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

Towards an Intelligent Database System Founded on the SP Theory of Computing and Cognition

The SP theory of computing and cognition, described in previous publications, is an attractive model for intelligent databases because it provides a simple but versatile format for different kinds of knowledge, it has capabilities in artificial intelligence, and it can also function like established database models when that is required. This paper describes how the SP model can emulate other models used in database applications and compares the SP model with those other models. The artificial intelligence capabilities of the SP model are reviewed and its relationship with other artificial intelligence systems is described. Also considered are ways in which current prototypes may be translated into an 'industrial strength' working system

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

Using the Virtual Heart Model to Validate the Mode-Switch Pacemaker Operation

Artificial pacemakers are one of the most widely-used implantable devices today, with millions implanted worldwide. The main purpose of an artificial pacemaker is to treat bradycardia, or slow heart beats, by pacing the atrium and ventricles at a faster rate. While the basic functionality of the device is fairly simple, there are many documented cases of death and injury due to device malfunctions. The frequency of malfunctions due to firmware problems will only increase as the pacemaker operations become more complex in an attempt to expand the use of the device. One reason these malfunctions arise is that there is currently no methodology for formal validation and verification of medical device software, as there are in the safety-critical domains of avionics and industrial control automation. We have developed a timed-automata based Virtual Heart Model (VHM) to act as platform for medical device software validation and verification. Through a case study involving multiple arrhythmias, this investigation shows how the VHM can be used with closed-loop operation of a pacemaker to validate the necessity and functionality of the complex mode-switch pacemaker operation. We demonstrate the correct pacemaker operation, to switch from one rhythm management mode to another, in patients with supraventricular tachycardias

New Limits on the Ultra-high Energy Cosmic Neutrino Flux from the ANITA Experiment

We report initial results of the first flight of the Antarctic Impulsive Transient Antenna (ANITA-1) 2006-2007 Long Duration Balloon flight, which searched for evidence of a diffuse flux of cosmic neutrinos above energies of 3 EeV. ANITA-1 flew for 35 days looking for radio impulses due to the Askaryan effect in neutrino-induced electromagnetic showers within the Antarctic ice sheets. We report here on our initial analysis, which was performed as a blind search of the data. No neutrino candidates are seen, with no detected physics background. We set model-independent limits based on this result. Upper limits derived from our analysis rule out the highest cosmogenic neutrino models. In a background horizontal-polarization channel, we also detect six events consistent with radio impulses from ultra-high energy extensive air showers.Comment: 4 pages, 2 table

A policy for a common European intelligence system

[The European Union (EU) is severely lacking in terms of intelligence capabilities, as members have repeatedly noted in various resolutions over the last five years. Despite existing models for intelligence-sharing, like Europol and the Schengen Information System, the EU has failed to build a central intelligence function to serve its Common Foreign and Security Policy. Several events in the last year have accelerated the need for a common European intelligence system: The terrorists who launched the attacks on the United States on Sept. 11, 2001 had been operating within EU member countries for some time, yet EU members only realized this after the attacks had happened, when European intelligence agencies began sharing information with each other and the United States. If such intelligence-sharing had existed prior to the attacks, the terrorists' plan may have been thwarted. The EU also has found an increasing need for its members to share criminal intelligence on organized crime, money laundering and counterfeiting since the EU unveiled its common currency, the euro, on Jan. 1, 2002. But the most pressing need for a common intelligence function is one to guide the EU's military force, which is to be deployed next year. There is a saying that an army is blind without intelligence, and the EU must develop an intelligence function before any troops are sent abroad. But there are a few challenges to building an intelligence system: Britain's cozy relationship with the United States, which threatens Britain's ties to fellow ED members; concern from NATO and the U.S. that an ED intelligence agency would compete with their intelligence systems; and long-held bilateral intelligence-sharing agreements among ED members which could be jeopardized if EU members must share all intelligence with each other. Yet these can be overcome. I will show that a common intelligence system is feasible and affordable if the ED takes advantage of its existing resources and those of its members.

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.

Design and Initial Performance of the Askaryan Radio Array Prototype EeV Neutrino Detector at the South Pole

We report on studies of the viability and sensitivity of the Askaryan Radio Array (ARA), a new initiative to develop a Teraton-scale ultra-high energy neutrino detector in deep, radio-transparent ice near Amundsen-Scott station at the South Pole. An initial prototype ARA detector system was installed in January 2011, and has been operating continuously since then. We report on studies of the background radio noise levels, the radio clarity of the ice, and the estimated sensitivity of the planned ARA array given these results, based on the first five months of operation. Anthropogenic radio interference in the vicinity of the South Pole currently leads to a few-percent loss of data, but no overall effect on the background noise levels, which are dominated by the thermal noise floor of the cold polar ice, and galactic noise at lower frequencies. We have also successfully detected signals originating from a 2.5 km deep impulse generator at a distance of over 3 km from our prototype detector, confirming prior estimates of kilometer-scale attenuation lengths for cold polar ice. These are also the first such measurements for propagation over such large slant distances in ice. Based on these data, ARA-37, the 200 km^2 array now under construction, will achieve the highest sensitivity of any planned or existing neutrino detector in the 10^{16}-10^{19} eV energy range.Comment: 25 pages, 37 figures, this version with improved ice attenuation length analysis; for submission to Astroparticle Physic

Ultra-Relativistic Magnetic Monopole Search with the ANITA-II Balloon-borne Radio Interferometer

We have conducted a search for extended energy deposition trails left by ultra-relativistic magnetic monopoles interacting in Antarctic ice. The non-observation of any satisfactory candidates in the 31 days of accumulated ANITA-II flight data results in an upper limit on the diffuse flux of relativistic monopoles. We obtain a 90% C.L. limit of order 10^{-19}/(cm^2-s-sr) for values of Lorentz boost factor 10^{10}<gamma at the anticipated energy E=10^{16} GeV. This bound is stronger than all previously published experimental limits for this kinematic range.Comment: updated to version accepted by Phys. Rev.