Assessment of risk-adjusted mortality ratio (RAMR) in bloodstream infections using all-patient refined diagnosis-related groups (APR-DRGs).

OBJECTIVES: To calculate a risk-adjusted mortality ratio (RAMR) for bloodstream infections (BSIs) using all-patient refined diagnosis-related groups (APR-DRGs) and compare it with the crude mortality rate (CMR). METHODS: Retrospective observational study of prevalent BSI at our institution from January 2019 to December 2022. In-hospital mortality was adjusted with a binary logistic regression model adjusting for sex, age, admission type and mortality risk for the hospitalization episode according to the four severity levels of APR DRGs. The RAMR was calculated as the ratio of observed to expected in-hospital mortality, and the CMR was calculated as the proportion of deaths among all bacteraemia episodes. RESULTS: Of 2939 BSIs, 2541 were included: Escherichia coli (n = 1310), Klebsiella pneumoniae (n = 428), Pseudomonas aeruginosa (n = 209), Staphylococcus aureus (n = 498) and candidaemia (n = 96). A total of 436 (17.2%) patients died during hospitalization and 279 died within the first 14 days after the onset of BSI. Throughout the period, all BSI cases had a mortality rate above the expected adjusted mortality (RAMR value greater than 1), except for Escherichia coli (1.03; 95% CI 0.86-1.21). The highest overall RAMR values were observed for P. aeruginosa, Candida and S. aureus with 2.06 (95% CI 1.57-2.62), 1.99 (95% CI 1.3-2.81) and 1.8 (95% CI 1.47-2.16), respectively. The temporal evolution of CMR may differ from RAMR, especially in E. coli, where it was reversed. CONCLUSIONS: RAMR showed higher than expected mortality for all BSIs studied except E. coli and provides complementary to and more clinically comprehensive information than CMR, the currently recommended antibiotic stewardship programme mortality indicator.

Genetic modifiers of cognitive decline in PSEN1 E280A Alzheimer's disease.

INTRODUCTION: Rate of cognitive decline (RCD) in Alzheimer's disease (AD) determines the degree of impairment for patients and of burden for caretakers. We studied the association of RCD with genetic variants in AD. METHODS: RCD was evaluated in 62 familial AD (FAD) and 53 sporadic AD (SAD) cases, and analyzed by whole-exome sequencing for association with common exonic functional variants. Findings were validated in post mortem brain tissue. RESULTS: One hundred seventy-two gene variants in FAD, and 227 gene variants in SAD associated with RCD. In FAD, performance decline of the immediate recall of the Rey-Osterrieth figure test associated with 122 genetic variants. Olfactory receptor OR51B6 showed the highest number of associated variants. Its expression was detected in temporal cortex neurons. DISCUSSION: Impaired olfactory function has been associated with cognitive impairment in AD. Genetic variants in these or other genes could help to identify risk of faster memory decline in FAD and SAD patients.

Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia.

Huntington's disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world's second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the HTT CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele's read peak and the slippage ratio of the allele's read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of p < 0.05. We found that the average HTT CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the HTT CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management.

A multifactorial model of pathology for age of onset heterogeneity in familial Alzheimer's disease.

Presenilin-1 (PSEN1) mutations cause familial Alzheimer's disease (FAD) characterized by early age of onset (AoO). Examination of a large kindred harboring the PSEN1-E280A mutation reveals a range of AoO spanning 30 years. The pathophysiological drivers and clinical impact of AoO variation in this population are unknown. We examined brains of 23 patients focusing on generation and deposition of beta-amyloid (Aß) and Tau pathology profile. In 14 patients distributed at the extremes of AoO, we performed whole-exome capture to identify genotype-phenotype correlations. We also studied kinome activity, proteasome activity, and protein polyubiquitination in brain tissue, associating it with Tau phosphorylation profiles. PSEN1-E280A patients showed a bimodal distribution for AoO. Besides AoO, there were no clinical differences between analyzed groups. Despite the effect of mutant PSEN1 on production of Aß, there were no relevant differences between groups in generation and deposition of Aß. However, differences were found in hyperphosphorylated Tau (pTau) pathology, where early onset patients showed severe pathology with diffuse aggregation pattern associated with increased activation of stress kinases. In contrast, late-onset patients showed lesser pTau pathology and a distinctive kinase activity. Furthermore, we identified new protective genetic variants affecting ubiquitin-proteasome function in early onset patients, resulting in higher ubiquitin-dependent degradation of differentially phosphorylated Tau. In PSEN1-E280A carriers, altered γ-secretase activity and resulting Aß accumulation are prerequisites for early AoO. However, Tau hyperphosphorylation pattern, and its degradation by the proteasome, drastically influences disease onset in individuals with otherwise similar Aß pathology, hinting toward a multifactorial model of disease for FAD. In sporadic AD (SAD), a wide range of heterogeneity, also influenced by Tau pathology, has been identified. Thus, Tau-induced heterogeneity is a common feature in both AD variants, suggesting that a multi-target therapeutic approach should be used to treat AD.

Executive Function and Theory of Mind in Children with ADHD: a Systematic Review.

In developmental research, the relationship between Executive Function (EF) and Theory of Mind (ToM) has been extensively assessed, and EF has been considered a condition for ToM. However, few researchers have studied the relationship between EF and ToM in clinical populations, especially that of Attention Deficit Hyperactivity Disorder (ADHD), a neurodevelopmental disorder characterized by symptoms of inattention and motor hyperactivity/impulsivity, in which EF is largely impaired. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model, 201 English and Spanish articles evaluating EF and ToM in ADHD were chosen. Fifteen papers met the inclusion criteria and were selected for further analysis. The first study dates from 2001. Most of the studies' designs are cross-sectional, include mostly male children, have a small sample size, and were conducted in European countries. Unlike tasks assessing EF, tasks assessing ToM were heterogeneous across studies. The EFs most correlated with ToM were inhibitory control, working memory, cognitive flexibility, and attention. Interest in studying the relationship between EF and ToM in ADHD is recent,but increasing based on new findings and tuning of ToM instruments. However, while an association between EF and ToM is indicated in ADHD, the degree of prediction and predictability of one over the other cannot yet be established because of the studies' heterogeneity.

Neuropsychological performance in patients with asymptomatic HIV-1 infection.

Human immunodeficiency virus (HIV-1) infection and acquired immunodeficiency syndrome (AIDS) lead to neurocognitive disorders; however, there is still much knowledge to be gained regarding HIV-associated neurocognitive disorders. The purpose of this study was to assess the cognitive performance, instrumental activities of daily living, depression, and anxiety in patients with asymptomatic HIV-1 infections compared with seronegative participants without neurocognitive impairment. We studied a sample consisted of 60 patients with asymptomatic HIV-1 infections and 60 seronegative participants without neurocognitive impairment from the city of Barranquilla, Colombia, with a mean age of 36.07 years. A protocol of neuropsychological and psychopathological tests was applied to the participants. The group of patients with asymptomatic HIV infections significantly underperformed on tasks that assessed global cognitive screening, attention span, learning, phonemic verbal fluency, auditory-verbal comprehension, information processing speed, cognitive flexibility, and motor skills compared to the group of seronegative participants. No significant differences were found in memory, visual confrontation naming, vocabulary, inhibition, and instrumental activities of daily living. Additionally, the patients with asymptomatic HIV-1 infection had a higher anxiety index than the seronegative participants, but no significant difference was found in depression. A correlation was found between depression and anxiety. In conclusion, the patients with asymptomatic HIV-1 infection had lower cognitive performances than the seronegative participants in the cognitive functions mentioned above and more anxiety but still performed the instrumental activities of daily living.

The allocation of valenced concepts onto 3D space.

The valence-space metaphor research area investigates the metaphorical mapping of valenced concepts onto space. Research findings from this area indicate that positive, neutral, and negative concepts are associated with upward, midward, and downward locations, respectively, in the vertical plane. The same research area has also indicated that such concepts seem to have no preferential location on the horizontal plane. The approach-avoidance effect consists in decreasing the distance between positive stimuli and the body (i.e. approach) and increasing the distance between negative stimuli and the body (i.e. avoid). Thus, the valence-space metaphor accounts for the mapping of valenced concepts onto the vertical and horizontal planes, and the approach-avoidance effect accounts for the mapping of valenced concepts onto the "depth" plane. By using a cube conceived for the study of allocation of valenced concepts onto 3D space, we show in three studies that positive concepts are placed in upward locations and near the participants' body, negative concepts are placed in downward locations and far from the participants' body, and neutral concepts are placed in between these concepts in both planes.

Definition of mutations in polyautoimmunity.

OBJECTIVES: Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing (WES) and linkage analysis are well suited for this purpose due to its strong resolution upon familial segregation patterns of functional protein coding and splice variants. The primary objective of this study was to identify potentially autoimmune causative variants using WES data from extreme pedigrees segregating polyautoimmunity phenotypes. METHODS: DNA of 47 individuals across 10 extreme pedigrees, ascertained from probands affected with polyautoimmunity and familial autoimmunity, were selected for WES. Variant calls were obtained through Genome Analysis Toolkit. Filtration and prioritization framework to identify mutation(s) were applied, and later implemented for genetic linkage analysis. Sanger sequencing corroborated variants with significant linkage. RESULTS: Novel and mostly rare variants harbored in SRA1, MLL4, ABCB8, DHX34 and PLAUR showed significant linkage (LOD scores are >3.0). The strongest signal was in SRA1, with a LOD score of 5.48. Network analyses indicated that SRA1, PLAUR and ABCB8 contribute to regulation of apoptotic processes. CONCLUSIONS: Novel and rare variants in genetic linkage with polyautoimmunity were identified throughout WES. Genes harboring these variants might be major players of autoimmunity.

A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease.

We previously reported age of onset (AOO) modifier genes in the world's largest pedigree segregating early-onset Alzheimer's disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty individuals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and common functional variants located in those previously reported as AOO modifier loci were selected. Multiloci linear mixed-effects models were used to test the association between these variants and AOO. An exonic missense mutation in the G72 (DAOA) gene (rs2391191, P = 1.94 × 10(-4), P FDR = 9.34 × 10(-3)) was found to modify AOO in PSEN1 E280A AD. Nominal associations of missense mutations in the CLUAP1 (rs9790, P = 7.63 × 10(-3), P FDR = 0.1832) and EXOC2 (rs17136239, P = 0.0325, P FDR = 0.391) genes were also found. Previous studies have linked polymorphisms in the DAOA gene with the occurrence of neuropsychiatric symptoms such as depression, apathy, aggression, delusions, hallucinations, and psychosis in AD. Our findings strongly suggest that this new conspicuous functional AOO modifier within the G72 (DAOA) gene could be pivotal for understanding the genetic basis of AD.

Mutations modifying sporadic Alzheimer's disease age of onset.

The identification of mutations modifying the age of onset (AOO) in Alzheimer's disease (AD) is crucial for understanding the natural history of AD and, therefore, for early interventions. Patients with sporadic AD (sAD) from a genetic isolate in the extremes of the AOO distribution were whole-exome genotyped. Single- and multi-locus linear mixed-effects models were used to identify functional variants modifying AOO. A posteriori enrichment and bioinformatic analyses were applied to evaluate the non-random clustering of the associate variants to physiopathological pathways involved in AD. We identified more than 20 pathogenic, genome-wide statistically significant mutations of major modifier effect on the AOO. These variants are harbored in genes implicated in neuron apoptosis, neurogenesis, inflammatory processes linked to AD, oligodendrocyte differentiation, and memory processes. This set of new genes harboring these mutations could be of importance for prediction, follow-up and eventually as therapeutical targets of AD. © 2016 Wiley Periodicals, Inc.

Novel and rare functional genomic variants in multiple autoimmune syndrome and Sjögren's syndrome.

BACKGROUND: Multiple autoimmune syndrome (MAS), an extreme phenotype of autoimmune disorders, is a very well suited trait to tackle genomic variants of these conditions. Whole exome sequencing (WES) is a widely used strategy for detection of protein coding and splicing variants associated with inherited diseases. METHODS: The DNA of eight patients affected by MAS [all of whom presenting with Sjögren's syndrome (SS)], four patients affected by SS alone and 38 unaffected individuals, were subject to WES. Filters to identify novel and rare functional (pathogenic-deleterious) homozygous and/or compound heterozygous variants in these patients and controls were applied. Bioinformatics tools such as the Human gene connectome as well as pathway and network analysis were applied to test overrepresentation of genes harbouring these variants in critical pathways and networks involved in autoimmunity. RESULTS: Eleven novel and rare functional variants were identified in cases but not in controls, harboured in: MACF1, KIAA0754, DUSP12, ICA1, CELA1, LRP1/STAT6, GRIN3B, ANKLE1, TMEM161A, and FKRP. These were subsequently subject to network analysis and their functional relatedness to genes already associated with autoimmunity was evaluated. Notably, the LRP1/STAT6 novel mutation was homozygous in one MAS affected patient and heterozygous in another. LRP1/STAT6 disclosed the strongest plausibility for autoimmunity. LRP1/STAT6 are involved in extracellular and intracellular anti-inflammatory pathways that play key roles in maintaining the homeostasis of the immune system. Further; networks, pathways, and interaction analyses showed that LRP1 is functionally related to the HLA-B and IL10 genes and it has a substantial impact within immunological pathways and/or reaction to bacterial and other foreign proteins (phagocytosis, regulation of phospholipase A2 activity, negative regulation of apoptosis and response to lipopolysaccharides). Further, ICA1 and STAT6 were also closely related to AIRE and IRF5, two very well known autoimmunity genes. CONCLUSIONS: Novel and rare exonic mutations that may account for autoimmunity were identified. Among those, the LRP1/STAT6 novel mutation has the strongest case for being categorised as potentially causative of MAS given the presence of intriguing patterns of functional interaction with other major genes shaping autoimmunity.

A distance-based kernel for classification via Support Vector Machines.

Support Vector Machines (SVMs) are a type of supervised machine learning algorithm widely used for classification tasks. In contrast to traditional methods that split the data into separate training and testing sets, here we propose an innovative approach where subsets of the original data are randomly selected to train the model multiple times. This iterative training process aims to identify a representative data subset, leading to improved inferences about the population. Additionally, we introduce a novel distance-based kernel specifically designed for binary-type features based on a similarity matrix that efficiently handles both binary and multi-class classification problems. Computational experiments on publicly available datasets of varying sizes demonstrate that our proposed method significantly outperforms existing approaches in terms of classification accuracy. Furthermore, the distance-based kernel achieves superior performance compared to other well-known kernels from the literature and those used in previous studies on the same datasets. These findings validate the effectiveness of our proposed classification method and distance-based kernel for SVMs. By leveraging random subset selection and a unique kernel design, we achieve notable improvements in classification accuracy. These results have significant implications for diverse classification problems in Machine Learning and data analysis.

Sex differences in population versus in-hospital use of aortic valve replacement procedures in Spain.

BACKGROUND AND AIMS: It is not well known if sex differences in the use and results of aortic valve replacement (AVR) are changing. The aim of the study is to assess the time trends in the differences by sex in the utilisation of AVR procedures in hospitals and in the community. METHODS: Retrospective observational analysis using data from the Spanish National Hospitalizations Administrative Database. All hospitalisations between 2016 and 2021 with a main diagnosis of aortic stenosis (ICD-10 codes: I35.0 and I35.2) were included. Time trends in hospitalisation, AVRs and hospital outcomes were analysed. Crude utilisation and population-standardised rates were calculated. RESULTS: During the study period, 64 384 hospitalisations in 55 983 patients (55.5% men) with 36 915 (65,9%) AVR were recorded. Of these, 15 563 (42.2%) were transcatheter and 21 432 (58.0%) surgical. At hospital level, transcatheter procedures were more frequently performed in women (32.3% vs 24.2%, p < 0.001) and surgical in men (42.9% vs. 32.5%, p < 0.001) but at the population level, surgical and transcatheter aortic valve replacements were used more frequently in men (12.6 surgical and 8.0 transcatheter per 100 000 population) vs women (6.4 and 5.8, respectively; p < 0.001 for both comparisons). Transcatheter procedures shifted from 17.3% in 2016 to 38.0% in 2021, overtaking surgical procedures in 2018 for women and 2021 for men. CONCLUSIONS: TAVR has displaced SAVR as the most frequent AVR procedure in Spain by 2020. This occurred earlier in women, who despite the greater weight of their age group in the older population, receive fewer AVRs, both SAVR and TAVR.

Optic nerve haemangioblastoma in association with von Hippel-Lindau syndrome: case report and literature review.

Optic nerve haemangioblastoma (ONH) is an uncommon, benign, non-meningothelial, mesenchymal tumour of unclear origin. Most are associated with von Hippel-Lindau (VHL) syndrome (71%), and only 40 cases have been reported in the medical literature. Most of the patients develop non-specific visual symptoms, including decreased visual acuity and/or loss of visual fields, exophthalmos, trigeminal neuralgia, and retroorbital pain. Optic nerve sheath meningioma and optic nerve glioma are among the differential diagnoses that may be considered in this location. Contrast-enhanced MRI is considered an optimal diagnostic tool, which helps to determine some characteristics that guide towards an adequate diagnosis and treatment. We present a 42-year-old patient with a history of VHL syndrome in whom a cerebellar lesion and optic nerve lesions were evidenced, and we did a review of the literature and case analysis.

Theory of Mind in Huntington's Disease: A Systematic Review of 20 Years of Research.

Background: People with Huntington's disease (HD) exhibit neurocognitive alterations throughout the disease, including deficits in social cognitive processes such as Theory of Mind (ToM). Objective: The aim is to identify methodologies and ToM instruments employed in HD, alongside relevant findings, within the scientific literature of the past two decades. Methods: We conducted a comprehensive search for relevant papers in the SCOPUS, PubMed, APA-PsyArticles, Web of Science, Redalyc, and SciELO databases. In the selection process, we specifically focused on studies that included individuals with a confirmed genetic status of HD and investigated ToM functioning in patients with and without motor symptoms. The systematic review followed the PRISMA protocol. Results: A total of 27 papers were selected for this systematic review, covering the period from 2003 to 2023. The findings consistently indicate that ToM is globally affected in patients with manifest motor symptoms. In individuals without motor symptoms, impairments are focused on the affective dimensions of ToM. Conclusions: Based on our analysis, affective ToM could be considered a potential biomarker for HD. Therefore, it is recommended that ToM assessment be included as part of neuropsychological evaluation protocols in clinical settings. Suchinclusion could aid in the identification of early stages of the disease and provide new opportunities for treatment, particularly with emerging drugs like antisense oligomers. The Prospero registration number for this review is CRD42020209769.

Changes in short-term health-related quality of life in women undergoing gynecologic oncologic laparotomy: an associated factor analysis.

PURPOSE: The primary purpose of this study is to evaluate health-related quality of life (HR-QOL) of gynecologic cancer patients undergoing laparotomy. METHODS: Women who underwent laparotomy by gynecologic cancer completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of life questionnaires (QLQ-C30 and QLQ-OV28) presurgery and at 1 month. RESULTS: Of the 181 women studied between January 2007 and March 2008, 116 women (64.1%) had ovarian cancer, 27 (14.9%) had cervical cancer, and 29 (16.0%) had endometrial cancer. By 1 month post-surgery, there was a significant decrease in HR-QOL on the global, abdominal/gastrointestinal (GI) score, body image, chemotherapy side effects, and other single items of the OV28 questionnaire, as well as on physical, role and social functioning, fatigue, nausea and vomiting, pain, insomnia, constipation, appetite loss, and financial difficulties items on C30 questionnaires. Emotional functioning on C30 questionnaires was significantly improved 1 month after surgery. The majority of these items persisted 1 month after surgery only in patients with ovarian cancer. Abdominal/GI score on OV28 questionnaires as well as role and physical functioning on C30 questionnaires were significantly lower between baseline and postsurgical HR-QOL in women with other gynecologic malignancies. CONCLUSION: The results suggest a significant impact of HR-QOL among gynecologic cancer patients 1 month after laparotomy, particularly among those with ovarian cancer.

Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1.

AIM: Difficulties in neurocognition and social interaction are the most prominent causes of morbidity and long-term disability in children with neurofibromatosis type 1 (NF1). Symptoms of attention-deficit-hyperactivity disorder (ADHD) have also been extensively recognized in NF1. However, systematic evaluation of symptoms of autism spectrum disorder (ASD) in children with NF1 has been limited. METHOD: We present a retrospective, cross-sectional study of the prevalence of symptoms of ASD and ADHD and their relationship in a consecutive series of 66 patients from our NF1 clinic. The Social Responsiveness Scale and the Vanderbilt ADHD Diagnostic Parent Rating Scale were used to assess symptoms of ASD and ADHD. RESULTS: Sixty-six participants (42 males, 24 females) were included in this study. Mean age at assessment was 10 years 11 months (SD 5 y 4 mo). Forty percent of our NF1 sample had raised symptom levels reaching clinical significance on the Social Responsiveness Scale (T ≥ 60), and 14% reached levels consistent with those seen in children with ASDs (T ≥ 75). These raised levels were not explained by NF1 disease severity or externalizing/internalizing behavioral disorders. There was a statistically significant relationship between symptoms of ADHD and ASD (χ(2) =9.11, df=1, p=0.003, φ=0.56). Particularly salient were the relationships between attention and hyperactivity deficits, with impairments in social awareness and social motivation. INTERPRETATION: We found that symptoms of ASD in our NF1 population were raised, consistent with previous reports. Further characterization of the specific ASD symptoms and their impact on daily function is fundamental to the development and implementation of effective interventions in this population, which will probably include a combination of medical and behavioral approaches.

Leading consumption patterns of psychoactive substances in Colombia: A deep neural network-based clustering-oriented embedding approach.

The number of health-related incidents caused using illegal and legal psychoactive substances (PAS) has dramatically increased over two decades worldwide. In Colombia, the use of illicit substances has increased up to 10.3%, while the consumption alcohol and tobacco has increased to 84% and 12%, respectively. It is well-known that identifying drug consumption patterns in the general population is essential in reducing overall drug consumption. However, existing approaches do not incorporate Machine Learning and/or Deep Data Mining methods in combination with spatial techniques. To enhance our understanding of mental health issues related to PAS and assist in the development of national policies, here we present a novel Deep Neural Network-based Clustering-oriented Embedding Algorithm that incorporates an autoencoder and spatial techniques. The primary goal of our model is to identify general and spatial patterns of drug consumption and abuse, while also extracting relevant features from the input data and identifying clusters during the learning process. As a test case, we used the largest publicly available database of legal and illegal PAS consumption comprising 49,600 Colombian households. We estimated and geographically represented the prevalence of consumption and/or abuse of both PAS and non-PAS, while achieving statistically significant goodness-of-fit values. Our results indicate that region, sex, housing type, socioeconomic status, age, and variables related to household finances contribute to explaining the patterns of consumption and/or abuse of PAS. Additionally, we identified three distinct patterns of PAS consumption and/or abuse. At the spatial level, these patterns indicate concentrations of drug consumption in specific regions of the country, which are closely related to specific geographic locations and the prevailing social and environmental contexts. These findings can provide valuable insights to facilitate decision-making and develop national policies targeting specific groups given their cultural, geographic, and social conditions.

Ancestry component as a major predictor of lithium response in the treatment of bipolar disorder.

BACKGROUND: Bipolar Disorder (BD) represents the seventh major cause of disability life-years-adjusted. Lithium remains as a first-line treatment, but clinical improvement occurs only in 30 % of treated patients. Studies suggest that genetics plays a major role in shaping the individual response of BD patients to lithium. METHODS: We used machine-learning techniques (Advance Recursive Partitioned Analysis, ARPA) to build a personalized prediction framework of BD lithium response using biological, clinical, and demographical data. Using the Alda scale, we classified 172 BD I-II patients as responders or non-responders to lithium treatment. ARPA methods were used to build individual prediction frameworks and to define variable importance. Two predictive models were evaluated: 1) demographic and clinical data, and 2) demographic, clinical and ancestry data. Model performance was assessed using Receiver Operating Characteristic (ROC) curves. RESULTS: The predictive model including ancestry yield the best performance (sensibility = 84.6 %, specificity = 93.8 % and AUC = 89.2 %) compared to the model without ancestry (sensibility = 50 %, Specificity = 94.5 %, and AUC = 72.2 %). This ancestry component best predicted lithium individual response. Clinical variables such as disease duration, the number of depressive episodes, the total number of affective episodes, and the number of manic episodes were also important predictors. CONCLUSION: Ancestry component is a major predictor and significantly improves the definition of individual Lithium response in BD patients. We provide classification trees with potential bench application in the clinical setting. While this prediction framework might be applied in specific populations, the used methodology might be of general use in precision and translational medicine.

Nitrate removal and environmental side-effects controlled by hydraulic residence time in woodchip bioreactors treating cold agricultural drainage water.

Denitrifying woodchip bioreactors (WBRs) remove nitrate (NO3-) from agricultural drainage water at field-scale, but their efficacy at cold temperatures remains uncertain. This study shows how hydraulic residence time (HRT) controls NO3- removal and environmental side-effects of WBRs at low water temperature under pilot-scale conditions with controlled operation of nine WBRs (94 dm3). Hydraulic properties were assessed by a bromide tracer test, and NO3- removal, emissions of nitrous oxide (N2O) and methane (CH4), and losses of dissolved organic carbon (DOC) were measured at HRTs of 5-30 h. Inlet NO3- concentrations were increasingly reduced at higher HRTs. The relationship between HRT and the efficiency (%) of NO3- removal was linear (Radj2 = 0.94), while the relationship between HRT and NO3- reduction rates (NRR) was logistic (Radj2 = 0.88). Gaseous emissions of N2O were equally low at HRTs of 10-30 h, but higher at 5 h (P < 0.05). Methane fluxes were small, but with consistent emissions at HRTs of 20-30 h and uptake at 5-15 h. HRT had limited effect on effluent DOC concentrations, but strong effect on mass losses that were five-fold higher (320 mg L-1) at the HRT of 5 h than at 30 h. In summary, at cold temperatures HRTs of ≤ 20 h resulted in suboptimal NRR, accelerating DOC losses, and increased risk of N2O losses at least below a threshold HRT of 5-10 h. HRTs of 20-30 h gave maximal NRR, smallest losses of DOC and N2O, but an increased risk of CH4 emissions.