Constraints From Gauge Coupling Unification On The Scale Of Supersymmetry Breaking

We reanalyze precision LEP data and coupling constant unification in the minimal supersymmetric $SU(5)$ model including the evolution of the gaugino masses. We derive general bounds on the primordial gaugino supersymmetry-breaking mass-scale $m_{1/2}$ in terms of the various input parameters. The model cannot accommodate m_{1/2}<1\TeV for values of \as < 0.115, even for extreme $1-\sigma$ values of the other inputs. We emphasize the sensitivity of this type of calculations to the various input parameters.Comment: 9 pages, 1 figure not included, ACT-10/9

An Open-Label, Multicenter, Phase I, Dose Escalation Study with Phase II Expansion Cohort to Determine the Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Intravenous TKM-080301 in Subjects with Advanced Hepatocellular Carcinoma.

Lessons learnedTKM-080301 showed a favorable toxicity profile at the studied dose.TKM-080301 targeting PLK1 through small interfering RNA mechanism did not demonstrate improved overall survival in patients with advanced hepatocellular carcinoma compared with historical control. Preliminary antitumor activity as shown in this early-phase study does not support further evaluation as a single agent.BackgroundPolo-like kinase 1 (PLK1) is overexpressed in hepatocellular carcinoma (HCC). Knockdown of PLK1 expression by PLK1 small interfering RNA (siRNA) in an HCC cell line showed reduced expression in RNA-induced silencing complex and a reduction in cell proliferation.MethodsA 3 + 3 dose escalation plus expansion cohort at the maximum tolerated dose (MTD) was implemented. Patients with HCC, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and Child-Pugh score A received TKM-080301 as an intravenous infusion once every week for 3 consecutive weeks, repeated every 28 days.ResultsThe study enrolled 43 patients. The starting dose of TKM-080301 was 0.3 mg/kg, and MTD was declared at 0.75 mg/kg. Following the development of grade 4 thrombocytopenia in two subjects on the expansion cohort, the MTD was redefined at 0.6 mg/kg. Four patients did not have any evaluable postbaseline scan. Of the other 39 subjects who had received at least 0.3 mg/kg, 18 subjects (46.2%) had stable disease (SD) by independent RECIST 1.1 criteria. By Choi criteria, eight subjects (23.1%) had a partial response (PR). For 37 assessable subjects, with 2 subjects censored, median progression-free survival (PFS) was 2.04 months. Median survival for the whole study population was 7.5 months.ConclusionTKM-080301 was generally well tolerated. In this early-phase study, antitumor effect for TKM 080301 was limited. Further evaluation as a single agent in large randomized trials is not warranted

Bounded and unitary elements in pro-C^*-algebras

A pro-C^*-algebra is a (projective) limit of C^*-algebras in the category of topological *-algebras. From the perspective of non-commutative geometry, pro-C^*-algebras can be seen as non-commutative k-spaces. An element of a pro-C^*-algebra is bounded if there is a uniform bound for the norm of its images under any continuous *-homomorphism into a C^*-algebra. The *-subalgebra consisting of the bounded elements turns out to be a C^*-algebra. In this paper, we investigate pro-C^*-algebras from a categorical point of view. We study the functor (-)_b that assigns to a pro-C^*-algebra the C^*-algebra of its bounded elements, which is the dual of the Stone-\v{C}ech-compactification. We show that (-)_b is a coreflector, and it preserves exact sequences. A generalization of the Gelfand-duality for commutative unital pro-C^*-algebras is also presented.Comment: v2 (accepted

Oral Antibiotics Bowel Preparation Without Mechanical Preparation For Minimally Invasive Colorectal Surgeries: Current Practice And Future Prospects.

The efficacy of preoperative oral antibiotics alone compared to mechanical bowel preparation and oral antibiotics in minimally invasive surgery is still a matter of ongoing debate. This study aimed to assess the trend of surgical site infection rates in parallel to the utilization of bowel preparation modality over time for minimally invasive surgery colorectal surgeries in the United States. Retrospective analysis. The American College of Surgeons National Surgical Quality Improvement Program database. Adult patients who underwent elective colorectal surgery and reported bowel preparation modality. The trends and compare surgical site infection rates for mutually exclusive groups according to the underlying disease (colorectal cancer, inflammatory bowel disease, and diverticular disease) who underwent bowel preparation using oral antibiotics or combined mechanical bowel preparation and oral antibiotics. Patients who had rectal surgery were analyzed separately. A total of 30,939 patients were included. Of them, 12,417 (40%) had rectal resections. Over the seven-year study period, mechanical bowel preparation and oral antibiotics utilization has increased from 29.3% in 2012 to 64.0% in 2018; p&lt;0.0001 at the expense of no preparation and mechanical bowel preparation alone. Similarly, oral antibiotics utilization has increased from 2.3% in 2012 to 5.5% in 2018; p&lt;0.0001. For colon cancer patients, patients who had oral antibiotics alone had higher superficial surgical site infection rates compared to patients who had combined mechanical bowel preparation and oral antibiotics (1.9% vs. 1.1%; p=0.043). Superficial, deep and organ space surgical site infection rates were similar for all other comparative colon surgery groups (cancer, inflammatory bowel disease, and diverticular disease). Patients with rectal cancer who had oral antibiotics had higher rates of deep surgical site infection (0.9% vs. 0.1%; p=0.004). However, superficial, deep and organ space surgical site infection rates were similar for all other comparative rectal surgery groups. Retrospective nature of the analysis. This study revealed widespread adoption of mechanical bowel preparation and oral antibiotics mechanical bowel preparation and oral antibiotics and increased adoption of oral antibiotics over the study period. Surgical site infection rates appear to be similar from a clinical relevance standpoint among most comparative groups, questioning systematic preoperative addition of mechanical bowel preparation to oral antibiotics alone in all patients for minimally invasive colorectal surgery. See Video Abstract at http://links.lww.com/DCR/B828

Safety and efficacy of cabozantinib for patients with advanced hepatocellular carcinoma who advanced to Child-Pugh B liver function at study week 8: a retrospective analysis of the CELESTIAL randomised controlled trial

Background: Patients with hepatocellular carcinoma (HCC) and Child–Pugh B liver cirrhosis have poor prognosis and are underrepresented in clinical trials. The CELESTIAL trial, in which cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with HCC and Child–Pugh A liver cirrhosis at baseline, was evaluated for outcomes in patients who had Child–Pugh B cirrhosis at Week 8. Methods: This was a retrospective analysis of adult patients with previously treated advanced HCC. Child–Pugh B status was assessed by the investigator. Patients were randomised 2:1 to cabozantinib (60 mg once daily) or placebo. Results: Fifty-one patients receiving cabozantinib and 22 receiving placebo had Child–Pugh B cirrhosis at Week 8. Safety and tolerability of cabozantinib for the Child–Pugh B subgroup were consistent with the overall population. For cabozantinib- versus placebo-treated patients, median OS from randomisation was 8.5 versus 3.8 months (HR 0.32, 95% CI 0.18–0.58), median PFS was 3.7 versus 1.9 months (HR 0.44, 95% CI 0.25–0.76), and best response was stable disease in 57% versus 23% of patients. Conclusions: These encouraging results with cabozantinib support the initiation of prospective studies in patients with advanced HCC and Child–Pugh B liver function. Clinical Trial Registration: NCT01908426

Identifying the Best Times for Cognitive Functioning Using New Methods: Matching University Times to Undergraduate Chronotypes

University days generally start at fixed times in the morning, often early morning, without regard to optimal functioning times for students with different chronotypes. Research has shown that later starting times are crucial to high school students' sleep, health, and performance. Shifting the focus to university, this study used two new approaches to determine ranges of start times that optimize cognitive functioning for undergraduates. The first is a survey-based, empirical model (SM), and the second a neuroscience-based, theoretical model (NM). The SM focused on students' self-reported chronotype and times they feel at their best. Using this approach, data from 190 mostly first and second year university students were collected and analyzed to determine optimal times when cognitive performance can be expected to be at its peak. The NM synthesized research in sleep, circadian neuroscience, sleep deprivation's impact on cognition, and practical considerations to create a generalized solution to determine the best learning hours. Strikingly the SM and NM results align with each other and confirm other recent research in indicating later start times. They add several important points: (1) They extend our understanding by showing that much later starting times (after 11 a.m. or 12 noon) are optimal; (2) Every single start time disadvantages one or more chronotypes; and (3) The best practical model may involve three alternative starting times with one afternoon shared session. The implications are briefly considered

Quality of life assessment of cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial

BACKGROUND: The CELESTIAL trial (NCT01908426) demonstrated overall survival benefit for cabozantinib versus placebo in patients with advanced hepatocellular carcinoma (aHCC) who had received prior sorafenib treatment. This analysis of CELESTIAL compared the impact of cabozantinib versus placebo on health-related quality of life (HRQoL). MATERIALS AND METHODS: Health status was assessed using the EuroQol five-dimension five-level (EQ-5D-5L) questionnaire over the 800-day follow-up period. EQ-5D-5L health states were mapped to health utility scores using reference values for the UK population. Quality-adjusted life years (QALYs) were calculated for each treatment group as the area under the curve for the plot of health utility score over time. The between-treatment group difference in restricted mean QALYs was calculated by generalized linear models and adjusted for baseline differences. A difference of 0.08 in health utility score (or in QALY) was deemed a minimally important difference and to be clinically significant. RESULTS: At week 5, the difference in mean health utility score between cabozantinib and placebo was -0.097 (95% confidence interval [95% CI]: -0.126, -0.067; p ≤ 0.001). Between-group differences in health utility scores diminished over time and were generally non-significant. The cabozantinib group accrued more QALYs than the placebo group over follow-up. Differences in mean QALYs (cabozantinib minus placebo) were statistically and clinically significant, ranging from +0.092 (95% CI: 0.016, 0.169) to +0.185 (95% CI: 0.126, 0.243) in favour of cabozantinib, depending on the reference value set used. CONCLUSIONS: These HRQoL findings support a positive benefit-risk profile for cabozantinib in previously treated patients with aHCC

Folding model analysis of elastic and inelastic proton scattering on Sulfur isotopes

The folding formalism for the nucleon-nucleus optical potential and inelastic form factor is applied to study elastic and inelastic proton scattering on 30-40S isotopes. A recently developed realistic density dependent M3Y interaction, well tested in the folding analysis of nucleus-nucleus elastic and inelastic scattering, is used as effective NN interaction. The nuclear ground state and transition densities (for the 2+ excitations in Sulfur isotopes) are obtained in the Hartree-Fock-BCS and QRPA approaches, respectively. The best fit ratios of transition moments Mn/Mp for the lowest 2+ states in Sulfur isotopes are compared to those obtained earlier in the DWBA analysis of the same data using the same structure model and inelastic form factors obtained with the JLM effective interaction. Our folding+DWBA analysis has shown quite a strong isovector mixing in the elastic and inelastic scattering channels for the neutron rich 38,40S nuclei. In particular, the relative strength of the isovector part of the transition potential required by the inelastic p+38S data is significantly stronger than that obtained with the corresponding QRPA transition density.Comment: 24 pages, 11 figures, accepted for publication in Nucl. Phys.