Editorial for the article: Hospitalization-based epidemiology of systemic and cardiac amyloidosis in the Veneto Region, Italy

Cardiac amyloidosis (CA) is a progressive infiltrative disease caused most commonly by the deposition of misfolded, cleaved and aggregated monoclonal immunoglobulin free light chain (AL) or transthyretin (ATTR) proteins in the myocardial extracellular space [1]. Recent advances in imaging techniques and the development of an algorithm for non-invasive confirmation of ATTR-CA [2] have transformed the diagnosis of this condition

ECG/echo indexes in the diagnostic approach to amyloid cardiomyopathy: A head-to-head comparison from the AC-TIVE study

Background and aims: The discordance between QRS voltages on electrocardiogram (ECG) and left ventricle (LV) wall thickness (LVWT) on echocardiogram (echo) is a recognized red flag (RF) of amyloid cardiomyopathy (AC) and can be measured by specific indexes. No head-to-head comparison of different ECG/echo indexes among subjects with echocardiographic suspicion of AC has yet been undertaken. The study aimed at evaluating the performance and the incremental diagnostic value of different ECG/echo indexes in this subset of patients. Methods: Electrocardiograms of subjects with LV hypertrophy, preserved ejection fraction and ≥ 1 echocardiographic RF of AC participating in the AC-TIVE study, an Italian prospective multicenter study, were independently analyzed by two cardiologists. Low QRS voltages and 8 different ECG/echo indexes were evaluated. Cohort specific cut-offs were computed. Results: Among 170 patients, 55 (32 %) were diagnosed with AC. Combination of low QRS voltages with interventricular septum ≥ 1,6 cm was the most specific (specificity 100 %, positive predictive value 100 %) ECG/echo index, while the ratio between the sum of all QRS voltages and LVWT <7,8 was the most sensitive and accurate (sensitivity 94 %, negative predictive value 97 %, accuracy 82 %). When the latter index was added to a model using easily-accessible clinical variables, the diagnostic accuracy for AC greatly increased (AUC from 0,84 to 0,95; p = 0,007). Conclusions: Among patients with non-dilated hypertrophic ventricles with normal ejection fraction and echocardiographic RF of AC, easily-measurable ECG/echo indexes, mainly when added to few clinical variables, can help the physician orient second level investigations. External validation of the results is warranted

Towards an Early Physics approach for secondary students

Some traditional approaches to teaching Physics at the secondary level of instruction have disclosed their limits, especially in distance learning. A consequence of such limits seems to be a somewhat diffused lack of students' scientific abilities, mainly caused by their learning difficulties. To overcome the shortcomings of tradition, we stimulated some teachers to get involved in a new teaching approach to develop their awareness of these limits and difficulties and exploit their PCK (Pedagogical Content Knowledge). This approach explores and intercepts the main learning features and needs in the first years of Physics studies. For that reason and the analogy in Math Education, we named it Early Physics

Intraspecific variability of leaf form and function across habitat types

Trait-based ecology has already revealed main independent axes of trait variation defining trait spaces that summarize plant adaptive strategies, but often ignoring intraspecific trait variability (ITV). By using empirical ITV-level data for two independent dimensions of leaf form and function and 167 species across five habitat types (coastal dunes, forests, grasslands, heathlands, wetlands) in the Italian peninsula, we found that ITV: (i) rotated the axes of trait variation that define the trait space; (ii) increased the variance explained by these axes and (iii) affected the functional structure of the target trait space. However, the magnitude of these effects was rather small and depended on the trait and habitat type. Our results reinforce the idea that ITV is context-dependent, calling for careful extrapolations of ITV patterns across traits and spatial scales. Importantly, our study provides a framework that can be used to start integrating ITV into trait space analyses

Fixed points and attractors of additive reaction systems

Reaction systems are discrete dynamical systems that simulate biological processes within living cells through finite sets of reactants, inhibitors, and products. In this paper, we study the computational complexity of deciding on the existence of fixed points and attractors in the restricted class of additive reaction systems, in which each reaction involves at most one reactant and no inhibitors. We prove that all the considered problems, that are known to be hard for other classes of reaction systems, are polynomially solvable in additive systems. To arrive at these results, we provide several non-trivial reductions to problems on a polynomially computable graph representation of reaction systems that might prove useful for addressing other related problems in the future

Systematic review for the development of a core outcome set for monofocal intraocular lenses for cataract surgery

Introduction: The aim of the study was to define a core outcome set (COS) to be measured following cataract surgery for the postoperative evaluation of monofocal intraocular lenses (IOLs). Compared to current COSs, the present work provides updates considering the advances in the technology due to the development of new generation monofocal IOLs, which are characterized by a safety profile comparable to standard monofocal IOLs but with an extended range of intermediate vision. Methods: Healthcare professionals (ophthalmologist surgeons) and patients were involved in the selection of outcomes to be included in the COS, starting from a list of indicators retrieved from a systematic literature search. The search considered observational studies with both a retrospective or prospective design, case studies and classic randomized controlled trials (RCTs). A mixed methodology integrating a Delphi-driven and an expert panel approach was adopted to reach an agreement among clinicians, while patients were involved in the completion of a questionnaire. Results: The final COS included 15 outcomes. Eleven outcomes, all clinical, were considered for inclusion after a joint discussion among ophthalmologists; seven outcomes were linked to visual acuity, while the remaining to contrast sensitivity, refractive errors, aberrations and adverse events. Measurement metrics, method of aggregation and measurement time point of these outcomes were specified. The most important aspects for the patients were (1) quality of life after cataract surgery, (2) the capacity to perform activities requiring good near vision (e.g., reading), (3) spectacle independence, and (4) safety of movements without fear of getting hurt or falling (intermediate vision). Discussion: In a context with limited healthcare resources, it is important to optimize their use considering also the preferences of end-users, namely patients. The proposed COS, developed involving both ophthalmologists and patients, provides an instrument for the postoperative evaluation of different technologies in the context of monofocal IOLs, which can be used not only in clinical trials but also in clinical practice to increase the body of real-world evidence

Joint AAPM Task Group 282/EFOMP Working Group Report: Breast dosimetry for standard and contrast‐enhanced mammography and breast tomosynthesis

: Currently, there are multiple breast dosimetry estimation methods for mammography and its variants in use throughout the world. This fact alone introduces uncertainty, since it is often impossible to distinguish which model is internally used by a specific imaging system. In addition, all current models are hampered by various limitations, in terms of overly simplified models of the breast and its composition, as well as simplistic models of the imaging system. Many of these simplifications were necessary, for the most part, due to the need to limit the computational cost of obtaining the required dose conversion coefficients decades ago, when these models were first implemented. With the advancements in computational power, and to address most of the known limitations of previous breast dosimetry methods, a new breast dosimetry method, based on new breast models, has been developed, implemented, and tested. This model, developed jointly by the American Association of Physicists in Medicine and the European Federation for Organizations of Medical Physics, is applicable to standard mammography, digital breast tomosynthesis, and their contrast-enhanced variants. In addition, it includes models of the breast in both the cranio-caudal and the medio-lateral oblique views. Special emphasis was placed on the breast and system models used being based on evidence, either by analysis of large sets of patient data or by performing measurements on imaging devices from a range of manufacturers. Due to the vast number of dose conversion coefficients resulting from the developed model, and the relative complexity of the calculations needed to apply it, a software program has been made available for download or online use, free of charge, to apply the developed breast dosimetry method. The program is available for download or it can be used directly online. A separate User's Guide is provided with the software

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Noncommunicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, agestandardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades

Blood Markers Predicting Clinically Occult Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma

Introduction: The presence of cervical lymph node metastases is an unfavorable prognostic factor in head and neck squamous cell carcinoma (HNSCC) and a potential cause of treatment failure. Occult lymph node metastasis occurs in approximately 15-20% of HNSCC patients with a clinically negative neck (cN0), greatly impacting on their prognosis. The present study aimed to investigate the role of pre-treatment peripheral blood markers in predicting clinically occult cervical lymph node metastasis. Methods: This multicenter, retrospective study was performed in a cohort of 472 patients diagnosed with cN0 HNSCC who underwent up-front surgery. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated from available blood parameters. Results: Oro-hypopharyngeal and oral cancers, locally advanced stage, moderately (G2), and poorly (G3) differentiated grade were associated with an increased risk of pathological lymph node involvement. NLR, LMR, PLR, SIM, and SII were significantly associated at multivariable analysis. NLR >2.12 was the most reliable at predicting occult lymph node metastasis (OR = 5.22; 95% CI: 2.14-12.75). We describe a predictive score integrating cancer site, local stage, and NLR which is effective at predicting positive lymph node pathological status. Conclusions: The present study provides evidence that pre-treatment peripheral blood markers, in particular NLR, represent reliable predictors of clinically occult cervical lymph node metastasis in cN0 HNSCC. Therefore, the present study provides a novel useful predictive score for directing the elective management of the neck in patients with cN0 HNSCC

Harnessing the Power of Collective Intelligence: the Case Study of Voxel-based Soft Robots

The field of Evolutionary Robotics (ER) is concerned with the evolution of artificial agents---robots. Albeit groundbreaking, progress in the field has recently stagnated. In the research community, there is a strong feeling that a paradigm change has become necessary to disentangle ER. In particular, a solution has emerged from ideas from Collective Intelligence (CI). In CI---which has many relevant examples in nature---behavior emerges from the interaction between several components. In the absence of central intelligence, collective systems are usually more adaptable. In this thesis, we set out to harness the power of CI, focusing on the case study of simulated Voxel-based Soft Robots (VSRs): they are aggregations of homogeneous and soft cubic blocks that actuate by altering their volume. We investigate two axes. First, the morphologies of VSRs are intrinsically modular and an ideal substrate for CI; nevertheless, controllers employed until now do not take advantage of such modularity. Our results prove that VSRs can truly be controlled by the CI of their modules. Second, we investigate the spatial and time scales of CI. In particular, we evolve a robot to detect its global body properties given only local information processing, and, in a different study, generalize better to unseen environmental conditions through Hebbian learning. We also consider how evolution and learning interact in VSRs. Looking beyond VSRs, we propose a novel soft robot formalism that more closely resembles natural tissues and blends local with global actuation.The field of Evolutionary Robotics (ER) is concerned with the evolution of artificial agents---robots. Albeit groundbreaking, progress in the field has recently stagnated. In the research community, there is a strong feeling that a paradigm change has become necessary to disentangle ER. In particular, a solution has emerged from ideas from Collective Intelligence (CI). In CI---which has many relevant examples in nature---behavior emerges from the interaction between several components. In the absence of central intelligence, collective systems are usually more adaptable. In this thesis, we set out to harness the power of CI, focusing on the case study of simulated Voxel-based Soft Robots (VSRs): they are aggregations of homogeneous and soft cubic blocks that actuate by altering their volume. We investigate two axes. First, the morphologies of VSRs are intrinsically modular and an ideal substrate for CI; nevertheless, controllers employed until now do not take advantage of such modularity. Our results prove that VSRs can truly be controlled by the CI of their modules. Second, we investigate the spatial and time scales of CI. In particular, we evolve a robot to detect its global body properties given only local information processing, and, in a different study, generalize better to unseen environmental conditions through Hebbian learning. We also consider how evolution and learning interact in VSRs. Looking beyond VSRs, we propose a novel soft robot formalism that more closely resembles natural tissues and blends local with global actuation