Stochastic processes and conformal invariance

We discuss a one-dimensional model of a fluctuating interface with a dynamic exponent $z=1$. The events that occur are adsorption, which is local, and desorption which is non-local and may take place over regions of the order of the system size. In the thermodynamic limit, the time dependence of the system is given by characters of the $c=0$ conformal field theory of percolation. This implies in a rigorous way a connection between CFT and stochastic processes. The finite-size scaling behavior of the average height, interface width and other observables are obtained. The avalanches produced during desorption are analyzed and we show that the probability distribution of the avalanche sizes obeys finite-size scaling with new critical exponents.Comment: 4 pages, 6 figures, revtex4. v2: change of title and minor correction

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Constraints on cosmic strings using data from the first Advanced LIGO observing run

Cosmic strings are topological defects which can be formed in grand unified theory scale phase transitions in the early universe. They are also predicted to form in the context of string theory. The main mechanism for a network of Nambu-Goto cosmic strings to lose energy is through the production of loops and the subsequent emission of gravitational waves, thus offering an experimental signature for the existence of cosmic strings. Here we report on the analysis conducted to specifically search for gravitational-wave bursts from cosmic string loops in the data of Advanced LIGO 2015-2016 observing run (O1). No evidence of such signals was found in the data, and as a result we set upper limits on the cosmic string parameters for three recent loop distribution models. In this paper, we initially derive constraints on the string tension Gμ and the intercommutation probability, using not only the burst analysis performed on the O1 data set but also results from the previously published LIGO stochastic O1 analysis, pulsar timing arrays, cosmic microwave background and big-bang nucleosynthesis experiments. We show that these data sets are complementary in that they probe gravitational waves produced by cosmic string loops during very different epochs. Finally, we show that the data sets exclude large parts of the parameter space of the three loop distribution models we consider

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

On the utility of fourier analysis of left ventricular pressure

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Evaluation of the Efficacy and Safety of Neostigmine in Reversing Neuromuscular Blockade

Purpose of Review: The minimum degree of neuromuscular recovery required before extubating the patient has progressively increased from a train-of-four ratio of 0.7 to a train-of-four ratio ≥ 0.9. The aim of the review is to evaluate the efficacy and the safety of neostigmine in antagonizing nondepolarizing neuromuscular block considering the new endpoint. Recent Findings: Increasing evidence suggests limited efficacy of neostigmine when a TOF ratio ≥ 0.9 is considered as appropriate endpoint. Summary: The currently accepted endpoint of adequate neuromuscular recovery challenges the efficacy of neostigmine. At least under volatile anesthesia, neostigmine can no longer be considered as an efficient drug to reverse moderate neuromuscular blockade, but it still allows to accelerate neuromuscular recovery when given at more advanced degrees of spontaneous recovery (i.e. a TOF ratio ≥ 0.4). Moreover, neostigmine-based reversal is associated with a higher incidence of adverse effects compared with sugammadex.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Factors affecting ease of ring formation. The effect of anchoring substitution on the rate of an intramolecular diels-alder reaction with furan-diene

Kinetic parameters for the IMDAF reaction of 2 and 3 were determined. For the equilibrium between 2b and 4b: ΔH° = -29.3 kJ/mol, ΔS° = -75 J/mol.K; for the conversion of 3 into 6 a significant rate enhancement by the anchoring tert-butyl group is observed: k(3b)/k(3a) = 240. The structure of 6b was proven via X-ray determination of 8. © 1988

Pancreas Transplantation at the University of Louvain : Results of 2 successive techniques

Today, combined kidney and pancreas transplantation is the best treatment for patients with type I diabetes and pre-end or end-stage renal disease due to the diabetic nephropathy. Thirty three patients (35 pancreases, 33 kidneys and 1/iver) underwent thatprocedure at our Institution (2 patients received 2 pancreases). Recent technical modifications - with the use of a whole pancreas graft with urinary drainage of the exocrine secretion in the recipient by peJforming a pancreaticoduodenocystostomy - allow the monitoring of the exocrine secretion which is a pertinent immunological marker for pancreas rejection. Current actuarial survival rates for patients, kidneys and pancreases are respective/y 87%, 81% and 77% at one year. In the next future, pancreas a/one should be consideree! safely using the same procedure, in non uremie diabetic recipients in whom extra-renal secondary complications are more serious than the potential side effects of chronic immunosuppression. That type of pancreas transplantation should benefit of the forthcoming immunosuppressive drugs