable to pandemic-related clinical restrictions.
Prunus persica9, a new occupational allergen from peach tree pollen involved in rhinitis and asthma
Authors: Victorio-Puche Laura , Somoza Maria Luisa , Martin-Pedraza Laura , Fernandez-Caldas Enrique , Abel Fernandez Eva , Moran Mirian , Subiza Jose Luis , Lopez-Sanchez Jose Damian , Villalba Mayte , Blanca Miguel
Published: October 2020

Objectives

Several studies have described peach tree (PT) as an occupational allergen. The aim of this work was to assess the effect ofPrunus persica9 (Pru p 9), a recently identified allergen from PT pollen, in exposed workers.

Methods

The study included people who reported respiratory symptoms after handling PT in orchards during the flowering period (Blanca village, Murcia region, south-east Spain). After completing a detailed questionnaire, participants underwent skin prick test (SPT) and nasal provocation test (NPT). The IgE response was analysed by SDS-PAGE and immunoblotting assays.

Results

A total of 21 cases were included (mean age 45 years; 57% women). Most were polysensitised to common pollens, although one person was sensitised only to PT pollen. All cases had a positive SPT to this pollen, and 43% also to Pru p 9. All participants reported having rhinitis, and six participants reported having also asthma. Immunoblotting showed a heterogeneous IgE pattern for several proteins, with Pru p 9 recognised in nine cases. Most participants sensitised to PT pollen and Pru p 9 had positive NPTs, while those who were not sensitised to Pru p 9 tested negative.

Conclusions

We demonstrate for the first time that Pru p 9, an allergen from PT pollen, can induce respiratory symptoms following occupational exposure. This must be considered a relevant allergen when people working with PT cultivars develop respiratory symptoms.
Exogenous nitrogen uptake and allocation in chestnut
Authors: Xu Cheng , Guo Sujuan , Wang Jing
Published: October 2020

Yield and quality of chestnut (Castanea mollissima Blume) are affected by nitrogen (N) availability; however, there are few reports on foliar and root absorption of different chemical forms of N in chestnut. To analyze the absorption characteristics of exogenous N fertilizer labeled by 15N in chestnut, nitrate and ammonium nitrogen uptake and allocation were determined in 1-yr-old seedlings that received soil and foliar 15NH4NO3 and NH415NO3. We found that 29% of the nitrate and 25% of the ammonium absorbed by the leaves were translocated to the roots, while 62.01% of the nitrate and 63.27% of the ammonium absorbed by the roots were translocated to the shoots. The seedlings absorbed more nitrate nitrogen than ammonium nitrogen, and their foliar N uptake was faster than their root uptake. Most of the N absorbed by the seedlings was fixed in the shoots in both foliar and soil uptake. The proportion of N fixed was greater in seedlings subjected to foliar fertilization than in those treated with soil fertilizer. Foliar fertilizer application can meet the N nutritional needs of fast-growing shoots more effectively than soil fertilizer application; however, soil fertilization was a better long-term N source than foliar fertilization. Thus, ensuring an adequate supply of nitrate N fertilizer in the soil accompanied by a commensurate increase in foliar fertilizer application can effectively meet the nutrient requirements associated with the rapid growth of chestnut seedling shoots.
Yet Another Tensor Toolbox for Discontinuous Galerkin Methods and Other Applications
Authors: Uphoff Carsten , Bader Michael
Published: October 2020

The numerical solution of partial differential equations is at the heart of many grand challenges in supercomputing. Solvers based on high-order discontinuous Galerkin (DG) discretisation have been shown to scale on large supercomputers with excellent performance and efficiency if the implementation exploits all levels of parallelism and is tailored to the specific architecture. However, every year new supercomputers emerge and the list of hardware-specific considerations grows simultaneously with the list of desired features in a DG code. Thus, we believe that a sustainable DG code needs an abstraction layer to implement the numerical scheme in a suitable language. We explore the possibility to abstract the numerical scheme as small tensor operations, describe them in a domain-specific language (DSL) resembling the Einstein notation, and to map them to small General Matrix-Matrix Multiplication routines. The compiler for our DSL implements classic optimisations that are used for large tensor contractions, and we present novel optimisation techniques such as
equivalent sparsity patterns
and optimal index permutations for temporary tensors. Our application examples, which include the earthquake simulation software SeisSol, show that the generated kernels achieve over 50% peak performance of a recent 48-core Skylake system while the DSL considerably simplifies the implementation.
A Shift Selection Strategy for Parallel Shift-invert Spectrum Slicing in Symmetric Self-consistent Eigenvalue Computation
Authors: Williams-Young David B. , Beckman Paul G. , Yang Chao
Published: October 2020

The central importance of large-scale eigenvalue problems in scientific computation necessitates the development of massively parallel algorithms for their solution. Recent advances in dense numerical linear algebra have enabled the routine treatment of eigenvalue problems with dimensions on the order of hundreds of thousands on the world’s largest supercomputers. In cases where dense treatments are not feasible, Krylov subspace methods offer an attractive alternative due to the fact that they do not require storage of the problem matrices. However, demonstration of scalability of either of these classes of eigenvalue algorithms on computing architectures capable of expressing massive parallelism is non-trivial due to communication requirements and serial bottlenecks, respectively. In this work, we introduce the SISLICE method: a parallel shift-invert algorithm for the solution of the symmetric self-consistent field (SCF) eigenvalue problem. The SISLICE method drastically reduces the communication requirement of current parallel shift-invert eigenvalue algorithms through various shift selection and migration techniques based on density of states estimation and k-means clustering, respectively. This work demonstrates the robustness and parallel performance of the SISLICE method on a representative set of SCF eigenvalue problems and outlines research directions that will be explored in future work.
Review of COVID-19 Antibody Therapies
Authors: Chen Jiahui , Gao Kaifu , Wang Rui , Nguyen Duc Duy , Wei Guo-Wei
Published: October 2020

In the global health emergency caused by coronavirus disease 2019 (COVID-19), efficient and specific therapies are urgently needed. Compared with traditional small-molecular drugs, antibody therapies are relatively easy to develop; they are as specific as vaccines in targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); and they have thus attracted much attention in the past few months. This article reviews seven existing antibodies for neutralizing SARS-CoV-2 with 3D structures deposited in the Protein Data Bank (PDB). Five 3D antibody structures associated with the SARS-CoV spike (S) protein are also evaluated for their potential in neutralizing SARS-CoV-2. The interactions of these antibodies with the S protein receptor-binding domain (RBD) are compared with those between angiotensin-converting enzyme 2 and RBD complexes. Due to the orders of magnitude in the discrepancies of experimental binding affinities, we introduce topological data analysis, a variety of network models, and deep learning to analyze the binding strength and therapeutic potential of the 14 antibody–antigen complexes. The current COVID-19 antibody clinical trials, which are not limited to the S protein target, are also reviewed.
Highly Reversible Plating/Stripping of Porous Zinc Anodes for Multivalent Zinc Batteries
Authors: Ko Jesse S. , Bishop Kelly , Seitzman Natalie , Chen Bor-Rong , Toney Michael F. , Nelson Weker Johanna
Published: October 2020

Zinc continues to garner immense interest due to its versatility as an anode material in several configurations utilizing either alkaline or mild-pH electrolytes. Current research on using mild-pH electrolytes has improved the rechargeability aspect of Zn-based batteries since Zn2+ is solely utilized for plating/stripping of Zn. Several studies have incorporated Zn metal foils, yet, dramatic improvements can be achieved by expressing Zn as a porous structure. Herein, we use a quasi-pulsed electrodeposition process to prepare a conformal Zn coating onto 3D porous copper foam. By tuning the electrodeposition parameters, we achieved an optimal Zn coating that undergoes reversible plating/stripping when tested in symmetric Zn cells, which supported a low overpotential of ∼60 mV for up to 100 cycles. We further investigated changes in the surface morphology by studying the Zn surface of both foil and 3D structure using scanning electron microscopy and X-ray micro-computed tomography. Both techniques showed that the Zn foil undergoes dramatic alterations at the surface, which results in inhomogeneous deposition of Zn, whereas the 3D form exhibited minimal changes. Lastly, we paired both Zn foil and 3D Zn with vanadium oxide and demonstrated that the porous structure supports high rate capability and high specific capacity.
Temperature Influence on Organic Molecular Interaction on Silicon Oxide Surface In Situ Measured Utilizing a Quartz Crystal Microbalance
Authors: Hori Kenta , Zhou Yifan , Kanai Tomohiko , Habuka Hitoshi
Published: October 2020

The influence of temperature on the molecular interaction between diethylphthalate (DEP) and L-Menthone (Mth) on a silicon native oxide surface was in situ real time evaluated utilizing a quartz crystal microbalance. By increasing the temperature from 25 °C to 35 °C in a single component system, the physisorption and desorption rate constants of DEP increased, while those of Mth showed significantly small changes. Simultaneously, the surface concentrations of DEP and Mth decreased with the increasing temperatures. In the two-component system, the surface concentration was measured by alternatively changing gas phase concentrations of DEP and Mth in order to evaluate whether it irreversibly or reversibly changed. Because the surface concentration change was irreversible at 25 °C, the molecular interaction between the DEP and Mth was considered to exist. In contrast, the change became reversible with the increasing temperature to produce a negligible molecular interaction between them. Such a behavior change occurred in the temperature range less than 10 °C. The low surface concentration by the increasing temperature was considered to weaken the attractive molecular interaction.
Acute effects of transcatheter aortic valve replacement on the ventricular-aortic interaction
Authors: Pagoulatou Stamatia , Stergiopulos Nikolaos , Bikia Vasiliki , Rovas Georgios , Licker Marc-Joseph , Müller Hajo , Noble Stéphane , Adamopoulos Dionysios
Published: October 2020

Transcatheter aortic valve replacement (TAVR) is linked with an immediate increase in aortic systolic blood pressure and maximal flow, as well as steeper aortic pressure and flow wave upstrokes. After TAVR, the forward wave pumped by the heart is enhanced. Although the arterial properties remain unchanged, the central augmentation index (AIx) is markedly decreased after TAVR. This challenges the interpretation of AIx as a solely vascular measure in patients with aortic valve stenosis.
A Dynamic Stackelberg–Cournot Duopoly Model with Heterogeneous Strategies through One-Way Spillovers
Authors: Long Jianjun , Huang Hui
Published: October 2020

Many works studied on complex dynamics of Cournot or Stackelberg games, but few references discussed a dynamic game model combined with the Cournot game phase and Stackelberg game phase. Under the assumption that R&D spillovers only flow from the R&D leader to the R&D follower, a duopoly Stackelberg–Cournot game with heterogeneous expectations is considered in this paper. Two firms with different R&D capabilities determine their R&D investments sequentially in the Stackelberg R&D phase and make output decisions simultaneously in the Cournot production phase. R&D spillovers, R&D investments, and technological innovation efficiency are introduced in our model. We find that: (i) the boundary equilibrium of the dynamic Stackelberg–Cournot duopoly system, where two players adopt boundedly rational expectation and naïve expectation, respectively, is unstable if the Nash equilibrium of the system is strictly positive. (ii) The Nash equilibrium of the dynamic Stackelberg–Cournot duopoly system, where two players adopt boundedly rational expectation and naïve expectation, respectively, is locally asymptotically stable only if the model parameters meet certain conditions. Especially, results indicate that small value of R&D spillovers or big value of output adjustment speed may yield bifurcations or even chaos. Numerical simulations are performed to exhibit maximum Lyapunov exponents, bifurcation diagrams, strange attractors, and sensitive dependence on initial conditions to verify our findings. It is also shown that the chaotic behaviors can be controlled with the state variables feedback and parameter variation method.
Significance of Detection of the HER2 Gene and PD-1/PD-L1 in Gastric Cancer
Authors: Yun Tian , Wang Sunan , Jiang Bo , Wang Changsong , Meng Nianlong , Yuan Xutao , Wang Yangkun
Published: October 2020

Objective. To explore the relationship between the HER2 gene and PD-1/PD-L1 in gastric cancer and its significance. Methods. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to detect HER2 protein expression, HER2 gene amplification, and PD-1/PD-L1 expression in 78 cases of gastric cancer. Results. The expression rate of HER2 protein was 43.6% (34/78), of which 19.4% (14/78) were HER2 3+, 14.1% (11/78) were HER2 2+, and 11.5% (9/78) were HER2 1+. The results showed that 19.2% (15/78) of samples had HER2 gene amplification, 3.8% (3/78) of samples had a HER2/CEP17 ratio <2.0, and 19.2% (15/78) of samples had HER2 gene amplificationf and HER2 copy/cell ≥6.0, as detected by FISH. The positive rate of PD-L1 was 38.5% (30/78) in gastric cancer cells and 50.0% (39/78) in interstitial lymphocytes. The expression of the HER2 gene, PD-L1, and PD-1 in gastric cancer was correlated with the stage and lymph node metastasis of gastric cancer (

P
<
0.05

). Conclusions. The combined detection of the HER2 gene and PD-1/PD-L1 in gastric cancer provides an important reference index for the prognosis of gastric cancer and the benefit of targeted antitumor drugs.
Effects of DMSO on the Pluripotency of Cultured Mouse Embryonic Stem Cells (mESCs)
Authors: Sousa Maria Inês , Correia Bibiana , Branco Ana Filipa , Rodrigues Ana Sofia , Ramalho-Santos João
Published: October 2020

DMSO is a commonly used solvent in biological studies, as it is an amphipathic molecule soluble in both aqueous and organic media. For that reason, it is the vehicle of choice for several water-insoluble substances used in research. At the molecular and cellular level, DMSO is a hydrogen-bound disrupter, an intercellular electrical uncoupler, and a cryoprotectant, among other properties. Importantly, DMSO often has overlooked side effects. In stem cell research, the literature is scarce, but there are reports on the effect of DMSO in human embryoid body differentiation and on human pluripotent stem cell priming towards differentiation, via modulation of cell cycle. However, in mouse embryonic stem cell (mESC) culture, there is almost no available information. Taking into consideration the almost ubiquitous use of DMSO in experiments involving mESCs, we aimed to understand the effect of very low doses of DMSO (0.0001%-0.2%), usually used to introduce pharmacological inhibitors/modulators, in mESCs cultured in two different media (2i and FBS-based media). Our results show that in the E14Tg2a mESC line used in this study, even the smallest concentration of DMSO had minor effects on the total number of cells in serum-cultured mESCs. However, these effects could not be explained by alterations in cell cycle or apoptosis. Furthermore, DMSO did not affect pluripotency or differentiation potential. All things considered, and although control experiments should be carried out in each cell line that is used, it is reasonable to conclude that DMSO at the concentrations used here has a minimal effect on this particular mESC line.
THBS2/CA19-9 Detecting Pancreatic Ductal Adenocarcinoma at Diagnosis Underperforms in Prediagnostic Detection: Implications for Biomarker Advancement
Authors: Udgata Shirsa , Takenaka Naomi , Bamlet William R. , Oberg Ann L. , Yee Stephanie S. , Carpenter Erica L. , Herman Daniel , Kim Jungsun , Petersen Gloria M. , Zaret Kenneth S.
Published: October 2020

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed too late for effective therapy. The classic strategy for early detection biomarker advancement consists of initial retrospective phases of discovery and validation with tissue samples taken from individuals diagnosed with disease, compared with controls. Using this approach, we previously reported the discovery of a blood biomarker panel consisting of thrombospondin-2 (THBS2) and CA19-9 that together could discriminate resectable stage I and IIa PDAC as well as stages III and IV PDAC, with c-statistic values in the range of 0.96 to 0.97 in two phase II studies. We now report that in two studies of blood samples prospectively collected from 1 to 15 years prior to a PDAC diagnosis (Mayo Clinic and PLCO cohorts), THBS2 and/or CA19-9 failed to discriminate cases from healthy controls at the AUC = 0.8 needed. We conclude that PDAC progression may be heterogeneous and for some individuals can be more rapid than generally appreciated. It is important that PDAC early-detection studies incorporate high-risk, prospective prediagnostic cohorts into discovery and validation studies.

Prevention Relevance: A blood biomarker panel of THBS2 and CA19-9 detects early stages of pancreatic ductal adenocarcinoma at diagnosis, but not when tested across a population up to 1 year earlier. Our findings suggest serial sampling over time, using prospectively collected samples for biomarker discovery, and more frequent screening of high-risk individuals.
Metastatic Squamous Cell Carcinoma of the Tonsil Mimicking Choroidal Melanoma
Authors: Binkley Elaine M. , Sampson Aron D. , Syed Nasreen A. , Boldt H. Culver
Published: October 2020

We describe a case of a 53-year-old man with a history of metastatic squamous cell carcinoma of the tonsil who presented with a large, dome-shaped, choroidal mass in the left eye with concern for extra-ocular extension. Standardized echography showed a choroidal mass with low-to-medium internal reflectivity, pockets of very low reflectivity, positive angle kappa, and 1+ vascularity that were concerning for primary choroidal melanoma. Biopsy of the lesion was consistent with metastatic squamous cell carcinoma of the tonsil rather than melanoma. This is only the second reported case of metastatic squamous cell carcinoma to the choroid presenting with a large vascular tumor with echographic characteristics consistent with choroidal melanoma. The unique vascularity present in some cases of squamous cell carcinoma of the tonsil may explain the vascularity and large height of this patient’s lesion. Tumor fine-needle aspiration biopsy can play an important role in patients with choroidal lesions in the setting of unusual primary tumors.
GPR68 Is a Neuroprotective Proton Receptor in Brain Ischemia
Authors: Wang Tao , Zhou Guokun , He Mindi , Xu Yuanyuan , Rusyniak W.G. , Xu Yan , Ji Yonghua , Simon Roger P. , Xiong Zhi-Gang , Zha Xiang-ming
Published: October 2020

Background and Purpose:

Brain acidosis is prevalent in stroke and other neurological diseases. Acidosis can have paradoxical injurious and protective effects. The purpose of this study is to determine whether a proton receptor exists in neurons to counteract acidosis-induced injury.

Methods:

We analyzed the expression of proton-sensitive GPCRs (G protein-coupled receptors) in the brain, examined acidosis-induced signaling in vitro, and studied neuronal injury using in vitro and in vivo mouse models.

Results:

GPR68, a proton-sensitive GPCR, was present in both mouse and human brain, and elicited neuroprotection in acidotic and ischemic conditions. GPR68 exhibited wide expression in brain neurons and mediated acidosis-induced PKC (protein kinase C) activation. PKC inhibition exacerbated pH 6-induced neuronal injury in a GPR68-dependent manner. Consistent with its neuroprotective function, GPR68 overexpression alleviated middle cerebral artery occlusion–induced brain injury.

Conclusions:

These data expand our knowledge on neuronal acid signaling to include a neuroprotective metabotropic dimension and offer GPR68 as a novel therapeutic target to alleviate neuronal injuries in ischemia and multiple other neurological diseases.
The Secret of the Untrembling Heart
Authors: Jackson Rova Peter
Published: October 2020

The poem by Parmenides is widely recognized as having a decisive influence on Greek philosophy. The text is also notorious for its interpretative problems owing to its obscure poetic style. Among the discordant quotes from the proem, Simplicius uniquely preserves a verse with the unparalleled genitive εὐκυκλέος (literally ‘of [the] well-wheeled’). Contrary to a recent editorial trend in opting for the lectio facilior
εὐπειθέος (‘of [the] well-persuasive’), I argue in this paper that the lectio difficilior is genuine testimony to a poetic device designed by Parmenides to perform a pivotal role in the proemial structure as a whole, and to redeploy a key concept in archaic verbal art by means of paronomasia: the ‘glory’ (κλέος) conveyed through the costly medium of song. The proem thus gives characteristic voice to the experimental spirit of inquiry in which Parmenides variously challenged and took his cue from the conceptual framework of encomiastic performance.
Ataraxia Vanquishes Eros
Authors: Eckerman Chris
Published: October 2020

This note details correspondences between Sappho fr. 16 (V.) and the proem to Book 2 of Lucretius’ De rerum natura. The author argues that Lucretius polemically alludes to Sappho.
Exploring the Factor Structure of the Glasgow Children’s Benefit Inventory: New Recommendations for Reporting Results
Authors: Kubba Haytham , Whitmer William M.
Published: October 2020

Objective:

Patient-reported outcomes can be useful for reporting benefit from non-life-saving interventions, but often they report a single overall score, which means that much information on the specific areas of benefit is lost. Our aim was to perform a new factor analysis on the Glasgow Children’s Benefit Inventory (GCBI) to create subscales reflecting domains of benefit. Further aims were to assess the internal consistency of the GCBI, and to develop guidelines for reporting both a total score and sub-scales in future studies.

Methods:

We collected 4 existing datasets of GCBI data from children who have undergone tonsillectomy, ventilation tube insertion, pinnaplasty, and submucous diathermy to the inferior turbinates. We performed exploratory factor analysis with principal axis factoring with varimax rotation, we sought redundancy in question items, and we measured internal consistency.

Results:

Using the combined dataset of 772 cases, we found 4 factors which accounted for 64% of the variance and which we have labeled “Psycho-social,” “Physical health,” “Behavior,” and “Vitality.” Subscale results varied in predictable ways depending on the nature of the intervention. Cronbach’s alpha was 0.928. Item-total correlations were high, and no item could be deleted to improve alpha. Floor effects were apparent for various questions but were not consistent between different interventions.

Conclusions:

The GCBI contains a range of questions which each add value in different clinical interventions. We can now make recommendations for reporting the results of the GCBI and its 4 new subscales.
Quetiapine withdrawal: A systematic review
Authors: Monahan Katherine , Cuzens-Sutton Jaimie , Siskind Dan , Kisely Steve
Published: October 2020

Objective:

Withdrawal from psychoactive medication such as quetiapine is a well-documented phenomenon. Despite the extensive use of quetiapine, there have been few studies into the presence of discontinuation symptoms. We therefore performed a systematic review of published literature for evidence of quetiapine withdrawal or symptoms associated with discontinuation.

Methods:

We searched PubMed, Embase, CINAHL, Medline, Web of Science, PsycINFO for articles containing the terms ‘Quetiapine’ AND ‘withdraw$’ OR ‘discontinue$’. We included all study types that reported on somatic withdrawal symptoms and had no language restrictions. We excluded studies where there was withdrawal from multiple medications or any other psychoactive substance, or where the only symptoms were psychological such as rebound psychosis or craving.

Results:

We included 13 papers, all of which were individual case reports. The quality of the individual case reports was sub-optimal, as assessed by the CARE Case Report Guidelines. There was an association between rapid cessation of quetiapine and onset of somatic symptoms such as nausea, vomiting, agitation, restlessness, diaphoresis, irritability, anxiety, dysphoria, sleep disturbance, insomnia, tachycardia, hypertension and dizziness. Three studies also reported the onset of a withdrawal dyskinesia characterised by abnormal choreiform movements as well as confusion and speech disturbance in some cases. However, these findings were limited by the number and quality of case reports identified.

Conclusion:

Discontinuation symptoms are an uncommon side effect of quetiapine cessation, which may have clinical implications. Clinicians should therefore be alert to the possibility of quetiapine withdrawal in individuals who present with somatic symptoms or choreiform movements. However, large prospective studies are required to clarify this association.
Peer-to-peer contact, social support and self-stigma among people with severe mental illness in Hong Kong
Authors: Li Xu-Hong , Zhang Tian-Ming , Yau Yuen Yum , Wang Yi-Zhou , Wong Yin-Ling Irene , Yang Lawrence , Tian Xiao-li , Chan Cecilia Lai-Wan , Ran Mao-Sheng
Published: October 2020

Background:

Self-stigma exerts a range of adversities for persons with severe mental illness (SMI), however, little is known about the association between peer contact, social support and self-stigma.

Aims:

This study aimed to explore the mediating role of social support on the relationship between peer contact and self-stigma among persons with SMI in Hong Kong.

Methods:

A total of 159 persons with SMI (schizophrenia and mood disorder) in community service centres participated in the study through completing a survey on self-stigma, social functioning, social support, perception of peer contact and mass media. Logistic regression was utilised to explore the influencing factors of self-stigma among the participants.

Results:

The results showed that 81.1% of participants reported moderate to severe levels of self-stigma. Self-stigma was significantly associated with diverse factors (e.g. social functioning). Importantly, positive peer contact was significantly associated with lower self-stigma of persons with SMI. Social support acted as a mediator between peer contact and self-stigma.

Conclusion:

The results of this study suggest that contact-based interventions, such as enhancing positive peer-to-peer contact, should be conducted for reducing self-stigma among persons with SMI.
Dimensional variation and evolution of mechanical properties of wet aged composites reinforced with flax fibers
Authors: Hachem Ziad El , Célino Amandine , Challita Georges , Branchu Samuel , Duigou Antoine Le , Fréour Sylvain
Published: October 2020

The aim of this study is to investigate the dimensional variation of polypropylene composites reinforced with UD flax fibers, and the modification of its dynamical mechanical properties after moisture absorption. The effects of fiber content, coupling agent and moisture content were also examined. Results have shown that the swelling increases significantly when increasing the fiber content and the moisture content. It was also concluded that the addition of a coupling agent reduces the swelling of the composite, by improving the adhesion at the fiber/matrix interface. It is interesting to note that the coefficient of hygroscopic swelling of the composites presents a non-linear evolution, with respect to moisture content. Moreover, it was proved that the addition of fiber and the presence of a coupling agent improve the dynamical mechanical properties of the material. However, following moisture absorption, the storage modulus seems to be decreasing, which might be due to the micro-cracks created as a result of the internal swelling of fibers. Additionally, the coupling agent was found to increase the storage modulus of the composite at dry state, whereas following moisture absorption, it was found that the coupling agent does not modify the storage modulus of the material. Moreover, the results reveal that the dynamic mechanical properties of the composites are hardly dependent on the quality of the material, such as the state of the adhesion at the fiber/matrix interface, a possible misalignment of the fibers within the material and the moisture content within the material at the testing time.
“Finding the Balance”: A Qualitative Study of the Experience of Nurses and Patients with Diabetes on an Insulin Pump in the Hospital
Authors: Kaisen Ann R. , Parkosewich Janet A. , McAvoy Karen H. , Bak Leigh B. , Knobf M. Tish
Published: October 2020

Purpose

The purpose of this study was to explore experiences of hospitalized patients as they transition insulin pump self-management from home to hospital and the experience of nurses caring for them. Patients are often more knowledgeable about the pump than their nurses, which could lead to undiscovered challenges. Little is known about the hospital experience related to insulin pump therapy from nurses’ and patients’ perspectives.

Methods

A qualitative approach with interpretive descriptive design and purposive sampling was used. Eligible patients were ≥18 years of age, able to read and speak English, and admitted to non-ICU settings ≥20 hours. Eligible nurses cared for at least 1 patient using an insulin pump. Patients and nurses were interviewed separately. Interviews were audiotaped and transcribed verbatim. Data were analyzed using a constant comparative method. Coding was performed independently and jointly to reach consensus on emerging themes.

Results

Hospitalized patients and nurses had an array of perceptions highlighting challenges and adaption to “finding the balance” in managing diabetes when patients wore their insulin pumps. There were 4 interrelated themes representing a continuum of trust to lack of trust, control versus lack of control, effective communication to limited communication, and staff knowledge to lack of knowledge.

Conclusions

Results of this study provide valuable insights into the challenges for both patients and nurses. A standardized approach to caring for this population is necessary. These findings can inform the development of nursing education programs and policies aimed at improving their experiences.