bluuebunny/crossref_metadata_2025_split huggingface dataset:
National Institute on Aging Workshop: Repurposing Drugs or Dietary Supplements for Their Senolytic or Senomorphic Effects: Considerations for Clinical Trials
Authors: Romashkan Sergei , Chang Henry , Hadley Evan C 
Published: February 2021

Abstract

Background
Cell senescence is implicated in numerous age-related conditions. Drugs and nutritional supplements developed for a variety of purposes kill senescent cells (senolytics) or suppress their secretions (senomorphics). There is interest in repurposing such drugs to treat or prevent age-related diseases. To date, only small-scale preliminary trials have been conducted.

Method
At a workshop convened by the National Institute on Aging in August 2019, academic, industry, and government scientists reviewed issues for phase II trials of potentially repurposable drugs, or dietary supplements, to assess benefits and risks of their senolytic (killing senescent cells) or senomorphic (altering senescent cells’ phenotypes) effects in treating or preventing age-related conditions.

Results
Participants reviewed mechanisms and effects of cellular senescence, senolytics, and senomorphics of several classes and their potential role in treating or preventing disease, modulators of the senescence-associated secretory phenotype, needs for senescence markers, data and specimen resources, infrastructure for planning trials, and potential effects on outcomes in older patients with multimorbidity and polypharmacy.

Conclusions
Participants noted the importance of considering potential effects of candidate drugs on multiple aging outcomes. It is important to assess drugs’ specificity for killing senescent cells and the balance between senolytic and cytotoxic effects. Markers of specific senescent cell types are needed to assess intervention responses. There are potential interactions with coexisting diseases and their treatments in older persons. Standardized measures could enhance comparisons and pooling of data. Additional characterization of human cell senescent phenotypes is needed for developing better and more specific senolytics and senomorphics.
Enhancing Older Adults’ Well-Being and Quality of Life Through Purposeful Activity: A Systematic Review of Intervention Studies
Authors: Owen Rebecca , Berry Katherine , Brown Laura J E 
Published: February 2021

Abstract

Background and Objectives
Population aging represents a significant challenge for health and social care services. Older adults who engage in activities that offer a sense of purpose have significantly better physical and psychological health outcomes. However, age-related functional limitations and losses of social roles can present barriers to engaging in purposeful activity, especially for those older adults within the “oldest-old” age range (i.e., 80 years and older). This review aimed to determine the nature and effectiveness of purposeful activity interventions in older adults, aged 80 years and older, with respect to well-being and quality-of-life outcomes.

Research Design and Methods
Three databases were searched from their inception to April 2020. The search yielded 8,916 records, which resulted in eight eligible studies.

Results
The interventions were divided into two groups: (a) interventions that gave participants a specific functional role, such as volunteer or mentor (n = 5), and (b) interventions that supported participants to develop a new skill (n = 3). The quality of the evidence was variable. The strongest evidence was for interventions that assigned a functional role, which appeared to be somewhat effective in improving well-being outcomes.

Discussion and Implications
There is preliminary evidence that purposeful activity interventions, particularly those that involved taking on a functional role, can improve well-being and quality-of-life outcomes in older adults aged 80 years and older. These findings have implications for professionals and carers to support older adults to access more purposeful social roles and create opportunities for helping and reciprocation.
On the adaptive spectral approximation of functions using redundant sets and frames
Authors: Coppé Vincent , Huybrechs Daan 
Published: February 2021

Abstract
The approximation of smooth functions with a spectral basis typically leads to rapidly decaying coefficients, where the rate of decay depends on the smoothness of the function and vice versa. The optimal number of degrees of freedom in the approximation can be determined with relative ease by truncating the coefficients once a threshold is reached. Recent approximation schemes based on redundant sets and frames extend the applicability of spectral approximations to functions defined on irregular geometries and to certain nonsmooth functions. However, due to their inherent redundancy, the expansion coefficients in frame approximations do not necessarily decay even for very smooth functions. In this paper, we highlight this lack of equivalence between smoothness and coefficient decay, and we explore approaches to determine an optimal number of degrees of freedom for such redundant approximations.
Strictly positive definite kernels on the 2-sphere: from radial symmetry to eigenvalue block structure
Authors: Buhmann Martin , Jäger Janin 
Published: February 2021

Abstract
The paper introduces a new characterization of strict positive definiteness for kernels on the 2-sphere without assuming the kernel to be radially (isotropic) or axially symmetric. The results use the series expansion of the kernel in spherical harmonics. Then additional sufficient conditions are proven for kernels with a block structure of expansion coefficients. These generalize the result derived by Chen et al. (2003, A necessary and sufficient condition for strictly positive definite functions on spheres. Proc. Amer. Math. Soc., 131, 2733–2740) for radial kernels to nonradial kernels.
Time and predictors of time to treatment for aneurysmal subarachnoid haemorrhage (aSAH): a systematic review
Authors: Phuong nguyen Thuy , Rehman Sabah , Stirling Christine , Chandra Ronil , Gall Seana 
Published: February 2021

Abstract

Background
Aneurysmal subarachnoid haemorrhage (aSAH) is a serious form of stroke, for which rapid access to specialist neurocritical care is associated with better outcomes. Delays in the treatment of aSAH appear to be common and may contribute to poor outcomes. We have a limited understanding of the extent and causes of these delays, which hinders the development of interventions to reduce delays and improve outcomes. The aim of this systematic review was to quantify and identify factors associated with time to treatment in aSAH.

Methods
This systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines and was registered in PROSPERO (Reg. No. CRD42019132748). We searched four electronic databases (MEDLINE, EMBASE, Web of Science and Google Scholar) for manuscripts published from January 1998 using pre-designated search terms and search strategy. Main outcomes were duration of delays of time intervals from onset of aSAH to definitive treatment and/or factors related to time to treatment.

Results
A total of 64 studies with 16 different time intervals in the pathway of aSAH patients were identified. Measures of time to treatment varied between studies (e.g. cut-off timepoints or absolute mean/median duration). Factors associated with time to treatment fell into two categories—individual (n = 9 factors, e.g. age, sex and clinical characteristics) and health system (n = 8 factors, e.g. pre-hospital delay or presentation out-of-hours). Demographic factors were not associated with time to treatment. More severe aSAH reduced treatment delay in most studies. Pre-hospital delays (patients delay, late referral, late arrival of ambulance, being transferred between hospitals or arriving at the hospital outside of office hours) were associated with treatment delay. In-hospital factors (patients with complications, procedure before definitive treatment, slow work-up and type of treatment) were less associated with treatment delay.

Conclusions
The pathway from onset to definitive treatment of patients with aSAH consists of multiple stages with multiple influencing factors. This review provides the first comprehensive understanding of extent and factors associated with time to treatment of aSAH. There is an opportunity to target modifiable factors to reduce time to treatment, but further research considering more factors are needed.
Bringing Researchers Back In: Debating the Role of Interpretive Epistemology in Global IR
Authors: Vandamme Dorothée 
Published: February 2021

Abstract
The article discusses interpretive epistemology in international relations (IR) and its advantages to address the field's sociological composition, its scholars’ identity, and knowledge structuration. The research proposes to engage in sociological reflexivity on IR methods and the way in which knowledge accumulation and structuration are driven by canonical assumptions of what are considered “normal”/“good” scientific procedures. The central argument focuses on interpretive epistemological approaches as possible venues for research to participate in the collective effort to address, and redress, the imbalance between the sociology of the field and its knowledge production and structuration processes. By allowing dialogue around meanings and interpretation among increasingly diverse members, an interpretive stance on IR opens the floor to criticism and rival interpretations. More specifically, the paper presents the methodology of interpretive phenomenological analysis as a method which both emphasizes context and actor specificity with regard to the subject of study and fully acknowledges the researcher's identity and voice in scientific inquiry.
Practice and market factors associated with provider volume of health information exchange
Authors: Apathy Nate C , Vest Joshua R , Adler-Milstein Julia , Blackburn Justin , Dixon Brian E , Harle Christopher A 
Published: February 2021

Abstract

Objective
To assess the practice- and market-level factors associated with the amount of provider health information exchange (HIE) use.

Materials and Methods
Provider and practice-level data was drawn from the Meaningful Use Stage 2 Public Use Files from the Centers for Medicare and Medicaid Services, the Physician Compare National Downloadable File, and the Compendium of US Health Systems, among other sources. We analyzed the relationship between provider HIE use and practice and market factors using multivariable linear regression and compared primary care providers (PCPs) to non-PCPs. Provider volume of HIE use is measured as the percentage of referrals sent with electronic summaries of care (eSCR) reported by eligible providers attesting to the Meaningful Use electronic health record (EHR) incentive program in 2016.

Results
Providers used HIE in 49% of referrals; PCPs used HIE in fewer referrals (43%) than non-PCPs (57%). Provider use of products from EHR vendors was negatively related to HIE use, while use of Athenahealth and Greenway Health products were positively related to HIE use. Providers treating, on average, older patients and greater proportions of patients with diabetes used HIE for more referrals. Health system membership, market concentration, and state HIE consent policy were unrelated to provider HIE use.

Discussion
HIE use during referrals is low among office-based providers with the capability for exchange, especially PCPs. Practice-level factors were more commonly associated with greater levels of HIE use than market-level factors.

Conclusion
This furthers the understanding that market forces, like competition, may be related to HIE adoption decisions but are less important for use once adoption has occurred.
A dynamic mammary gland model describing colostrum immunoglobulin transfer and milk production in lactating sows
Authors: Krogh Uffe , Quesnel Hélène , Le Floch Nathalie , Simongiovanni Aude , van Milgen Jaap 
Published: February 2021

Abstract
The physiology of the sow mammary gland is qualitatively well described and understood. However, the quantitative effect of various biological mechanisms contributing to the synthesis of colostrum and milk is lacking and more complicated to obtain. The objective of this study was to integrate physiological and empirical knowledge of the production of colostrum and milk in a dynamic model of a single sow mammary gland to understand and quantify parameters controlling mammary gland output. In 1983, Heather Neal and John Thornley published a model of the mammary gland in cattle, which was used as a starting point for the development of this model. The original cattle model was reparameterized, modified, and extended to describe the production of milk by the sow mammary gland during lactation and the prepartum production of colostrum as the combined output of immunoglobulins (Ig) and milk. Initially, the model was reparameterized to simulate milk synthesis potential of a single gland by considering biological characteristics and empirical estimations of sows and piglets. Secondly, the model was modified to simulate more accurately the responses to changes in milk removal rates. This was done by linking the ejectable milk storage capacity to the number of secretory cells rather than being constant throughout lactation. Finally, the model was extended to include the prepartum synthesis of milk and the kinetics of Ig into and out of the mammary gland. A progressive capacity of secretory cells to synthesize milk was used to differentiate the time between the onset of milk synthesis and Ig transfer. Changes in maximum milk removal rate, duration of milk ejection, and nursing interval exerted a great impact on the modeled milk output. Changes by ±60% in one of these parameters were capable of increasing milk output by 28% to 39% during the first 4 wk in lactation compared with the reference parameterization. This suggests that the ability of the piglet to remove milk from the gland exerts a key control on milk synthesis during lactation. Modeling colostrum as the combined output of Ig and milk allowed to represent the rapid decline in Ig concentration observed during the first hours after farrowing. In conclusion, biological and empirical knowledge was integrated into a model of the sow mammary gland and constitutes a simple approach to explore in which conditions and to what extent individual parameters influence Ig kinetics and milk production.
A quasi-3D model of the whole lung: airway extension to the tracheobronchial limit using the constrained constructive optimization and alveolar modeling, using a sac–trumpet model
Authors: Kannan Ravishekar (Ravi) , Singh Narender , Przekwas Andrzej , Zhou Xianlian Alex , Walenga Ross , Babiskin Andrew 
Published: February 2021

Abstract
Existing computational models used for simulating the flow and species transport in the human airways are zero-dimensional (0D) compartmental, three-dimensional (3D) computational fluid dynamics (CFD), or the recently developed quasi-3D (Q3D) models. Unlike compartmental models, the full CFD and Q3D models are physiologically and anatomically consistent in the mouth and the upper airways, since the starting point of these models is the mouth–lung surface geometry, typically created from computed tomography (CT) scans. However, the current resolution of CT scans limits the airway detection between the 3rd–4th and 7th–9th generations. Consequently, CFD and the Q3D models developed using these scans are generally limited to these generations. In this study, we developed a method to extend the conducting airways from the end of the truncated Q3D lung to the tracheobronchial (TB) limit. We grew the lung generations within the closed lung lobes using the modified constrained constructive optimization, creating an aerodynamically optimized network aiming to produce equal pressure at the distal ends of the terminal segments. This resulted in a TB volume and lateral area of ∼165 cc and ∼2000 cm2, respectively. We created a “sac–trumpet” model at each of the TB outlets to represent the alveoli. The volumes of the airways and the individual alveolar generations match the anatomical values by design: with the functional residual capacity at 2611 cc. Lateral surface areas were scaled to match the physiological values. These generated Q3D whole lung models can be efficiently used for conducting multiple breathing cycles of drug transport and deposition simulations.
Semi-exact local absorbing boundary condition for seismic wave simulation
Authors: Izadian Saeed , Aghazade Kamal , Amini Navid , Wang Yanghua 
Published: February 2021

AbstractAn absorbing boundary condition is necessary in seismic wave simulation for eliminating the unwanted artificial reflections from model boundaries. Existing boundary condition methods often have a trade-off between numerical accuracy and computational efficiency. We proposed a local absorbing boundary condition for frequency-domain finite-difference modelling. The proposed method benefits from exact local plane-wave solution of the acoustic wave equation along predefined directions that effectively reduces the dispersion in other directions. This method has three features: simplicity, accuracy and efficiency. Numerical simulation demonstrated that the proposed method has higher efficiency than the conventional methods such as the second-order absorbing boundary condition and the perfectly matched layer (PML) method. Meanwhile, the proposed method shared the same low-cost feature as the first-order absorbing boundary condition method.
Underground and Over the Sea: More Community Prophylactics in Europe, 1100-1600
Authors: Geltner G , Weeda Claire 
Published: February 2021

Abstract
Public health historians have repeatedly shown that the theory, policy, and practice of group prophylactics far predate their alleged birth in industrial modernity, and regularly draw on Galenic principles. While the revision overall has been successful, its main focus on European cities entails a major risk, since city dwellers were a minority even in Europe’s most urbanised regions. At the same time, cities continue to be perceived and presented as typically European, which stymies transregional and comparative studies based at least in part on non- or extra-urban groups. Thus, any plan to both offer an accurate picture of public health’s deeper past and fundamentally challenge a narrative of civilizational progress wedded to Euro-American modernity (“stagism”) would benefit from looking beyond cities and their unique health challenges. The present article begins to do so by focusing on two ubiquitous groups, often operating outside cities and facing specific risks: miners and shipmates. Evidence for these communities’ preventative interventions and the extent to which they drew on humoral theory is rich yet uneven for Europe between the thirteenth and sixteenth centuries. Methodological questions raised by this unevenness can be addressed by connecting different scales of evidence, as this article demonstrates. Furthermore, neither mining nor maritime trade was typically European, thus building a broader base for transregional studies and comparisons.
Do Economic Crises Trigger Treaty–Based Investor–State Arbitration Disputes?
Authors: Bellak Christian , Leibrecht Markus 
Published: February 2021

ABSTRACT
The number of investor–state arbitration disputes has increased to more than 1000 to date, but their determinants are still not fully understood. We argue that in the wake of severe macroeconomic turmoil—economic crisis—policymakers have strong incentives to implement regulatory changes, even if these allegedly breach protection standards are provided by International Investment Agreements (IIAs). We base our empirical analysis on a unique country-dyadic dataset containing 961 investor–state arbitration claims over the 1987–2017 period. Our findings support the results of the related literature, which stresses the importance of good governance for avoiding arbitration cases. In contrast to this literature, we provide robust evidence consistent with a positive statistical association of economic crises and the number of investor–state arbitration disputes. Our investigation suggests that governments risk paying compensation to foreign investors for their actions in times when public regulation is needed in other areas. This may warrant a reconsideration of economic emergency measures of governments and the national security clause in International Investment Agreements in the current reform debate.
Is Article 8(3) EUTMR applicable only to identical marks and identical goods? ‘No’, says the Court of Justice
Authors: Martin Stefan , Boyd Jonathan 
Published: February 2021

Abstract
Court of Justice of the European Union, MINERAL MAGIC/MAGIC MINERALS BY JEROME ALEXANDER et al, C-809/18 P, EU: C:2020:902, 11/11/2020
The Court of Justice provides clear guidance on the test to be applied under Article 8(3) of the EU Trade Mark Regulation 2017/1001 (‘EUTMR).
Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients
Authors: Lai Shicong , Long Xingbo , Wu Pengjie , Liu Jianyong , Seery Samuel , Hou Huimin , Liu Ming , Li Yuan , Wang Jianye 
Published: February 2021

Abstract

Objective
To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients.

Methods
This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models.

Results
With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P &lt; 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas’ model in terms of discriminative capacity (all P &lt; 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients’ net benefit.

Conclusions
This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.