Miracle-dz/UniFAR-FTUs huggingface dataset:
Positive v. Normative Justifications for Benefit-Cost Analysis

What is the rationale for benefit-cost analysis (BCA)? The answer is critical for determining how BCA results should be interpreted, their implications for policy, and how BCA should be conducted. There are at least two possible bases for justifying BCA, positive and normative. The positive basis is that BCA identifies policy changes that satisfy the Kaldor-Hicks compensation test, so that those who benefit could hypothetically compensate those who are harmed. The normative basis is that BCA identifies social improvements, e.g., by approximating a utilitarian calculus or promoting more consistent decisions by protecting against cognitive error. When human behavior differs from that which is assumed in standard economic models, the justifications may conflict. Individuals whose behavior differs from the models may disprefer a change in circumstances that normative models predict they should prefer. The positive justification is consistent with respect for individual autonomy and provides clarity about methodological choices in the analysis but can require endorsing cognitive and behavioral errors that individuals would wish to avoid. The normative justification implies rejecting policies that the population prefers and requires determining what preferences are normatively acceptable. JEL classification: D61, D81, H40, Q50
Environmental Barcoding: A Next-Generation Sequencing Approach for Biomonitoring Applications Using River Benthos

Timely and accurate biodiversity analysis poses an ongoing challenge for the success of biomonitoring programs. Morphology-based identification of bioindicator taxa is time consuming, and rarely supports species-level resolution especially for immature life stages. Much work has been done in the past decade to develop alternative approaches for biodiversity analysis using DNA sequence-based approaches such as molecular phylogenetics and DNA barcoding. On-going assembly of DNA barcode reference libraries will provide the basis for a DNA-based identification system. The use of recently introduced next-generation sequencing (NGS) approaches in biodiversity science has the potential to further extend the application of DNA information for routine biomonitoring applications to an unprecedented scale. Here we demonstrate the feasibility of using 454 massively parallel pyrosequencing for species-level analysis of freshwater benthic macroinvertebrate taxa commonly used for biomonitoring. We designed our experiments in order to directly compare morphology-based, Sanger sequencing DNA barcoding, and next-generation environmental barcoding approaches. Our results show the ability of 454 pyrosequencing of mini-barcodes to accurately identify all species with more than 1% abundance in the pooled mixture. Although the approach failed to identify 6 rare species in the mixture, the presence of sequences from 9 species that were not represented by individuals in the mixture provides evidence that DNA based analysis may yet provide a valuable approach in finding rare species in bulk environmental samples. We further demonstrate the application of the environmental barcoding approach by comparing benthic macroinvertebrates from an urban region to those obtained from a conservation area. Although considerable effort will be required to robustly optimize NGS tools to identify species from bulk environmental samples, our results indicate the potential of an environmental barcoding approach for biomonitoring programs.
miR-145 suppresses the proliferation, invasion and migration of NSCLC cells by regulating the BAX/BCL-2 ratio and the caspase-3 cascade

Although microRNA (miR)-145 has been identified to be a tumor suppressor in various types of tumor, it promotes the progression of non-small cell lung cancer (NSCLC). However, the precise underlying molecular mechanism of its action remains unclear. The present study investigated the effects of miR-145 on the proliferation, invasion, metastasis and apoptosis of the NSCLC A549 cell line and the underlying molecular mechanism of its action. In vitro cell proliferation, invasion, migration and apoptosis assays were employed, and the expression levels of matrix metalloproteinase (MMP)-2, MMP-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3and poly(ADP-ribose) polymerase (PARP) were evaluated by western blot analysis. The results demonstrated that ectopic expression of miR-145 inhibited the proliferation, invasion and migration of A549 cells, but promoted the apoptosis of A549 cells. Western blot analysis indicated that increased miR-145 levels led to a marked decrease in the expression of MMP-2, MMP-9 and Bcl-2. Upregulation of miR-145 expression increased the expression of Bax, thus increasing the Bax/Bcl-2 ratio. Additionally, the results indicated that miR-145 over expression promoted the cleavage of caspase-3 and PARP. Taken together, these results indicated that miR-145 suppresses the proliferative, invasive and migratory ability of A549 cells. Additionally, miR-145 upregulation induced apoptosis of A549 cells possibly by decreasing MMP-2 and MMP-9 expression, the Bax/Bcl-2 ratio and the activity of the caspase-3 cascade.
Recurrence of cervical artery dissection

Objective To explore the recurrence of cervical artery dissection (CeAD). Methods A single-center consecutive series of 282 CeAD patients was prospectively recruited during first admission from 1995 to 2012. Patients with a follow-up of at least 1 year (n = 238) were eligible for the current analysis. All patients with clinical symptoms or signs of recurrent CeAD on ultrasound were examined by MRI. Dermal connective tissue morphology was studied in 108 (45.4%) patients. Results Median follow-up was 52 months (range 12–204 months). In all, 221 (92.8%) patients presented with monophasic CeAD, including 188 (79.0%) patients with a single CeAD event, 11 (4.6%) with simultaneous dissections in multiple cervical arteries, and 22 (9.2%) with subsequent events within a single phase of 4 weeks. Seventeen patients (7.1%) had late (>1 month after the initial event) recurrent CeAD events, including 5 (2.1%) with multiple recurrences. Patients with late recurrences were younger (37.5 ± 6.9 years) than those without (43.8 ± 9.9; p = 0.011). Ischemic stroke occurred in 164 (68.9%) patients at first diagnosis, but only 4 of 46 (8.7%) subsequent events caused stroke (p < 0.0001), while 19 (41.3%) were asymptomatic. Connective tissue abnormalities were found in 54 (56.3%) patients with monophasic and 8 (66.7%) with late recurrent dissections (p = 0.494). Conclusion Twenty-two (9.2%) patients had new CeAD events within 1 month and 17 (7.1%) later recurrences. The risk for new events was significantly higher (about 60-fold) during the acute phase than during later follow-up. Connective tissue abnormalities were not more frequent in patients with late recurrent events than in those with monophasic CeAD.
Media Exposure in Low-Income Preschool-Aged Children Is Associated with Multiple Measures of Self-Regulatory Behavior

Objective: Excessive screen media exposure in childhood is associated with parent-reported self-regulation difficulties. No studies have used laboratory-based or teacher-reported measures of child self-regulatory behaviors. This study examines cross-sectional associations between preschooler screen media exposure and multiple measures of self-regulatory behaviors. Methods: Preintervention data were used from 541 preschoolers in the Growing Healthy study, an obesity prevention trial (2011–2015). Screen media exposure was measured by daily screen media exposure (hr/d), television (TV) in the bedroom, frequency of background TV, and TV with meals (1 = rarely/never, 4 = frequently). Child self-regulatory behaviors were measured by the following: child ability to delay gratification, a standardized waiting paradigm; teacher-reported Social Competence and Behavior Evaluation; and parent-reported difficult temperament on the Child Behavior Questionnaire (CBQ). Multivariate regression analyses modeled screen media exposure predicting each self-regulatory measure, adjusting for child age, sex, parent age, education, marital status, income-to-needs ratio, number of adults in household, parent depressive symptoms, and sensitivity. Results: Children were aged 4.1 years (SD = 0.5), parents were aged 29.6 years (SD = 6.8), 48% had high school education or less, and 67% were married. Daily screen media exposure and background TV were associated with weaker observed self-regulation (&bgr;: −10.30 seconds for each hr/d media, −12.63 seconds for 1-point increase, respectively). Background TV and TV with meals were associated with greater parent-reported difficult temperament (&bgr;: 0.04 and 0.05 CBQ, respectively, for 1-point increase). Conclusion: Greater screen media exposure had small but significant associations with weaker observed and parent-reported, but not teacher-reported, self-regulatory behaviors. Longitudinal studies are needed to determine the directionality of associations.
Diverse Synaptic Distributions of G Protein‐coupled Estrogen Receptor 1 in Monkey Prefrontal Cortex with Aging and Menopause

Abstract Age‐ and menopause‐related impairment in working memory mediated by the dorsolateral prefrontal cortex (dlPFC) occurs in humans and nonhuman primates. Long‐term cyclic 17&bgr;‐estradiol treatment rescues cognitive deficits in aged ovariectomized rhesus monkeys while restoring highly plastic synapses. Here we tested whether distributions of G protein‐coupled estrogen receptor 1 (GPER1) within monkey layer III dlPFC synapses are sensitive to age and estradiol, and coupled to cognitive function. Ovariectomized young and aged monkeys administered vehicle or estradiol were first tested on a delayed response test of working memory. Then, quantitative serial section immunoelectron microscopy was used to determine the distributions of synaptic GPER1. GPER1‐containing nonperforated axospinous synapse density was reduced with age, and partially restored with estrogen treatment. The majority of synapses expressed GPER1, which was predominately localized to presynaptic cytoplasm and mitochondria. GPER1 was also abundant at plasmalemmas, and within cytoplasmic and postsynaptic density (PSD) domains of dendritic spines. GPER1 levels did not differ with age or treatment, and none of the variables examined were tightly associated with cognitive function. However, greater representation of GPER1 subjacent to the PSD accompanied higher synapse density. These data suggest that GPER1 is positioned to support diverse functions key to synaptic plasticity in monkey dlPFC.
The Spi1/PU.1 transcription factor accelerates replication fork progression by increasing PP1 phosphatase in leukemia

Oncogenes trigger replicative stress that can lead to genetic instability, which participates in cancer progression. Thus, determining how cells cope with replicative stress can help our understanding of oncogenesis and lead to the identification of new antitumor treatment targets. We previously showed that constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads to pre-leukemic cells that have a shortened S phase duration with an increased replication fork speed and increased mutability in the absence of DNA breaks. Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence that this is not due to negative control of its primary kinase ATR. Notably, we found that the expression of the CHK1 phosphatase PP1α is increased in Spi1/PU.1-overexpressing cells. By exogenously modulating its activity, we demonstrate that PP1α is required to maintain CHK1 in a dephosphorylated state and, more importantly, that it is responsible for the accelerated replication fork progression in Spi1/PU.1-overexpressing cells. These results identify a novel pathway by which an oncogene influences replication in the absence of DNA damage.
Birds on the move in the face of climate change: High species turnover in northern Europe

Abstract Species richness is predicted to increase in the northern latitudes in the warming climate due to ranges of many southern species expanding northwards. We studied changes in the composition of the whole avifauna and in bird species richness in a period of already warming climate in Finland (in northern Europe) covering 1,100 km in south–north gradient across the boreal zone (over 300,000 km2). We compared bird species richness and species‐specific changes (for all 235 bird species that occur in Finland) in range size (number of squares occupied) and range shifts (measured as median of area of occupancy) based on bird atlas studies between 1974–1989 and 2006–2010. In addition, we tested how the habitat preference and migration strategy of species explain species‐specific variation in the change of the range size. The study was carried out in 10 km squares with similar research intensity in both time periods. The species richness did not change significantly between the two time periods. The composition of the bird fauna, however, changed considerably with 37.0% of species showing an increase and 34.9% a decrease in the numbers of occupied squares, that is, about equal number of species gained and lost their range. Altogether 95.7% of all species (225/235) showed changes either in the numbers of occupied squares or they experienced a range shift (or both). The range size of archipelago birds increased and long‐distance migrants declined significantly. Range loss observed in long‐distance migrants is in line with the observed population declines of long‐distance migrants in the whole Europe. The results show that there is an ongoing considerable species turnover due to climate change and due to land use and other direct human influence. High bird species turnover observed in northern Europe may also affect the functional diversity of species communities.
From data to text in the Neonatal Intensive Care Unit: Using NLG technology for decision support and information management

Contemporary Neonatal Intensive Care Units collect vast amounts of patient data in various formats, making efficient processing of information by medical professionals difficult. Moreover, different stakeholders in the neonatal scenario, which include parents as well as staff occupying different roles, have different information requirements. This paper describes recent and ongoing work on building systems that automatically generate textual summaries of neonatal data. Our evaluation results show that the technology is viable and comparable in its effectiveness for decision support to existing presentation modalities. We discuss the lessons learned so far, as well as the major challenges involved in extending current technology to deal with a broader range of data types, and to improve the textual output in the form of more coherent summaries.
Family Planning and the Samburu: A Qualitative Study Exploring the Thoughts of Men on a Population Health and Environment Programme in Rural Kenya

Population Health and Environment (PHE) strategies are argued to improve ecosystem and human health by addressing family size and its effects on natural resource use, food security, and reproductive health. This study investigates men’s views on a PHE family planning (FP) programme delivered among the pastoral Samburu tribe in rural northern Kenya. Three focus group discussions and nine semi-structured interviews were conducted with 27 Samburu men. These discussions revealed support for environmentally-sensitised family planning promotion. Men highlighted their dependency on natural resources and challenges faced in providing for large families and maintaining livestock during drought. These practices were said to lead to natural resource exhaustion, environmental degradation, and wildlife dispersal, undermining key economic benefits of environmental and wildlife conservation. Relating family size to the environment is a compelling strategy to improve support for FP among Samburu men. Kenyan policy-makers should consider integrating community-based PHE strategies among underserved pastoral groups living in fragile ecosystems.
LRP 4 promotes synapse number and function of excitatory CNS neurons

Precise coordination of synaptic connections ensures proper information flow within circuits. The activity of presynaptic organizing molecules signaling to downstream pathways is essential for such coordination, though such entities remain incompletely known. We show that LRP4, a conserved transmembrane protein known for its postsynaptic roles, functions presynaptically as an organizing molecule. In the Drosophila brain, LRP4 localizes to the nerve terminals at or near active zones. Loss of presynaptic LRP4 reduces excitatory (not inhibitory) synapse number, impairs active zone architecture, and abolishes olfactory attraction the latter of which can be suppressed by reducing presynaptic GABAB receptors. LRP4 overexpression increases synapse number in excitatory and inhibitory neurons, suggesting an instructive role and a common downstream synapse addition pathway. Mechanistically, LRP4 functions via the conserved kinase SRPK79D to ensure normal synapse number and behavior. This highlights a presynaptic function for LRP4, enabling deeper understanding of how synapse organization is coordinated. DOI: 10.7554/eLife.27347. 001
Antifungal Tc17 cells are durable and stable, persisting as long-lasting vaccine memory without plasticity towards IFNγ cells

Our understanding of persistence and plasticity of IL-17A+ memory T cells is clouded by conflicting results in models analyzing T helper 17 cells. We studied memory IL-17A+ CD8+ T-cell (Tc17) homeostasis, persistence and plasticity during fungal vaccine immunity. We report that vaccine-induced memory Tc17 cells persist with high fidelity to the type 17 phenotype. Tc17 cells persisted durably for a year as functional IL-17A+ memory cells without converting to IFNγ+ (Tc1) cells, although they produced multiple type I cytokines in the absence of residual vaccine antigen. Memory Tc17 cells were canonical CD8+ T cells with phenotypic features distinct from Tc1 cells, and were Ror(γ)thi, TCF-1hi, T-betlo and EOMESlo. In investigating the bases of Tc17 persistence, we observed that memory Tc17 cells had much higher levels of basal homeostatic proliferation than did Tc1 cells. Conversely, memory Tc17 cells displayed lower levels of anti-apoptotic molecules Bcl-2 and Bcl-xL than Tc1 cells, yet were resistant to apoptosis. Tc1 cells required Bcl-2 for their survival, but Bcl-2 was dispensable for the maintenance of Tc17 cells. Tc17 and Tc1 cells displayed different requirements for HIF-1α during effector differentiation and sustenance and memory persistence. Thus, antifungal vaccination induces durable and stable memory Tc17 cells with distinct requirements for long-term persistence that distinguish them from memory Tc1 cells.
Confidence intervals in repeatability and reproducibility using the Bootstrap method

The repeatability and reproducibility (R&R) study--also called a gauge capability study--has been employed as part of the statistical process control program in many organizations. The objective of the study is to determine whether a measurement procedure or instrument is adequate for monitoring the performance of a process. The classical control chart method can be easily performed and calculations can be done with a spreadsheet or statistical computer software. However, this approach only provides the point estimates on the variance components of the measurement error study. In many situations, confidence intervals are more useful than point estimates, because an interval estimate enables an engineer to see both how small and how large an effect may be. In this paper, the Bootstrap method is used for obtaining the confidence intervals of the gauge variability when the control chart method is use for finding the point estimates. One real-life example is used to show the application of this control chart with the Bootstrapping method and comparisons are made with three experimental design procedures in terms of point estimates and confidence intervals for repeatability, reproducibility and total gauge variability.
Serum parathyroid hormone and risk of adverse outcomes in patients with stable coronary heart disease

Background and objective Recent longitudinal studies have suggested an association of high serum parathyroid hormone levels (PTH) with elevated cardiovascular risk in the general population. This study presents analyses of the prognostic value of baseline PTH for subsequent cardiovascular events and all-cause mortality in a high-risk population with stable coronary heart disease. Methods Based on measurements of PTH levels in 1133 patients recruited at two German rehabilitation clinics and followed over 8 years, multivariate Cox regression analysis was performed to estimate the risk of secondary cardiovascular events (including myocardial infarction, stroke and death due to cardiovascular diseases) and all-cause-mortality according to PTH quartiles (Q1–Q4) and continuous PTH concentrations. Results During follow-up, 153 cardiovascular events and 124 deaths occurred. Age and sex-adjusted Cox regression analysis yielded statistically significant positive associations of PTH with both cardiovascular event incidence and all-cause mortality (HR (95% CI) per SD increase of PTH: 1.35 (1.21–1.51) and 1.25 (1.11–1.42), respectively). Associations remained essentially unchanged after additional adjustment for multiple cardiovascular risk factors. More detailed dose–response analyses showed strong risk elevation for above-normal levels of PTH (>95th percentile), with essentially no association at lower levels. Conclusion The results of this first detailed study in a cohort of patients with stable coronary heart disease suggest an independent predictive value of above-normal PTH for the prognosis in patients with stable coronary heart disease.
1 Report for SHINE

Reduced folate status is now accepted as the most important risk factor for the occurrence (and recurrence) of NTD affected births (MRC Trial 1991). Consistent with this is a study that shows a graduation in risk in going for a reduced to an optimal folate status (Daly et al 1995). This study showed that in the index pregnancy (i.e. one in which the child had an NTD) there was a progressive relationship where the risk for mother with the lowest folate status was 7 per 1,000 births, reducing in a consistent way to where at an optimum folate status the risk had gone down tenfold to 0.7 per 1000 births. A further study (Daly et al 1997) showed that as little as 200 ug of extra folic acid per day could bring about a change in status from the highest to the lowest risk. These studies are consistent with the now wellestablished reduction in risk seen earlier in intervention trials and subsequently with folic acid fortification (MRC Trial 1991).