Reliability and inter-observer agreement of dermoscopic diagnosis of melanoma and melanocytic naevi

The aim of this study was to analyse the reliability and the inter- observer agreement of dermoscopy in the diagnosis of melanocytic skin lesions. Nine dermatologists, with a different training experience and who routinely used dermoscopy in different hospitals in Italy, evaluated clinical and dermoscopy photographs of 15 melanocytic lesions (four invasive melanomas, four histologically common naevi, and seven naevi with histological atypia). A further series of dermoscopic photographs of 40 melanocytic lesions was evaluated to quantify inter-observer concordance in recognizing dermoscopic criteria. Compared to the true (histological) diagnosis, clinical diagnosis (categories: melanoma, common naevus, atypical naevus) was correct in 40% of cases (range, 27-53%). The percentage raised to 55% (40-73%) by the use of dermoscopy, with an average improvement of 15.6%. Concerning melanoma, clinical diagnosis resulted in a sensitivity of 41.9%, specificity of 77.8%, positive predictive value (PPV) of 36.1%, negative predictive value (NPV) of 81.8%. By using dermoscopy, an improvement of diagnostic performance was found (sensitivity 75%, specificity 88.8%, VPP 71.0%, VPN 90.7%). The inter-observer agreement in melanoma diagnosis, by using dermoscopy, was similar to that obtained by clinical examination (k statistics = 0.54 and 0.52, respectively). Concerning dermoscopic criteria, the best agreement among observers was found for pseudopods, a dermoscopic parameter related to the radial growth phase of melanoma. We conclude that dermoscopy is an useful tool for a non-invasive diagnosis of melanocytic skin lesions, improving the diagnostic performance compared to clinical examination

Definition and diagnostic criteria of sleep-related hypermotor epilepsy

The syndrome known as nocturnal frontal lobe epilepsy is recognized worldwide and has been studied in a wide range of clinical and scientific settings (epilepsy, sleep medicine, neurosurgery, pediatric neurology, epidemiology, genetics). Though uncommon, it is of considerable interest to practicing neurologists because of complexity in differential diagnosis from more common, benign sleep disorders such as parasomnias, or other disorders like psychogenic nonepileptic seizures. Moreover, misdiagnosis can have substantial adverse consequences on patients' lives. At present, there is no consensus definition of this disorder and disagreement persists about its core electroclinical features and the spectrum of etiologies involved. To improve the definition of the disorder and establish diagnostic criteria with levels of certainty, a consensus conference using formal recommended methodology was held in Bologna in September 2014. It was recommended that the name be changed to sleep-related hypermotor epilepsy (SHE), reflecting evidence that the attacks are associated with sleep rather than time of day, the seizures may arise from extrafrontal sites, and the motor aspects of the seizures are characteristic. The etiology may be genetic or due to structural pathology, but in most cases remains unknown. Diagnostic criteria were developed with 3 levels of certainty: witnessed (possible) SHE, video-documented (clinical) SHE, and video-EEG-documented (confirmed) SHE. The main research gaps involve epidemiology, pathophysiology, treatment, and prognosis

Definition and diagnostic criteria of sleep-related hypermotor epilepsy.

The syndrome known as nocturnal frontal lobe epilepsy is recognized worldwide and has been studied in a wide range of clinical and scientific settings (epilepsy, sleep medicine, neurosurgery, pediatric neurology, epidemiology, genetics). Though uncommon, it is of considerable interest to practicing neurologists because of complexity in differential diagnosis from more common, benign sleep disorders such as parasomnias, or other disorders like psychogenic nonepileptic seizures. Moreover, misdiagnosis can have substantial adverse consequences on patients' lives. At present, there is no consensus definition of this disorder and disagreement persists about its core electroclinical features and the spectrum of etiologies involved. To improve the definition of the disorder and establish diagnostic criteria with levels of certainty, a consensus conference using formal recommended methodology was held in Bologna in September 2014. It was recommended that the name be changed to sleep-related hypermotor epilepsy (SHE), reflecting evidence that the attacks are associated with sleep rather than time of day, the seizures may arise from extrafrontal sites, and the motor aspects of the seizures are characteristic. The etiology may be genetic or due to structural pathology, but in most cases remains unknown. Diagnostic criteria were developed with 3 levels of certainty: witnessed (possible) SHE, video-documented (clinical) SHE, and video-EEG-documented (confirmed) SHE. The main research gaps involve epidemiology, pathophysiology, treatment, and prognosis

Estimation of traffic matrices for LRD traffic

The estimation of traffic matrices in a communications network on the basis of a set of traffic measurements on the network links is a well known problem, for which a number of solutions have been proposed when the traffic does not show dependence over time, as in the case of the Poisson process. However, extensive measurements campaigns conducted on IP networks have shown that the traffic exhibits long range dependence. Here two methods are proposed for the estimation of traffic matrices in the case of long range dependence, their asymptotic properties are studied, and their relative merits are compared

The global burden of cancer 2013 global burden of disease cancer collaboration

Importance Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. Objective To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. Evidence Review The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. Findings In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. Conclusions and Relevance Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation

Non-invasive positive pressure ventilation in acute hypercapnic respiratory failure: clinical experience of a respiratory ward

Background: Although a controlled trial demonstrated that non-invasive positive pressure ventilation (NIV) can be successfully applied to a respiratory ward (RW) for selected cases of acute hypercapnic respiratory failure (AHRF), clinical practice data about NIV use in this setting are limited. The aim of this observational study is to assess the feasibility and efficacy of NIV applied to AHRF in a RW in everyday practice. Methods: Twenty-two percent (216/984) of patients consecutively admitted for AHRF to our RW in Arezzo (years: 1996-2003) received NIV in addition to standard therapy, according to pre-defined routinely used criteria. Tolerance, effects upon arterial blood gases (ABG), success rate (avoidance a priori criteria for intubation) and predictors of failure of NIV were analysed. Results: Nine patients (4.2%) were found to be intolerant to NIV, while the remaining 207 (M: 157, F: 50; mean (SD) age: 73.2 (8.9) yrs; COPD: 71.5%) were ventilated for >1 hour. ABG significantly improved after two hours of NIV (pH: 7.32 (0.06) versus median (Interquartiles) 7.28 (7.24-7.31), p<0.0001; PaCO2: 71.9 (13.5) mmHg versus 80.0 (15.2) mmHg, p<0.0001; PaO2/FiO2: 212 (66) versus 184 (150-221), p<0.0001). NIV succeeded in avoiding intubation in 169/207 patients (81.6%) with hospital mortality of 15.5%. NIV failure was independently predicted by Activity of Daily Living score, pneumonia as cause of AHRF and Acute Physiology and Chronic Health Evaluation III score. Conclusions: In clinical practice NIV is feasible, effective in improving ABG and useful in avoiding intubation in most AHRF episodes that do not respond to the standard therapy managed in an RW adequately trained in NIV

Climate change effects on bread wheat phenology and grain quality: A case study in the north of Italy

Increasing temperatures, heat waves, and reduction of annual precipitation are all the expressions of climate change (CC), strongly affecting bread wheat (Triticum aestivum L.) grain yield in Southern Europe. Being temperature the major driving force of plants' phenological development, these variations also have effects on wheat phenology, with possible consequences on grain quality, and gluten protein accumulation. Here, through a case study in the Bolognese Plain (North of Italy), we assessed the effects of CC in the area, the impacts on bread wheat phenological development, and the consequences on grain gluten quality. The increasing trend in mean annual air temperature in the area since 1952 was significant, with a breakpoint identified in 1989, rising from 12.7 to 14.1°C, accompanied by the signals of increasing aridity, i.e., increase in water table depth. Bread wheat phenological development was compared in two 15-year periods before and after the breakpoint, i.e., 1952-1966 (past period), and 2006-2020 (present period), the latest characterized by aridity and increased temperatures. A significant shortening of the chronological time necessary to reach the main phenological phases was observed for the present period compared to the past period, finally shortening the whole life cycle. This reduction, as well as the higher temperature regime, affected gluten accumulation during the grain-filling process, as emerged analyzing gluten composition in grain samples of the same variety harvested in the area both before and after the breakpoint in temperature. In particular, the proportion of gluten polymers (i.e., gliadins, high and low molecular weight glutenins, and their ratio) showed a strong and significant correlation with cumulative growing degree days (CGDDs) accumulated during the grain filling. Higher CGDD values during the period, typical of CC in Southern Europe, accounting for higher temperature and faster grain filling, correlated with gliadins, high molecular weight glutenins, and their proportion with low molecular weight glutenins. In summary, herein reported, data might contribute to assessing the effects of CC on wheat phenology and quality, representing a tool for both predictive purposes and decision supporting systems for farmers, as well as can guide future breeding choices for varietal innovation

A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a “candidate interactome” (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning