Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost-Effectiveness Uncertainty Analysis Methods

Objectives. To compare model input influence on incremental net monetary benefit (INMB) across 3 uncertainty methods: 1) 1-way sensitivity analysis; 2) probabilistic analysis of covariance (ANCOVA); and 3) expected value of partial perfect information (EVPPI). Methods. In a preliminary model, we used a published cost-effectiveness model and assumed £20,000 per quality-adjusted life-year (QALY) willingness-to-pay (Case 1: lower decision uncertainty) and £8000/QALY willingness-to-pay (Case 2: higher decision uncertainty). We conducted 1-way sensitivity, ANCOVA (10,000 Monte Carlo draws), and EVPPI for each model input (1000 inner and 1000 outer draws). We ranked inputs based on influence of INMB and compared input ranks across methods within case using Spearman’s rank correlation. We replicated this approach in 3 follow-up models: an additional linear model, a less linear model with uncorrelated inputs, and a less linear model with correlated inputs. Results. In the preliminary model, lower and higher decision uncertainty cases had the same top 3 influential parameters across uncertainty methods. The 2 most influential inputs contributed 78% and 49% of variation in outcome based on ANCOVA for lower decision uncertainty and higher decision uncertainty cases, respectively. In the follow-up models, input rank order correlations were higher across uncertainty methods in the linear model compared with both of the less linear models. Conclusions. Evidence across models suggests influential input rank agreement between 1-way and more advanced uncertainty analyses for relatively linear models with uncorrelated parameters but less agreement for less linear models. Although each method provides unique information, the additional resources needed to generate and communicate advanced analyses should be weighed, especially when outcome decision uncertainty is low. For less linear models or those with correlated inputs, performing and reporting deterministic and probabilistic uncertainty analyses appear prudent and conservative.
Step-to-step spatiotemporal variables and ground reaction forces of intra-individual fastest sprinting in a single session

ABSTRACT We aimed to investigate the step-to-step spatiotemporal variables and ground reaction forces during the acceleration phase for characterising intra-individual fastest sprinting within a single session. Step-to-step spatiotemporal variables and ground reaction forces produced by 15 male athletes were measured over a 50-m distance during repeated (three to five) 60-m sprints using a long force platform system. Differences in measured variables between the fastest and slowest trials were examined at each step until the 22nd step using a magnitude-based inferences approach. There were possibly–most likely higher running speed and step frequency (2nd to 22nd steps) and shorter support time (all steps) in the fastest trial than in the slowest trial. Moreover, for the fastest trial there were likely–very likely greater mean propulsive force during the initial four steps and possibly–very likely larger mean net anterior–posterior force until the 17th step. The current results demonstrate that better sprinting performance within a single session is probably achieved by 1) a high step frequency (except the initial step) with short support time at all steps, 2) exerting a greater mean propulsive force during initial acceleration, and 3) producing a greater mean net anterior–posterior force during initial and middle acceleration.
Development of Ultra-Precision Grinding Machine for Grazing Incidence X-Ray Mirrors.

In order to fabricate grazing incidence X-ray mirrors made of hard and brittle CVD-SiC, a large 5 axis control ultra-precision grinding machine has been developed. The machine must be capable of generating non-axisymmetric aspheric surfaces by ductile grinding. So as to obtain precise profile accuracy, new mechanisms such as flexible coupling, guide rails with fine deformation mechanism and leveling blocks for correcting warp of guide rails are applied to hydrostatic linear slideways. As experimental results, excellent straightness of X axis slide of 0.05 μm in a 500mm traverse is obtained on the grinding machine. Non-axisymmetric aspheric mirrors have been ground within a profile error of 0. 9μm with the machine.
Emulsion Based Gel Technique: Novel Approach for Enhancing Topical Drug Delivery of Hydrophobic Drugs

These modern days there is an upsurge in topical formulations such that it can be prepared by varying physico-chemical properties and providing better localized action. The patient adherence to topical formulations is significant in relation to chronic skin diseases, like fungal infections, acne, psoriasis. Emulgel is one of the recent technology in NDDS used topically having characteristics of dual control release i.e. emulsion as well as gel. Despite of many advantages of gels there is a major limitation of delivering the hydrophobic drug. Henceforth emulgel has been emerged as an auspicious topical drug delivery system for hydrophobic drugs and proves a boon for dermal care and cosmetology. It is prepared by different polymers which work as an emulsifier and thickener because the gelling capacity of these compounds give rise to stable emulsions and creams by decreasing surface and interfacial tension while at the same time increasing the viscosity of the aqueous phase. Emulgel are having major advantages on novel vesicular systems as well as on conventional systems considering various aspects. Numerous permeation enhancers can potentiate the effect of decreasing skin barrier resistance on the other hand promoting solubility of the drug in vehicle is also feasible. The use of emulgels can be considered well in analgesics and antifungal drugs.
FORMULATION AND OPTIMIZATION OF NANOSTRUCTURED LIPID MATRICES OF REPAGLINIDE USING FACTORIAL DESIGN

The purpose of the present research work was to overcome the poor solubility of repaglinide, reduce dosing frequency and increase the bioavailability by formulating repaglinide nanostructured lipid matrices and subject the formulation for optimization by using factorial design. Repaglinide, an antidiabetic drug is used for the management of type II diabetes mellitus. It is practically insoluble in water and undergoes hepatic first pass metabolism and hence shows bioavailability of 56%. It is having short half-life of 1 h. Repaglinide NLCs were formulated by using different lipid: co-emulsifier ratio and surfactant ratio using factorial design. Prepared repaglinide nanostructured lipid carriers were characterized for FT-IR study, DSC study, entrapment efficiency, in vitro drug release, particle size analysis, SEM study, zeta potential, polydispersity index, in vivo antidiabetic study and stability studies. FTIR and DSC studies showed there is no interaction of drug with lipids and polymers. Average particle size was found to be in the range of 10.38 to 200.68 nm. SEM studies revealed that particles were irregular in shape and rough in nature. Zeta potential was found to be in the range of -28.65 to -58.32 mV showed good stability of NLCs. Highest entrapment efficiency and cumulative drug release of 85.46±0.041% and 86.16±0.45% was predicted. In vivo antidiabetic study for blood glucose level showed an effective marked decrease in blood glucose level of repaglinide NLCs (F6) on 3 rd and 7 th day as compared to repaglinide standard. The results showed no or little change in entrapment efficiency and cumulative drug release before and after stability studies.
Advances in Engineering the Fly Genome with the CRISPR-Cas System

Drosophila has long been a premier model for the development and application of cutting-edge genetic approaches. The CRISPR-Cas system now adds the ability to manipulate the genome with ease and precision, providing a rich toolbox to interrogate relationships between genotype and phenotype, to delineate and visualize how the genome is organized, to illuminate and manipulate RNA, and to pioneer new gene drive technologies. Myriad transformative approaches have already originated from the CRISPR-Cas system, which will likely continue to spark the creation of tools with diverse applications. Here, we provide an overview of how CRISPR-Cas gene editing has revolutionized genetic analysis in Drosophila and highlight key areas for future advances.
Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression

Thyroid cancer is common, yet the sequence of alterations that promote tumor formation are incompletely understood. Here, we describe a novel model of thyroid carcinoma in zebrafish that reveals temporal changes due to BRAFV600E. Through the use of real-time in vivo imaging, we observe disruption in thyroid follicle structure that occurs early in thyroid development. Combinatorial treatment using BRAF and MEK inhibitors reversed the developmental effects induced by BRAFV600E. Adult zebrafish expressing BRAFV600E in thyrocytes developed invasive carcinoma. We identified a gene expression signature from zebrafish thyroid cancer that is predictive of disease-free survival in patients with papillary thyroid cancer. Gene expression studies nominated TWIST2 as a key effector downstream of BRAF. Using CRISPR/Cas9 to genetically inactivate a TWIST2 orthologue, we suppressed the effects of BRAFV600E and restored thyroid morphology and hormone synthesis. These data suggest that expression of TWIST2 plays a role in an early step of BRAFV600E-mediated transformation. DOI: http://dx.doi. org/10.7554/eLife.20728. 001
Bacterial Community Composition in Three Freshwater Reservoirs of Different Alkalinity and Trophic Status

In order to investigate the factors controlling the bacterial community composition (BCC) in reservoirs, we sampled three freshwater reservoirs with contrasted physical and chemical characteristics and trophic status. The BCC was analysed by 16S rRNA gene amplicon 454 pyrosequencing. In parallel, a complete dataset of environmental parameters and phytoplankton community composition was also collected. BCC in the analysed reservoirs resembled that of epilimnetic waters of natural freshwater lakes with presence of Actinobacteria, Alpha- and Betaproteobacteria, Cytophaga–Flavobacteria–Bacteroidetes (CFB) and Verrucomicrobia groups. Our results evidenced that the retrieved BCC in the analysed reservoirs was strongly influenced by pH, alkalinity and organic carbon content, whereas comparatively little change was observed among layers in stratified conditions.
Transparency When Things Go Wrong: Physician Attitudes About Reporting Medical Errors to Patients, Peers, and Institutions

Objectives Transparent communication after medical error includes disclosing the mistake to the patient, discussing the event with colleagues, and reporting to the institution. Little is known about whether attitudes about these transparency practices are related. Understanding these relationships could inform educational and organizational strategies to promote transparency. Methods We analyzed responses of 3038 US and Canadian physicians to a medical error communication survey. We used bivariate correlations, principal components analysis, and linear regression to determine whether and how physician attitudes about transparent communication with patients, peers, and the institution after error were related. Results Physician attitudes about disclosing errors to patients, peers, and institutions were correlated (all P's < 0.001) and represented 2 principal components analysis factors, namely, communication with patients and communication with peers/institution. Predictors of attitudes supporting transparent communication with patients and peers/institution included female sex, US (vs Canadian) doctors, academic (vs private) practice, the belief that disclosure decreased likelihood of litigation, and the belief that system changes occur after error reporting. In addition, younger physicians, surgeons, and those with previous experience disclosing a serious error were more likely to agree with disclosure to patients. In comparison, doctors who believed that disclosure would decrease patient trust were less likely to agree with error disclosure to patients. Previous disclosure education was associated with attitudes supporting greater transparency with peers/institution. Conclusions Physician attitudes about discussing errors with patients, colleagues, and institutions are related. Several predictors of transparency affect all 3 practices and are potentially modifiable by educational and institutional strategies.
Real-time imaging of DNA loop extrusion by condensin

Live imaging of DNA loop extrusion To spatially organize chromosomes, ring-shaped protein complexes including condensin and cohesin have been hypothesized to extrude DNA loops. Condensin has been shown to exhibit a DNA-translocating motor function, but extrusion has not been observed directly. Using single-molecule imaging, Ganji et al. visualized in real time a condensin-mediated, adenosine triphosphate-dependent, fast DNA loop extrusion process. Loop extrusion occurred asymmetrically, with condensin reeling in only one end of the DNA. These data provide unambiguous evidence of a loop extrusion mechanism for chromosome organization. Science, this issue p. 102 Single-molecule imaging supports a loop extrusion mechanism for the spatial organization of chromosomes. It has been hypothesized that SMC protein complexes such as condensin and cohesin spatially organize chromosomes by extruding DNA into large loops. We directly visualized the formation and processive extension of DNA loops by yeast condensin in real time. Our findings constitute unambiguous evidence for loop extrusion. We observed that a single condensin complex is able to extrude tens of kilobase pairs of DNA at a force-dependent speed of up to 1500 base pairs per second, using the energy of adenosine triphosphate hydrolysis. Condensin-induced loop extrusion was strictly asymmetric, which demonstrates that condensin anchors onto DNA and reels it in from only one side. Active DNA loop extrusion by SMC complexes may provide the universal unifying principle for genome organization.
PAWS1 controls Wnt signalling through association with casein kinase 1α

The BMP and Wnt signalling pathways determine axis specification during embryonic development. Our previous work has shown that PAWS1 (also known as FAM83G) interacts with SMAD1 and modulates BMP signalling. Here, surprisingly, we show that overexpression of PAWS1 in Xenopus embryos activates Wnt signalling and causes complete axis duplication. Consistent with these observations in Xenopus, Wnt signalling is diminished in U2OS osteosarcoma cells lacking PAWS1, while BMP signalling is unaffected. We show that PAWS1 interacts and co‐localises with the α isoform of casein kinase 1 (CK1), and that PAWS1 mutations incapable of binding CK1 fail both to activate Wnt signalling and to elicit axis duplication in Xenopus embryos.
Exercise, ageing and the lung

This review provides a pulmonary-focused description of the age-associated changes in the integrative physiology of exercise, including how declining lung function plays a role in promoting multimorbidity in the elderly through limitation of physical function. We outline the ageing of physiological systems supporting endurance activity: 1) coupling of muscle metabolism to mechanical power output; 2) gas transport between muscle capillary and mitochondria; 3) matching of muscle blood flow to its requirement; 4) oxygen and carbon dioxide carrying capacity of the blood; 5) cardiac output; 6) pulmonary vascular function; 7) pulmonary oxygen transport; 8) control of ventilation; and 9) pulmonary mechanics and respiratory muscle function. Deterioration in function occurs in many of these systems in healthy ageing. Between the ages of 25 and 80 years pulmonary function and aerobic capacity each decline by ∼40%. While the predominant factor limiting exercise in the elderly likely resides within the function of the muscles of ambulation, muscle function is (at least partially) rescued by exercise training. The age-associated decline in pulmonary function, however, is not recovered by training. Thus, loss in pulmonary function may lead to ventilatory limitation in exercise in the active elderly, limiting the ability to accrue the health benefits of physical activity into senescence. Exercise performance depends on integrated organ-system response, each subject to differential age-related decline http://ow.ly/YRNh3022S7w
Deposition of IGZO or ITZO Thin Films by Co-Sputtering of IZO and GZO or ITO Targets

New transparent conducting oxide (TCO) materials, indium-gallium-zinc-oxide (IGZO) and indium-tin-zinc-oxide (ITZO) were deposited on glass substrate by DC co-sputtering using IZO-GZO and IZO-ITO target combinations, respectively. Amorphous indium-gallium-zinc-oxide (a-IGZO) films possessing electron mobility of as high as 12 cm2V-1s-1 and resistivity of 0. 15Ω・cm could be deposited. Hall mobility was ten times higher than that of amorphous silicon (a-Si), and comparable to that of commercial IGZO thin films. A good electrical resistivity of 0. 17Ω・cm with a relatively high mobility of 10 cm2V-1s-1 was found for the ITZO films. These values were similar to those observed for the IGZO films in the present study.
Gender Nonconformity of Identical Twins With Discordant Sexual Orientations: Evidence From Childhood Photographs

Childhood gender nonconformity (femininity in males, masculinity in females) predicts a nonstraight (gay, lesbian, or bisexual) sexual orientation in adulthood. In previous work, nonstraight twins reported more childhood gender nonconformity than their genetically identical, but straight, cotwins. However, self-reports could be biased. We therefore assessed gender nonconformity via ratings of photographs from childhood and adulthood. These ratings came from independent observers naïve to study hypotheses. Identical twins with discordant sexual orientations (24 male pairs, 32 female pairs) visibly differed in their gender nonconformity from mid-childhood, with higher levels of gender nonconformity observed in the nonstraight twins. This difference was smaller than the analogous difference between identical twins who were concordant straight (4 male pairs, 11 female pairs) and identical twins unrelated to them who were concordant nonstraight (19 male pairs, 8 female pairs). Further, twins in discordant pairs correlated in their observer-rated gender nonconformity. Nongenetic factors likely differentiated the discordant twins’ gender-related characteristics in childhood, but shared influences made them similar in some respects. We further tested how recall of past rejection from others related to gender nonconformity. Rejection generally increased with gender nonconformity, but this effect varied by the twins’ sexual orientation.
Long-Term MRI Cell Tracking after Intraventricular Delivery in a Patient with Global Cerebral Ischemia and Prospects for Magnetic Navigation of Stem Cells within the CSF

Background The purpose of the study was to evaluate the long-term clinical tracking of magnetically labeled stem cells after intracerebroventricular transplantation as well as to investigate in vitro feasibility for magnetic guidance of cell therapy within large fluid compartments. Method After approval by our Institutional Review Board, an 18-month-old patient, diagnosed as being in a vegetative state due to global cerebral ischemia, underwent cell transplantation to the frontal horn of the lateral ventricle, with umbilical cord blood-derived stem cells labeled with superparamagnetic iron oxide (SPIO) contrast agent. The patient was followed over 33 months with clinical examinations and MRI. To evaluate the forces governing the distribution of cells within the fluid compartment of the ventricular system in vivo, a gravity-driven sedimentation assay and a magnetic field-driven cell attraction assay were developed in vitro. Results Twenty-four hours post-transplantation, MR imaging (MRI) was able to detect hypointense cells in the occipital horn of the lateral ventricle. The signal gradually decreased over 4 months and became undetectable at 33 months. In vitro, no significant difference in cell sedimentation between SPIO-labeled and unlabeled cells was observed (p = NS). An external magnet was effective in attracting cells over distances comparable to the size of human lateral ventricles. Conclusions MR imaging of SPIO-labeled cells allows monitoring of cells within lateral ventricles. While the initial biodistribution is governed by gravity-driven sedimentation, an external magnetic field may possibly be applied to further direct the distribution of labeled cells within large fluid compartments such as the ventricular system.
Education, Socioeconomic Status, and Intelligence in Childhood and Stroke Risk in Later Life: A Meta-analysis

Background: Stroke is the second most common cause of death, and a common cause of dependency and dementia. Adult vascular risk factors and socioeconomic status (SES) are associated with increased risk, but less is known about early life risk factors, such as education, childhood SES, or intelligence (IQ). Methods: We comprehensively searched Medline, PsycINFO, and EMBASE from inception to November 2015. We included all studies reporting data on >50 strokes examining childhood/premorbid IQ, SES, and education. Two reviewers independently screened full texts and extracted and cross-checked data, including available risk factor adjustments. We meta-analyzed stroke risk using hazard ratios (HR), odds ratios (OR), and mean differences (MD). We tested effects of study and participant characteristics in sensitivity analyses and meta-regression, and assessed heterogeneity and publication bias. Results: We identified 90 studies examining stroke risk and education (79), SES (10), or IQ (nine) including approximately 164,683 stroke and over 5 million stroke-free participants. Stroke risk increased with lower education (OR = 1.35, 95% CI = 1.24, 1.48), SES (OR = 1.28, 95% CI = 1.12, 1.46), and IQ (HR = 1.17, 95% CI = 1.00, 1.37) in studies reporting point estimates, with similar associations for MD. We found minimal publication bias. Between-study heterogeneity was partly explained by participant age and case ascertainment method. Conclusions: Education, childhood SES, and intelligence have modest but important associations with lifetime stroke, and hence dementia, risks. Future studies distinguishing between the individual and combined effects of education, childhood SES and intelligence are needed to determine the independent contribution of each factor to stroke risk. See video abstract at, http://links.lww. com/EDE/B210.
The fear of dying and occurrence of posttraumatic stress symptoms after an acute coronary syndrome: A prospective observational study

The purpose of the study was to investigate whether experiencing fear of dying after acute coronary syndrome predicts later posttraumatic stress symptoms. We enrolled 90 patients hospitalized with main diagnosis of acute coronary syndrome and assessed baseline characteristics. One month after discharge, we collected the Posttraumatic Stress Scale. A total of 24 patients (26.7%) developed posttraumatic stress symptoms 1 month after the acute coronary syndrome event. Patients with posttraumatic stress symptoms reported significantly greater fear of dying, helplessness, avoidance-focused coping, and severe anxiety. In our prospective study, fear of dying was associated with occurrence of posttraumatic stress symptoms in patients hospitalized with acute coronary syndrome.
Full‐length nucleotide sequence of ERMAP alleles encoding Scianna (SC) antigens

Scianna (SC) blood group system comprises two antithetical antigens, Sc1 and Sc2, and five additional antigens. The antigens reside on a glycoprotein encoded by the erythroblast membrane–associated protein (ERMAP) gene. For the common ERMAP alleles, we determined the full‐length nucleotide sequence that encodes the Scianna glycoprotein.