992 research outputs found
Restaurant Revenue Management: Applying Yield Management to the Restaurant Industry
The crucial element in a strategy for boosting restaurant revenues may be to relate prices to the length of time guests spend at the table. But, as the Witch of the West told Dorothy, the issue is how to do it
And then there were four: a study of UK market concentration - causes, consequences and the scope for market adjustment
While concentration measures are a good indicator of market structure, the link with competitiveness is more complex than often assumed. In particular, the modern theory of industrial organisation makes no clear statement regarding the impact of concentration on competition - the focus of this paper is concentration and no inferences are made about competitive aspects of the market. The extent and nature of concentration within the UK listed company audit market as at April, 2002 and, pro forma, after the collapse of Andersen is documented and analysed in detail (by firm, market segment and industry sector). The largest four firms held 90 per cent of the market (based on audit fees) in 2002, rising to 96 per cent with the demise of Andersen. A single firm, Pricewaterhouse-Coopers, held 70 per cent or more of the share of six out of 38 industry sectors, with a share of 50 per cent up to 70 per cent in a further seven sectors. The provision of non-audit services (NAS) by incumbent auditors is also considered. As at April 2002, the average ratio of non-audit fees (paid to auditor) to audit fees was 208 per cent, and exceeded 300 per cent in seven sectors. It is likely, however, that disposals by firms of their management consultancy and outsource firms, combined with the impact of the Smith Report on audit committees will serve to reduce these ratios. Another finding is that audit firms with expertise in a particular sector appeared to earn significantly higher nonaudit fees from their audit clients in that sector. The paper thus provides a solid empirical basis for debate. The subsequent discussion considers the implications for companies and audit firms of the high level of concentration in the current regulatory climate, where no direct regulatory intervention is planned
Response to COVID-19 vaccination in patients on cancer therapy:Analysis in a SARS-CoV-2-naïve population
Background: Cancer patients have increased morbidity and mortality from COVID-19, but may respond poorly to vaccination. The Evaluation of COVID-19 Vaccination Efficacy and Rare Events in Solid Tumors (EVEREST) study, comparing seropositivity between cancer patients and healthy controls in a low SARS-CoV-2 community-transmission setting, allows determination of vaccine response with minimal interference from infection. Methods: Solid tumor patients from The Canberra Hospital, Canberra, Australia, and healthy controls who received COVID-19 vaccination between March 2021 and January 2022 were included. Blood samples were collected at baseline, pre-second vaccine dose and at 1, 3 (primary endpoint), and 6 months post-second dose. SARS-CoV-2 anti-spike-RBD (S-RBD) and anti-nucleocapsid IgG antibodies were measured. Results: Ninety-six solid tumor patients and 20 healthy controls were enrolled, with median age 62 years, and 60% were female. Participants received either AZD1222 (65%) or BNT162b2 (35%) COVID-19 vaccines. Seropositivity 3 months post vaccination was 87% (76/87) in patients and 100% (20/20) in controls (p =.12). Seropositivity was observed in 84% of patients on chemotherapy, 80% on immunotherapy, and 96% on targeted therapy (differences not satistically significant). Seropositivity in cancer patients increased from 40% (6/15) after first dose, to 95% (35/37) 1 month after second dose, then dropped to 87% (76/87) 3 months after second dose. Conclusion: Most patients and all controls became seropositive after two vaccine doses. Antibody concentrations and seropositivity showed a decrease between 1 and 3 months post vaccination, highlighting need for booster vaccinations. SARS-CoV-2 infection amplifies S-RBD antibody responses; however, cannot be adequately identified using nucleocapsid serology. This underlines the value of our COVID-naïve population in studying vaccine immunogenicity.</p
Goldstone Fermion Dark Matter
We propose that the fermionic superpartner of a weak-scale Goldstone boson
can be a natural WIMP candidate. The p-wave annihilation of this `Goldstone
fermion' into pairs of Goldstone bosons automatically generates the correct
relic abundance, whereas the XENON100 direct detection bounds are evaded due to
suppressed couplings to the Standard Model. Further, it is able to avoid
indirect detection constraints because the relevant s-wave annihilations are
small. The interactions of the Goldstone supermultiplet can induce non-standard
Higgs decays and novel collider phenomenology.Comment: 25 pages, 6 figures. References added, minor typos corrected.
Submitted to JHE
Symmetry Control of Unconventional Spin–Orbit Torques in IrO\u3csub\u3e2\u3c/sub\u3e
Spin–orbit torques generated by a spin current are key to magnetic switching in spintronic applications. The polarization of the spin current dictates the direction of switching required for energy-efficient devices. Conventionally, the polarizations of these spin currents are restricted to be along a certain direction due to the symmetry of the material allowing only for efficient in-plane magnetic switching. Unconventional spin–orbit torques arising from novel spin current polarizations, however, have the potential to switch other magnetization orientations such as perpendicular magnetic anisotropy, which is desired for higher density spintronic-based memory devices. Here, it is demonstrated that low crystalline symmetry is not required for unconventional spin–orbit torques and can be generated in a nonmagnetic high symmetry material, iridium dioxide (IrO2), using epitaxial design. It is shown that by reducing the relative crystalline symmetry with respect to the growth direction large unconventional spin currents can be generated and hence spin–orbit torques. Furthermore, the spin polarizations detected in (001), (110), and (111) oriented IrO2 thin films are compared to show which crystal symmetries restrict unconventional spin transport. Understanding and tuning unconventional spin transport generation in high symmetry materials can provide a new route towards energy-efficient magnetic switching in spintronic devices
Long-term treatment with rilzabrutinib in patients with immune thrombocytopenia
Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibodymediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and a predisposition to bleeding. The ongoing, global phase 1/2 study showed that rilzabrutinib, a Bruton tyrosine kinase inhibitor specifically developed to treat autoimmune disorders, could be an efficacious and well-tolerated treatment for ITP. Clinical activity, durability of response, and safety were evaluated in 16 responding patients who continued rilzabrutinib 400 mg twice daily in the long-term extension (LTE) study. At LTE entry, the median platelet count was 87 × 109/L in all patients, 68 × 109/L in those who had rilzabrutinib monotherapy (n = 5), and 156 × 109/L in patients who received concomitant ITP medication (thrombopoietin-receptor agonists and/or corticosteroids, n = 11). At a median duration of treatment of 478 days (range, 303-764), 11 of 16 patients (69%) continued to receive rilzabrutinib. A platelet count of =50 × 109/L was reported in 93% of patients for more than half of their monthly visits. The median percentage of LTE weeks with platelet counts =30 × 109/L and =50 × 109/L was 100% and 88%, respectively. Five patients discontinued concomitant ITP therapy and maintained median platelet counts of 106 × 109/L at 3 to 6 months after stopping concomitant ITP therapy. Adverse events related to treatment were grade 1 or 2 and transient, with no bleeding, thrombotic, or serious adverse events. With continued rilzabrutinib treatment in the LTE, platelet responses were durable and stable over time with no new safety signals.</p
mTORC1 Inhibition Protects Human Regulatory T Cells From Granzyme-B-Induced Apoptosis
Regulatory T cells (T-regs) have shown great promise as a means of cellular therapy in a multitude of allo- and auto-immune diseases-due in part to their immunosuppressive potency. Nevertheless, the clinical efficacy of human T-regs in patients has been limited by their poor in vivo homeostasis. To avert apoptosis, T-regs require stable antigenic (CD3 zeta/T-cell-receptor-mediated), co-stimulatory (CD28-driven), and cytokine (IL-2-dependent) signaling. Notably, this sequence of signals supports an activated T-reg phenotype that includes a high expression of granzymes, particularly granzyme B (GrB). Previously, we have shown that aside from the functional effects of GrB in lysing target cells to modulate allo-immunity, GrB can leak out of the intracellular lysosomal granules of host T-regs, initiating pro-apoptotic pathways. Here, we assessed the role of inhibiting mechanistic target of rapamycin complex 1 (mTORC1), a recently favored drug target in the transplant field, in regulating human T-reg apoptosis via GrB. Using ex vivo models of human T-reg culture and a humanized mouse model of human skin allotransplantation, we found that by inhibiting mTORC1 using rapamycin, intracytoplasmic expression and functionality of GrB diminished in host T-regs; lowering human T-reg apoptosis by in part decreasing the phosphorylation of S6K and c-Jun. These findings support the already clinically validated effects of mTORC1 inhibition in patients, most notably their stabilization of T-reg bioactivity and in vivo homeostasis
Magnetic inflation and Stellar Mass. II. On the radii of wingle, rapidly rotating, fully convective M-dwarf stars
Main-sequence, fully convective M dwarfs in eclipsing binaries are observed to be larger than stellar evolutionary models predict by as much as 10%–15%. A proposed explanation for this discrepancy involves effects from strong magnetic fields, induced by rapid rotation via the dynamo process. Although, a handful of single, slowly rotating M dwarfs with radius measurements from interferometry also appear to be larger than models predict, suggesting that rotation or binarity specifically may not be the sole cause of the discrepancy. We test whether single, rapidly rotating, fully convective stars are also larger than expected by measuring their distribution. We combine photometric rotation periods from the literature with rotational broadening () measurements reported in this work for a sample of 88 rapidly rotating M dwarf stars. Using a Bayesian framework, we find that stellar evolutionary models underestimate the radii by 10 \% \mbox{--}15{ \% }_{-2.5}^{+3}, but that at higher masses (0.18 < M < 0.4 M Sun), the discrepancy is only about 6% and comparable to results from interferometry and eclipsing binaries. At the lowest masses (0.08 < M < 0.18 M Sun), we find that the discrepancy between observations and theory is 13%–18%, and we argue that the discrepancy is unlikely to be due to effects from age. Furthermore, we find no statistically significant radius discrepancy between our sample and the handful of M dwarfs with interferometric radii. We conclude that neither rotation nor binarity are responsible for the inflated radii of fully convective M dwarfs, and that all fully convective M dwarfs are larger than models predict.The authors would like to thank the referee for the thoughtful report, which greatly improved the manuscript. The authors would also like to thank Lisa Prato and Larissa Nofi for IGRINS training, and Heidi Larson, Jason Sanborn, and Andrew Hayslip for operating the DCT during our observations. We would also like to thank Jen Winters, Jonathan Irwin, Paul Dalba, Mark Veyette, Eunkyu Han, and Andrew Vanderburg for useful discussions and helpful comments on this work. Some of this work was supported by the NASA Exoplanet Research Program (XRP) under grant No. NNX15AG08G issued through the Science Mission Directorate.These results made use of the Lowell Observatory's Discovery Channel Telescope, supported by Discovery Communications, Inc., Boston University, the University of Maryland, the University of Toledo and Northern Arizona University; the Immersion Grating Infrared Spectrograph (IGRINS) that was developed under a collaboration between the University of Texas at Austin and the Korea Astronomy and Space Science Institute (KASI) with the financial support of the US National Science Foundation under grant AST-1229522, of the University of Texas at Austin, and of the Korean GMT Project of KASI; data taken at The McDonald Observatory of The University of Texas at Austin; and data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by NASA and the NSF. (NNX15AG08G - NASA Exoplanet Research Program (XRP); Discovery Communications, Inc.; Boston University; University of Maryland; University of Toledo; Northern Arizona University; AST-1229522 - US National Science Foundation; University of Texas at Austin; Korean GMT Project of KASI; NASA; NSF
Recommended from our members
ENSO feedbacks and their relationships with the mean state in a flux adjusted ensemble
The El Niño Southern Oscillation (ENSO) is governed by a combination of amplifying and damping ocean–atmosphere feedbacks in the equatorial Pacific. Here we quantify these feedbacks in a flux adjusted HadCM3 perturbed physics ensemble under present day conditions and a future emissions scenario using the Bjerknes Stability Index (BJ index). Relationships between feedbacks and both the present day biases and responses under climate change of the mean equatorial Pacific climate are investigated. Despite minimised mean sea surface temperature biases through flux adjustment, the important dominant ENSO feedbacks still show biases with respect to observed feedbacks and inter-ensemble diversity. The dominant positive thermocline and zonal advective feedbacks are found to be weaker in ensemble members with stronger mean zonal advection. This is due to a weaker sensitivity of the thermocline slope and zonal surface ocean currents in the east Pacific to surface wind stress anomalies. A drier west Pacific is also found to be linked to weakened shortwave and latent heat flux damping, suggesting a link between ENSO characteristics and the hydrological cycle. In contrast to previous studies using the BJ index that find positive relationships between the index and ENSO amplitude, here they are weakly or negatively correlated, both for present day conditions and for projected differences. This is caused by strong thermodynamic damping which dominates over positive feedbacks, which alone approximate ENSO amplitude well. While the BJ index proves useful for individual linear feedback analysis, we urge caution in using the total linear BJ index alone to assess the reasons for ENSO amplitude biases and its future change in models
Three-dimensional holographic optical manipulation through a high-numerical-aperture soft-glass multimode fibre
Holographic optical tweezers (HOT) hold great promise for many applications in biophotonics, allowing the creation and measurement of minuscule forces on biomolecules, molecular motors and cells. Geometries used in HOT currently rely on bulk optics, and their exploitation in vivo is compromised by the optically turbid nature of tissues. We present an alternative HOT approach in which multiple three-dimensional (3D) traps are introduced through a high-numerical-aperture multimode optical fibre, thus enabling an equally versatile means of manipulation through channels having cross-section comparable to the size of a single cell. Our work demonstrates real-time manipulation of 3D arrangements of micro-objects, as well as manipulation inside otherwise inaccessible cavities. We show that the traps can be formed over fibre lengths exceeding 100 mm and positioned with nanometric resolution. The results provide the basis for holographic manipulation and other high-numerical-aperture techniques, including advanced microscopy, through single-core-fibre endoscopes deep inside living tissues and other complex environments
- …