{\eta} and {\eta}' mesons from Nf=2+1+1 twisted mass lattice QCD

We determine mass and mixing angles of eta and eta' states using Nf=2+1+1 Wilson twisted mass lattice QCD. We describe how those flavour singlet states need to be treated in this lattice formulation. Results are presented for three values of the lattice spacing, a=0.061 fm, a=0.078 fm and a=0.086 fm, with light quark masses corresponding to values of the charged pion mass in a range of 230 to 500 MeV and fixed bare strange and charm quark mass values. We obtain 557(15)(45) MeV for the eta mass (first error statistical, second systematic) and 44(5) degrees for the mixing angle in the quark flavour basis, corresponding to -10(5) degrees in the octet-singlet basis.Comment: 28 pages, 9 figures, version to appear in JHEP, extended discussion of autocorrelation times and comparison to results available in the literature, added a comment for FS-effects and clarified the description of our blocking procedur

Up, down, strange and charm quark masses with N-f=2+1+1 twisted mass lattice QCD

We present a lattice QCD calculation of the up, down, strange and charm quark masses performed using the gauge configurations produced by the European Twisted Mass Collaboration with N-f = 2 + 1 + 1 dynamical quarks, which include in the sea, besides two light mass degenerate quarks, also the strange and charm quarks with masses close to their physical values. The simulations are based on a unitary setup for the two light quarks and on a mixed action approach for the strange and charm quarks. The analysis uses data at three values of the lattice spacing and pion masses in the range 210-450 MeV, allowing for accurate continuum limit and controlled chiral extrapolation. The quark mass renormalization is carried out non-perturbatively using the RI'-MOM method. The results for the quark masses converted to the (MS) over bar scheme are: m(ud) (2 GeV) = 3.70(17) MeV, m(s)(2 GeV) = 99.6(4.3) MeV and m(c)(m(c)) = 1.348(46) GeV. We obtain also the quark mass ratios m(s)/m(ud) = 26.66(32) and m(c)/m(s) = 11.62(16). By studying the mass splitting between the neutral and charged kaons and using available lattice results for the electromagnetic contributions, we evaluate m(u)/m(d) = 0.470(56), leading to m(u) = 2.36(24) MeV and m(d) = 5.03(26) MeV

Взаимосвязь показателей кровообращения мышц бедра и плеча с координационной точностью при совершенствовании ударных баллистических движений

В работе была исследована взаимосвязь показателей кровообращения мышц бедра и плеча с координационной точностью при совершенствовании ударных баллистических движений. Для этого было сформировано две группы: в экспериментальной группе в качестве предупреждения травматизма кисти использовались боксерские перчатки (10 унций), а в контрольной - снарядные перчатки. В результате после нанесения одиночного акцентированного прямого удара правой рукой в голову по боксерскому мешку в течение раунда было получено, что в экспериментальной группе происходило увеличение интенсивности кровенаполнения задней поверхности правого бедра и увеличение венозного оттока. Можно предположить, что спортсмены экспериментальной группы больше опираются на правую ногу в заключительной фазе ударного действия, что является более правильно с биомеханической точки зрения нанесения ударов. Интенсивность кровенаполнения и венозного оттока плеча в экспериментальной группе, наоборот, падала. Это позволяет сделать предположение о том, что мышцы плеча при выполнении ударных движений лишь незначительно задействуются спортсменами старших спортивных разрядов в завершающей фазе ударного действия. Данный факт им позволяет наносить удары с большей точностью и эффективностью

The Immune System Strikes Back: Cellular Immune Responses against Indoleamine 2,3-dioxygenase

The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses.The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T lymphocytes (CTL) from the peripheral blood of cancer patients were cloned and expanded. The functional capacity of the established CTL clones was examined by chrome release assays. The study unveiled spontaneous cytotoxic T-cell reactivity against IDO in peripheral blood as well as in the tumor microenvironment of different cancer patients. We demonstrate that these IDO reactive T cells are indeed peptide specific, cytotoxic effector cells. Hence, IDO reactive T cells are able to recognize and kill tumor cells including directly isolated AML blasts as well as IDO-expressing dendritic cells, i.e. one of the major immune suppressive cell populations.IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, IDO-based immunotherapy holds the promise to boost anti-cancer immunotherapy in general

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+) tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non–small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy–induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens

Accuracy of Electronic Health Record Data for Identifying Stroke Cases in Large-Scale Epidemiological Studies: A Systematic Review from the UK Biobank Stroke Outcomes Group

Long-term follow-up of population-based prospective studies is often achieved through linkages to coded regional or national health care data. Our knowledge of the accuracy of such data is incomplete. To inform methods for identifying stroke cases in UK Biobank (a prospective study of 503,000 UK adults recruited in middle-age), we systematically evaluated the accuracy of these data for stroke and its main pathological types (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage), determining the optimum codes for case identification.We sought studies published from 1990-November 2013, which compared coded data from death certificates, hospital admissions or primary care with a reference standard for stroke or its pathological types. We extracted information on a range of study characteristics and assessed study quality with the Quality Assessment of Diagnostic Studies tool (QUADAS-2). To assess accuracy, we extracted data on positive predictive values (PPV) and-where available-on sensitivity, specificity, and negative predictive values (NPV).37 of 39 eligible studies assessed accuracy of International Classification of Diseases (ICD)-coded hospital or death certificate data. They varied widely in their settings, methods, reporting, quality, and in the choice and accuracy of codes. Although PPVs for stroke and its pathological types ranged from 6-97%, appropriately selected, stroke-specific codes (rather than broad cerebrovascular codes) consistently produced PPVs >70%, and in several studies >90%. The few studies with data on sensitivity, specificity and NPV showed higher sensitivity of hospital versus death certificate data for stroke, with specificity and NPV consistently >96%. Few studies assessed either primary care data or combinations of data sources.Particular stroke-specific codes can yield high PPVs (>90%) for stroke/stroke types. Inclusion of primary care data and combining data sources should improve accuracy in large epidemiological studies, but there is limited published information about these strategies