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ObjectivesThe Nutrition Risk in the Critically Ill (NUTRIC) score has been advocated as a screening tool for nutrition risk assessment in critically ill patients. It was developed and validated to predict 28-day mortality using Acute Physiology and Chronic Health Evaluation II (APACHE II) score as one of its components. However, nowadays the Simplified Acute Physiology Score 3 (SAPS 3) demonstrates better performance. We aimed to test the performance of NUTRIC score in predicting 28-day mortality after replacement of APACHE II by SAPS 3, and the interaction between nutrition adequacy and mortality.MethodsAdult patients who received nutrition therapy and remained >3 days in intensive care unit were retrospectively evaluated. In order to replace APACHE II component, we used ranges of SAPS 3 with similar predicted mortality. Discrimination between these tools in predicting 28-day mortality was assessed using the ROC curve, calibration was evaluated with calibration belt, and correlation with intraclass correlation. The relationship between nutritional adequacy and mortality was assessed in a subgroup with available data.Results542 patients were analyzed (median age of 78 years old, 73.4% admitted for non-surgical reasons and 28-day mortality was 18.1%). Mortality prediction discrimination did not differ between tools (p>0.05), but showed a good agreement (intraclass correlation 0.86) with good calibration. In the subgroup analysis for nutritional adequacy (n = 99), no association with mortality was observed.ConclusionPerformance of NUTRIC score with SAPS 3 is similar to the original tool. Therefore, it might be used in settings where APACHE II is not available.

Abstract Analysis on spatial-temporal data has several benefits that range from an improved traffic network in a city to increased earnings for drivers and ridesharing companies. A common analysis technique is clustering. However, most clustering techniques consider a constrained representation of clusters that is limited to a single timestamp. Evolving clusters exist through several timestamps and interact with other spatial-temporal objects or clusters, having cluster relationships. When many evolving clusters exist for analysis, a graph can be used to represent cluster evolution. In this article, we propose a framework for graph-based cluster evolution representation and analysis. The framework represents cluster structure and relationships as well as provides a graph representation of cluster evolution for analysis. Evaluation is done in three case studies with spatial-temporal data about taxis that can identify important phenomena or trends in movements in a city for traffic improvement.

Objetivo: Avaliar a satisfação da equipe da unidade de terapia intensiva com o prontuário eletrônico do paciente e comparar a relevância do conceito de registro eletrônico de ordens médicas entre os profissionais de saúde da unidade de terapia intensiva. Métodos: Estudo transversal de levantamento para avaliar a satisfação da equipe da unidade de terapia intensiva com o prontuário eletrônico do paciente em uma unidade de terapia intensiva clínica e cirúrgica para pacientes adultos com 30 leitos, utilizando um questionário de autopreenchimento. As questões utilizadas para graduar os níveis de satisfação foram respondidas segundo uma escala numérica, que variava de 1 (baixo grau de satisfação) a 10 pontos (elevado grau de satisfação). Resultados: As pessoas que responderam ao questionário (n=250) eram, em sua maioria, do gênero feminino (66%) com idades entre 30 e 35 anos (69%). O grau geral de satisfação com o prontuário eletrônico do paciente foi de 5,74±2,14 pontos. O grau de satisfação foi mais baixo entre os médicos (n=42) do que entre enfermeiros, técnicos de enfermagem, terapeutas respiratórios, farmacêuticos clínicos e nutricionistas (4,62±1,79 em comparação com 5,97±2,14; p

How instructional sequences guide learning processes are often regarded as a neutral act. However, does designing instruction carry a politics? This investigation explores how instruction is made as a pedagogical object. The purpose is to explore the epistemological principles and conceptual framework that produce instruction's formalized pedagogical processes, each of which carries uncontested cultural and political aspects. Through textual analysis, the article considers theoretically and historically the problem of how instruction's design entangles people, power, and technology to operate as social technology, making up human kinds when instruction is designed as rule-bound programming--as an algorithm. Such algorithms engineer cultural action to engineer more harmonious human relations, embodying a greater political project that closes a technocultural lag, ameliorating human deficiencies while producing social exclusion and inequality.

Most of the northeastern region of Brazil (NEB) has a maize production system based on family farming, with no technological advances and totally dependent on the natural rainfall regime, which is concentrated in 4 to 5 months in most parts of the region. This means that the productivity of this crop is low in the NEB. In the northern mesoregions of the NEB, rainfall is concentrated between January and June, in the east of the NEB from April to September, and in the west of the NEB from October to March. The growing season takes place during these semesters. With this in mind, our objective was to develop a model based on canonical correlation analysis (CCA) to predict corn production in the mesoregions of the NEB between 1981 and 2010, using accumulated precipitation per semester as the predictor variable and predicting the observed production in kg/ha. Our results showed that the CCA model presented higher correlations between observed and simulated production than that obtained simply from the direct relationship between accumulated rainfall and production. The other two metrics used, RMSE and NRMSE, showed that, on average, in most mesoregions, the simulation error was around 200 kg/ha, but the accuracy was predominantly moderate, around 29% in most mesoregions, with values below 20% in six mesoregions, indicative of better model accuracy, and above 50% in two mesoregions, indicative of low accuracy. In addition, we investigated how the different combinations between two modes of climate variability with a direct influence on precipitation in the NEB impacted production in these 30 years, with the combination of El Niño and a positive Atlantic dipole being the most damaging to harvests, while years when La Niña and a negative Atlantic dipole acted together were the most favorable. Despite the satisfactory results and the practical applicability of the model developed, it should be noted that the use of only one predictor, rainfall, is a limiting factor for better model simulations since other meteorological variables and non-climatic factors have a significant impact on crops. However, the simplicity of the model and the promising results could help agricultural managers make decisions in all the states that make up the NEB.

Abstract Introduction Tralokinumab and dupilumab are biological agents licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients who are candidates for systemic treatment. However, no head-to-head studies of their efficacy have been conducted. This study indirectly compared the efficacy of tralokinumab and dupilumab, both in combination with topical corticosteroids (TCS), at week 32. Methods An unanchored matching-adjusted indirect comparison was conducted using individual patient data (IPD) from the ECZTRA 3 tralokinumab trial and aggregate data from the LIBERTY AD CHRONOS dupilumab trial. IPD were selected by applying inclusion criteria from LIBERTY AD CHRONOS and weighting to match summary baseline characteristics—age, sex, race, body mass index, disease duration, Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and SCORing Atopic Dermatitis index—of patients treated with dupilumab. Week 32 outcomes of interest were 50%, 75% or 90% improvements in EASI (EASI-50, EASI-75 and EASI-90), IGA scores of 0 or 1 (IGA 0/1), ≥ 4-point improvement in worst daily pruritus numerical rating scale (NRS) score, and mean improvements in DLQI and the Patient Oriented Eczema Measure (POEM). Results After matching, tralokinumab and dupilumab, both in combination with TCS, showed similar efficacy across clinical response endpoints at week 32 (IGA 0/1, tralokinumab 49.9% vs dupilumab 39.3%; EASI-50, 78.9% vs 77.5%; EASI-75, 71.5% vs 71.9%; EASI-90, 53.3% vs 56.2%). The mean change from baseline in DLQI was statistically significantly larger in the matched tralokinumab plus TCS population than in the dupilumab plus TCS arm (− 12.1 vs − 10.4, p = 0.005). Changes in POEM and worst daily pruritus NRS were similar in the two groups. Conclusion The results of this analysis demonstrate that, in combination with TCS, tralokinumab and dupilumab have similar efficacy in the treatment of moderate-to-severe AD at 32 weeks of therapy.

Novels that make the Booker prize shortlist often get overlooked in the TLS's Books of the Year feature. This year, however, Percival Everett's reimagining of Huckleberry Finn, James, received more [...]

Contemplating his likely end, Vladimir Putin's gadfly opponent Alexei Navalny joked that his memoir, Patriot (reviewed by Wendy Slater), was bound to be a bestseller--'The book's author has been murdered [...]

Asked why he liked horror films, or terror films as he preferred to call them, Kingsley Amis wrote: 'like Mark Twain on a dissimilar occasion, I have an answer to [...]

The popular story of the glory that was Greece begins at the monumental Lion Gate of the Bronze Age citadel of Mycenae, attributed to the work of giant Cyclopes by [...]

Sylvia Plath once said that 'nothing stinks like a pile of unpublished writing'. Ted Hughes curated two editions of her prose in 1977 and 1979, but admitted that his selections [...]

'Does Britain have a national literature?', asks Tim Parks in his first Afterthoughts column. Once upon a time the Italians drove nothing but Italian cars, owned Italian refrigerators, ate and [...]

James Baldwin declared that "the great problem" was "how to be--in the best sense of that kaleidoscopic word--a man". Ralf Webb's study of literary masculinity in mid-century America, Strange Relations, [...]

The Victorians astound us with their energy. The most famous Victorian of them all, after the queen herself, William Gladstone chopped down trees for exercise. With equal vigour he kept [...]

Moral panic over the habits of the young will always be with us. 'Reefer madness' in the 1930s was followed by the 'posture panic' over slouching American teenagers in the [...]

The most common and destructive form of conflict is civil war', writes Brian Holden Reid in his review of the latest edition of The New Makers of Modern Strategy, for [...]

Is Joe Biden fit to serve a second term as president of the United States? After a faltering performance in his first debate with Donald Trump last month, many of [...]

In the musical My Fair Lady, Henry Higgins, an archetypal male intellectual bully, complains: 'Why can't a woman be more like a man?' The anthropologist and primatologist Sarah Blaffer Hrdy's [...]

Some writers have peculiar ideas about getting away from it all. One of Mary Beard's choices for our Summer Books feature is brave, even masochistic. The TLS's Classics Editor thinks [...]

Sigmund Freud gets his turn on the couch in this week's TLS. Frank Tallis's Mortal Secrets, reviewed by George Prochnik, asks intriguing questions of psychoanalysis's founding father that bear on [...]

Abstract Introduction Bacterial meningitis in infants is an infrequent but life-threatening condition. Empiric therapy should begin as soon as meningitis is thought likely. Consequently, the causative microorganisms may not always be detected using culturing techniques, as cerebrospinal fluid (CSF) cultures are influenced by antibiotics. Nucleic acid amplification tests, such as polymerase chain reaction (PCR) (multiplex panels), may overcome this limitation but require a priori knowledge of the likely pathogen present within the sample. With this in mind, we investigated to what extent a culture-free, broad-range 16S rRNA gene next-generation sequencing (NGS) platform (MYcrobiota) could add to the microbiological diagnosis of meningitis. Methods Retrospective cohort study at level III neonatal intensive care unit. Included were all infants with suspected meningitis admitted between 10 November 2017 and 31 December 2020. A comparison was made of the bacterial pathogen detection rate between MYcrobiota and conventional bacterial culture. Results In a 3-year period, 37 CSF samples (diagnostic and follow-up) from 35 infants with proven or possible meningitis were available for MYcrobiota testing. MYcrobiota detected the presence of bacterial pathogens in 11 samples (30%), in contrast with the conventional CSF culture, which detected bacteria in 2 of 36 samples (5.6%). Conclusion Addition of 16S rRNA sequencing to conventional culturing greatly improved the identification of the aetiology of bacterial meningitis compared to culturing of CSF samples alone.

Trypanosomatid parasites undergo developmental regulation to adapt to the different environments encountered during their life cycle. In Trypanosoma brucei, a genome wide selectional screen previously identified a regulator of the protein family ESAG9, which is highly expressed in stumpy forms, a morphologically distinct bloodstream stage adapted for tsetse transmission. This regulator, TbREG9.1, has an orthologue in Trypanosoma congolense, despite the absence of a stumpy morphotype in that parasite species, which is an important cause of livestock trypanosomosis. RNAi mediated gene silencing of TcREG9.1 in Trypanosoma congolense caused a loss of attachment of the parasites to a surface substrate in vitro, a key feature of the biology of these parasites that is distinct from T. brucei. This detachment was phenocopied by treatment of the parasites with a phosphodiesterase inhibitor, which also promotes detachment in the insect trypanosomatid Crithidia fasciculata. RNAseq analysis revealed that TcREG9.1 silencing caused the upregulation of mRNAs for several classes of surface molecules, including transferrin receptor-like molecules, immunoreactive proteins in experimental bovine infections, and molecules related to those associated with stumpy development in T. brucei. Depletion of TcREG9.1 in vivo also generated an enhanced level of parasites in the blood circulation consistent with reduced parasite attachment to the microvasculature. The morphological progression to insect forms of the parasite was also perturbed. We propose a model whereby TcREG9.1 acts as a regulator of attachment and development, with detached parasites being adapted for transmission.

ABSTRACT BACKGROUND: Achalasia is an esophageal motility disorder, with clinical presentation of dysphagia and regurgitation. This is a chronic condition with no cure. Current treatment options aim to reduce lower esophageal sphincter tone by pharmacological, endoscopic or surgical means, with the aim of improving patients’ symptoms. Peroral endoscopic myotomy (POEM) is an alternative endoscopic surgery to Heller cardiomyotomy, in which the procedure is performed orally, by endoscopy, offering efficacy comparable to surgical myotomy, with relative ease and minimal invasion, without external incisions. AIMS: To study the safety of POEM by analyzing its results, adverse events and perioperative complications and the main ways to overcome them, in addition to evaluating the effectiveness of the procedure and the short-term postoperative quality of life. METHODS: A qualitative and quantitative, observational and cross-sectional study that analyzed patients who underwent the POEM in a reference center, from December 2016 to December 2022, maintaining the technical standard of pre-, peri- and postoperative protocol. RESULTS: A total of 94 patients were included in the study, and only three had postoperative complications. The average early postoperative Eckardt score was 0.93 and the late 1.40, with a mean improvement of 7.1 in early results and 6.63 in late results (p

Abstract Background This work describes the first genome-wide analysis of the transcriptional landscape of the pig. A new porcine Affymetrix expression array was designed in order to provide comprehensive coverage of the known pig transcriptome. The new array was used to generate a genome-wide expression atlas of pig tissues derived from 62 tissue/cell types. These data were subjected to network correlation analysis and clustering. Results The analysis presented here provides a detailed functional clustering of the pig transcriptome where transcripts are grouped according to their expression pattern, so one can infer the function of an uncharacterized gene from the company it keeps and the locations in which it is expressed. We describe the overall transcriptional signatures present in the tissue atlas, where possible assigning those signatures to specific cell populations or pathways. In particular, we discuss the expression signatures associated with the gastrointestinal tract, an organ that was sampled at 15 sites along its length and whose biology in the pig is similar to human. We identify sets of genes that define specialized cellular compartments and region-specific digestive functions. Finally, we performed a network analysis of the transcription factors expressed in the gastrointestinal tract and demonstrate how they sub-divide into functional groups that may control cellular gastrointestinal development. Conclusions As an important livestock animal with a physiology that is more similar than mouse to man, we provide a major new resource for understanding gene expression with respect to the known physiology of mammalian tissues and cells. The data and analyses are available on the websites http://biogps.org and http://www.macrophages.com/pig-atlas.

Abstract Background Mutualistic interactions are wide-spread but the mechanisms underlying their evolutionary stability and ecological dynamics remain poorly understood. Cultivation mutualisms in which hosts consume symbionts occur in phylogenetically diverse groups, but often have symbiont monocultures for each host. This is consistent with the prediction that symbionts should avoid coexistence with other strains so that host services continue to benefit relatives, but it is less clear whether hosts should always favor monocultures and what mechanisms they might have to manipulate symbiont diversity. Few mutualisms have been studied in sufficient genetic detail to address these issues, so we decided to characterize symbiont diversity in the complex mutualism between multiple root aphid species and Lasius flavus ants. After showing elsewhere that three of these aphid species have low dispersal and mostly if not exclusively asexual reproduction, we here investigate aphid diversity within and between ant nest mounds. Results The three focal species (Geoica utricularia, Forda marginata and Tetraneura ulmi) had considerable clonal diversity at the population level. Yet more than half of the ant mounds contained just a single aphid species, a significantly higher percentage than expected from a random distribution. Over 60% of these single-species mounds had a single aphid clone, and clones tended to persist across subsequent years. Whenever multiple species/clones co-occurred in the same mound, they were spatially separated with more than 95% of the aphid chambers containing individuals of a single clone. Conclusions L. flavus “husbandry” is characterized by low aphid “livestock” diversity per colony, especially at the nest-chamber level, but it lacks the exclusive monocultures known from other cultivation mutualisms. The ants appear to eat most of the early instar aphids, so that adult aphids are unlikely to face limited phloem resources and scramble competition with other aphids. We suggest that such culling of carbohydrate-providing symbionts for protein ingestion may maintain maximal host yield per aphid while also benefitting the domesticated aphids as long as their clone-mates reproduce successfully. The cost-benefit logic of this type of polyculture husbandry has striking analogies with human farming practices based on slaughtering young animals for meat to maximize milk-production by a carefully regulated adult livestock population.

Abstract Background Salmonella enterica serovar Enteritidis (S. Enteritidis) has caused major epidemics of gastrointestinal infection in many different countries. In this study we investigate genome divergence and pathogenic potential in S. Enteritidis isolated before, during and after an epidemic in Uruguay. Results 266 S. Enteritidis isolates were genotyped using RAPD-PCR and a selection were subjected to PFGE analysis. From these, 29 isolates spanning different periods, genetic profiles and sources of isolation were assayed for their ability to infect human epithelial cells and subjected to comparative genomic hybridization using a Salmonella pan-array and the sequenced strain S. Enteritidis PT4 P125109 as reference. Six other isolates from distant countries were included as external comparators. Two hundred and thirty three chromosomal genes as well as the virulence plasmid were found as variable among S. Enteritidis isolates. Ten out of the 16 chromosomal regions that varied between different isolates correspond to phage-like regions. The 2 oldest pre-epidemic isolates lack phage SE20 and harbour other phage encoded genes that are absent in the sequenced strain. Besides variation in prophage, we found variation in genes involved in metabolism and bacterial fitness. Five epidemic strains lack the complete Salmonella virulence plasmid. Significantly, strains with indistinguishable genetic patterns still showed major differences in their ability to infect epithelial cells, indicating that the approach used was insufficient to detect the genetic basis of this differential behaviour. Conclusion The recent epidemic of S. Enteritidis infection in Uruguay has been driven by the introduction of closely related strains of phage type 4 lineage. Our results confirm previous reports demonstrating a high degree of genetic homogeneity among S. Enteritidis isolates. However, 10 of the regions of variability described here are for the first time reported as being variable in S. Enteritidis. In particular, the oldest pre-epidemic isolates carry phage-associated genetic regions not previously reported in S. Enteritidis. Overall, our results support the view that phages play a crucial role in the generation of genetic diversity in S. Enteritidis and that phage SE20 may be a key marker for the emergence of particular isolates capable of causing epidemics.

Abstract Background Trypanosomes undergo extensive developmental changes during their complex life cycle. Crucial among these is the transition between slender and stumpy bloodstream forms and, thereafter, the differentiation from stumpy to tsetse-midgut procyclic forms. These developmental events are highly regulated, temporally reproducible and accompanied by expression changes mediated almost exclusively at the post-transcriptional level. Results In this study we have examined, by whole-genome microarray analysis, the mRNA abundance of genes in slender and stumpy forms of T.brucei AnTat1.1 cells, and also during their synchronous differentiation to procyclic forms. In total, five biological replicates representing the differentiation of matched parasite populations derived from five individual mouse infections were assayed, with RNAs being derived at key biological time points during the time course of their synchronous differentiation to procyclic forms. Importantly, the biological context of these mRNA profiles was established by assaying the coincident cellular events in each population (surface antigen exchange, morphological restructuring, cell cycle re-entry), thereby linking the observed gene expression changes to the well-established framework of trypanosome differentiation. Conclusion Using stringent statistical analysis and validation of the derived profiles against experimentally-predicted gene expression and phenotypic changes, we have established the profile of regulated gene expression during these important life-cycle transitions. The highly synchronous nature of differentiation between stumpy and procyclic forms also means that these studies of mRNA profiles are directly relevant to the changes in mRNA abundance within individual cells during this well-characterised developmental transition.

Abstract Background Gene copy number variation (CNV) is responsible for several important phenotypes of the malaria parasite Plasmodium falciparum, including drug resistance, loss of infected erythrocyte cytoadherence and alteration of receptor usage for erythrocyte invasion. Despite the known effects of CNV, little is known about its extent throughout the genome. Results We performed a whole-genome survey of CNV genes in P. falciparum using comparative genome hybridisation of a diverse set of 16 laboratory culture-adapted isolates to a custom designed high density Affymetrix GeneChip array. Overall, 186 genes showed hybridisation signals consistent with deletion or amplification in one or more isolate. There is a strong association of CNV with gene length, genomic location, and low orthology to genes in other Plasmodium species. Sub-telomeric regions of all chromosomes are strongly associated with CNV genes independent from members of previously described multigene families. However, ~40% of CNV genes were located in more central regions of the chromosomes. Among the previously undescribed CNV genes, several that are of potential phenotypic relevance are identified. Conclusion CNV represents a major form of genetic variation within the P. falciparum genome; the distribution of gene features indicates the involvement of highly non-random mutational and selective processes. Additional studies should be directed at examining CNV in natural parasite populations to extend conclusions to clinical settings.

Abstract Background Genetic mapping is a powerful method to identify mutations that cause drug resistance and other phenotypic changes in the human malaria parasite Plasmodium falciparum. For efficient mapping of a target gene, it is often necessary to genotype a large number of polymorphic markers. Currently, a community effort is underway to collect single nucleotide polymorphisms (SNP) from the parasite genome. Here we evaluate polymorphism detection accuracy of a high-density 'tiling' microarray with 2.56 million probes by comparing single feature polymorphisms (SFP) calls from the microarray with known SNP among parasite isolates. Results We found that probe GC content, SNP position in a probe, probe coverage, and signal ratio cutoff values were important factors for accurate detection of SFP in the parasite genome. We established a set of SFP calling parameters that could predict mSFP (SFP called by multiple overlapping probes) with high accuracy (≥ 94%) and identified 121,087 mSFP genome-wide from five parasite isolates including 40,354 unique mSFP (excluding those from multi-gene families) and ~18,000 new mSFP, producing a genetic map with an average of one unique mSFP per 570 bp. Genomic copy number variation (CNV) among the parasites was also cataloged and compared. Conclusion A large number of mSFP were discovered from the P. falciparum genome using a high-density microarray, most of which were in clusters of highly polymorphic genes at chromosome ends. Our method for accurate mSFP detection and the mSFP identified will greatly facilitate large-scale studies of genome variation in the P. falciparum parasite and provide useful resources for mapping important parasite traits.

Abstract Background Phagocytosis plays a major role in the defense of higher organisms against microbial infection and provides also the basis for antigen processing in the immune response. Cells of the model organism Dictyostelium are professional phagocytes that exploit phagocytosis of bacteria as the preferred way to ingest food, besides killing pathogens. We have investigated Dictyostelium differential gene expression during phagocytosis of non-pathogenic bacteria, using DNA microarrays, in order to identify molecular functions and novel genes involved in phagocytosis. Results The gene expression profiles of cells incubated for a brief time with bacteria were compared with cells either incubated in axenic medium or growing on bacteria. Transcriptional changes during exponential growth in axenic medium or on bacteria were also compared. We recognized 443 and 59 genes that are differentially regulated by phagocytosis or by the different growth conditions (growth on bacteria vs. axenic medium), respectively, and 102 genes regulated by both processes. Roughly one third of the genes are up-regulated compared to macropinocytosis and axenic growth. Functional annotation of differentially regulated genes with different tools revealed that phagocytosis induces profound changes in carbohydrate, aminoacid and lipid metabolism, and in cytoskeletal components. Genes regulating translation and mitochondrial biogenesis are mostly up-regulated. Genes involved in sterol biosynthesis are selectively up-regulated, suggesting a shift in membrane lipid composition linked to phagocytosis. Very few changes were detected in genes required for vesicle fission/fusion, indicating that the intracellular traffic machinery is mostly in common between phagocytosis and macropinocytosis. A few putative receptors, including GPCR family 3 proteins, scaffolding and adhesion proteins, components of signal transduction and transcription factors have been identified, which could be part of a signalling complex regulating phagocytosis and adaptational downstream responses. Conclusion The results highlight differences between phagocytosis and macropinocytosis, and provide the basis for targeted functional analysis of new candidate genes and for comparison studies with transcriptomes during infection with pathogenic bacteria.