bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of menopausal characteristics and risk of coronary heart disease: a pan-European case–cohort analysis
Authors: Dam Veerle , van der Schouw Yvonne T , Onland-Moret N Charlotte , Groenwold Rolf H H , Peters Sanne A E , Burgess Stephen , Wood Angela M , Chirlaque Maria-Dolores , Moons Karel G M , Oliver-Williams Clare , Schuit Ewoud , Tikk Kaja , Weiderpass Elisabete , Holm Marianne , Tjønneland Anne , Kühn Tilman , Fortner Renée T , Trichopoulou Antonia , Karakatsani Anna , La Vecchia Carlo , Ferrari Pietro , Gunter Marc , Masala Giovanna , Sieri Sabina , Tumino Rosario , Panico Salvatore , Boer Jolanda M A , Verschuren W M Monique , Salamanca-Fernández Elena , Arriola Larraitz , Moreno-Iribas Conchi , Engström Gunnar , Melander Olle , Nordendahl Maria , Wennberg Patrik , Key Timothy J , Colorado-Yohar Sandra , Matullo Giuseppe , Overvad Kim , Clavel-Chapelon Francoise , Boeing Heiner , Quiros J Ramon , di Angelantonio Emanuele , Langenberg Claudia , Sweeting Michael J , Riboli Elio , Wareham Nicholas J , Danesh John , Butterworth Adam 
Published: February 2019

Abstract

Background
Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors.

Methods
We used data from EPIC-CVD, a case–cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders.

Results
After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01–1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10–1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96–1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors.

Conclusions
Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
An argument for reporting data standardization procedures in multi-site predictive modeling: case study on the impact of LOINC standardization on model performance
Authors: Barda Amie J , Ruiz Victor M , Gigliotti Tony , Tsui Fuchiang (Rich) 
Published: February 2019

Abstract

Objectives
We aimed to gain a better understanding of how standardization of laboratory data can impact predictive model performance in multi-site datasets. We hypothesized that standardizing local laboratory codes to logical observation identifiers names and codes (LOINC) would produce predictive models that significantly outperform those learned utilizing local laboratory codes.

Materials and Methods
We predicted 30-day hospital readmission for a set of heart failure-specific visits to 13 hospitals from 2008 to 2012. Laboratory test results were extracted and then manually cleaned and mapped to LOINC. We extracted features to summarize laboratory data for each patient and used a training dataset (2008–2011) to learn models using a variety of feature selection techniques and classifiers. We evaluated our hypothesis by comparing model performance on an independent test dataset (2012).

Results
Models that utilized LOINC performed significantly better than models that utilized local laboratory test codes, regardless of the feature selection technique and classifier approach used.

Discussion and Conclusion
We quantitatively demonstrated the positive impact of standardizing multi-site laboratory data to LOINC prior to use in predictive models. We used our findings to argue for the need for detailed reporting of data standardization procedures in predictive modeling, especially in studies leveraging multi-site datasets extracted from electronic health records.
Risk Factors for Infection After Intramedullary Nailing of Open Tibial Shaft Fractures in Low- and Middle-Income Countries
Authors: Whiting Paul S. , Galat Daniel D. , Zirkle Lewis G. , Shaw Michael K. , Galat Jeremiah D. 
Published: February 2019

Objectives:
(1) To determine the infection rate after fixation of open tibial shaft fractures using the Surgical Implant Generation Network (SIGN) intramedullary nail in low- and middle-income countries (LMICs) and (2) to identify risk factors for infection.

Design:
Prospective cohort study using an international online database.

Setting:
Multiple hospitals in LMICs worldwide.

Patients/Participants:
A total of 1061 open tibia fractures treated with the SIGN nail in LMICs between March 2000 and February 2013.

Intervention:
Intravenous antibiotic administration, surgical debridement, and definitive intramedullary nailing within 14 days of injury.

Main Outcome Measurements:
Deep or superficial infection at follow-up, implant breakage/loosening, angular deformity >10 degrees, repeat surgery, radiographic union, weight bearing, and ability to kneel.

Results:
The overall infection rate was 11.9%. Infection rates by the Gustilo and Anderson classification were type 1: 5.1%, type II: 12.6%, type IIIa: 12.5%, type IIIb: 29.1%, and type IIIc: 16.7% (P = 0.001 between groups). Patients who developed infection had a longer mean time from injury to definitive surgery (4.7 vs. 3.9 days, P = 0.03) and from injury to wound closure (13.7 vs. 3.6 days, P < 0.001). Distal fractures had a higher infection rate than midshaft fractures (13.3% vs. 8.2%, P = 0.03). Infection rates were not associated with time from injury to initial debridement, time from injury to initial antibiotic administration, or total duration of antibiotics.

Conclusions:
Open tibia fractures can be managed effectively using the SIGN intramedullary nail in LMICs with an overall infection rate of 11.9%. Risk factors for infection identified include more severe soft-tissue injury, delayed nailing, delayed wound closure, and distal fracture location.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Long-term Chronological Changes in Very Asymmetric Keratoconus
Authors: Koh Shizuka , Inoue Ryota , Maeda Naoyuki , Kabata Daijiro , Shintani Ayumi , Jhanji Vishal , Klyce Stephen D. , Maruyama Kazuichi , Nishida Kohji 
Published: February 2019

Purpose:
To investigate chronological changes in patients with very asymmetric keratoconus (KC) by Scheimpflug-based corneal tomographic evaluation.

Methods:
We retrospectively reviewed the clinical records of 382 patients with KC attending a university hospital. Patients who were diagnosed with KC in one eye and forme fruste keratoconus in the other eye at the last visit and followed up with Scheimpflug-based tomographic corneal imaging were included. The anterior radius of curvature (ARC) and posterior radius of curvature (PRC) obtained at a 3.0-mm optical zone and the thinnest pachymetry reading of corneal thickness (Tmin), were used to investigate the chronological changes in tomographic parameters.

Results:
Twenty-six patients aged 16 to 66 years met the inclusion criteria. The mean observation period was 6 years and 4 months. There was a significant increase in annual change in PRC with a longer follow-up period after initial examination (P = 0.011). Moreover, a greater increase in annual change in ARC was observed in patients in whom the initial examination was performed at a younger age than in those in whom it was performed at an older age (P < 0.001).

Conclusions:
On the basis of tomographic evaluation, even if the measured values are almost stable and within normal limits, a long-term clinical follow-up is warranted in forme fruste keratoconus eyes. Younger patients with very asymmetric keratoconus should be monitored carefully.
Effectiveness and safety of 5% lidocaine-medicated plaster on localized neuropathic pain after knee surgery: a randomized, double-blind controlled trial
Authors: Pickering Gisèle , Voute Marion , Macian Nicolas , Ganry Hervé , Pereira Bruno 
Published: February 2019

Abstract
Localized neuropathic pain symptoms are reported after knee surgery in 30% to 50% of patients. 5% lidocaine plaster (LP5) is recommended for localized neuropathic pain, but evidence in postsurgery neuropathic pain is missing. This study focuses on the effectiveness of LP5 on allodynia, hyperalgesia, and thermal stimuli in postsurgery knee localized neuropathic pain. A randomized double-blind, 2 parallel groups, controlled trial (NCT02763592) took place in 36 patients (age, 69.4 ± 7.3 years) at the Clinical Pharmacology Center, University Hospital Clermont-Ferrand, France. Patients randomly received LP5 or placebo plaster during 3 months. Neuropathic pain intensity and several parameters (dynamic mechanical allodynia, mechanical [von Frey], heat and cold detection and pain thresholds [Pathway Medoc], and size of the allodynic area were recorded at each visit [inclusion, day 7, 15, month 1, 2, and 3]). From day 7 onwards, dynamic mechanical allodynia diminished progressively of ≥ 30% over 3 months (P = 0.003) in 96% of patients (23/24) and of ≥ 50% in 83% of patients (20/24). Cold pain and maximal mechanical pain thresholds improved over 3 months (P = 0.001 and P = 0.007, respectively). This study shows for the first time the effectiveness of LP5 on dynamic mechanical allodynia, pain, pressure, and cold thresholds over 3 months in knee localized neuropathic pain. Beyond the inhibition of sodium channels by LP5, these findings suggest the involvement of cold and mechanical receptors that participate to pain chronicisation and also of the non-negligible placebo effect of the patch, items that need to be explored further and challenged in other etiologies of localized neuropathic pain.
Analgesic prescribing trends in a national sample of older veterans with osteoarthritis: 2012-2017
Authors: Trentalange Mark , Runels Tessa , Bean Andrew , Kerns Robert D. , Bair Matthew J. , Brody Abraham A. , Brandt Cynthia A. , Hwang Ula ,   the EAASE (Evaluating Arthritis Analgesic Safety and Effectiveness) Investigators
Published: February 2019

Abstract
Few investigations examine patterns of opioid and nonopioid analgesic prescribing and concurrent pain intensity ratings before and after institution of safer prescribing programs such as the October 2013 Veterans Health Administration system-wide Opioid Safety Initiative (OSI) implementation. We conducted a quasi-experimental pre–post observational study of all older U.S. veterans (≥50 years old) with osteoarthritis of the knee or hip. All associated outpatient analgesic prescriptions and outpatient pain intensity ratings from January 1, 2012 to December 31, 2016, were analyzed with segmented regression of interrupted time series. Standardized monthly rates for each analgesic class (total, opioid, nonsteroidal anti-inflammatory drug, acetaminophen, and other study analgesics) were analyzed with segmented negative binomial regression models with overall slope, step, and slope change. Similarly, segmented linear regression was used to analyze pain intensity ratings and percentage of those reporting pain. All models were additionally adjusted for age, sex, and race. Before OSI implementation, total analgesic prescriptions showed a steady rise, abruptly decreasing to a flat trajectory after OSI implementation. This trend was primarily due to a decrease in opioid prescribing after OSI. Total prescribing after OSI implementation was partially compensated by continuing increased prescribing of other study analgesics as well as a significant rise in acetaminophen prescriptions (post-OSI). No changes in nonsteroidal anti-inflammatory drug prescribing were seen. A small rise in the percentage of those reporting pain but not mean pain intensity ratings continued over the study period with no changes associated with OSI. Changes in analgesic prescribing trends were not paralleled by changes in reported pain intensity for older veterans with osteoarthritis.
Effect of Prescription Size on Opioid Use and Patient Satisfaction After Minor Hand Surgery
Authors: Gaddis Andrew , Dowlati Ehsan , Apel Peter J. , Bravo Cesar J. , Dancea Horatiu C. , Hagan Hugh J. , Mierisch Cay M. , Metzger Tom A. , Mierisch Cassandra 
Published: February 2019

Objective:
To determine the influence of initial prescription size on opioid consumption after minor hand surgeries. Secondary outcomes include efficacy of pain control, patient satisfaction, and refill requests.

Background:
Retrospective studies have shown that opioid prescriptions for acute pain after surgical procedures are often excessive in size, which encourages misuse. This is the first prospective randomized trial on the influence of initial prescription size on opioid consumption in the setting of acute postsurgical pain.

Methods:
In a prospective randomized trial at a single-academic institution, patients were provided an initial prescription of either 10 or 30 hydrocodone/acetaminophen (5/325 mg) pills after surgery. Two hundred opioid-naive patients, aged 19 to 69, undergoing elective outpatient minor hand surgeries were enrolled over 9 months, with a follow-up period of 10 to 14 days.

Results:
One hundred seventy-four patients were included in this analysis. Patients initially prescribed 30 pills (n = 79), when compared with patients initially prescribed 10 pills (n = 95), used significantly more opioid (P = <0.001, mean 11.9 vs 6.4 pills), had significantly more leftover medication (P = <0.001, mean 20.0 vs 5.2 pills), and were over 3 times more likely to still be taking opioid at follow-up (15% vs 4%). There was no significant difference in refills requested, or in patient satisfaction with postoperative pain control.

Conclusions:
Providing large opioid prescriptions for the management of acute pain after minor upper extremity surgeries increases overall opioid use when compared with smaller initial prescriptions. The size of initial opioid prescription is a modifiable variable that should be considered both in patient care and research design.
An economical viable tokamak fusion reactor based on the ITER experience
Authors: Janeschitz G. 
Published: February 2019

This is my personal vision and outlook towards a fusion reactor based on my extensive experience from being part of the ITER design, and now construction, as well as leading the largest fusion technology program worldwide (KIT—Karlsruhe Institute of Technology) for 7 years. In particular, I want to discuss how a fusion reactor can be economically viable without employing too advanced physics and technology. It certainly will be a pulsed machine (approx. 20 000 s pulses) with thermal energy storage (turbine is steady state). I also want to discuss the optimum machine size and toroidal field for such a machine and why I think that high field and smaller plasmas may not necessarily make a fusion reactor more competitive. When one extrapolates from today's knowledge on ITER construction, even considering that ITER can be built much cheaper, it is clear that a fusion power plant will cost more than 10 or more likely more than 15 billion Euros/Dollars (the first of a kind even approx. 30 billion). Therefore, in order to have an economically attractive fusion reactor, it needs to produce a large amount of power (on the order of 2.5 GW electric). The possible size (R ∼ 10 m) and reasonably conservative physics basis of such a machine will be briefly described in the presentation. If we are successful in achieving advanced physics in a burning plasma, e.g. in ITER, then we can make the machine slightly smaller but the principal arguments for a large machine will not change significantly. Key technologies and their status will be discussed with particular emphasis on a realistic blanket and divertor design and the size and issues of a tritium-plant (T-plant) for such a machine as well as the challenges which have to be overcome beyond what is needed for ITER. Finally, a simple economic consideration will be discussed to show that a large machine could be economically viable, even in today's environment, in particular, in competition with renewables.
This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’.
Engineering challenges for accelerated fusion demonstrators
Authors: Surrey E. 
Published: February 2019

There are several programmes within the fusion community that are engaged in the design of fusion devices to follow the International Thermonuclear Experimental Reactor (ITER), referred to as ‘demonstrators’. These programmes have identified many issues over the past decade, and research now concentrates on optimizing the combination of systems against a set of Key Performance Indicators (KPI) which may vary between programmes. While the return on investment in and experience from ITER is seen as an important factor in this research there are significant differences in the operational conditions and KPI of demonstrators that generate additional problems requiring different solutions. Among these problems are the necessary use of uncommon materials for structural and functional purposes, the impact of the availability KPI on basic machine design, configuration and component lifetime and the integration of the tritium fuel and thermodynamic cycles. These raise issues of component manufacture and standards and of resource availability in the required quantities and quality that are independent of device size and design. Interpreting ‘accelerating fusion’ in a wider sense, the impact of these issues, analysed in respect of developmental timescales, shows that a strategy of early engagement with the industrial supply chain and the development of computational engineering testing and verification will be essential to prevent prolonged timescales to fusion progress.
This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’
Can the development of fusion energy be accelerated? An introduction to the proceedings
Authors: Windsor Colin 
Published: February 2019

This introduction reviews the unique opportunity of fusion power to deliver safe, carbon-free, abundant, base-load power. The differences from fission power are considered: especially why a Chernobyl, Three Mile Island or Fukushima accident could not happen with a fusion reactor. The Lawson triple product is introduced, along with tokamaks, or magnetic bottles, whose ability to approach close to the fusion burn conditions has so far put them above their competitors. Our last fusion power Discussion Meeting was organized by Derek Robinson FRS in 1998, and the progress since then is reviewed. Tokamaks are introduced, and the advantages of spherical tokamaks are listed along with the special engineering challenges that they introduce. Their key advantage is high plasma pressure, and the importantβparameter indicating the efficiency of the magnetic field use is introduced. High-temperature superconductors are described along with the opportunities they allow for higher magnetic fields at higher current densities and more modest cryogenic temperatures. The question posed is whether the two developments of spherical tokamaks and high-temperature superconductors could lead to more economical fusion power plants and faster development than the current route through ITER and DEMO.This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’.
Characterizing and inferring quantitative cell cycle phase in single-cell RNA-seq data analysis
Authors: Hsiao Chiaowen Joyce , Tung PoYuan , Blischak John D. , Burnett Jonathan E. , Barr Kenneth A. , Dey Kushal K. , Stephens Matthew , Gilad Yoav 
Published: February 2019

AbstractCellular heterogeneity in gene expression is driven by cellular processes such as cell cycle and cell-type identity, and cellular environment such as spatial location. The cell cycle, in particular, is thought to be a key driver of cell-to-cell heterogeneity in gene expression, even in otherwise homogeneous cell populations. Recent advances in single-cell RNA-sequencing (scRNA-seq) facilitate detailed characterization of gene expression heterogeneity, and can thus shed new light on the processes driving heterogeneity. Here, we combined fluorescence imaging with scRNA-seq to measure cell cycle phase and gene expression levels in human induced pluripotent stem cells (iPSCs). Using these data, we developed a novel approach to characterize cell cycle progression. While standard methods assign cells to discrete cell cycle stages, our method goes beyond this, and quantifies cell cycle progression on a continuum. We found that, on average, scRNA-seq data from only five genes predicted a cell’s position on the cell cycle continuum to within 14% of the entire cycle, and that using more genes did not improve this accuracy. Our data and predictor of cell cycle phase can directly help future studies to account for cell-cycle-related heterogeneity in iPSCs. Our results and methods also provide a foundation for future work to characterize the effects of the cell cycle on expression heterogeneity in other cell types.
A new mechanism for tree mortality due to drought and heatwaves
Authors: Cochard Hervé 
Published: February 2019

AbstractPlants tend to die earlier in hot and drought conditions, but the underlying mechanisms are not yet understood. I propose here a new mechanism by which excessive residual water losses caused by high cuticular permeabilities and a high leaf-to-air vapor pressure deficits would trigger uncontrolled and sudden cavitation events. The combination of heat and drought stresses may therefore lead to an unsuspected risk of hydraulic failure. I explored this hypothesis with a new mechanistic model. The simulations support this hypothesis and highlight the critical role played by the cuticle phase transition temperature. Experiments are now awaited to confirm these predictions.