Coupling Constant Dependence in the Thermodynamics of N=4 Supersymmetric Yang-Mills Theory

The free energy of the maximally supersymmetric SU(N) gauge theory at temperature T is expected to scale, in the large N limit, as N^2 T^4 times a function of the 't Hooft coupling, f(g_{YM}^2 N). In the strong coupling limit the free energy has been deduced from the near-extremal 3-brane geometry, and its normalization has turned out to be 3/4 times that found in the weak coupling limit. In this paper we calculate the leading correction to this result in inverse powers of the coupling, which originates from the R^4 terms in the tree level effective action of type IIB string theory. The correction to 3/4 is positive and of order (g_{YM}^2 N)^{-3/2}. Thus, f(g_{YM}^2 N) increases as the 't Hooft coupling is decreased, in accordance with the expectation that it should be approaching 1 in the weak coupling limit. We also discuss similar corrections for other conformal theories describing coincident branes. In particular, we suggest that the coupling-independence of the near extremal entropy for D1-branes bound to D5-branes is related to the vanishing of the Weyl tensor of AdS_3\times S^3.Comment: 24 pages; a paragraph about the 5-form background added in section 3; in the Note Added we clarify the meaning of the metric found in section 3; sign in eq. (34) correcte

Higher-Derivative Quantum Cosmology

The quantum cosmology of a higher-derivative derivative gravity theory arising from the heterotic string effective action is reviewed. A new type of Wheeler-DeWitt equation is obtained when the dilaton is coupled to the quadratic curvature terms. Techniques for solving the Wheeler-DeWitt equation with appropriate boundary conditions shall be described, and implications for semiclassical theories of inflationary cosmology will be outlined.Comment: 11 pages TeX. A term has been removed from equation (13

Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer:study protocol of the INDIBLADE trial

Introduction: Studies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer. Methods: The INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response. Discussion: This is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer. Clinical Trial Registration: The INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988).</p

γ-Tubulin regulates the anaphase-promoting complex/cyclosome during interphase

Activation of the APC/C requires microtubule-nucleating independent aspects of γ-tubulin function

Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial

Introduction: Studies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer. Methods: The INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response. Discussion: This is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer. Clinical Trial Registration: The INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988)

Stereotactic Body radiotherapy and pedicLE screw fixatioN During one hospital visit for patients with symptomatic unstable spinal metastases: a randomized trial (BLEND RCT) using the Trials within Cohorts (TwiCs) design

BACKGROUND: Spinal metastases can lead to unremitting pain and neurological deficits, which substantially impair daily functioning and quality of life. Patients with unstable spinal metastases receive surgical stabilization followed by palliative radiotherapy as soon as wound healing allows. The time between surgery and radiotherapy delays improvement of mobility, radiotherapy-induced pain relief, local tumor control, and restart of systemic oncological therapy. Stereotactic body radiotherapy (SBRT) enables delivery of preoperative high-dose radiotherapy while dose-sparing the surgical field, allowing stabilizing surgery within only hours. Patients may experience earlier recovery of mobility, regression of pain, and return to systemic oncological therapy. The BLEND RCT evaluates the effectiveness of SBRT followed by surgery within 24 h for the treatment of symptomatic, unstable spinal metastases. METHODS: This phase III randomized controlled trial is embedded within the PRospective Evaluation of interventional StudiEs on boNe meTastases (PRESENT) cohort. Patients with symptomatic, unstable spinal metastases requiring stabilizing surgery and radiotherapy will be randomized (1:1). The intervention group (n = 50) will be offered same-day SBRT and surgery, which they can accept or refuse. According to the Trial within Cohorts (TwiCs) design, the control group (n = 50) will not be informed and receive standard treatment (surgery followed by conventional radiotherapy after 1-2 weeks when wound healing allows). Baseline characteristics and outcome measures will be captured within PRESENT. The primary outcome is physical functioning (EORTC-QLQ-C15-PAL) 4 weeks after start of treatment. Secondary endpoints include pain response, time until return to systemic oncological therapy, quality of life, local tumor control, and adverse events up to 3 months post-treatment. DISCUSSION: The BLEND RCT evaluates the effect of same-day SBRT and stabilizing surgery for the treatment of symptomatic, unstable spinal metastases compared with standard of care. We expect better functional outcomes, faster pain relief, and continuation of systemic oncological therapy. The TwiCs design enables efficient recruitment within an ongoing cohort, as well as prevention of disappointment bias and drop-out as control patients will not be informed about the trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05575323. Registered on October 11, 2022