Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimation of Multivariate Frailty Models Using Penalized Partial Likelihood

Summary. There exists a growing literature on the estimation of gamma distributed multiplicative shared frailty models. There is, however, often a need to model more complicated frailty structures, but attempts to extend gamma frailties run into complications. Motivated by hip replacement data with a more complicated dependence structure, we propose a model based on multiplicative frailties with a multivariate log‐normal joint distribution. We give a justification and an estimation procedure for this generally structured frailty model, which is a generalization of the one presented by McGilchrist (1993, Biometrics49, 221‐225). The estimation is based on Laplace approximation of the likelihood function. This leads to estimating equations based on a penalized fixed effects partial likelihood, where the marginal distribution of the frailty terms determines the penalty term. The tuning parameters of the penalty function, i.e., the frailty variances, are estimated by maximizing an approximate profile likelihood. The performance of the approximation is evaluated by simulation, and the frailty model is fitted to the hip replacement data.
A New Species of Hydra (Cnidaria: Hydrozoa: Hydridae) and Molecular Phylogenetic Analysis of Six Congeners from China

A new species of genus Hydra (Cnidaria: Hydrozoa: Hydridae), Hydra shenzhensis sp. nov. from Guangdong Province, China, is described and illustrated. Most polyps have five tentacles. Column length reaches 11 mm when relaxed. Buds do not acquire tentacles synchronously. Stenotele is broad and pyriform in shape, 1.2 times as long as its width. Holotrichous isorhiza is asymmetrical and slender (more than 2.7 times as long as its width), with transverse and slanting coils. Atrichous isorhiza is long, resembling a melon-seed in shape. Desmoneme is asymmetrically pyriform in shape. The new species, belonging to the vulgaris group, is dioecious; sexual reproduction was found to occur mostly during November and December under conditions of dense culture or food shortage. Two to thirteen testes, cone-like shape with papilla, formed beneath the tentacles. One to three ovaries, with an egg cup, milky white in color, formed on body column. Ninety percent of individuals developed only one ovum. On a mother polyp, a fertilized ovum developed an embryonic theca covering its surface. The embryotheca is brown, with a spine-like structure, covering a layer of transparent, membrane-like material. For phylogenetic analysis, the mitochondrial cytochrome oxidase subunit I gene (COI) of six hydra species collected from China was amplified by polymerase chain reaction (PCR) and sequenced. Morphological characters in combination with molecular evidence support the hydra described here as a new species.
Adenosine-induced ST segment depression with normal perfusion.

BACKGROUND Intravenous adenosine in conjunction with myocardial perfusion imaging is commonly used for the detection of coronary artery disease and risk assessment. We have previously shown that patients with ischemic changes on the 12-lead electrocardiogram (ECG) in response to adenosine but with normal perfusion pattern have a benign outcome on short intermediate follow-up. The long-term outcome of these patients is unknown. METHODS Patients with ischemic ECG response (> or = 1 mm ST depression) to adenosine infusion but with normal perfusion on single-photon emission computed tomography (SPECT) imaging in the absence of a history of myocardial infarction or coronary revascularization were followed up for mortality, myocardial infarctions, and coronary revascularization. RESULTS The cohort consisted of 73 patients (81% women) who were followed up for mortality for a mean of 61 +/- 15 months. There were 10 deaths, and the cause of death was determined to be non-cardiac in half of those. Follow-up for the other endpoints was complete for 21 +/- 10 months during which no patient had myocardial infarction and seven underwent coronary revascularization. CONCLUSIONS Patients with ischemic ECG response to intravenous adenosine administration and normal perfusion on SPECT are at low risk of cardiovascular events. The ST segment response to adenosine in this setting is likely related to non-ischemic mechanisms.
Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma.

BACKGROUND Given the significant activity and tolerability of gemcitabine in patients with relapsed Hodgkin's lymphoma (HL), the critical role that nuclear factor kappa B (NF-kappaB) appears to play in the pathogenesis of this tumor, the ability of bortezomib to inhibit NF-kappaB activity, and laboratory studies suggesting synergistic antitumor effects of gemcitabine and bortezomib, we hypothesized that this combination would be efficacious in patients with relapsed or refractory HL. PATIENTS AND METHODS A total of 18 patients participated. Patients received 3-week cycles of bortezomib 1 mg/m(2) on days 1, 4, 8, and 11 plus gemcitabine 800 mg/m(2) on days 1 and 8. RESULTS The overall response rate for all patients was 22% (95% confidence interval 3% to 42%). Three patients developed grade III transaminase elevation: one was removed from the study and two had doses of gemcitabine held. Almost all patients exhibited inhibition of proteasome activity with treatment. CONCLUSIONS The combination of gemcitabine and bortezomib is a less active and more toxic regimen in relapsed HL than other currently available treatments. It poses a risk of severe liver toxicity and should be pursued with caution in other types of cancer.
Concepts of democracy in democratic and nondemocratic countries

Democratic experience constitutes an essential part of people’s world view and affects their understanding of democracy. This statement is confirmed by evidence from the World Values Survey (WVS) showing that the concept of democracy among citizens differs in democratic and nondemocratic societies. Democratic citizens associate democracy principally with gender equality, while people in nondemocratic countries associate it more strongly with a prospering economy and social control. People in democratic countries are also less likely to associate democracy with army rule and the intervention of religious authorities in political life than people in nondemocratic countries.
Effects of maize residue and mineral nitrogen applications on maize yield in conservation-agriculture-based cropping systems of Southern Africa

Abstract Conservation agriculture (CA) and no-till (NT)-based cropping systems could address soil degradation and fertility decline in southern Africa. A multi-location and multi-year experiment was carried out between 2008 and 2014 to assess the effects of different levels of maize residue biomass (0, 2, 4, 6 and 8 t ha−1) and nitrogen (N) fertilizer (0, 30, 90 kg ha−1) on maize performance under no-tillage. In some sites, different (N) fertilizer levels were superimposed to test their effects on maize grain yield and leaf chlorophyll content under different maize residue biomass levels. The different residue levels had no significant effect on maize yield in most growing seasons. Maize residue cover increased grain yield in eight out of 39 site-years across the sites used. However, in some sites, maize yield decreased with increases in residue level in cropping seasons that had average to above average rainfall. At a few sites maize yield increased with increase in residue level. Seasonal rainfall pattern influenced the effect of different residue levels on grain yield at most sites. Nitrogen fertilizer increased maize yield regardless of the residue level applied. This study demonstrates that mulching with maize residues in CA/NT systems results in limited maize yield gains – at least within the first 6 years in different agro-ecological conditions of southern Africa.
Re‐evaluating the role of astrocytes in blood‐brain barrier induction

Neural tissue induces brain capillary endothelial cells to express a diverse array of characteristics that allow them to regulate the passage of solutes between the blood and the brain; these features are collectively referred to as the blood‐brain barrier (BBB). Because astrocytes are intimately associated with brain capillaries, they have been thought to be the cell type responsible for barrier induction. Widely accepted support of this hypothesis has been derived from experiments showing that astrocytes implanted into the anterior chamber of the rat eye, or onto the chorioallantoic membrane of the chicken embryo, remain unstained by circulating Evan's blue, while grafts of fibroblasts in these sites stain intensely.
Granulocyte‐colony stimulating factor is neuroprotective in a model of Parkinson's disease

We have recently shown that the hematopoietic Granulocyte‐Colony Stimulating Factor (G‐CSF) is neuroprotective in rodent stroke models, and that this action appears to be mediated via a neuronal G‐CSF receptor. Here, we report that the G‐CSF receptor is expressed in rodent dopaminergic substantia nigra neurons, suggesting that G‐CSF might be neuroprotective for dopaminergic neurons and a candidate molecule for the treatment of Parkinson's disease. Thus, we investigated protective effects of G‐CSF in 1‐methyl‐4‐phenylpyridinium (MPP+)‐challenged PC12 cells and primary neuronal midbrain cultures, as well as in the mouse 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) model of Parkinson's disease. Substantial protection was found against MPP+‐induced dopaminergic cell death in vitro. Moreover, subcutaneous application of G‐CSF at a dose of 40 μg/Kg body weight daily over 13 days rescued dopaminergic substantia nigra neurons from MPTP‐induced death in aged mice, as shown by quantification of tyrosine hydroxylase‐positive substantia nigra cells. Using HPLC, a corresponding reduction in striatal dopamine depletion after MPTP application was observed in G‐CSF‐treated mice. Thus our data suggest that G‐CSF is a novel therapeutic opportunity for the treatment of Parkinson's disease, because it is well‐tolerated and already approved for the treatment of neutropenic conditions in humans.
Nursing morale: what is it like and why?

BACKGROUND There has been increased concern in the United Kingdom about the problems of recruitment and retention in the nursing profession, and how this is influenced by low morale. Despite this, however, there are relatively few studies, particularly of a qualitative nature, where nurses are asked about their morale and what factors affect it. AIMS The present study aimed to explore nursing morale and determine the factors which nurses believed to influence it. By doing so, it was hoped that factors which affect nurse recruitment and retention could be identified. METHODS Fifty-eight nurses (28 males, 30 females) working in the National Health Service in Scotland were interviewed in depth about their morale and their concerns about their career. Thematic analysis was carried out and a number of main issues emerged. FINDINGS Morale in this group was very low. A large number of nurses were considering leaving the profession and the majority would discourage others from becoming a nurse. The themes that emerged, which related to their disillusionment, included low pay, lack of support for education, limited opportunity for promotion, lack of resources and job insecurity. CONCLUSIONS The findings suggest that while recent salary increases may have helped to improve morale, other factors must also be addressed if further decline in morale and a subsequent nursing shortage is to be avoided.
Impact of prandial plus basal vs basal insulin on glycemic variability in type 2 diabetic patients.

OBJECTIVE To determine whether metformin-treated patients with type 2 diabetes given an analogue mixture of basal and rapid-acting insulins (insulin lispro protamine suspension plus insulin lispro) would have less glycemic variability than patients given basal insulin glargine. METHODS Two post hoc analyses were used to compare 7-point blood glucose profiles from 3 published studies comparing basal plus prandial premixed insulin lispro mixtures with insulin glargine in metformin-treated patients with type 2 diabetes. Glycemic variability indices used included standard deviation of mean daily blood glucose, coefficient of variation, M-value, mean amplitude of glycemic excursion, and J-index. RESULTS Patients on the twice-daily insulin lispro mix 75/25 (75% insulin lispro protamine suspension/25% insulin lispro) plus metformin regimen had significantly lower standard deviation, M-value, and J-index than patients on the insulin glargine plus metformin regimen, but not lower coefficient of variation or mean amplitude of glycemic excursion. Patients on the 3 times daily insulin lispro mix 50/50 (50% insulin lispro protamine suspension/50% insulin insulin lispro) plus metformin regimen had significantly lower values for all 5 indices than patients on the insulin glargine plus metformin regimen. CONCLUSION Use of basal plus prandial insulin lispro mixtures at 2 or 3 meals was associated with lower glycemic variability in metformin-treated patients with type 2 diabetes.
Exploiting heterogeneous publicly available data sources for drug safety surveillance: computational framework and case studies

ABSTRACT Objective: Driven by the need of pharmacovigilance centres and companies to routinely collect and review all available data about adverse drug reactions (ADRs) and adverse events of interest, we introduce and validate a computational framework exploiting dominant as well as emerging publicly available data sources for drug safety surveillance. Methods: Our approach relies on appropriate query formulation for data acquisition and subsequent filtering, transformation and joint visualization of the obtained data. We acquired data from the FDA Adverse Event Reporting System (FAERS), PubMed and Twitter. In order to assess the validity and the robustness of the approach, we elaborated on two important case studies, namely, clozapine-induced cardiomyopathy/myocarditis versus haloperidol-induced cardiomyopathy/myocarditis, and apixaban-induced cerebral hemorrhage. Results: The analysis of the obtained data provided interesting insights (identification of potential patient and health-care professional experiences regarding ADRs in Twitter, information/arguments against an ADR existence across all sources), while illustrating the benefits (complementing data from multiple sources to strengthen/confirm evidence) and the underlying challenges (selecting search terms, data presentation) of exploiting heterogeneous information sources, thereby advocating the need for the proposed framework. Conclusions: This work contributes in establishing a continuous learning system for drug safety surveillance by exploiting heterogeneous publicly available data sources via appropriate support tools.
Determinants of small for gestational age birth at term.

BACKGROUND Being born small for gestational age (SGA) is an indicator of intrauterine growth restriction (IUGR) and later health risks. This study investigated determinants of severe and moderate SGA (respectively, birthweight <3rd percentile and 3rd to <10th percentile for gestational age and sex). METHODS A total of 2195 term pregnancies from a prospective cohort were studied. Prenatal data arose from maternal interview at 10-22 weeks of gestation and perinatal data were collected from hospital charts. Severe and moderate SGA were classified by Canadian population standards. Risk factors for SGA were identified from fitting multivariable logistic regression models. RESULTS Multivariable associations with severe SGA were: maternal age ≥ 35 [odds ratio (OR) 3.2 [95% confidence interval (CI) 1.4, 6.9]], maternal smoking during pregnancy (OR 5.3 [95% CI 2.4, 11.7]), preeclampsia (OR 4.6 [95% CI 1.6, 13.2]) and threatened preterm labour (OR 3.9 [95% CI 1.3, 11.4]). Primiparity was associated with both severe and moderate SGA with OR 2.4 [95% CI 1.1, 5.1] and OR 1.9 [95% CI 1.3, 2.9] respectively. Underweight pre-pregnancy body mass index was associated with moderate SGA (OR 2.4 [95% CI 1.2, 5.0]). Inclusion of placental weight, in the final model attenuated the associations. CONCLUSIONS This study demonstrated different determinants for severe and moderate SGA. We speculate that the majority of severe SGA infants are IUGR while moderate SGA infants may be a mixture of IUGR and constitutionally small newborns. This study has also contributed evidence linking preterm labour and SGA as two, potentially related, outcomes of overlapping causal mechanisms reflective of ischaemic placental disease.
The Economic Impact of Road Accidents: The Case of Sri Lanka

The purpose of this study is to disclose accident-related indices and investigate the extent to which the road accidents impact on the economic performance of Sri Lanka during the period from 1977 to 2016. Annual time-series data are used to evaluate the accident indices for econometric analysis. Augmented Dickey–Fuller (ADF) unit root analysis and Johansen’s maximum likelihood estimator of the parameters of a cointegrating vector error correction model (VECM) are employed to test the stationary properties of the time series and to examine the long-run relationship between the variables, respectively. The results derived from the analysis confirm the existence of long-run relationship between the accident-related indices and macroeconomic indicators. The long-run elasticity values imply the signs and magnitude of impact of the accident indices on macroeconomic indicators. JEL: R41, H510, I310, I32
Infringements on Digital Information: Modern State of the Problem

Continuous expansion of the scope of network information technologies application permanently create the background for the appearance of new threats to the security of individuals, society and the state, including information security. Especially dangerous are terrorist acts potential threats by using information resources in the appropriate infrastructure of society and the state individual institutions. The current state of the problem of criminal liability for trespass to digital information, their dynamics and impact on Russia's technological and industrial potential, as well as the negative consequences of committing crimes in the sphere of digital information are considered in the article. A wide use of information and communication technologies (ICT) is an integral requirement of time representing an indicator of the development of a modern economy, both private and national, i.e. state. However, an increase in the share of information crime interferes with the progressive development of ICT. When using the methodological approach in science, measures of general prevention, as well as measures of special prevention aimed at digital crime countering are singled out. The most effective of them are special preventive measures, such as the current criminal, criminal procedure and information legislation improvement; the judicial practice improvement; the creation of new and improvement of existing methods of investigation and prevention of digital security crimes; the qualified personnel training in the field of information security (including specialized research institutes and government agencies of the relevant areas); as well as the need to keep within the necessary information security limits by the users themselves, both in the workplace and in everyday communication. This article is devoted to discussing some of these special preventive measures.
Stress‐related Responses in Alexandrium tamarense Cells Exposed to Environmental Changes

Organisms tend to be sensitive to drastic changes in environmental conditions. For unicellular microorganisms, variations in physico‐chemical conditions are particularly challenging and may result in acclimation, entrance into quiescence, or death through necrotic or autocatalytic pathways. This study focuses on the thecate dinoflagellate Alexandrium tamarense. Cellular responses to oxidative, thermal, and nutrient stress were characterized using stress indicators, such as pigment content, efficiency of photosystem II or production of reactive oxygen species (ROS), as well as hallmarks of apoptosis including activity of caspase‐like enzymes and expression of a metacaspase gene homolog. The formation of temporary cysts, a survival strategy of short‐term quiescence, was also monitored. Cellular responses appeared to depend on multifactorial influences where type and intensity of stimulus as well as position in cell cycle may act in combination. Sequences of events observed implicate ROS production as a key determinant of stress‐related pathways, playing potential roles in intracellular signaling, formation of temporary cysts, or cellular damage. Variations observed in caspase‐like activities and metacaspase gene expression did not appear to be associated with programmed cell death pathways; our results suggest a wider range of functions for these proteases in phytoplankton cells, including roles in survival pathways and cell cycle progression.
Depressive symptoms and the risk of type 2 diabetes mellitus in a US sample

There is some evidence to suggest that individuals with depression are at an almost twofold increased risk of developing type 2 diabetes mellitus, but results are far from conclusive. Therefore, to determine if depressive symptoms increased the risk of type 2 diabetes, we conducted longitudinal analyses using data from the NHANES I Epidemiologic Follow‐up Survey (NHEFS).
Existing knowledge of linguistic structure mitigates associative memory deficits in older adults

ABSTRACT Background/Study Context: Older adults show lower memory performance than younger adults when a task requires them to create associations (Naveh-Benjamin, 2000, Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1170–1187). In this study, associative memory was examined in order to assess whether age differences in performance were mitigated when the word pairs to be learned utilized a familiar pattern seen in everyday language (adjective-noun), which we propose as a type of schematic support that capitalizes upon linguistic structure. Methods: Thirty older (66–87 years old) and younger (18–22 years old) adults from the University of Missouri and the surrounding community studied word pairs in noun-noun, adjective-noun, and noun-adjective sequences. A mixed-measures analysis of variance (ANOVA) was used to analyze differences in memory sensitivity (d’) and response bias (C) from separate item and associative recognition memory tests between age groups and between word pair sequences. Results: As expected, older participants did show lower associative memory for noun-noun and noun-adjective pairs than younger adults, a hallmark of an age-related associative binding deficit, but there were no age differences in associative memory for adjective-noun pairs. The latter supports our hypothesis that seeing word pairs in a familiar adjective-noun linguistic sequence can provide support in older adults’ associative processing to mitigate difficulties experienced when binding together word pairs.Conclusion: The results obtained show that older adults can use prior existing knowledge to attenuate their cognitive shortcomings, specifically linguistic structural knowledge, to mitigate their associative binding deficit. Further research is necessary to determine the exact mechanism of improvement mediated by this form of schematic support, namely, whether it results in more effective recruitment of strategic processes such as unitization.