Generalitat de Catalunya

During the last 3 years, a number of approaches for the normalization of RNA sequencing data have emerged in the literature, differing both in the type of bias adjustment and in the statistical strategy adopted. However, as data continue to accumulate, there has been no clear consensus on the appropriate normalization method to be used or the impact of a chosen method on the downstream analysis. In this work, we focus on a comprehensive comparison of seven recently proposed normalization methods for the differential analysis of RNA-seq data, with an emphasis on the use of varied real and simulated datasets involving different species and experimental designs to represent data characteristics commonly observed in practice. Based on this comparison study, we propose practical recommendations on the appropriate normalization method to be used and its impact on the differential analysis of RNA-seq data.

AIMS/HYPOTHESIS: The Di@bet.es Study is the first national study in Spain to examine the prevalence of diabetes and impaired glucose regulation. METHODS: A population-based, cross-sectional, cluster sampling study was carried out, with target population being the entire Spanish population. Five thousand and seventy-two participants in 100 clusters (health centres or the equivalent in each region) were randomly selected with a probability proportional to population size. Participation rate was 55.8%. Study variables were a clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, BMI, waist and hip circumference, blood pressure) and OGTT (75 g). RESULTS: Almost 30% of the study population had some carbohydrate disturbance. The overall prevalence of diabetes mellitus adjusted for age and sex was 13.8% (95% CI 12.8, 14.7%), of which about half had unknown diabetes: 6.0% (95% CI 5.4, 6.7%). The age- and sex-adjusted prevalence rates of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG-IGT were 3.4% (95% CI 2.9, 4.0%), 9.2% (95% CI 8.2, 10.2%) and 2.2% (95% CI 1.7, 2.7%), respectively. The prevalence of diabetes and impaired glucose regulation increased significantly with age (p < 0.0001), and was higher in men than in women (p < 0.001). CONCLUSIONS/INTERPRETATION: The Di@bet.es Study shows, for the first time, the prevalence rates of diabetes and impaired glucose regulation in a representative sample of the Spanish population.

BACKGROUND: Since the beginning of December 2019, the coronavirus disease (COVID-19) has spread rapidly around the world, which has led to increased discussions across online platforms. These conversations have also included various conspiracies shared by social media users. Amongst them, a popular theory has linked 5G to the spread of COVID-19, leading to misinformation and the burning of 5G towers in the United Kingdom. The understanding of the drivers of fake news and quick policies oriented to isolate and rebate misinformation are keys to combating it. OBJECTIVE: The aim of this study is to develop an understanding of the drivers of the 5G COVID-19 conspiracy theory and strategies to deal with such misinformation. METHODS: This paper performs a social network analysis and content analysis of Twitter data from a 7-day period (Friday, March 27, 2020, to Saturday, April 4, 2020) in which the #5GCoronavirus hashtag was trending on Twitter in the United Kingdom. Influential users were analyzed through social network graph clusters. The size of the nodes were ranked by their betweenness centrality score, and the graph's vertices were grouped by cluster using the Clauset-Newman-Moore algorithm. The topics and web sources used were also examined. RESULTS: Social network analysis identified that the two largest network structures consisted of an isolates group and a broadcast group. The analysis also revealed that there was a lack of an authority figure who was actively combating such misinformation. Content analysis revealed that, of 233 sample tweets, 34.8% (n=81) contained views that 5G and COVID-19 were linked, 32.2% (n=75) denounced the conspiracy theory, and 33.0% (n=77) were general tweets not expressing any personal views or opinions. Thus, 65.2% (n=152) of tweets derived from nonconspiracy theory supporters, which suggests that, although the topic attracted high volume, only a handful of users genuinely believed the conspiracy. This paper also shows that fake news websites were the most popular web source shared by users; although, YouTube videos were also shared. The study also identified an account whose sole aim was to spread the conspiracy theory on Twitter. CONCLUSIONS: The combination of quick and targeted interventions oriented to delegitimize the sources of fake information is key to reducing their impact. Those users voicing their views against the conspiracy theory, link baiting, or sharing humorous tweets inadvertently raised the profile of the topic, suggesting that policymakers should insist in the efforts of isolating opinions that are based on fake news. Many social media platforms provide users with the ability to report inappropriate content, which should be used. This study is the first to analyze the 5G conspiracy theory in the context of COVID-19 on Twitter offering practical guidance to health authorities in how, in the context of a pandemic, rumors may be combated in the future.

Providing therapies tailored to each patient is the vision of precision medicine, enabled by the increasing ability to capture extensive data about individual patients. In this position paper, we argue that the second enabling pillar towards this vision is the increasing power of computers and algorithms to learn, reason, and build the 'digital twin' of a patient. Computational models are boosting the capacity to draw diagnosis and prognosis, and future treatments will be tailored not only to current health status and data, but also to an accurate projection of the pathways to restore health by model predictions. The early steps of the digital twin in the area of cardiovascular medicine are reviewed in this article, together with a discussion of the challenges and opportunities ahead. We emphasize the synergies between mechanistic and statistical models in accelerating cardiovascular research and enabling the vision of precision medicine.

Purpose The purpose of this paper is to explain the changes in the Web Content Accessibility Guidelines (WCAG) 2.0 compared with WCAG 1.0 within the context of its historical development. Design/methodology/approach In order to compare WCAG 2.0 with WCAG 1.0 a diachronic analysis of the evolution of these standards is done. Known authors and publications in the field, the Web Accessibility Initiative (WAI) web pages, WebAIM and the blogosphere were also monitored for comments and third‐party analyses. The analysis of the main changes from WCAG 1.0 to WCAG 2.0 was based on personal experience with WAI guidelines, experimentation with some of the new guidelines, and a selection of best practice online services in the application of the WCAG, including WAI documentation. Findings WCAG 2.0 is more educational and is applied to more technologies than WCAG 1.0. The limitations of WCAG 1.0 are mostly due to its origin. In changing from one to the other, new priorities and new elements must be taken into account. The paper concludes that though these guidelines are a useful tool for governments, they are only the first step towards accessibility, which can only be achieved through user‐centred design. Originality/value This paper explains the significance and limitations of the WCAG and gives a short guide to adapting web sites to the new regulations.

Soil treatments with Metarhizium brunneum EAMa 01/58-Su strain conducted in both Northern and Southern Spain reduced the olive fly (Bactrocera oleae) population density emerging from the soil during spring up to 70% in treated plots compared with controls. A model to determine the influence of rainfall on the conidial wash into different soil types was developed, with most of the conidia retained at the first 5 cm, regardless of soil type, with relative percentages of conidia recovered ranging between 56% and 95%. Furthermore, the possible effect of UV-B exposure time on the pathogenicity of this strain against B. oleae adults coming from surviving preimaginals and carrying conidia from the soil at adult emergence was also evaluated. The UV-B irradiance has no significant effect on M. brunneum EAMa 01/58-Su pathogenicity with B. oleae adult mortalities of 93, 90, 79, and 77% after 0, 2, 4, and 6 of UV-B irradiance exposure, respectively. In a next step for the use of these M. brunneum EAMa 01/58-Sun soil treatments within a B. oleae IPM strategy, its possible effect of on the B. oleae cosmopolitan parasitoid Psyttalia concolor, its compatibility with the herbicide oxyfluorfen 24% commonly used in olive orchards and the possible presence of the fungus in the olive oil resulting from olives previously placed in contact with the fungus were investigated. Only the highest conidial concentration (1×108 conidia ml-) caused significant P. concolor adult mortality (22%) with enduing mycosis in 13% of the cadavers. There were no fungal propagules in olive oil samples resulting from olives previously contaminated by EAMa 01/58-Su conidia. Finally, the strain was demonstrated to be compatible with herbicide since the soil application of the fungus reduced the B. oleae population density up to 50% even when it was mixed with the herbicide in the same tank. The fungal inoculum reached basal levels four months after treatments (1.6×103 conidia g soil-1). These results reveal both the efficacy and environmental and food safety of this B. oleae control method, protecting olive groves and improving olive oil quality without negative effects on the natural enemy P. concolor.

AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

The addictive use of video games is recognized as a problem with clinical relevance and is included in international diagnostic manuals and classifications of diseases. The association between "Internet addiction" and mental health has been well documented across a range of investigations. However, a major drawback of these studies is that no controls have been placed on the type of Internet use investigated. The aim of this study is to review systematically the current literature in order to explore the association between Internet Gaming Disorder (IGD) and psychopathology. An electronic literature search was conducted using PubMed, PsychINFO, ScienceDirect, Web of Science and Google Scholar (r.n. CRD42018082398). The effect sizes for the observed correlations were identified or computed. Twenty-four articles met the eligibility criteria. The studies included comprised 21 cross-sectional and three prospective designs. Most of the research was conducted in Europe. The significant correlations reported comprised: 92% between IGD and anxiety, 89% with depression, 85% with symptoms of attention deficit hyperactivity disorder (ADHD), and 75% with social phobia/anxiety and obsessive-compulsive symptoms. Most of the studies reported higher rates of IGD in males. The lack of longitudinal studies and the contradictory results obtained prevent detection of the directionality of the associations and, furthermore, show the complex relationship between both phenomena.

This study was designed to estimate the dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the general population of Catalonia, Spain. The concentrations of these elements were determined in food samples randomly acquired in seven cities of Catalonia between June and August 2000. A total of 11 food groups were included in the study. As, Cd, Hg, and Pb levels were measured by ICP-MS and AAS. The dietary intake of these elements was determined by a total diet study. Calculations were carried out on the basis of recent data on the consumption of the selected food items. Trace element intake was estimated for five population groups: children, adolescents, male and female adults, and seniors. The highest dietary intakes of As (223.6 microg/day), Cd (15.7 microg/day), Hg (21.2 microg/day), and Pb (28.4 microg/day) corresponded to male adults. For all analyzed elements, fish and shellfish was the group showing the highest contribution to the respective intakes. In comparison with previous results, a general decrease in As, Cd, Hg, and Pb intake has occurred. The dietary intake of these elements was also compared with the provisional tolerable weekly intake (PTWI). Dietary intakes of As, Cd, Hg, and Pb by the population of Catalonia are currently well below the respective PTWIs.

OBJECTIVE: Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death. RESEARCH DESIGN AND METHODS: We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths. RESULTS: We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes. CONCLUSIONS: Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes.

El nuevo coronavirus SARS-CoV-2 es un virus de ARN monocatenario positivo que puede traducirse inmediatamente e integrarse en la célula huésped con su propio mensajero de ARN, facilitando la replicación dentro de la célula y la infectividad. La rápida progresión de la enfermedad presenta un verdadero desafío en todas las partes del mundo. A medida que se excede la capacidad habitual de atención sanitaria a los ciudadanos pueden generarse tensiones entre los profesionales de la salud y los gobiernos. Una de las estrategias más importantes para reducir y mitigar el avance de la epidemia son las medidas de distanciamiento social. Aquí es donde la telemedicina puede ayudar y brindar apoyo a los sistemas de salud, especialmente en las áreas de salud, prevención y prácticas clínicas, tal como se está están haciendo en otros sectores. La telemedicina conecta la conveniencia, el bajo costo y la fácil accesibilidad de la información y la comunicación relacionadas con la salud a través de Internet y las tecnologías asociadas. La telemedicina durante la epidemia de coronavirus ha sido la primera línea de defensa de los sanitarios para para frenar la propagación del coronavirus, brindando servicios por teléfono o videoconferencia para atención personalizada en casos leves y limitando los recursos sanitarios para los casos más urgentes. The novel coronavirus SARS-CoV-2 is a positive single-stranded RNA virus that can be immediately translated and integrated into the host cell with its own RNA messenger, facilitating replication inside the cell and infectivity. The rapid progression of the disease presents a real challenge for the whole world. As the usual capacity for citizen care is exceeded, health professionals and governments struggle. One of the most important strategies to reduce and mitigate the advance of the epidemic are social distance measures; this is where telemedicine can help, and provide support to the healthcare systems, especially in the areas of public health, prevention and clinical practices, just as it is doing in others sectors. Telemedicine connects the convenience, low cost, and ready accessibility of health-related information and communication using the Internet and associated technologies. Telemedicine during the coronavirus epidemic has been the doctors’ first line of defense to slow the spread of the coronavirus, keeping social distancing and providing services by phone or videoconferencing for mild to focus personal care and limited supplies to the most urgent cases.

BACKGROUND: Autologous platelet-rich plasma (PRP) is a treatment that contains fibrin and high concentrations of growth factors with the potential to improve the healing of chronic wounds. This is the first update of a review first published in 2012. OBJECTIVES: To determine whether autologous PRP promotes the healing of chronic wounds. SEARCH METHODS: In June 2015, for this first update, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library): Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched for ongoing and unpublished clinical trials in the WHO International Clinical Trials Registry Platform (ICTRP) (searched January 2015). We did not impose any restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared autologous PRP with placebo or alternative treatments for any type of chronic wound in adults. We did not apply any date or language restrictions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology, including two reviewers independently selecting studies for inclusion, extracting data, and assessing risk of bias. MAIN RESULTS: The search identified one new RCT, making a total of 10 included RCTs (442 participants, 42% women). The median number of participants per RCT was 29 (range 10 to 117). Four RCTs recruited people with a range of chronic wounds; three RCTs recruited people with venous leg ulcers, and three RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range 8 to 40 weeks).It is unclear whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment (with or without placebo) (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.95 to 1.50; I(2) = 27%, low quality evidence, 8 RCTs, 391 participants). Autologous PRP may increase the healing of foot ulcers in people with diabetes compared with standard care (with or without placebo) (RR 1.22, 95% CI 1.01 to 1.49; I(2) = 0%, low quality evidence, 2 RCTs, 189 participants). It is unclear if autologous PRP affects the healing of venous leg ulcers (RR 1.02, 95% CI 0.81 to 1.27; I(2) = 0% ). It is unclear if there is a difference in the risk of adverse events in people treated with PRP or standard care (RR 1.05, 95% CI 0.29 to 3.88; I(2) = 0%, low quality evidence from 3 trials, 102 participants). AUTHORS' CONCLUSIONS: PRP may improve the healing of foot ulcers associated with diabetes, but this conclusion is based on low quality evidence from two small RCTs. It is unclear whether PRP influences the healing of other chronic wounds. The overall quality of evidence of autologous PRP for treating chronic wounds is low. There are very few RCTs evaluating PRP, they are underpowered to detect treatment effects, if they exist, and are generally at high or unclear risk of bias. Well designed and adequately powered clinical trials are needed.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in a variety of materials, including synthetic polymers and textiles. Although these chemicals have been detected in environmental samples and human tissues, there is little information about human exposure to PBDEs through the diet. In the present study, we determined the concentrations of PBDEs in a number of food samples acquired in Catalonia (Spain) during 2000. The dietary intake of PBDEs was estimated for the general population living in this Spanish region. The highest PBDE concentrations were found in oils and fats, fish and shellfish, meat and meat products, and eggs, while the lowest levels corresponded to fruits, vegetables, and tubers. The dietary intake of PBDEs for an adult male was 97.3 ng/day (assuming not detected (ND) = (1)/(2) limit of detection (LOD)) or 81.9 ng/day (assuming ND = 0) The greatest contribution to these values corresponded to fish and shellfish, with approximately one-third of the total intake. TetraBDEs and pentaBDEs were the homologues showing the highest percentages of contribution to the sum of total PBDEs. The comparison of the current dietary intake with the suggested lowest observed adverse effect level value of 1 mg/kg/day for the most sensitive endpoints for toxic effects of PBDEs results in a safety factor over 5 orders of magnitude in relation to PBDE exposure from food.

AIMS: To identify suitable short versions of the Alcohol Use Disorders Identification Test (AUDIT) and to evaluate their effectiveness as screening tests for 'risky drinking' among men and women in primary health care (PHC) settings. METHODS: A total of 255 patients attending five PHC centres in Catalonia (Spain) were interviewed by clinicians regarding health status and drinking pattern. Patients also completed the AUDIT. Clinicians' diagnosis of risky drinking was used as a gold standard to evaluate the effectiveness of three forms of AUDIT. RESULTS: AUDIT-3 and AUDIT-4 performed similarly to AUDIT-10 in detecting risky drinking and had equivalent receiver operating characteristics curves and their areas under the curve. CONCLUSIONS: Both short forms of AUDIT seem to be as effective as the full AUDIT for detecting risky drinking among men and women in PHC settings.

BACKGROUND: No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. METHODS: Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. RESULTS: A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (-1.41 vs -1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (-3.37 vs -3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. CONCLUSIONS: In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.

A study of aggregate data collected from the literature and official sources was undertaken to estimate expected and observed prevalence of Trypanosoma cruzi infection, annual incidence of congenital transmission and rate of underdiagnosis of Chagas disease among Latin American migrants in the nine European countries with the highest prevalence of Chagas disease. Formal and informal data sources were used to estimate the population from endemic countries resident in Europe in 2009, diagnosed cases of Chagas disease and births from mothers originating from endemic countries. By 2009, 4,290 cases had been diagnosed in Europe, compared with an estimated 68,000 to 122,000 expected cases. The expected prevalence was very high in undocumented migrants (on average 45% of total expected cases) while the observed prevalence rate was 1.3 cases per 1,000 resident migrants from endemic countries. An estimated 20 to 183 babies with congenital Chagas disease are born annually in the study countries. The annual incidence rate of congenital transmission per 1,000 pregnancies in women from endemic countries was between none and three cases. The index of under diagnosis of T. cruzi infection was between 94% and 96%. Chagas disease is a public health challenge in the studied European countries. Urgent measures need to be taken to detect new cases of congenital transmission and take care of the existing cases with a focus on migrants without legal residency permit and potential difficulty accessing care.

Procyanindin extract (PE) is a mixture of polyphenols, mainly procyanidins, obtained from grape seed with putative antiinflammatory activity. We evaluated the PE effect on RAW 264.7 macrophages stimulated with lipopolysaccharide plus interferon-gamma that show a rapid enhanced production of prostaglandin E2 (PGE2) and nitric oxide (NO). Our results demonstrated that PE significantly inhibited the overproduction of NO, dose and time dependently. PE caused a marked inhibition of PGE2 synthesis when administered during activation. Moreover, PE pretreatment diminished iNOS mRNA and protein amount dose dependently (10-65 microg/mL). PE (65 microg/mL) pretreatment inhibited NFkappaB (p65) translocation to nucleus by nearly 40%. Trimeric and longer oligomeric-rich procyanidin fractions from PE (5-30 microg/mL) inhibited iNOS expression but not the monomeric forms catechin and epicatechin. Thus, we show that the degree of polymerization is important in determining procyanidin effects. PE was considerably a more effective inhibitor of NO biosynthesis (IC50 = 50 microg/mL) in comparison to other antiinflammatories, such as aspirin (3 mM), indomethacin (20 microM), and dexamethasone (9 nM). In conclusion, PE modulates inflammatory response in activated macrophages by the inhibition of NO and PGE2 production, suppression of iNOS expression, and NFkB translocation. These results demonstrate an immunomodulatory role of grape seed procyanidins and thus a potential health-benefit in inflammatory conditions that exert an overproduction of NO and PGE2.

BACKGROUND: Of deaths in high-income countries, 75% are caused by progressive advanced chronic conditions. Palliative care needs to be extended from terminal cancer to these patients. However, direct measurement of the prevalence of people in need of palliative care in the population has not been attempted. AIM: Determine, by direct measurement, the prevalence of people in need of palliative care among advanced chronically ill patients in a whole geographic population. DESIGN: Cross-sectional, population-based study. MAIN OUTCOME MEASURE: prevalence of advanced chronically ill patients in need of palliative care according to the NECPAL CCOMS-ICO(©) tool. NECPAL+ patients were considered as in need of palliative care. SETTING/PARTICIPANTS: County of Osona, Catalonia, Spain (156,807 inhabitants, 21.4% > 65 years). Three randomly selected primary care centres (51,595 inhabitants, 32.9% of County's population) and one district general hospital, one social-health centre and four nursing homes serving the patients. Subjects were all patients attending participating settings between November 2010 and October 2011. RESULTS: A total of 785 patients (1.5% of study population) were NECPAL+: mean age = 81.4 years; 61.4% female. Main disease/condition: 31.3% advanced frailty, 23.4% dementia, 12.9% cancer (ratio of cancer/non-cancer = 1/7), 66.8% living at home and 19.7% in nursing home; only 15.5% previously identified as requiring palliative care; general clinical indicators of severity and progression present in 94% of cases. CONCLUSIONS: Direct measurement of prevalence of palliative care needs on a population basis is feasible. Early identification and prevalence determination of these patients is likely to be the cornerstone of palliative care public health policies.

The mechanisms used by antisense transcripts to regulate their corresponding sense mRNAs are not fully understood. Herein, we have addressed this issue for the vimentin (VIM) gene, a member of the intermediate filament family involved in cell and tissue integrity that is deregulated in different types of cancer. VIM mRNA levels are positively correlated with the expression of a previously uncharacterized head-to-head antisense transcript, both transcripts being silenced in colon primary tumors concomitant with promoter hypermethylation. Furthermore, antisense transcription promotes formation of an R-loop structure that can be disfavored in vitro and in vivo by ribonuclease H1 overexpression, resulting in VIM down-regulation. Antisense knockdown and R-loop destabilization both result in chromatin compaction around the VIM promoter and a reduction in the binding of transcriptional activators of the NF-κB pathway. These results are the first examples to our knowledge of R-loop-mediated enhancement of gene expression involving head-to-head antisense transcription at a cancer-related locus.

We tested the effect of nutrient inputs from wastewater treatment plants (WWTPs) on stream nutrient retention efficiency by examining the longitudinal patterns of ammonium, nitrate, and phosphate concentrations downstream of WWTP effluents in 15 streams throughout Catalonia (Spain). We hypothesized that large nutrient loadings would saturate stream communities, lowering nutrient retention efficiency (i.e., nutrient retention relative to nutrient flux) relative to less polluted streams. Longitudinal variation in ambient nutrient concentration reflected the net result of physical, chemical, or biological uptake and release processes. Therefore, gradual increases in nutrient concentration indicate that the stream acts as a net source of nutrients to downstream environments, whereas gradual declines indicate that the stream acts as a net sink. In those streams where gradual declines in nutrient concentration were observed, we calculated the nutrient uptake length as an indicator of the stream nutrient retention efficiency. No significant decline was found in dilution-corrected concentrations of dissolved inorganic nitrogen (DIN) and phosphate in 40 and 45% of streams, respectively. In the remaining streams, uptake length (estimated based on the decline of nutrient concentrations at ambient levels) ranged from 0.14 to 29 km (DIN), and from 0.14 to 14 km (phosphate). Overall, these values are longer (lower retention efficiency) than those from nonpolluted streams of similar size, supporting our hypothesis, and suggest that high nutrient loads affect fluvial ecosystem function. This study demonstrates that the efficiency of stream ecosystems to remove nutrients has limitations because it can be significantly altered by the quantity and quality of the receiving water.