Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduction potential of urban PM2.5 mortality risk using modern ventilation systems in buildings.

UNLABELLED Urban PM2.5 (particulate matter with aerodynamic diameter smaller than 2.5 microm) is associated with excess mortality and other health effects. Stationary sources are regulated and considerable effort is being put into developing low-pollution vehicles and environment-friendly transportation systems. While waiting for technological breakthroughs in emission controls, the current work assesses the exposure reductions achievable by a complementary means: efficient filtration of supply air in buildings. For this purpose infiltration factors for buildings of different ages are quantified using Exposures of Adult Urban Populations in Europe Study (EXPOLIS) measurements of indoor and outdoor concentrations in a population-based probability sample of residential and occupational buildings in Helsinki, Finland. These are entered as inputs into an evaluated simulation model to compare exposures in the current scenario with an alternative scenario, where the distribution of ambient PM2.5 infiltration factors in all residential and occupational buildings are assumed to be similar to the subset of existing occupational buildings using supply air filters. In the alternative scenario exposures to ambient PM2.5 were reduced by 27%. Compared with source controls, a significant additional benefit is that infiltration affects particles from all outdoor sources. The large fraction of time spent indoors makes the reduction larger than what probably can be achieved by local transport policies or other emission controls in the near future. PRACTICAL IMPLICATIONS It has been suggested that indoor concentrations of ambient particles and the associated health risks can be reduced by using mechanical ventilation systems with supply air filtering in buildings. The current work quantifies the effects of these concentration reductions on population exposures using population-based data from Helsinki and an exposure model. The estimated exposure reductions suggest that correctly defined building codes may reduce annual premature mortality by hundreds in Finland and by tens of thousands in the developed world altogether.
Postpartum hemorrhage: When uterotonics and sutures fail

Systemic bleeding at the time of postpartum hemorrhage (PPH) is usually the result of coagulopathy that has developed acutely as a result of massive hemorrhage after uterotonics and sutures have failed. Occasionally, the patient has a preexisting coagulopathy, but more often, coagulopathy arises acutely as the result of massive hemorrhage, which is usually related to obstetrical and less often surgical bleeding. Despite being able to identify risk factors for PPH in the antenatal and intrapartum period, the majority of women who ultimately develop PPH do not have any such factors and every pregnancy is at risk. The coagulopathy associated with massive PPH may be due to hemodilution, failure of liver synthetic function as occurs with acute liver failure of pregnancy, or disseminated intravascular coagulation (DIC). There are no data from clinical trials to help guide management of transfusion in PPH, although the management of blood component therapy in severe PPH is similar to that in other massive hemorrhage. Standard practice is to replace fibrinogen to maintain a level of ≥100 mg/dL, yet recent evidence suggests that the level of fibrinogen needed to prevent PPH is at least 400 mg/dL. Recombinant activated factor VIIa (rFVIIa) has been used in the management of severe PPH unresponsive to blood component therapy. Coagulation laboratory evaluation may be useful in guiding hemostatic management during massive PPH, but for the results to be useful, they must be rapidly available and provide information that would not be available from clinical assessment alone. The hematologist or hemostasis expert has the opportunity to make the difference between life and death for the patient experiencing massive PPH. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Global and regional effects of land-use change on climate in 21st century simulations with interactive carbon cycle

Abstract. Biogeophysical (BGP) and biogeochemical (BGC) effects of land-use and land cover change (LULCC) are separated at the global and regional scales in new interactive CO2 simulations for the 21st century. Results from four earth system models (ESMs) are analyzed for the future RCP8.5 scenario from simulations with and without land-use and land cover change (LULCC), contributing to the Land-Use and Climate, IDentification of robust impacts (LUCID) project. Over the period 2006–2100, LULCC causes the atmospheric CO2 concentration to increase by 12, 22, and 66 ppm in CanESM2, MIROC-ESM, and MPI-ESM-LR, respectively. Statistically significant changes in global near-surface temperature are found in three models with a BGC-induced global mean annual warming between 0.07 and 0.23 K. BGP-induced responses are simulated by three models in areas of intense LULCC of varying sign and magnitude (between −0.47 and 0.10 K). Modifications of the land carbon pool by LULCC are disentangled in accordance with processes that can lead to increases and decreases in this carbon pool. Global land carbon losses due to LULCC are simulated by all models: 218, 57, 35 and 34 Gt C by MPI-ESM-LR, MIROC-ESM, IPSL-CM5A-LR and CanESM2, respectively. On the contrary, the CO2-fertilization effect caused by elevated atmospheric CO2 concentrations due to LULCC leads to a land carbon gain of 39 Gt C in MPI-ESM-LR and is almost negligible in the other models. A substantial part of the spread in models' responses to LULCC is attributed to the differences in implementation of LULCC (e.g., whether pastures or crops are simulated explicitly) and the simulation of specific processes. Simple idealized experiments with clear protocols for implementing LULCC in ESMs are needed to increase the understanding of model responses and the statistical significance of results, especially when analyzing the regional-scale impacts of LULCC.
Photoprotection in a purple phototrophic bacterium mediated by oxygen-dependent alteration of carotenoid excited-state properties

Carotenoids are known to offer protection against the potentially damaging combination of light and oxygen encountered by purple phototrophic bacteria, but the efficiency of such protection depends on the type of carotenoid. Rhodobacter sphaeroides synthesizes spheroidene as the main carotenoid under anaerobic conditions whereas, in the presence of oxygen, the enzyme spheroidene monooxygenase catalyses the incorporation of a keto group forming spheroidenone. We performed ultrafast transient absorption spectroscopy on membranes containing reaction center-light-harvesting 1-PufX (RC-LH1-PufX) complexes and showed that when oxygen is present the incorporation of the keto group into spheroidene, forming spheroidenone, reconfigures the energy transfer pathway in the LH1, but not the LH2, antenna. The spheroidene/spheroidenone transition acts as a molecular switch that is suggested to twist spheroidenone into an s-trans configuration increasing its conjugation length and lowering the energy of the lowest triplet state so it can act as an effective quencher of singlet oxygen. The other consequence of converting carotenoids in RC-LH1-PufX complexes is that S2/S1/triplet pathways for spheroidene is replaced with a new pathway for spheroidenone involving an activated intramolecular charge-transfer (ICT) state. This strategy for RC-LH1-PufX-spheroidenone complexes maintains the light-harvesting cross-section of the antenna by opening an active, ultrafast S1/ICT channel for energy transfer to LH1 Bchls while optimizing the triplet energy for singlet oxygen quenching. We propose that spheroidene/spheroidenone switching represents a simple and effective photoprotective mechanism of likely importance for phototrophic bacteria that encounter light and oxygen.
Cardiac Endothelial Cells Regulate Reactive Oxygen Species-induced Cardiomyocyte Apoptosis through Neuregulin-1β/erbB4 Signaling*

Neuregulin (NRG)-1β has a prosurvival effect on cardiac myocytes via the phosphatidylinositol-3-kinase/Akt pathway, but the physiological regulators of this system in the intact heart are unknown. In this study, we tested the hypothesis that reactive oxygen species regulate NRG/erbB signaling. We used isolated adult rat ventricular myocytes (ARVMs) or cardiac microvascular endothelial cells (CMECs) in monoculture, or together in coculture. H2O2 induced NRG-1β release from CMECs in a concentration-dependent manner, and conditioned medium from H2O2-treated CMEC activated ARVM erbB4. NRG-1β release occurred via proteolytic cleavage of 115-kDa transmembrane NRG-1β and was inhibited by the metalloproteinase inhibitor 1,10-phenanthroline. In myocyte monoculture, H2O2 induced erbB4-dependent, but NRG-independent, activation of Akt. To elucidate the bioactivity of CMEC-derived NRG-1β on ARVMs, we examined H2O2-induced myocyte apoptosis in co-culture using an antibody to NRG-1β. The percentages of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were significantly higher in the anti-NRG-1β group than in the control group. The change in apoptosis induced by anti-NRG-1β in co-culture was similar in magnitude to the protection of myocytes by addition of recombinant NRG-1β to ARVM monocultures. Activation of NRG/erbB paracrine signaling was also seen in the intact heart subjected to oxidative stress by ischemia-reperfusion injury. Isolated perfused mouse hearts subjected to 15 min of ischemia, followed by 30 min of reperfusion, showed complete proteolytic cleavage of 115-kDa NRG-1β, with concomitant erbB4 phosphorylation. These results demonstrate that reactive oxygen species activate NRG-1β/erbB4 paracrine signaling in the heart and suggest that this system is involved in cardiac adaptation to oxidative stress.
Role of neuropsin in parvalbumin immunoreactivity changes in hippocampal basket terminals of mice reared in various environments

In vitro approaches have suggested that neuropsin (or kallikrein 8/KLK8), which controls gamma-aminobutyric acid (GABA) neurotransmission through neuregulin-1 (NRG-1) and its receptor (ErbB4), is involved in neural plasticity (Tamura et al., 2012, 2013). In the present study, we examined whether parvalbumin (PV)-positive neuronal networks, the majority of which are ErbB4-positive GABAergic interneurons, are controlled by neuropsin in tranquil and stimulated voluntarily behaving mice. Parvalbumin-immunoreactive fibers surrounding hippocampal pyramidal and granular neurons in mice reared in their home cage were decreased in neuropsin-deficient mice, suggesting that neuropsin controls PV immunoreactivity. One- or two-week exposures of wild mice to novel environments, in which they could behave freely and run voluntarily in a wheel resulted in a marked upregulation of both neuropsin mRNA and protein in the hippocampus. To elucidate the functional relevance of the increase in neuropsin during exposure to a rich environment, the intensities of PV-immunoreactive fibers were compared between neuropsin-deficient and wild-type (WT) mice under environmental stimuli. When mice were transferred into novel cages (large cages with toys), the intensity of PV-immunoreactive fibers increased in WT mice and neuropsin-deficient mice. Therefore, behavioral stimuli control a neuropsin-independent form of PV immunoreactivity. However, the neuropsin-dependent part of the change in PV-immunoreactive fibers may occur in the stimulated hippocampus because increased levels of neuropsin continued during these enriched conditions.
Gestational Diabetes Mellitus and Sleep-Disordered Breathing

OBJECTIVE: To examine the link between gestational diabetes mellitus (GDM) and sleep-disordered breathing using complete polysomnography and questionnaires in a case–control study of pregnant women. METHODS: Pregnant women (body mass index [BMI] less than 35, no prior diabetes or hypertension) were eligible as cases (n=26) if diagnosed with GDM by routine 75-g oral glucose tolerance test. Women in the control group without GDM (n=26) were matched for gestational age at polysomnography, BMI, and age. Polysomnography were conducted at home at 24–32 weeks of gestation. Sleepiness score (Epworth Sleepiness Scale), subjective sleep quality (Pittsburgh Sleep Quality Index), risk for depression (Edinburgh Postnatal Depression Scale), and restless legs syndrome were assessed by questionnaire. RESULTS: Primary outcome apnea–hypopnea index (4.2±3.9 events per hour in women in the case group compared with 3.8±2.3 events per hour in women in the control group) as well as other objective and subjective sleep measures, including oxygen desaturation index, snoring, and flow limitation, were not significantly different between groups. Sleepiness was greater in women in the case group than in women in the control group (9.8±3.6 compared with 7.2±3.6, P=.05). Additionally, 23% of women in the case group compared with 0% of women in the control group (P<.01) reported an Edinburgh Scale score of at least 10 (suggesting significant depression) and 46% of women with GDM reported restless legs syndrome compared to 19% of women in the control group (P=.07). CONCLUSION: There was no association between GDM and sleep-disordered breathing in pregnant women with prepregnancy BMIs under 35 and no medical comorbidities. LEVEL OF EVIDENCE: II
How training in project management can help businesses to get back on track

Purpose – In the 1990s project management was a growing area, now it is almost impossible to go to any organization where there is not a project. This growth has been so fast that many people find themselves in charge of projects, with none of the special skills required. This paper aims to focus on the issues.Design/methodology/approach – The solution is to provide training as it is through the discipline of project management that all the enablers for change required to survive in the business world today canbe delivered. There is a de facto process based method for effective project management, widely used by the UK government and the private sector both in the UK and internationally, known as PRINCE2®. Findings – Effective project management training emphasizes structure, creativity and flexibility. The right type of training can offer multiple benefits to an organization to provide a tighter control over resources and an improved level of project risk. It can also raise the management skills of indivi.
The Type Ia Supernova Rate at z ≈ 0.5 from the Supernova Legacy Survey

We present a measurement of the distant Type Ia supernova (SN Ia) rate derived from the first 2 yr of the Canada-France-Hawaii Telescope Supernova Legacy Survey. We observed four 1° × 1° fields with a typical temporal frequency of ⟨Δt⟩ ∼ 4 observer-frame days over time spans of 158-211 days per season for each field, with breaks during the full Moon. We used 8-10 m class telescopes for spectroscopic follow-up to confirm our candidates and determine their redshifts. Our starting sample consists of 73 spectroscopically verified SNe Ia in the redshift range 0.2 < z < 0.6. We derive a volumetric SN Ia rate of rV(⟨z⟩ = 0.47) = × 10-4 yr-1 Mpc3, assuming h = 0.7, Ωm = 0.3, and a flat cosmology. Using recently published galaxy luminosity functions derived in our redshift range, we derive a SN Ia rate per unit luminosity of rL(⟨z⟩ = 0.47) = 0.154(syst.)(stat.) SN units. Using our rate alone, we place an upper limit on the component of SN Ia production that tracks the cosmic star formation history of 1 SN Ia per 103 M⊙ of stars formed. Our rate and other rates from surveys using spectroscopic sample confirmation display only a modest evolution out to z = 0.55.
Invasive and non-invasive fractional flow reserve index in validation of hemodynamic severity of intracoronary lesions

This review discusses visual and functional evaluation of the hemodynamic significance of the degree of stenosis in coronary angiography, with respect to the indications for revascularization. The concept of the coronary flow reserve is defined, and the theoretical assumptions of the invasive measurement of the fractional flow reserve (FFR) are presented. In the following part, the publication describes the basic steps of numerical stimulations in terms of computational fluid dynamics (CFD) in calculating the fractional flow reserve based on computed tomography (CT) coronary angiography (FFRCT). The numerical FFRCT estimation in correlation with invasive measurements, as well as benefits deriving from FFRCT in the diagnosis of coronary artery disease, is presented in the example of the multicentre prospective DISCOVER-FLOW trial and the DeFACTO project. The CDF method enables to obtain hemodynamic significance of stenosis solely from the coronary anatomy vizualized by CT angiography. The calculation of FFRCT increases the diagnostic reliability of coronary flow reserve estimations. It contributes to the improvement in patients’ qualification for contrast coronarography. If the accuracy of FFRCT is confirmed in clinical practice, and the time required for computational processing is shortened, it may turn out that the algorithms of coronary heart disease diagnosis will be verified and it will be to a greater extent based on the CT results.
Decreased PM10 Exposure Attenuates Age-Related Lung Function Decline: Genetic Variants in p53, p21, and CCND1 Modify This Effect

Background Decreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to air pollution. Objective We determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF25–75) associated with improved air quality. Methods Subjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter ≤ 10 μm (PM10) to each participant’s residential history 12 months before the baseline and follow-up assessments. Results The effect of diminishing PM10 exposure on FEF25–75 decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-μg/m3 decline in aver-age PM10 exposure over an 11-year period attenuated the average annual decline in FEF25–75 by 21.33 mL/year (95% confidence interval, 10.57–32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38–22.06) among GA genotypes, and by 6.00 mL/year (−4.54 to 16.54) among AA genotypes. Conclusions Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults.
Mapping Determinants of Gene Expression Plasticity by Genetical Genomics in C. elegans

Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 °C and 24 °C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains CB4856 (Hawaii) and N2 (Bristol). No less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment interaction, here termed plasticity quantitative trait loci. In contrast, only 8% of an estimated 188 cis-acting genes showed such interaction. This indicates that heritable differences in plastic responses of gene expression are largely regulated in trans. This regulation is spread over many different regulators. However, for one group of trans-genes we found prominent evidence for a common master regulator: a transband of 66 coregulated genes appeared at 24 °C. Our results suggest widespread genetic variation of differential expression responses to environmental impacts and demonstrate the potential of genetical genomics for mapping the molecular determinants of phenotypic plasticity.
Analysis of Decision Postponement Strategies for Aircraft Assignment under Uncertainty

The ability to effectively match supply and demand can result in significant revenue benefits in the airline industry, where supply and demand mismatches are common. We study the benefits of a decision postponement strategy for aircraft assignment under uncertainty. Our Demand Driven Swapping approach takes advantage of the inherent flexibilities in the system, and dynamically swaps aircraft as departures near and more accurate demand information is gathered. We analyze several swapping strategies characterized in terms of their frequency and timing. Our analytical results show that strategies that make the swapping decision early in time (so as to minimize disturbances to operations) perform very well on routes, where the demand uncertainty is low and the expected demands on the legs are well balanced. Otherwise, a swapping strategy, which revises the swapping decision over time, should be implemented. Our simulation results, based on real data obtained from United Airlines, confirm our analytical findings.
Haploidentical hematopoietic stem cell transplantation in adults with Philadelphia‐negative acute lymphoblastic leukemia: No difference in the high‐ and low‐risk groups

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective post‐consolidation therapy and curative option for adult patients with Philadelphia chromosome‐negative (Ph‐negative) acute lymphoblastic leukemia (ALL) in first complete remission (CR1). A human leukocyte antigen (HLA)‐haploidentical related donor (haplo‐RD) is one of the most important alternative sources for those without HLA‐identical sibling donor (ISD). The present study aimed to evaluate the outcomes of haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) in adult Ph‐negative ALL CR1 patients (n = 183). We produced an unmanipulated haplo‐HSCT protocol including granulocyte colony stimulating factor (G‐CSF) for all donors, intensive immune suppression, anti‐thymocyte globulin, and combination of G‐CSF‐primed bone marrow harvest and G‐CSF‐mobilized peripheral blood stem cells harvest as the source of stem cell grafts. The median age for high‐risk versus low‐risk groups were 29 versus 23 years. Three‐year incidences of relapse mortality and nonrelapse mortality for high‐risk versus low‐risk groups were 7.1% versus 11.1% (p = 0.498) and 18.0% versus 16.2% (p = 0.717), respectively. Three‐year probabilities of disease‐free survival and overall survival for high‐risk versus low‐risk groups were 67.6% versus 68.2% (p = 0.896) and 74.9% versus 72.7% (p = 0.981), respectively. Multivariate analysis showed that limited cGVHD and a lower pre‐HSCT comorbidity burden were associated with better outcomes. In summary, comparable outcomes were observed among high‐ and low‐risk Ph‐negative ALL CR1 patients after haplo‐HSCT. Haplo‐RD could be considered for adults with Ph‐negative ALL in CR1 as an important alternative source of donors in cases when no ISD is available.