Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost-effectiveness of a transitional pharmaceutical care program for patients discharged from the hospital

Background To improve continuity of care at hospital admission and discharge and to decrease medication errors pharmaceutical care programs are developed. This study aims to determine the cost-effectiveness of the COACH program in comparison with usual care from a societal perspective. Methods A controlled clinical trial was performed at the Internal Medicine department of a general teaching hospital. All admitted patients using at least one prescription drug were included. The COACH program consisted of medication reconciliation, patient counselling at discharge, and communication to healthcare providers in primary care. The primary outcome was the proportion of patients with an unplanned rehospitalisation within three months after discharge. Also, the number of quality-adjusted life-years (QALYs) was assessed. Cost data were collected using cost diaries. Uncertainty surrounding cost differences and incremental cost-effectiveness ratios between the groups was estimated by bootstrapping. Results In the COACH program, 168 patients were included and in usual care 151 patients. There was no significant difference in the proportion of patients with unplanned rehospitalisations (mean difference 0.17%, 95% CI -8.85;8.51), and in QALYs (mean difference -0.0085, 95% CI -0.0170;0.0001). Total costs for the COACH program were non-significantly lower than usual care (-€1160, 95% CI -3168;847). Cost-effectiveness planes showed that the program was not cost-effective compared with usual care for unplanned rehospitalisations and QALYs gained. Conclusion The COACH program was not cost-effective in comparison with usual care. Future studies should focus on high risk patients and include other outcomes (e.g. adverse drug events) as this may increase the chances of a cost-effective intervention. Dutch trial register NTR1519
Overqualification, Job Dissatisfaction, and Increasing Dispersion in the Returns to Graduate Education

Increasing dispersion in the returns to graduate education is found, using quantile regression. This trend is related to rising overqualification. We distinguish between and validate measures of Real and Formal overqualification, according to whether it is or is not accompanied by underutilisation of skill; and using a unique data series in Britain we report the trend in overqualification types between 1992 and 2006. The distinction between types is relevant because employees in the Real Overqualification group experience greater, and more sharply rising, pay penalties than those in the Formal Overqualification group. Real Overqualification, but not Formal Overqualification, is associated with job dissatisfaction. Formal Overqualification has been increasing over time, and in 2006 characterised nearly one in four graduates. Real Overqualification has been steady or rising only slowly; in 2006 it affected less than one in ten graduates. Conditioning on graduates being matched to graduate jobs, it is found that there is no significant increase in the dispersion of returns to graduate education. The normative implication drawn is that the state should provide regular public information on the distribution of the returns to graduate education.
Neuropathies associated with paraproteinemia.

A number of common disorders of the peripheral nervous system, termed paraproteinemic neuropathies, are closely connected with the presence of excessive amounts of an abnormal immunoglobulin in the blood. These immunoglobulins can be detected by immunoelectrophoresis or the more sensitive immunofixation test. An estimated 10 percent of idiopathic polyneuropathies are of this type.1–3 The anomalous blood proteins are usually monoclonal (termed M protein or M spike) and are the product of a single clone of plasma cells. They are clinically important because some of them have the properties of antibodies directed at components of the myelin or the axolemma.
Ncbi reference sequence (refseq): a curated non - redundant sequence database of genomes

An edge surface (18) of an article (16) is treated in a fluid (52) with a minimum effect on other adjacent side surfaces of the article by contacting the edge surface to the surface of the fluid such that the fluid wets the side surfaces and forms a meniscus adjacent to each of the side surfaces. In the meniscus the fluid stagnates and quickly becomes an inactive barrier which shields the side surfaces of the article, while the edge surface of the article remains exposed for the duration of the treatment to the active bulk of the fluid.
Lateral magma propagation during the emplacement of La Gloria Pluton, central Chile

La Gloria Pluton (LGP) in central Chile is a shallow, north-northwest–elongated granitoid body of 18 km length and 4–6 km width, belonging to a regional north-south trend of Miocene plutons, from the San Francisco Batholith and porphyries in the north, to Mesón Alto, and San Gabriel in the south. New U-Pb zircon ages of the LGP indicate that crystallization occurred mostly within an interval between 11.3–10.2 Ma, with a pattern of decreasing ages along the pluton axis from south to north. The progression of zircon ages can be explained either by gradual northwestward migration of the feeder zone that supplied magma to the shallow pluton or, more likely, by shallow lateral magma propagation southeastward from a fixed feeder zone located beneath the northern margin of the pluton. The age progression, together with existing data of subhorizontal mineral and magnetic lineations in the LGP parallel to the pluton axis, indicate lateral propagation of magma during reservoir construction along the hinge of an anticline of the volcanic host sequences. In addition to controlling the position of possible volcanic output, such horizontal migration of silicic magmas in the upper crust significantly increases the surface footprint over which fluids are exsolved and outgas, strongly decreasing the potential for magmatic–hydrothermal ore formation above laterally emplaced laccoliths in the shallow crust.
Strontium ranelate: a novel treatment for postmenopausal osteoporosis: a review of safety and efficacy

Strontium ranelate is a new orally administered agent for the treatment of women with postmenopausal osteoporosis that reduces the risk of vertebral and hip fractures. Evidence for the safety and efficacy of strontium ranelate comes from two large multinational trials, the SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment Of Postmenopausal Osteoporosis) studies. The SOTI study evaluated vertebral fracture prevention in 1649 postmenopausal women with a mean age of 69 y. The subjects all had at least one previous vertebral fracture and a low spine bone mineral density (BMD) (equivalent to a Hologic spine T-score below −1.9). The strontium ranelate group had a 41% lower risk of a new vertebral fracture than the placebo group over the three-year study period (relative risk [RR]=0.59; 95% confidence interval [CI]: 0.48–0.73; p<0.001). The TROPOS study evaluated non-vertebral fracture prevention in 5091 postmenopausal women with a mean age of 77 y. The subjects were aged 74 y and over (or 70–74 y with one additional risk factor) and a low femoral neck BMD (equivalent to an NHANES III [Third National Health and Nutrition Examination Survey] T-score below −2.2). Over the three-year study period there was a 16% reduction in all non-vertebral fractures (RR=0.84; 95% CI 0.702–0.995; p=0.04) and a 19% reduction at the principal sites for non-vertebral fractures. The TROPOS study was not powered to investigate hip fracture risk. However, in a high risk group of women aged 74 y and over and with an NHANES III femoral neck T-score less than −2.4 there was a 36% reduction in hip fracture risk (RR=0.64; 95% CI: 0.412–0.997; p=0.046). The overall incidence of adverse events did not differ significantly from placebo and were generally mild and transient, the most common being nausea and diarrhea. Strontium ranelate is a useful addition to the range of anti-fracture treatments available for treating postmenopausal women with osteoporosis and is the only treatment proven to be effective at preventing both vertebral and hip fractures in women aged 80 y and over.
Potential Role of Induced Pluripotent Stem Cells (IPSCs) for Cell-Based Therapy of the Ocular Surface

The integrity and normal function of the corneal epithelium are crucial for maintaining the cornea’s transparency and vision. The existence of a cell population with progenitor characteristics in the limbus maintains a dynamic of constant epithelial repair and renewal. Currently, cell-based therapies for bio replacement—cultured limbal epithelial transplantation (CLET) and cultured oral mucosal epithelial transplantation (COMET)—present very encouraging clinical results for treating limbal stem cell deficiency (LSCD) and restoring vision. Another emerging therapeutic approach consists of obtaining and implementing human progenitor cells of different origins in association with tissue engineering methods. The development of cell-based therapies using stem cells, such as human adult mesenchymal or induced pluripotent stem cells (IPSCs), represent a significant breakthrough in the treatment of certain eye diseases, offering a more rational, less invasive, and better physiological treatment option in regenerative medicine for the ocular surface. This review will focus on the main concepts of cell-based therapies for the ocular surface and the future use of IPSCs to treat LSCD.
Rapid Production of Novel Pre-MicroRNA Agent hsa-mir-27b in Escherichia coli Using Recombinant RNA Technology for Functional Studies in Mammalian Cells

Noncoding microRNAs (miRNAs or miRs) have been revealed as critical epigenetic factors in the regulation of various cellular processes, including drug metabolism and disposition. However, research on miRNA functions is limited to the use of synthetic RNA and recombinant DNA agents. Herein, we show that novel pre-miRNA-27b (miR-27b) agents can be biosynthesized in Escherichia coli using recombinant RNA technology, and recombinant transfer RNA (tRNA)/mir-27b chimera was readily purified to a high degree of homogeneity (>95%) using anion-exchange fast protein liquid chromatography. The tRNA-fusion miR-27b was revealed to be processed to mature miRNA miR-27b in human carcinoma LS-180 cells in a dose- and time-dependent manner. Moreover, recombinant tRNA/miR-27b agents were biologically active in reducing the mRNA and protein expression levels of cytochrome P450 3A4 (CYP3A4), which consequently led to lower midazolam 1′-hydroxylase activity. These findings demonstrate that pre-miRNA agents can be produced by recombinant RNA technology for functional studies.
Galvanic vestibular stimulation in hemi-spatial neglect

Hemi-spatial neglect is an attentional disorder in which the sufferer fails to acknowledge or respond to stimuli appearing in contralesional space. In recent years, it has become clear that a measurable reduction in contralesional neglect can occur during galvanic vestibular stimulation, a technique by which transmastoid, small amplitude current induces lateral, attentional shifts via asymmetric modulation of the left and right vestibular nerves. However, it remains unclear whether this reduction persists after stimulation is stopped. To estimate longevity of effect, we therefore conducted a double-blind, randomized, dose-response trial involving a group of stroke patients suffering from left-sided neglect (n = 52, mean age = 66 years). To determine whether repeated sessions of galvanic vestibular stimulation more effectively induce lasting relief than a single session, participants received 1, 5, or 10 sessions, each lasting 25 min, of sub-sensory, left-anodal right-cathodal noisy direct current (mean amplitude = 1 mA). Ninety five percent confidence intervals indicated that all three treatment arms showed a statistically significant improvement between the pre-stimulation baseline and the final day of stimulation on the primary outcome measure, the conventional tests of the Behavioral Inattention Test. More remarkably, this change (mean change = 28%, SD = 18) was still evident 1 month later. Secondary analyses indicated an allied increase of 20% in median Barthel Index (BI) score, a measure of functional capacity, in the absence of any adverse events or instances of participant non-compliance. Together these data suggest that galvanic vestibular stimulation, a simple, cheap technique suitable for home-based administration, may produce lasting reductions in neglect that are clinically important. Further protocol optimization is now needed ahead of a larger effectiveness study.
Intensity of statin therapy and new hospitalizations for heart failure in patients with type 2 diabetes

Objective To examine a relationship between statin intensity and heart failure (HF) incidence in diabetes. Research design and methods We performed a retrospective cohort study of patients with type 2 diabetes (n=600; age, 66.3 years; men, 68%). Patients were categorized into three groups by baseline statin treatments—moderate-intensity, low-intensity, or no statin—and the independent association between the statin category and HF hospitalization during follow-up was examined. Results Over the course of the median 6-year follow-up, 17.7% of the patients were hospitalized for HF. Cox regression analysis revealed a significant association between the baseline statin category and HF incidence (p=0.002), independently of age, sex, hypertension, B-type natriuretic peptide, glycated hemoglobin, estimated glomerular filtration rate, and low-density lipoprotein (LDL) cholesterol levels. The moderate-intensity statin group had a significantly lower risk for HF than the low-intensity statin group with an adjusted HR of 0.31 (95% CI 0.13 to 0.65, p=0.0014). Interestingly, among patients with prevalent coronary artery diseases (CAD) and with baseline LDL controlled to less than 100 mg/dL, the frequency of HF was still significantly lower in the moderate-intensity group than in the low-intensity group or the no statin group. The effect of baseline statin category on HF was independent of incident CAD events during follow-up. Conclusions In type 2 diabetes, moderate-intensity statins, in comparison to low-intensity or no statin, were associated with lower HF incidence independently of LDL levels or of CAD events.
Single Particle Tracking of α7 Nicotinic AChR in Hippocampal Neurons Reveals Regulated Confinement at Glutamatergic and GABAergic Perisynaptic Sites

α7 neuronal nicotinic acetylcholine receptors (α7-nAChR) form Ca2+-permeable homopentameric channels modulating cortical network activity and cognitive processing. They are located pre- and postsynaptically and are highly abundant in hippocampal GABAergic interneurons. It is unclear how α7-nAChRs are positioned in specific membrane microdomains, particularly in cultured neurons which are devoid of cholinergic synapses. To address this issue, we monitored by single particle tracking the lateral mobility of individual α7-nAChRs labeled with α-bungarotoxin linked to quantum dots in live rat cultured hippocampal interneurons. Quantitative analysis revealed different modes of lateral diffusion of α7-nAChR dependent on their subcellular localization. Confined receptors were found in the immediate vicinity of glutamatergic and GABAergic postsynaptic densities, as well as in extrasynaptic clusters of α-bungarotoxin labeling on dendrites. α7-nAChRs avoided entering postsynaptic densities, but exhibited reduced mobility and long dwell times at perisynaptic locations, indicative of regulated confinement. Their diffusion coefficient was lower, on average, at glutamatergic than at GABAergic perisynaptic sites, suggesting differential, synapse-specific tethering mechanisms. Disruption of the cytoskeleton affected α7-nAChR mobility and cell surface expression, but not their ability to form clusters. Finally, using tetrodotoxin to silence network activity, as well as exposure to a selective α7-nAChR agonist or antagonist, we observed that α7-nAChRs cell surface dynamics is modulated by chronic changes in neuronal activity. Altogether, given their high Ca2+-permeability, our results suggest a possible role of α7-nAChR on interneurons for activating Ca2+-dependent signaling in the vicinity of GABAergic and glutamatergic synapses.
The RHO-1 RhoGTPase Modulates Fertility and Multiple Behaviors in Adult C. elegans

The Rho family of small GTPases are essential during early embryonic development making it difficult to study their functions in adult animals. Using inducible transgenes expressing either a constitutively active version of the single C. elegans Rho ortholog, RHO-1, or an inhibitor of endogenous Rho (C3 transferase), we demonstrate multiple defects caused by altering Rho signaling in adult C. elegans. Changes in RHO-1 signaling in cholinergic neurons affected locomotion, pharyngeal pumping and fecundity. Changes in RHO-1 signaling outside the cholinergic neurons resulted in defective defecation, ovulation, and changes in C. elegans body morphology. Finally both increased and decreased RHO-1 signaling in adults resulted in death within hours. The multiple post-developmental roles for Rho in C. elegans demonstrate that RhoA signaling pathways continue to be used post-developmentally and the resulting phenotypes provide an opportunity to further study post-developmental Rho signaling pathways using genetic screens.
A systematic review of outcomes following staged and synchronous carotid endarterectomy and coronary artery bypass.

OBJECTIVES to determine the overall cardiovascular risk for patients with combined cardiac and carotid artery disease undergoing synchronous coronary artery bypass (CABG) and carotid endarterectomy (CEA), staged CEA then CABG and reverse staged CABG then CEA. DESIGN systematic review of 97 published studies following 8972 staged or synchronous operations. RESULTS mortality was highest in patients undergoing synchronous CEA+CABG (4.6%, 95% CI 4.1-5.2). Reverse staged procedures (CABG-CEA) were associated with the highest risk of ipsilateral stroke (5.8%, 95% CI 0.0-14.3) and any stroke (6.3%, 95% CI 1.0-11.7). Peri-operative myocardial infarction (MI) was lowest following the reverse staged procedure (0.9%, 95% CI 0.5-1.4) and highest in patients undergoing staged CEA-CABG (6.5%, 95% CI 3.2-9.7). The risk of death+/-any stroke was highest in patients undergoing synchronous CEA+CABG (8.7%, 95% CI 7.7-9.8) and lowest following staged CEA-CABG (6.1%, 95% CI 2.9-9.3). The risk of death/stroke or MI was 11.5% (95% CI 10.1-12.9) following synchronous procedures versus 10.2% (95% CI 7.4-13.1) after staged CEA then CABG. CONCLUSIONS 10-12% of patients undergoing staged or synchronous procedures suffered death or major cardiovascular morbidity (stroke, MI) within 30 days of surgery. Overall, there was no significant difference in outcomes for staged and synchronous procedures and no comparable data for patients with combined cardiac and carotid disease not undergoing staged or synchronous surgery.
Sample size for testing and estimating the difference between two paired and unpaired proportions: a ‘two‐step’ procedure combining power and the probability of obtaining a precise estimate

Clinical trials and scientific research studies are currently planned calculating sample sizes to fulfill power requirements, but the simultaneous need to obtain a satisfactorily precise effect estimate is not widely recognized. I have devised a ‘two‐step’ iterative procedure for comparing two binomial parameters for two paired and unpaired proportions (the most frequent situations in scientific research), which takes into account power and the probability of obtaining a predetermined precision of the effect estimate. The first step provides the sample size for the power of the statistical test, the expected width of its corresponding confidence interval, and the probability of obtaining, under the alternative hypothesis, confidence intervals whose width is less than that expected. The second step iteratively increases this sample size until the probability of obtaining such confidence intervals exceeds a required threshold. Copyright 2004 © John Wiley & Sons, Ltd.
Clinicopathological and prognostic impact of imaging of breast cancer angiogenesis and hypoxia using diffuse optical spectroscopy

Near‐infrared diffuse optical spectroscopy (DOS) imaging can non‐invasively measure tumor hemoglobin concentration using high contrast to normal tissue, thus providing vascularity and oxygenation status. We assessed the clinical usefulness of DOS imaging in primary breast cancer. In all, 118 women with a histologically confirmed diagnosis of primary malignant tumor were enrolled. All participants underwent testing using time‐resolved DOS before treatment initiation. Visual assessment of DOS imaging for detecting tumors was carried out by two readers blinded to the clinical data. Relative total hemoglobin (rtHb) and oxygen saturation (stO2) of the tumors was compared with clinicopathological variables and 10‐year prognosis was calculated. Sensitivity for detecting a tumor based on the rtHb breast map was 62.7% (74/118). The sensitivity depended on T stage: 100% (7/7) for T3, 78.9% (45/57) for T2, 44.7% (17/38) for T1, and 31.3% (5/16) for Tis. Tumors showed unique features of higher rtHb with a wider range of stO2 than normal breast tissue, depending on histological type. There was a significant correlation of rtHb with tumor size, lymphatic vascular invasion, and histological grade, and of stO2 with age and tumor size. Neither rtHb nor stO2 correlated with intrinsic biomarkers such as estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2; rtHb inversely correlated with 10‐year relapse‐free survival and overall survival, with statistical significance. Diffuse optical spectroscopy imaging has limited utility for the early detection of breast cancer; nonetheless, the findings suggest that the degree of tumor angiogenesis and hypoxia may be associated with tumor aggressiveness and poor prognosis.
Noise Limitations on the Recovery of Average Values of Velocity Profiles in Pipelines by Simple Imaging Systems

This letter deals with a recently proposed two-step algorithm for the reconstruction of dielectric and velocity profiles of axially moving cylinders. In particular, the aim of the present work is to investigate the limitations and capabilities in reconstructing the velocity profile. By considering a best-case scenario, it is shown that, although the algorithm should be able to work even in the presence of flows with very small axial velocity values, reliable results can only be obtained when the axial speed is larger than a lower bound. This bound is shown to be an intrinsic limitation of the algorithm which is only related to the cross-polarization isolation of the measurement system. Other simulations, based on worst-case scenarios, confirm that such a bound is independent of the type of flow considered, of the configuration of the measurement system, and of the errors coming from the step devoted to the reconstruction of the dielectric profile. Finally, the same simulations show that the algorithm is reliable in a wide range of speed values, provided sensors with large cross-polarization isolations are exploited.
New results on partial fraction expansion based frequency weighted balanced truncation

In this paper, we present some new results on frequency weighted balanced truncation technique based on well-known partial-fraction-expansion idea. The reduced order models which are guaranteed to be stable in case of double-sided weighting are obtained by direct truncation. Two sets of simple, elegant and easily calculatable a priori error bounds are also derived. A numerical example and comparison with other well-known techniques show the effectiveness of the proposed method.