Pancreas Cancer-Associated Weight Loss.

Unintentional weight loss in patients with pancreatic cancer is highly prevalent and contributes to low therapeutic tolerance, reduced quality of life, and overall mortality. Weight loss in pancreatic cancer can be due to anorexia, malabsorption, and/or cachexia. Proper supportive care can stabilize or reverse weight loss in patients and improve outcomes. We review the literature on supportive care relevant to pancreatic cancer patients, and offer evidence-based recommendations that include expert nutritional assessment, counseling, supportive measures to ensure adequate caloric intake, pancreatic enzyme supplementation, nutritional supplement replacement, orexigenic agents, and exercise. Pancreatic Cancer Action Network-supported initiatives will spearhead the dissemination and adoption of these best supportive care practices. IMPLICATIONS FOR PRACTICE: Weight loss in pancreatic cancer patients is endemic, as 85% of pancreatic cancer patients meet the classic definition of cancer cachexia. Despite its significant prevalence and associated morbidity, there is no established approach to this disease entity. It is believed that this is due to an important knowledge gap in understanding the underlying biology and lack of optimal treatment approaches. This article reviews the literature regarding pancreas cancer-associated weight loss and establishes a new framework from which to view this complex clinical problem. An improved approach and understanding will help educate clinicians, improve clinical care, and provide more clarity for future clinical investigation

Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study.

BACKGROUND:Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer's disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individual's amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC). We further examined its potential association with subtle cognitive impairments in this population at elevated risk for Alzheimer's disease (AD). METHODS:The monocentric INSIGHT-preAD cohort includes 318 cognitively intact older individuals with SMC. All individuals underwent 18F-florbetapir PET scanning and extensive neuropsychological testing. We projected the regional amyloid uptake signal into the previously proposed hierarchical staging model of in vivo amyloid progression. We determined the adherence to this model across all cases and tested the association between increasing in vivo amyloid stage and cognitive performance using ANCOVA models. RESULTS:In total, 156 participants (49%) showed evidence of regional amyloid deposition, and all but 2 of these (99%) adhered to the hierarchical regional pattern implied by the in vivo amyloid progression model. According to a conventional binary classification based on global signal (SUVRCereb = 1.10), individuals in stages III and IV were classified as amyloid-positive (except one in stage III), but 99% of individuals in stage I and even 28% of individuals in stage II were classified as amyloid-negative. Neither in vivo amyloid stage nor conventional binary amyloid status was significantly associated with cognitive performance in this preclinical cohort. CONCLUSIONS:The proposed hierarchical staging scheme of PET-evidenced amyloid deposition generalizes well to data from an independent cohort of older people at elevated risk for AD. Future studies will determine the prognostic value of the staging approach for predicting longitudinal cognitive decline in older individuals at increased risk for AD

Higgs production in association with top quark pair at e+e- colliders in theories of higher dimensional gravity

The models of large extra compact dimensions, as suggested by Arkani-Hamed, Dimopoulos and Dvali, predict exciting phenomenological consequences with gravitational interactions becoming strong at the TeV scale. Such theories can be tested at the existing and future colliders. In this paper, we study the contribution of virtual Kaluza-Klein excitations in the process $e^+e^- \to t \bar t H$ at future linear collider (NLC). We find that the virtual exchange KK gravitons can modify the cross-section $\sigma(e^+e^- \to t \bar t H)$ significantly from its Standard Model value and will allow the effective string scale to be probed up to 7.9 TeV.Comment: 10 pages, Latex, 4 postscript figure

Pseudoscalar Higgs boson production associated with a single bottom quark at hadron colliders

We compute the complete next-to-leading order (NLO) SUSY-QCD corrections for the associated production of a pseudoscalar Higgs boson with a bottom quark via bottom-gluon fusion at the CERN Large Hadron Collider (LHC) and the Fermilab Tevatron. We find that the NLO QCD correction in the MSSM reaches $40$ at the LHC and $45$ at the Tevatron in our chosen parameter space

Common Origin of Soft mu-tau and CP Breaking in Neutrino Seesaw and the Origin of Matter

Neutrino oscillation data strongly support mu-tau symmetry as a good approximate flavor symmetry of the neutrino sector, which has to appear in any viable theory for neutrino mass-generation. The mu-tau breaking is not only small, but also the source of Dirac CP-violation. We conjecture that both discrete mu-tau and CP symmetries are fundamental symmetries of the seesaw Lagrangian (respected by interaction terms), and they are only softly broken, arising from a common origin via a unique dimension-3 Majorana mass-term of the heavy right-handed neutrinos. From this conceptually attractive and simple construction, we can predict the soft mu-tau breaking at low energies, leading to quantitative correlations between the apparently two small deviations \theta_{23} - 45^o and \theta_{13} - 0^o. This nontrivially connects the on-going measurements of mixing angle \theta_{23} with the upcoming experimental probes of \theta_{13}. We find that any deviation of \theta_{23} - 45^o must put a lower limit on \theta_{13}. Furthermore, we deduce the low energy Dirac and Majorana CP violations from a common soft-breaking phase associated with mu-tau breaking in the neutrino seesaw. Finally, from the soft CP breaking in neutrino seesaw we derive the cosmological CP violation for the baryon asymmetry via leptogenesis. We fully reconstruct the leptogenesis CP-asymmetry from the low energy Dirac CP phase and establish a direct link between the cosmological CP-violation and the low energy Jarlskog invariant. We predict new lower and upper bounds on the \theta_{13} mixing angle, 1^o < \theta_{13} < 6^o. In addition, we reveal a new hidden symmetry that dictates the solar mixing angle \theta_12 by its group-parameter, and includes the conventional tri-bimaximal mixing as a special case, allowing deviations from it.Comment: 60pp, JCAP in Press, v2: only minor stylistic refinements (added Daya Bay's future sensitivity in Figs.2+8, shortened some eqs, added new Appendix-A and some references), comments are welcome

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P&lt;0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

A More Flavored Higgs boson in Supersymmetric models

A More flavored Higgs boson arises when the flavor structure encoded in SUSY extensions of the SM is transmited to the Higgs sector. The flavor-Higgs transmition mechanism can have a radiative or mixing origin, as it is illustrated with several examples, and can produce interesting Higgs signatures that can be probed at future high-energy colliders. Within the MSSM, the flavor mediation mechanism can be of radiative type, as it is realized trhough gaugino-slepton loops, which transmit the flavor structture of the soft-breaking sector to the Higgs bosons. In particular we focus on evaluating the contributions from the general trilinear terms to the lepton flavor violating Higgs (LFV) vertices. On the other hand, as an example of flavor mediation through mixing, we discuss an E_6 inspired multi-Higgs model, with an abelian flavor symmetry, where LFV as well as lepton flavor conserving Higgs effects are found to arise, though in this case at tree-level. We find that Tevatron and LHC can provide information on the flavor structure of these models through the detection of the LFV higgs mode h-> tau+mu, while NLC can perform high-precision measurements of the LFC mode h-> tau tau.Comment: 17 pages, 5 tables, 3 figures; corrected mistake in last section, results changed but conclusions remmai

Graduate employability skills

This report examines how universities currently develop and teach undergraduate students employability skills, and how graduate employability skills might be assessed and reported on in the future. The report presents recommendations based on an integrated approach that emphasises improved processes for identifying, developing, assessing and reporting on graduate employability skills. Examples and descriptions of similar work already being carried out across the higher education sector are provided in the main body of the report

Prognostic value of histopathological DCIS features in a large-scale international interrater reliability study

Purpose: For optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk. Methods: Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff’s alpha (KA) and Gwet’s AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression. Results: Interrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2 + 3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05–6.11); grade 3 versus 1 + 2 (HR 2.64, 95% CI 1.35–5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34–10.23) were independently associated with a higher iIBC risk. Conclusions: Using majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features