A Modern Approach to Stability Studies via Bayesian Linear Mixed Models Incorporating Auxiliary Effects.

In preparation to the launch of a pharmaceutical product, an estimate of its shelf life via stability testing is required by regulatory agencies. The ICH-Q1E guidance has been the worldwide reference to reach this objective, but in recent years several authors have criticized many of its aspects. To that end we discuss a complete Bayesian transcript of the ICH-Q1E, treating all the apparent shortcomings, while also addressing the presence of multiple batches using a linear mixed model (LMM) for proper shelf life prediction by explicitly modelling the batch-to-batch variability.

Synthesis and Properties of 5,7-Diazaullazines.

Hitherto unknown 5,8-substituted-pyrimido[4,5,6-]pyrrolo[2,1,5-]quinolizines (5,7-diazaullazines) were prepared by a three-step synthesis via Clauson-Kaas, Sonogashira, and cycloisomerization reactions with diverse functionalization. The properties, including cyclovoltammetry and UV-vis and fluorescence spectroscopy, as well as solvatochromism, were studied for selected derivatives and supported by density functional theory calculations. Results were compared in detail with previously reported 5- and 6-azaullazines, and the impact of introduced nitrogen atoms was analyzed.

Dibenzoacridines: synthesis by alkyne-carbonyl-metathesis and properties.

Dibenzo[,]acridines and regioisomeric dibenzo[,]acridines were synthesized from a common starting material, 2,3,5,6-tetrachloropyridine, by combination of site-selective cross-coupling reaction followed by ring-closing alkyne-carbonyl metathesis using simple Brønsted acids. The two regioisomeric series were accessed by change of the order of Sonogashira and Suzuki-Miyaura reactions. The optical properties of the products were studied by steady-state absorption spectroscopy and time-resolved emission measurements.

The importance of birth cohort studies to low and middle income countries.

In order to discern the causes of the health and developmental problems of children, and thence develop preventative strategies, longitudinal cohort studies offer major advantages. They can monitor the consequences of exposure to physical and psychological events and thence identify antecedents of various disorders. We describe the historical background to the development in the UK of this study design, and the uptake of longitudinal birth cohorts in low- and middle-income countries (LMICs), using the cohorts in Jamaica, South Africa and Brazil as exemplars.

Development and application of redox-active cyclometallating ligands based on W(II) alkyne complexes.

The assembly of dinuclear complexes with the ultimate smallest ditopic ligands based on complexes of methyl substituted alkynes is presented. In fact, the coordination of Ru(II) and Ir(III) by a W alkyne complex based cyclometallating metalla-ligand causes close intermetallic electronic cooperation, which substantially changes the electrochemical and photophysical properties of the single isolated moieties.

Specific domains of early parenting, their heritability and differential association with adolescent behavioural and emotional disorders and academic achievement.

Variations in parenting across large populations have rarely been described. It also remains unclear which specific domains of parenting are important for which specific offspring developmental outcomes. This study describes different domains of early parenting behaviours and their genetic heritability, then determines the extent to which specific domains of parenting are associated with later offspring outcomes.

Anti-IL6-Receptor Tocilizumab in Refractory and Noninfectious Uveitic Cystoid Macular Edema: Multicenter Study of 25 Patients.

Purpose: Cystoid macular edema (CME) is a leading cause of blindness. This study assessed the efficacy and safety of tocilizumab (TCZ) in refractory CME.

Design: Retrospective case series.

Disciplinary Parenting Practice and Child Mental Health: Evidence From the UK Millennium Cohort Study.

Objective: To investigate whether a longitudinal association exists between differential disciplinary parenting practices at 3 years of age and later child psychopathology at 11 years.

Method: Data were obtained from the Millennium Cohort Study, a UK-wide cohort. Discipline style was assessed using a validated maternal reported questionnaire at 3 years of age for which later outcome data were available.

Medical treatment of cystic echinococcosis: systematic review and meta-analysis.

Background: Cystic echinococcosis (CE) is a well-known neglected parasitic disease. However, evidence supporting the four current treatment modalities is inadequate, and treatment options remain controversial. The aim of this work is to analyse the available data to answer clinical questions regarding medical treatment of CE.

Nutritional status of children from low-income countries arriving in Spain.

Background: Nutritional problems, anaemia and infectious diseases are the main causes of morbidity and mortality in children and adolescents in tropical and subtropical areas. The main objective of this study was to determine the nutritional status in children from low-income countries who migrated to Spain and the value of the usual biochemistry markers of nutrition in these children, as well as to evaluate the nutritional status associated with imported infectious diseases. Moreover, we evaluated the association between anaemia and nutrition problems.

Transcriptomics as a tool to discover new antibacterial targets.

The emergence of antibiotic-resistant pathogens, multiple drug-resistance, and extremely drug-resistant strains demonstrates the need for improved strategies to discover new drug-based compounds. The development of transcriptomics, proteomics, and metabolomics has provided new tools for global studies of living organisms. However, the compendium of expression profiles produced by these methods has introduced new scientific challenges into antimicrobial research.

Imported cystic echinococcosis in western Spain: a retrospective study.

Background: In Spain, 12% of the population are immigrants. The impact of immigration in Spain on cystic echinococcosis (CE) is unknown. The aim of this study was to describe the epidemiology of CE in immigrants in western Spain.

Maternal perinatal mental health and offspring academic achievement at age 16: the mediating role of childhood executive function.

Background: Elucidating risk pathways for under-achieving at school can inform strategies to reduce the number of adolescents leaving school without passing grades in core subjects. Maternal depression can compromise the quality of parental care and is associated with multiple negative child outcomes. However, only a few small studies have investigated the association between perinatal maternal depression and poor academic achievement in adolescence.

Validation of the Chilean version of the Ages and Stages Questionnaire (ASQ-CL) in Community Health Settings.

Objective: To validate the translated and cross culturally adapted Chilean version of the 8 and 18month Ages and Stages Questionnaire (ASQ-CL) in a community sample.

Participants: Parents of 1572 term children (82.9%) and 324 children at risk for developmental delay (17.

Genomic analysis of clonal eosinophils by CGH arrays reveals new genetic regions involved in chronic eosinophilia.

To assess the presence of genetic imbalances in patients with myeloproliferative neoplasms (MPNs), 38 patients with chronic eosinophilia were studied by array comparative genomic hybridization (aCGH): seven had chronic myelogenous leukaemia (CML), BCR-ABL1 positive, nine patients had myeloproliferative neoplasia Ph- (MPN-Ph-), three had a myeloid neoplasm associated with a PDGFRA rearrangement, and the remaining two cases were Lymphoproliferative T neoplasms associated with eosinophilia. In addition, 17 patients had a secondary eosinophilia and were used as controls. Eosinophilic enrichment was carried out in all cases.

Validity of the ages and stages questionnaires in term and preterm infants.

Background: This study assessed the concurrent validity of the parent-completed developmental screening measure Ages and Stages Questionnaires, Third Edition (ASQ-3) compared with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) in children born term, late preterm, or extremely preterm at 8, 18, or 30 months of corrected gestational ages (CGA).

Methods: Data were collected from 306 term and preterm children ages 8, 18, and 30 months' CGA recruited from an ambulatory well-child clinic in Santiago, Chile. Parents completed the ASQ-3 in their homes, and afterward a trained professional administered the Bayley-III in a clinic setting.

Undetectable hepatitis C virus RNA at week 4 as predictor of sustained virological response in HIV patients with chronic hepatitis C.

Background: Low baseline serum hepatitis C virus (HCV)-RNA and clearance of viraemia at week 4 with pegylated interferon (pegIFN) plus ribavirin therapy predict sustained virological response (SVR) and enable a shorter duration of therapy in patients with chronic hepatitis C. It is unclear whether this applies to HIV/HCV-co-infected patients.

Patients And Methods: In the Peginterferon Ribavirin ESpaña COinfection (PRESCO) trial, 389 co-infected patients received pegIFN-alpha2a 180 microg/week plus ribavirin 1000-1200 mg/day.

[Diagnosing imported helminthiasis].

In recent years, there has been an increase in cases of imported helminthiasis in Spain because of two complementary causes: immigration and international travel. Although the prevalence of helminthiasis is high in the immigrant population, the risk of transmission to the Spanish population is low. In this review, we provide clues to aid in the diagnosis of the helminthiasis, highlighting the geographic characteristics, clinical findings and analytical results of the most frequent types.

Abnormal cytokine production by circulating monocytes and dendritic cells of myeloid origin in ART-treated HIV-1+ patients relates to CD4+ T-cell recovery and HCV co-infection.

HIV-1 infection is associated with dysregulation of cytokine production by peripheral blood (PB) monocytes and dendritic cells (DC), but controversial results have been reported. We aimed to analyze the effect of antiretroviral therapy (ART) on the in vitro production of inflammatory cytokines by PB-stimulated monocytes and DC of myeloid origin -CD33(high+ ) myeloid DC (mDC) and CD33(+)/CD14(-/dim+)/CD16(high+) DC- from HIV-1+ patients and its relationship with CD4+ T-cell recovery and co-infection with hepatitis C virus (HCV). In vitro cytokine production was analyzed at the single cell level in 32 HIV-1+ patients, grouped according to the number of CD4+ T-cells/microl in PB (<200 CD4 versus >200 CD4).

Application of an ELISA test using Schistosoma bovis adult worm antigens in travellers and immigrants from a schistosomiasis endemic area and its correlation with clinical findings.

We have recently evaluated an ELISA for the diagnosis of human schistosomiasis using S. bovis adult worm antigens (AWA Sb), showing a sensitivity of 94% and a specificity of 97% for patients diagnosed by egg detection. Nevertheless, the comparison of this AWA Sb ELISA with direct parasitological findings as the gold standard could introduce a selection bias, due to the well-known lack of sensitivity of direct methods in the detection of acute schistosomiasis and of low burden infections.