Miracle-dz/UniFAR-FTUs huggingface dataset:
Within‐drug benefit‐risk evaluation of olanzapine long‐acting injection at one and two years of treatment

We sought to evaluate the within‐drug benefit‐risk of olanzapine long‐acting injection (LAI) using both quantitative and qualitative methods. Subjects included 1192 adult patients with schizophrenia or schizoaffective disorder who participated in clinical trials with the opportunity for at least two years of continuous treatment with olanzapine LAI (45–405 mg every two to four weeks). Using the Benefit Risk Action Team (BRAT) framework, we evaluated frequency versus duration of benefits and risks commonly observed with atypical antipsychotics. We then used the Transparent Uniform Risk/Benefit Overview (TURBO) method, which weighs the drug's two most medically serious and/or frequent adverse events versus its primary benefit (effectiveness) and an ancillary benefit. The most frequent events among all patients were remaining free of relapse (91.4% for an average of 306 days at one year, 88.4% for 546 days at two years) and symptomatic remission (81.7% for an average of 239 days at one year, 84.1% for 438 days at two years). One‐ and two‐year incidence of ≥7% weight gain was 33.3% and 41.7%. Incidences for sexual dysfunction, hyperprolactinemia, and post‐injection delirium/sedation syndrome (PDSS) were <2%. TURBO ratings unanimously selected PDSS and weight gain as key risks and resulted in an average score in the acceptable benefit‐risk balance range. Copyright © 2014 John Wiley & Sons, Ltd.
Pioglitazone Improves Cardiac Function and Alters Myocardial Substrate Metabolism Without Affecting Cardiac Triglyceride Accumulation and High-Energy Phosphate Metabolism in Patients With Well-Controlled Type 2 Diabetes Mellitus

Background— Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy phosphate, glucose, and fatty acid metabolism and triglyceride content in T2DM patients. Methods and Results— Seventy-eight T2DM men without structural heart disease or inducible ischemia as assessed by dobutamine stress echocardiography were assigned to pioglitazone (30 mg/d) or metformin (2000 mg/d) and matching placebo for 24 weeks. The primary end point was change in cardiac diastolic function from baseline relative to myocardial metabolic changes, measured by magnetic resonance imaging, proton and phosphorus magnetic resonance spectroscopy, and [18F]-2-fluoro-2-deoxy-d-glucose and [11C]palmitate positron emission tomography. No patient developed heart failure. Both therapies similarly improved glycemic control, whole-body insulin sensitivity, and blood pressure. Pioglitazone versus metformin improved the early peak flow rate (P=0.047) and left ventricular compliance. Pioglitazone versus metformin increased myocardial glucose uptake (P<0.001), but pioglitazone-related diastolic improvement was not associated with changes in myocardial substrate metabolism. Metformin did not affect myocardial function but decreased cardiac work relative to pioglitazone (P=0.006), a change that was paralleled by a reduced myocardial glucose uptake and fatty acid oxidation. Neither treatment affected cardiac high-energy phosphate metabolism or triglyceride content. Only pioglitazone reduced hepatic triglyceride content (P<0.001). Conclusions— In T2DM patients, pioglitazone was associated with improvement in some measures of left ventricular diastolic function, myocardial glucose uptake, and whole-body insulin sensitivity. The functional changes, however, were not associated with myocardial substrate and high-energy phosphate metabolism.
Transdiagnostic cognitive-behavioral therapy for patients with eating disorders: a two-site trial with 60-week follow-up.

OBJECTIVE The aim of this study was to compare two cognitive-behavioral treatments for outpatients with eating disorders, one focusing solely on eating disorder features and the other a more complex treatment that also addresses mood intolerance, clinical perfectionism, low self-esteem, or interpersonal difficulties. METHOD A total of 154 patients who had a DSM-IV eating disorder but were not markedly underweight (body mass index over 17.5), were enrolled in a two-site randomized controlled trial involving 20 weeks of treatment and a 60-week closed period of follow-up. The control condition was an 8-week waiting list period preceding treatment. Outcomes were measured by independent assessors who were blind to treatment condition. RESULTS Patients in the waiting list control condition exhibited little change in symptom severity, whereas those in the two treatment conditions exhibited substantial and equivalent change, which was well maintained during follow-up. At the 60-week follow-up assessment, 51.3% of the sample had a level of eating disorder features less than one standard deviation above the community mean. Treatment outcome did not depend on eating disorder diagnosis. Patients with marked mood intolerance, clinical perfectionism, low self-esteem, or interpersonal difficulties appeared to respond better to the more complex treatment, with the reverse pattern evident among the remaining patients. CONCLUSIONS These two transdiagnostic treatments appear to be suitable for the majority of outpatients with an eating disorder. The simpler treatment may best be viewed as the default version, with the more complex treatment reserved for patients with marked additional psychopathology of the type targeted by the treatment.
Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).
Impact of Matching Network on Bandwidth of Compact Antenna Arrays

We analyze the impact of the matching network on compact multiple-input multiple-output systems. Existing studies have found that the matching network has a significant influence on the performance of multiple antenna systems when the antennas are in close proximity. However, none has examined the wide-band case. In this paper, we investigate the wide-band performance of four different matching networks for multiple dipole antennas. The performance of the matching networks is given in terms of the bandwidths of correlation and matching efficiency, which are extensions of the single-antenna concept of bandwidth to multiple antenna systems. We also investigate the impact of the propagation conditions on the matching and bandwidth. For a uniform two-dimensional (2-D) angular power spectrum, we find that while individual-port matching can achieve in excess of 3% fractional correlation bandwidth for envelope correlation of 0.5 at an antenna separation of 0.01lambda, multiport matching is required for efficiency bandwidth to exist for a return loss of -6 dB. Moreover, even with multiport matching, both correlation and efficiency bandwidths decrease drastically at small antenna separations. At 0.01lambda, the correlation and efficiency bandwidths are 0.4% and 0.2%, respectively. Similar evaluations were performed for measured outdoor-to-indoor channels with moderate to small 2-D angular spreads. We find that the efficiency advantage of multiport matching over individual-port matching diminishes with decreasing angular spread
What Drives Productivity Growth?

Economists have long debated the best way to explain the sources of productivity growth. Neoclassical theory and 'new growth' theory both regard investment - broadly defined to include purchases of tangible assets, human capital expenditures, and research and development efforts - as a critical source of productivity growth, but they differ in fundamental ways. Most notably, the neoclassical framework focuses on diminishing and internal returns to aggregate capital, while new growth models emphasize constant returns to capital that may yield external benefits. This article finds that despite their differences, both theories help explain productivity growth. The methodological tools of the neoclassical economists allow one to measure the rate of technical change, and the models of the new growth theorists provide an internal explanation for technical progress.
Nefeli: Hint-Based Execution of Workloads in Clouds

Virtualization of computer systems has made feasible the provision of entire distributed infrastructures in the form of services. Such services do not expose the internal operational and physical characteristics of the underlying machinery to either users or applications. In this way, infrastructures including computers in data-centers, clusters of workstations, and networks of machines are shrouded in "clouds". Mainly through the deployment of virtual machines, such networks of computing nodes become cloud-computing environments. In this paper, we propose Nefeli, a virtual infrastructure gateway that is capable of effectively handling diverse workloads of jobs in cloud environments. By and large, users and their workloads remain agnostic to the internal features of clouds at all times. Exploiting execution patterns as well as logistical constraints, users provide Nefeli with hints for the handling of their jobs. Hints provide no hard requirements for application deployment in terms of pairing virtual-machines to specific physical cloud elements. Nefeli helps avoid bottlenecks within the cloud through the realization of viable virtual machine deployment mappings. As the types of jobs change over time, deployment mappings must follow suit. To this end, Nefeli offers mechanisms to migrate virtual machines as needed to adapt to changing performance needs. Using our prototype system, we show significant improvements in overall time needed and energy consumed for the execution of workloads in both simulated and real cloud computing environments.
Genetic Susceptibility to Refractive Error: Association of Vasoactive Intestinal Peptide Receptor 2 (VIPR2) with High Myopia in Chinese

Myopia is the most common ocular disease worldwide. We investigated the association of high myopia with the common single nucleotide polymorphisms (SNPs) of five candidate genes – early growth response 1 (EGR1), v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS), jun oncogene (JUN), vasoactive intestinal peptide (VIP), and vasoactive intestinal peptide receptor 2 (VIPR2). We recruited 1200 unrelated Chinese subjects with 600 cases (spherical equivalent ≤−8.00 diopters) and 600 controls (spherical equivalent within ±1.00 diopter). A discovery sample set was formed from 300 cases and 300 controls, and a replication sample set from the remaining samples. Tag SNPs were genotyped for the discovery sample set, and the most significant haplotypes and their constituent SNPs were followed up with the replication sample set. The allele and haplotype frequencies in cases and controls were compared by logistic regression adjusted for sex and age to give P a values, and multiple comparisons were corrected by permutation test to give P aemp values. Odd ratios (OR) were calculated accordingly. In the discovery phase, EGR1, JUN and VIP did not show any significant association while FOS and VIPR2 demonstrated significant haplotype association with high myopia. In the replication phase, the haplotype association for VIPR2 was successfully replicated, but not FOS. In analysis combining both sample sets, the most significant association signals of VIPR2 were the single marker rs2071625 (P a = 0.0008, P aemp = 0.0046 and OR = 0.75) and the 4-SNP haplotype window rs2071623-rs2071625-rs2730220-rs885863 (omnibus test, P a = 9.10e-10 and P aemp = 0.0001) with one protective haplotype (GGGG: P aemp = 0.0002 and OR = 0.52) and one high-risk haplotype (GAGA: P aemp = 0.0027 and OR = 4.68). This 4-SNP haplotype window was the most significant in all sample sets examined. This is the first study to suggest a role of VIPR2 in the genetic susceptibility to high myopia. EGR1, JUN, FOS and VIP are unlikely to be important in predisposing humans to high myopia.
Improvement in Gastrointestinal Symptoms After Cognitive Behavior Therapy for Refractory Irritable Bowel Syndrome.

BACKGROUND & AIMS There is an urgent need for safe treatments for irritable bowel syndrome (IBS) that relieve treatment-refractory symptoms and their societal and economic burden. Cognitive behavior therapy (CBT) is an effective treatment that has not been broadly adopted into routine clinical practice. We performed a randomized controlled trial to assess clinical responses to home-based CBT compared with clinic-based CBT and patient education. METHODS We performed a prospective study of 436 patients with IBS, based on Rome III criteria, at 2 tertiary centers from August 23, 2010, through October 21, 2016. Subjects (41.4 ± 14.8 years old; 80% women) were randomly assigned to groups that received the following: standard-CBT (S-CBT, n = 146, comprising 10 weekly, 60-minute sessions that emphasized the provision of information about brain-gut interactions; self-monitoring of symptoms, their triggers, and consequences; muscle relaxation; worry control; flexible problem solving; and relapse prevention training), or 4 sessions of primarily home-based CBT requiring minimal therapist contact (MC-CBT, n = 145), in which patients received home-study materials covering the same procedures as S-CBT), or 4 sessions of IBS education (EDU, n = 145) that provided support and information about IBS and the role of lifestyle factors such as stress, diet, and exercise. The primary outcome was global improvement of IBS symptoms, based on the IBS-version of the Clinical Global Impressions-Improvement Scale. Ratings were performed by patients and board-certified gastroenterologists blinded to treatment allocation. Efficacy data were collected 2 weeks, 3 months, and 6 months after treatment completion. RESULTS A higher proportion of patients receiving MC-CBT reported moderate to substantial improvement in gastrointestinal symptoms 2 weeks after treatment (61.0% based on ratings by patients and 55.7% based on ratings by gastroenterologists) than those receiving EDU (43.5% based on ratings patients and 40.4% based on ratings by gastroenterologists) (P < .05). Gastrointestinal symptom improvement, rated by gastroenterologists, 6 months after the end of treatment also differed significantly between the MC-CBT (58.4%) and EDU groups (44.8%) (P = .05). Formal equivalence testing applied across multiple contrasts indicated that MC-CBT is at least as effective as S-CBT in improving IBS symptoms. Patients tended to be more satisfied with CBT vs EDU (P < .05) based on immediate posttreatment responses to the Client Satisfaction Questionnaire. Symptom improvement was not significantly related to concomitant use of medications. CONCLUSIONS In a randomized controlled trial, we found that a primarily home-based version of CBT produced significant and sustained gastrointestinal symptom improvement for patients with IBS compared with education. Clinicaltrials.gov no.: NCT00738920.
An fMRI study of anticipation and learning of smooth pursuit eye movements in humans

We studied the neural substrate of anticipation and learning of smooth pursuit eye movements in humans using fMRI. Both predictable and non-predictable eye movements, compared to baseline, activated a common network previously associated with oculomotor function. The temporal dynamics of activity in a subset of these areas suggested a strong correlation with type of condition. Specifically, differential decreases in activity were seen in dorsolateral prefrontal cortex and the intraparietal sulcus during the predictable condition. During the non- predictable condition the same areas exhibited evidence of high levels of activity that further increased throughout the condition. In contrast, differential increases associated with the predictable condition were seen in anterior cingulate and preSMA cortex regions. These changes in activity mirror the time course of the short-term learning of eye movements seen behaviourally, and are congruent with learning-related changes that have been reported for other motor paradigms.
Row Ratios of Intercropping Maize and Soybean Can Affect Agronomic Efficiency of the System and Subsequent Wheat

Intercropping is regarded as an important agricultural practice to improve crop production and environmental quality in the regions with intensive agricultural production, e.g., northern China. To optimize agronomic advantage of maize (Zea mays L.) and soybean (Glycine max L.) intercropping system compared to monoculture of maize, two sequential experiments were conducted. Experiment 1 was to screening the optimal cropping system in summer that had the highest yields and economic benefits, and Experiment 2 was to identify the optimum row ratio of the intercrops selected from Experiment 1. Results of Experiment 1 showed that maize intercropping with soybean (maize || soybean) was the optimal cropping system in summer. Compared to conventional monoculture of maize, maize || soybean had significant advantage in yield, economy, land utilization ratio and reducing soil nitrate nitrogen (N) accumulation, as well as better residual effect on the subsequent wheat (Triticum aestivum L.) crop. Experiment 2 showed that intercropping systems reduced use of N fertilizer per unit land area and increased relative biomass of intercropped maize, due to promoted photosynthetic efficiency of border rows and N utilization during symbiotic period. Intercropping advantage began to emerge at tasseling stage after N topdressing for maize. Among all treatments with different row ratios, alternating four maize rows with six soybean rows (4M:6S) had the largest land equivalent ratio (1.30), total N accumulation in crops (258 kg ha-1), and economic benefit (3,408 USD ha-1). Compared to maize monoculture, 4M:6S had significantly lower nitrate-N accumulation in soil both after harvest of maize and after harvest of the subsequent wheat, but it did not decrease yield of wheat. The most important advantage of 4M:6S was to increase biomass of intercropped maize and soybean, which further led to the increase of total N accumulation by crops as well as economic benefit. In conclusion, alternating four maize rows with six soybean rows was the optimum row ratio in maize || soybean system, though this needs to be further confirmed by pluri-annual trials.
Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies.
ALMOST ALL ELLIPTIC CURVES ARE SERRE CURVES

Using a multidimensional large sieve inequality, we obtain a bound for the mean-square error in the Chebotarev theorem for division fields of elliptic curves that is as strong as what is implied by the Generalized Riemann Hypothesis. As an application we prove that, according to height, almost all elliptic curves are Serre curves, where a Serre curve is an elliptic curve whose torsion subgroup, roughly speaking, has as much Galois symmetry as possible.
Temperature determination via STJ optical spectroscopy

ESA's Superconducting Tunnel Junction (STJ) optical photon-counting camera (S-Cam2) incorporates an array of pixels with intrinsic energy sensitivity. Using the spectral fitting technique common in X-ray astronomy, we fit black bodies to nine stellar spectra, ranging from cool flare stars to hot white dwarfs. The measured temperatures are consistent with literature values at the expected level of accuracy based on the predicted gain stability of the instrument. Having also demonstrated that systematic eects due to count rate are likely to be small, we then proceed to apply the temperature determination method to four cataclysmic variable (CV) binary systems. In three cases we measure the temperature of the accretion stream, while in the fourth we measure the temperature of the white dwarf. The results are discussed in the context of existing CV results. We conclude by outlining the prospects for future versions of S-Cam.
Local Reasoning with First-Class Heaps, and a New Frame Rule

Separation Logic (SL) brought an advance to program verification of data structures by interpreting (recursively defined) predicates as implicit heaps, and using a separating conjoin operator to construct heaps from disjoint subheaps. While the Frame Rule of SL facilitated local reasoning in program fragments, its restriction to disjoint subheaps means that any form of sharing between predicates is problematic. With this as background motivation, we begin with an assertion language in which subheaps may be explicitly defined within predicates, and the effect of separation obtained by specifying that certain heaps are disjoint. The strength of this base language is not just its expressiveness, but it is amenable to symbolic execution and therefore automatic program verification. In this paper, we extend this base language with a new frame rule to accommodate subheaps and nonseparating conjoining of subheaps so as to provide compositional reasoning. This significantly extends both the expressiveness and automatability of the base language. Finally we demonstrate our framework to automatically prove two significant example programs, one concerning a summary of a program fragments, and one exhibiting structure sharing in data structures.