Treatment outcomes of patients with Cutibacterium acnes-positive cultures during total joint replacement revision surgery: a minimum 2-year follow-up

INTRODUCTION Periprosthetic joint infection (PJI) is a devastating complication following total joint replacement (TJR). Cutibacterium acnes (C. acnes) is a low virulent skin commensal, commonly found during TJR revision surgery for "aseptic" causes. The purpose of the present study was to report the treatment outcomes of patients with C. acnes contamination or infection in the presence of a TJR treated with a revision surgery ± implant exchange ± prolonged (≥ 8 weeks) postoperative antibiotics. METHODS Medical records of patients with at least one positive C. acnes culture in intraoperative tissue samples or sonication fluid from a TJR revision surgery between January 2005 and December 2014 were retrospectively evaluated. The primary endpoint was infection eradication according to Delphi criteria. The diagnostic accuracy of preoperative TJR aspiration regarding the diagnosis of C. acnes PJI was also investigated. RESULTS A total of 52 TJR (28 shoulders, 17 hips, 7 knees) in 52 patients (35 males, 17 females) with an average age of 63 ± 11 (33-86) years were included. At an average follow-up of 67 ± 33 (24-127) months, the infection eradication of C. acnes PJI was 97% regardless of the surgical treatment or administration of prolonged postoperative antibiotics. The incidence of unsuspected C. acnes PJI was 28.8%. The sensitivity and specificity of preoperative joint aspiration in detecting C. acnes PJI were 59% and 88%, whereas the PPV and NNV were 83% and 67%, respectively. CONCLUSION Infection eradication of C. acnes PJI was very high at a minimum follow-up of 24 months, suggesting that C. acnes PJI could be adequately treated with a combination of revision surgery and prolonged postoperative antibiotics. The preoperative diagnosis of C. acnes PJI might be challenging with more than one-quarter of patients presenting without suspicion of C. acnes PJI. The appropriate treatment of patients with a single positive culture remains still unclear. A negative TJR aspiration should not rule out a C. acnes PJI, especially in the presence of clinical correlates of infection. LEVEL OF EVIDENCE Retrospective case-control study, Level III. IRB APPROVAL Kantonale Ethikkommission Zürich, BASEC Nr.:2017-00567

Evaluating Scalable Distributed Erlang for Scalability and Reliability

Large scale servers with hundreds of hosts and tens of thousands of cores are becoming common. To exploit these platforms software must be both scalable and reliable, and distributed actor languages like Erlang are a proven technology in this area. While distributed Erlang conceptually supports the engineering of large scale reliable systems, in practice it has some scalability limits that force developers to depart from the standard language mechanisms at scale. In earlier work we have explored these scalability limitations, and addressed them by providing a Scalable Distributed (SD) Erlang library that partitions the network of Erlang Virtual Machines (VMs) into scalable groups (s_groups). This paper presents the first systematic evaluation of SD Erlang s_groups and associated tools, and how they can be used. We present a comprehensive evaluation of the scalability and reliability of SD Erlang using three typical benchmarks and a case study. We demonstrate that s_groups improve the scalability of reliable and unreliable Erlang applications on up to 256 hosts (6,144 cores). We show that SD Erlang preserves the class-leading distributed Erlang reliability model, but scales far better than the standard model. We present a novel, systematic, and tool-supported approach for refactoring distributed Erlang applications into SD Erlang. We outline the new and improved monitoring, debugging and deployment tools for large scale SD Erlang applications. We demonstrate the scaling characteristics of key tools on systems comprising up to 10 K Erlang VMs

The METCRAX II Field Experiment: A Study of Downslope Windstorm-Type Flows in Arizona\u2019s Meteor Crater

The second Meteor Crater Experiment (METCRAX II) was conducted in October 2013 at Arizona\u2019s Meteor Crater. The experiment was designed to investigate nighttime downslope windstorm 12type flows that form regularly above the inner southwest sidewall of the 1.2-km diameter crater as a southwesterly mesoscale katabatic flow cascades over the crater rim. The objective of METCRAX II is to determine the causes of these strong, intermittent, and turbulent inflows that bring warm-air intrusions into the southwest part of the crater. This article provides an overview of the scientific goals of the experiment; summarizes the measurements, the crater topography, and the synoptic meteorology of the study period; and presents initial analysis results

Scaling Reliably: Improving the Scalability of the Erlang Distributed Actor Platform

Distributed actor languages are an effective means of constructing scalable reliable systems, and the Erlang programming language has a well-established and influential model. While the Erlang model conceptually provides reliable scalability, it has some inherent scalability limits and these force developers to depart from the model at scale. This article establishes the scalability limits of Erlang systems and reports the work of the EU RELEASE project to improve the scalability and understandability of the Erlang reliable distributed actor model. We systematically study the scalability limits of Erlang and then address the issues at the virtual machine, language, and tool levels. More specifically: (1) We have evolved the Erlang virtual machine so that it can work effectively in large-scale single-host multicore and NUMA architectures. We have made important changes and architectural improvements to the widely used Erlang/OTP release. (2) We have designed and implemented Scalable Distributed (SD) Erlang libraries to address language-level scalability issues and provided and validated a set of semantics for the new language constructs. (3) To make large Erlang systems easier to deploy, monitor, and debug, we have developed and made open source releases of five complementary tools, some specific to SD Erlang. Throughout the article we use two case studies to investigate the capabilities of our new technologies and tools: a distributed hash table based Orbit calculation and Ant Colony Optimisation (ACO). Chaos Monkey experiments show that two versions of ACO survive random process failure and hence that SD Erlang preserves the Erlang reliability model. While we report measurements on a range of NUMA and cluster architectures, the key scalability experiments are conducted on the Athos cluster with 256 hosts (6,144 cores). Even for programs with no global recovery data to maintain, SD Erlang partitions the network to reduce network traffic and hence improves performance of the Orbit and ACO benchmarks above 80 hosts. ACO measurements show that maintaining global recovery data dramatically limits scalability; however, scalability is recovered by partitioning the recovery data. We exceed the established scalability limits of distributed Erlang, and do not reach the limits of SD Erlang for these benchmarks at this scal

A Prediction Model to Prioritize Individuals for a SARS-CoV-2 Test Built from National Symptom Surveys

Background: The gold standard for COVID-19 diagnosis is detection of viral RNA through PCR. Due to global limitations in testing capacity, effective prioritization of individuals for testing is essential. Methods: We devised a model estimating the probability of an individual to test positive for COVID-19 based on answers to 9 simple questions that have been associated with SARS-CoV-2 infection. Our model was devised from a subsample of a national symptom survey that was answered over 2 million times in Israel in its first 2 months and a targeted survey distributed to all residents of several cities in Israel. Overall, 43,752 adults were included, from which 498 self-reported as being COVID-19 positive. Findings: Our model was validated on a held-out set of individuals from Israel where it achieved an auROC of 0.737 (CI: 0.712–0.759) and auPR of 0.144 (CI: 0.119–0.177) and demonstrated its applicability outside of Israel in an independently collected symptom survey dataset from the US, UK, and Sweden. Our analyses revealed interactions between several symptoms and age, suggesting variation in the clinical manifestation of the disease in different age groups. Conclusions: Our tool can be used online and without exposure to suspected patients, thus suggesting worldwide utility in combating COVID-19 by better directing the limited testing resources through prioritization of individuals for testing, thereby increasing the rate at which positive individuals can be identified. Moreover, individuals at high risk for a positive test result can be isolated prior to testing. Funding: E.S. is supported by the Crown Human Genome Center, Larson Charitable Foundation New Scientist Fund, Else Kroener Fresenius Foundation, White Rose International Foundation, Ben B. and Joyce E. Eisenberg Foundation, Nissenbaum Family, Marcos Pinheiro de Andrade and Vanessa Buchheim, Lady Michelle Michels, and Aliza Moussaieff and grants funded by the Minerva foundation with funding from the Federal German Ministry for Education and Research and by the European Research Council and the Israel Science Foundation. H.R. is supported by the Israeli Council for Higher Education (CHE) via the Weizmann Data Science Research Center and by a research grant from Madame Olga Klein – Astrachan

Ultrasensitivity of the Bacillus subtilis sporulation decision

Starving Bacillus subtilis cells execute a gene expression program resulting in the formation of stress-resistant spores. Sporulation master regulator, Spo0A, is activated by a phosphorelay and controls the expression of a multitude of genes, including the forespore- specific sigma factor σF and the mother cell-specific sigma factor σE. Identification of the system-level mechanism of the sporulation decision is hindered by a lack of direct control over Spo0A activity. This limitation can be overcome by using a synthetic system in which Spo0A activation is controlled by inducing expression of phosphorelay kinase KinA. This induction results in a switch-like increase in the number of sporulating cells at a threshold of KinA. Using a combination of mathematical modeling and single-cell microscopy, we investigate the origin and physiological significance of this ultrasensitive threshold. The results indicate that the phosphorelay is unable to achieve a sufficiently fast and ultrasensitive response via its positive feedback architecture, suggesting that the sporulation decision is made downstream. In contrast, activation of σF in the forespore and of σE in the mother cell compartments occurs via a cascade of coherent feed-forward loops, and thereby can produce fast and ultrasensitive responses as a result of KinA induction. Unlike σF activation, σE activation in the mother cell compartment only occurs above the KinA threshold, resulting in completion of sporulation. Thus, ultrasensitive σE activation explains the KinA threshold for sporulation induction. We therefore infer that under uncertain conditions, cells initiate sporulation but postpone making the sporulation decision to average stochastic fluctuations and to achieve a robust population response

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad