The distinct problems of physical inconsistency and of multivariate bias potentially involved in the statistical adjustment of climate simulations

Bias adjustment of numerical climate model simulations involves several technical and epistemological arguments wherein the notion of physical inconsistency is often referred to, either for rejecting the legitimacy of bias adjustment in general or for justifying the necessity of sophisticated multivariate techniques. However, this notion is often mishandled, in part because the literature generally proceeds without defining it. In this context, the central objective of this study is to clarify and illustrate the distinction between physical inconsistency and multivariate bias, by investigating the effect of bias adjustment on two different kinds of inter-variable relationships, namely a physical constraint expected to hold at every step of a time series and statistical properties that emerge with potential bias over a climatic time scale. The study involves the application of 18 alternative bias adjustment techniques on 10 climate simulations and over 12 sites across North America. Adjusted variables are temperature, pressure, relative humidity and specific humidity, linked by a thermodynamic constraint. The analysis suggests on the one hand that a clear instance of potential physical inconsistency can be avoided with either a univariate or a multivariate technique, if and only if the bias adjustment strategy explicitly considers the physical constraint to be preserved. On the other hand, it also suggests that sophisticated multivariate techniques alone aren’t complete adjustment strategies in presence of a physical constraint, as they cannot replace its explicit consideration. As a supplementary objective, this study relates common optional adjustment procedures with likely effects on diverse basic statistical properties, as an effort to guide climate information users in the determination of adequate bias adjustment strategies for their research purposes.

Improving the Virtual Trichrome Assessment through Bridge Category Models

Non-alcoholic steatohepatitis (NASH) is a liver disease characterized by excessive lipid accumulation and disease progression is typically assessed through inspection of a Trichrome stain for Fibrosis staging. As the public health burden of NASH worsens due to evolving lifestyle habits, pathology laboratory resources will become increasingly strained due to rising demand for specialized stains. Virtual staining processes, computational methods which can synthesize the application of chemical staining reagents, can potentially provide resource savings by obviating the need to acquire specialized stains. Virtual staining technologies are assessed by comparing virtual and real tissue stains for their realism and ability to stage. However, these assessment methods are rife with statistical mistreatment of observed phenomena that are difficult to account for. Bridge category ratings represent a phenomenon where a pathologist may assign two adjacent stages simultaneously, which may bias and/or reduce the power of research findings. Such stage assignments were frequently reported in a large-scale assessment of Virtual Trichrome technologies yet were unaccounted for since no statistical adjustment procedures existed. In this work, we provide an updated assessment of Virtual Trichrome technologies using Bridge Category Models, which account for these bridge ratings. We report that two of four pathologists tended to assign lower Fibrosis stages to virtually stained tissue while the other two pathologists assigned similar stages. These research findings differ when bridge ratings are not accounted for. While promising, these results indicate further room for algorithmic finetuning of Virtual Trichrome technologies.

The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction

Impaired HDL-mediated macrophage cholesterol efflux and higher circulating concentrations of trimethylamine N-oxide (TMAO) levels are independent risk factors for cardiovascular mortality. The TMAO precursors, γ-butyrobetaine (γBB) and Trimethyllysine (TML), have also been recently associated with cardiovascular death, but their interactions with HDL-mediated cholesterol efflux remain unclear. We aimed to determine the associations between APOB depleted plasma-mediated macrophage cholesterol efflux and plasma TMAO, γBB, and TML concentrations and explore their association with two-year follow-up mortality in patients with acute ST-elevation myocardial infarction (STEMI) and unstable angina (UA). Baseline and ATP-binding cassette transporter ABCA1 and ABCG1 (ABCA1/G1)-mediated macrophage cholesterol efflux to APOB-depleted plasma was decreased in patients with STEMI, and the latter was further impaired in those who died during follow-up. Moreover, the circulating concentrations of TMAO, γBB, and TML were higher in the deceased STEMI patients when compared with the STEMI survivors or UA patients. However, after statistical adjustment, only ABCA1/G1-mediated macrophage cholesterol efflux remained significantly associated with mortality. Furthermore, neither the TMAO, γBB, nor TML levels altered the HDL-mediated macrophage cholesterol efflux in vitro. We conclude that impaired ABCA1/G1-mediated macrophage cholesterol efflux is independently associated with mortality at follow-up in STEMI patients.

Spontaneous Reporting of Adverse Drug Reaction Among Health Professionals In Kpone-Katamanso District, Ghana

Background: Spontaneous reporting of adverse drug reactions (ADR) is an effective means of ensuring postmarketing surveillance of drugs, and health professionals play a cardinal role through voluntary reporting of ADR. However, the pharmacovigilance system in Ghana is plagued with under-reporting issues, which is of public health concern. Method: A questionnaire-based cross-sectional study involving 268 health professionals at Kpone-Katamanso District was carried out. Data on spontaneous reporting of ADR, demographics of participants, knowledge, and attitudes of professionals towards reporting and factors that may influence ADR reporting were collected. Logistic regression models were used to examine the association of the independent variables with spontaneous reporting of ADR.Result: Overall, 77.6% (208) of the 268 respondents had witnessed ADR; however, only 17.3% of the respondents have ever reported an ADR to the FDA. Health professionals who had adequate knowledge on spontaneous reporting of ADR were 51.9%, while 30.3% had very good knowledge of spontaneous reporting of ADR. After statistical adjustment, Age (AOR=2.26, 95%CI= 1.25–4.10), Fear of Legal Consequences (AOR=0.15, 95%CI=0.41–0.51), Time Constraint (AOR=0.3, 95%CI=0.10–0.91), Pharmacovigilance training (AOR= 18.78, 95%CI= 5.46–64.59) and Unavailability of Reporting form (AOR=0.28, 95%CI=0.09– 0.88) were found to be significantly associated spontaneous reporting of ADR. Conclusion: The proportion of health professionals in the Kpone-Katamanso District who spontaneously report observed ADR is low. Our findings underscore the need for the FDA to intensify awareness through media sensitization and engage all relevant stakeholders on the need for the entire population to report ADR.

College Adaptation Among Colombian Freshmen Students: Internal Structure of the Student Adaptation to College Questionnaire (SACQ)

The aim of this research is to assess the internal structure and reliability of the Student Adaptation to College Questionnaire (SACQ) in a sample comprising 739 students (64% of them women), attending second-half classes at a private university in the Caribbean Region of Colombia. The SACQ is a 67-item self-report that evaluates four aspects related to university adjustment namely, the academic, institutional, social, and personal-emotional areas. To fulfill its goals, different measurement models were assessed through various confirmatory factor analyses, and the results indicate that the Peruvian model (four dimensions, 27 items) has the best statistical adjustment, presenting evidence in support of its internal structure. Similarly, high reliability indicators were obtained, both with regard to the construct and scoring. In conclusion, the SACQ’s psychometric properties are satisfactory as regards its internal structure (tetra-factorial model) and reliability, enabling its use to evaluate adjustment to college life.

The association between preoperative modified frailty index and postoperative complications in Chinese elderly patients with hip fractures

Objectives To investigate the role of a preoperative modified frailty index (mFI) based on data from medical records in predicting postoperative complications among older Chinese patients with hip fractures. Methods This retrospective cohort study included consecutive older patients with hip fracture admitted to the Department of Orthopaedics, West China Hospital, Sichuan University, from December 2010 to June 2017 who underwent surgical repair. We selected 33 variables, including characteristics of hip fracture, to construct a mFI. Each variable was coded with a value of 0 when a deficit was absent or 1 when it was present. We calculated the mFI as the proportion of positive items and defined frailty as mFI value greater than or equal to 0.21 according to threshold proposed by Hoover et al. We examined the relationship between mFI and severity of postoperative complications and the occurrence of in-hospital pneumonia including statistical adjustment for several demographics (e.g. age, gender, and marital status) and habits (smoking and alcohol intake), time from fracture to surgery in the multivariable model. Results We included 965 patients (34% male; mean age: 76.77 years; range: 60 to 100 years) with a prevalence of frailty of 13.06%. The presence of frailty was associated with a higher severity of complications (OR: 2.07; 95% CI: 1.40 to 3.05). Frail patients were more likely to develop in-hospital pneumonia than non-frail patients (OR: 2.08; 95% CI: 1.28 to 3.39). Conclusion The preoperative modified frailty index based on data from medical records proved significantly associated with postoperative complications among older patients with hip fractures undergoing hip surgery.

Full Mortality risk in patients with adrenal insufficiency using Prednisolone or Hydrocortisone: A Retrospective Cohort study

Context Prednisolone has been recommended rather than hydrocortisone for glucocorticoid replacement in adrenal insufficiency due its longer duration of action and lower cost. Objective To determine mortality rates with prednisolone versus hydrocortisone. Design Observational study. Setting A UK primary care database (Clinical Practice Research Datalink). Participants Patients with primary and secondary adrenal insufficiency, treated with either prednisolone or hydrocortisone, and controls individually matched for age, sex, period and place of follow-up. Interventions Nil Outcomes Mortality relative to individually matched controls. Results As expected, mortality in adrenal insufficiency irrespective of cause was increased, based on 5478 patients (4228 on hydrocortisone; 1250 on prednisolone) and 54314 controls (41934 and 12380, respectively). Overall, the adjusted hazard ratio (HR) was similar with the two treatments (prednisolone, 1.76 [95% CI, 1.54-2.01] vs. hydrocortisone 1.69 [1.57-1.82]; p=0.65). This was also the case for secondary adrenal insufficiency. In primary disease (1405 on hydrocortisone vs. 137 on prednisolone:13965 and 1347 controls, respectively), prednisolone-users were older, more likely to have another autoimmune disease and malignancy, and less likely to have mineralocorticoid replacement. Nevertheless, after adjustment, the HR for prednisolone-treated patients remained higher than for those taking hydrocortisone (2.92 [2.19-3.91] vs. 1.90 [1.66-2.16]; p=0.0020). Conclusions In primary but not in secondary adrenal insufficiency mortality was higher with prednisolone. The study was large, but the number of prednisolone-treated patients was small, and they had greater risk factors. Nonetheless the increased mortality associated with prednisolone persisted despite statistical adjustment. Further evidence is needed regarding the long-term safety of prednisolone as routine replacement.

Scale Effect and Correlation between Uniaxial Compressive Strength and Point Load Index for Limestone and Travertine

Determining the uniaxial compressive strength of intact rock is the primary objective of a geomechanical project, and a reliable estimate in the early phases saves time and costs for more sophisticated laboratory tests. The problem is knowing which of the correlations between the resistance to uniaxial compression and point load index are reliable, those that cover one or several types of rock (depending on the type of statistical adjustment). In this work, they were evaluated with respect to limestone and travertine from experimental results, and the statistical models of the scale effect of the point load index were determined, and the uniaxial compressive strength being estimated from correlations reported in literature. The limestone model was ascending (strength increases as diameter increases), while the travertine model was descending (strength decreases as diameter increases), obtaining similar exponents for the scale effect equations modeled from the uniaxial compressive strength and point load index in both cases.

Lipidomics-Based Comparison of Molecular Compositions of Green, Yellow, and Red Bell Peppers

Identifying and annotating the molecular composition of individual foods will improve scientific understanding of how foods impact human health and how much variation exists in the molecular composition of foods of the same species. The complexity of this task includes distinct varieties and variations in natural occurring pigments of foods. Lipidomics, a sub-field of metabolomics, has emerged as an effective tool to help decipher the molecular composition of foods. For this proof-of-principle research, we determined the lipidomic profiles of green, yellow and red bell peppers (Capsicum annuum) using liquid chromatography mass spectrometry and a novel tool for automated annotation of compounds following database searches. Among 23 samples analyzed from 6 peppers (2 green, 1 yellow, and 3 red), over 8000 lipid compounds were detected with 315 compounds (106 annotated) found in all three colors. Assessments of relationships between these compounds and pepper color, using linear mixed effects regression and false discovery rate (<0.05) statistical adjustment, revealed 11 compounds differing by color. The compound most strongly associated with color was the carotenoid, β-cryptoxanthin (p-value = 7.4 × 10−5; FDR adjusted p-value = 0.0080). These results support lipidomics as a viable analytical technique to identify molecular compounds that can be used for unique characterization of foods.

Associations between Dietary Patterns and Inflammatory Markers during Pregnancy: A Systematic Review

Elevated inflammation in pregnancy has been associated with multiple adverse pregnancy outcomes and potentially an increased susceptibility to future chronic disease. How maternal dietary patterns influence systemic inflammation during pregnancy requires further investigation. The purpose of this review was to comprehensively evaluate studies that assessed dietary patterns and inflammatory markers during pregnancy. This review was guided by the Preferred Reporting Items for Systematic Review and Meta-Analyses. Included studies were sourced from EMBASE, PubMed, Web of Science, and Scopus and evaluated using The Quality Assessment Tool for Quantitative Studies. Inclusion criteria consisted of human studies published in English between January 2007 and May 2020 that addressed associations between dietary patterns and inflammatory markers during pregnancy. Studies focused on a single nutrient, supplementation, or combined interventions were excluded. A total of 17 studies were included. Despite some inconsistent findings, maternal diets characterized by a higher intake of animal protein and cholesterol and/or a lower intake of fiber were shown to be associated with certain pro-inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α), IL-8, serum amyloid A (SAA), and glycoprotein acetylation (GlycA)). Future studies that explore a broader range of inflammatory markers in the pregnant population, reduce measurement errors, and ensure adequate statistical adjustment are warranted.