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ObjectiveThe impact of a screening programme on colorectal cancer (CRC) incidence in its target population depends on several variables, including coverage with invitations, participation rate, positivity rate of the screening test, compliance with an invitation to second-level assessment and endoscopists’ sensitivity. We propose a synthetic indicator that may account for all the variables influencing the potential impact of a screening programme on CRC incidence.DesignWe defined the ‘rate of advanced adenoma on the target population’ (AA-TAP) as the rate of patients who received a diagnosis of advanced adenoma within a screening programme, divided by the programme target population. We computed the AA-TAP for the CRC Italian screening programmes (biennial faecal immunochemical test, target population 50–69 year olds) using the data of the Italian National Survey from 2003 to 2016, overall and by region, and assessed the association between AA-TAP and CRC incidence fitting a linear regression between the trend of regional CRC incidence rates in 50–74 year old subjects and the cumulative AA-TAP.ResultsIn 2016, the AA-TAP at a national level was 105×100 000, whereas significant differences were observed between the northern and central regions (respectively 126 and 149×100 000) and the South and Islands (36×100 000). The cumulative AA-TAP from 2004 to 2012 was significantly correlated with the difference between CRC incidence rates in 2013–2014 and those in 2003–2004 (p=0.009).ConclusionThe AA-TAP summarises into a single indicator the potential impact of a screening programme in reducing CRC incidence rates.

Background Diabetes is a health emergency: in Italy over 3 million people are diabetics. In Lazio region a high percentage of population is affected by diabetes. Data are collected from two Italian population surveillance systems, Passi during 2015-18 and Passi d'Argento (PdA) during 2016-2018; this trasversal study was conducted to investigate diabetes awareness and clinical management in Lazio. Methods Passi and PdA collect representative data providing a telephone interview with a standardized questionnaire to a representing sample (18-69 and over 65 aged respectively), randomly selected and sex-and-age stratified. In both questionnaires a diabetes section assesses diagnosis, knowledge of HbA1c, health setting and number of annual checks. Data refer to whom affirm to be diagnosed with diabetes. Results are shown by prevalence and 95% CI. Results Diabetes prevalence grows with age, it does not reach 1% in people under 50 years, it is 9% for the age group 50-69 years and 20% in over 75. Serious economic difficulties and low education level are related to higher prevalence. Among diabetics, 18.7% (15.42-22.46) from Passi and 24.2% (20.29- 28.61) from PdA ignore HbA1c. About clinical management, 1.5% (0.73-2.90) in Passi do not receive any care from doctor; the whole sample of PdA receives medical care. Most of the respondents in both surveillance are managed by diabetes care team (43.76% in Passi - 39.87% in PdA), reporting to receive care about three times a year on average. No significant differences are observed between economic and education levels. Conclusions High percentage of diabetics, not knowing HbA1c, are not aware about disease. Patient empowerment is necessary to gain control over disease and increases capacity to act on it. Health education should be improved and diagnostic and therapeutic pathways, recently introduced in Lazio Region, should be better structured. Population surveillances allow to plan and evaluate programs and interventions. Key messages Fight the lack of awareness with patient empowerment to gain control over diabetes. Population surveillances are valuable tools to plan and evaluate programs and interventions in Public Health.

Integrin alpha 6 beta 4 is a member of a large family of heterodimeric receptors that mediate cell-cell and cell-extracellular matrix adhesion. This transmembrane protein is composed of noncovalently linked alpha 6 and beta 4 subunits encoded by distinct genes. Both alpha 6 and beta 4 polypeptides display a cytoplasmic domain that interacts with the cytoskeleton and with signaling molecules, a transmembrane region, and a large extracellular domain connected with the extracellular matrix. The comparative analysis of the deduced amino acidic sequences of alpha 6 and beta 4 with the other alpha and beta integrin subunits, respectively, has evidenced many common structural features suggesting the existence of two gene families. Nevertheless, the beta 4 chain exemplifies a clear divergence from the other beta subunits, in that this polypeptide contains an unusually large cytoplasmic domain ( similar to 1000 amino acids). The alpha 6 beta 4 integrin is predominantly expressed in epithelia and distributed only on the basal side of basal cells. The localization close to the basement membrane has suggested an important role of this protein in cell-matrix adhesion. Indeed, alpha 6 beta 4 is a laminin receptor and a component of hemidesmosomes, the dense cytoplasmic devices that mediate the attachment of stratified squamous epithelia to the underlying dermis. In particular, it has been demonstrated that the exceptionally large cytoplasmic domain of beta 4 integrin, a portion of which displays high homology with two related proteins of the myofibrillar cytoskeleton, is connected to the keratin intermediate filaments and harbors domains that are essential for the assembly of alpha 6 beta 4 into hemidesmosomes. However, alpha 6 beta 4 has also been detected in simple epithelia that do not possess hemidesmosomes. Furthermore, beta 4 isoforms with tissue-specific expression have been described, and their functional role is still unknown. Previous studies have shown a reduced number of rudimentary hemidesmosomes in skin from patients with junctional epidermolysis bullosa (JEB), a group of hereditary blistering disorders in which the epidermis detaches from the basement membrane. In particular, the expression of alpha 6 beta 4 is greatly reduced or even absent in a variant of JEB associated with pyloric atresia (PA-JEB; MIM 226730). A recent report has demonstrated that in a PA-JEB patient the disease resulted from two distinct mutations in the beta 4 integrin subunit gene (ITGB4). The pivotal role of integrin beta 4 in cell adhesion and formation of hemidesmosomes has been confirmed by the inactivation of the ITGB4 gene, which in mice leads to a phenotype similar to JEB. In fact, the homozygous beta 4 null mice, which die shortly after birth, display extensive disadhesion of the epithelia and decreased resistance to mechanical stress of the basal epithelial cells. To facilitate mutation analysis in JEB patients and functional studies on the integrin beta 4 isoforms, we have determined the structure of human ITGB4 by elucidating its exon-intron organization and derived a physical map of this genetic locus.

Microrobots (MRs) have attracted significant interest for their potentialities in diagnosis and non-invasive intervention in hard-to-reach body areas. Fine control of biomedical MRs requires real-time feedback on their position and configuration. Ultrasound (US) imaging stands as a mature and advantageous technology for MRs tracking, but it suffers from disturbances due to low contrast resolution. To overcome these limitations and make US imaging suitable for monitoring and tracking MRs, we propose a US contrast enhancement mechanism for MR visualization in echogenic backgrounds (e.g., tissue). Our technique exploits the specific acoustic phase modulation produced by the MR characteristic motions. By applying this principle, we performed real-time visualization and position tracking of a magnetic MR rolling on a lumen boundary, both in static flow and opposing flow conditions, with an average error of 0.25 body-lengths. Overall, the reported results unveil countless possibilities to exploit the proposed approach as a robust feedback strategy for monitoring and tracking biomedical MRs in-vivo.

The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer. In this population-based study, we analysed 135 847 children (aged 0–14 years) diagnosed during 2000–13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival. 5-year survival for all childhood cancer combined in Europe in 2010–14 was 81% (95% CI 81–82), showing an increase of three percentage points compared with 2004–06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% [95% CI 60–79] to 87% [77–93]). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010–13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73–75) in 1998–2001 to 80% (79–81) in 2010–13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74–100) for retinoblastoma to 60% (58–63) for CNS tumours and reached 90% (95% CI 87–93) for lymphoid leukaemia and 70% (67–73) for acute myeloid leukaemia. Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care. European Commission.

Load forecasting has become a key tool, especially for distribution system operators, to ensure optimal grid management and control. In recent years, attention has shifted toward probabilistic load forecasting (PLF), as it can model forecast uncertainty. Because electricity demand is strongly influenced by time-dependent factors such as seasonal patterns and daily habits, non-parametric PLF methods are particularly suitable because they make no assumptions about the distribution of variables. This study focuses on quantile regression (QR), a widely studied non-parametric PLF technique that models forecast uncertainty by only assuming a linear dependency among variables. It is applied every hour to forecast the daily consumption of three large public buildings—an elderly healthcare center, a biomedical research facility, and a polyclinic—with different demand variability profiles. Forecasts are carried out using real-world consumption data and evaluated considering both univariate and multivariate approaches. The performance of both QR approaches is rigorously evaluated against that of two persistence-based methods through standard evaluation metrics. For the univariate case, two aggregation levels are considered: single buildings and aggregation of buildings. The results confirm the effectiveness of both uQR and mQR, which consistently outperform persistence-based benchmarks. In terms of the pinball loss (PL) function, the QR approaches exhibit values ranging from 1% to 1.8% across all case studies. Both approaches demonstrate reliable and sharp prediction intervals (PIs); for example, for the PI(10–90) using the uQR, the PI coverage probability (PICP) ranges from 0.78 to 0.89 and the PI normalized average width (PINAW) from 0.09 to 0.26. Overall, uQR achieves lower PL, whereas mQR yields slightly better PICP and PINAW results for the building characterized by an irregular and unpredictable consumption profile.

Multiplex networks describe a large number of complex social, biological and transportation networks where a set of nodes is connected by links of different nature and connotation. Here we uncover the rich community structure of multiplex networks by associating a community to each multilink where the multilinks characterize the connections existing between any two nodes of the multiplex network. Our community detection method reveals the rich interplay between the mesoscale structure of the multiplex networks and their multiplexity. For instance some nodes can belong to many layers and few communities while others can belong to few layers but many communities. Moreover the multilink communities can be formed by a different number of relevant layers. These results point out that mesoscopically there can be large differences in the compressibility of multiplex networks.

Community structures in collaboration networks reflect the natural tendency of individuals to organize their work in groups in order to better achieve common goals. In most of the cases, individuals exploit their connections to introduce themselves to new areas of interests, giving rise to multifaceted collaborations which span different fields. In this paper, we analyse collaborations in science and among movie actors as multiplex networks, where the layers represent respectively research topics and movie genres, and we show that communities indeed coexist and overlap at the different layers of such systems. We then propose a model to grow multiplex networks based on two mechanisms of intra and inter-layer triadic closure which mimic the real processes by which collaborations evolve. We show that our model is able to explain the multiplex community structure observed empirically, and we infer the strength of the two underlying social mechanisms from real-world systems. Being also able to correctly reproduce the values of intra-layer and inter-layer assortativity correlations, the model contributes to a better understanding of the principles driving the evolution of social networks.