Nearly Optimal Pricing for Multiproduct Firms

In principle, a multiproduct firm can set separate prices for all possible bundled combinations of its products (i.e., "mixed bundling"). However, this is impractical for firms with more than a few products, because the number of prices increases exponentially with the number of products. In this study we show that simple pricing strategies are often nearly optimal -- i.e., with surprisingly few prices a firm can obtain 99% of the profit that would be earned by mixed bundling. Specifically, we show that bundle-size pricing -- setting prices that depend only on the size of bundle purchased -- tends to be more profitable than offering the individual products priced separately, and tends to closely approximate the profits from mixed bundling. These findings are based on an array of numerical experiments covering a broad range of demand and cost scenarios, as well as an empirical analysis of the pricing problem for an 8-product firm (a theater company).

ISSLS PRIZE IN BIOENGINEERING SCIENCE 2019: biomechanical changes in dynamic sagittal balance and lower limb compensatory strategies following realignment surgery in adult spinal deformity patients.

Study designA longitudinal cohort study.ObjectiveTo define a set of objective biomechanical metrics that are representative of adult spinal deformity (ASD) post-surgical outcomes and that may forecast post-surgical mechanical complications. Current outcomes for ASD surgical planning and post-surgical assessment are limited to static radiographic alignment and patient-reported questionnaires. Little is known about the compensatory biomechanical strategies for stabilizing sagittal balance during functional movements in ASD patients.MethodsWe collected in-clinic motion data from 15 ASD patients and 10 controls during an unassisted sit-to-stand (STS) functional maneuver. Joint motions were measured using noninvasive 3D depth mapping sensor technology. Mathematical methods were used to attain high-fidelity joint-position tracking for biomechanical modeling. This approach provided reliable measurements for biomechanical behaviors at the spine, hip, and knee. These included peak sagittal vertical axis (SVA) over the course of the STS, as well as forces and muscular moments at various joints. We compared changes in dynamic sagittal balance (DSB) metrics between pre- and post-surgery and then separately compared pre- and post-surgical data to controls.ResultsStandard radiographic and patient-reported outcomes significantly improved following realignment surgery. From the DSB biomechanical metrics, peak SVA and biomechanical loads and muscular forces on the lower lumbar spine significantly reduced following surgery (- 19 to - 30%, all p < 0.05). In addition, as SVA improved, hip moments decreased (- 28 to - 65%, all p < 0.05) and knee moments increased (+ 7 to + 28%, p < 0.05), indicating changes in lower limb compensatory strategies. After surgery, DSB data approached values from the controls, with some post-surgical metrics becoming statistically equivalent to controls.ConclusionsLongitudinal changes in DSB following successful multi-level spinal realignment indicate reduced forces on the lower lumbar spine along with altered lower limb dynamics matching that of controls. Inadequate improvement in DSB may indicate increased risk of post-surgical mechanical failure. These slides can be retrieved under Electronic Supplementary Material

Supernova Remnants and Star Formation in the Large Magellanic Cloud

It has often been suggested that supernova remnants (SNRs) can trigger star formation. To investigate the relationship between SNRs and star formation, we have examined the known sample of 45 SNRs in the Large Magellanic Cloud to search for associated young stellar objects (YSOs) and molecular clouds. We find seven SNRs associated with both YSOs and molecular clouds, three SNRs associated with YSOs but not molecular clouds, and eight SNRs near molecular clouds but not associated with YSOs. Among the 10 SNRs associated with YSOs, the association between the YSOs and SNRs can be either rejected or cannot be convincingly established for eight cases. Only two SNRs have YSOs closely aligned along their rims; however, the time elapsed since the SNR began to interact with the YSOs' natal clouds is much shorter than the contraction timescales of the YSOs, and thus we do not see any evidence of SNR-triggered star formation in the LMC. The 15 SNRs that are near molecular clouds may trigger star formation in the future when the SNR shocks have slowed down to <45 km/s. We discuss how SNRs can alter the physical properties and abundances of YSOs.Comment: 24 pages, 5 figures, 1 table, Accepted for publication in the August 2010 edition of the Astronomical Journa

Membrane transporters in drug development

Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important drug transporter interactions. The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling. © 2010 Macmillan Publishers Limited

Breath analysis by ultra-sensitive broadband laser spectroscopy detects SARS-CoV-2 infection

Rapid testing is essential to fighting pandemics such as COVID-19, the disease caused by the SARS-CoV-2 virus. Exhaled human breath contains multiple volatile molecules providing powerful potential for non-invasive diagnosis of diverse medical conditions. We investigated breath detection of SARS-CoV-2 infection using cavity-enhanced direct frequency comb spectroscopy (CE-DFCS), a state-of-the-art laser spectroscopic technique capable of a real-time massive collection of broadband molecular absorption features at ro-vibrational quantum state resolution and at parts-per-trillion volume detection sensitivity. Using a total of 170 individual breath samples (83 positive and 87 negative with SARS-CoV-2 based on Reverse Transcription Polymerase Chain Reaction tests), we report excellent discrimination capability for SARS-CoV-2 infection with an area under the Receiver-Operating-Characteristics curve of 0.849(4). Our results support the development of CE-DFCS as an alternative, rapid, non-invasive test for COVID-19 and highlight its remarkable potential for optical diagnoses of diverse biological conditions and disease states

Deep Learning Based Fall Detection using WiFi Channel State Information

Falls have always been one of the major threats to the health and well-being of elderly people, particularly for those living alone. Both wearable and non-wearable fall detection systems have already been developed. However, the fall detection systems using WiFi channel state information (CSI) have attracted a significant interest from researchers due to their non-intrusive and low-cost nature. There are existing machine learning (ML) based fall detection systems using WiFi CSI; however, most systems trained with comprehensive datasets tend to achieve relatively lower accuracy compared to that of the systems trained with less inclusive datasets. To address these issues, we propose a novel, deep learning based fall detection technique. First, we implement different WiFi CSI collection tools and evaluate their potential for fall detection. To develop a highly accurate fall detection technique, we construct a comprehensive dataset, which consists of over 700 CSI samples including different types of falls and other daily activities, performed in four different indoor environments on and off the dominant paths. With this dataset, we then develop a deep learning based classifier using an image classification algorithm. The proposed technique, unlike the other fall detection systems, only requires down sampling and reshaping in pre-processing. The proposed fall detection system is evaluated with the constructed dataset, and it outperforms two other existing systems. It achieves over 96% accuracy for CSI collected in all four environments and 99% accuracy for CSI collected in certain combinations of the environments

Coupled surface plasmons and optical guided wave exploration of near-surface director profile

Copyright © 2007 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft. This is the published version of an article published in New Journal of Physics Vol. 9, article 49. DOI: 10.1088/1367-2630/9/3/049For a liquid crystal (LC) cell with thin silver claddings it is possible, using a high index coupling prism, to excite both surface plasmon modes and ordinary optical guided modes. In a situation where the tilt of the director varies from homogeneous to homeotropic through the cell, then for p-polarized incident radiation the p-polarized surface plasmon mode and the ordinary guided waves may couple to each other. When the plane containing the director is normal to the incident plane, there is also polarization conversion leading to strong coupling between the p-polarized surface plasmon and s-like guided modes. From theoretical analyses together with numerical modelling it is shown how this coupling between the surface plasmon mode and guided waves gives a high sensitivity to the surface director tilt profile near the walls, higher than that of the surface plasmon mode alone. Experimental confirmation of this has been realized using a hybrid aligned nematic (HAN) LC cell with the director in a plane normal to the incident plane. The results fully confirm the model predictions showing that this coupling of surface plasmons to guided waves provides a powerful tool for near-surface director studies

Fenebrutinib in H1 antihistamine-refractory chronic spontaneous urticaria: a randomized phase 2 trial

Bruton’s tyrosine kinase (BTK) is crucial for FcεRI-mediated mast cell activation and essential for autoantibody production by B cells in chronic spontaneous urticaria (CSU). Fenebrutinib, an orally administered, potent, highly selective, reversible BTK inhibitor, may be effective in CSU. This double-blind, placebo-controlled, phase 2 trial (EudraCT ID 2016-004624-35) randomized 93 adults with antihistamine-refractory CSU to 50 mg daily, 150 mg daily and 200 mg twice daily of fenebrutinib or placebo for 8 weeks. The primary end point was change from baseline in urticaria activity score over 7 d (UAS7) at week 8. Secondary end points were the change from baseline in UAS7 at week 4 and the proportion of patients well-controlled (UAS7 ≤ 6) at week 8. Fenebrutinib efficacy in patients with type IIb autoimmunity and effects on IgG-anti-FcεRI were exploratory end points. Safety was also evaluated. The primary end point was met, with dose-dependent improvements in UAS7 at week 8 occurring at 200 mg twice daily and 150 mg daily, but not at 50 mg daily of fenebrutinib versus placebo. Asymptomatic, reversible grade 2 and 3 liver transaminase elevations occurred in the fenebrutinib 150 mg daily and 200 mg twice daily groups (2 patients each). Fenebrutinib diminished disease activity in patients with antihistamine-refractory CSU, including more patients with refractory type IIb autoimmunity. These results support the potential use of BTK inhibition in antihistamine-refractory CSU

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM

The Evolution of Massive YSOs in the LMC: Part I. Identification and Spectral Classification

We present and categorize Spitzer IRS spectra of 294 objects in the Large Magellanic Cloud (LMC) to create the largest and most complete catalog of massive young stellar object (YSO) spectra in the LMC. Target sources were identified from infrared photometry and multi-wavelength images indicative of young, massive stars highly enshrouded in their natal gas and dust clouds. Our sample primarily consists of 277 objects we identify as having spectral features indicative of embedded YSOs. The remaining sources are comprised of 7 C-rich evolved sources, 8 sources dominated by broad silicate emission, and 1 source with multiple broad emission features. Those with YSO-like spectra show a range of spectral features including polycyclic aromatic hydrocarbon emission, deep silicate absorption, fine-structure lines, and ice absorption features. Based upon the relative strengths of these features, we have classified the YSO candidates into several distinct categories using the widely-used statistical procedure known as principal component analysis. We propose that these categories represent a spectrum of evolutionary stages during massive YSO formation. We conclude that massive pre-main sequence stars spend a majority of their massive, embedded lives emitting in the UV. Half of the sources in our study have features typical of compact HII regions, suggesting that massive YSOs can create a detectable compact HII region half-way through the formation time present in our sample. This study also provides a check on commonly used source-selection procedures including the use of photometry to identify YSOs. We determine a high success rate (>95%) of identifying objects with YSO-like spectra can be achieved through careful use of infrared CMDs, SEDs, and image inspections.Comment: Accepted to The Astrophysical Journa