A noncanonical function of cGAMP in inflammasome priming and activation

Recognition of pathogen-associated molecular patterns and danger-associated molecular patterns by host cells is an important step in innate immune activation. The DNA sensor cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) binds to DNA and produces cGAMP, which in turn binds to stimulator of interferon genes (STI N G) to activate IFN-I. Here we show that cGAMP has a noncanonical function in inflammasome activation in human and mouse cells. Inflammasome activation requires two signals, both of which are activated by cGAMP. cGAMP alone enhances expression of inflammasome components through IFN-I, providing the priming signal. Additionally, when combined with a priming signal, cGAMP activates the inflammasome through an AIM2, NLRP3, ASC, and caspase-1 dependent process. These two cGAMP-mediated functions, priming and activation, have differential requirements for STI N G. Temporally, cGAMP induction of IFN-I precedes inflammasome activation, which then occurs when IFN-I is waning. In mice, cGAS/cGAMP amplify both inflammasome and IFN-I to control murine cytomegalovirus. Thus, cGAMP activates the inflammasome in addition to IFN-I, and activation of both is needed to control infection by a DNA virus

Human Resource Flexibility as a Mediating Variable Between High Performance Work Systems and Performance

Much of the human resource management literature has demonstrated the impact of high performance work systems (HPWS) on organizational performance. A new generation of studies is emerging in this literature that recommends the inclusion of mediating variables between HPWS and organizational performance. The increasing rate of dynamism in competitive environments suggests that measures of employee adaptability should be included as a mechanism that may explain the relevance of HPWS to firm competitiveness. On a sample of 226 Spanish firms, the study’s results confirm that HPWS influences performance through its impact on the firm’s human resource (HR) flexibility

A review of literature on the use of clickers in the business and management discipline

YesClassroom response systems (clickers), in their various forms, are widely used across disciplines, demonstrating effectiveness across a range of different educational settings. However, only a few literature reviews on this technology have been undertaken in general, and no review has yet been performed on this topic in the business and management context. Realising the existing research gap, this article reviews 33 clicker-related studies from the business and management discipline that are largely focused on student perceptions and outcomes. The purpose of this paper is to provide a critical and balanced review of articles from the business and management discipline on various themes such as learner's engagement, performance, learning, participation, satisfaction, feedback, attendance, enjoyability, motivation, and interactivity, to name a few. The review also provides a brief account of lessons learned from the literature published in other disciplines and recommendations provided by studies from the business and management discipline

Implications of serial measurements of natriuretic peptides in heart failure: insights from BIOSTAT‐CHF

No abstract available

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Field control of cassava mosaic in Coast Province, Kenya

Meeting: International Society for Tropical Root Crops Symposium, 4th, 1-7 Aug. 1976, Cali, COIn IDL-133

The use of implementation intentions and the decision balance sheet in promoting exercise behaviour

Although increasing exercise and fitness has often been associated with positive health outcomes, infrequent exercise participation has remained a problem. Since two distinct motivational and volitional phases to goal pursuit have been proposed (Heckhausen, 1991; Gollwitzer, 1993), a combined motivational (decision balance sheet, DBS) and volitional (implementation intentions) intervention was predicted to be more effective in increasing exercise behaviour than a control or either strategy alone. A total of 86 students were randomly assigned to one of the four conditions, and were all asked to try to exercise two more times a week than they currently did, over a four week period. Their fitness levels were measured through fitness tests conducted pre and post-intervention. A priori orthogonal contrasts indicated that the experimental strategies produced a greater increase in exercise frequency and total time spent exercising per week and accordingly showed greater fitness improvements than the control group. Moreover, the volitional groups taken together produced greater increase in time spent exercising and a marginally greater improvement in frequency than the DBS alone. The combined intervention led to improvements in fitness and marginal increases in frequency over the implementation intention alone group. It is proposed that for the combined group the DBS may have aided recall of the implementation intention or increased commitment to it, as remembering and then acting on the plan, in the stated place and time, mediated the implementation intention-behaviour relationship. The combined intervention produced the greatest fitness improvements, indicating that this strategy can lead to important health benefits