Group Testing Identification: Objective Functions, Implementation, and Multiplex Assays

Group testing is the process of combining items into groups to test for a binary characteristic. One of its most widely used applications is infectious disease testing. In this context, specimens (e.g., blood, urine) are amalgamated into groups and tested. For groups that test positive, there are many algorithmic retesting procedures available to identify positive individuals. The appeal of group testing is that the overall number of tests needed is significantly less than for individual testing when disease prevalence is small and an appropriate algorithm is chosen. Group testing has a number of applications beyond infectious disease testing, such as drug discovery, food contamination detection, and diagnosis of faulty network sensors. An important decision that needs to be made prior to implementation is the group sizes to use. In best practice, an objective function is minimized to determine the optimal set of group sizes, known as the optimal testing configuration (OTC). We examine several different objective functions and show that the OTCs and corresponding results (e.g., number of tests, accuracy) are largely the same for these functions when using standard group testing algorithms. Both estimating the probability of disease and identifying positive individuals are goals of group testing. We present the first general R functions for identification and make these available in the new binGroup2 package. We also include in this package estimation functions from the binGroup package by creating a unified framework for them. We developed a web-based Shiny application to assist laboratory personnel in determining how well a group testing algorithm is expected to perform before implementation. The app utilizes binGroup2 functions to calculate the expected number of tests and diagnostic accuracy measures for a wide variety of algorithms using one- and two-disease assays. The OTC can be found with the app as well. Most group testing research using one-disease assays makes the assumption of equal sensitivity and equal specificity values across all stages of testing. We present derivations of operating characteristics for group testing algorithms that allow the diagnostic test accuracy to differ across stages of testing. These resulting expressions are incorporated into the binGroup2 package. Adviser: Christopher R. Bilde

UNL Libraries Book Use by Broad Discipline (Social Sciences, Sciences, and Humanities): Circulations and Renewals: Books Acquired 2003/04 – 2007/08 via Approval Plan Selection, Librarian Firm Order, and ILL Patron-Driven Acquisition

On numerous occasions over the course of the UNL Libraries’ continuing discussions concerning the allocation of collections monies, the UNL Libraries’ liaison librarians have made a variety of assertions, arguments, and claims concerning their patrons and their patrons’ needs. For example, the humanities librarians have repeatedly staked a claim to the humanities’ being the “book” discipline and have made a variety of assertions concerning humanities patrons and humanities books that could be treated as testable hypothesis. For example: 1) Humanities patrons use books more than do other disciplines’ patrons; 2) Humanities patrons use more books than do other disciplines’ patrons; 3) Humanities books are used more than are other disciplines’ books; 4) Humanities books’ circulation is an inadequate and/or inaccurate measure of humanities’ patrons’ need for and/or use of their books because it does not account for in-house usage, for ILL requests for returnables, or for circulation renewals (Note: this last argument has been that humanities patrons use books for deeper scholarship and for longer periods, so some portion of their potential circulations will be transformed into and lost as renewals); 5) …and so forth. It would be, of course, impossible to provide a complete and comprehensive analysis of collections usage that would address every issue and objection, but the authors hope here to address a few of the above points somewhat. Unfortunately, we cannot address the points concerning humanities patrons using books more or using more books than do the patrons of the other disciplines. Not least because of privacy concerns, the UNL Libraries simply does not track their patrons in a way that would allow for those analyses. Likely, patrons’ revealed preferences in this area could only be approached somewhat obliquely via citation analysis. For similar reasons, we cannot address the point concerning in-house usage by patron affiliation without arranging for data to be collected through direct observation and demographic interviews. The point concerning ILL borrowing of returnables might be addressable in future as the Delivery/ILL department collects a tremendous amount of data, but that data is not available for analysis at the moment. The questions that we can somewhat address here involve the books themselves: 1) Was a greater percentage of any one discipline’s books circulated over the interval? Renewed? Did it matter who selected the book? 2) Did any one discipline’s books experience more circulations? More circulations-and-renewals? 3) Which variables, in future, might be useful for predictively modelling circulation and/or circulations-and-renewals? 4) Could early relative performance predict future performance

PRELIMINARY STUDY: INTERPRETATION OF BARBELL BACK SQUAT KINEMATICS USING PRINCIPAL COMPONENT ANALYSIS

The purpose of this study was to reduce the number of kinematic variables of the barbell back squat for easier interpretation by coaches and athletes. Young active adults (N=25) performed the back squat with an intensity of 60%. A total of 10 lower body and trunk measurements were considered for principal components analysis (PCA). Based on the PCA, two components were revealed. The primary component related range of motions (ROMs) in the ankle and knee joints with greater peak flexion angles of ankle, knee, and shank and thigh segments. A secondary component related hip ROMs and hip posterior displacement with greater hip and trunk segment peak flexion angles. Based on this analysis, coaches teaching the barbell back squat should consider two sources of movement variability, one above and one below the hip

THE EFFECTS OF WEIGHTLIFTING SHOES ON SQUAT KINEMATICS

Athletes may not always consider footwear when performing the barbell back squat during training. Several footwear companies have designed shoes claimed to enhance performance in weightlifting and powerlifting. The purpose of this study was to compare the kinematics of the barbell back squat wearing either running shoes (RS) or weightlifting shoes (WLS). Young, healthy active adult males (N=20) were filmed in the sagittal plane while performing barbell back squats for each shoe condition at an intensity of 60% of one repetition maximum (1RM). While a number of kinematic parameters were similar between conditions, the shank maintained a more vertical position and the bar and hip were displaced less when wearing WLS, suggesting a more erect trunk posture. WLS may make small changes that allow for a safer, more effective squat performance

NASA's Space Launch System: Unprecedented Payload Capabilities

As NASA turns 60 and plans to transition the International Space Station (ISS) and other low-Earth orbit (LEO) activities to commercial enterprises, the Agency's human exploration program turns its focus to deep space. With missions planned to send astronauts back to the Moon and to construct a lunar orbiting Gateway for surface access as well as science experiments and technology demonstrations, NASA requires a vehicle with capabilities for launching more mass and volume than is currently commercially available. To that end, NASA and its private sector partners are building the Space Launch System (SLS) super heavy-lift launch vehicle, which will send the new Orion crew capsule, eventually with a complement of four astronauts, to cislunar space for the first time since the Apollo Program in the 1960s and 1970s. NASA Kennedy Space Center's (KSC's) Exploration Ground Systems (EGS) Program has upgraded and refurbished ground and launch facilities to process, assemble and launch NASA's new deep space exploration system, which is managed by the Exploration Systems Development (ESD) organization in the Human Exploration and Operations Mission Directorate (HEOMD). Offering an unmatched combination of power, payload capacity and departure energy, the evolvable SLS features the world's most proven propulsion system: solid rocket boosters and RS-25 main engines with a modified Delta Cryogenic Second Stage (DCSS) cryogenic upper stage. The initial SLS configuration, Block 1, will deliver at least 26 metric tons (t) to trans-lunar injection (TLI). The second variant, Block 1B, will deliver at least 34 t to TLI in its crew configuration and at least 40 t to TLI in its cargo configuration. The Block 1 cargo vehicle will fly with an industry-standard 5 m fairing while the Block 1B cargo configuration will accommodate 8 m-diameter fairings in varying lengths. The Block 2 vehicle will incorporate upgraded boosters and possibly larger fairings for launching Mars-class payloads to deep space. Although designed to enable human exploration of deep space, the vehicle also provides game-changing benefits for large science payloads and even harnesses excess capacity to provide small satellites with access to deep space. Three flights of the Block 1 vehicle are now planned; the first vehicle, being built for a test flight known as Exploration Mission-1 (EM-1), is nearing completion at NASA and contractor sites across the United States. In fact, hardware for the second mission has also been built. This paper will provide an overview of the SLS vehicle, with a focus on its payload accommodations and the missions enabled by the unprecedented payload volume and departure energy of SLS. This paper also describes the status of the manufacturing and integration for first flight and beyond

NASA's Space Launch System: A New Opportunity for CubeSats

Designed for human exploration missions into deep space, NASA's Space Launch System (SLS) represents a new spaceflight infrastructure asset, enabling a wide variety of unique utilization opportunities. Together with the Orion crew vehicle and ground operations at NASA's Kennedy Space Center in Florida, SLS is a foundational capability for NASA's Journey to Mars. From the beginning of the SLS flight program, utilization of the vehicle will also include launching secondary payloads, including CubeSats, to deep-space destinations. Currently, SLS is making rapid progress toward readiness for its first launch in 2018, using the initial configuration of the vehicle, which is capable of delivering 70 metric tons (t) to Low Earth Orbit (LEO). On its first flight, Exploration Mission-1, SLS will launch an uncrewed test flight of the Orion spacecraft into distant retrograde orbit around the moon. Accompanying Orion on SLS will be 13 CubeSats, which will deploy in cislunar space. These CubeSats will include not only NASA research, but also spacecraft from industry and international partners and potentially academia. Following its first flight and potentially as early as its second, which will launch a crewed Orion spacecraft into cislunar space, SLS will evolve into a more powerful configuration with a larger upper stage. This configuration will initially be able to deliver 105 t to LEO and will continue to be upgraded to a performance of greater than 130 t to LEO. While the addition of the more powerful upper stage will mean a change to the secondary payload accommodations from Block 1, the SLS Program is already evaluating options for future secondary payload opportunities. Early discussions are also already underway for the use of SLS to launch spacecraft on interplanetary trajectories, which could open additional opportunities for CubeSats. This presentation will include an overview of the SLS vehicle and its capabilities, including the current status of progress toward first launch. It will also explain the opportunities the vehicle offers for CubeSats and secondary payloads, including an overview of the CubeSat manifest for Exploration Mission-1 in 2018

A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck.

BackgroundAfatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy.Patients and methodsAn open-label, randomized, phase II trial was conducted in 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m(2)/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). The primary end point was tumor shrinkage before crossover assessed by investigator (IR) and independent central review (ICR).ResultsA total of 121 patients were treated (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36 respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5.4%/10.1% with cetuximab (P = 0.46/0.30). Objective response rate was 16.1%/8.1% with afatinib and 6.5%/9.7% with cetuximab (IR/ICR). Comparable disease control rates were observed with afatinib (50%) and cetuximab (56.5%) by IR; similar results were seen by ICR. Most common grade ≥3 drug-related AEs (DRAEs) were rash/acne (18% versus 8.3%), diarrhea (14.8% versus 0%), and stomatitis/mucositis (11.5% versus 0%) with afatinib and cetuximab, respectively. Patients with DRAEs leading to treatment discontinuation were 23% with afatinib and 5% with cetuximab. In stage II, disease control rate (IR/ICR) was 38.9%/33.3% with afatinib and 18.8%/18.8% with cetuximab.ConclusionAfatinib showed antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase II trial, although more patients on afatinib discontinued treatment due to AEs. Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover, suggesting a lack of cross-resistance

BACE1-/- mice exhibit seizure activity that does not correlate with sodium channel level or axonal localization

<p>Abstract</p> <p>Background</p> <p>BACE1 is a key enzyme in the generation of the Aβ peptide that plays a central role in the pathogenesis of Alzheimer's disease. While BACE1 is an attractive therapeutic target, its normal physiological function remains largely unknown. Examination of BACE1^-/-mice can provide insight into this function and also help anticipate consequences of BACE1 inhibition. Here we report a seizure-susceptibility phenotype that we have identified and characterized in BACE1^-/-mice.</p> <p>Results</p> <p>We find that electroencephalographic recordings reveal epileptiform abnormalities in some BACE1^-/-mice, occasionally including generalized tonic-clonic and absence seizures. In addition, we find that kainic acid injection induces seizures of greater severity in BACE1^-/-mice relative to BACE1^+/+littermates, and causes excitotoxic cell death in a subset of BACE1^-/-mice. This hyperexcitability phenotype is variable and appears to be manifest in approximately 30% of BACE1^-/-mice. Finally, examination of the expression and localization of the voltage-gated sodium channel α-subunit Na_v1.2 reveals no correlation with BACE1 genotype or any measure of seizure susceptibility.</p> <p>Conclusions</p> <p>Our data indicate that BACE1 deficiency predisposes mice to spontaneous and pharmacologically-induced seizure activity. This finding has implications for the development of safe therapeutic strategies for reducing Aβ levels in Alzheimer's disease. Further, we demonstrate that altered sodium channel expression and axonal localization are insufficient to account for the observed effect, warranting investigation of alternative mechanisms.</p

Space Launch System Spacecraft and Payload Elements: Making Progress Toward First Launch

Significant and substantial progress continues to be accomplished in the design, development, and testing of the Space Launch System (SLS), the most powerful human-rated launch vehicle the United States has ever undertaken. Designed to support human missions into deep space, SLS is one of three programs being managed by the National Aeronautics and Space Administration's (NASA's) Exploration Systems Development directorate. The Orion spacecraft program is developing a new crew vehicle that will support human missions beyond low Earth orbit, and the Ground Systems Development and Operations (GSDO) program is transforming Kennedy Space Center (KSC) into next-generation spaceport capable of supporting not only SLS but also multiple commercial users. Together, these systems will support human exploration missions into the proving ground of cislunar space and ultimately to Mars. SLS will deliver a near-term heavy-lift capability for the nation with its 70 metric ton Block 1 configuration, and will then evolve to an ultimate capability of 130 metric tons. The SLS program marked a major milestone with the successful completion of the Critical Design Review in which detailed designs were reviewed and subsequently approved for proceeding with full-scale production. This marks the first time an exploration class vehicle has passed that major milestone since the Saturn V vehicle launched astronauts in the 1960s during the Apollo program. Each element of the vehicle now has flight hardware in production in support of the initial flight of the SLS - Exploration Mission-1 (EM-1), an uncrewed mission to orbit the moon and return, and progress in on track to meet the initial targeted launch date in 2018. In Utah and Mississippi, booster and engine testing are verifying upgrades made to proven shuttle hardware. At Michoud Assembly Facility (MAF) in Louisiana, the world's largest spacecraft welding tool is producing tanks for the SLS core stage. This paper will particularly focus on work taking place at Marshall Space Flight Center (MSFC) and United Launch Alliance (ULA) in Alabama, where upper stage and adapter elements of the vehicle are being constructed and tested. Providing the Orion crew capsule/launch vehicle interface and in-space propulsion via a cryogenic upper stage, the Spacecraft/Payload Integration and Evolution (SPIE) Element serves a key role in achieving SLS goals and objectives. The SPIE element marked a major milestone in 2014 with the first flight of original SLS hardware, the Orion Stage Adapter (OSA) which was used on Exploration Flight Test-1 with a design that will be used again on EM-1. Construction is already underway on the EM-1 Interim Cryogenic Propulsion Stage (ICPS), an in-space stage derived from the Delta Cryogenic Second Stage. Manufacture of the Orion Stage Adapter and the Launch Vehicle Stage Adapter is set to begin at the Friction Stir Facility located at MSFC while structural test articles are either completed (OSA) or nearing completion (Launch Vehicle Stage Adapter). An overview is provided of the launch vehicle capabilities, with a specific focus on SPIE Element qualification/testing progress, as well as efforts to provide access to deep space regions currently not available to the science community through a secondary payload capability utilizing CubeSat-class satellites

The Scholarly Impact of Books Acquired via Approval Plan Selection, Librarian Orders, and Patron-Driven Acquisitions as Measured by Citation Counts

Patron-driven acquisition has been an important, if contentious, topic for decades, with numerous programs having been piloted, adopted, and reported on, largely favorably, in the library literature. Still, questions and doubts persist for academic libraries, especially where the composition of vendor plans and packages and the judgment of patrons are concerned. Past literature has approached the assessment of patron-driven acquisition by analyzing circulation/usage, comparing peer-library holdings, seeking patrons’ or librarians’ judgments of utility and suitability, looking for evidence of collection imbalances, and testing for overlap in patrons’ and librarians’ purchases. To contribute to this literature, this study addresses scholarly impact and examines whose selections—approval plans’, librarians’, or patrons’—have been most heavily cited. For the social sciences, the sciences, and the humanities, the authors gathered topic-matched random samples of books acquired via approval plans and librarian orders during the first five years of operation of their institutions’ interlibrary loan purchase-on-demand patron-driven acquisition program and compared their citation counts to the counts of books acquired via the program. Google Scholar was employed to tally citations