Overcoming Operational Challenges to Ebola Case Investigation in Sierra Leone.

The Ebola virus disease (EVD) epidemic that hit West Africa in 2013 was the worst outbreak of EVD in recorded history. While much has been published regarding the international and national-level EVD responses, there is a dearth of literature on district-level coordination and operational structures, successes, and failures. This article seeks to understand how the EVD response unfolded at the district level, namely the challenges to operationalizing EVD surveillance over the course of the outbreak in Port Loko and Kambia districts of Sierra Leone. We present here GOAL Global's understanding of the fundamental challenges to case investigation operations during the EVD response, including environmental and infrastructural, sociocultural, and political and organizational challenges, with insight complemented by a survey of 42 case investigators. Major challenges included deficiencies in transportation and communication resources, low morale and fatigue among case investigators, mismanagement of data, mistrust among communities, and leadership challenges. Without addressing these operational challenges, technical surveillance solutions are difficult to implement and hold limited relevance, due to the poor quality and quantity of data being collected. The low prioritization of operational needs came at a high cost. To mediate this, GOAL addressed these operational challenges by acquiring critical transportation and communication resources to facilitate case investigation, including vehicles, boats, fuel, drivers, phones, and closed user groups; addressing fatigue and low morale by hiring more case investigators, making timely payments, arranging for time off, and providing meals and personal protective equipment; improving data tracking efforts through standard operating procedures, training, and mentorship to build higher-quality case histories and make it easier to access information; strengthening trust in communities by ensuring familiarity and consistency of case investigators; and improving operational leadership challenges through meetings and regular coordination, establishing an active surveillance strategy in Port Loko, and conducting an after-action review. Resolving or addressing these challenges was of primary importance, and requisite for the implementation of technical epidemiological complements to EVD case investigation

FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy.

Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-β-catenin, aldehyde dehydrogenase activities, intrinsic platinum resistance, and tumorsphere formation are here associated with spontaneous gains in Kras, Myc and FAK (KMF) genes in a new aggressive murine model of ovarian cancer. Adhesion-independent FAK signaling sustained KMF and human tumorsphere proliferation as well as resistance to cisplatin cytotoxicity. Platinum-resistant tumorspheres can acquire a dependence on FAK for growth. Accordingly, increased FAK tyrosine phosphorylation was observed within HGSOC patient tumors surviving neo-adjuvant chemotherapy. Combining a FAK inhibitor with platinum overcame chemoresistance and triggered cell apoptosis. FAK transcriptomic analyses across knockout and reconstituted cells identified 135 targets, elevated in HGSOC, that were regulated by FAK activity and β-catenin including Myc, pluripotency and DNA repair genes. These studies reveal an oncogenic FAK signaling role supporting chemoresistance

Coherent radar reflections from an electron-beam induced particle cascade

Experiment T-576 ran at SLAC in 2018, in development of a new radar-based detection scheme for ultra-high energy neutrinos. In this experiment, the electron beam (N∼109e− at ∼10 GeV) was directed into a plastic target to simulate a 1019 eV neutrino-induced shower in ice. This shower was interrogated with radio frequency (RF) radiation, in an attempt to measure a radar-like reflection from the ionization produced in the target during the particle shower. This technique could be employed to detect the rare interactions of ultra-high-energy neutrinos in dense material, such as polar ice sheets, extending the extant energy range of detected neutrinos up to EeV and beyond. In this proceeding, we detail the experiment and present results from the analysis and the observation of a signal consistent with a radar signal

Reduced Risk of Reoperations With Modern Deep Brain Stimulator Systems: Big Data Analysis From a United States Claims Database

Objective: There have been significant improvements in the design and manufacturing of deep brain stimulation (DBS) systems, but no study has considered the impact of modern systems on complications. We sought to compare the relative occurrence of reoperations after de novo implantation of modern and traditional DBS systems in patients with Parkinson\u27s disease (PD) or essential tremor (ET) in the United States. Design: Retrospective, contemporaneous cohort study. Setting: Multicenter data from the United States Centers for Medicare and Medicaid Services administrative claims database between 2016 and 2018. Participants: This population-based sample consisted of 5,998 patients implanted with a DBS system, of which 3,869 patients had a de novo implant and primary diagnosis of PD or ET. Follow-up of 3 months was available for 3,810 patients, 12 months for 3,561 patients, and 24 months for 1,812 patients. Intervention: Implantation of a modern directional (MD) or traditional omnidirectional (TO) DBS system. Primary and Secondary Outcome Measures: We hypothesized that MD systems would impact complication rates. Reoperation rate was the primary outcome. Associated diagnoses, patient characteristics, and implanting center details served as covariates. Kaplan-Meier analysis was performed to compare rates of event-free survival and regression models were used to determine covariate influences. Results: Patients implanted with modern systems were 36% less likely to require reoperation, largely due to differences in acute reoperations and intracranial lead reoperations. Risk reduction persisted while accounting for practice differences and implanting center experience. Risk reduction was more pronounced in patients with PD. Conclusions: In the first multicenter analysis of device-related complications including modern DBS systems, we found that modern systems are associated with lower reoperation rates. This risk profile should be carefully considered during device selection for patients undergoing DBS for PD or ET. Prospective studies are needed to further investigate underlying causes

Racial Disparities in Access to DBS: Results of a Real-World U.S. Claims Data Analysis

INTRODUCTION: Deep brain stimulation (DBS) is an effective and standard-of-care therapy for Parkinson\u27s Disease and other movement disorders when symptoms are inadequately controlled with conventional medications. It requires expert care for patient selection, surgical targeting, and therapy titration. Despite the known benefits, racial/ethnic disparities in access have been reported. Technological advancements with smartphone-enabled devices may influence racial disparities. Real-world evidence investigations can shed further light on barriers to access and demographic disparities for DBS patients. METHODS: A retrospective cross-sectional study was performed using Medicare claims linked with manufacturer patient data tracking to analyze 3,869 patients who received DBS. Patients were divided into two categories: traditional omnidirectional DBS systems with dedicated proprietary controllers ( traditional ; RESULTS: A significant disparity in DBS utilization was evident. White individuals comprised 91.4 and 89.9% of traditional and smartphone-enabled DBS groups, respectively. Non-White patients were significantly more likely to live closer to implanting facilities compared with White patients. CONCLUSION: There is great racial disparity in utilization of DBS therapy. Smartphone-enabled systems did not significantly impact racial disparities in receiving DBS. Minoritized patients were more likely to live closer to their implanting facility than White patients. Further research is warranted to identify barriers to access for minoritized patients to receive DBS. Technological advancements should consider the racial discrepancy of DBS utilization in future developments

Implications of ultra-high energy neutrino flux constraints for Lorentz-invariance violating cosmogenic neutrinos

We consider the implications of Lorentz-invariance violation (LIV) on cosmogenic neutrino observations, with particular focus on the constraints imposed on several well-developed models for ultra-high energy cosmogenic neutrino production by recent results from the Antarctic Impulsive Transient Antenna (ANITA) long-duration balloon payload, and Radio Ice Cherenkov Experiment (RICE) at the South Pole. Under a scenario proposed originally by Coleman and Glashow, each lepton family may attain maximum velocities that can exceed the speed of light, leading to energy-loss through several interaction channels during propagation. We show that future observations of cosmogenic neutrinos will provide by far the most stringent limit on LIV in the neutrino sector. We derive the implied level of LIV required to suppress observation of predicted fluxes from several mainstream cosmogenic neutrino models, and specifically those recently constrained by the ANITA and RICE experiments. We simulate via detailed Monte Carlo code the propagation of cosmogenic neutrino fluxes in the presence of LIV-induced energy losses. We show that this process produces several detectable effects in the resulting attenuated neutrino spectra, even at LIV-induced neutrino superluminality of (u_{\nu}-c)/c ~ 10^{-26}, about 13 orders of magnitude below current bounds.Comment: 6 pages, 4 figures; updates to introduction & references; To appear in PR

Observation of Ultra-high-energy Cosmic Rays with the ANITA Balloon-borne Radio Interferometer

We report the observation of sixteen cosmic ray events of mean energy of 1.5 x 10^{19} eV, via radio pulses originating from the interaction of the cosmic ray air shower with the Antarctic geomagnetic field, a process known as geosynchrotron emission. We present the first ultra-wideband, far-field measurements of the radio spectral density of geosynchrotron emission in the range from 300-1000 MHz. The emission is 100% linearly polarized in the plane perpendicular to the projected geomagnetic field. Fourteen of our observed events are seen to have a phase-inversion due to reflection of the radio beam off the ice surface, and two additional events are seen directly from above the horizon.Comment: 5 pages, 5 figures, new figure adde

Constraints on the Ultra-High Energy Neutrino Flux from Gamma-Ray Bursts from a Prototype Station of the Askaryan Radio Array

We report on a search for ultra-high-energy (UHE) neutrinos from gamma-ray bursts (GRBs) in the data set collected by the Testbed station of the Askaryan Radio Array (ARA) in 2011 and 2012. From 57 selected GRBs, we observed no events that survive our cuts, which is consistent with 0.12 expected background events. Using NeuCosmA as a numerical GRB reference emission model, we estimate upper limits on the prompt UHE GRB neutrino fluence and quasi-diffuse flux from $10^{7}$ to $10^{10}$ GeV. This is the first limit on the prompt UHE GRB neutrino quasi-diffuse flux above $10^{7}$ GeV.Comment: 14 pages, 8 figures, Published in Astroparticle Physics Journa

Observational Constraints on the Ultra-high Energy Cosmic Neutrino Flux from the Second Flight of the ANITA Experiment

The Antarctic Impulsive Transient Antenna (ANITA) completed its second long-duration balloon flight in January 2009, with 31 days aloft (28.5 live days) over Antarctica. ANITA searches for impulsive coherent radio Cherenkov emission from 200 to 1200 MHz, arising from the Askaryan charge excess in ultra-high energy neutrino-induced cascades within Antarctic ice. This flight included significant improvements over the first flight in the payload sensitivity, efficiency, and a flight trajectory over deeper ice. Analysis of in-flight calibration pulses from surface and sub-surface locations verifies the expected sensitivity. In a blind analysis, we find 2 surviving events on a background, mostly anthropogenic, of 0.97+-0.42 events. We set the strongest limit to date for 1-1000 EeV cosmic neutrinos, excluding several current cosmogenic neutrino models.Comment: 6 pages, 5 figures, submitted to Phys. Rev.