Zonal expression of StARD1 and oxidative stress in alcoholic-related liver disease.

Alcoholic-related liver disease (ALD) is one of the leading causes of chronic liver disease and morbidity. Unfortunately, the pathogenesis of ALD is still incompletely understood. StARD1 has emerged as a key player in other etiologies of chronic liver disease, and alcohol-induced liver injury exhibits zonal distribution. Here, we report that StARD1 is predominantly expressed in perivenous (PV) zone of liver sections from mice-fed chronic and acute-on-chronic ALD models compared to periportal (PP) area and is observed as early as 10 days of alcohol feeding. Ethanol and chemical hypoxia induced the expression of StARD1 in isolated primary mouse hepatocytes. The zonal-dependent expression of StARD1 resulted in the accumulation of cholesterol in mitochondria and increased lipid peroxidation in PV hepatocytes compared to PP hepatocytes, effects that were abrogated in PV hepatocytes upon hepatocyte-specific Stard1 KO mice. Transmission electron microscopy indicated differential glycogen and lipid droplets content between PP and PV areas, and alcohol feeding decreased glycogen content in both areas while increased lipid droplets content preferentially in PV zone. Moreover, transmission electron microscopy revealed that mitochondria from PV zone exhibited reduced length with respect to PP area, and alcohol feeding increased mitochondrial number, particularly, in PV zone. Extracellular flux analysis indicated lower maximal respiration and spared respiratory capacity in control PV hepatocytes that were reversed upon alcohol feeding. These findings reveal a differential morphology and functional activity of mitochondria between PP and PV hepatocytes following alcohol feeding and that StARD1 may play a key role in the zonal-dependent liver injury characteristic of ALD.

Microglial cell loss after ischemic stroke favors brain neutrophil accumulation.

Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood-brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia.

Transcription-dependent radial distribution of TCF7L2 regulated genes in chromosome territories.

Human chromosomes occupy distinct territories in the interphase nucleus. Such chromosome territories (CTs) are positioned according to gene density. Gene-rich CTs are generally located in the center of the nucleus, while gene-poor CTs are positioned more towards the nuclear periphery. However, the association between gene expression levels and the radial positioning of genes within the CT is still under debate. In the present study, we performed three-dimensional fluorescence in situ hybridization experiments in the colorectal cancer cell lines DLD-1 and LoVo using whole chromosome painting probes for chromosomes 8 and 11 and BAC clones targeting four genes with different expression levels assessed by gene expression arrays and RT-PCR. Our results confirmed that the two over-expressed genes, MYC on chromosome 8 and CCND1 on chromosome 11, are located significantly further away from the center of the CT compared to under-expressed genes on the same chromosomes, i.e., DLC1 and SCN3B. When CCND1 expression was reduced after silencing the major transcription factor of the WNT/ß-catenin signaling pathway, TCF7L2, the gene was repositioned and mostly detected in the interior of the CT. Thus, we suggest a non-random distribution in which over-expressed genes are located more towards the periphery of the respective CTs.

A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl4-treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-ß1 (TGF-ß1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P < 0.05). The decrease of EndMT in cirrhotic livers correlated with a significant decrease in liver fibrosis (P < 0.05) and an improvement in the vascular disorganization rate (P < 0.05). We demonstrated the acquisition of the EndMT phenotype by a subpopulation of endothelial cells from cirrhotic livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization.NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-ß1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization.

[Can psychopathy be detected psychophysiologically?]. / Ist Psychopathie psychophysiologisch fassbar?

The aim of the present study was to determine whether pupillometry was able to identify and differentiate psychopathic personality traits in criminally responsible mentally disordered offenders (§ 21/2 StGB). Psychopathic disorder has not only behavioral, but also psychophysiological correlates, which may be evaluated by pupillometry. This might make it possible to diagnose psychopathy by means of a non-invasive method and in a further step to adapt therapeutic measures accordingly. Psychopathic behavior and personality traits were identified by means of the Hare Psychopathy Checklist-Revised (PCL-R) and offenders were divided into 4 groups with PCL-R scores of 0-10, 11-20, 21-30 and 31-40, respectively. Pupillometry makes it possible to objectively measure amplitudes of pupillary oscillations, which may serve as an indicator of central nervous activation/deactivation. The study at hand showed that the higher the PCL-R values, the smaller the amplitudes. Thus, it can be concluded that central nervous activation decreases with higher PCL-R values and psychopathy is associated with central nervous deactivation.

Systemic delivery of AAV-GCDH ameliorates HLD-induced phenotype in a glutaric aciduria type I mouse model.

Glutaric aciduria type 1 (GA1) is a rare inherited metabolic disorder caused by a deficiency of glutaryl-coenzyme A dehydrogenase (GCDH), with accumulation of neurotoxic metabolites, resulting in a complex movement disorder, irreversible brain damage, and premature death in untreated individuals. While early diagnosis and a lysine restricted diet can extend survival, they do not prevent neurological damage in approximately one-third of treated patients, and more effective therapies are required. Here we report the efficacy of adeno-associated virus 9 (AAV9)-mediated systemic delivery of human GCDH at preventing a high lysine diet (HLD)-induced phenotype in Gcdh -/- mice. Neonatal treatment with AAV-GCDH restores GCDH expression and enzyme activity in liver and striatum. This treatment protects the mice from HLD-aggressive phenotype with all mice surviving this exposure; in stark contrast, a lack of treatment on an HLD triggers very high accumulation of glutaric acid, 3-hydroxyglutaric acid, and glutarylcarnitine in tissues, with about 60% death due to brain accumulation of toxic lysine metabolites. AAV-GCDH significantly ameliorates the striatal neuropathology, minimizing neuronal dysfunction, gliosis, and alterations in myelination. Magnetic resonance imaging findings show protection against striatal injury. Altogether, these results provide preclinical evidence to support AAV-GCDH gene therapy for GA1.

A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation.

Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has been implicated in critical biological processes such as DNA replication, protection against mutations, and tissue repair. In this work, we retrospectively evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) upon the outcome of 448 patients subjected to allogeneic stem cell transplantation (allo-SCT) from an human leukocyte antigen (HLA)-identical sibling donor. The TYMP genotype of patients correlated with overall survival-carriers of the minor allele (A) being at an increased risk of dying after transplantation (hazard ratio, HR = 1.9; P = 0.004). This effect was mostly due to differences in transplant toxicity-related mortality (HR = 2.5; P = 0.029). In addition, the TYMP genotype of donors was associated with the risk of chronic graft-versus-host disease (GVHD)-carriers of the minor allele being at an increased risk of developing this complication ([HR] = 1.7; P = 0.039). The impact of such polymorphism on the risk of chronic GVHD is limited to patients transplanted in early stage disease (HR = 2.2; P = 0.019). The combination of a donor harboring the minor allele with a patient homozygous for the major allele was associated with the highest risk of chronic GVHD (HR = 2.8; P = 0.008). These findings provide the first evidence of the significant impact of the TYMP genotype upon the clinical outcome of patients treated with HLA-identical sibling allo-SCT.

[Comparative analysis of serological tests performed in immigrants in the Lleida health area]. / Análisis comparativo de las serologías realizadas a los inmigrantes en la región sanitaria de Lleida.

OBJECTIVE: Evaluate the process of screening and detection of HIV, HBV, HCV and syphilis in the province of Lleida by determining the proportions of positive results in the different groups during one year. DESIGN: Descriptive, multicentre study of all the serological tests performed in immigrants and natives attended in 2007. SETTING: Province of Lleida (Spain). PARTICIPANTS: 255,410 users. MAIN MEASUREMENTS: Age, sex, country of origin and period of residence in Spain, and the results for HIV, hepatitis B, hepatitis C and syphilis. We calculated the proportions in which a serological test had been requested, and examined the association between the rates of positive tests and the geographical area of origin, and calculated age-adjusted rates taking the age distribution of the native population as the reference. RESULTS: Risk of HBV was 4.6 times higher in immigrants than in natives (11.7 times in sub-Saharan Africans). The rate of positive syphilis tests was three times higher in the immigrant group. For HIV the PR was 2.3 (sub-Saharan Africans 7.4). For hepatitis C the risk was lower in immigrants than in natives (PR=0.4). CONCLUSIONS: Immigrants have a higher probability of testing positive in screening in hepatitis B, syphilis and HIV. The rates differ significantly according to the origin of the immigrant.

Characterization of microglia behaviour in healthy and pathological conditions with image analysis tools.

Microglia are very sensitive to changes in the environment and respond through morphological, functional and metabolic adaptations. To depict the modifications microglia undergo under healthy and pathological conditions, we developed free access image analysis scripts to quantify microglia morphologies and phagocytosis. Neuron-glia cultures, in which microglia express the reporter tdTomato, were exposed to excitotoxicity or excitotoxicity + inflammation and analysed 8 h later. Neuronal death was assessed by SYTOX staining of nucleus debris and phagocytosis was measured through the engulfment of SYTOX+ particles in microglia. We identified seven morphologies: round, hypertrophic, fried egg, bipolar and three 'inflamed' morphologies. We generated a classifier able to separate them and assign one of the seven classes to each microglia in sample images. In control cultures, round and hypertrophic morphologies were predominant. Excitotoxicity had a limited effect on the composition of the populations. By contrast, excitotoxicity + inflammation promoted an enrichment in inflamed morphologies and increased the percentage of phagocytosing microglia. Our data suggest that inflammation is critical to promote phenotypical changes in microglia. We also validated our tools for the segmentation of microglia in brain slices and performed morphometry with the obtained mask. Our method is versatile and useful to correlate microglia sub-populations and behaviour with environmental changes.

[Does the duration of confinement of criminally responsible mentally disordered offenders (§ 21/2 StGB) play a role in the development of a functional psychosyndrome? - A pupillometric investigation]. / Spielt die Haftdauer von Untergebrachten gemäß § 21/2 StGB eine Rolle in Bezug auf die Entstehung eines funktionellen Psychosyndroms? - Eine Untersuchung mittels der Methode der Pupillometrie.

BACKGROUND: Pupillometry is a non-invasive investigation based on the concept that pupillary reagibility depends on a number of specific sensory, mental and emotional variables. By means of the receptor test based on the topical application of the cholinergic antagonist tropicamide cognitive deficits can be evaluated. The present study focuses on the question whether the receptor test is able to differentiate criminally responsible mentally disordered offenders (§ 21/2 StGB) with different durations of confinement concerning the presence of a functional psychosyndrome, as defined by Grünberger. METHODS: Four groups of offenders with different durations of confinement (group A: confinement 0-2 years, n = 26, X = 33; group B: 2-5 years, n = 29, X = 34; group C: 5-10 years, n = 6, X = 36; group D: >10 years, n = 10, X = 43) were investigated by means of a computer-assisted TV pupillometer. After a baseline measurement 0.01% tropicamide was instilled into the eye. The second measurement was conducted 20 min after the first, the 3rd and 4th measurements in intervals of 20 min. RESULTS: The groups with a longer duration of confinement showed a reduced activation and vigilance and increased fatigability as compared with the groups of shorter confinement. In the receptor test the group that had been imprisoned for 0-2 years showed more cognitive deficits than those imprisoned for ≥5 years. CONCLUSIONS: Evaluation of activation, fatigability and vigilance indicates that the duration of confinement plays a role in the development of a functional psychosyndrome. The results of the receptor test, in which the group with a longer duration of confinement showed less pronounced cognitive deficits and no significant changes of the tropicamide effect over time, suggest that in this group a dose change might be required to make the cognitive deficits evident.

Aberrant TIMP-1 overexpression in tumor-associated fibroblasts drives tumor progression through CD63 in lung adenocarcinoma.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an important regulator of extracellular matrix turnover that has been traditionally regarded as a potential tumor suppressor owing to its inhibitory effects of matrix metalloproteinases. Intriguingly, this interpretation has been challenged by the consistent observation that increased expression of TIMP-1 is associated with poor prognosis in virtually all cancer types including lung cancer, supporting a tumor-promoting function. However, how TIMP-1 is dysregulated within the tumor microenvironment and how it drives tumor progression in lung cancer is poorly understood. We analyzed the expression of TIMP-1 and its cell surface receptor CD63 in two major lung cancer subtypes: lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), and defined the tumor-promoting effects of their interaction. We found that TIMP-1 is aberrantly overexpressed in tumor-associated fibroblasts (TAFs) in ADC compared to SCC. Mechanistically, TIMP-1 overexpression was mediated by the selective hyperactivity of the pro-fibrotic TGF-ß1/SMAD3 pathway in ADC-TAFs. Likewise, CD63 was upregulated in ADC compared to SCC cells. Genetic analyses revealed that TIMP-1 secreted by TGF-ß1-activated ADC-TAFs is both necessary and sufficient to enhance growth and invasion of ADC cancer cells in culture, and that tumor cell expression of CD63 was required for these effects. Consistently, in vivo analyses revealed that ADC cells co-injected with fibroblasts with reduced SMAD3 or TIMP-1 expression into immunocompromised mice attenuated tumor aggressiveness compared to tumors bearing parental fibroblasts. We also found that high TIMP1 and CD63 mRNA levels combined define a stronger prognostic biomarker than TIMP1 alone. Our results identify an excessive stromal TIMP-1 within the tumor microenvironment selectively in lung ADC, and implicate it in a novel tumor-promoting TAF-carcinoma crosstalk, thereby pointing to TIMP-1/CD63 interaction as a novel therapeutic target in lung cancer.

Pretransplantation EASIX predicts intensive care unit admission in allogeneic hematopoietic cell transplantation.

The Endothelial Activation and Stress Index (EASIX) is a laboratory-based prognosis index defined as creatinine × lactate dehydrogenase/platelets. When measured at pretransplantation evaluation (EASIX-PRE), it predicts allogeneic hematopoietic cell transplantation (alloHCT) mortality. This study explores its ability to predict intensive care unit (ICU) admission and validates EASIX-PRE predictive power for overall survival (OS) and nonrelapse mortality (NRM) in 167 consecutive patients undergoing alloHCT. EASIX-PRE was calculated retrospectively in all patients and transformed into log2 values (log2-EASIX-PRE). Log2-EASIX-PRE predicted ICU admission (hazard ratio [HR], 1.41; P < .001), OS (HR, 1.19; P = .011), and NRM (HR, 1.28; P = .004). The most discriminating EASIX-PRE cutoff value for risk of ICU admission was the 75th percentile (2.795); for OS and NRM, it was the median value (1.703). Patients with EASIX-PRE >2.795 had higher incidence of ICU admission in comparison with patients with lower EASIX-PRE values (day +180, 35.8% vs 12.8%; HR, 2.28; P = .010). Additionally, patients with EASIX-PRE >1.073 had lower OS (2 years, 57.7% vs 68.7%; HR, 1.98; P = .006) and higher NRM (2 years, 38.7% vs 18.5%; HR, 2.92; P = .001) than patients with lower EASIX-PRE results. Log2-EASIX-PRE was not associated with incidence of transplantation-associated microangiopathy, sinusoidal obstruction syndrome, or acute graft-versus-host disease. This study proposes EASIX-PRE as a prognostic tool to identify patients undergoing alloHCT at increased risk of severe organ dysfunction and who would therefore require ICU admission. Early identification of patients at high risk of severe events could contribute to personalized intervention design. Additionally, it validates the association between EASIX-PRE and OS and NRM in those undergoing alloHCT.

Swept-source optical coherence tomography objective composite activity score for uveitis.

PURPOSE: To develop an objective intraocular inflammation composite score. METHODS: Cross-sectional study. Non-invasive image acquisition and processing were conducted from April 2017 to April 2019. Inflammation-grade stratified eyes from patients with active, inactive uveitis and healthy controls were recruited. After clinical assessment, four anterior and posterior segment image acquisition protocols per eye, using swept-source optical coherence tomography (SS-OCT), were performed at inclusion. Eight imaging biomarkers in three domains: anterior, intermediate and posterior were studied. They were ranked and selected by discriminatory power and correlation with clinical scores. A final SS-OCT-derived composite uveitis activity score (SS-UAS) was developed through multiple linear regression. RESULTS: We studied 224 eyes with uveitis (165 active and 59 inactive) from 165 patients (mean age 46.6 SD 15.5 years; 55.3% women) and 38 eyes from 19 healthy controls (mean age 43.6 SD 17.1; 47% women). The selected SS-OCT-derived biomarkers to build the final score were anterior chamber hyper-reflective dots (anterior), high-definition relative vitreous intensity (intermediate) and the averaged thickened retinal index (posterior). Swept-source (SS)-UAS was highly discriminant between active and inactive, and between active and healthy eyes (means 2.06 SD 1.86, 0.93 SD 0.44, and 0.96 SD 0.38, respectively, both p -, Mann-Whitney U). Construct validity (Cronbach's alpha = 0.7), internal consistency, criterion validity and reliability (concordance correlation coefficient intra-rater = 0.99, 95% CI: 0.98-0.99; inter-rater = 0.98, 95% CI: 0.96-0.99) were favourable. CONCLUSIONS: Global intraocular inflammation can potentially be staged and scored objectively, continuously, consistently and in a valid manner through the combined processing of SS-OCT scans.

[Observational study on drug spending in the immigrant and the indigenous population in the Lleida (Catalonia) health region]. / Estudio observacional del gasto farmacéutico en población inmigrante y autóctona de la región sanitaria de Lleida (Cataluña).

OBJECTIVE: To evaluate whether there are differences in drug spending between immigrant and Spanish-born populations and to assess whether drug consumption is associated with living environment (urban/rural). DESIGN: Observational cross-sectional study. SETTING: Lleida Health Region (LHR). PARTICIPANTS: 22,847 immigrants and 174,768 native born subjects, aged 15 to 64 years, residing in the LHR. MAIN MEASUREMENTS: Drug spending during the year 2007, demographical variables, region of origin and residence area (urban/rural). RESULTS: Native-born subjects spent more in all therapeutic drug groups than immigrants. In men, the relative risk ratio (RRR) of being in the highest quartile of expenditure was 3.2 (95% CI: 2.96-3.44) for native born versus immigrant and in women it was 2.1 (95% CI: 1.97-2.27). Immigrants from eastern Europe had the lowest risk of being in the highest quartile of expenditure, with statistically significant differences. Residents in the rural environment were more likely to have a higher pharmaceutical consumption than residents in the urban environment. CONCLUSION: Inequalities in drug spending were observed between immigrants and native born subjects. Further studies, either qualitative or mixed, should explore which factors are related to these differences and propose strategies addressed to reducing them.

Palliative Care Physicians and Palliative Radiotherapy, Knowledge and Barriers for Referring: A Cross-sectional Study.

CONTEXT: Palliative radiotherapy is effective in the management of symptoms resulting from advanced cancer. However, it remains underutilized. In developed countries, many factors have been linked to this phenomenon but data in developing and low-income countries, particularly in Latin America, are lacking. OBJECTIVES: To conduct a cross-sectional survey to explore palliative care physicians' knowledge of palliative radiotherapy and to investigate possible factors that limit patient referral. METHODS: This is a cross-sectional survey. An online questionnaire was sent to palliative care physicians (n = 170) registered in the Chilean Medical Society of Palliative Care directory. RESULTS: The overall response rate was 58.8%. Nearly all respondents (98%) considered radiotherapy to be a useful treatment. Less than half the respondents (43%) had good knowledge of palliative radiotherapy. Knowledge was correlated with self-reported knowledge (P = 0.015), discussing cases with radiation oncologist (P = 0.001), and having attended educational events on palliative radiotherapy (P = 0.001). Patient reluctance, poor performance status, and family reluctance were identified as major barriers to the use of palliative radiotherapy. Physicians from cities other than the capital were more likely to be concerned about barriers such as distance to radiotherapy facilities (P = 0.01), the duration of the referral process (P = 0.01), and the lack of a radiation oncologist available for discussing cases (P = 0.01). CONCLUSIONS: Several barriers affect referral to palliative radiotherapy. Some barriers seem to be more significant for physicians practicing in cities far from cancer centers. Physicians' knowledge is less than optimal and has been identified as a barrier to referral. Educational interventions and broadening the availability of cancer treatment resources are needed to improve the referral process.

Automated Quantitative Analysis of Mitochondrial Morphology.

Mitochondria are dynamic organelles that in most cells behave as a dynamic network and can change their biogenesis and structure depending on the cell needs or as a response to different conditions. Analyzing the architecture of mitochondria is determinant to describe their state and function. In this chapter, image processing techniques are applied in a workflow manner to segment the mitochondrial network and extract the most relevant parameters that enable an accurate morphology analysis. This workflow is programmed with ImageJ macro language and can be applied to automatically analyze multiple cells from multiple images or tiles. When combined with multiwell plates and automated microscopy, this method may allow to perform high content image analysis of hundreds of cells under different conditions.

Sick leave among native and immigrant workers in Spain--a 6-month follow-up study.

OBJECTIVES: The incidence and the duration of sick leave were studied among immigrants and the native-born population in Spain. METHODS: This observational follow-up study included 1427 immigrants and 2793 Spanish natives treated at five primary care centers in Lleida in 2005 and followed for 6 months. The sick leave causes were coded according to the International Classification of Diseases (10th revision). Multivariate Poisson regressions estimated the rate ratio (RR) for sick leave adjusted for age, and linear regressions evaluated the effect of age, gender, and region of origin on the total number of sick-leave days. RESULTS: Altogether 19.5% of the natives and 12.7% of the immigrants had at least one sick-leave episode. The incidence of new episodes per 100 person-years was lower for the immigrants than for the natives (32.5 versus 43.3 for the men and 18.6 versus 35.6 for the women, respectively). The mean duration of sick leave in the 6-month period was 19.4 (SD 29.4) days for the immigrants and 33.5 (SD 39.2) days for the natives. For the men, the risk of sick leave was greater for the natives than for the immigrants (adjusted RR 1.70, 95% confidence interval 1.43-2.02). After adjustment for age, the duration of sick leave for the native workers was 1.5 times greater than for the immigrants. CONCLUSIONS: Even though sick leave was less frequent among the immigrants than among the natives and the immigrant sick-leave periods were of shorter duration, the two study populations did not show differences in the causes of disability.

Scene classification using a hybrid generative/discriminative approach.

We investigate whether dimensionality reduction using a latent generative model is beneficial for the task of weakly supervised scene classification. In detail we are given a set of labelled images of scenes (e.g. coast, forest, city, river, etc) and our objective is to classify a new image into one of these categories. Our approach consists of first discovering latent "topics" using probabilistic Latent Semantic Analysis (pLSA), a generative model from the statistical text literature here applied to a bag of visual words representation for each image, and subsequently training a multi-way classifier on the topic distribution vector for each image. We compare this approach to that of representing each image by a bag of visual words vector directly, and training a multi-way classifier on these vectors. To this end we introduce a novel vocabulary using dense colour SIFT descriptors, and then investigate the classification performance under changes in the size of the visual vocabulary, the number of latent topics learnt, and the type of discriminative classifier used (k-nearest neighbour or SVM). We achieve superior classification performance to recent publications that have used a bag of visual word representation, in all cases using the authors' own datasets and testing protocols. We also investigate the gain in adding spatial information. We show applications to image retrieval with relevance feedback and to scene classification in videos.

Differences in pharmaceutical consumption and expenses between immigrant and Spanish-born populations in Lleida, (Spain): a 6-months prospective observational study.

BACKGROUND: There are few studies comparing pharmaceutical costs and the use of medications between immigrants and the autochthonous population in Spain. The objective of this study is to evaluate whether there are differences in pharmaceutical consumption and expenses between immigrant and Spanish-born populations. METHODS: Prospective observational study in 1,630 immigrants and 4,154 Spanish-born individuals visited by fifteen primary care physicians at five public Primary Care Clinics (PCC) during 2005 in the city of Lleida, Catalonia (Spain). Data on pharmaceutical consumption and expenses was obtained from a comprehensive computerized data-collection system. Multinomial regression models were used to estimate relative risks and confidence intervals of pharmaceutical expenditure, adjusting for age and sex. RESULTS: The percentage of individuals that purchased medications during a six-month period was 53.7% in the immigrant group and 79.2% in the autochthonous group. Pharmaceutical expenses and consumption were lower in immigrants than in autochthonous patients in all age groups and both genders. The relative risks of being in the highest quartile of expenditure, for Spanish-born versus immigrants, were 6.9, 95% CI = (4.2, 11.5) in men and 5.3, 95% CI = (3.5, 8.0) in women, with the reference category being not having any pharmaceutical expenditure. CONCLUSION: Pharmaceutical expenses are much lower for immigrants with respect to autochthonous patients, both in the percentage of prescriptions filled at pharmacies and the number of containers of medication obtained, as well as the prices of the medications used. Future studies should explore which factors explain the observed differences in pharmaceutical expenses and if these disparities produce health inequalities.

Emergency hospital services utilization in Lleida (Spain): A cross-sectional study of immigrant and Spanish-born populations.

BACKGROUND: The use of emergency hospital services (EHS) has increased steadily in Spain in the last decade while the number of immigrants has increased dramatically. Studies show that immigrants use EHS differently than native-born individuals, and this work investigates demographics, diagnoses and utilization rates of EHS in Lleida (Spain). METHODS: Cross-sectional study of all the 96,916 EHS visits by patients 15 to 64 years old, attended during the years 2004 and 2005 in a public teaching hospital. Demographic data, diagnoses of the EHS visits, frequency of hospital admissions, mortality and diagnoses at hospital discharge were obtained. Utilization rates were estimated by group of origin. Poisson regression was used to estimate the rate ratios of being visited in the EHS with respect to the Spanish-born population. RESULTS: Immigrants from low-income countries use EHS services more than the Spanish-born population. Differences in utilization patterns are particularly marked for Maghrebi men and women and sub-Saharan women. Immigrant males are at lower risk of being admitted to the hospital, as compared with Spanish-born males. On the other hand, immigrant women are at higher risk of being admitted. After excluding the visits with gynecologic and obstetric diagnoses, women from sub-Saharan Africa and the Maghreb are still at a higher risk of being admitted than their Spanish-born counterparts. CONCLUSION: In Lleida (Spain), immigrants use more EHS than the Spanish born population. Future research should indicate whether the same pattern is found in other areas of Spain and whether EHS use is attributable to health needs, barriers to access to the primary care services or similarities in the way immigrants access health care in their countries of origin.