On the Possibility of Optical Unification in Heterotic Strings

Recently J. Giedt discussed a mechanism, entitled optical unification, whereby string scale unification is facilitated via exotic matter with intermediate scale mass. This mechanism guarantees that a virtual MSSM unification below the string scale is extrapolated from the running of gauge couplings upward from M_Z^o when an intermediate scale desert is assumed. In this letter we explore the possibility of optical unification within the context of weakly coupled heterotic strings. In particular, we investigate this for models of free fermionic construction containing the NAHE set of basis vectors. This class is of particular interest for optical unification, because it provides a standard hypercharge embedding within SO(10), giving the standard k_Y = 5/3 hypercharge level, which was shown necessary for optical unification. We present a NAHE model for which the set of exotic SU(3)_C triplet/anti-triplet pairs, SU(2)_L doublets, and non-Abelian singlets with hypercharge offers the possibility of optical unification. Whether this model can realize optical unification is conditional upon these exotics not receiving Fayet-Iliopoulos (FI) scale masses when a flat direction of scalar vacuum expectation values is non-perturbatively chosen to cancel the FI D-term, xi, generated by the anomalous U(1)-breaking Green-Schwarz-Dine-Seiberg-Wittten mechanism. A study of perturbative flat directions and their phenomenological implications for this model is underway. This paper is a product of the NFS Research Experiences for Undergraduates and the NSF High School Summer Science Research programs at Baylor University.Comment: 16 pages. Standard Late

An Extreme Solar Event of 20 January 2005: Properties of the Flare and the Origin of Energetic Particles

The extreme solar and SEP event of 20 January 2005 is analyzed from two perspectives. Firstly, we study features of the main phase of the flare, when the strongest emissions from microwaves up to 200 MeV gamma-rays were observed. Secondly, we relate our results to a long-standing controversy on the origin of SEPs arriving at Earth, i.e., acceleration in flares, or shocks ahead of CMEs. All emissions from microwaves up to 2.22 MeV line gamma-rays during the main flare phase originated within a compact structure located just above sunspot umbrae. A huge radio burst with a frequency maximum at 30 GHz was observed, indicating the presence of a large number of energetic electrons in strong magnetic fields. Thus, protons and electrons responsible for flare emissions during its main phase were accelerated within the magnetic field of the active region. The leading, impulsive parts of the GLE, and highest-energy gamma-rays identified with pi^0-decay emission, are similar and correspond in time. The origin of the pi^0-decay gamma-rays is argued to be the same as that of lower energy emissions. We estimate the sky-plane speed of the CME to be 2000-2600 km/s, i.e., high, but of the same order as preceding non-GLE-related CMEs from the same active region. Hence, the flare itself rather than the CME appears to determine the extreme nature of this event. We conclude that the acceleration, at least, to sub-relativistic energies, of electrons and protons, responsible for both the flare emissions and the leading spike of SEP/GLE by 07 UT, are likely to have occurred simultaneously within the flare region. We do not rule out a probable contribution from particles accelerated in the CME-driven shock for the leading GLE spike, which seemed to dominate later on.Comment: 34 pages, 14 Postscript figures. Solar Physics, accepted. A typo corrected. The original publication is available at http://www.springerlink.co

Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial.

IMPORTANCE: Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly. OBJECTIVE: To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma. DESIGN, SETTING, AND PARTICIPANTS: After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis. INTERVENTIONS: Treatment with TTFields was delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m2/d) was given for 5 days of each 28-day cycle. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up. RESULTS: The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to-treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7-25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004). CONCLUSIONS AND RELEVANCE: In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00916409

A community-based, multi-level, multi-setting, multi-component intervention to reduce weight gain among low socioeconomic status Latinx children with overweight or obesity: The Stanford GOALS randomised controlled trial

Background: There are few long-term studies of interventions to reduce in low socioeconomic status children with overweight or obesity. The Stanford GOALS trial evaluated a 3-year, community-based, multi-level, multi-setting, multi-component (MMM) systems intervention, to reduce weight gain among low socioeconomic status, Latinx children with overweight or obesity. Methods: We did a two-arm, parallel group, randomised, open-label, active placebo-controlled trial with masked assessment over 3 years. Families from low-income, primarily Latinx communities in Northern California, CA, USA, with 7–11-year-old children with overweight or obesity were randomly assigned to a MMM intervention or a Health Education (HE) comparison intervention. The MMM intervention included home environment changes and behavioural counselling, community after school team sports, and reports to primary health-care providers. The primary outcome was child BMI trajectory over three years. Secondary outcomes included one- and two-year changes in BMI. This trial is registered with ClinicalTrials.gov NCT01642836. Findings: Between July 13, 2012, and Oct 3, 2013, 241 families were recruited and randomly assigned to MMM (n=120) or HE (n=121). Children's mean age was 9·5 (SD 1·4) years, 134 (56%) were female and 107 (44%) were male, and 236 (98%) were Latinx. 238 (99%) children participated in year 1, 233 (97%) in year 2, and 227 (94%) in year 3 of follow-up assessments. In intention-to-treat analysis, over 3 years, the difference between intervention groups in BMI trajectory was not significant (mean adjusted difference −0·25 [95% CI −0·90 to 0·40] kg/m2; Cohen's d=0.10; p=0·45). Children in the MMM intervention group gained less BMI over 1 year than did children in the HE intervention group (−0·73 [–1·07 to −0·39] kg/m2, d=0.55); the same was true over 2 years (−0·63 [–1·13 to −0·14] kg/m2; d =0.33). No differential adverse events were observed. Interpretation: The MMM intervention did not reduce BMI gain versus HE over 3 years but the effects over 1 and 2 years in this rigorous trial show the promise of this systems intervention approach for reducing weight gain and cardiometabolic risk factors in low socioeconomic status communities. Funding: US National Institutes of Health

Co-evolution, opportunity seeking and institutional change: Entrepreneurship and the Indian telecommunications industry 1923-2009

"This is an Author's Original Manuscript of an article submitted for consideration in Business History [copyright Taylor & Francis]; Business History is available online at http://www.tandfonline.com/." 10.1080/00076791.2012.687538In this paper, we demonstrate the importance for entrepreneurship of historical contexts and processes, and the co-evolution of institutions, practices, discourses and cultural norms. Drawing on discourse and institutional theories, we develop a model of the entrepreneurial field, and apply this in analysing the rise to global prominence of the Indian telecommunications industry. We draw on entrepreneurial life histories to show how various discourses and discursive processes ultimately worked to generate change and the creation of new business opportunities. We propose that entrepreneurship involves more than individual acts of business creation, but also implies collective endeavours to shape the future direction of the entrepreneurial field

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Ultra-rare sarcomas: a consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities

Background Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies.Methods The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan.Results It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately <= 1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types.conclusions Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.Experimentele farmacotherapi