Effect of a machine learning-based severe sepsis prediction algorithm on patient survival and hospital length of stay: a randomised clinical trial.

IntroductionSeveral methods have been developed to electronically monitor patients for severe sepsis, but few provide predictive capabilities to enable early intervention; furthermore, no severe sepsis prediction systems have been previously validated in a randomised study. We tested the use of a machine learning-based severe sepsis prediction system for reductions in average length of stay and in-hospital mortality rate.MethodsWe conducted a randomised controlled clinical trial at two medical-surgical intensive care units at the University of California, San Francisco Medical Center, evaluating the primary outcome of average length of stay, and secondary outcome of in-hospital mortality rate from December 2016 to February 2017. Adult patients (18+) admitted to participating units were eligible for this factorial, open-label study. Enrolled patients were assigned to a trial arm by a random allocation sequence. In the control group, only the current severe sepsis detector was used; in the experimental group, the machine learning algorithm (MLA) was also used. On receiving an alert, the care team evaluated the patient and initiated the severe sepsis bundle, if appropriate. Although participants were randomly assigned to a trial arm, group assignments were automatically revealed for any patients who received MLA alerts.ResultsOutcomes from 75 patients in the control and 67 patients in the experimental group were analysed. Average length of stay decreased from 13.0 days in the control to 10.3 days in the experimental group (p=0.042). In-hospital mortality decreased by 12.4 percentage points when using the MLA (p=0.018), a relative reduction of 58.0%. No adverse events were reported during this trial.ConclusionThe MLA was associated with improved patient outcomes. This is the first randomised controlled trial of a sepsis surveillance system to demonstrate statistically significant differences in length of stay and in-hospital mortality.Trial registrationNCT03015454

X-56A Structural Dynamics Ground Testing Overview and Lessons Learned

The X-56A Multi-Utility Technology Testbed (MUTT) is a subscale, fixed-wing aircraft designed for high-risk aeroelastic flight demonstration and research. Structural dynamics ground testing for model validation was especially important for this vehicle because the structural model was directly used in the development of a flight control system with active flutter suppression capabilities. Structural dynamics ground tests of the X-56A MUTT with coupled rigid-body and structural modes provided a unique set of challenges. An overview of the ground vibration test (GVT) and moment of inertia (MOI) test setup and execution is presented. The series of GVTs included the wing by itself attached to a strongback and complete vehicle at two mass conditions: empty and full fuel. Two boundary conditions for the complete-vehicle test were studied: on landing gear and suspended free-free. Pitch MOI tests were performed using a compound pendulum method and repeated with two different pendulum lengths for independent verification. The original soft-support test configuration for the GVT used multiple bungees, resulting in unforeseen coupling interactions between the soft-support bungees and the vehicle structural modes. To resolve this problem, the soft-support test setup underwent multiple iterations. The various GVT configurations and boundary-condition modifications are highlighted and explained. Lessons learned are captured for future consideration when performing structural dynamics testing with similar vehicles

Inter-individual variation in DNA repair capacity: A need for multi-pathway functional assays to promote translational DNA repair research

Why does a constant barrage of DNA damage lead to disease in some individuals, while others remain healthy? This article surveys current work addressing the implications of inter-individual variation in DNA repair capacity for human health, and discusses the status of DNA repair assays as potential clinical tools for personalized prevention or treatment of disease. In particular, we highlight research showing that there are significant inter-individual variations in DNA repair capacity (DRC), and that measuring these differences provides important biological insight regarding disease susceptibility and cancer treatment efficacy. We emphasize work showing that it is important to measure repair capacity in multiple pathways, and that functional assays are required to fill a gap left by genome wide association studies, global gene expression and proteomics. Finally, we discuss research that will be needed to overcome barriers that currently limit the use of DNA repair assays in the clinic

Rare-gas optics-free stable extreme-ultraviolet photon spectrometer for solar system studies

We have developed a prototype spectrometer for space applications that require long-term stable EUV photon flux measurements. In this recently developed spectrometer, the energy spectrum of the incoming photons is transformed directly into an electron energy spectrum by taking advantage of the photoelectric effect in one of several rare gases at low pressures. Using an electron energy spectrometer operating at a few electron volts, and followed by an electron multiplying detector, pulses due to individual electrons are counted. The overall efficiency of this process is essentially independent of gain drifts in the signal path, and the secular degradation of optical components that is often a problem in other techniques is avoided

Ordering intermetallic alloys by ion irradiation: a way to tailor magnetic media

Combining He ion irradiation and thermal mobility below 600K, we both trigger and control the transformation from chemical disorder to order in thin films of an intermetallic ferromagnet (FePd). Kinetic Monte Carlo simulations show how the initial directional short range order determines order propagation. Magnetic ordering perpendicular to the film plane was achieved, promoting the initially weak magnetic anisotropy to the highest values known for FePd films. This post-growth treatment should find applications in ultrahigh density magnetic recording.Comment: 7 pages, 3 Figure

Alkylation-induced colon tumorigenesis in mice deficient in the Mgmt and Msh6 proteins

O[superscript 6]-methylguanine DNA methyltransferase (MGMT) suppresses mutations and cell death that result from alkylation damage. MGMT expression is lost by epigenetic silencing in a variety of human cancers including nearly half of sporadic colorectal cancers, suggesting that this loss maybe causal. Using mice with a targeted disruption of the Mgmt gene, we tested whether Mgmt protects against azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF), against AOM and dextran sulfate sodium (DSS)-induced colorectal adenomas and against spontaneous intestinal adenomas in Apc[superscript Min] mice. We also examined the genetic interaction of the Mgmt null gene with a DNA mismatch repair null gene, namely Msh6. Both Mgmt and Msh6 independently suppress AOM-induced ACF, and combination of the two mutant alleles had a multiplicative effect. This synergism can be explained entirely by the suppression of alkylation-induced apoptosis when Msh6 is absent. In addition, following AOM+DSS treatment Mgmt protected against adenoma formation to the same degree as it protected against AOM-induced ACF formation. Finally, Mgmt deficiency did not affect spontaneous intestinal adenoma development in Apc[superscript Min/+] mice, suggesting that Mgmt suppresses intestinal cancer associated with exogenous alkylating agents, and that endogenous alkylation does not contribute to the rapid tumor development seen in Apc[superscript Min/+] mice.National Institutes of Health (U.S.) (grant ES02109)National Institutes of Health (U.S.) (grant CA75576)American Cancer Society (Research Professor

Remotely controlled mirror of variable geometry for small angle x-ray diffraction with synchrotron radiation

A total-reflecting mirror of 120-cm length was designed and built to focus synchrotron radiation emanating from the electron-positron storage ring at the Stanford Linear Accelerator Center (SPEAR). The reflecting surface is of unpolished float glass. The bending and tilt mechanism allows very fine control of the curvature and selectability of the critical angle for wavelengths ranging from 0.5 to 3.0 Å. Elliptical curvature is used to minimize aberrations. The mirror is placed asymmetrically onto the ellipse so as to achieve a tenfold demagnification of the source. The bending mechanism reduces nonelastic deformation (flow) and minimizes strains and stresses in the glass despite its length. Special design features assure stability of the focused image. The mirror reduces the intensity of shorter wavelength harmonics by a factor of approximately 100

Signal Processing

Contains reports on three research projects.Joint Services Electronics Programs (U.S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-0300U. S. Coast Guard (Contract DOT-CG -13446-A)M.I.T. Lincoln Laboratory Purchase Order CC-57

The interaction between ALKBH2 DNA repair enzyme and PCNA is direct, mediated by the hydrophobic pocket of PCNA and perturbed in naturally-occurring ALKBH2 variants

Human AlkB homolog 2 (ALKBH2) is a DNA repair enzyme that catalyzes the direct reversal of DNA methylation damage through oxidative demethylation. While ALKBH2 colocalizes with proliferating cell nuclear antigen (PCNA) in DNA replication foci, it remains unknown whether these two proteins alone form a complex or require additional components for interaction. Here, we demonstrate that ALKBH2 can directly interact with PCNA independent from other cellular factors, and we identify the hydrophobic pocket of PCNA as the key domain mediating this interaction. Moreover, we find that PCNA association with ALKBH2 increases significantly during DNA replication, suggesting that ALKBH2 forms a cell-cycle dependent complex with PCNA. Intriguingly, we show that an ALKBH2 germline variant, as well as a variant found in cancer, display altered interaction with PCNA. Our studies reveal the ALKBH2 binding interface of PCNA and indicate that both germline and somatic ALKBH2 variants could have cellular effects on ALKBH2 function in DNA repair.Swiss National Science Foundation (31003A_133100/1)National Institutes of Health (U.S.) (grant CA055042)National Institutes of Health (U.S.) (grant ES002109)Universität Züric