Towards precise predictions for Higgs-boson production in the MSSM

We study the production of scalar and pseudoscalar Higgs bosons via gluon fusion and bottom-quark annihilation in the MSSM. Relying on the NNLO-QCD calculation implemented in the public code SusHi, we provide precise predictions for the Higgs-production cross section in six benchmark scenarios compatible with the LHC searches. We also provide a detailed discussion of the sources of theoretical uncertainty in our calculation. We examine the dependence of the cross section on the renormalization and factorization scales, on the precise definition of the Higgs-bottom coupling and on the choice of PDFs, as well as the uncertainties associated to our incomplete knowledge of the SUSY contributions through NNLO. In particular, a potentially large uncertainty originates from uncomputed higher-order QCD corrections to the bottom-quark contributions to gluon fusion.Comment: 62 pages, 24 pdf figures; v2: minor clarifications, improved plot quality, matches published versio

Phosphotyrosine Signaling Analysis in Human Tumors Is Confounded by Systemic Ischemia-Driven Artifacts and Intra-Specimen Heterogeneity

Tumor protein phosphorylation analysis may provide insight into intracellular signaling networks underlying tumor behavior, revealing diagnostic, prognostic or therapeutic information. Human tumors collected by The Cancer Genome Atlas program potentially offer the opportunity to characterize activated networks driving tumor progression, in parallel with the genetic and transcriptional landscape already documented for these tumors. However, a critical question is whether cellular signaling networks can be reliably analyzed in surgical specimens, where freezing delays and spatial sampling disparities may potentially obscure physiologic signaling. To quantify the extent of these effects, we analyzed the stability of phosphotyrosine (pTyr) sites in ovarian and colon tumors collected under conditions of controlled ischemia and in the context of defined intratumoral sampling. Cold-ischemia produced a rapid, unpredictable, and widespread impact on tumor pTyr networks within 5 minutes of resection, altering up to 50% of pTyr sites by more than 2-fold. Effects on adhesion and migration, inflammatory response, proliferation, and stress response pathways were recapitulated in both ovarian and colon tumors. In addition, sampling of spatially distinct colon tumor biopsies revealed pTyr differences as dramatic as those associated with ischemic times, despite uniform protein expression profiles. Moreover, intratumoral spatial heterogeneity and pTyr dynamic response to ischemia varied dramatically between tumors collected from different patients. Overall, these findings reveal unforeseen phosphorylation complexity, thereby increasing the difficulty of extracting physiologically relevant pTyr signaling networks from archived tissue specimens. In light of this data, prospective tumor pTyr analysis will require appropriate sampling and collection protocols to preserve in vivo signaling features.National Institutes of Health (U.S.) (Grant U24 CA159988

Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine. A post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial

Background: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. Methods: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. Results: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). Conclusions: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. Trial registration: ClinicalTrials.gov identifier: NCT02686034

Shifting Winds: Using Ancestry DNA to Explore Multiracial Individuals\u27 Patterns of Articulating Racial Identity

This study explored how genotype information affects identification narratives of multiracial individuals. Twenty-one multiracial individuals completed individual interviews before and after receiving a DNA analysis to clarify their genetically based racial ancestry. Based on results, this article proposes patterns of articulating racial identity by multiracial individuals. Four patterns extend evolving research in multiracial identification, namely (1) the individual articulates a monoracial identity; (2) the individual articulates one identity, but this can shift in response to various conditions; (3) the individual articulates an extraracial identity, opting out of traditional categories applied to race; and (4) the person distinguishes traditional categories of race from culture and owns the two identities in different ways. Implications of these findings are discussed. First, adding new ancestry DNA information further muddles the neat categories of race, consistent with the view of race as socially constructed. Second, results emphasize the fluidity of identification for multiracial individuals. Third, DNA information challenges the neat percentages people tend to associate with their backgrounds. Particularly for younger multiracial individuals, there was less of a sense that race was a real thing and more that culture played a big part in how they saw themselves

Analysis of Immune Checkpoint Drug Targets and Tumor Proteotypes in Non-Small Cell Lung Cancer

New therapeutics targeting immune checkpoint proteins have significantly advanced treatment of non-small cell lung cancer (NSCLC), but protein level quantitation of drug targets presents a critical problem. We used multiplexed, targeted mass spectrometry (MS) to quantify immunotherapy target proteins PD-1, PD-L1, PD-L2, IDO1, LAG3, TIM3, ICOSLG, VISTA, GITR, and CD40 in formalin-fixed, paraffin-embedded (FFPE) NSCLC specimens. Immunohistochemistry (IHC) and MS measurements for PD-L1 were weakly correlated, but IHC did not distinguish protein abundance differences detected by MS. PD-L2 abundance exceeded PD-L1 in over half the specimens and the drug target proteins all displayed different abundance patterns. mRNA correlated with protein abundance only for PD-1, PD-L1, and IDO1 and tumor mutation burden did not predict abundance of any protein targets. Global proteome analyses identified distinct proteotypes associated with high PD-L1-expressing and high IDO1-expressing NSCLC. MS quantification of multiple drug targets and tissue proteotypes can improve clinical evaluation of immunotherapies for NSCLC

Physics at the e+ e- Linear Collider

A comprehensive review of physics at an e+e- Linear Collider in the energy range of sqrt{s}=92 GeV--3 TeV is presented in view of recent and expected LHC results, experiments from low energy as well as astroparticle physics.The report focuses in particular on Higgs boson, Top quark and electroweak precision physics, but also discusses several models of beyond the Standard Model physics such as Supersymmetry, little Higgs models and extra gauge bosons. The connection to cosmology has been analyzed as well.Comment: 179 pages, plots and references updated, version to be published at EPJ

Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands