bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inclusion of Plasma Prolactin Levels in Current Risk Prediction Models of Premenopausal and Postmenopausal Breast Cancer
Authors: Gabrielson Marike , Ubhayasekera Kumari , Ek Bo , Andersson Franko Mikael , Eriksson Mikael , Czene Kamila , Bergquist Jonas , Hall Per 
Published: October 2018

Abstract

Background
Circulating plasma prolactin is associated with breast cancer risk and may improve our ability to identify high-risk women. Mammographic density is a strong risk factor for breast cancer, but the association with prolactin is unclear. We studied the association between breast cancer, established breast cancer risk factors and plasma prolactin, and improvement of risk prediction by adding prolactin.

Methods
We conducted a nested case-control study including 721 breast cancer patients and 1400 age-matched controls. Plasma prolactin levels were assayed using immunoassay and mammographic density measured by STRATUS. Odds ratios (ORs) were calculated by multivariable adjusted logistic regression, and improvement in the area under the curve for the risk of breast cancer by adding prolactin to established risk models. Statistical tests were two-sided.

Results
In multivariable adjusted analyses, prolactin was associated with risk of premenopausal (OR, top vs bottom quintile = 1.9; 1.88 (95% confidence interval [CI] = 1.08 to 3.26) but not with postmenopausal breast cancer. In postmenopausal cases prolactin increased by 10.6% per cBIRADS category (Ptrend = .03). In combined analyses of prolactin and mammographic density, ORs for women in the highest vs lowest tertile of both was 3.2 (95% CI = 1.3 to 7.7) for premenopausal women and 2.44 (95% CI = 1.44 to 4.14) for postmenopausal women. Adding prolactin to current risk models improved the area under the curve of the Gail model (+2.4 units, P = .02), Tyrer-Cuzick model (+3.8, P = .02), and the CAD2Y model (+1.7, P = .008) in premenopausal women.

Conclusion
Circulating plasma prolactin and mammographic density appear independently associated with breast cancer risk among premenopausal women, and prolactin may improve risk prediction by current risk models.
ALMACAL V: absorption-selected galaxies with evidence for excited ISMs
Authors: Klitsch A , Zwaan M A , Péroux C , Smail I , Oteo I , Popping G , Swinbank A M , Ivison R J , Biggs A D 
Published: October 2018

ABSTRACT
Gas-rich galaxies are selected efficiently via quasar absorption lines. Recently, a new perspective on such absorption-selected systems has opened up by studying the molecular gas content of absorber host galaxies using ALMA CO emission line observations. Here, we present an analysis of multiple CO transitions ($L^{\prime }_{\rm CO} \sim 10^9$ K km s−1) in two z ∼ 0.5 galaxies associated with one Ly α absorber towards J0238+1636. The CO spectral line energy distributions (CO SLEDs) of these galaxies appear distinct from that of typical star-forming galaxies at similar redshifts and is comparable with that of luminous infrared galaxies or active galactic nucleus (AGN). Indeed, these galaxies are associated with optically identified AGN activity. We infer that the CO line ratios and the αCO conversion factor differ from the Galactic values. Our findings suggest that at least a fraction of absorption-selected systems shows interstellar medium conditions deviating from those of normal star-forming galaxies. For a robust molecular gas mass calculation, it is therefore important to construct the CO SLED. Absorption line selection identifies systems with widely distributed gas, which may preferentially select interacting galaxies, which in turn will have more excited CO SLEDs than isolated galaxies. Furthermore, we raise the question whether quasar absorbers preferentially trace galaxy overdensities.
Cosmological simulations of the circumgalactic medium with 1 kpc resolution: enhanced H i column densities
Authors: van de Voort Freeke , Springel Volker , Mandelker Nir , van den Bosch Frank C , Pakmor Rüdiger 
Published: October 2018

ABSTRACT
The circumgalactic medium (CGM), i.e. the gaseous haloes around galaxies, is both the reservoir of gas that fuels galaxy growth and the repository of gas expelled by galactic winds. Most cosmological, hydrodynamical simulations focus their computational effort on the galaxies themselves and treat the CGM more coarsely, which means small-scale structure cannot be resolved. We get around this issue by running zoom-in simulations of a Milky Way-mass galaxy with standard mass refinement and additional uniform spatial refinement within the virial radius. This results in a detailed view of its gaseous halo at unprecedented (1 kpc) uniform resolution with only a moderate increase in computational time. The improved spatial resolution does not impact the central galaxy or the average density of the CGM. However, it drastically changes the radial profile of the neutral hydrogen column density, which is enhanced at galactocentric radii larger than 40 kpc. The covering fraction of Lyman-Limit Systems within 150 kpc is almost doubled. We therefore conclude that some of the observational properties of the CGM are strongly resolution dependent. Increasing the resolution in the CGM, without increasing the resolution of the galaxies, is a promising and computationally efficient method to push the boundaries of state-of-the-art simulations.
activPAL-measured sitting levels and patterns in 9–10 years old children from a UK city
Authors: Sherry Aron P , Pearson Natalie , Ridgers Nicola D , Barber Sally E , Bingham Daniel D , Nagy Liana C , Clemes Stacy A 
Published: October 2018

Abstract

Background
There is insufficient evidence of sitting time in UK children from validated objective measures. This study explored sitting patterns in primary school children from Bradford, UK, using the validated activPAL inclinometer.

Methods
Overall, 79 children (9.8 (SD 0.3) years old, 52% boys; 70% South Asian) wore activPALs for 7 days. Total sitting time, sitting time accumulated in different bout lengths, and the proportion of wear time spent in these variables were explored and compared across different periods of the week.

Results
Children spent 614 ± 112 (median ± IQR) min/day on school days and 690 ± 150 min/day on weekend days sitting. The proportion of time spent sitting was significantly higher on weekend days compared to school days (mean±SD: 74 ± 10% versus 68 ± 8%,P &lt; 0.001), as was the proportion of time accumulated in &gt;30 min sitting bouts (mean±CI: 28 ± 27–33% versus 20 ± 20–22%, P &lt; 0.001). The proportion of time spent sitting after school was significantly higher than during school time (mean±SD: 70 ± 8.4% versus 63 ± 8.3%,P &lt; 0.001), as was the proportion of time spent in prolonged (&gt;30 min) sitting bouts (mean±CI: 19 ± 16–22% versus 11 ± 10–14%, P &lt; 0.001).

Conclusions
Children spent large proportions of their waking day sitting, often accumulated in prolonged uninterrupted bouts and particularly after school and on weekends. Interventions to reduce sitting time in children are urgently needed.
Is Welfare a Magnet for Migration? Examining Universal Welfare Institutions and Migration Flows
Authors: Ponce Aaron 
Published: October 2018

AbstractThis study extends macro-structural research on international migration flows by going beyond conventional economic, demographic, and geographic explanations. Prior extensions suggest that migrants are drawn to places where welfare benefits are generous. I test the welfare magnet hypothesis while proposing an alternative explanation for migration: the prospect for inclusion. The analysis uses a comprehensive point-to-point migration dataset for a sample of robust welfare states, the universalist countries of Nordic Europe, and similarly positioned destinations representing other welfare types to examine destinations’ commitments to inclusion, humanitarianism, and welfare generosity. Results reveal no evidence for a magnet effect to the most generous welfare states in the world net of other recognized factors, and even suggest a negative influence linked to the region’s high cost of living. Migrants are instead drawn by the promise of social and political inclusion, migrating to destinations where co-ethnics have become full-fledged citizens. Additional evidence points to the role of international commitments to humanitarianism in augmenting flows. Findings integrate insights on contexts of immigrant reception with research on migration flows, thus contributing to a political sociology of immigration and citizenship and opening new avenues for research on the determinants of migration to newer, more distant locations.
Biological treatments for severe asthma: where do we stand?
Authors: Busse William W. 
Published: October 2018

Purpose of review
For patients with severe asthma, disease control is not achieved resulting in persistent morbidity and risks for exacerbations. The advent of biologics is providing a new form of treatment for many with severe asthma.

Recent findings
Four mAb biologics are approved for clinical use: omalizumab (anti-IgE) and three antieosinophilic interventions (mepolizumab, reslizumab, and benralizumab). These four biologics target components of the type 2-inflammatory pathway which is reflected by biomarkers: peripheral blood eosinophils and exhaled nitric oxide. In severe asthma, biologics have reduced asthma exacerbations. The antieosinophilic biologics have also improved lung function. The safety profile of these biologics has been good.

Summary
For patients with severe asthma and biomarkers indicating a type 2 inflammatory pathway, the addition of biologics has proven to be an effective approach to achieve disease control and is an appropriate next step treatment.
The challenge of cardiomyopathies and heart failure in pregnancy
Authors: Limongelli Giuseppe , Rubino Marta , Esposito Augusto , Russo Mariagiovanna , Pacileo Giuseppe 
Published: October 2018

Purpose of review
To discuss the risk preexisting or new onset cardiomyopathy/heart failure (CMP/heart failure) in pregnant woman, and recent insights regarding their management and therapy.

Recent findings
Recent data from the European Registry on Pregnancy and Heart disease of the European Society of Cardiology (ROPAC) suggest that, after an adequate prepregnancy evaluation in specialized centres, the vast majority of pregnancies are safe for both mother and foetus. A tailored approach is required according to cardiac phenotype (i.e. type of cardiomyopathy), clinical and functional status, and new potential treatments (i.e. bromocriptine in patients with peripartum cardiomyopathy).

Summary
In clinical practice, prepregnancy cardiac evaluation is mandatory, including evaluation of the clinical status, standard ECG (and 24–48 h monitoring, whenever required), and imaging, to define the individual risk profile. In presence of severe symptoms (advanced New York Heart Association class), cardiac dysfunction (moderate–severe reduced ejection fraction), haemodynamic load (left ventricular outflow tract obstruction, pulmonary hypertension), pregnancy is contraindicated. A tailored monitoring is warranted in other cases (mild–moderate risk pregnancies). Likewise, in women who develop PPCM, a risk stratification and tailored monitoring and therapy should be achieved by an expert, multidisciplinary team, including cardiologists, gynaecologists, obstetricians, genetic counsellor, and psychologists.
A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin Scarring
Authors: Gale Jeremy D. , Jensen Jeff , Berman Gabe , Freimuth William , Li Gang , Pleil Andreas , Kutty Malik , Rosenthal Andrew , Boswell C.B. , Noah V., E. Magnus , Young Leroy 
Published: October 2018

Background:
Connective tissue growth factor (CTGF) is a matricellular protein that plays a key role in wound healing and scar formation. Inhibition of CTGF by a specific antisense oligonucleotide significantly reduced scarring and fibrosis in animal models. This study examined whether an antisense oligonucleotide that inhibits human CTGF expression could reduce the severity of hypertrophic scar formation in patients following surgical revision of preexisting breast scars.

Methods:
This study was a 24-week multicenter, randomized, double-blind, within-subject, placebo-controlled phase 2b study evaluating the efficacy and safety of PF-06473871 in 2 regimens of either 3 or 4 intradermal injections (postsurgery weeks 2, 5, 8, and 11) of 5 mg/cm adjacent to the new surgical incision. One hundred subjects with bilateral hypertrophic scars resulting from prior breast surgery were randomized. Efficacy was determined by the Patient and Observer Scar Assessment Scale (POSAS).

Results:
The Physician/Observer POSAS overall opinion score at (week 24) for the 4-injection regimen demonstrated a statistically significant (P = 0.022) treatment difference from placebo of 0.68, and the treatment difference for the 3-injection regimen was nonsignificant (P = 0.4). Physician evaluation of scar severity at (week 24) with the photo-guide in the 4-injection regimen had a significant reduction (point estimate of treatment difference of 0.43 favoring PF-06473871). The surgical effect was approximately 2.0 at week 24 and was nearly 3 times greater than the treatment effect. Patient evaluations using the POSAS and photo-guide were not significantly improved with either dose regimen. PF-06473871 was generally well tolerated systemically and locally.

Conclusion:
The 4-dose regimen of PF-06473871 provided statistically significant improvement, inhibiting severity of hypertrophic scar formation based on physician assessment. However, the effect of revision surgery alone is significant and may dominate the treatment effect of PF-06473871.
Is Self-Reported Knee Stability Associated With Symptoms, Function, and Quality of Life in People With Knee Osteoarthritis After Anterior Cruciate Ligament Reconstruction?
Authors: Hart Harvi F. , Collins Natalie J. , Ackland David C. , Crossley Kay M. 
Published: October 2018

Objective:
This study aimed to investigate the association of self-reported knee stability with symptoms, function, and quality of life in individuals with knee osteoarthritis after anterior cruciate ligament reconstruction (ACLR).

Setting:
Cross-sectional.

Participants:
Twenty-eight individuals with knee osteoarthritis, 5 to 12 years after ACLR.

Main Outcome Measures:
Self-reported knee stability was assessed using visual analogue scales (VAS) during hop for distance (HD), side-to-side hop (SSH), and one-leg rise (OLR). Symptoms [Knee Injury and Osteoarthritis Outcome Score (KOOS) pain, Anterior Knee Pain Scale (AKPS), and International Knee Documentation Committee form], self-reported function (KOOS-sport/rec), performance-based function (hopping and OLR), and quality of life (KOOS-QOL) were assessed. K-means clustering categorized individuals into low (n = 8) and high self-reported knee stability (n = 20) groups based on participants' VAS scores during functional tasks.

Results:
The low self-reported knee stability group had worse knee symptoms than the high self-reported knee stability group [KOOS-pain: mean difference −17 (95% confidence interval, −28 to −5); AKPS: −10 (−20 to −1)], and worse self-reported function [KOOS-sport/rec: −33 (−48 to −18)] and performance-based function [HD: −28 (−53 to −3); SSH: −10 (−20 to −1), OLR: −18 (−32 to −50)].

Conclusion:
Low self-reported stability is associated with worse symptoms, and worse self-reported and performance-based function. Further research is required to determine the causation relation of self-reported knee stability to knee symptoms and function in individuals with knee osteoarthritis after ACLR.
Optimal duration of antibiotic treatment in Gram-negative infections
Authors: De Waele Jan J. , Martin-Loeches Ignacio 
Published: October 2018

Purpose of review
Whilst many guidelines recommend limiting the use of antibiotics because of the increase in antimicrobial resistance (AMR), this strategy becomes challenging when dealing with severe infections in critically ill patients. Moreover, some Gram-negative bacilli (GNB) can exhibit mechanisms of resistance that make the patient more vulnerable to recurrence of infections. We reviewed recent data on the optimal duration of antibiotic therapy in these patients.

Recent findings
Apart from having no additional clinical benefit at a certain point after initiation, antibiotics might have negative effects. Prolonged antibiotic exposure has been associated to development of AMR and represents a strong reason to avoid long courses of antibiotic therapy in GNB infections. Recent data suggest that also patients with severe infections, in whom source control is adequate, can be managed with short-course antibiotic therapy.

Summary
The optimal duration of antibiotic therapy depends on many factors, but overall, many infections in the critically ill can be treated with short-course antibiotic therapy (7 days or less). The integration of signs of resolution, biomarkers, clinical judgment, and microbiologic eradication might help to define this optimal duration in patients with life-threatening infections caused by GNB.
Perfusion of Porcine Kidneys With Macromolecular Heparin Reduces Early Ischemia Reperfusion Injury
Authors: Sedigh Amir , Nordling Sofia , Carlsson Fredrik , Larsson Erik , Norlin Bo , Lübenow Norbert , Lennmyr Fredrik , Tufveson Gunnar , Magnusson Peetra U. , Lorant Tomas 
Published: October 2018

Background
Previously, we have been able to demonstrate the possibility of coating the inner surface of the renal arteries in porcine kidneys with a heparin conjugate during hypothermic machine perfusion (HMP). The purpose of this study was to assess the efficacy of this treatment in reducing early ischemia-reperfusion injury.

Method
Brain death was induced in male landrace pigs by stepwise volume expansion of an epidural balloon catheter until negative cerebral perfusion pressure (CPP) was obtained. Both kidneys (matched pairs; n = 6 + 6) were preserved for 20 hours by HMP during which 50 mg heparin conjugate was added to one of the HMP systems (treated group). A customized ex vivo normothermic oxygenated perfusion (NP) system with added exogenous creatinine was used to evaluate early kidney function. Blood, urine and histological samples were collected during the subsequent 3 hours of NP.

Results
Kidney weight was lower at the end of NP (P = 0.017) in the treated group compared with control kidneys. The rate of decline in creatinine level was faster (P = 0.024), total urinary volume was higher (P = 0.031), and the level of urine neutrophil gelatinase-associated lipocalin (NGAL) was lower (P = 0.031) in the treated group. Histologically, less tubular changes were seen (P = 0.046). During NP intrarenal resistance remained lower (P < 0.0001) in the treated group.

Conclusions
Perfusion of porcine kidneys with heparin conjugate during HMP reduces preservation injury and improves organ function shortly after reperfusion. No increased risk of bleeding was seen in this setup. This protective strategy may potentially improve the quality of transplanted kidneys in the clinical setting.
Spatio-temporal patterns of thermal anomalies and drought over tropical forests driven by recent extreme climatic anomalies
Authors: Jimenez Juan C. , Barichivich Jonathan , Mattar Cristian , Takahashi Ken , Santamaría-Artigas Andrés , Sobrino José A. , Malhi Yadvinder 
Published: October 2018

The recent 2015–2016 El Niño (EN) event was considered as strong as the EN in 1997–1998. Given such magnitude, it was expected to result in extreme warming and moisture anomalies in tropical areas. Here we characterize the spatial patterns of temperature anomalies and drought over tropical forests, including tropical South America (Amazonia), Africa and Asia/Indonesia during the 2015–2016 EN event. These spatial patterns of warming and drought are compared with those observed in previous strong EN events (1982–1983 and 1997–1998) and other moderate to strong EN events (e.g. 2004–2005 and 2009–2010). The link between the spatial patterns of drought and sea surface temperature anomalies in the central and eastern Pacific is also explored. We show that indeed the EN2015–2016 led to unprecedented warming compared to the other EN events over Amazonia, Africa and Indonesia, as a consequence of the background global warming trend. Anomalous accumulated extreme drought area over Amazonia was found during EN2015–2016, but this value may be closer to extreme drought area extents in the other two EN events in 1982–1983 and 1997–1998. Over Africa, datasets disagree, and it is difficult to conclude which EN event led to the highest accumulated extreme drought area. Our results show that the highest values of accumulated drought area over Africa were obtained in 2015–2016 and 1997–1998, with a long-term drying trend not observed over the other tropical regions. Over Indonesia, all datasets suggest that EN 1982–1983 and EN 1997–1998 (or even the drought of 2005) led to a higher extreme drought area than EN2015–2016. Uncertainties in precipitation datasets hinder consistent estimates of drought severity over tropical regions, and improved reanalysis products and station records are required.
This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
A successful prediction of the record CO2rise associated with the 2015/2016 El Niño
Authors: Betts Richard A. , Jones Chris D. , Knight Jeff. R. , Keeling Ralph. F. , Kennedy John. J. , Wiltshire Andrew J. , Andrew Robbie M. , Aragão Luiz E. O. C. 
Published: October 2018

In early 2016, we predicted that the annual rise in carbon dioxide concentration at Mauna Loa would be the largest on record. Our forecast used a statistical relationship between observed and forecast sea surface temperatures in the Niño 3.4 region and the annual CO2rise. Here, we provide a formal verification of that forecast. The observed rise of 3.4 ppm relative to 2015 was within the forecast range of 3.15 ± 0.53 ppm, so the prediction was successful. A global terrestrial biosphere model supports the expectation that the El Niño weakened the tropical land carbon sink. We estimate that the El Niño contributed approximately 25% to the record rise in CO2, with 75% due to anthropogenic emissions. The 2015/2016 CO2rise was greater than that following the previous large El Niño in 1997/1998, because anthropogenic emissions had increased. We had also correctly predicted that 2016 would be the first year with monthly mean CO2above 400 ppm all year round. We now estimate that atmospheric CO2at Mauna Loa would have remained above 400 ppm all year round in 2016 even if the El Niño had not occurred, contrary to our previous expectations based on a simple extrapolation of previous trends.This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.