Privacy-preserving model learning on a blockchain network-of-networks.

ObjectiveTo facilitate clinical/genomic/biomedical research, constructing generalizable predictive models using cross-institutional methods while protecting privacy is imperative. However, state-of-the-art methods assume a "flattened" topology, while real-world research networks may consist of "network-of-networks" which can imply practical issues including training on small data for rare diseases/conditions, prioritizing locally trained models, and maintaining models for each level of the hierarchy. In this study, we focus on developing a hierarchical approach to inherit the benefits of the privacy-preserving methods, retain the advantages of adopting blockchain, and address practical concerns on a research network-of-networks.Materials and methodsWe propose a framework to combine level-wise model learning, blockchain-based model dissemination, and a novel hierarchical consensus algorithm for model ensemble. We developed an example implementation HierarchicalChain (hierarchical privacy-preserving modeling on blockchain), evaluated it on 3 healthcare/genomic datasets, as well as compared its predictive correctness, learning iteration, and execution time with a state-of-the-art method designed for flattened network topology.ResultsHierarchicalChain improves the predictive correctness for small training datasets and provides comparable correctness results with the competing method with higher learning iteration and similar per-iteration execution time, inherits the benefits of the privacy-preserving learning and advantages of blockchain technology, and immutable records models for each level.DiscussionHierarchicalChain is independent of the core privacy-preserving learning method, as well as of the underlying blockchain platform. Further studies are warranted for various types of network topology, complex data, and privacy concerns.ConclusionWe demonstrated the potential of utilizing the information from the hierarchical network-of-networks topology to improve prediction

Comparison of Anesthesia for Dental/Oral Surgery by Office-based Dentist Anesthesiologists versus Operating Room-based Physician Anesthesiologists

Few studies have examined the practice characteristics of dentist anesthesiologists and compared them to other anesthesia providers. Using outcomes from the National Anesthesia Clinical Outcomes Registry and the Society for Ambulatory Anesthesia Clinical Outcomes Registry for dental/oral surgery procedures, we compared 7133 predominantly office-based anesthetics by dentist anesthesiologists to 106,420 predominantly operating room anesthetics performed by physician anesthesia providers. These encounters were contrasted with 34,191 previously published encounters from the practices of oral and maxillofacial surgeons. Children younger than 6 years received the greatest proportion of general anesthetic services rendered by both dentist anesthesiologists and hospital-based anesthesia providers. These general anesthesia services were primarily provided for complete dental rehabilitation for early childhood caries. Overall treatment time for complete dental rehabilitation in the office-based setting by dentist anesthesiologists was significantly shorter than comparable care provided in the hospital operating room and surgery centers. The anesthesia care provided by dentist anesthesiologists was found to be separate and distinct from anesthesia care provided by oral and maxillofacial surgeons, which was primarily administered to adults for very brief surgical procedures. Cases performed by dentist anesthesiologists and hospital-based anesthesia providers were for much younger patients and of significantly longer duration when compared with anesthesia administered by oral and maxillofacial surgeons. Despite the limited descriptive power of the current registries, office-based anesthesia rendered by dentist anesthesiologists is clearly a unique and efficient mode of anesthesia care for dentistry

Ultrasound-Guided Lateral Femoral Cutaneous Nerve Cryoneurolysis for Analgesia in Patients With Burns.

Autologous skin grafting from the thigh is frequently required for treatment of burns and is associated with intense pain at the donor site. Local anesthetic-based (LA) nerve blocks of the lateral femoral cutaneous nerve (LFCN) have been demonstrated to provide analgesia when the graft is taken from the lateral thigh. However, the duration of these single injection blocks has been reported to average only 9 hours, whereas the pain from the procedure lasts days or weeks. Continuous LA nerve blocks can also be used to provide analgesia during serial debridement of burns, although this requires placement of a perineural catheter which may increase infection risk in a population with an increased susceptibility to infection. Cryoneurolysis of the LFCN can potentially provide analgesia of the lateral thigh for skin graft harvesting or serial burn debridement that lasts far longer than conventional LA nerve blocks. Here, we present a series of three patients who received a combination of a LA nerve block and cryoneurolysis nerve block of the LFCN for analgesia of the lateral thigh. Two of these patients had the blocks placed before harvesting a split thickness skin graft. The third received the blocks for outpatient wound care of a burn to the lateral thigh. In all cases, the resulting analgesia lasted more than 1 week. A single cryoneurolysis block of the LFCN successfully provided extended duration analgesia of the lateral thigh for autologous skin graft donor site or wound care of a burn in three patients

Prediction of Agricultural Implement Hydraulic Power Requirements Using Controller Area Network Bus Data

One of the important challenges in agricultural machinery research is the ability to effectively determine power requirements of a given field operation. The Controller Area Network (CAN) Bus, also known as ISOBUS, has proven to be an effective digital tool for tractor and implement data collection. This study attempted to determine implement hydraulic power requirements using a combination of existing public tractor CAN messages and minimal added sensors. The sensor signals were published on the CAN bus for ease of simultaneous sensor signal and CAN message data collection. Based upon the available CAN messages, this study attempted to measure hydraulic flow rate distributed by a tractor’s directional control valve without the incorporation of a flowmeter. For instances when a valve received its requested flow rate by the operator, the valve’s flow rate was predicted as a function of the valve’s spool position. The resulting curve of best fit had a coefficient of determination of 0.9993 and a root-mean-square-error of 0.8805 Lmin-1 for the combination of multiple implement loads. When the valve became flow-limited, and the effective flow rate could no longer be determined by spool position, predicting the flow rate from a measured pressure drop across a minor loss in the system was investigated. From data collected on a flow-limited valve caused by reduced engine speed, a piece-wise line of best fit was found, predicting the flow rate based upon the pressure drop. Additional pressure sensors were used to determine the flow-state of the valve

Membrane Insertion for the Detection of Lipopolysaccharides: Exploring the Dynamics of Amphiphile-in-Lipid Assays

Shiga toxin-producing Escherichia coli is an important cause of foodborne illness, with cases attributable to beef, fresh produce and other sources. Many serotypes of the pathogen cause disease, and differentiating one serotype from another requires specific identification of the O antigen located on the lipopolysaccharide (LPS) molecule. The amphiphilic structure of LPS poses a challenge when using classical detection methods, which do not take into account its lipoglycan biochemistry. Typically, detection of LPS requires heat or chemical treatment of samples and relies on bioactivity assays for the conserved lipid A portion of the molecule. Our goal was to develop assays to facilitate the direct and discriminative detection of the entire LPS molecule and its O antigen in complex matrices using minimal sample processing. To perform serogroup identification of LPS, we used a method called membrane insertion on a waveguide biosensor, and tested three serogroups of LPS. The membrane insertion technique allows for the hydrophobic association of LPS with a lipid bilayer, where the exposed O antigen can be targeted for specific detection. Samples of beef lysate were spiked with LPS to perform O antigen specific detection of LPS from E. coli O157. To validate assay performance, we evaluated the biophysical interactions of LPS with lipid bilayers both in- and outside of a flow cell using fluorescence microscopy and fluorescently doped lipids. Our results indicate that membrane insertion allows for the qualitative and reliable identification of amphiphilic LPS in complex samples like beef homogenates. We also demonstrated that LPS-induced hole formation does not occur under the conditions of the membrane insertion assays. Together, these findings describe for the first time the serogroup-specific detection of amphiphilic LPS in complex samples using a membrane insertion assay, and highlight the importance of LPS molecular conformations in detection architectures

Suture-method versus Through-the-needle Catheters for Continuous Popliteal-sciatic Nerve Blocks: A Randomized Clinical Trial.

BACKGROUND:The basic perineural catheter design has changed minimally since inception, with the catheter introduced through or over a straight needle. The U.S. Food and Drug Administration recently cleared a novel perineural catheter design comprising a catheter attached to the back of a suture-shaped needle that is inserted, advanced along the arc of its curvature pulling the catheter past the target nerve, and then exited through the skin in a second location. The authors hypothesized that analgesia would be noninferior using the new versus traditional catheter design in the first two days after painful foot/ankle surgery with a primary outcome of average pain measured with the Numeric Rating Scale. METHODS:Subjects undergoing painful foot or ankle surgery with a continuous supraparaneural popliteal-sciatic nerve block 5 cm proximal to the bifurcation were randomized to either a suture-type or through-the-needle catheter and subsequent 3-day 0.2% ropivacaine infusion (basal 6 ml/h, bolus 4 ml, lockout 30 min). Subjects received daily follow-up for the first four days after surgery, including assessment for evidence of malfunction or dislodgement of the catheters. RESULTS:During the first two postoperative days the mean ± SD average pain scores were lower in subjects with the suture-catheter (n = 35) compared with the through-the-needle (n = 35) group (2.7 ± 2.4 vs. 3.4 ± 2.4) and found to be statistically noninferior (95% CI, -1.9 to 0.6; P < 0.001). No suture-style catheter was completely dislodged (0%), whereas the tips of three (9%) traditional catheters were found outside of the skin before purposeful removal on postoperative day 3 (P = 0.239). CONCLUSIONS:Suture-type perineural catheters provided noninferior analgesia compared with traditional catheters for continuous popliteal-sciatic blocks after painful foot and ankle surgery. The new catheter design appears to be a viable alternative to traditional designs used for the past seven decades

A Gravitationally Lensed Supernova with an Observable Two-Decade Time Delay

When the light from a distant object passes very near to a foreground galaxy or cluster, gravitational lensing can cause it to appear as multiple images on the sky. If the source is variable, it can be used to constrain the cosmic expansion rate and dark energy models. Achieving these cosmological goals requires many lensed transients with precise time delay measurements. Lensed supernovae (SN) are attractive for this purpose because they have relatively simple photometric behavior, with well-understood light curve shapes and colours $-$ in contrast to the stochastic variation of quasars. Here we report the discovery of a multiply-imaged supernova, AT2016jka ("SN Requiem"). It appeared in an evolved galaxy at $z=1.95$, gravitationally lensed by a foreground galaxy cluster. It is likely a Type Ia supernova $-$ the explosion of a low-mass stellar remnant, whose light curve can be used to measure cosmic distances. In archival Hubble Space Telescope imaging, three lensed images of the supernova are detected with relative time delays of $<$200 days. We predict a fourth image will appear close to the cluster core in the year 2037$\pm$2. Observation of the fourth image could provide a time delay precision of $\approx$7 days, $<1\%$ of the extraordinary 20 year baseline. The SN classification and the predicted reappearance time could be improved with further lens modelling and a comprehensive analysis of systematic uncertainties.Comment: Accepted for publication in a peer-reviewed journal. Main text = 6 pages, 3 figures, 1 table; Full document = 28 pages, 12 figures with Methods, Supplemental Info and references. v2: reformatted; minor corrections in S

A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants

Individuals with Lynch syndrome (LS), have an increased risk of developing cancer. Common genetic variants of telomerase reverse transcriptase (TERT) have been associated with a wide range of cancers, including colorectal cancer (CRC) in LS. We combined genotype data from 1881 LS patients, carrying pathogenic variants in MLH1, MSH2 or MSH6, for rs2075786 (G>A, intronic variant), 1207 LS patients for rs2736108 (C>T, upstream variant) and 1201 LS patients for rs7705526 (C>A, intronic variant). The risk of cancer was estimated by heterozygous/homozygous odds ratio (OR) with mixed-effects logistic regression to adjust for gene/gender/country of sample origin considering family identity. The AA genotype of SNP rs2075786 is associated with 85% higher odds at developing cancer compared to GG genotype in MSH2 pathogenic variant carriers (p = 0.0160). Kaplan-Meier analysis also shows an association for rs2075786; the AA allele for MSH2 variant carriers confers risk for earlier diagnosis of LS cancer (log-rank p = 0.0011). We report a polymorphism in TERT to be a possible modifier of disease risk in MSH2 pathogenic variant carriers. The rs2075786 SNP in TERT is associated with a differential risk of developing cancer for MSH2 pathogenic variant carriers. Use of this information has the potential to personalise screening protocols for LS patients

Type Ia Supernova Distances at z > 1.5 from the Hubble Space Telescope Multi-Cycle Treasury Programs: The Early Expansion Rate

We present an analysis of 15 Type Ia supernovae (SNe Ia) at redshift z > 1 (9 at 1.5 < z < 2.3) recently discovered in the CANDELS and CLASH Multi-Cycle Treasury programs using WFC3 on the Hubble Space Telescope. We combine these SNe Ia with a new compilation of 1050 SNe Ia, jointly calibrated and corrected for simulated survey biases to produce accurate distance measurements. We present unbiased constraints on the expansion rate at six redshifts in the range 0.07 < z < 1.5 based only on this combined SN Ia sample. The added leverage of our new sample at z > 1.5 leads to a factor of ~3 improvement in the determination of the expansion rate at z = 1.5, reducing its uncertainty to ~20%, a measurement of H(z=1.5)/H0=2.67 (+0.83,-0.52). We then demonstrate that these six measurements alone provide a nearly identical characterization of dark energy as the full SN sample, making them an efficient compression of the SN Ia data. The new sample of SNe Ia at z > 1 usefully distinguishes between alternative cosmological models and unmodeled evolution of the SN Ia distance indicators, placing empirical limits on the latter. Finally, employing a realistic simulation of a potential WFIRST SN survey observing strategy, we forecast optimistic future constraints on the expansion rate from SNe Ia.Comment: 14 pages, 5 figures, 7 tables; submitted to Ap