bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-eclampsia and risk of dementia later in life: nationwide cohort study
Authors: Basit Saima , Wohlfahrt Jan , Boyd Heather A 
Published: October 2018

AbstractObjectiveTo explore associations between pre-eclampsia and later dementia, overall and by dementia subtype and timing of onset.DesignNationwide register based cohort study.SettingDenmark.PopulationAll women with at least one live birth or stillbirth between 1978 and 2015.Main outcome measureHazard ratios comparing dementia rates among women with and without a history of pre-eclampsia, estimated using Cox regression.ResultsThe cohort consisted of 1 178 005 women with 20 352 695 person years of follow-up. Women with a history of pre-eclampsia had more than three times the risk of vascular dementia (hazard ratio 3.46, 95% confidence interval 1.97 to 6.10) later in life, compared with women with no history of pre-eclampsia. The association with vascular dementia seemed to be stronger for late onset disease (hazard ratio 6.53, 2.82 to 15.1) than for early onset disease (2.32, 1.06 to 5.06) (P=0.08). Adjustment for diabetes, hypertension, and cardiovascular disease attenuated the hazard ratios only moderately; sensitivity analyses suggested that body mass index was unlikely to explain the association with vascular dementia. In contrast, only modest associations were observed for Alzheimer’s disease (hazard ratio 1.45, 1.05 to 1.99) and other/unspecified dementia (1.40, 1.08 to 1.83).ConclusionsPre-eclampsia was associated with an increased risk of dementia, particularly vascular dementia. Cardiovascular disease, hypertension, and diabetes were unlikely to mediate the associations substantially, suggesting that pre-eclampsia and vascular dementia may share underlying mechanisms or susceptibility pathways. Asking about a history of pre-eclampsia could help physicians to identify women who might benefit from screening for early signs of disease, allowing for early clinical intervention.
Short-term and long-term cost-effectiveness of a pedometer-based exercise intervention in primary care: a within-trial analysis and beyond-trial modelling
Authors: Anokye Nana , Fox-Rushby Julia , Sanghera Sabina , Cook Derek G , Limb Elizabeth , Furness Cheryl , Kerry Sally Margaret , Victor Christina R , Iliffe Steve , Ussher Michael , Whincup Peter H , Ekelund Ulf , deWilde Stephen , Harris Tess 
Published: October 2018

ObjectivesA short-term and long-term cost-effectiveness analysis (CEA) of two pedometer-based walking interventions compared with usual care.Design(A) Short-term CEA: parallel three-arm cluster randomised trial randomised by household. (B) Long-term CEA: Markov decision model.SettingSeven primary care practices in South London, UK.Participants(A) Short-term CEA: 1023 people (922 households) aged 45–75 years without physical activity (PA) contraindications. (b) Long-term CEA: a cohort of 100 000 people aged 59–88 years.InterventionsPedometers, 12-week walking programmes and PA diaries delivered by post or through three PA consultations with practice nurses.Primary and secondary outcome measuresAccelerometer-measured change (baseline to 12 months) in average daily step count and time in 10 min bouts of moderate to vigorous PA (MVPA), and EQ-5D-5L quality-adjusted life-years (QALY).MethodsResource use costs (£2013/2014) from a National Health Service perspective, presented as incremental cost-effectiveness ratios for each outcome over a 1-year and lifetime horizon, with cost-effectiveness acceptability curves and willingness to pay per QALY. Deterministic and probabilistic sensitivity analyses evaluate uncertainty.Results(A) Short-term CEA: At 12 months, incremental cost was £3.61 (£109)/min in ≥10 min MVPA bouts for nurse support compared with control (postal group). At £20 000/QALY, the postal group had a 50% chance of being cost saving compared with control. (B) Long-term CEA: The postal group had more QALYs (+759 QALYs, 95% CI 400 to 1247) and lower costs (−£11 million, 95% CI −12 to −10) than control and nurse groups, resulting in an incremental net monetary benefit of £26 million per 100 000 population. Results were sensitive to reporting serious adverse events, excluding health service use, and including all participant costs.ConclusionsPostal delivery of a pedometer intervention in primary care is cost-effective long term and has a 50% chance of being cost-effective, through resource savings, within 1 year. Further research should ascertain maintenance of the higher levels of PA, and its impact on quality of life and health service use.Trial registration numberISRCTN98538934; Pre-results.
Genetic depletion of 5-HT increases central apnea frequency and duration and dampens arousal but does not impact the circadian modulation of these variables
Authors: Mateika Jason H. , Komnenov Dragana , Pop Alexandru , Kuhn Donald M. 
Published: October 2018

We examined the impact of serotonin (5-HT) on the frequency and duration of central apneic events and the frequency of accompanying arousals during nonrapid and rapid eye movement (NREM and REM, respectively) sleep across the light/dark cycle. Electroencephalography, electromyography, core body temperature, and activity were recorded for 24 h following implantation of telemeters in wild-type (Tph2+/+) and tryptophan hydroxylase 2 knockout (Tph2−/−) male mice. The frequency and duration of central apneic events were increased, the number of apneic events coupled to an arousal was decreased, and the ventilatory sensitivity to hypoxia and hypercapnia was decreased in the Tph2−/−compared with the Tph2+/+mice during NREM sleep. Apnea frequency and duration were similar in the Tph2−/−and Tph2+/+mice during REM sleep. The duration of apneic events during REM compared with NREM sleep was similar in the Tph2−/−mice. In contrast, the duration was greater during REM sleep in the Tph2+/+mice. Our results also revealed that apnea frequency was greater during the light compared with the dark cycle. Circadian modulation of this variable was evident in both the Tph2−/−and Tph2+/+mice during NREM and REM sleep. We conclude that depletion of 5-HT increases the frequency and duration of central apneic events, dampens arousal, and blunts the ventilatory response to hypoxia and hypercapnia during NREM sleep but is not essential for the circadian modulation of these variables.NEW & NOTEWORTHY The presence of serotonin (5-HT) in the central nervous system diminishes the frequency of central apneic events. This neuromodulator also moderates the duration of central apneic events and promotes arousal from central events if they occur during nonrapid eye movement (NREM) sleep. However, 5-HT is not responsible for the circadian modulation of apnea frequency, which we found was greater during NREM sleep in the light compared with the dark cycle.
Perisaccadic perceptual mislocalization is different for upward saccades
Authors: Grujic Nikola , Brehm Nils , Gloge Cordula , Zhuo Weijie , Hafed Ziad M. 
Published: October 2018

Saccadic eye movements, which dramatically alter retinal images, are associated with robust perimovement perceptual alterations. Such alterations, thought to reflect brain mechanisms for maintaining perceptual stability in the face of saccade-induced retinal image disruptions, are often studied by asking subjects to localize brief stimuli presented around the time of horizontal saccades. However, other saccade directions are not usually explored. Motivated by recently discovered asymmetries in upper and lower visual field representations in the superior colliculus, a structure important for both saccade generation and visual analysis, we observed significant differences in perisaccadic perceptual alterations for upward saccades relative to other saccade directions. We also found that, even for purely horizontal saccades, perceptual alterations differ for upper vs. lower retinotopic stimulus locations. Our results, coupled with conceptual modeling, suggest that perisaccadic perceptual alterations might critically depend on neural circuits, such as superior colliculus, that asymmetrically represent the upper and lower visual fields. NEW & NOTEWORTHY Brief visual stimuli are robustly mislocalized around the time of saccades. Such mislocalization is thought to arise because oculomotor and visual neural maps distort space through foveal magnification. However, other neural asymmetries, such as upper visual field magnification in the superior colliculus, may also exist, raising the possibility that interactions between saccades and visual stimuli would depend on saccade direction. We confirmed this behaviorally by exploring and characterizing perisaccadic perception for upward saccades.
Zebrafish: Speeding Up the Cancer Drug Discovery Process
Authors: Letrado Patricia , de Miguel Irene , Lamberto Iranzu , Díez-Martínez Roberto , Oyarzabal Julen 
Published: October 2018

Abstract
Zebrafish (Danio rerio) is an ideal in vivo model to study a wide variety of human cancer types. In this review, we provide a comprehensive overview of zebrafish in the cancer drug discovery process, from (i) approaches to induce malignant tumors, (ii) techniques to monitor cancer progression, and (iii) strategies for compound administration to (iv) a compilation of the 355 existing case studies showing the impact of zebrafish models on cancer drug discovery, which cover a broad scope of scenarios. Finally, based on the current state-of-the-art analysis, this review presents some highlights about future directions using zebrafish in cancer drug discovery and the potential of this model as a prognostic tool in prospective clinical studies. Cancer Res; 78(21); 6048–58. ©2018 AACR.
Identification of Serum Biomarker Panels for the Early Detection of Pancreatic Cancer
Authors: Song Jin , Sokoll Lori J. , Pasay Jered J. , Rubin Abigail L. , Li Hanying , Bach Dylan M. , Chan Daniel W. , Zhang Zhen 
Published: October 2018

Abstract

Background:
Pancreatic cancer is a deadly disease for which available biomarkers, such as CA19-9, lack the desired sensitivity and specificity for early detection. Additional biomarkers are needed to improve both its sensitivity and specificity.

Methods:
Multiplex immunoassays were developed for selected biomarkers using a Bio-Plex 200 system, and analytical performance was optimized. All proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC; n = 188) or benign pancreatic conditions (131) and healthy controls (89). The clinical performance of these markers was evaluated individually or in combination for their ability to complement CA19-9 for the early detection of pancreatic cancer.

Results:
A 6-plex immunoassay was developed with negligible cross-reactivity, wide dynamic range, recovery of 89% to 104%, and intra-assay and interassay precision of 10.2% to 19.6% and 13.7% to 29.3%, respectively. Individually, the best biomarkers to separate PDAC early stage from chronic pancreatitis or intraductal papillary mucinous neoplasm (IPMN) were CA19-9 and MIA or CA19-9 and MIC-1. Logistic regression modeling selected the two-marker panels that significantly improved the individual biomarker performance in discriminating PDAC early stage from chronic pancreatitis (AUCCA19-9+MIA = 0.86 vs. AUCCA19-9 = 0.81 or AUCMIA = 0.75 only, P &lt; 0.05) or IPMN (AUCCA19-9+MIC-1 = 0.81 vs. AUCCA19-9 = 0.75 or AUCMIC-1 = 0.73 only, P &lt; 0.05). It was observed that osteopontin (OPN) outperformed CA19-9 in separating IPMN from chronic pancreatitis (AUCOPN = 0.80 vs. AUCCA19-9 = 0.70, P &lt; 0.01).

Conclusions:
The biomarker panels evaluated by assays with high analytical performance demonstrated potential complementary values to CA19-9, warranting additional clinical validation to determine their role in early detection of pancreatic cancer.

Impact:
The validated biomarker panels could lead to earlier intervention and better outcomes.
Drivers of Precipitation Change: An Energetic Understanding
Authors: Richardson T. B. , Forster P. M. , Andrews T. , Boucher O. , Faluvegi G. , Fläschner D. , Hodnebrog Ø. , Kasoar M. , Kirkevåg A. , Lamarque J.-F. , Myhre G. , Olivié D. , Samset B. H. , Shawki D. , Shindell D. , Takemura T. , Voulgarakis A. 
Published: October 2018

AbstractThe response of the hydrological cycle to climate forcings can be understood within the atmospheric energy budget framework. In this study precipitation and energy budget responses to five forcing agents are analyzed using 10 climate models from the Precipitation Driver Response Model Intercomparison Project (PDRMIP). Precipitation changes are split into a forcing-dependent fast response and a temperature-driven hydrological sensitivity. Globally, when normalized by top-of-atmosphere (TOA) forcing, fast precipitation changes are most sensitive to strongly absorbing drivers (CO2, black carbon). However, over land fast precipitation changes are most sensitive to weakly absorbing drivers (sulfate, solar) and are linked to rapid circulation changes. Despite this, land-mean fast responses to CO2 and black carbon exhibit more intermodel spread. Globally, the hydrological sensitivity is consistent across forcings, mainly associated with increased longwave cooling, which is highly correlated with intermodel spread. The land-mean hydrological sensitivity is weaker, consistent with limited moisture availability. The PDRMIP results are used to construct a simple model for land-mean and sea-mean precipitation change based on sea surface temperature change and TOA forcing. The model matches well with CMIP5 ensemble mean historical and future projections, and is used to understand the contributions of different drivers. During the twentieth century, temperature-driven intensification of land-mean precipitation has been masked by fast precipitation responses to anthropogenic sulfate and volcanic forcing, consistent with the small observed trend. However, as projected sulfate forcing decreases, and warming continues, land-mean precipitation is expected to increase more rapidly, and may become clearly observable by the mid-twenty-first century.
Recent Sea Ice Decline Did Not Significantly Increase the Total Liquid Freshwater Content of the Arctic Ocean
Authors: Wang Qiang , Wekerle Claudia , Danilov Sergey , Sidorenko Dmitry , Koldunov Nikolay , Sein Dmitry , Rabe Benjamin , Jung Thomas 
Published: October 2018

Abstract
The freshwater stored in the Arctic Ocean is an important component of the global climate system. Currently the Arctic liquid freshwater content (FWC) has reached a record high since the beginning of the last century. In this study we use numerical simulations to investigate the impact of sea ice decline on the Arctic liquid FWC and its spatial distribution. The global unstructured-mesh ocean general circulation model Finite Element Sea Ice–Ocean Model (FESOM) with 4.5-km horizontal resolution in the Arctic region is applied. The simulations show that sea ice decline increases the FWC by freshening the ocean through sea ice meltwater and modifies upper ocean circulation at the same time. The two effects together significantly increase the freshwater stored in the Amerasian basin and reduce its amount in the Eurasian basin. The salinification of the upper Eurasian basin is mainly caused by the reduction in the proportion of Pacific Water and the increase in that of Atlantic Water (AW). Consequently, the sea ice decline did not significantly contribute to the observed rapid increase in the Arctic total liquid FWC. However, the changes in the Arctic freshwater spatial distribution indicate that the influence of sea ice decline on the ocean environment is remarkable. Sea ice decline increases the amount of Barents Sea branch AW in the upper Arctic Ocean, thus reducing its supply to the deeper Arctic layers. This study suggests that all the dynamical processes sensitive to sea ice decline should be taken into account when understanding and predicting Arctic changes.
Perioperative Risk Factors Associated With Morbidity and Mortality Following Pediatric Inpatient Sinus Surgery
Authors: Burton Brittany N. , Gilani Sapideh , Desai Milli , Saddawi-Konefka Robert , Willies-Jacobo Lindia , Gabriel Rodney A. 
Published: October 2018

Objectives: Pediatric sinus surgery is indicated for a wide range of sinonasal and skull base pathologies, but it is most commonly performed for recalcitrant chronic rhinosinusitis or complicated acute sinusitis. The authors aim to report medical risk factors of morbidity and mortality following inpatient sinus surgery in the pediatric population. Methods: Using data from the Kids’ Inpatient Database from 2003 to 2012, patients with International Classification of Diseases, Ninth Revision, procedure codes for primary sinus surgery were identified. Mixed-effect multivariable logistic regression was used to identify risk factors of inpatient postoperative morbidity and mortality. Results: The final sample included a weighted estimate of 4965 pediatric patients. The rates of inpatient morbidity and mortality were 6% and 1%, respectively. Respiratory complications (2.5%) were the most prevalent postoperative adverse events. The most prevalent comorbidities were chronic sinusitis (59.8%), acute sinusitis (27.8%), and cystic fibrosis (26.4%). Compared with patients who did not experience any morbidity, patients with inpatient morbidity had higher rates of pneumonia, mycoses, and nasal or paranasal benign neoplasm ( P < .05). The odds of inpatient morbidity and mortality were highest for patients with leukemia (odds ratio, 2.74; 95% confidence interval, 1.59-4.72; P < .001) and mycoses (odds ratio, 15.84; 95% confidence interval, 6.45-38.89; P < .001), respectively. Conclusions: This study is the first to report the national comorbidity burden and risk factors for postoperative adverse events following inpatient sinus surgery. Knowledge of the comorbidities and independent factors associated with morbidity and mortality will help in directing preoperative optimization and counseling. Level of Evidence: 2c
Assessing the cost-effectiveness of a routine versus an extensive laboratory work-up in the diagnosis of anaemia in Dutch general practice
Authors: Kip Michelle MA , Schop Annemarie , Stouten Karlijn , Dekker Soraya , Dinant Geert-Jan , Koffijberg Hendrik , Bindels Patrick JE , IJzerman Maarten J , Levin Mark-David , Kusters Ron 
Published: October 2018

Background Establishing the underlying cause of anaemia in general practice is a diagnostic challenge. Currently, general practitioners individually determine which laboratory tests to request (routine work-up) in order to diagnose the underlying cause. However, an extensive work-up (consisting of 14 tests) increases the proportion of patients correctly diagnosed. This study investigates the cost-effectiveness of this extensive work-up. Methods A decision-analytic model was developed, incorporating all societal costs from the moment a patient presents to a general practitioner with symptoms suggestive of anaemia (aged ≥ 50 years), until the patient was (correctly) diagnosed and treated in primary care, or referred to (and diagnosed in) secondary care. Model inputs were derived from an online survey among general practitioners, expert estimates and published data. The primary outcome measure was expressed as incremental cost per additional patient diagnosed with the correct underlying cause of anaemia in either work-up. Results The probability of general practitioners diagnosing the correct underlying cause increased from 49.6% (95% CI: 44.8% to 54.5%) in the routine work-up to 56.0% (95% CI: 51.2% to 60.8%) in the extensive work-up (i.e. +6.4% [95% CI: −0.6% to 13.1%]). Costs are expected to increase slightly from €842/patient (95% CI: €704 to €994) to €845/patient (95% CI: €711 to €994), i.e. +€3/patient (95% CI: €−35 to €40) in the extensive work-up, indicating incremental costs of €43 per additional patient correctly diagnosed. Conclusions The extensive laboratory work-up is more effective for diagnosing the underlying cause of anaemia by general practitioners, at a minimal increase in costs. As accompanying benefits in terms of quality of life and reduced productivity losses could not be captured in this analysis, the extensive work-up is likely cost-effective.
No Effect of Cue Format on Automation Dependence in an Aided Signal Detection Task
Authors: Bartlett Megan L. , McCarley Jason S. 
Published: October 2018

Objective: To investigate whether manipulating the format of an automated decision aid’s cues can improve participants’ information integration strategies in a signal detection task. Background: Automation-aided decision making is often suboptimal, falling well short of statistically ideal levels. The choice of format in which the cues from the aid are displayed may help users to better understand and integrate the aid’s judgments with their own. Method: Participants performed a signal detection task that asked them to classify random dot images as either blue or orange dominant. They made their judgments either unaided or with assistance from a 93% reliable automated decision aid. The aid provided a binary judgment, along with an estimate of signal strength in the form of either a raw value, a likelihood ratio, or a confidence rating (Experiments 1 and 2) or a binary judgment along with either a verbal or verbal-visuospatial expression of confidence (Experiment 3). Aided sensitivity was benchmarked to the predictions of various statistical models of collaborative decision making. Results and Conclusion: Aided performance was suboptimal, matching the predictions of some of the least efficient models. Most importantly, performance was similar across cue formats. Application: Results indicate that changes to the format in which cues from a signal detection aid are rendered are unlikely to dramatically improve the efficiency of automation-aided decision making.
Assessing the trends of energy use of public non-domestic buildings in England and Wales
Authors: Hong S , Mylona A , Davies H , Ruyssevelt P , Mumovic D 
Published: October 2018

Accessing sufficient data for understanding how energy is used in non-domestic buildings is deemed to be a challenge in many countries. In the UK, such a challenge has led to limited understanding of long-term changes in energy use of buildings. This study aims to develop a deeper understanding of the trends in energy use across the public sector non-domestic buildings in England. Display energy certificate (DEC) data which relate to 59,740 public sector non-domestic buildings in England and Wales were analysed. Statistical analyses were carried out to understand both the latest patterns of energy use and how they have changed between 2010 and 2016. The patterns of energy use of various public-sector buildings were found to have gradually changed over the seven-year period. An imminent release of a revised dataset was deemed necessary for understanding the performance of buildings to support the aspirations set out in the clean growth strategy. The study pointed to a need for regularly gathering and sharing data for understanding the changes in the patterns of energy use of the stock. Developing a framework that can facilitate this would enable various stakeholders make informed decisions for improving energy efficiency of the UK’s non-domestic buildings. Practical application: Statistics on electrical and fossil-thermal energy use intensity provide up-to-date reference points for assessing operational energy efficiency of public sector buildings. Principles for developing a framework are provided to support various stakeholders make informed decisions on for example setting design targets or making capital investments.