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Quality by Design (QbD) and chemometric models are different sides of the same coin. While QbD models utilize experimentally designed settings for optimization of some quality attributes, these settings can also be utilized for chemometric prediction of the same attributes. We aimed to synchronize optimization of comparative dissolution results of carvedilol immediate release tablets with chemometric prediction of dissolution profile and content uniformity of the product. As an industrial application, selection of variables for optimization was done by performing risk assessment utilizing the archived product records at the pharmaceutical site. Experimental tablets were produced with 20 different settings with the variables being contents of sucrose, sodium starch glycolate, lactose monohydrate, and avicel Ph 101. Contents of the excipients were modelled with F1 dissimilarity factor and F2 similarity factor in HCL, acetate, and USP dissolution media to determine the design space. We initiatively utilized Partial Least Square based Structural Equation Modelling (PLS-SEM) to explore how the excipients and their NIR records explained dissolution of the product. Finally, the optimized formula was utilized with varied content of carvedilol for chemometric prediction of the content uniformity.

Background & Aims Autoimmune liver disease (AILD) is thought to result from a complex interplay between genetics and the environment. Studies to date have focussed on primary biliary cholangitis (PBC) and demonstrated higher disease prevalence in more urban, polluted, and socially deprived areas. This study utilises a large cohort of patients with PBC and primary sclerosing cholangitis (PSC) to investigate potential environmental contributors to disease and to explore whether the geo-epidemiology of PBC and PSC are disease-specific or pertain to cholestatic AILD in general. Methods All adult patients with PBC and PSC in a tightly defined geographical area within the UK were identified. Point- and area-based analyses and structural equation modelling (SEM) were used to investigate for disease clustering and examine for relationships between prevalence, distribution of environmental contaminants, and socio-economic status. Results We identified 2,150 patients with PBC and 472 with PSC. Significant spatial clustering was seen for each disease. A high prevalence of PBC was found in urban, post-industrial areas with a strong coal-mining heritage and increased environmental cadmium levels, whereas a high PSC prevalence was found in rural areas and inversely associated with social deprivation. Conclusions This study demonstrates spatial clustering of PBC and PSC and adds to our understanding of potential environmental co-variates for both diseases. Disease clustering, within the same geographical area but over different scales, is confirmed for each disease with distinct risk profiles identified and associations with separate putative environmental factors and socio-economic status. This suggests that different triggers and alternative pathways determine phenotypic expression of autoimmunity in the affected population. Co-variate analysis points towards the existence of specific disease triggers. Lay summary This study looked for potential environmental triggers in patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) living in the north-east of England and north Cumbria. We found that PBC was more common in urban areas with a history of coal mining and high levels of cadmium whereas PSC was more common in rural areas with lower levels of social deprivation., Graphical abstract, Highlights • Clustering of PBC and PSC patients occurs with notable geographical differences. • A high prevalence of PBC is seen in urban, post-industrial areas. • PSC is more common in rural areas and inversely associated with social deprivation. • PBC risk is associated with proximity to coal mines and environmental cadmium levels. • Comprehensive epidemiological study can increase understanding of disease aetiology.

Highlights • At symptom level, IL-6 is associated with diurnal variation in mood, concentration difficulties, fatigue and sleep disturbances. • These are so-called somatic/neurovegetative symptoms of depression. • At dimension level, IL-6 is associated with both somatic/neurovegetative and psychological symptom dimensions. • Somatic/neurovegetative symptoms could be useful treatment targets and markers of treatment response in clinical trials of anti-inflammatory treatment for depression., Background Low-grade inflammation is associated with depression, but studies of specific symptoms are relatively scarce. Association between inflammatory markers and specific symptoms may provide insights into potential mechanism of inflammation-related depression. Using longitudinal data, we have tested whether childhood serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels are associated with specific depressive symptoms in early adulthood. Methods In the ALSPAC birth cohort, serum IL-6 and CRP levels were assessed at age 9 years and 19 depressive symptoms were assessed at age 18 years. We used modified Poisson generalised linear regression with robust error variance to estimate the risk ratio (RR) and 95% confidence interval (95% CI) for each depressive symptom. In addition, we used confirmatory factor analysis to create two continuous latent variables representing somatic/neurovegetative and psychological dimension scores. Structural equation modelling was used to test the associations between IL-6 and these dimension scores. Results Based on data from 2731 participants, IL-6 was associated with diurnal mood variation, concentration difficulties, fatigue and sleep disturbances. The adjusted RRs for these symptoms at age 18 years for participants in top, compared with bottom, third of IL-6 at age 9 years were 1.75 (95% CI, 1.13–2.69) for diurnal mood variation, 1.50 (95% CI, 1.11–2.02) for concentration difficulties, 1.31 (95% CI, 1.12–1.54) for fatigue, and 1.24 (95% CI, 1.01–1.52) for sleep disturbances. At dimension level, IL-6 was associated with both somatic/neurovegetative (β = 0.059, SE = 0.024, P = 0.013) and psychological (β = 0.056, SE = 0.023, P = 0.016) scores. Conclusions Inflammation is associated with specific symptoms of depression. Associations with so-called somatic/neurovegetative symptoms of depression such as fatigue, sleep disturbances and diurnal mood variation indicate that these symptoms could be useful treatment targets and markers of treatment response in clinical trials of anti-inflammatory treatment for depression.

There are three dominant globalization pathways affecting noncommunicable diseases in Sub-Saharan Africa (SSA): urbanization, trade liberalization, and investment liberalization. Urbanization carries potential health benefits due to improved access to an increased variety of food imports, although for the growing number of urban poor, this has often meant increased reliance on cheap, highly processed food commodities. Reduced barriers to trade have eased the importation of such commodities, while investment liberalization has increased corporate consolidation over global and domestic food chains. Higher profit margins on processed foods have promoted the creation of ‘obesogenic’ environments, which through progressively integrated global food systems have been increasingly ‘exported’ to developing nations. This article explores globalization processes, the food environment, and dietary health outcomes in SSA through the use of trend analyses and structural equation modelling. The findings are considered in the context of global barriers and facilitators for healthy public policy.

Background The Euro-D depression scale consists of symptom clusters that may be differentially related to demographic and cognitive characteristics in older adults. This hypothesis needs further investigation and the role of measurement bias on substantive conclusions remains to be established. Method The study sample comprised 10,405 community-dwelling older adults from six Latin American countries. We applied a Multiple Indicators Multiple Causes (MIMIC) model for a concurrent investigation of measurement bias and of the association between Euro-D symptom clusters and background variables. Results The factorial validity of Euro-D, with a two-dimensional structure – affective suffering and motivation disturbance, was consistently supported in all countries. Although complete measurement invariance could not be assumed across countries, measurement bias was minor. Both Euro-D factors were unrelated to age, but related to gender, as well as to impairment in memory and verbal fluency. Gender differences were larger for affective suffering than for motivation disturbance, whereas differences in verbal fluency impairment were more strongly related to motivation disturbance. Limitations Our analytic strategies could only examine invariance at the level of indicator thresholds. The generalisability of current findings needs to be examined in clinical populations. A wider set of cognitive tests is needed. We did not examine the compositional factors that could have accounted for the variation in Euro-D scores across countries, as this was beyond the aims of the paper. Conclusion The current study adds evidence for the construct validity of Euro-D and for the possible differential association of depression symptom-clusters with gender and verbal fluency in older adults. An understanding of the heterogeneity of late-life depression may carry clinical implications for the diagnosis and treatment of depression in old age., Highlights • The Euro-D factor structure was invariant across Latin American countries. • Measurement bias was minor and did not alter substantive conclusions. • Depression domains were differentially related to gender and cognitive function. • Depression domains were unrelated to age. • Cognitive function levels confounded the effect of age on depression domains.