Bayesian variable selection and survival modeling: assessing the Most important comorbidities that impact lung and colorectal cancer survival in Spain

ancer survival represents one of the main indicators of interest in cancer epidemiology. However, the survival of cancer patients can be affected by several factors, such as comorbidities, that may interact with the cancer biology. Moreover, it is interesting to understand how different cancer sites and tumour stages are affected by different comorbidities. Identifying the comorbidities that affect cancer survival is thus of interest as it can be used to identify factors driving the survival of cancer patients. This information can also be used to identify vulnerable groups of patients with comorbidities that may lead to worst prognosis of cancer. We address these questions and propose a principled selection and evaluation of the effect of comorbidities on the overall survival of cancer patients. In the first step, we apply a Bayesian variable selection method that can be used to identify the comorbidities that predict overall survival. In the second step, we build a general Bayesian survival model that accounts for time-varying effects. In the third step, we derive several posterior predictive measures to quantify the effect of individual comorbidities on the population overall survival. We present applications to data on lung and colorectal cancers from two Spanish population-based cancer registries. The proposed methodology is implemented with a combination of the R-packages mombf and rstan. We provide the code for reproducibility at https://github.com/migariane/BayesVarImpComorbiCancer

Inhibition of calcium-independent phospholipase A impairs agonist-induced calcium entry in keratinocytes

BACKGROUND: In many cells, depletion of intracellular calcium (Ca2+) reservoirs triggers Ca2+ entry through store-operated Ca2+ channels in the plasma membrane. However, the mechanisms of agonist-induced calcium entry (ACE) in keratinocytes are not fully understood. OBJECTIVES: This study was designed to determine if pharmacological inhibition of calcium-independent phospholipase A (iPLA(2)) impairs ACE in normal human epidermal keratinocytes. METHODS: Confocal laser scanning microscopy was used to monitor the dynamics of Ca2+ signalling in keratinocytes loaded with the calcium-sensitive dye Fluo-4. Cells were stimulated with extracellular nucleotides [adenosine triphosphate (ATP) or uridine triphosphate (UTP)] or with lysophosphatidic acid (LPA), a bioactive lipid that regulates keratinocyte proliferation and differentiation. RESULTS: Both ATP and UTP induced Ca2+ release in primary human keratinocytes. This was not followed by robust Ca2+ influx when the experiments were performed in low Ca2+ (70 micromol L(-1)) medium. Upon elevation of extracellular Ca2+ to 1.2 mmol L(-1), however, a biphasic response consisting of an initial Ca2+ peak followed by an elevated plateau was observed. The plateau phase was inhibited when cells were treated with bromoenol lactone, a specific pharmacological inhibitor of iPLA(2). These findings indicate that iPLA(2) activity is required for ACE in keratinocytes. LPA also evoked Ca2+ release in keratinocytes but failed to induce sustained Ca2+ entry even when extracellular Ca2+ was elevated to 1.2 mmol L(-1). CONCLUSION: Our results demonstrate for the first time an important role for iPLA(2) in regulating ACE in primary human keratinocytes

Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression

Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm(2) to 475/mm(2) in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3 alpha and PPAR coactivator-1 alpha (PGC-1 alpha) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis. Copyright (C) 2012 S. Karger AG, Base

HIV Types, Groups, Subtypes and Recombinant Forms: Errors in Replication, Selection Pressure and Quasispecies

HIV-1 is a chimpanzee virus which was transmitted to humans by several zoonotic events resulting in infection with HIV-1 groups M P, and in parallel transmission events from sooty mangabey monkey viruses leading to infections with HIV-2 groups A H. Both viruses have circulated in the human population for about 80 years. In the infected patient, HIV mutates, and by elimination of some of the viruses by the action of the immune system individual quasispecies are formed. Along with the selection of the fittest viruses, mutation and recombination after superinfection with HIV from different groups or subtypes have resulted in the diversity of their patterns of geographic distribution. Despite the high variability observed, some essential parts of the HIV genome are highly conserved. Viral diversity is further facilitated in some parts of the HIV genome by drug selection pressure and may also be enhanced by different genetic factors, including HLA in patients from different regions of the world. Viral and human genetic factors influence pathogenesis. Viral genetic factors are proteins such as Tat, Vif and Rev. Human genetic factors associated with a better clinical outcome are proteins such as APOBEC, langerin, tetherin and chemokine receptor 5 (CCR5) and HLA B27, B57, DRB1{*}1303, KIR and PARD3B. Copyright (C) 2012 S. Karger AG, Base

Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Long-term results of breast conservation and immediate volume replacement with myocutaneous latissimus dorsi flap

<p>Abstract</p> <p>Background</p> <p>Published long-term outcomes of oncoplastic breast-conserving surgery are scarce and, specifically, aesthetic outcomes assessed with an objective method have not previously been published.</p> <p>Methods</p> <p>A cohort of 41 patients treated with a quadrantectomny and immediate reconstruction using a myocutaneous latissimus dorsi flap were analyzed and their aesthetic outcomes were evaluated objectively by BCCT.core software.</p> <p>Results</p> <p>At the end of a 58-month follow-up from the date of initial diagnosis, one patient (2.4%) developed an ipsilateral recurrence, six patients developed distant metastases and three patients died (7.3%) without ipsilateral recurrence, one of them presenting hepatic metastases at the time of the initial diagnosis. We were able to evaluate aesthetic results in 23 patients, 3 assessed as excellent, 12 good and 8 fair.</p> <p>Conclusion</p> <p>This oncoplastic volume replacement technique obtained a good local control and satisfactory and stable aesthetic results which have maintained unchanged after a long period of time.</p

Pure-quartic solitons

Temporal optical solitons have been the subject of intense research due to their intriguing physics and applications in ultrafast optics and supercontinuum generation. Conventional bright optical solitons result from the interaction of anomalous group-velocity dispersion and self-phase modulation. Here we experimentally demonstrate a class of bright soliton arising purely from the interaction of negative fourth-order dispersion and self-phase modulation, which can occur even for normal group-velocity dispersion. We provide experimental and numerical evidence of shape-preserving propagation and flat temporal phase for the fundamental pure-quartic soliton and periodically modulated propagation for the higher-order pure-quartic solitons. We derive the approximate shape of the fundamental pure-quartic soliton and discover that is surprisingly Gaussian, exhibiting excellent agreement with our experimental observations. Our discovery, enabled by precise dispersion engineering, could find applications in communications, frequency combs and ultrafast lasers

Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.