Miracle-dz/UniFAR-FTUs huggingface dataset:
Complex Drug Interactions of HIV Protease Inhibitors 2: In Vivo Induction and In Vitro to In Vivo Correlation of Induction of Cytochrome P450 1A2, 2B6, and 2C9 by Ritonavir or Nelfinavir

Drug-drug interactions (DDIs) with the HIV protease inhibitors (PIs) are complex, paradoxical (e.g., ritonavir/alprazolam), and involve multiple mechanisms. As part of a larger study to better understand these DDIs and to devise a framework for in vitro to in vivo prediction of these DDIs, we determined the inductive effect of ∼2 weeks of administration of two prototypic PIs, nelfinavir (NFV), ritonavir (RTV), and rifampin (RIF; induction positive control) on the cytochrome P450 enzymes CYP1A2, CYP2B6, CYP2C9, and CYP2D6 and the inductive or inductive plus inhibitory effect of NFV, RTV, or RIF on CYP3A and P-glycoprotein in healthy human volunteers. Statistically significant induction of CYP1A2 (2.1-, 2.9-, and 2.2-fold), CYP2B6 (1.8-, 2.4-, and 4-fold), and CYP2C9 (1.3-, 1.8-, and 2.6-fold) was observed after NFV, RTV, or RIF treatment, respectively (as expected, CYP2D6 was not induced). Moreover, we accurately predicted the in vivo induction of these enzymes by quantifying their induction by the PIs in human hepatocytes and by using RIF as an in vitro to in vivo scalar. On the basis of the modest in vivo induction of CYP1A2, CYP2B6, or CYP2C9, the in vivo paradoxical DDIs with the PIs are likely explained by mechanisms other than induction of these enzymes such as induction of other metabolic enzymes, transporters, or both.
Development and validation of a prediction algorithm for the onset of common mental disorders in a working population

Objective: Common mental disorders are the most common reason for long-term sickness absence in most developed countries. Prediction algorithms for the onset of common mental disorders may help target indicated work-based prevention interventions. We aimed to develop and validate a risk algorithm to predict the onset of common mental disorders at 12 months in a working population. Methods: We conducted a secondary analysis of the Household, Income and Labour Dynamics in Australia Survey, a longitudinal, nationally representative household panel in Australia. Data from the 6189 working participants who did not meet the criteria for a common mental disorders at baseline were non-randomly split into training and validation databases, based on state of residence. Common mental disorders were assessed with the mental component score of 36-Item Short Form Health Survey questionnaire (score ⩽45). Risk algorithms were constructed following recommendations made by the Transparent Reporting of a multivariable prediction model for Prevention Or Diagnosis statement. Results: Different risk factors were identified among women and men for the final risk algorithms. In the training data, the model for women had a C-index of 0.73 and effect size (Hedges’ g) of 0.91. In men, the C-index was 0.76 and the effect size was 1.06. In the validation data, the C-index was 0.66 for women and 0.73 for men, with positive predictive values of 0.28 and 0.26, respectively Conclusion: It is possible to develop an algorithm with good discrimination for the onset identifying overall and modifiable risks of common mental disorders among working men. Such models have the potential to change the way that prevention of common mental disorders at the workplace is conducted, but different models may be required for women.
Identification of Major and Minor QTL for Ecologically Important Morphological Traits in Three-Spined Sticklebacks (Gasterosteus aculeatus)

Quantitative trait locus (QTL) mapping studies of Pacific three-spined sticklebacks (Gasterosteus aculeatus) have uncovered several genomic regions controlling variability in different morphological traits, but QTL studies of Atlantic sticklebacks are lacking. We mapped QTL for 40 morphological traits, including body size, body shape, and body armor, in a F2 full-sib cross between northern European marine and freshwater three-spined sticklebacks. A total of 52 significant QTL were identified at the 5% genome-wide level. One major QTL explaining 74.4% of the total variance in lateral plate number was detected on LG4, whereas several major QTL for centroid size (a proxy for body size), and the lengths of two dorsal spines, pelvic spine, and pelvic girdle were mapped on LG21 with the explained variance ranging from 27.9% to 57.6%. Major QTL for landmark coordinates defining body shape variation also were identified on LG21, with each explaining ≥15% of variance in body shape. Multiple QTL for different traits mapped on LG21 overlapped each other, implying pleiotropy and/or tight linkage. Thus, apart from providing confirmatory data to support conclusions born out of earlier QTL studies of Pacific sticklebacks, this study also describes several novel QTL of both major and smaller effect for ecologically important traits. The finding that many major QTL mapped on LG21 suggests that this linkage group might be a hotspot for genetic determinants of ecologically important morphological traits in three-spined sticklebacks.
Lazy Solid Texture Synthesis

Existing solid texture synthesis algorithms generate a full volume of color content from a set of 2D example images. We introduce a new algorithm with the unique ability to restrict synthesis to a subset of the voxels, while enforcing spatial determinism. This is especially useful when texturing objects, since only a thick layer around the surface needs to be synthesized. A major difficulty lies in reducing the dependency chain of neighborhood matching, so that each voxel only depends on a small number of other voxels.
Haematological Changes at Altitude

Hypobaric hypoxia is associated with an increase in erythropoesis and an increased thrombotic risk. This is true of long haul air travel, mountaineering expeditions and longer stays at altitude. Studies looking at clotting on mountaineering expeditions are further complicated by the effects of exercise, plasma volume changes and the catecholamine response to hypoxia. This review examines the evidence for changes in clotting factors and functional clotting at altitude and considers the implications of altitude travel for those with pre-existing medical conditions.
HQEMU: a multi-threaded and retargetable dynamic binary translator on multicores

Dynamic binary translation (DBT) is a core technology to many important applications such as system virtualization, dynamic binary instrumentation and security. However, there are several factors that often impede its performance: (1) emulation overhead before translation; (2) translation and optimization overhead, and (3) translated code quality. On the dynamic binary translator itself, the issues also include its retargetability to support guest applications from different instruction-set architectures (ISAs) to host machines also with different ISAs, an important feature for system virtualization. In this work, we take advantage of the ubiquitous multicore platforms, using multithreaded approach to implement DBT. By running the translators and the dynamic binary optimizers on different threads on different cores, it could off-load the overhead caused by DBT on the target applications; thus, afford DBT of more sophisticated optimization techniques as well as the support of its retargetability. Using QEMU (a popular retargetable DBT for system virtualization) and LLVM (Low Level Virtual Machine) as our building blocks, we demonstrated in a multi-threaded DBT prototype, called HQEMU, that it could improve QEMU performance by a factor of 2.4X and 4X on the SPEC 2006 integer and floating point benchmarks for x86 to x86-64 emulations, respectively, i.e. it is only 2.5X and 2.1X slower than native execution of the same benchmarks on x86-64, as opposed to 6X and 8.4X slowdown on QEMU. For ARM to x86-64 emulation, HQEMU could gain a factor of 2.4X speedup over QEMU for the SPEC 2006 integer benchmarks.
Information behaviour, health self-efficacy beliefs and health behaviour in Icelanders' everyday life

Introduction. The aim of this study is to gather knowledge about how different groups of Icelanders take advantage of information about health and lifestyle in their everyday life. Method. A random sample of 1,000 people was used in the study and data was gathered as a postal survey. Response rate was 50.8%. Analysis. K-means cluster analysis was used to draw four clusters based on the participants' purposive information seeking. To validate the cluster classification and describe the clusters further, they were examined in relation to a number of external variables related to information behaviour, as well as the variables sex, age and education. The health self-efficacy beliefs and the health behaviour of the clusters were also examined. Results. The results indicate that four distinct groups of people exist, that differ not only regarding their information behaviour, but also in relation to their health self-efficacy beliefs and health behaviour. Conclusions. The findings indicate that information seeking which is accompanied by a critical approach in the selection of information sources and low information behaviour barriers, together with high health self-efficacy beliefs, relates to the most healthy behaviour. Abstract
Broadcasting Policy in a New Cultural Regime the Case of Australian Television

The idea that Western industrial capitalist societies are in transition from the crisis period of the 1970s and 1980s to a phase of restructuring and transformation has become a commonplace of both political economy and cultural studies. This article looks at the extent to which this restructuring will critically shape the emerging cultural and social terrain, and in particular its relevance to broadcasting policy. It considers the major current theoretical approaches to new technologies, and the implications of developments such as globalisation, post-fordism, and the emergence of cultural industries and cultural policy. Particular consideration is given to theories relating to postmodernism and the dilemmas of media culture.
Hepatitis B virus X protein stimulates gene expression selectively from extrachromosomal DNA templates

Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cancer development. HBV encodes the hepatitis B virus X (HBx) protein that promotes transcription of the viral episomal DNA genome by the host cell RNA polymerase II. Here we provide evidence that HBx accomplishes this task by a conserved and unusual mechanism. Thus, HBx strongly stimulates expression of transiently transfected reporter constructs, regardless of the enhancer and promoter sequences. This activity invariably requires HBx binding to the cellular UV‐damaged DDB1 E3 ubiquitin ligase, suggesting a common mechanism. Unexpectedly, none of the reporters tested is stimulated by HBx when integrated into the chromosome, despite remaining responsive to their cognate activators. Likewise, HBx promotes gene expression from the natural HBV episomal template but not from a chromosomally integrated HBV construct. The same was observed with the HBx protein of woodchuck HBV. HBx does not affect nuclear plasmid copy number and functions independently of CpG dinucleotide methylation. Conclusion: We propose that HBx supports HBV gene expression by a conserved mechanism that acts specifically on episomal DNA templates independently of the nature of the cis‐regulatory sequences. Because of its uncommon property and key role in viral transcription, HBx represents an attractive target for new antiviral therapies. (HEPATOLOGY 2012;56:2116–2124)
[Intelligence and prognosis in severe traumatic brain injury: a neuropsychological study with the Wechsler adult intelligence scale (WAIS-III)].

OBJECTIVE To evaluate the utility of the Wechsler adult intelligence scale III (WAIS-III) as a measure of intelligence after severe brain injury, and to elucidate prognostic factors associated with intelligence coefficients (IQs). METHODS Forty-six patients (age: 27.4 +/- 12.8 years) attending our service after a severe head injury were included in our study (chronicity: 315.3 +/- 330 days after injury). All patients were assessed with the WAIS-III. WAIS-III IQs were correlated (Pearson and Spearman) with clinical and demographic data. A significance level of p < 0.05 was used in all comparisons. IQs between 1 and 2 standard deviation (SD) below normative data were considered "mild abnormal" while indexes below 2 SD were considered "abnormal". RESULTS Only eleven patients (25 %) showed normal total IQ with predominance of manipulative (77.7 %) compared to verbal (64.5 %) impairment. Thirty-eight patients (95 %) had difficulties in speed processing, thirty-six (85.6 %) had problems with working-memory, twenty-five (62.5 %) showed impairments in perceptual organization, and twenty-six (62 %) had verbal comprehension deficits. WAIS-III IQs showed significant correlations with length of coma and posttraumatic amnesia duration (p < 0.05). CONCLUSIONS The WAIS-III is a valid and sensible tool to detect cognitive deficits associated with brain injury. Almost all patients with severe brain injury show abnormal IQs with a slow processing speed as predominant symptom. Length of coma and posttraumatic amnesia seems to be the most relevant parameter related to intelligence in severe brain-injured patients.
Fitted BVH for Fast Raytracing of Metaballs

Raytracing metaballs is a problem that has numerous applications in the rendering of dynamic soft objects such as fluids. However, current techniques are either limited in the visual effects that they can render or their performance drops as the number of metaballs and their density increase. We present a new acceleration structure based on BVH and kd‐tree for efficient raytracing of a large number of metaballs. This structure is built from an adapted SAH using a fast greedy algorithm and allows the visualization of several hundreds of thousands metaballs at interactive‐to‐real‐time framerates. Our method can handle arbitrary rays to simulate any complex secondary effects such as reflections or soft shadows, and is robust with respect to the density of metaballs. We achieve this performance thanks to a balanced CPU‐GPU (using CUDA) implementation of the animation, structure creation, and rendering.
Sacred moments in psychotherapy from the perspectives of mental health providers and clients: Prevalence, predictors, and consequences.

This article reports on the first empirical attempt to analyze “sacred moments” in the therapist-client relationship, and their implications for the client, the provider, and the therapeutic alliance. In the first study, 58 mental health providers from a large school of medicine completed a survey that asked them to describe an important moment in their work with a client over the past year. They then responded to questions about (a) the degree to which they attributed sacred qualities to the important moment; (b) predictors of the sacredness of these moments; and (c) consequences of these moments for the client, provider, and therapeutic alliance. More than half of providers (55.5%) indicated that their important moment in treatment was sacred. Perceptions of the sacredness of the moment were strongly correlated with greater perceived client gains, therapeutic relationship gains, provider gains, and work motivation. These findings were largely replicated in a second study of 519 clients who had been in mental health treatment during the past year. Sacred moments in treatment represent a potentially important resource that may contribute to the well-being of providers, clients, and the therapeutic relationship. More generally, these findings point to the value of attending to the spiritual dimension of the relationship between providers and clients.
Incidence Angle Normalization of Radar Backscatter Data

The National Aeronautics and Space Administration's (NASA) proposed Soil Moisture Active Passive (SMAP) satellite mission ( ~ 2014) will include a radar system that will provide L-band multi-polarization backscatter at a constant incidence angle of 40 °. During the pre-launch phase of the project, there is a need for observations that will support the radar-based soil moisture algorithm development and validation. A valuable resource for providing these observations is the NASA Jet Propulsion Laboratory Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR). However, SMAP will observe at a constant incidence angle of 40 °, and UAVSAR collects data over a wide range of incidence angles (25 °-60°). In this investigation, a technique was developed and tested for normalizing UAVSAR data to a constant incidence angle. The approach is based on a histogram matching procedure. The data used to develop and demonstrate this approach were collected as part of the Canadian Soil Moisture Experiment 2010 (CanEx-SM10). Land cover in the region included agriculture and forest. Evaluation was made possible by the acquisition of numerous overlapping UAVSAR flight lines that provided multiple incidence angle observations of the same locations. Actual observations at a 40° incidence angle were compared to the normalized data to assess performance of the normalization technique. An optimum technique should be able to reduce the systematic error (Bias) to 0 dB and to lower the total root mean square error (RMSE) computed after correction to the level of the initial residual error (RMSEres) present in the data set. The normalization approach developed here achieved both of these. Bias caused by the incidence angle variability was minimized to ~ 0 dB, whereas the residual error caused by instrument related random errors and amplitude fluctuations due to ground variability was reduced to approximately 3 dB for agricultural areas and 2.6 dB for forests; these values were consistent with the initial RMSEres estimated using the un-corrected data. The residual error can be reduced further by aggregating the radar observations to a coarser grid spacing. The technique adequately adjusted the backscatter over the full swath width irrespective of the original incidence angle, polarization, and ground conditions (vegetation cover and soil moisture). In addition to providing a basis for fully exploiting UAVSAR (or similar aircraft systems) for SMAP algorithm development and validation, the technique could also be adapted to satellite radar systems. This normalization approach will also be beneficial in terms of reducing the number of flight lines required to cover a study area, which would eventually result in more cost-effective soil moisture field campaigns.
Diabetes Quality of Care and Outpatient Utilization Associated With Electronic Patient-Provider Messaging: A Cross-Sectional Analysis

OBJECTIVE To test the hypothesis that electronic patient-provider messaging is associated with high care quality for diabetes and lower outpatient utilization. RESEARCH DESIGN AND METHODS We conducted a cross-sectional analysis of electronic patient-provider messaging over a 15-month period between 1 January 2004 and 31 March 2005. The study was set at Group Health Cooperative—a consumer-governed, nonprofit health care system that operates in Washington and Idaho. Participants included all patients aged ≥18 years with a diagnosis of diabetes. In addition to usual care, all patients had the option to use electronic messaging to communicate with their care providers. The primary outcome measures were diabetes-related quality-of-care indicators (A1C, blood pressure, and LDL cholesterol) and outpatient visits (primary care, specialty care, and emergency). RESULTS Nineteen percent of patients with diabetes used electronic messaging to communicate with their care providers during the study period (n = 2,924) (overall study cohort: 15,427 subjects). In multivariate models, frequent use of electronic messaging was associated with A1C <7% (relative risk [RR] 1.36 [95% CI 1.16–1.58]). Contrary to our hypothesis, frequent use of electronic messaging was also associated with a higher rate of outpatient visits (1.39 [1.26–1.53]). CONCLUSIONS Frequent use of electronic secure messaging is associated with better glycemic control and increased outpatient utilization. Electronic patient-provider communication may represent one strategy to meet the health care needs of this unique population. More research is necessary to assess the effect of electronic messaging on care quality and utilization.
The Clinical Significance of Unknown Sequence Variants in BRCA Genes

Germline mutations in BRCA1/2 genes are responsible for a large proportion of hereditary breast and/or ovarian cancers. Many highly penetrant predisposition alleles have been identified and include frameshift or nonsense mutations that lead to the translation of a truncated protein. Other alleles contain missense mutations, which result in amino acid substitution and intronic variants with splicing effect. The discovery of variants of uncertain/unclassified significance (VUS) is a result that can complicate rather than improve the risk assessment process. VUSs are mainly missense mutations, but also include a number of intronic variants and in-frame deletions and insertions. Over 2,000 unique BRCA1 and BRCA2 missense variants have been identified, located throughout the whole gene (Breast Cancer Information Core Database (BIC database)). Up to 10–20% of the BRCA tests report the identification of a variant of uncertain significance. There are many methods to discriminate deleterious/high-risk from neutral/low-risk unclassified variants (i.e., analysis of the cosegregation in families of the VUS, measure of the influence of the VUSs on the wild-type protein activity, comparison of sequence conservation across multiple species), but only an integrated analysis of these methods can contribute to a real interpretation of the functional and clinical role of the discussed variants. The aim of our manuscript is to review the studies on BRCA VUS in order to clarify their clinical relevance.
Advertising's Influence on Subsequent Product Trial Processing

Abstract Several studies have shown that pretrial ad exposure can positively influence a subsequent product trial experience. In this study, we investigate several specific, positive ad effects on product trial using an experiment that exposes subjects to a trial only, an ad only, or an ad and trial. In general, the pretrial ad appeared to encourage consumers to process a subsequent product trial more deeply, purposefully, and carefully than was the case with the trial alone. Subjects exposed to a pretrial ad rated the subsequent trial higher in diagnosticity, formed more confidently held beliefs, and formed higher expectancy value and purchase intentions. In addition, consumers exposed to an ad prior to trial showed stronger structural relationships among expectancy value, brand attitude, and purchase intentions compared with those consumers that experienced a product trial alone. Such results suggest that posttrial responses are the result of more careful and focused processing of the trial information. Advertising and product trial were also shown to differ significantly in their ability to foster strongly held beliefs about experiential and nonexperiential product attributes. As expected, advertising was superior at communicating nonexperiential beliefs, and trial excelled at fostering experiential attribute beliefs.