Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Associação entre risco cardiovascular e hipertensão arterial em professores universitários Association between cardiovascular risk and hypertension in universities professors

A hipertensão arterial é uma das mais importantes causas modificáveis de morbi-mortalidade cardiovascular precoce na população adulta mundial, além de ser fator de risco independente para doenças cardiovasculares. Assim objetivou-se verificar a associação entre indicadores de risco cardiovascular e hipertensão arterial em professores universitários. Foram avaliados 145 professores da Universidade Federal de Viçosa (UFV), no ano de 2009, analisando-se as variáveis: sexo, idade, índice de massa corporal (IMC), relação cintura/quadril (RCQ), circunferência abdominal (CA), percentual de gordura (%G), colesterol total (CT), triacilglicerol (TG), glicose, pressão arterial sistólica (PAS) e diastólica (PAD) de repouso e consumo máximo de oxigênio (VO2máx). Utilizou-se o teste ANOVA one way para comparação entre indivíduos normotensos e pré-hipertensos e hipertensos. Calculou-se a razão de chances de desenvolvimento de quadros de PA elevada entre os indivíduos que apresentavam níveis indicativos de risco cardiovascular. Todos os tratamentos possuíram nível de significância de p < 0,05. Os homens apresentaram valores significativamente maiores para idade, peso, estatura, IMC, RCQ, CA, PAS e PAD. Já as mulheres possuíam um %G significativamente elevado. Os indivíduos com níveis pressóricos elevados apresentaram valores maiores para todas as variáveis, à exceção do VO2máx. Observou-se associação os fatores de risco e elevação da PA somente para as variáveis: sexo, idade, IMC, CA, %G e TG. Conclui-se que o gênero, a idade, o IMC, a circunferência abdominal, o percentual de gordura corporal e os triacilgliceróis foram considerados indicadores de risco cardiovascular por apresentarem associação com a hipertensão arterial na amostra de professores avaliados.<br>Hypertension is one of the most important modifiable causes of precocious cardiovascular morbid-mortality in the adult population worldwide, and it's an independent risk factor for cardiovascular disease. Thus we aimed to investigate the association between cardiovascular risk and blood pressure on universities professors. 145 professors from Universidade Federal de Viçosa (UFV) were evaluated, in 2009, analyzing the variables: gender, age, body mass index (BMI), waist / hip ratio (WHR), abdominal circumference (AC), percent body fat (% BF), total cholesterol (TC), triglyceride (TG), glucose, systolic blood pressure (SBP) and diastolic (DBP) at rest and maximal oxygen uptake (VO2max). We used ANOVA one way test for comparison between normotensive and prehypertensive and hypertensive individuals. It was calculated the odds ratio of high BP expansion among individuals who had indicative levels of cardiovascular risk. All treatments possessed a significance level of p < 0.05. Men showed significantly higher values for age, weight, height, BMI, WHR, AC, SBP and DBP. The women have had significantly higher % BF. Individuals with high blood pressure had higher values for all variables, except for VO2max. Association between risk factors and blood pressure increase was only observed to gender, age, BMI, % BF and BT. It is concluded that gender, age, BMI, abdominal circumference, percentage body fat and triglycerides were considered risk factors for cardiovascular disease associated with hypertension in the sample of professors evaluated

Search for dark matter produced in association with heavy-flavor quark pairs in proton-proton collisions at √s=13TeV

A search is presented for an excess of events with heavy-flavor quark pairs (tt¯ and bb¯) and a large imbalance in transverse momentum in data from proton–proton collisions at a center-of-mass energy of 13TeV. The data correspond to an integrated luminosity of 2.2fb-1 collected with the CMS detector at the CERN LHC. No deviations are observed with respect to standard model predictions. The results are used in the first interpretation of dark matter production in tt¯ and bb¯ final states in a simplified model. This analysis is also the first to perform a statistical combination of searches for dark matter produced with different heavy-flavor final states. The combination provides exclusions that are stronger than those achieved with individual heavy-flavor final states. © 2017, CERN for the benefit of the CMS collaboration

Measurement of differential cross sections for Z boson production in association with jets in proton-proton collisions at √s=13TeV

The production of a Z boson, decaying to two charged leptons, in association with jets in proton-proton collisions at a centre-of-mass energy of 13TeV is measured. Data recorded with the CMS detector at the LHC are used that correspond to an integrated luminosity of 2.19fb-1. The cross section is measured as a function of the jet multiplicity and its dependence on the transverse momentum of the Z boson, the jet kinematic variables (transverse momentum and rapidity), the scalar sum of the jet momenta, which quantifies the hadronic activity, and the balance in transverse momentum between the reconstructed jet recoil and the Z boson. The measurements are compared with predictions from four different calculations. The first two merge matrix elements with different parton multiplicities in the final state and parton showering, one of which includes one-loop corrections. The third is a fixed-order calculation with next-to-next-to-leading order accuracy for the process with a Z boson and one parton in the final state. The fourth combines the fully differential next-to-next-to-leading order calculation of the process with no parton in the final state with next-to-next-to-leading logarithm resummation and parton showering. © 2018, CERN for the benefit of the CMS collaboration

Measurements of triple-differential cross sections for inclusive isolated-photon+jet events in p p collisions at √s=8TeV

Measurements are presented of the triple-differential cross section for inclusive isolated-photon+jet events in p p collisions at s=8 TeV as a function of photon transverse momentum (pTγ), photon pseudorapidity (ηγ), and jet pseudorapidity (ηjet). The data correspond to an integrated luminosity of 19.7fb-1 that probe a broad range of the available phase space, for | ηγ| &amp;lt; 1.44 and 1.57 &amp;lt; | ηγ| &amp;lt; 2.50 , | ηjet| &amp;lt; 2.5 , 40&amp;lt;pTγ&amp;lt;1000GeV, and jet transverse momentum, pTjet, &amp;gt; 25GeV. The measurements are compared to next-to-leading order perturbative quantum chromodynamics calculations, which reproduce the data within uncertainties. © 2019, CERN for the benefit of the CMS collaboration

Azimuthal separation in nearly back-to-back jet topologies in inclusive 2- and 3-jet events in pp collisions at √s=13Te

A measurement for inclusive 2- and 3-jet events of the azimuthal correlation between the two jets with the largest transverse momenta, Δϕ12, is presented. The measurement considers events where the two leading jets are nearly collinear (“back-to-back”) in the transverse plane and is performed for several ranges of the leading jet transverse momentum. Proton-proton collision data collected with the CMS experiment at a center-of-mass energy of 13Te and corresponding to an integrated luminosity of 35.9fb-1 are used. Predictions based on calculations using matrix elements at leading-order and next-to-leading-order accuracy in perturbative quantum chromodynamics supplemented with leading-log parton showers and hadronization are generally in agreement with the measurements. Discrepancies between the measurement and theoretical predictions are as large as 15%, mainly in the region 177 ∘&amp;lt; Δϕ12&amp;lt; 180 ∘. The 2- and 3-jet measurements are not simultaneously described by any of models. © 2019, CERN for the benefit of the CMS collaboration