Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple Testing Problems in Pharmaceutical Statistics

Multiplicity Problems in Clinical Trials: A Regulatory Perspective, Mohammad Huque and Joachim Rohmel Introduction Common multiplicity problems in clinical trials Reducing multiplicity in clinical trials Multiplicity concerns in special situations Multiplicity in the analysis of safety endpoints Concluding remarks Multiple Testing Methodology, Alex Dmitrienko, Frank Bretz, Peter H. Westfall, James Troendle, Brian L. Wiens, Ajit C. Tamhane, and Jason C. Hsu Introduction Error rate definitions Multiple testing principles Adjusted significance levels, p-values, and confidence intervals Common multiple testing procedures Multiple testing procedures based on univariate p-values Parametric multiple testing procedures Resampling-based multiple testing procedures Software implementation Multiple Testing in Dose Response Problems, Frank Bretz, Ajit C. Tamhane, and Jose Pinheiro Introduction Dose response trend tests Target dose estimation using multiple hypothesis testing Power and sample size calculation for target dose estimation Hybrid approaches combining multiple testing and modeling Analysis of Multiple Endpoints in Clinical Trials, Ajit C. Tamhane and Alex Dmitrienko Introduction Inferential goals At-least-one procedures Global testing procedures All-or-none procedures Superiority-noninferiority procedures Software implementation Gatekeeping Procedures in Clinical Trials, Alex Dmitrienko and Ajit C. Tamhane Introduction Motivating examples Serial gatekeeping procedures Parallel gatekeeping procedures Tree gatekeeping procedures Software implementation Adaptive Designs and Confirmatory Hypothesis Testing, Willi Maurer, Michael Branson, and Martin Posch Introduction Basic principles and methods of error rate control Principles of adaptive testing procedures Adaptive multiple testing procedures Case studies Discussion Design and Analysis of Microarray Experiments for Pharmacogenomics, Jason C. Hsu, Youlan Rao, Yoonkyung Lee, Jane Chang, Kristin Bergsteinsdottir, Magnus Karl Magnusson, Tao Wang, and Eirikur Steingrimsson Potential uses of biomarkers Clinical uses of genetic profiling Two stages of pharmacogenomic development Multiplicity in pharmacogenomics Designing pharmacogenomic studies Analyzing microarray data by modeling A proof of concept experiment Software implementation Bibliography
Using a data-driven approach for the development and evaluation of phenotype algorithms for systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin. The objective of this research was to develop phenotype algorithms for SLE suitable for use in epidemiological studies using empirical evidence from observational databases. Methods We used a process for empirically determining and evaluating phenotype algorithms for health conditions to be analyzed in observational research. The process started with a literature search to discover prior algorithms used for SLE. We then used a set of Observational Health Data Sciences and Informatics (OHDSI) open-source tools to refine and validate the algorithms. These included tools to discover codes for SLE that may have been missed in prior studies and to determine possible low specificity and index date misclassification in algorithms for correction. Results We developed four algorithms using our process: two algorithms for prevalent SLE and two for incident SLE. The algorithms for both incident and prevalent cases are comprised of a more specific version and a more sensitive version. Each of the algorithms corrects for possible index date misclassification. After validation, we found the highest positive predictive value estimate for the prevalent, specific algorithm (89%). The highest sensitivity estimate was found for the sensitive, prevalent algorithm (77%). Conclusion We developed phenotype algorithms for SLE using a data-driven approach. The four final algorithms may be used directly in observational studies. The validation of these algorithms provides researchers an added measure of confidence that the algorithms are selecting subjects correctly and allows for the application of quantitative bias analysis.
DYNAMICAL EVOLUTION IN THE OPEN CLUSTER NGC 6819

We have conducted VI CCD photometry of the open cluster NGC 6819 in order to understand the effects of dynamical evolution in old open clusters. Our photometry covers 18` 18` on the sky, centered on the cluster, which seems to cover the whole cluster field. Our photometry reaches down to V 20.5, which allows us to analyze the luminosity function and spatial distribution of stars brighter than Mv 8.5. There is a clear evidence for mass segregation in NGC 6819, i.e., the giants and upper main-sequence stars are concentrated in the inner regions, whereas the lower main-sequence stars distribute almost uniformly throughout the cluster. The luminosity function of the main-sequence stars of NGC 6819 is almost flat. The flat luminosity function indicates that a large number of low mass stars has escaped from the cluster unless its initial mass function is much different from the Salpeter type (${\phi}(m){\propto} m^{-(1+x)},x
Spatio-temporal and transmission dynamics of sarcoptic mange in an endangered New World kit fox

Sarcoptic mange poses a serious conservation threat to endangered San Joaquin kit foxes (Vulpes macrotis mutica). After first appearing in Bakersfield, California in spring 2013, mange reduced the kit fox population approximately 50% until the epidemic ended with minimally detectable endemic cases after 2020. Mange is lethal and thus, with such a high force of infection and lack of immunity, it remains unclear why the epidemic did not burn itself out rapidly and how it persisted so long. Here we explored spatio-temporal patterns of the epidemic, analyzed historical movement data, and created a compartment metapopulation model (named “metaseir”) to evaluate whether movement of foxes among patches and spatial heterogeneity would reproduce the eight years epidemic with 50% population reduction observed in Bakersfield. Our main findings from metaseir were that: 1) a simple metapopulation model can capture the Bakersfield-like disease epidemic dynamics even when there is no environmental reservoir or external spillover host, 2) the most impactful parameter on persistence and magnitude of the epidemic is the projection, β/αβ (transmission over decay rate of transmission over space), 3) heterogeneity in patch carrying capacities changes the critical value of the projection needed to achieve an epidemic but makes little difference to epidemic persistence time, and 4) the epidemic is relatively insensitive to birth rates and density vs. frequency-dependent transmission. Our model can help guide management and assessment of metapopulation viability of this vulpid subspecies, while the exploratory data analysis and model will also be valuable to understand mange in other, particularly den-occupying, species.
Determination of Epidemiological Cutoff Values for Antimicrobial Resistance of Enterococcus cecorum

Enterococcus cecorum, a commensal Gram-positive bacterium of the chicken gut, has emerged as a worldwide cause of lameness in poultry, particularly in fast-growing broilers. It is responsible for osteomyelitis, spondylitis, and femoral head necrosis, causing animal suffering, mortality, and antimicrobial use. ABSTRACT Enterococcus cecorum, a commensal Gram-positive bacterium of the chicken gut, has emerged as a worldwide cause of lameness in poultry, particularly in fast-growing broilers. It is responsible for osteomyelitis, spondylitis, and femoral head necrosis, causing animal suffering, mortality, and antimicrobial use. Research on the antimicrobial resistance of E. cecorum clinical isolates in France is scarce, and epidemiological cutoff (ECOFF) values are unknown. To determine tentative ECOFF (COWT) values for E. cecorum and to investigate the antimicrobial resistance patterns of isolates from mainly French broilers, we tested the susceptibility of a collection of commensal and clinical isolates (n = 208) to 29 antimicrobials by the disc diffusion (DD) method. We also determined the MICs of 23 antimicrobials by the broth microdilution method. To detect chromosomal mutations conferring antimicrobial resistance, we investigated the genomes of 118 E. cecorum isolates obtained mainly from infectious sites and described previously in the literature. We determined the COWT values for more than 20 antimicrobials and identified two chromosomal mutations explaining fluoroquinolone resistance. The DD method appears better suited for detecting E. cecorum antimicrobial resistance. Although tetracycline and erythromycin resistances were persistent in clinical and nonclinical isolates, we found little or no resistance to medically important antimicrobials.
Fluctuation of Mass Flux in a Cloud-Resolving Simulation with Interactive Radiation

Abstract It was shown by Craig and Cohen that fluctuations of cumulus clouds under homogeneous large-scale forcing satisfy the Gibbs canonical ensemble in a strict radiative–convective equilibrium (RCE). In the limit of random noninteracting convective cells, an analytical expression for the distribution function of total mass flux over a region of given size was derived. The authors examine the consistency of the Gibbs canonical ensemble as a representation for the mass flux fluctuations when the large-scale forcing is time dependent. A cloud-resolving simulation (CRM) with interactive radiation, fixed imposed surface temperature, and diurnally varying solar forcing to mimic the diurnal cycle over the tropical ocean is used. As a necessary condition for the existence of a state of quasi-equilibrium, the time-scale separation between convective processes and forcing is studied. Detailed evaluation of time scales of convective adjustment and memory in a three-month run confirms the hypothesis of time-scale.
In vitro and in vivo acute toxicity of an artificial butter flavoring

ABSTRACT Flavorings used in cookies, electronic cigarettes, popcorn, and breads contain approximately 30 chemical compounds, which makes it difficult to determine and correlate signs and symptoms of acute, subacute or chronic toxicity. The aim of this study was to characterize a butter flavoring chemically and subsequently examine the in vitro and in vivo toxicological profile using cellular techniques, invertebrates, and lab mammals. For the first time, the ethyl butanoate was found as the main compound of a butter flavoring (97.75%) and 24 h-toxicity assay employing Artemia salina larvae revealed a linear effect and LC50 value of 14.7 (13.7–15.7) mg/ml (R2 = 0.9448). Previous reports about higher oral doses of ethyl butanoate were not found. Observational screening with doses between 150–1000 mg/kg by gavage displayed increased amount of defecation, palpebral ptosis, and grip strength reduction, predominantly at higher doses. The flavoring also produced clinical signs of toxicity and diazepam-like behavioral changes in mice, including loss of motor coordination, muscle relaxation, increase of locomotor activity and intestinal motility, and induction of diarrhea, with deaths occurring after 48 h exposure. This substance fits into category 3 of the Globally Harmonized System. Data demonstrated that butter flavoring altered the emotional state in Swiss mice and disrupted intestinal motility, which may be a result of neurochemical changes or direct lesions in the central/peripheral nervous systems.
Association of a Mediterranean Diet With Outcomes for Patients Treated With Immune Checkpoint Blockade for Advanced Melanoma

Key Points Question Is a habitual diet associated with tumor response to immune checkpoint blockade (ICB) in advanced melanoma? Findings In this cohort study of 91 patients with advanced melanoma in the UK and the Netherlands, higher adherence to the principles of a Mediterranean diet was associated with a higher probability of response to treatment with ICB. Meaning The results of this study suggest that while further studies across different countries will be needed to confirm the findings and offer patient-specific advice, habitual diet may have a role in improving responses to ICB.
Determinants of good vitamin A consumption in the 12 East Africa Countries using recent Demographic and health survey

Background Vitamin A one of the important micronutrients that it cannot be made in the human body and must be taken from outside the body through the diet. Ensuring that vitamin A is available in any form in sufficient quantities remains a challenge, especially in regions where access to vitamin A-containing foods and healthcare interventions is limited. As a result, vitamin A deficiency (VAD) becomes a common form of micronutrient deficiency. To the best of our knowledge, there is limited evidence on determinants of good Vitamin A consumption in East African countries. Therefore, this study aimed to assess the magnitude and determinants of good vitamin A consumption in East African countries. Methods A recent Demographic and Health Survey (DHS) of twelve East African countries were included to determine the magnitude and determinants of good vitamin A consumption. A total of 32,275 study participants were included in this study. A multilevel logistic regression model was used to estimate the association between the likelihood of good vitamin A-rich food consumption. Both community and individual levels were used as independent variables. Adjusted odds ratio and its 95% confidence interval were used to see the strength of the association. Result The pooled magnitude of good vitamin A consumption was 62.91% with a 95% CI of 62.3 to 63.43. The higher proportion of good vitamin A consumption 80.84% was recorded in Burundi and the smallest good vitamin A consumption 34.12% was recorded in Kenya. From the multilevel logistic regression model, women’s age, marital status, maternal education, wealth index, maternal occupation, children’s age in a month, media exposure, literacy rate, and parity were significantly associated with good vitamin A consumption in East Africa. Conclusion The magnitude of good vitamin A consumption in twelve East African countries is low. To increase good vitamin A consumption health education through the mass media and enhancing the economic status of women is recommended. Planners and implementers should give attention and priority to identified determinants to enhance good vitamin A consumption.
New simulation software to predict postoperative corneal stiffness before laser vision correction

A new predictive simulation-based software was developed and validated to estimate postoperative corneal stiffness after refractive surgery using preoperative information. The software showed high predictability in normal and ectasia eyes. Purpose: To develop a new virtual surgery simulation platform to predict postoperative corneal stiffness (Kcmean) after laser vision correction (LVC) surgery. Setting: Narayana Nethralaya Eye Hospital and Sankara Nethralaya, India; Humanitas Clinical and Research Center, Italy. Design: Retrospective observational case series. Methods: 529 eyes from 529 patients from 3 eye centers and 10 post–small-incision lenticule extraction (SMILE) ectasia eyes were included. The software (called AcuSimX) derived the anisotropic, fibril, and extracellular matrix biomechanical properties (using finite element calculation) of the cornea using the preoperative Corvis-ST, Pentacam measurement, and inverse finite element method assuming published healthy collagen fibril orientations. Then, the software-computed postoperative Kcmean was adjusted with an artificial intelligence (AI) model (Orange AI) for measurement uncertainties. A decision tree was developed to classify ectasia from normal eyes using the software-computed and preoperative parameters. Results: In the training cohort (n = 371 eyes from 371 patients), the mean absolute error and intraclass correlation coefficient were 6.24 N/m and 0.84 (95% CI, 0.80-0.87), respectively. Similarly, in the test cohort (n = 158 eyes from 158 patients), these were 6.47 N/m and 0.84 (0.78-0.89), respectively. In the 10 ectasia eyes, the measured in vivo (74.01 [70.01-78.01]) and software-computed (74.1 [69.03-79.17]) Kcmean were not statistically different (P = .96). Although no statistically significant differences in these values were observed between the stable and ectasia groups (P ≥ .14), the decision tree classification had an area under the receiver operating characteristic curve of 1.0. Conclusions: The new software provided an easy-to-use virtual surgery simulation platform for post-LVC corneal stiffness prediction by clinicians and was assessed in post-SMILE ectasia eyes. Further assessments with ectasia after surgeries are required.
The effects of social media (Snapchat) interventions on the knowledge of oral health during pregnancy among pregnant women in Saudi Arabia

Background There is growing interest in using social media to improve pregnant women’s well-being. This study aimed to evaluate the effects of social media (Snapchat) dissemination of health-promoting interventions on knowledge of oral health during pregnancy among pregnant women in Saudi Arabia. Materials and methods Using a single-blinded parallel group randomized controlled trial design, 68 volunteers were assigned to either a study group (SG) or a control group (CG). The SG received information about oral health during pregnancy via Snapchat, while the CG received the same information using WhatsApp. The participants were assessed three times: T1 prior to the intervention, T2 immediately following the intervention, and T3 as a follow-up 1 month later. Results A total of 63 participants completed the study in the SG or CG. According to paired t-test, total knowledge scores in the SG and CG increased significantly from T1 to T2 (p < 0.001) and from T1 to T3 (p < 0.001), but there was no significant change from T2 to T3 in either the SG or CG (p = 0.699 and p = 0.111, respectively). Using t-test, no significant differences were found between the SG and CG at T2 (p = 0.263) or T3 (p = 0.622). Also using t-test, no significant differences were found in the scores of the SG and CG from T2 to T1 (p = 0.720), T3 to T2 (p = 0.339), or T3 to T1 (p = 0.969). Conclusions Using social media (e.g., Snapchat and WhatsApp) as a health-promoting intervention is a promising method for improving women’s knowledge about oral health during pregnancy for short term. However, further studies are needed to compare social media with conventional standard lecturing methods. also, to assess the longevity of the impact (short or long term).
Chronic Disseminated Candidiasis in Children and the Role of Corticosteroids Therapy

Background: Little is known about chronic disseminated candidiasis (CDC) in children. This study was done to describe the epidemiology, risk factors and outcome of CDC in children managed at Sultan Qaboos University Hospital (SQUH), Oman, and to describe the role of corticosteroids in the management of immune reconstitution inflammatory syndrome (IRIS) complicating CDC. Methods: We retrospectively reported demographic, clinical and laboratory data of all children managed in our center for CDC between January 2013 and December 2021. In addition, we discuss the available literature on the role of corticosteroids for management of CDC-related IRIS in children since 2005. Results: Between January 2013 and December 2021, 36 immunocompromised children were diagnosed with invasive fungal infection at our center, of whom 6 had CDC (all with acute leukemia). Their median age was 5.75 years. Prolonged fever despite broad-spectrum antibiotics (6/6) followed by skin rash (4/6) were the most common clinical features of CDC. Four children grew Candida tropicalis from blood or skin. CDC-related IRIS was documented in 5 children (83%) and 2 received corticosteroids. Our literature review revealed that 28 children were managed with corticosteroids for CDC-related IRIS since 2005. The majority of these children had defervescence of fever within 48 hours. Prednisolone of 1–2 mg/kg/day for 2–6 weeks was the most common regimen used. No major side effects reported in these patients. Conclusion: CDC is more common in children with acute leukemia and CDC-related IRIS is not uncommon. Corticosteroid therapy looks effective and safe as adjunctive therapy for CDC-related IRIS.
On the limiting profile arising from orthonormalizing shifts of exponentially decaying functions

It is shown that, under certain conditions, orthonormalizing the positive integer shifts of an exponentially decaying function on the half line by the Gram-Schmidt process leads to a limiting profile given by orthonormalizing all their integer shifts on the whole line. These results derive from properties of Cholesky factorization of bi-infinite and semi-infinite matrices. An example is provided by the negative exponential function and conjectures are given, supported by numerical evidence, for the Gaussian and Lorentz function.
Psychosocial barriers to, and enablers of, intimate partner violence disclosure among Asian-American immigrant women

Abstract Although Asian women immigrants to the USA rarely disclose intimate partner violence, local research indicates that among them domestic abuse is prevalent. This study aimed to determine the main psychosocial barriers and enablers to disclosure among Asian-American women in California, and whether barriers outweighed benefits. We used a novel qualitative methodology of indirect and direct questioning with sixty married women from four ethnicities (Korean, Chinese, Thai and Vietnamese). Overall, barriers to disclosure were more compelling and tangible than enablers, particularly among Mandarin Chinese and Korean speakers. Five main barriers were found: victim-blaming, beliefs in female inferiority and male dominance, familial shame, individual shame and fear of undesirable consequences. Only extreme violence and the need to protect children from harm were seen as warranting disclosure. As a result, health and other providers’ encouragement of disclosure is unlikely to be sufficient to achieve behavioural change. Abused Asian immigrant women need anonymous ways of obtaining professional counselling, information and resources. In addition, community-level awareness programmes in Asian languages are needed to reduce victim-blaming and misinformation.
The long-period companions of multiple stars tend to have moderate eccentricities

We examined the statistics of an angle between the radius vector of a visual companion of a mul- tiple star and the vector of its apparent relative motion in the system. Its distribution f() is related to the orbital eccentricity distribution in the investigated sample. We found that for the wide physical subsystems of the 174 objects from the Multiple Star Catalogue f() is bell-shaped. The Monte-Carlo simulations have shown that our f() corresponds to the population of the moderate-eccentricity orbits and is not compatible with the linear distribution f(e )=2 e which follows from stellar dynamics and seems to hold for wide binaries. This points to the absence of highly elongated orbits among the outer subsystems of multiple stars. The constraint of dynamical stability of triple systems is not sucient to explain the \rounded-o" outer orbits; instead, we speculate that it can result from the angular momentum exchange in multiple systems during their early evolution.