Intraoperative contrast-enhanced sonography of bowel blood flow: preliminary experience

The potential to predict, and therefore avoid, anastomotic failure has eluded generations of colon and rectal surgeons to date. A reliable, reproducible method of assessing bowel blood flow therefore would be of enormous potential clinical relevance. To our knowledge, intraoperative contrast-enhanced sonography of the bowel has not been performed previously. We present our study assessing the feasibility of using contrast-enhanced sonography to study bowel perfusion intraoperatively. We studied 8 patients (4 male and 4 female) with an age range of 52 to 81 years who underwent colorectal surgery (right hemicolectomies, n = 3; Hartmann procedure, n = 1; anterior resections, n = 2; and bowel resections with ileocolic anastomoses, n = 2). A 5-mL bolus of a sulfur hexafluoride contrast agent solution was injected before and after vascular ligation with simultaneous noncompression ultrasound scanning directly over the large bowel. The patients were followed clinically to assess for leaks. Contrast-enhanced sonographic time-intensity curves were generated for the time to peak and maximum amplitude. Moderate interobserver agreement was shown for the time to peak (κ = 0.50) and maximum amplitude (κ = 0.42), and moderate intraobserver agreement was shown for the time to peak (κ= 0.53) and maximum amplitude (κ= 0.53). No significant differences were shown between the time to peak (P = .28) and maximum amplitude (P = .49) for the preligation and postligation scans. To our knowledge, intraoperative contrast-enhanced sonography of the bowel has not been performed previously. We have shown the technique to be feasible with good intraobserver and interobserver agreement. Further work is ongoing to optimize the technique and assess its use in predicting anastomotic breakdown.published_or_final_versio

The skin you're in: Design of experiments optimization of lipid nanoparticle self-amplifying RNA formulations in human skin explants

Messenger RNA (mRNA) is a promising tool for biotherapeutics, and self-amplifying mRNA (saRNA) is particularly advantageous as it results in abundant protein expression and production is easily scalable. While mRNA therapeutics have been shown to be highly effective in small animals, the outcomes do not scale linearly when these formulations are translated to dose-escalation studies in humans. Here, we utilize a Design of Experiments (DoE) approach to optimize the formulation of saRNA lipid nanoparticles in human skin explants. We first observed that luciferase expression from saRNA peaked after 11 days in human skin. Using DoE inputs of complexing lipid identity, lipid nanoparticle dose, lipid concentration, particle concentration, and ratio of zwitterionic to cationic lipids, we optimized the saRNA-induced luciferase expression in skin explants. Lipid identity and lipid concentration were found to be significant parameters in the DoE model, and the optimized formulation resulted in ~7-fold increase in luciferase expression relative to initial DOTAP formulation. Using flow cytometry, we observed that optimized formulations delivered the saRNA to ~2% of the resident cells in the human skin explants. Although immune cells make up only 7% of the total population of cells in skin, immune cells were found to express ~50% of the RNA. This study demonstrates the powerful combination of using a DoE approach paired with clinically relevant human skin explants to optimize nucleic acid formulations. We expect that this system will be useful for optimizing both formulation and molecular designs of clinically translational nucleic acid vaccines and therapeutics

Edible crabs “Go West”: migrations and incubation cycle of Cancer pagurus revealed by electronic tags

Crustaceans are key components of marine ecosystems which, like other exploited marine taxa, show seasonable patterns of distribution and activity, with consequences for their availability to capture by targeted fisheries. Despite concerns over the sustainability of crab fisheries worldwide, difficulties in observing crabs’ behaviour over their annual cycles, and the timings and durations of reproduction, remain poorly understood. From the release of 128 mature female edible crabs tagged with electronic data storage tags (DSTs), we demonstrate predominantly westward migration in the English Channel. Eastern Channel crabs migrated further than western Channel crabs, while crabs released outside the Channel showed little or no migration. Individual migrations were punctuated by a 7-month hiatus, when crabs remained stationary, coincident with the main period of crab spawning and egg incubation. Incubation commenced earlier in the west, from late October onwards, and brooding locations, determined using tidal geolocation, occurred throughout the species range. With an overall return rate of 34%, our results demonstrate that previous reluctance to tag crabs with relatively high-cost DSTs for fear of loss following moulting is unfounded, and that DSTs can generate precise information with regards life-history metrics that would be unachievable using other conventional means

Does observability affect prosociality?

The observation of behaviour is a key theoretical parameter underlying a number of models of prosociality. However, the empirical findings showing the effect of observability on prosociality are mixed. In this meta-analysis, we explore the boundary conditions that may account for this variability, by exploring key theoretical and methodological moderators of this link. We identified 117 papers yielding 134 study level effects (Total N = 788, 164) and found a small but statistically significant, positive association between observability and prosociality (r = .141, 95% CI = .106, .175). Moderator analysis showed that observability produced stronger effects on prosociality (1) in the presence of passive observers (i.e., people whose role was to only observe participants) vs perceptions of being watched, (2) when participants decisions were consequential (vs non-consequential), (3) when the studies were performed in the laboratory (as opposed to in the field/online), (4) when studies used repeated measures (instead of single games) and (5) when studies involved social dilemmas (instead of bargaining games). These effects show the conditions under which observability effects on prosociality will be maximally observed. We describe the theoretical and practical significance of 14 these results

Hippocrates revisited? Old ideals and new realities

Individual genomics has arrived, personal decisions to make use of it are a new reality. What are the implications for the patient–physician relationship? In this article we address three factors that call the traditional concept of confidentiality into question. First, the illusion of absolute data safety, as shown by medical informatics. Second, data sharing as a standard practice in genomics research. Comprehensive data sets are widely accessible. Third, genotyping has become a service that is directly available to consumers. The availability and accessibility of personal health data strongly suggest that the roles in the clinical encounter need to be remodeled. The old ideal of physicians as keepers of confidential information is outstripped by the reality of individuals who decide themselves about the way of using their data

Methods for estimating between-study variance and overall effect in meta-analysis of odds-ratios

In random-effects meta-analysis the between-study variance (τ 2) has a key role in assessing heterogeneity of study-level estimates and combining them to estimate an overall effect. For odds ratios the most common methods suffer from bias in estimating τ 2 and the overall effect and produce confidence intervals with below-nominal coverage. An improved approximation to the moments of Cochran's Q statistic, suggested by Kulinskaya and Dollinger (KD), yields new point and interval estimators of τ 2 and of the overall log-odds-ratio. Another, simpler approach (SSW) uses weights based only on study-level sample sizes to estimate the overall effect. In extensive simulations we compare our proposed estimators with established point and interval estimators for τ 2 and point and interval estimators for the overall log-odds-ratio (including the Hartung-Knapp-Sidik-Jonkman interval). Additional simulations included three estimators based on generalized linear mixed models and the Mantel-Haenszel fixed-effect estimator. Results of our simulations show that no single point estimator of τ 2 can be recommended exclusively, but Mandel-Paule and KD provide better choices for small and large numbers of studies, respectively. The KD estimator provides reliable coverage of τ 2. Inverse-variance-weighted estimators of the overall effect are substantially biased, as are the Mantel-Haenszel odds ratio and the estimators from the generalized linear mixed models. The SSW estimator of the overall effect and a related confidence interval provide reliable point and interval estimation of the overall log-odds-ratio