Discharge home from critical care: safety assessment in a resource constrained system

Background High bed occupancy rates have delayed patient discharges from UK critical care units, especially in acute medical hospitals. As a result, more patients are discharged home directly from critical care (DH). Methods In this observational, retrospective study, we quantify the trends in DH from 2013 to 2018, and assess readmission rates and outcome in this group when compared to patients discharged from a ward, from 2014 to 2016. Results DH rates, as a proportion of critical care admissions, increased every year (2.47% in 2013 to 19.36% in 2018). In 2014–16, the most common admission diagnoses in DH patients were diabetic ketoacidosis (DKA; 35%), drug overdose (12%), seizures (8%) and respiratory failure (8%). DH patients were younger and had shorter critical care stay. Readmission rates in DH patients were comparable to the rest of the hospital. Patients with DKA and seizures were more likely to be readmitted. Conclusions Our data suggest that direct home discharge from critical care is increasingly common but safe in selected patient groups

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe

Functional genomics of severe sepsis and septic shock

Sepsis is the systemic inflammatory response to an infection. Severe sepsis with multi organ failure is one of the commonest causes of admission to intensive care units, and is associated with poor early and late outcomes. The pathophysiology of sepsis is complex, and poorly understood. This is reflected in the limited and contentious treatment options for sepsis.Genetic factors have been shown to be associated with the risk of and subsequent outcomes from infection. However, clear associations with bacterial sepsis are rare, and even when associations are present their functional effects are often unknown.Gene expression signatures in sepsis are investigated in this project using serial samples obtained from patients admitted to intensive care units with community-acquired pneumonia or faecal peritonitis.The evolving gene expression signatures that define the response to sepsis were identified with large changes seen in genes coding for ribosomal proteins RPS4Y1 and RPS26P54. The differences in the sepsis response between the two diagnostic classes were examined. The gene expression predictors of mortality in sepsis were determined and include genes from the class II MHC HLA-DRB4, HLA-DRB5 and the T cell differentiation protein MAL. The effects of important covariates on gene expression were investigated and their impact on survival related expression determined. The findings were confirmed in a validation cohort. A novel clustering of samples representing distinct inflammatory patterns in a clinically homogeneous population of sepsis patients was identified and related to differences in clinical behaviour. The biological relevance of the differentially expressed genes was ascertained by identifying enriched gene sets.The gene expression changes in sepsis were examined in the context of related clinically relevant immune phenomena: the sterile systemic inflammatory response in patients undergoing elective cardiac surgery and the phenomenon of endotoxin tolerance in PBMCs derived from healthy volunteers.The results highlight the complexities of clinical sepsis and identify hypotheses for future investigations.This thesis is not currently available in ORA

Genetic determinants of HSP70 gene expression following heat shock

The regulation of heat shock protein expression is of significant physiological and pathophysiological significance. Here we show that genetic diversity is an important determinant of heat shock protein 70 expression involving local, likely cis-acting, polymorphisms. We define DNA sequence variation for the highly homologous HSPA1A and HSPA1B genes in the major histocompatibility complex on chromosome 6p21 and establish quantitative and specific assays for determining transcript abundance. We show for lymphoblastoid cell lines established from individuals of African ancestry that following heat shock, expression of HSPA1B is associated with rs400547 (P 3.88 × 10(-8)) and linked single nucleotide polymorphisms (SNPs) located 62-93 kb telomeric to HSPA1B. This association was found to explain 31 and 29% of the variance in HSPA1B expression following heat shock or in resting cells, respectively. The associated SNPs show marked variation in minor allele frequency among populations, being more common in individuals of African ancestry, and are located in a region showing population-specific haplotypic block structure. The work illustrates how analysis of a heritable induced expression phenotype can be highly informative in defining functionally important genetic variation

Generic Characters of Penaeus, Fenneropenaeus, Melicertus, Marsupenaeus and Funchalia

Rostrum armed with dorsal and ventral teeth; pleurobranchia on somite 14 glaborous (smooth) and polished; 3 short well-defined circatrices on sixth abdominal somite; adrostral sulcus and carina short falling distinctly short or extending to about level of epigastric tooth; gastrofrontal carina absent, hepatic carina prominent; thelycum closed, petasma with ventral costa long reaching distal margin of lateral lobe (Pérez Farfante, 1997)

Effectiveness of bedtime levothyroxine intake as compared to morning levothyroxine intake in children

Background: The study was conducted to assess the effectiveness of bedtime Levothyroxine administration as compared to morning Levothyroxine administration in thyroid profile, renal and lipid parameters, anthropometric and vital parameters in children attending endocrinology OPD at a tertiary care center in Southern India.Methods: It is an open label randomized control study. 154 children who were diagnosed to have hypothyroidism, on levothyroxine supplementation and in euthyroid state at the start of study were included. Children were randomly allocated into two groups. One group received levothyroxine in early morning (1hr before food) and another group received levothyroxine in bedtime (2hrs after food) up to 3 months. At baseline, 6 weeks and 12weeks, thyroid profile, renal and lipid parameters and vital parameters were measured during follow up. Anthropometric parameters were measured at baseline and 12 weeks.Results: In 6th week analysis, mean TSH level of morning group (2.35±0.38 mIU/L) and bedtime group (2.42±0.40 mIU/L) did not show any statistical difference (p=0.8). In 12th week analysis mean TSH level of morning group (2.18±0.34 mIU/L) and bedtime group (1.90±0.33 mIU/L) did not show any statistical difference (p=0.24). At 6th week analysis, mean free T4 level of bedtime group (1.45±0.08 ng/dl) is higher than morning group (1.33±0.2 ng/dl). This difference is statistically significant (p= 0.03). At 12 th week analysis, mean free T4 level of bedtime group (1.65±0.04 ng/dl) is higher than morning group (1.31±0.06 ng/dl). This difference is statistically significant (p&lt;0.00001). A 12weeks, the difference in mean serum cholesterol of morning group (152.79±4.59 mg/dl) and bedtime group (143.58±3.059 mg/dl) is statistically significant (p=0.001). At 6 and12 weeks, other parameters like serum triglycerides, HDL cholesterol, renal parameters, anthropometry, vital parameters of morning group and bedtime group did not show any statistical significant difference.Conclusions: There is a significant improvement in free T4 level when levothyroxine was taken at bedtime. The efficacy of bedtime regimen of levothyroxine is quite comparable to the efficacy of morning regimen. There is considerable decrease in serum cholesterol level when levothyroxine was taken at bedtime. Bedtime regimen may result in good compliance in school going children. Parents should be allowed to choose either morning or bedtime regimen depending on their convenience. </jats:p

A Bio-inspired and Low-power 2D Machine Vision with Adaptive Machine Learning and Forgetting

Abstract Natural intelligence has many dimensions, and in animals, learning about the environment and making behavioral changes are some of its manifestations. In primates vision plays a critical role in learning. The underlying biological neural networks contain specialized neurons and synapses which not only sense and process the visual stimuli but also learns and adapts, with remarkable energy efficiency. Forgetting also plays an active role in learning. Mimicking the adaptive neurobiological mechanisms for seeing, learning, and forgetting can, therefore, accelerate the development of artificial intelligence (AI) and bridge the massive energy gap that exists between AI and biological intelligence. Here we demonstrate a bio-inspired machine vision based on large area grown monolayer 2D phototransistor array integrated with analog, non-volatile, and programmable memory gate-stack that not only enables direct learning, and unsupervised relearning from the visual stimuli but also offers learning adaptability under photopic (bright-light), scotopic (low-light), as well as noisy illumination conditions at miniscule energy expenditure. In short, our “all-in-one” hardware vision platform combines “sensing”, “computing” and “storage” not only to overcome the von Neumann bottleneck of conventional complementary metal oxide semiconductor (CMOS) technology but also to eliminate the need for peripheral circuits and sensors.</jats:p