Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

<p>Abstract</p> <p>Background</p> <p>Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions) are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN) may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC) or squamous cell skin carcinomas (SCSC).</p> <p>Methods</p> <p>Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor.</p> <p>Results</p> <p>Sixteen elder (median 70 years-old) patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination), 40% PR (>30% tumor reduction), and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated.</p> <p>Conclusion</p> <p>The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials.</p> <p>Trial registration</p> <p>Current Controlled Trials RPCEC00000052.</p

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Fin Spine Bone Resorption in Atlantic Bluefin Tuna, Thunnus thynnus, and Comparison between Wild and Captive-Reared Specimens

Bone resorption in the first spine of the first dorsal fin of Atlantic bluefin tuna (ABFT) has long been considered for age estimation studies. In the present paper spine bone resorpion was assessed in wild (aged 1 to 13 years) and captive-reared (aged 2 to 11 years) ABFT sampled from the Mediterranean Sea. Total surface (TS), solid surface (SS) and reabsorbed surface (RS) were measured in spine transverse sections in order to obtain proportions of SS and RS. The spine section surface was found to be isometrically correlated to the fish fork length by a power equation. The fraction of solid spine bone progressively decreased according to a logarithmic equation correlating SS/TS to both fish size and age. The values ranged from 57% in the smallest examined individuals to 37% in the largest specimens. This phenomenon was further enhanced in captive-reared ABFT where SS/TS was 22% in the largest measured specimen. The difference between the fraction of SS of wild and captive-reared ABFT was highly significant. In each year class from 1- to 7-year-old wild specimens, the fraction of spine reabsorbed surface was significantly higher in specimens collected from March to May than in those sampled during the rest of the year. In 4-year-old fish the normal SS increase during the summer did not occur, possibly coinciding with their first sexual maturity. According to the correlations between SS/TS and age, the rate of spine bone resorption was significantly higher, even almost double, in captive-reared specimens. This could be attributed to the wider context of systemic dysfunctions occurring in reared ABFT, and may be related to a number of factors, including nutritional deficiencies, alteration of endocrine profile, cortisol-induced stress, and loss of spine functions during locomotion in rearing conditions.Versión del editor4,411

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015 : a systematic analysis from the Global Burden of Disease Study 2015

Background The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed. Methods We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI). Findings Worldwide, the age-standardised prevalence of daily smoking was 25.0% (95% uncertainty interval [UI] 24.2-25.7) for men and 5.4% (5.1-5.7) for women, representing 28.4% (25.8-31.1) and 34.4% (29.4-38.6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11.5% of global deaths (6.4 million [95% UI 5.7-7.0 million]) were attributable to smoking worldwide, of which 52.2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015. Interpretation The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years.Peer reviewe

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Mitochondrial respiratory states and rate

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followguidelines of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute to reproducibility between laboratories and thussupport the development of databases of mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

Combined measurement of differential and total cross sections in the H → γγ and the H → ZZ* → 4ℓ decay channels at s=13 TeV with the ATLAS detector

A combined measurement of differential and inclusive total cross sections of Higgs boson production is performed using 36.1 fb−1 of 13 TeV proton–proton collision data produced by the LHC and recorded by the ATLAS detector in 2015 and 2016. Cross sections are obtained from measured H→γγ and H→ZZ*(→4ℓ event yields, which are combined taking into account detector efficiencies, resolution, acceptances and branching fractions. The total Higgs boson production cross section is measured to be 57.0−5.9 +6.0 (stat.) −3.3 +4.0 (syst.) pb, in agreement with the Standard Model prediction. Differential cross-section measurements are presented for the Higgs boson transverse momentum distribution, Higgs boson rapidity, number of jets produced together with the Higgs boson, and the transverse momentum of the leading jet. The results from the two decay channels are found to be compatible, and their combination agrees with the Standard Model predictions