Clinicopathological factors influencing outcome in metastatic colorectal cancer patients treated with fluoropyrimidine and bevacizumab maintenance treatment vs observation: an individual patient data meta-analysis of two phase 3 trials

BACKGROUND: The CAIRO3 and AIO 0207 trials demonstrated the efficacy of fluoropyrimidine plus bevacizumab (FP+Bev) maintenance treatment in metastatic colorectal cancer (mCRC) patients. In this individual patient data meta-analysis with updated follow-up, we aim to provide more precise estimates of treatment effects and to identify subgroups that benefit most from maintenance treatment or observation. METHODS: In 871 patients, randomised to FP+Bev maintenance treatment or observation, we investigated whether treatment effect was modified by sex, age, performance status, response to induction treatment, primary tumour location, number of metastatic sites, disease stage and primary tumour resection, serum LDH, platelet count, CEA, and RAS/BRAF mutation status. Primary end point was time to second progression after reintroduction of the induction regimen (PFS2). Secondary end points were first progression-free survival (PFS1) and overall survival (OS). RESULTS: At a median follow-up of 68.5 months (IQR 54.6-87.0 months), maintenance treatment was more effective compared with observation in PFS1 (HR 0.40(95% CI 0.34-0.47)) and PFS2 (HR 0.70(0.60-0.81)). No subgroups were identified that did not benefit from maintenance treatment in PFS1 and PFS2; no clinically relevant subgroup effects were observed. Regarding OS, pooled results were not significant (HR 0.91(0.78-1.05)), and the trials showed marked heterogeneity in overall treatment effect and subgroup effects. CONCLUSIONS: FP+Bev maintenance treatment is effective in all patients, regardless of the investigated subgroups.info:eu-repo/semantics/publishedVersio

Drug resistance in non-B subtype HIV-1: Impact of HIV-1 reverse transcriptase inhibitors

Human immunodeficiency virus (HIV) causes approximately 2.5 million new infections every year, and nearly 1.6 million patients succumb to HIV each year. Several factors, including cross-species transmission and error-prone replication have resulted in extraordinary genetic diversity of HIV groups. One of these groups, known as group M (main) contains nine subtypes (A-D, F-H and J-K) and causes ∼95% of all HIV infections. Most reported data on susceptibility and resistance to anti-HIV therapies are from subtype B HIV infections, which are prevalent in developed countries but account for only ∼12% of all global HIV infections, whereas non-B subtype HIV infections that account for ∼88% of all HIV infections are prevalent primarily in low and middle-income countries. Although the treatments for subtype B infections are generally effective against non-B subtype infections, there are differences in response to therapies. Here, we review how polymorphisms, transmission efficiency of drug-resistant strains, and differences in genetic barrier for drug resistance can differentially alter the response to reverse transcriptase-targeting therapies in various subtypes

Organometallic neptunium(III) complexes

Studies of transuranic organometallic complexes provide a particularly valuable insight into covalent contributions to the metal–ligand bonding, in which the subtle differences between the transuranium actinide ions and their lighter lanthanide counterparts are of fundamental importance for the effective remediation of nuclear waste. Unlike the organometallic chemistry of uranium, which has focused strongly on UIII and has seen some spectacular advances, that of the transuranics is significantly technically more challenging and has remained dormant. In the case of neptunium, it is limited mainly to NpIV. Here we report the synthesis of three new NpIII organometallic compounds and the characterization of their molecular and electronic structures. These studies suggest that NpIII complexes could act as single-molecule magnets, and that the lower oxidation state of NpII is chemically accessible. In comparison with lanthanide analogues, significant d- and f-electron contributions to key NpIII orbitals are observed, which shows that fundamental neptunium organometallic chemistry can provide new insights into the behaviour of f-elements

On Poincare and logarithmic Sobolev inequalities for a class of singular Gibbs measures

This note, mostly expository, is devoted to Poincar{\'e} and log-Sobolev inequalities for a class of Boltzmann-Gibbs measures with singular interaction. Such measures allow to model one-dimensional particles with confinement and singular pair interaction. The functional inequalities come from convexity. We prove and characterize optimality in the case of quadratic confinement via a factorization of the measure. This optimality phenomenon holds for all beta Hermite ensembles including the Gaussian unitary ensemble, a famous exactly solvable model of random matrix theory. We further explore exact solvability by reviewing the relation to Dyson-Ornstein-Uhlenbeck diffusion dynamics admitting the Hermite-Lassalle orthogonal polynomials as a complete set of eigenfunctions. We also discuss the consequence of the log-Sobolev inequality in terms of concentration of measure for Lipschitz functions such as maxima and linear statistics.Comment: Minor improvements. To appear in Geometric Aspects of Functional Analysis -- Israel Seminar (GAFA) 2017-2019", Lecture Notes in Mathematics 225

Supergoop Dynamics

We initiate a systematic study of the dynamics of multi-particle systems with supersymmetric Van der Waals and electron-monopole type interactions. The static interaction allows a complex continuum of ground state configurations, while the Lorentz interaction tends to counteract this configurational fluidity by magnetic trapping, thus producing an exotic low temperature phase of matter aptly named supergoop. Such systems arise naturally in $\mathcal{N}=2$ gauge theories as monopole-dyon mixtures, and in string theory as collections of particles or black holes obtained by wrapping D-branes on internal space cycles. After discussing the general system and its relation to quiver quantum mechanics, we focus on the case of three particles. We give an exhaustive enumeration of the classical and quantum ground states of a probe in an arbitrary background with two fixed centers. We uncover a hidden conserved charge and show that the dynamics of the probe is classically integrable. In contrast, the dynamics of one heavy and two light particles moving on a line shows a nontrivial transition to chaos, which we exhibit by studying the Poincar\'e sections. Finally we explore the complex dynamics of a probe particle in a background with a large number of centers, observing hints of ergodicity breaking. We conclude by discussing possible implications in a holographic context.Comment: 35 pages,11 figures. v2: updated references to include a previous proof of classical integrability, exchanged a figure for a prettier versio

Sonography of ruptured appendicitis

Three girls and 4 boys with the final diagnosis of ruptured appendicitis underwent 19 sonographic studies, 5 before any therapy was instituted and 14 follow-up studies. Four abscesses identified before treatment and 2 seen postoperatively were ovoid, irregularly marginated, and contained lowamplitude echoes. Gastrointestinal ileus with gas- and fluid-filled loops of bowel made the studies technically difficult. Follow-up studies also showed fluid collections distant from the original abscesses. The complete resolution of the abscess was followed sonographically in 1 patient treated with antibiotics. Ultrasound can be useful in confirming or suggesting the diagnosis of ruptured appendicitis in the child with abdominal pain, but careful attention to detail is necessary in these technically difficult studies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48131/1/261_2005_Article_BF02035110.pd

Impact on diarrhoeal illness of a community educational intervention to improve drinking water quality in rural communities in Puerto Rico

<p>Abstract</p> <p>Background</p> <p>Waterborne disease is a major risk for small water supplies in rural settings. This study was done to assess the impact of an educational intervention designed to improve water quality and estimate the contribution of water to the incidence of diarrhoeal disease in poor rural communities in Puerto Rico a two-part study was undertaken.</p> <p>Methods</p> <p>An educational intervention was delivered to communities relying on community water supplies. This intervention consisted of student operators and administrators supervising and assisting community members who voluntarily "operate" these systems. These voluntary operators had no previous training and were principally concerned with seeing that some water was delivered. The quality of that water was not something they either understood or addressed. The impact of this intervention was measured through water sampling for standard bacteriological indicators and a frank pathogen. In addition, face-to-face epidemiological studies designed to determine the base-line occurrence of diarrhoeal disease in the communities were conducted. Some 15 months after the intervention a further epidemiological study was conducted in both the intervention communities and in control communities that had not received any intervention.</p> <p>Results</p> <p>Diarrhoeal illness rates over a four week period prior to the intervention were 3.5%. <it>Salmonella </it>was isolated from all of 5 distributed samples prior to intervention and from only 2 of 12 samples after the intervention. In the 15 months follow-up study, illness rates were lower in the intervention compared to control communities (2.5% <it>vs </it>3.6%%) (RR = 0.70, 95%CI 0.43, 1.15), though this was not statistically significant. However, in the final Poisson regression model living in an intervention system (RR = 0.318; 95%CI 0.137 - 0.739) and owning a dog (RR = 0.597, 95%CI 0.145 - 0.962) was negatively associated with illness. Whilst size of system (RR = 1.006, 95%CI 1.001 - 1.010) and reporting problems with sewage system (RR = 2.973, 95%CI 1.539 - 5.744) were positively associated with illness.</p> <p>Conclusions</p> <p>Educational interventions directed both at identified individuals and the community in general in small communities with poor water quality is a way of giving communities the skills and knowledge to manage their own drinking water quality. This may also have important and sustainable health benefits, though further research preferably using a randomised control trial design is needed.</p

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Fractional Zaslavsky and Henon Discrete Maps

This paper is devoted to the memory of Professor George M. Zaslavsky passed away on November 25, 2008. In the field of discrete maps, George M. Zaslavsky introduced a dissipative standard map which is called now the Zaslavsky map. G. Zaslavsky initialized many fundamental concepts and ideas in the fractional dynamics and kinetics. In this paper, starting from kicked damped equations with derivatives of non-integer orders we derive a fractional generalization of discrete maps. These fractional maps are generalizations of the Zaslavsky map and the Henon map. The main property of the fractional differential equations and the correspondent fractional maps is a long-term memory and dissipation. The memory is realized by the fact that their present state evolution depends on all past states with special forms of weights.Comment: 26 pages, LaTe

Muscle nonshivering thermogenesis in a feral mammal

Muscle nonshivering thermogenesis (NST) was recently suggested to play an important role in thermoregulation of species lacking brown adipose tissue (BAT). The mechanism, which is independent of muscle contractions, produces heat based on the activity of an ATPase pump in the sarcoplasmic reticulum (SERCA1a) and is controlled by the protein sarcolipin. To evaluate whether muscle NST could indeed play an important role in thermoregulation in species lacking BAT, we investigated the thermogenic capacities of newborn wild boar piglets. During cold exposure over the first 5 days of life, total heat production was improved while shivering intensity decreased, indicating an increasing contribution of NST. Sampling skeletal muscle tissue for analyses of SERCA activity as well as gene expression of SERCA1a and sarcolipin, we found an age-related increase in all three variables as well as in body temperature. Hence, the improved thermogenesis during the development of wild boars is not due to shivering but explained by the observed increase in SERCA activity. Our results suggest that muscle NST may be the primary mechanism of heat production during cold stress in large mammals lacking BAT, strengthening the hypothesis that muscle NST has likely played an important role in the evolution of endothermy