Pancreatic ductal adenocarcinoma and chronic pancreatitis may be diagnosed by exhaled-breath profiles:a multicenter pilot study

Background: The diagnosis of pancreatic adenocarcinoma and chronic pancreatitis often rely on expensive and invasive diagnostic approaches, which are not always discriminative since patients with chronic pancreatitis and pancreatic adenocarcinoma may present with similar symptoms. Volatile organic compounds (VOCs) in expired breath, could be used as a non-invasive diagnostic biological marker for detection of pancreatic pathology. Detection and discrimination of pancreatic pathology with an electronic nose has not yet been reported. Purpose: The objective of this pilot study was to determine the diagnostic potential of an electronic nose to identify pancreatic adenocarcinoma and chronic pancreatitis by analyzing volatile organic compoundg (VOC) profiles in exhaled air. Patients and methods: In a multicenter study, the exhaled air of 56 chronic pancreatitis patients, 29 pancreatic adenocarcinoma patients, and 74 disease controls were analyzed using an electronic nose based on 3 metal oxide sensors (MOS). The measurements were evaluated utilizing an artificial neural network. Results: VOC profiles of chronic pancreatitis patients could be discriminated from disease controls with an accuracy of 0.87 (AUC 0.95, sensitivity 80%, specificity 92%). Also, VOC profiles of patients with pancreatic adenocarcinoma differed from disease controls with an accuracy of 0.83 (AUC 0.87, sensitivity 83%, specificity 82%). Discrimination between chronic pancreatitis and pancreatic adenocarcinoma showed an accuracy of 0.75 (AUC 0.83, sensitivity 83%, specificity 71%). Conclusion: An electronic nose may be a valuable diagnostic tool in diagnosis of pancreatic adenocarcinoma and chronic pancreatitis. The current study shows the potential of an electronic nose for discriminating between chronic pancreatitis, pancreatic adenocarcinoma and healthy controls. The results from this proof-of-concept study warrant external validation in larger cohorts

LiFePO4 spray drying scale-up and carbon-cage for improved cyclability

The growing market for electrical vehicles requires inexpensive, long-lasting batteries. LiFePO4 (LFP) melt-synthesized from ore concentrate fits this role, but the manufacturing process requires additional steps that includes grinding large ingots into a nanoparticle suspension followed by a dessication step. Spray drying, rather than tray drying, creates a mesopomus powder that enhances wettability. Adding lactose and high-Mw polyvinyl alcohol (PVA) to the suspension of nanostructures followed by pyrolysis, creates a carbon-cage that interconnects the cathode nanoparticles, imparting better capacity (LiFePO4/C: 161 mA h g(-1) at 0.1C), discharge rate (flat plateau, 145 mA h g(-1) at 5C), and cyclability (91% capacity retention after 750 cycles at 1C). Particle size affects battery stability; PVA increases the suspension's viscosity and alters the powder morphology, from spherical to hollow particles. A model describes the non-Newtonian suspension's rheology changing: shear, temperature, LFP and PVA loading. Carbon precursors prevent the nanoparticles from sintering during calcination but lactose gasifies 50% of the carbon, according to the chemical and allotropic composition measurements (CS analyzer, XPS, and Raman). The carbon-cage imparts micmporosity and we correlate the SEM and TEM powder's morphology with N2 physisorption porosimetry. Ultrasonication of the suspension fragments the PVA chain, which is detrimental to the final cathode performance

UV friendly T-parity in the SU(6)/Sp(6) little Higgs model

Electroweak precision tests put stringent constraints on the parameter space of little Higgs models. Tree-level exchange of TeV scale particles in a generic little Higgs model produce higher dimensional operators that make contributions to electroweak observables that are typically too large. To avoid this problem a discrete symmetry dubbed T-parity can be introduced to forbid the dangerous couplings. However, it was realized that in simple group models such as the littlest Higgs model, the implementation of T-parity in a UV completion could present some challenges. The situation is analogous to the one in QCD where the pion can easily be defined as being odd under a new $Z_2$ symmetry in the chiral Lagrangian, but this $Z_2$ is not a symmetry of the quark Lagrangian. In this paper we examine the possibility of implementing a T-parity in the low energy $SU(6)/Sp(6)$ model that might be easier to realize in the UV. In our model, the T-parity acts on the low energy non-linear sigma model field in way which is different to what was originally proposed for the Littlest Higgs, and lead to a different low energy theory. In particular, the Higgs sector of this model is a inert two Higgs doublets model with an approximate custodial symmetry. We examine the contributions of the various sectors of the model to electroweak precision data, and to the dark matter abundance.Comment: 21 pages,4 figures. Clarifications added, typos corrected and references added. Published in JHE

Long-lived charged Higgs at LHC as a probe of scalar Dark Matter

We study inert charged Higgs boson $H^\pm$ production and decays at LHC experiments in the context of constrained scalar dark matter model (CSDMM). In the CSDMM the inert doublet and singlet scalar's mass spectrum is predicted from the GUT scale initial conditions via RGE evolution. We compute the cross sections of processes $pp\to H^+H^-,\, H^\pm S_i^0$ at the LHC and show that for light $H^\pm$ the first one is dominated by top quark mediated 1-loop diagram with Higgs boson in s-channel. In a significant fraction of the parameter space $H^\pm$ are long-lived because their decays to predominantly singlet scalar dark matter (DM) and next-to-lightest (NL) scalar, $H^\pm\to S_{\text{DM, NL}} ff',$ are suppressed by the small singlet-doublet mixing angle and by the moderate mass difference $\Delta M=M_{H^+}-M_{\text{DM}} .$ The experimentally measurable displaced vertex in $H^\pm$ decays to leptons and/or jets and missing energy allows one to discover the $H^+H^-$ signal over the huge $W^+W^-$ background. We propose benchmark points for studies of this scenario at the LHC. If, however, $H^\pm$ are short-lived, the subsequent decays $S_{\text{NL}}\to S_{\text{DM}} f\bar f$ necessarily produce additional displaced vertices that allow to reconstruct the full $H^\pm$ decay chain.Comment: 15 pages, 5 figure

Dark Matter and Higgs Sector

The inert doublet model is an extension of the Standard Model of Elementary Particles that is defined by the only addition of a second Higgs doublet without couplings to quarks or leptons. This minimal framework has been studied for many reasons. In particular, it has been suggested that the new degrees of freedom contained in this doublet can account for the Dark Matter of the Universe.Comment: 6 pages, 3 figures,To appear in the Proceedings of the sixth International Workshop on the Dark Side of the Universe (DSU2010) Leon, Guanajuato, Mexico 1-6 June 201

Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study

BACKGROUND: There is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features. RESULTS: After correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with qval = 0.029 and qval = 0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL. CONCLUSIONS: Alcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses indicated that dietary folate and alcohol intake may be associated with genomic regions with tumor suppressor activity such as the GSDMD and HOXA5 genes. These results were in line with the hypothesis that epigenetic mechanisms play a role in the association between folate and alcohol, although further studies are warranted to clarify the importance of these mechanisms in cancer

Developmental expression of retinoic acid receptors (RARs)

Here, I review the developmental expression features of genes encoding the retinoic acid receptors (RARs) and the 'retinoid X' or rexinoid receptors (RXRs). The first detailed expression studies were performed in the mouse over two decades ago, following the cloning of the murine Rar genes. These studies revealed complex expression features at all stages of post-implantation development, one receptor gene (Rara) showing widespread expression, the two others (Rarb and Rarg) with highly regionalized and/or cell type-specific expression in both neural and non-neural tissues. Rxr genes also have either widespread (Rxra, Rxrb), or highly-restricted (Rxrg) expression patterns. Studies performed in zebrafish and Xenopus demonstrated expression of Rar and Rxr genes (both maternal and zygotic), at early pre-gastrulation stages. The eventual characterization of specific enzymes involved in the synthesis of retinoic acid (retinol/retinaldehyde dehydrogenases), or the triggering of its catabolism (CYP26 cytochrome P450s), all of them showing differential expression patterns, led to a clearer understanding of the phenomenons regulated by retinoic acid signaling during development. Functional studies involving targeted gene disruptions in the mouse, and additional approaches such as dominant negative receptor expression in other models, have pinpointed the specific, versus partly redundant, roles of the RARs and RXRs in many developing organ systems. These pleiotropic roles are summarized hereafter in relationship to the receptors’ expression patterns