Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.

CONTEXT The optimal duration of treatment of women with postmenopausal osteoporosis is uncertain. OBJECTIVE To compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years. DESIGN AND SETTING Randomized, double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial (FIT). PARTICIPANTS One thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment. INTERVENTION Randomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo (n = 437) for 5 years (1998-2003). MAIN OUTCOME MEASURES The primary outcome measure was total hip bone mineral density (BMD); secondary measures were BMD at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence. RESULTS Compared with continuing alendronate, switching to placebo for 5 years resulted in declines in BMD at the total hip (-2.4%; 95% confidence interval [CI], -2.9% to -1.8%; P<.001) and spine (-3.7%; 95% CI, -4.5% to -3.0%; P<.001), but mean levels remained at or above pretreatment levels 10 years earlier. Similarly, those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate: 55.6% (P<.001) for C-telopeptide of type 1 collagen, 59.5% (P < .001) for serum n = propeptide of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker levels remained somewhat below pretreatment levels 10 years earlier. After 5 years, the cumulative risk of nonvertebral fractures (RR, 1.00; 95% CI, 0.76-1.32) was not significantly different between those continuing (19%) and discontinuing (18.9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities, with bone turnover (double labeling) seen in all specimens. CONCLUSIONS Women who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT 00398931.
An Improved Model for the Rate–Level Functions of Auditory-Nerve Fibers

Acoustic information is conveyed to the brain by the spike patterns in auditory-nerve fibers (ANFs). In mammals, each ANF is excited via a single ribbon synapse in a single inner hair cell (IHC), and the spike patterns therefore also provide valuable information about those intriguing synapses. Here we reexamine and model a key property of ANFs, the dependence of their spike rates on the sound pressure level of acoustic stimuli (rate–level functions). We build upon the seminal model of Sachs and Abbas (1974), which provides good fits to experimental data but has limited utility for defining physiological mechanisms. We present an improved, physiologically plausible model according to which the spike rate follows a Hill equation and spontaneous activity and its experimentally observed tight correlation with ANF sensitivity are emergent properties. We apply it to 156 cat ANF rate–level functions using frequencies where the mechanics are linear and find that a single Hill coefficient of 3 can account for the population of functions. We also demonstrate a tight correspondence between ANF rate–level functions and the Ca2+ dependence of exocytosis from IHCs, and derive estimates of the effective intracellular Ca2+ concentrations at the individual active zones of IHCs. We argue that the Hill coefficient might reflect the intrinsic, biochemical Ca2+ cooperativity of the Ca2+ sensor involved in exocytosis from the IHC. The model also links ANF properties with properties of psychophysical absolute thresholds.
Practice Audit in Gastroenterology (PAGE) program: a novel approach to continuing professional development.

BACKGROUND Practice audit is an important component of continuing professional development that may more readily be undertaken if it were less complex. This qualitative study assessed the use of personal digital assistants to facilitate data collection and review. METHODS Personal digital assistants programmed with standard questionnaires related to upper gastrointestinal endoscopies (Practice Audit in Gastroenterology-Endoscopy ['PAGE-Endo']) and colonoscopies (PAGE-Colonoscopy ['PAGE-Colo']) were provided to Canadian gastroenterologists, surgeons and internists. Over a three-week audit period, participants recorded indications, and the expected (E) and reported (R) findings for each procedure. Thereafter, participants recorded compliance with reporting, the ease of use and value of the PAGE program, and their willingness to perform another audit. RESULTS Over 15 to 18 months, 173 participants completed PAGE-Endo (6168 procedures) and 111 completed PAGE-Colo (4776 procedures). Most respondents noted that PAGE was easy to use (99%), beneficial (88% to 95%), and that they were willing undertake another audit (92% to 95%). In PAGE-Endo, alarm features were prevalent (55%), but major reported findings were less common than expected: esophagitis (E 29.9%, R 14.8%), esophageal stricture (E 8.3%, R 3.6%), gastric ulcer (E 17.0%, R 4.7%), gastric cancer (E 4.3%, R 1.0%) and duodenal ulcer (E 11.5%, R 5.7%). In PAGE-Colo, more colonoscopies were performed for symptom investigation (55%) than for screening (25%) or surveillance (20%). There were marked interprovincial variations with respect to sedation, biopsies and technical aspects of colonoscopy. CONCLUSION Secure, real-time data entry with review of aggregate and individual data in the PAGE program provided an acceptable, straightforward methodology for accredited practice audit activities. PAGE has considerable potential for continuing professional development in gastroenterology and other specialties.
The Incidence of Schizophrenia in Nottingham

Attempts were made to identify, and include in a two-year follow-up study, every patient living in the catchment area of the Mapperley group of psychiatric hospitals in Nottingham (population 390 000) who made their first-ever contact with the psychiatric services for a potentially schizophrenic illness during a two-year period (1 August 1978 to 31 July 1980). Screening was based upon symptoms rather than diagnosis, covering both in-patient and out-patient services; a consensus diagnosis using ICD-9 was made by the project team. The Nottingham Psychiatric Case Register was used in a retrospective Leakage Study which added nine cases to the 99 identified by the screening procedures. Incidence rates are given for both broad and narrow concepts of schizophrenia, and for DSM-III diagnosis. The Nottingham incidence rates are similar to those reported from other UK centres, and are near the middle of the range found in the other collaborating centres in the WHO study on Determinants of Outcome of Severe Mental Disorders. At entry to the study, 27 patients were out-patients, and 11 were never admitted to hospital at any time in the two-year follow-up period. Reasons for believing that the Nottingham administrative incidence may be close to the incidence in the community are discussed.
Evaluating the response of neoadjuvant chemotherapy for treatment of breast cancer: are tumor biomarkers and dynamic contrast enhanced MR images useful predictive tools?

OBJECTIVE In order to evaluate the therapeutic response to neoadjuvant chemotherapy (NAC) for breast cancer, this research focused on the changes in expression of tumor biomarkers and the correlations associated with changes of magnetic resonance imaging (MRI) pre- and post-NAC. We also compared the accuracy of MRI and pathology in terms of residual tumor extent after NAC. METHODS MRI was performed before and after four courses of cyclophosphamide, epirubicin and paclitaxel (CET) NAC on 114 patients treated in Huashan Hospital (Fudan University) from December 2009 to January 2013. All patients were pathologically diagnosed with invasive breast cancer via core needle biopsy. A series of tumor biomarkers, including P-glycoprotein (P-gp) and Ki-67, was tested by immunohistochemistry in both core needle biopsy and surgical specimens. The changes in tumor biomarker expression and the shrinkage of tumor on MRI were observed. The residual tumor extent after NAC was compared in terms of MRI and histopathology, and the accuracy of MRI was evaluated by both residual tumor extent and by NAC therapeutic effect. Together, these methods enabled a prognostic estimate of NAC. RESULTS The P-gp expression before NAC was used to evaluate the therapeutic effect of NAC. The up-regulation of P-gp expression after NAC was associated with poor therapeutic effect (P=0.0011). The expression of Ki-67 was significantly down-regulated (P<0.0001) but it had no association with NAC response (P=0.9645). The mean extent of residual tumor after NAC as seen on MRI was 20.83 mm (±4.14 mm, 95% CI) and that of surgically removed specimens, 18.89 mm (±3.71 mm, 95% CI). The sensitivity of MRI was 95.1%, the specificity was 28.6%, the positive predictive value was 79.6%, and the negative predictive value was 66.7%. CONCLUSIONS P-gp status was an important factor affecting the pathological complete response (pCR) rate. The change in P-gp expression, from negative to positive following NAC treatment, indicated the emergence of drug resistance resulting from chemotherapy. The down-regulation of Ki-67 was associated with the decline of tumor proliferation. However, compared to the pre-NAC P-gp status, the pre-NAC Ki-67 status had little prognostic value. Additionally, the evaluation of the efficacy of NAC by either MRI or histopathology was inconclusive.
Feasibility of an empirically based program for parents of preschoolers with autism spectrum disorder

This article reports on the feasibility of implementing an existing empirically based program, The Incredible Years, tailored to parents of young children with autism spectrum disorder. Parents raising preschool-aged children (aged 3–6 years) with autism spectrum disorder (N = 17) participated in a 15-week pilot trial of the intervention. Quantitative assessments of the program revealed fidelity was generally maintained, with the exception of program-specific videos. Qualitative data from individual post-intervention interviews reported parents benefited most from child emotion regulation strategies, play-based child behavior skills, parent stress management, social support, and visual resources. More work is needed to further refine the program to address parent self-care, partner relationships, and the diverse behavioral and communication challenges of children across the autism spectrum. Furthermore, parent access and retention could potentially be increased by providing in-home childcare vouchers and a range of times and locations in which to offer the program. The findings suggest The Incredible Years is a feasible intervention for parents seeking additional support for child- and family-related challenges and offers guidance to those communities currently using The Incredible Years or other related parenting programs with families of children with autism spectrum disorder.
Structured Exercise Does Not Stabilize Cognitive Function in Individuals With Mild Cognitive Impairment Residing in a Structured Living Facility

ABSTRACT Exercise has been shown to have positive effects on the brain and cognition in healthy older adults, though no study has directly examined possible cognitive benefits of formal exercise programs in persons with mild cognitive impairment (MCI) living in structured facilities. Thirty-one participants completed neuropsychological testing and measures of cardiovascular fitness at baseline and after 6 months of a structured exercise program that included aerobic and resistance training. While exercise improved cardiovascular fitness in persons with MCI, there was no improvement in cognitive function. Rather, MCI patients in this sample declined in performance on several tests sensitive to Alzheimer's disease. Examined in the context of past work, it appears exercise may be beneficial prior to the onset of MCI, though less helpful after its onset.
Equine platelet lysate as an alternative to fetal bovine serum in equine mesenchymal stromal cell culture - too much of a good thing?

REASONS FOR PERFORMING STUDY Multipotent mesenchymal stromal cells (MSC) are often culture-expanded in vitro. Presently, expansion medium (EM) for MSC is supplemented with fetal bovine serum (FBS). However, increasing cost, variable composition and potential risks associated with bovine antigens call for alternatives. Platelet lysate (PL) has shown promise as an alternative supplement. OBJECTIVES To determine how equine umbilical cord blood (CB) MSC proliferate in EM enriched with PL or FBS at various concentrations. STUDY DESIGN Randomised dose escalation study. METHODS Platelet concentrate was generated from 5 equine whole blood samples through a double centrifugation method and standardised to 1 × 10(12) platelets/l prior to a freeze/thaw cycle to produce PL. Pooled PL or pooled FBS was added to EM at concentrations of 5% to 60%. Proliferation of 4 equine CB-MSC cultures was determined after 4 days using a resazurin semiquantitative assay. RESULTS Cord blood-MSC proliferated with a dose-dependent response with no significant difference found between PL and FBS up to a 30% concentration. Beyond 30%, proliferation fell in the PL-cultured cells, while continued dose-dependent proliferation was noted in the FBS-cultured cells. Despite reduced cell numbers in high PL concentrations, live/dead staining revealed that adherent cells remained viable. CONCLUSIONS Expansion medium enriched with PL can support short-term equine CB-MSC proliferation at conventional culture concentrations. Based on the unexpected suppression of CB-MSC at higher PL concentrations, an in vivo dose study is indicated to investigate if combinational therapies of CB-MSC and platelet-rich plasma are associated with synergistic or antagonistic effect on CB-MSC function.
Performance based seismic assessment of bridges designed according to Canadian Highway Bridge Design Code

Recent research efforts have focused on the development of performance based seismic design methodologies for structures. However, the seismic design rules prescribed in the current Canadian Highway Bridge Design Code (CHBDC) is based largely on force based design principles. Although a set of performance requirements (performance objectives) for different return period earthquake events have been specified, there is no explicit requirement in the CHBDC to check the attainment of such performance objectives for the designed bridges. Also, no engineering parameters have been assigned to the specified performance objectives. This paper correlates seismic performance objectives (both qualitative and quantitative) with engineering parameters, based on the data collected from published experimental investigations and field investigation reports of recent earthquakes. A simple method has been developed and validated with experimental results for assessing the performance of bridges designed according to CHBDC.
A Two-Level Routing Scheme for Wireless Sensor Network

A new two-level routing scheme is proposed using the energy features of wireless sensor network. The proposed scheme consists of two levels: (i) sink node level and (ii) sensor node level. The proposed scheme exploits independent gradients for each sink node so that the exploratory messages forwarded by the intermediate sensor nodes can be significantly reduced. Experiments are conducted using two evaluation criterions, which are average dissipated energy and hop counts, to demonstrate the superior performance of the proposed scheme.
The DNA Binding and Catalytic Domains of Poly(ADP-Ribose) Polymerase 1 Cooperate in the Regulation of Chromatin Structure and Transcription

ABSTRACT We explored the mechanisms of chromatin compaction and transcriptional regulation by poly(ADP-ribose) polymerase 1 (PARP-1), a nucleosome-binding protein with an NAD+-dependent enzymatic activity. By using atomic force microscopy and a complementary set of biochemical assays with reconstituted chromatin, we showed that PARP-1 promotes the localized compaction of chromatin into supranucleosomal structures in a manner independent of the amino-terminal tails of core histones. In addition, we defined the domains of PARP-1 required for nucleosome binding, chromatin compaction, and transcriptional repression. Our results indicate that the DNA binding domain (DBD) of PARP-1 is necessary and sufficient for binding to nucleosomes, yet the DBD alone is unable to promote chromatin compaction and only partially represses RNA polymerase II-dependent transcription in an in vitro assay with chromatin templates (∼50% of the repression observed with wild-type PARP-1). Furthermore, our results show that the catalytic domain of PARP-1, which does not bind nucleosomes on its own, cooperates with the DBD to promote chromatin compaction and efficient transcriptional repression in a manner independent of its enzymatic activity. Collectively, our results have revealed a novel function for the catalytic domain in chromatin compaction. In addition, they show that the DBD and catalytic domain cooperate to regulate chromatin structure and chromatin-dependent transcription, providing mechanistic insights into how these domains contribute to the chromatin-dependent functions of PARP-1.
Concurrent learning adaptive control in the presence of uncertain control allocation matrix

We consider the problem of solving adaptive control problems in the presence of an uncertain control allocation matrix. Concurrent learning adaptive control architectures are presented that simultaneously stabilize the system and estimate parameters of the system B matrix. Sufficient conditions for the boundedness of the architecture are presented. The validity of our approach is demonstrated through numerical simulations on linear multi-input multi-output models.
Serum Prolactrin and Blood Glucose Levels Before and After an Oral Glucse-load in Patients with Diabetes Mellitus and Liver Cirrhosis

Serum prolactin and blood glucose levels were measured in 13 patients with type II diabetes mellitus and nine patients with liver cirrhosis (Bilharzial or post-hepatic or mixed) in addition to 13 normal controls. Basal serum prolactin levels in diabetic patients did not differ significantly from levels reported for control, while those of liver cirrhosis patients were significantly higher than those of both diabetic patients and controls. After oral glucose load, all the patients showed decreased glucose tolerance accompanied with hyperprolactinemia that was more apparent and persistent in liver-cirrhosis patients. Serum insulin levels that were feasible to be measured in six liver-cirrhosis patients, showed concomitant delayed insulin rise following the glucose load that was maintained longer than in control. These findings of glucose intolerance and hyperprolactinemia were discussed and interpreted on a suggestion to be secondary to various mechanisms including peripheral insulin resistance, gluconeogenesis and/or altered response of pancreatic B-cells to glucose loading.
Evolutionary Visual Exploration: Evaluation of an IEC Framework for Guided Visual Search

We evaluate and analyse a framework for evolutionary visual exploration (EVE) that guides users in exploring large search spaces. EVE uses an interactive evolutionary algorithm to steer the exploration of multidimensional data sets toward two-dimensional projections that are interesting to the analyst. Our method smoothly combines automatically calculated metrics and user input in order to propose pertinent views to the user. In this article, we revisit this framework and a prototype application that was developed as a demonstrator, and summarise our previous study with domain experts and its main findings. We then report on results from a new user study with a clearly predefined task, which examines how users leverage the system and how the system evolves to match their needs. While we previously showed that using EVE, domain experts were able to formulate interesting hypotheses and reach new insights when exploring freely, our new findings indicate that users, guided by the interactive evolutionary algorithm, are able to converge quickly to an interesting view of their data when a clear task is specified. We provide a detailed analysis of how users interact with an evolutionary algorithm and how the system responds to their exploration strategies and evaluation patterns. Our work aims at building a bridge between the domains of visual analytics and interactive evolution. The benefits are numerous, in particular for evaluating interactive evolutionary computation (IEC) techniques based on user study methodologies.
Metabolic parameters of postmenopausal women after quinoa or corn flakes intake – a prospective and double-blind study

Abstract A prospective and double-blind study was conducted on 35 women with weight excess who consumed 25 grams of quinoa flakes (QF) or corn flakes (CF) daily during a period of four consecutive weeks. At the beginning (T1) and at the end (T2) of the intervention, total calorie intake was evaluated, anthropometric assessment was performed, blood was collected for the determination of glucose, total cholesterol and fractions, oxidative stress markers, vitamin E and enterolignans. Significant reductions were detected in serum triglyceride (CF group = 133.9 ± 89.4 to 113.7 ± 57 mg/dl and QF group = 112.3 ± 35 to 107.9 ± 33.1 mg/dl), TBARS (CF group = 3.2 ± 0.8 to 2.9 ± 0.5 µmol/l and QF group = 3.06 ± 0.6 to 2.89 ± 0.5 µmol/l) and vitamin E concentrations (CF group = 19.5 ± 5 to 17.9 ± 4 µM and QF group = 17.9 ± 4 to 16.9 ± 3 µM) and an increase in urinary excretion of enterolignans (CF group = 2.05 ± 1.3 to 2.24 ± 1.4 nm/ml and QF group = 2.9 ± 1.6 to 3.2 ± 2.7 nm/l), in both study groups. The reduction of total cholesterol (191 ± 35 to 181 ± 28 mg/dl) and LDL-cholesterol (LDL-c) (129 ± 35 to 121 ± 26 mg/dl), and the increase in GSH (1.78 ± 0.4 to 1.91 ± 0.4 µmol/l) occurred only in the QF group, showing a possible beneficial effect of QF intake.