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Deep Generative Models: The winning key for large and easily accessible ECG datasets?

Large high-quality datasets are essential for building powerful artificial intelligence (AI) algorithms capable of supporting advancement in cardiac clinical research. However, researchers working with electrocardiogram (ECG) signals struggle to get access and/or to build one. The aim of the present work is to shed light on a potential solution to address the lack of large and easily accessible ECG datasets. Firstly, the main causes of such a lack are identified and examined. Afterward, the potentials and limitations of cardiac data generation via deep generative models (DGMs) are deeply analyzed. These very promising algorithms have been found capable not only of generating large quantities of ECG signals but also of supporting data anonymization processes, to simplify data sharing while respecting patients' privacy. Their application could help research progress and cooperation in the name of open science. However several aspects, such as a standardized synthetic data quality evaluation and algorithm stability, need to be further explored

Il gioco è una cosa seria” Il diritto al gioco per bambine e bambini con disabilità: una ricerca sul campo

Il gioco è una cosa tanto seria da essere considerato un diritto (www.unicef.it) e molti sono gli autori che si sono interessati alle funzioni che il gioco può esercitare: una via d’accesso privilegiata al mondo intra-psichico del bambino; una possibilità di liberare angosce e paure; uno spazio di transizione, un ponte tra sé e ambiente; un supporto alla conoscenza della realtà e all’apprendimento; un supporto allo sviluppo del pensiero individuale e del pensiero sociale; una funzione linguistica e cooperativa, oltre che una possibilità per approfondire la conoscenza di se stessi (S. Freud,1915-1917; Mead 1934; Vygotskij, 1934; Piaget, 1945; Klein, 1953; Erikson, 1963; A. Freud, 1965). Il presente lavoro di ricerca si fonda sul presupposto che, considerata la grande rilevanza delle sue funzioni, l’attività di gioco sia imprescindibile per tutti i bambini. Tuttavia, ad oggi, non è possibile identificare giocattoli pensati specificatamente per bambini con sviluppo atipico che, oltre a supportare una maturazione delle abilità deficitarie configurandosi come contesti di apprendimento, mantengano la loro intrinseca natura ludico-ricreativa. Con l’obiettivo di riformulare l’insieme dei prodotti attualmente disponibili nel catalogo di una nota azienda produttrice di giocattoli la prima fase della ricerca ha consentito di evidenziare le caratteristiche dei prodotti particolarmente adatti/compatibili/funzionali/utili alla crescita di bambini e bambine con disabilità, tenendo conto della necessità di esercitare le capacità residue attraverso formati di gioco (Bruner, 1983), mantenendo connotati ludici e ricreativi. Per effettuare tali valutazioni sono state identificate sulla base del DSM V e dell’ICF le macro-categorie di disabilità: sensoriale visiva, sensoriale uditiva, grosso-motoria, fine-motoria, cognitiva e emotivo-relazionale. Ciascun gioco in catalogo è stato valutato da tre diverse figure professionali secondo i parametri di autonomia, adeguatezza, motivazione, decifrabilità cognitiva e relazionalità rispetto alle singole categorie di disabilità. I punteggi sono stati attribuiti in modo indipendente dai tre ricercatori utilizzando una scala da 1 (inadatto) a 5 (decisamente consigliato); l’accordo inter-giudici effettuato sul 50% dei punteggi attribuiti ha consentito di controllare l’effettivo allineamento delle valutazioni. L’indice di adeguatezza complessivo è stato calcolato sulla base del totale dei punteggi medi assegnati. I risultati mettono in evidenza che per quanto riguarda la disabilità sensoriale visiva e uditiva i giocattoli più adeguati sono quelli che sfruttano i canali sensoriali non compromessi, senza risultare eccessivamente complicati nell’utilizzo, al fine di preservare un buon indice di autonomia (giochi con materiali, forme e superfici diversificate, con luci/colori e suoni/vibrazioni secondo il tipo di compromissione). Considerando invece la disabilità di tipo motorio è emerso che i giocattoli con punteggi più alti sono quelli che mantengano alto l’indice di motivazione, senza quindi frustrare il bambino nel loro utilizzo, pur supportando, almeno parzialmente, le funzioni deficitarie (per la disabilità grosso-motoria giocattoli di grandi dimensioni, per esempio cavalcabili; per la disabilità fine-motoria giocattoli che favoriscano la sperimentazione di diverse prese e diversi tipi di manipolazione). Rispetto alla disabilità cognitiva sono risultati migliori giocattoli stimolanti dal punto di vista delle competenze emotivo-relazionali oppure di tipo creativo, poiché particolarmente motivanti; hanno ricevuto punteggi inferiori quei giocattoli che pur essendo utili nell’esercizio di abilità cognitive di base (didattico-educativi con sollecitazione di processi attentivi, mnemonici, di ragionamento, di orientamento e pianificazione) non mantengono un buon indice di autonomia nell’utilizzo da parte del bambino. Infine per la disabilità emotivo-relazionale sono stati valutati come adatti quei giochi che, mantenendo alto l’indice motivazionale, favoriscano allo stesso tempo le funzioni deficitarie (giocattoli interattivi e relazionali, con turni di gioco, che incoraggiano la previsione della risposta; giochi con situazioni di vita reale, di ruolo, di imitazione o di azioni figurate; giochi ricchi di dettagli, che esercitano l’attenzione). Il quadro complessivo che emerge dai risultati ottenuti attraverso questa prima analisi qualitativa dei cataloghi di prodotti suggerisce che sono già numerosi i giocattoli che possono rivelarsi adatti ai bambini con disabilità. Tali risultati sono confermati dalle osservazioni qualitative svolte al fine di valutare empiricamente la modalità d’interazione bambino-giocattolo allo scopo di arricchire e approfondire il quadro teorico costruito attraverso l’analisi dei giocattoli con evidenze e rimandi concreti

Evolution of macrolide resistance in streptococcus pyogenes over 14 years in an area of central Italy

We evaluated temporal fluctuations in macrolide resistance rates, analysing genetic determinants of resistance and clonal evolution in a population of 2744 S. pyogenes isolates collected in the period 2000–2013. The total resistance rate to erythromycin of the isolates was 17.9%. A maximum of erythromycin resistance emerged in 2000 (38.6%), followed by a significant decrease to 5.2% in 2012 (P<0.0001). Molecular analysis revealed the presence and co-presence of known genetic resistance determinants mefA, mefE, ermTR and ermB, in line with phenotypes. PFGE analysis identified genetically related groups in 2000 and 2007–2008, mainly the MLS and M phenotypes, respectively. The most prevalent emm types among a representative subset of resistant isolates were emm2, emm75 and emm77. All emm2 and 88.2% of the strains harbouring the emm75 gene were only recorded in M-phenotype strains, whilst all emm77-positive strains had the inducible MLS phenotype. The analysed susceptible isolates showed several emm types partially shared with resistant ones. Our results suggest that changes in bacterial population clonality, rather than horizontal transfer of resistance determinants, plays a major epidemiological role in S. pyogenes. Continuous monitoring of microbiological epidemiology seems to be crucial for correct and effective management of streptococcal infections

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR &lt;0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted &lt;4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (&lt;10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR&gt;6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS &lt;50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR&lt;0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

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Entropy contribution to the nickel(III)/nickel(II) redox change in six-coordinating systems. Investigation of the role of the negative charge of the ligand in the stabilization of high oxidation states of the metal center

Entropy changes ΔS°rc assocd. with the 2 half-reactions (i) [NiIIIL2]3+ + e- = [NiIIL2]2+ and (ii) [NiIIIY]0 + e- = [NiIIY] (L = 1,4,7-triazacyclononane H3Y = 1,4,7-triazacyclononane-N,N',N''-triacetic acid) were detd. through the investigation of the temp. dependence of the E1/2(NiIII/NiII) parameter over the 0.1-3.5M concn. range of the background electrolyte (NaCl). The ΔS°rc for half-reaction (i) is pos., and its value decreases with an increasing concn. of the supporting electrolyte, whereas ΔS°rc for half-reaction ii is neg. and its value increases (becoming less neg.) with an increasing concn. of NaCl. The above results were interpreted in terms of variation in the size of the hydration sphere of the electroactive species, which are related to changes of the elec. charge on the complexes. In particular, it was shown that such polyneg. charged ligands as Y3- favor access to unusually high oxidn. states of the metal center due a very favorable entropy term: this reflects a substantial increase of translational entropy, assocd. with the release of H2O mols. from the hydration sphere of the complex during the [NiIIY]/[NiIIIY]0 oxidn. proces