A national approach to pediatric sepsis surveillance

Pediatric sepsis is a major public health concern, and robust surveillance tools are needed to characterize its incidence, outcomes, and trends. The increasing use of electronic health records (EHRs) in the United States creates an opportunity to conduct reliable, pragmatic, and generalizable population-level surveillance using routinely collected clinical data rather than administrative claims or resource-intensive chart review. In 2015, the US Centers for Disease Control and Prevention recruited sepsis investigators and representatives of key professional societies to develop an approach to adult sepsis surveillance using clinical data recorded in EHRs. This led to the creation of the adult sepsis event definition, which was used to estimate the national burden of sepsis in adults and has been adapted into a tool kit to facilitate widespread implementation by hospitals. In July 2018, the Centers for Disease Control and Prevention convened a new multidisciplinary pediatric working group to tailor an EHR-based national sepsis surveillance approach to infants and children. Here, we describe the challenges specific to pediatric sepsis surveillance, including evolving clinical definitions of sepsis, accommodation of agedependent physiologic differences, identifying appropriate EHR markers of infection and organ dysfunction among infants and children, and the need to account for children with medical complexity and the growing regionalization of pediatric care. We propose a preliminary pediatric sepsis event surveillance definition and outline next steps for refining and validating these criteria so that they may be used to estimate the national burden of pediatric sepsis and support site-specific surveillance to complement ongoing initiatives to improve sepsis prevention, recognition, and treatment

The handbook for standardised field and laboratory measurements in terrestrial climate-change experiments and observational studies

Climate change is a worldwide threat to biodiversity and ecosystem structure, functioning, and services. To understand the underlying drivers and mechanisms, and to predict the consequences for nature and people, we urgently need better understanding of the direction and magnitude of climate‐change impacts across the soil–plant–atmosphere continuum. An increasing number of climate‐change studies is creating new opportunities for meaningful and high‐quality generalisations and improved process understanding. However, significant challenges exist related to data availability and/or compatibility across studies, compromising opportunities for data re‐use, synthesis, and upscaling. Many of these challenges relate to a lack of an established “best practice” for measuring key impacts and responses. This restrains our current understanding of complex processes and mechanisms in terrestrial ecosystems related to climate change

Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most

Planck early results. VI. The High Frequency Instrument data processing

We describe the processing of the 336 billion raw data samples from the High Frequency Instrument (HFI) which we performed to produce six temperature maps from the first 295 days of Planck-HFI survey data. These maps provide an accurate rendition of the sky emission at 100, 143, 217, 353, 545 and 857GHz with an angular resolution ranging from 9.9 to 4.4 . The white noise level is around 1.5 μK degree or less in the 3 main CMB channels (100–217 GHz). The photometric accuracy is better than 2% at frequencies between 100 and 353 GHz and around 7% at the two highest frequencies. The maps created by the HFI Data Processing Centre reach our goals in terms of sensitivity, resolution, and photometric accuracy. They are already sufficiently accurate and well-characterised to allow scientific analyses which are presented in an accompanying series of early papers. At this stage, HFI data appears to be of high quality and we expect that with further refinements of the data processing we should be able to achieve, or exceed, the science goals of the Planck project

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

Potencial alelopático de plantas de acapu (Vouacapoua americana): efeitos sobre plantas daninhas de pastagens Allelopathic potential of "acapu" (Vouacapoua americana) plants: effects on pasture weed

Extratos aquosos de folhas e cascas de plantas de acapu (Vouacapoua americana) foram preparados nas concentrações de 0, 1, 2, 3 e 5% (v/v), visando identificar e caracterizar a atividade potencialmente alelopática dessa espécie. Analisaram-se os efeitos dos extratos sobre a germinação de sementes e o alongamento da raiz primária das plantas daninhas malícia (Mimosa pudica) e malva (Urena lobata). Os bioensaios de germinação foram desenvolvidos em condições de 25 ºC e fotoperíodo de 12 horas. Para os bioensaios de alongamento da raiz primária, as condições estabelecidas foram de 25 ºC e fotoperíodo de 24 horas. Os resultados obtidos indicaram variações de respostas em função da fonte do extrato aquoso, do parâmetro analisado e da concentração do extrato. As reduções observadas tanto na germinação como no alongamento da raiz primária foram crescentes com o aumento da concentração do extrato, sendo os efeitos mais intensos observados na concentração de 5%. Independentemente da espécie receptora e do parâmetro analisado, o extrato preparado a partir das cascas do acapu evidenciou maior atividade alelopática inibitória. O alongamento da raiz primária foi o parâmetro mais sensível aos efeitos potencialmente alelopáticos do que a germinação das sementes. Comparativamente, cascas e folhas apresentaram diferenças em relação às classes de substâncias químicas. Nas cascas foram encontradas cumarinas que não estavam presentes nas folhas, as quais, por sua vez, apresentaram esteróides e triterpenóides, que não foram identificados nas cascas do acapu.<br>Aqueous extracts from leaves and bark of "Acapu" plants were prepared in concentration levels of 0, 1, 2, 3 and 5% to identify and characterize potential allelopathic activity of such plants. The extract effects on seed germination and primary root elongation of pasture weeds, such as Mimosa pudica and Urena lobata, were analyzed. The germination bioassays were developed under 25 ºC and a photoperiod of 12 hours. For the primary root elongation, the bioassay conditions were 25 ºC and photoperiod of 24 hours. The results indicated a variation in response, according to the source of aqueous extract, the analyzed parameter and the extract concentration. The reductions observed both in germination and primary root elongation increased with the increase of extract concentration. The most intense effects were observed at an extract concentration level of 5%. Regardless of the receiving species and the analyzed parameter, the extract prepared from the bark showed greater inhibiting allelopathic activity. The parameter primary root elongation was more sensitive to the potential allelopathic effects than seed germination. Comparatively, bark and leaves showed differences in relation to the chemical compound classes. Cumarins were identified in the bark but not in the leaves, while steroids and triterpenoids were observed in the leaves but not in the bark