Three-Dimensional Supergravity and the Cosmological Constant

Witten has argued that in $2+1$ dimensions local supersymmetry can ensure the vanishing of the cosmological constant without requiring the equality of bose and fermi masses. We find that this mechanism is implemented in a novel fashion in the (2+1)-dimensional supersymmetric abelian Higgs model coupled to supergravity. The vortex solitons are annihilated by half of the supersymmetry transformations. The covariantly constant spinors required to define these supersymmetries exist by virtue of a surprising cancellation between the Aharonov-Bohm phase and the phase associated with the holonomy of the spin connection. However the other half of the supersymmetry transformations, whose actions ordinarily generate the soliton supermultiplet, are not well-defined and bose-fermi degeneracy is consequently absent in the soliton spectrum.Comment: 12 pages, phyzz

Electrical impedance myography for reducing sample size in Duchenne muscular dystrophy trials

OBJECTIVE: To evaluate the sensitivity of electrical impedance myography (EIM) to disease progression in both ambulatory and non-ambulatory boys with DMD. METHODS AND PARTICIPANTS: A non-blinded, longitudinal cohort study of 29 ambulatory and 15 non-ambulatory boys with DMD and age-similar healthy boys. Subjects were followed for up to 1 year and assessed using the Myolex((R)) mView(TM) EIM system as part of a multicenter study. RESULTS: In the ambulatory group, EIM 100 kHz resistance values showed significant change compared to the healthy boys. For example, in lower extremity muscles, the average change in EIM 100 kHz resistance values over 12 months led to an estimated effect size of 1.58. Based on these results, 26 DMD patients/arm would be needed for a 12-month clinical trial assuming a 50% treatment effect. In non-ambulatory boys, EIM changes were greater in upper limb muscles. For example, biceps at 100kHz resistance gave an estimated effect size of 1.92 at 12 months. Based on these results, 18 non-ambulatory DMD patients/arm would be needed for a 12-month clinical trial assuming a 50% treatment effect. Longitudinal changes in the 100 kHz resistance values for the ambulatory boys correlated with the longitudinal changes in the timed supine-to-stand test. EIM was well-tolerated throughout the study. INTERPRETATION: This study supports that EIM 100 kHz resistance is sensitive to DMD progression in both ambulatory and non-ambulatory boys. Given the technology\u27s ease of use and broad age range of utility it should be employed as an exploratory endpoint in future clinical therapeutic trials in DMD. TRIAL REGISTRATION: Clincialtrials.gov registration #NCT02340923

Pathologic response rates after neoadjuvant therapy for sarcoma: A single institution study

(1) Background: Pathologic necrosis of soft tissue sarcomas (STS) has been used to determine treatment response, but its relationship to neoadjuvant treatments remains indeterminate. In this retrospective, single institution study, we hypothesized that neoadjuvant chemoradiation (NA-CRT) yields higher rates of pathologic complete response (pCR) than neoadjuvant radiation (NA-XRT) or chemotherapy (NA-CT) alone. (2) Methods: Patients with extremity STS between 2011–2020 who received neoadjuvant treatment were included. pCR was defined as percent necrosis of the surgical specimen greater than or equal to 90%. (3) Results: 79 patients were analyzed. 51.9% of the population were male with a mean age of 58.4 years. 49.4% identified as Non-Hispanic White. Twenty-six (32.9%) patients achieved pCR while 53 (67.1%) did not. NA-CT (OR 15.82, 95% CI = 2.58–96.9, p = 0.003 in univariate (UVA) and OR 24.7, 95% CI = 2.88–211.2, p = 0.003 in multivariate (MVA), respectively) and NA-XRT (OR 5.73, 95% CI = 1.51–21.8, p = 0.010 in UVA and OR 7.95, 95% CI = 1.87–33.7, p = 0.005 in MVA, respectively) was significantly associated with non-pCR when compared to NA-CRT. The analysis also demonstrated that grade 3 tumors, when using grade 2 as reference, also had significantly higher odds of achieving pCR (OR 0.23, 95% CI = 0.06–0.80, p = 0.022 in UVA and OR 0.16, 95% CI = 0.04–0.70, p = 0.015 in MVA, respectively). (4) Conclusion: NA-CRT yields superior pCR compared to other neoadjuvant regimens. This extends to higher grade tumors

Comparing the frequency of common genetic variants and haplotypes between carriers and non-carriers of BRCA1 and BRCA2 deleterious mutations in Australian women diagnosed with breast cancer before 40 years of age

BACKGROUND: BRCA1 and BRCA2 mutations are found in a proportion of families with multiple early-onset breast cancers. There are a large number of different deleterious mutations in both genes, none of which would be detectable using standard genetic association studies. Single common variants and haplotypes of common variants may capture groups of deleterious mutations since some low prevalence haplotypes of common variants occur more frequently among chromosomes that carry rare, deleterious mutations than chromosomes that do not. METHODS: DNA sequence data for BRCA1 and BRCA2 was obtained from 571 participants from the Australian Breast Cancer Family Study. Genetic variants were classified as either deleterious mutations or common genetic variants. Variants tagging common polymorphisms were selected and haplotypes resolved using Haploview. Their frequency was compared to those with and without deleterious mutations using a permutation test. RESULTS: A common genetic variant in BRCA1 (3232A > G) was found to be over-represented in deleterious mutation carriers (p = 0.05), whereas a common genetic variant in BRCA2 (1342A > C) occurred less frequently in deleterious mutation carriers (p = 0.04). All four of the common BRCA1 variants used to form haplotypes occurred more frequently in the deleterious mutation carriers when compared to the non-carriers, but there was no evidence of a difference in the distributions between the two groups (p = 0.34). In BRCA2, all four common variants were found to occur less frequently in the deleterious mutation carriers when compared to non-carriers, but the evidence for difference in the distribution between the two groups was weak (p = 0.16). Several less common haplotypes of common BRCA1 variants were found to be over-represented among deleterious mutation carriers but there was no evidence for this at the population level. In BRCA2, only the most common haplotype was found to occur more frequently in deleterious mutation carriers, with again no evidence at the population level. CONCLUSIONS: We observed differences in the frequency of common genetic variants of the BRCA1 and BRCA2 and their haplotypes between early-onset breast cancer cases who did and did not carry deleterious mutations in these genes. Although our data provide only weak evidence for a difference in frequencies at the population level, the number of deleterious mutation carriers was low and the results may yet be substantiated in a larger study using pooled data

Donor power and the news:The influence of foundation funding on international public service journalism

How does donor funding affect the independence, role-perceptions and ideology of the journalism it supports? We begin to answer this increasingly important but under-researched question with a year-long case study of the humanitarian newswire IRIN as it transitioned from being funded by the United Nations to a private foundation, run by a Malaysian billionaire. Using content analysis, in-depth interviews, and ethnographic research we document the changes that occurred in IRIN’s outputs, target audience and public service values and the complex interplay of influences which produced these changes. We find that, in this case, donor power operated entirely indirectly and always in concert with the dominant professional values within IRIN. In doing so, this case study highlights the importance of journalistic agency and contextual variables in the journalist-donor relationship, as well as the potential significance of contradictory dynamics. We also use this case to test whether Benson, Hesserus and Sedel’s model of media owner power can help to explain the workings of donor power

Modeling the effect of age in T1-2 breast cancer using the SEER database

BACKGROUND: Modeling the relationship between age and mortality for breast cancer patients may have important prognostic and therapeutic implications. METHODS: Data from 9 registries of the Surveillance, Epidemiology, and End Results Program (SEER) of the United States were used. This study employed proportional hazards to model mortality in women with T1-2 breast cancers. The residuals of the model were used to examine the effect of age on mortality. This procedure was applied to node-negative (N0) and node-positive (N+) patients. All causes mortality and breast cancer specific mortality were evaluated. RESULTS: The relationship between age and mortality is biphasic. For both N0 and N+ patients among the T1-2 group, the analysis suggested two age components. One component is linear and corresponds to a natural increase of mortality with each year of age. The other component is quasi-quadratic and is centered around age 50. This component contributes to an increased risk of mortality as age increases beyond 50. It suggests a hormonally related process: the farther from menopause in either direction, the more prognosis is adversely influenced by the quasi-quadratic component. There is a complex relationship between hormone receptor status and other prognostic factors, like age. CONCLUSION: The present analysis confirms the findings of many epidemiological and clinical trials that the relationship between age and mortality is biphasic. Compared with older patients, young women experience an abnormally high risk of death. Among elderly patients, the risk of death from breast cancer does not decrease with increasing age. These facts are important in the discussion of options for adjuvant treatment with breast cancer patients

Tumor-Infiltrating T Cells Correlate with NY-ESO-1-Specific Autoantibodies in Ovarian Cancer

BACKGROUND: Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC). A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens. METHODOLOGY AND PRINCIPAL FINDINGS: We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B) and other immunological markers (CD20, MHC class I and MHC class II). Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35) of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004). Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-gamma ELISPOT and MHC class I pentamer staining. CONCLUSION AND SIGNIFICANCE: We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant T cell antigens for immunotherapy

Does self monitoring of blood glucose as opposed to urinalysis provide additional benefit in patients newly diagnosed with type 2 diabetes receiving structured education? The DESMOND SMBG randomised controlled trial protocol

BackgroundThe benefit of self-monitoring of blood glucose (SMBG) in people with type 2 diabetes on diet or oral agents other than sulphonylureas remains uncertain. Trials of interventions incorporating education about self-monitoring of blood glucose have reported mixed results. A recent systematic review concluded that SMBG was not cost-effective. However, what was unclear was whether a cheaper method of self-monitoring (such as urine glucose monitoring) could produce comparable benefit and patient acceptability for less cost.Methods/DesignThe DESMOND SMBG trial is comparing two monitoring strategies (blood glucose monitoring and urine testing) over 18 months when incorporated into a comprehensive self-management structured education programme. It is a multi-site cluster randomised controlled trial, conducted across 8 sites (7 primary care trusts) in England, UK involving individuals with newly diagnosed Type 2 diabetes.The trial has 80% power to demonstrate equivalence in mean HbA1c (the primary end-point) at 18 months of within ± 0.5% assuming 20% drop out and 20% non-consent. Secondary end-points include blood pressure, lipids, body weight and psychosocial measures as well as a qualitative sub-study.Practices were randomised to one of two arms: participants attend a DESMOND programme incorporating a module on self-monitoring of either urine or blood glucose. The programme is delivered by accredited educators who received specific training about equipoise. Biomedical data are collected and psychosocial scales completed at baseline, and 6, 12, and 18 months post programme. Qualitative research with participants and educators will explore views and experiences of the trial and preferences for methods of monitoring.DiscussionThe DESMOND SMBG trial is designed to provide evidence to inform the debate about the value of self-monitoring of blood glucose in people with newly diagnosed type 2 diabetes. Strengths include a setting in primary care, a cluster design, a health economic analysis, a comparison of different methods of monitoring while controlling for other components of training within the context of a quality assured structured education programme and a qualitative sub-study