A novel methodology for epidemic risk assessment of COVID-19 outbreak.

We propose a novel data-driven framework for assessing the a-priori epidemic risk of a geographical area and for identifying high-risk areas within a country. Our risk index is evaluated as a function of three different components: the hazard of the disease, the exposure of the area and the vulnerability of its inhabitants. As an application, we discuss the case of COVID-19 outbreak in Italy. We characterize each of the twenty Italian regions by using available historical data on air pollution, human mobility, winter temperature, housing concentration, health care density, population size and age. We find that the epidemic risk is higher in some of the Northern regions with respect to Central and Southern Italy. The corresponding risk index shows correlations with the available official data on the number of infected individuals, patients in intensive care and deceased patients, and can help explaining why regions such as Lombardia, Emilia-Romagna, Piemonte and Veneto have suffered much more than the rest of the country. Although the COVID-19 outbreak started in both North (Lombardia) and Central Italy (Lazio) almost at the same time, when the first cases were officially certified at the beginning of 2020, the disease has spread faster and with heavier consequences in regions with higher epidemic risk. Our framework can be extended and tested on other epidemic data, such as those on seasonal flu, and applied to other countries. We also present a policy model connected with our methodology, which might help policy-makers to take informed decisions.

Radiobiological quantities in proton-therapy: Estimation and validation using Geant4-based Monte Carlo simulations.

PURPOSE: The Geant4 Monte Carlo simulation toolkit was used to reproduce radiobiological parameters measured by irradiating three different cancerous cell lines with monochromatic and clinical proton beams. METHODS: The experimental set-up adopted for irradiations was fully simulated with a dedicated open-source Geant4 application. Cells survival fractions was calculated coupling the Geant4 simulations with two analytical radiobiological models: one based on the LEM (Local Effect Model) approach and the other on a semi-empirical parameterisation. Results was evaluated and compared with experimental data. RESULTS AND CONCLUSIONS: The results demonstrated the Geant4 ability to reproduce radiobiological quantities for different cell lines.

Monte Carlo GEANT4-based application for in vivo RBE study using small animals at LNS-INFN preclinical hadrontherapy facility.

Preclinical studies represent an important step towards a deep understanding of the biological response to ionizing radiations. The effectiveness of proton therapy is higher than photons and, for clinical purposes, a fixed value of 1.1 is used for the relative biological effectiveness (RBE) of protons considered 1.1. Recent in vitro studies have reported that the RBE along the spread-out Bragg peak (SOBP) is not constant and, in particular, the RBE value increases on the distal part of SOBP. The present work has been carried-out in the perspective of a preclinical hadrontherapy facility at LNS-INFN and was focused on the experimental preparation of an in vivo study concerning the RBE variation along the SOBP. The main purpose of this work was to determine, using GEANT4-based Monte Carlo simulations, the best configuration for small animal treatments. The developed GEANT4 application simulates the proton-therapy beam line of LNS-INFN (CATANA facility) and allows to import the DICOM-CT images as targets. The RBE will be evaluated using a deterministic radiation damage like myelopathy as end-point. In fact, the dose at which the 50% of animals will show the myelopathy is supposed to be LET-dependent. In this work, we studied different treatment configurations in order to choose the best two that maximize the LET difference reducing as much as possible the dose released to healthy tissue. The results will be useful to plan hadrontherapy treatments for preclinical in vivo studies and, in particular, for the future in vivo RBE studies.

Assessing the effects of habitat patches ensuring propagule supply and different costs inclusion in marine spatial planning through multivariate analyses.

Marine Protected Areas are considered key tools for conservation of coastal ecosystems. However, many reserves are characterized by several problems mainly related to inadequate zonings that often do not protect high biodiversity and propagule supply areas precluding, at the same time, economic important zones for local interests. The Gulf of Naples is here employed as a study area to assess the effects of inclusion of different conservation features and costs in reserve design process. In particular eight scenarios are developed using graph theory to identify propagule source patches and fishing and exploitation activities as costs-in-use for local population. Scenarios elaborated by MARXAN, software commonly used for marine conservation planning, are compared using multivariate analyses (MDS, PERMANOVA and PERMDISP) in order to assess input data having greatest effects on protected areas selection. MARXAN is heuristic software able to give a number of different correct results, all of them near to the best solution. Its outputs show that the most important areas to be protected, in order to ensure long-term habitat life and adequate propagule supply, are mainly located around the Gulf islands. In addition through statistical analyses it allowed us to prove that different choices on conservation features lead to statistically different scenarios. The presence of propagule supply patches forces MARXAN to select almost the same areas to protect decreasingly different MARXAN results and, thus, choices for reserves area selection. The multivariate analyses applied here to marine spatial planning proved to be very helpful allowing to identify i) how different scenario input data affect MARXAN and ii) what features have to be taken into account in study areas characterized by peculiar biological and economic interests.

'Survival': a simulation toolkit introducing a modular approach for radiobiological evaluations in ion beam therapy.

One major rationale for the application of heavy ion beams in tumour therapy is their increased relative biological effectiveness (RBE). The complex dependencies of the RBE on dose, biological endpoint, position in the field etc require the use of biophysical models in treatment planning and clinical analysis. This study aims to introduce a new software, named 'Survival', to facilitate the radiobiological computations needed in ion therapy. The simulation toolkit was written in C++ and it was developed with a modular architecture in order to easily incorporate different radiobiological models. The following models were successfully implemented: the local effect model (LEM, version I, II and III) and variants of the microdosimetric-kinetic model (MKM). Different numerical evaluation approaches were also implemented: Monte Carlo (MC) numerical methods and a set of faster analytical approximations. Among the possible applications, the toolkit was used to reproduce the RBE versus LET for different ions (proton, He, C, O, Ne) and different cell lines (CHO, HSG). Intercomparison between different models (LEM and MKM) and computational approaches (MC and fast approximations) were performed. The developed software could represent an important tool for the evaluation of the biological effectiveness of charged particles in ion beam therapy, in particular when coupled with treatment simulations. Its modular architecture facilitates benchmarking and inter-comparison between different models and evaluation approaches. The code is open source (GPL2 license) and available at https://github.com/batuff/Survival.

Mobile health clinic for the medical management of clinical sequelae experienced by survivors of the 2013-2016 Ebola virus disease outbreak in Sierra Leone, West Africa.

An Ebola survivor Mobile Health Clinic (MHC) was established to implement lasting changes in communities it operates by providing effective and efficient mobile healthcare. After months of development, the MHC solution was operationalised in February 2015, aiming to provide integrated primary healthcare services to address the medical and psychosocial needs of Ebola virus (EBOV) survivors living in areas with low medical coverage. A total of 910 medical consultations for 246 EBOV survivors were performed between 7 February 2015 and 10 June 2016. Females constituted 148 (60.2%) whereas 6 (2.44%) were children under 5 years of age. The most common complication was arthralgia 185 (75.2%), headache 98 (39.8%), abdominal pain 167 (68%), myalgia 182 (73.6%), and skin disease 25 (10%). Moreover, ocular problems were diagnosed in 84 survivors (34.1%), and 60 (24.4%) suffered from psycho-trauma. Some 16 female survivors (10.8%) had miscarriages, whereas 9 (6.1%) had complaints of oligomenorrhea, 7 (4.7%) loss of sexual desire and 4 (2.7%) premature menopause. Five male survivors (5.1%) reported erectile dysfunction and 10 (10.2%) loss of sexual desire. At least 221 (89.8%) reported more than one complication. Other infectious diseases were common and no clinically relevant differences were established from haematology and clinical biochemistry laboratory results. Ibuprofen, paracetamol, anti-malaria drugs and antibiotics were the most common medicines prescribed. Community participation is critical for implantation of MHC among EBOV survivors. Future strategies for the mobile clinics should include enrolment of survivors at discharge from treatment centres with close monitoring follow-up activities, to address sequelae as they arise, to reduce the potential for development of long-term disabilities.

Design and characterisation of a real time proton and carbon ion radiography system based on scintillating optical fibres.

This paper describes the design and characterization of a charged particle imaging system composed of a position sensitive detector and residual range detector. The position detector consists of two identical overlying and orthogonal planes each of which consists of two layers of pre-aligned and juxtaposed scintillating fibres. The 500µm square section fibres are optically coupled to two Silicon Photomultiplier arrays using a channel reduction system patented by the Istituto Nazionale di Fisica Nucleare. The residual range detector consists of sixty parallel layers of the same fibres used in the position detector each of which is optically coupled to a Silicon Photomultiplier array by wavelength shifting fibres. The sensitive area of the two detectors is 9×9cm(2). Characterising the position sensitive and the residual range detectors to reconstruct the radiography, is fundamental to validating the detectors' designs. The proton radiography of a calibrated target in imaging conditions is presented. The spatial resolution of the position sensitive detector is about 150µm and the range resolution is about 170µm. The performance of the prototypes were tested at CATANA proton therapy facility (Laboratori Nazionali del Sud, INFN, Catania) with energy up to 58MeV and rate of about 10(6) particles per second. The comparison between the simulations and measurements confirms the validity of this system.

A method for the assessment of time-varying brain shift during navigated epilepsy surgery.

PURPOSE: Image guidance is widely used in neurosurgery. Tracking systems (neuronavigators) allow registering the preoperative image space to the surgical space. The localization accuracy is influenced by technical and clinical factors, such as brain shift. This paper aims at providing quantitative measure of the time-varying brain shift during open epilepsy surgery, and at measuring the pattern of brain deformation with respect to three potentially meaningful parameters: craniotomy area, craniotomy orientation and gravity vector direction in the images reference frame. METHODS: We integrated an image-guided surgery system with 3D Slicer, an open-source package freely available in the Internet. We identified the preoperative position of several cortical features in the image space of 12 patients, inspecting both the multiplanar and the 3D reconstructions. We subsequently repeatedly tracked their position in the surgical space. Therefore, we measured the cortical shift, following its time-related changes and estimating its correlation with gravity and craniotomy normal directions. RESULTS: The mean of the median brain shift amount is 9.64 mm ([Formula: see text] mm). The brain shift amount resulted not correlated with respect to the gravity direction, the craniotomy normal, the angle between the gravity and the craniotomy normal and the craniotomy area. CONCLUSIONS: Our method, which relies on cortex surface 3D measurements, gave results, which are consistent with literature. Our measurements are useful for the neurosurgeon, since they provide a continuous monitoring of the intra-operative sinking or bulking of the brain, giving an estimate of the preoperative images validity versus time.

[Effects of dose of erythropoiesis stimulating agents on cardiovascular outcomes, quality of life and costs of haemodialysis. the clinical evaluation of the DOSe of erythropoietins (C.E. DOSE) Trial]. / Effetti della dose degli agenti stimolanti l'eritropoiesi su esiti cardio-cerebrovascolari, qualità di vita e costi in emodialisi.

BACKGROUND: Anaemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies, higher haemoglobin (Hb) levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to Hb levels around 9-10 g/dL. Randomized studies found that targeting higher Hb levels with ESA causes an increased risk of death, mainly due to adverse cardiovascular outcomes. It is possible that this is mediated by ESA dose rather than haemoglobin concentration, although this hypothesis has never been formally tested. METHODS: We present the protocol of the Clinical Evaluation of the Dose of Erythropoietins (C.E. DOSE) trial, which will assess the benefits and harms of a high versus a low ESA dose therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD). This is a randomized, prospective open label blinded end-point (PROBE) design trial due to enroll 900 haemodialysis patients. Patients will be randomized 1:1 to 4000 UI/week i. v. versus 18000 UI/week i. v. of epoetin alfa, beta or any other epoetin in equivalent doses. The primary outcome of the trial is a composite of cardiovascular events. In addition, quality of life and costs of these two strategies will be assessed. The study has been approved and funded by the Italian Agency of Drugs (Agenzia Italiana del Farmaco (AIFA)) within the 2006 funding plan for independent research on drugs (registered at www.clinicaltrials.gov (NCT00827021)).

Balance and walking in facioscapulohumeral muscular dystrophy: multiperspective assessment.

BACKGROUND: In the Facioscapulohumeral muscular dystrophy (FSHD), the association of ankle muscle impairment with knee, hip and abdominal weakness causes complex alterations of static (postural) and dynamic (walking) balance, increasing the risk of recurrent falls. Stereophotogrammetric system and body-worn gyroscopes were used to focus on locomotor capacity and upper body movements in FSHD patients respectively. No data have been reported about static balance (plantar pressure and stabilometric parameters) and dynamic balance (spatio-temporal parameters during walking) in patients with FSHD. Moreover it is not known if the balance involvement influences disability and quality of life (QoL) of these patients. AIM: The aim of this study is to quantitatively assess static and dynamic balance in FSHD patients and their influence on disability and QoL. DESIGN: Case control-study. SETTING: Outpatient Rehabilitation Department. POPULATION: Sixteen FSHD patients were compared with 16 matched healthy subjects. METHODS: A baropodometric platform was used to measure plantar pressure and centre of pressure in stance (static evaluation), and spatio-temporal parameters during walking (dynamic evaluation). These quantitative results in FSHD patients were also correlated with validated clinical (Clinical Severity Scale), performance (10m and 2 min Walking Test), disability (Berg Balance Scale, Rivermead Mobility Index) and quality of life (QoL) measures (SF-36, NASS). RESULTS: The patients moved the plantar pressure forward from hindfoot to forefoot. Static balance was significantly reduced in patients compared with healthy subjects. Dynamic evaluation of walking showed a significant reduction of velocity and step length in the patients, and a significant increase in step width. Dynamic and static parameters were significantly related to a reduction of 10 mWT performance while only dynamic parameters were strongly related to disability and QoL. CONCLUSION: FSHD patients present an abnormal static and dynamic balance and they show compensation strategies to avoid falling . The involvement of the dynamic balance worsens the physical aspects of QoL and induces disability. The involvement of static balance induces a reduction of the performance in brief distances. CLINICAL REHABILITATION IMPACT: The balance training should be considered in the rehabilitation program of FSHD patients; the compensation strategies adopted by these patients should be considered in the ankle foot orthosis treatment. The static and dynamic balance assessment in FSHD patients can be used in natural history studies.

Neuropsychological assessment in prepubertal patients with congenital adrenal hyperplasia: preliminary study.

AIM: Individuals with congenital adrenal hyperplasia (CAH) provide a test population for the theory that elevated testosterone levels alter pre-/perinatal brain development. METHODS: Seven prepuberal girls with CAH and seven matched controls has been submitted to a neuropsychological evaluation. We measured abilities where gender differences repeatedly has been observed or that had earlier shown differences between CAH subjects and controls. The following cognitive functions were tested: general intelligence, attention, verbal and non-verbal abilities, cerebral dominance for verbal and non-verbal material, frontal functions, peripheral dominance and motor fluency. Since several animal studies shown hippocampal morphological changes induced by prolonged hydrocortisone exposure, we also investigated memory functions. RESULTS: No differences were recorded between two groups on those abilities that are not sexually dimorphic. The mean general intelligence level of the patients was significantly lower than the controls', in agreement with previous studies. The verbal and non-verbal tasks revealed an age-related male-like pattern (i.e., verbal disadvantage) and an inversion of the hemispheric dominances. The latter observation was supported by a right-to-left shift of the peripheral dominances. The patients memory performances were all inferior to the controls'. The results are discussed in the light of possible hormonal influences. CONCLUSION: Our main findings support the hypothesis that elevated pre-/perinatal androgen exposure can influence some cognitive pattern of specific sexual dimorphic abilities in prepubertal subjects.

A RICH detector for hadron identification at JLab.

The "standard" Hall A apparatus at Jefferson Lab (TOF and aerogel threshold Cherenkov detectors) does not provide complete identification for proton, kaon and pion. To this aim, a proximity focusing C(6)F(14)/CsI RICH (Ring Image CHerenkov) detector has been designed, built, tested and operated to separate kaons from pions with a pion contamination of a few percent up to 2.4GeV/c. Two quite different experimental investigations have benefitted of the RICH identification: on one side, the high-resolution hypernuclear spectroscopy series of experiments on carbon, beryllium and oxygen, devoted to the study of the lambda-nucleon potential. On the other side, the measurements of the single spin asymmetries of pion and kaon on a transversely polarized (3)He target are of utmost interest in understanding QCD dynamics in the nucleon. We present the technical features of such a RICH detector and comment on the presently achieved performance in hadron identification.

[Laws relevant to international missions of health cooperation]. / Le norme applicabili a missioni di cooperazione sanitaria internazionale.

Both medical doctors and humanitarian operators engaged in health relief or development missions abroad, are called to respect the general principles of international law, that is to say, customary law that is legally compulsory for the International Community and rules deriving from Treaties and International Conventions. Humanitarian operators have to observe also the rules and regulations of the hosting country. They have to respect all rules applying to their humanitarian action and they have to take responsibility towards beneficiaries and donors alike.

Influence of family history to type 2 diabetes on the body composition and homeostasis model assessment: a comparison between young active and sedentary men.

AIM: Family history (FH) to type 2 diabetes mellitus (DM) is a risk factor to the development of illness, inducing early anthropometric and metabolic modifications in sedentary subjects. The aim of this paper was to study the FH to DM influence on body composition and glucose metabolism in young sedentary and active men. METHODS: In a cross-section analysis, we recorded anthropometric data, body composition (by BIA), plasmatic insulin and glucose in 60 young healthy Sicilian men (31 athletes and 29 sedentary subjects); FH was defined FH+ if subjects referred to have at least one family member of first degree with documented DM; men without FH to DM were defined FH-. RESULTS: In sedentary subjects, FH+ was associated with the highest values of body mass index (P<0.05) and an increase in the waist-hip ratio (P<0.0585). Sedentary FH+ had a worse body composition, because of an increase in fat mass (P<0.05 for absolute and percent values). Compared to FH- sedentary men, FH+, with lower basal plasmatic insulin, had lower levels of homeostasis model assessment (HOMA) (P<0.05). Between FH+ and FH- athletes no differences were found. CONCLUSIONS: In young men subjects, study confirms influence of FH to DM on physical data, body composition and glucose metabolism and the protective role of a regular physical activity. In subjects FH+ the promotion of health education can prevent the arising of obesity and diabetes; other studies on subjects of both sexes are necessary to assess relation between FH degree to type 2 DM and early physical and metabolic modifications.

The basal energy expenditure of female athletes vs. sedentary women as related to their family history of type 2 diabetes.

The purpose of this study was to investigate the basal metabolic rate (BMR) in 16 professional sportswomen (soccer players) versus 15 sedentary women, as related to the presence (FH+) or absence (FH-) of a family history of type 2 diabetes. The sportswomen, in toto, had a significantly higher BMR than expected from predictive equations (+14.92%). However, the difference was limited only to FH- sportswomen (+18.66%, p<0.0005). FH- sportswomen showed a significantly higher measured BMR than FH+ sportswomen (p<0.005), and FH+ (p=0.058) and than FH- (p<0.05) sedentary women. There were no other significant differences relative to physical, metabolic and plasmatic data between the groups. The sportswomen with familiarity to type 2 diabetes had a BMR lower than that of FH- sportswomen, and similar to that of sedentary sedentary women. It appears that FH+ sportswomen have a "sub-clinical metabolic inertia", representing a precocious signal in young diabetes-prone subjects, despite the modifications induced from activity on their body composition (increased FFM, even though marginally significant).

Quantitative assessment of cerebral vascular reserve by means of transcranial Doppler ultrasound and rebreathing maneuver: bedside test and mathematical modeling.

Cerebral vascular reserve was measured by means of the transcranial Doppler (TCD) technique from carbon dioxide (CO2) tests, in healthy individuals and patients with unilateral internal carotid artery (ICA) occlusion. The percentage changes in middle cerebral arteries blood flow velocity (VMCA) per mmHg of pCO2 variations (reactivity index, RI) were separately computed during hypocapnia and hypercapnia, the latter obtained by a rebreathing maneuver. Clinical data have been compared with predictions obtained using an original mathematical model of intracranial dynamics, in order to search a theoretical explanation of the hemodynamic events observed during clinical testing. This analysis has also been considered in order to support the choice between different CO2 tests for quantitative assessment of vascular reactivity. Clinical data and model simulations agree in showing that side-to-side reactivity differences (Irel) measured from hypercapnia test allow a good discrimination of patients with poor compensatory capacity. They suggest that an Irel significantly greater than 30% after hypercapnia test can be considered indicative of patients with poor compensatory capacity. These preliminary results encourage a long-term follow-up of cerebral vascular reserve by means of TCD during "rebreathing test", for selecting patients with poor vascular reserve that may benefit from brain revascularization.

A cost-benefit analysis of voluntary routine HIV-antibody testing for hospital patients.

The objectives of this paper are threefold: first, to develop a taxonomy of potential benefits from voluntary, routine HIV-antibody testing of hospital patients; second, to inform attending healthcare workers, hospital patients and policy makers of the potential benefits from such testing; and third, to make inferences about whether such testing is warranted by a cost-benefit criterion. Benefits stemming from information about a patient's HIV serostatus accrue to: (1) healthcare workers if extra precautions reduce their HIV-exposure rate; (2) the patient if knowledge of HIV serostatus allows life-extending prophylactic treatment to be initiated; and (3) the patient's sex partners if the patient is less likely to transmit HIV after undergoing HIV testing. Using recent estimates on the value of life, hospital-specific HIV-prevalence rates, the effectiveness of prophylactic treatment, rates of HIV exposure and conversion by healthcare workers, and reduction in high-risk sexual behaviors by seropositive patients, we estimate the benefits of testing as the value of statistical life saved. The opportunity cost of HIV testing is calculated as the reported cost of a standard HIV-test protocol with pre- and post-test counseling. Information about a patient's HIV serostatus provides small expected benefits to healthcare workers ($3.34) because the risk of HIV transmission is small; benefits to attending healthcare workers are insufficient to warrant routine HIV testing on a stand-alone basis even in high HIV-prevalence hospitals. However, an HIV-seropositive test result provides large expected benefits to the patient ($11,202) and to the patient's sex partners ($5271). Adding these nonrivalrous benefits, we find that routine, voluntary HIV-testing of hospital patients passes a cost-benefit test even in low HIV-prevalence hospitals. Four major qualifications of the cost-benefit analysis should be considered. (1) The benefits to some parties can only be achieved if the patient's serostatus is disclosed to them. (2) The net benefits may be negative if HIV-testing induces riskier behavior. (3) The analysis does not incorporate the significant potential for third-parties (employers, insurers, healthcare workers) to use the test to impose costs on HIV-seropositive patients. (4) The sample of inpatients choosing voluntary HIV testing may not be representative of the overall hospital population. These unmeasured factors suggest that policymakers should exercise caution in implementing a voluntary HIV-testing program.

[Short account of modern history of surgery in temporal lobe epilepsy]. / Cenni di storia moderna della chirurgia delle epilessie del lobo temporale.

We make an overview of the most significant historical steps of the temporal lobe epilepsies surgical treatment, from the first description, at the end of 19th century, to recent times. We also describe the history of neuropsichological testing (mainly Wada test), extra- and intra-cranial EEG-recordings, synchronised electro-clinical monitoring, structural and functional neuroimaging. We mainly tried to point out that the selection of candidates to surgical treatment should be based, despite any technological development, on a synoptical anatomo-electroclinical reasoning.

Household health care facility utilization in the Philippines.

This paper presents probit estimates of household utilization of health care facilities in the Philippines. Using household data from the 1987 National Health Survey and supply data from the Department of Health, separate probit equations are estimated for each of the four major types of facilities in the Philippines: Public hospitals, private hospitals, major rural health units and barangay (village) health stations. The probability that a household will utilize services from these facilities is estimated as a function of socioeconomic, demographic and supply variables. The results indicate substantial differences in utilization patterns by income class. Households in the highest income quartile are approximately twice as likely (0.451 versus 0.236) to utilize private hospital services vis-à-vis households in the lowest income quartile, ceteris paribus. The results also indicate substantial substitution between public and private services. An increase in the availability of private hospital beds significantly reduces the probability that a household will utilize government facilities.