Working Papers, Open Access and Cyber-Infrastructure in Classical Studies

Princeton–Stanford Working Papers in Classics is a web-based series of work-in-progress scripts by members of two leading departments of classics. It introduces the humanities to a new form of scholarly communication and represents a major advance in the free availability of classical-studies scholarship in cyberspace. This article both reviews the initial performance of this open-access experiment and the benefits and challenges of working papers more generally for classical studies. After two years of operation Princeton–Stanford Working Papers in Classics has proven to be a clear success. This series has built up a large international readership and a sizeable body of preprints and performs important scholarly and community-outreach functions. As this performance is largely due to its congruency with the working arrangements of ancient historians and classicists and the global demand for open-access scholarship, the series confirms the viability of this means of scholarly communication and the likelihood of its expansion in our discipline. But modifications are required to increase the benefits this series brings and the amount of scholarship it makes freely available online. Finally departments wishing to replicate its success will have to consider other important developments, such as the increasing availability of postprints, the linking of research funding to open access, and the emergence of new cyber-infrastructure

Novel Approaches to Treat Experimental Pulmonary Arterial Hypertension: A Review

Background. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an increase in pulmonary artery pressure leading to right ventricular (RV) hypertrophy, RV failure, and ultimately death. Current treatments can improve symptoms and reduce severity of the hemodynamic disorder but gradual deterioration in their condition often necessitates a lung transplant. Methods and Results. In experimental models of PAH, particularly the model of monocrotaline-induced pulmonary hypertension, efficacious treatment options tested so far include a spectrum of pharmacologic agents with actions such as anti-mitogenic, proendothelial function, proangiogenic, antiinflammatory and antioxidative. Emerging trends in PAH treatment are gene and cell therapy and their combination, like (progenitor) cells enriched with eNOS or VEGF gene. More animal data should be collected to investigate optimal cell type, in vitro cell transduction, route of administration, and number of cells to inject. Several recently discovered and experimentally tested interventions bear potential for therapeutic purposes in humans or have been shown already to be effective in PAH patients leading to improved life expectation and better quality of life. Conclusion. Since many patients remain symptomatic despite therapy, we should encourage research in animal models of PAH and implement promising treatments in homogeneous groups of PAH patients

Care trajectories of chronically ill older adult patients discharged from hospital:a quantitative cross-sectional study using health insurance claims data

Background For older adults, a good transition from hospital to the primary or long-term care setting can decrease readmissions. This paper presents the 6-month post-discharge healthcare utilization of older adults and describes the numbers of readmissions and deaths for the most frequently occurring aftercare arrangements as a starting point in optimizing the post-discharge healthcare organization. Methods This cross-sectional study included older adults insured with the largest Dutch insurance company. We described the utilization of healthcare within 180 days after discharge from their first hospital admission of 2015 and the most frequently occurring combinations of aftercare in the form of geriatric rehabilitation, community nursing, long-term care, and short stay during the first 90 days after discharge. We calculated the proportion of older adults that was readmitted or had died in the 90-180 days after discharge for the six most frequent combinations. We performed all analyses in the total group of older adults and in a sub-group of older adults who had been hospitalized due to a hip fracture. Results A total of 31.7% of all older adults and 11.4% of the older adults with a hip fracture did not receive aftercare. Almost half of all older adults received care of a community nurse, whereas less than 5% received long-term home care. Up to 18% received care in a nursing home during the 6 months after discharge. Readmissions were lowest for older adults with a short stay and highest in the group geriatric rehabilitation + community nursing. Mortality was lowest in the total group of older aldults and subgroup with hip fracture without aftercare. Conclusions The organization of post-discharge healthcare for older adults may not be organized sufficiently to guarantee appropriate care to restore functional activity. Although receiving aftercare is not a clear predictor of readmissions in our study, the results do seem to indicate that older adults receiving community nursing in the first 90 days less often die compared to older adults with other types of aftercare or no aftercare. Future research is necessary to examine predictors of readmissions and mortality in both older adult patients discharged from hospital.</p

Seventh supplement to the Federated Malay States Government Gazette of Friday, the 7th of December, 1925 (Vol. XVII, No. 24).

No. 779

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Associations between sitting time and a range of symptoms in mid-age women

Objective. The aim of this study was to explore longitudinal associations between sitting and physical and psychological symptoms in mid-age women

A mixed-methods study to define Textbook Outcome for the treatment of patients with uncomplicated symptomatic gallstone disease with hospital variation analyses in Dutch trial data

Background: International consensus on the ideal outcome for treatment of uncomplicated symptomatic gallstone disease is absent. This mixed-method study defined a Textbook Outcome (TO) for this large group of patients. Methods: First, expert meetings were organised with stakeholders to design the survey and identify possible outcomes. To reach consensus, results from expert meetings were converted in a survey for clinicians and for patients. During the final expert meeting, clinicians and patients discussed survey outcomes and a definitive TO was formulated. Subsequently, TO-rate and hospital variation were analysed in Dutch hospital data from patients with uncomplicated gallstone disease. Results: First expert meetings returned 32 outcomes. Outcomes were distributed in a survey among 830 clinicians from 81 countries and 645 Dutch patients. Consensus-based TO was defined as no more biliary colic, no biliary and surgical complications, and the absence or reduction of abdominal pain. Analysis of individual patient data showed that TO was achieved in 64.2% (1002/1561). Adjusted-TO rates showed modest variation between hospitals (56.6-74.9%). Conclusion: TO for treatment of uncomplicated gallstone disease was defined as no more biliary colic, no biliary and surgical complications, and absence or reduction of abdominal pain.TO may optimise consistent outcome reporting in care and guidelines for treating uncomplicated gallstone disease

A Prediction Model for Successful Increase of Adalimumab Dose Intervals in Patients with Crohn’s Disease:Secondary Analysis of the Pragmatic Open-Label Randomised Controlled Non-inferiority LADI Trial

Background: In the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn’s disease (CD) in clinical and biochemical remission. Aims: To develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data. Methods: Patients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (&gt; 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction. Results: We included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval. Conclusion: The final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice. Clinical Trial Registration Number: ClinicalTrials.gov, number NCT03172377.</p

A multi-stakeholder approach to eHealth development: promoting sustained healthy living among cardiovascular patients

Background: Healthy living is key in the prevention and rehabilitation of cardiovascular disease (CVD). Yet, supporting and maintaining a healthy lifestyle is exceptionally difficult and people differ in their needs regarding optimal support for healthy lifestyle interventions.Objective: The goals of this study were threefold: to uncover stakeholders' needs and preferences, to translate these to core values, and develop eHealth technology based on these core values. Our primary research question is: What type of eHealth application to support healthy living among people with (a high risk of) CVD would provide the greatest benefit for all stakeholders? Methods: User-centered design principles from the CeHRes roadmap for eHealth development were followed to guide the uncovering of important stakeholder values. Data were synthesized from various qualitative studies (i. e., literature studies, interviews, think-aloud sessions, focus groups) and usability tests (i.e., heuristic evaluation, cognitive walkthrough, think aloud study). We also developed an innovative application evaluation tool to perform a competitor analysis on 33 eHealth applications. Finally, to make sure to take into account all end-users needs and preferences in eHealth technology development, we created personas and a customer journey.Results: We uncovered 10 universal values to which eHealth-based initiatives to support healthy living in the context of CVD prevention and rehabilitation should adhere to (e.g., providing social support, stimulating intrinsic motivation, offering continuity of care). These values were translated to 14 desired core attributes and then prototype designs. Interestingly, we found that the primary attribute of good eHealth technology was not a single intervention principle, but rather that the technology should be in the form of a digital platform disseminating various interventions, i.e., a 'one-stop-shop'.Conclusion: Various stakeholders in the field of cardiovascular prevention and rehabilitation may benefit most from utilizing one personalized eHealth platform that integrates a variety of evidence-based interventions, rather than a new tool. Instead of a one-size-fits-all approach, this digital platform should aid the matchmaking between patients and specific interventions based on personal characteristics and preferences.Cardiolog

A multi-stakeholder approach to eHealth development: Promoting sustained healthy living among cardiovascular patients

Background: Healthy living is key in the prevention and rehabilitation of cardiovascular disease (CVD). Yet, supporting and maintaining a healthy lifestyle is exceptionally difficult and people differ in their needs regarding optimal support for healthy lifestyle interventions. Objective: The goals of this study were threefold: to uncover stakeholders’ needs and preferences, to translate these to core values, and develop eHealth technology based on these core values. Our primary research question is: What type of eHealth application to support healthy living among people with (a high risk of) CVD would provide the greatest benefit for all stakeholders? Methods: User-centered design principles from the CeHRes roadmap for eHealth development were followed to guide the uncovering of important stakeholder values. Data were synthesized from various qualitative studies (i.e., literature studies, interviews, think-aloud sessions, focus groups) and usability tests (i.e., heuristic evaluation, cognitive walkthrough, think aloud study). We also developed an innovative application evaluation tool to perform a competitor analysis on 33 eHealth applications. Finally, to make sure to take into account all end-users needs and preferences in eHealth technology development, we created personas and a customer journey. Results: We uncovered 10 universal values to which eHealth-based initiatives to support healthy living in the context of CVD prevention and rehabilitation should adhere to (e.g., providing social support, stimulating intrinsic motivation, offering continuity of care). These values were translated to 14 desired core attributes and then prototype designs. Interestingly, we found that the primary attribute of good eHealth technology was not a single intervention principle, but rather that the technology should be in the form of a digital platform disseminating various interventions, i.e., a ‘one-stop-shop’. Conclusion: Various stakeholders in the field of cardiovascular prevention and rehabilitation may benefit most from utilizing one personalized eHealth platform that integrates a variety of evidence-based interventions, rather than a new tool. Instead of a one-size-fits-all approach, this digital platform should aid the matchmaking between patients and specific interventions based on personal characteristics and preferences