Progress in the design and construction of SPES at INFN-LNL

INFN-LNL is constructing an ISOL (Isotope Separation On Line) facility delivering neutron rich ion beams at 10 A MeV or beyond, making use of the linear accelerator ALPI as the secondary accelerator. The facility includes a direct ISOL target based on UCx and able to reach 1013 fissions/s. In parallel, an applied physics facility will be developed, with applications in medicine and neutron production. The SPES project is a national facility, approved and funded. Commissioning with the first exotic species is expected in 2019. The primary accelerator is a commercial cyclotron, which will send a 40 MeV, 200 μA proton beam onto an UCx target, connected to SIS, PIS and LIS ion sources. The extracted beam is purified through a Low Resolution Mass Separator (LMRS, i.e. a Wien filter and a dispersive dipole), a beam cooler and a High Resolution Mass Separator (HRMS) and sent to an ECR charge breeder to boost the exotic beam charge state. The highly charged exotic beam is further separated in a MRMS (Medium Resolution Mass Separator) and injected into a 100% duty cycle RFQ and into the existing superconducting linac ALPI, which will be refurbished and upgraded to be an efficient exotic beam accelerator. The upgrade of ALPI will give ∼10 A MeV energy to 132Sn19+, taken as the reference ion beam. The paper presents the status of the design and construction of the SPES facility

Epidemiology of Strongyloides stercoralis in northern Italy: Results of a multicentre case-control study, February 2013 to July 2014

Strongyloides stercoralis is a soil-transmitted helminth widely diffused in tropical and subtropical regions of the world. Autochthonous cases have been also diagnosed sporadically in areas of temperate climate. We aimed at defining the epidemiology of strongyloidiasis in immigrants and Italians living in three northern Italian Regions. Screening for S. stercoralis infection was done with serology, confirmation tests were a second serological method or stool agar culture. A case-control approach was adopted and patients with a peripheral eosinophil count 65 500/mcL were classified as cases. Of 2,701 individuals enrolled here 1,351 were cases and 1,350 controls; 86% were Italians, 48% women. Italians testing positive were in 8% (97/1,137) cases and 1% (13/1,178) controls (adjusted odds ratio (aOR) 8.2; 95% confidence interval (CI): 4.5-14.8), while positive immigrants were in 17% (36/214) cases and in 2% (3/172) controls (aOR 9.6; 95% CI: 2.9-32.4). Factors associated with a higher risk of infection for all study participants were eosinophilia (p < 0.001) and immigration (p = 0.001). Overall, strongyloidiasis was nine-times more frequent in individuals with eosinophilia than in those with normal eosinophil count

Autochthonous human and canine strongyloides stercoralis infection in europe: Report of a human case in an italian teen and systematic review of the literature

Autochthonous human and canine strongyloidiasis is reported in Europe but is unclear whether the transmission of infection still occurs. We report a previously unpublished human case in an Italian teen and perform a systematic review of literature on autochthonous human and canine strongyloidiasis in Europe to investigate the current dynamic of transmission. Overall, 109 papers published after 1987 were included and one previously unpublished Italian case was added. Eighty case reports were retrieved and 42 of them (52.5%) had severe strongyloidiasis. Most cases were diagnosed in Spain, Italy and France. The median age was 58, the most represented age group was 61–70 years, 11 patients were under 30, and 7 of them were diagnosed after 2000. Epidemiological studies on human strongyloidiasis showed prevalence ranging from 0.56% to 28%. Overall, agriculture work, mine work and walking barefoot were the most commonly reported risk factors for infection. Canine strongyloidiasis was reported mainly in Italy (68 cases), but a few cases occurred also in Iceland, Finland, England, Germany, France, Switzerland, Russia, Slovakia, Romania and Greece. Autochthonous strongyloidiasis is still reported in Europe and sporadic transmission still occurs. Health care professionals should be aware of this issue to identify infected subjects and avoid adverse outcomes, especially in immunosuppressed patients. Further investigations are needed to clarify the zoonotic transmission of this nematode

Malaria in illegal Chinese immigrants, Italy.

A cluster of 22 imported malaria cases, 21 caused by Plasmodium falciparum, was observed among illegal Chinese immigrants in northern Italy in the summer of 2000. The rate of severe disease was high because the patients were not immune and they sought health-care services late in their illness because of their clandestine status. Recognition of the outbreak was delayed because no regional alert system among infectious diseases hospitals was in place

Superconducting RFQs

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Interpreting genotype-by-environment interaction for biomass production in hybrid poplars under short-rotation coppice in Mediterranean environments

Understanding genotype × environment interaction (GEI) is crucial to optimize the deployment of clonal material to field conditions in short‐rotation coppice poplar plantations. Hybrid poplars are grown for biomass production under a wide range of climatic and edaphic conditions, but their adaptive performance in Mediterranean areas remains poorly characterized. In this work, site regression (SREG) and factorial regression mixed models are combined to gain insight into the nature and causes underlying GEI for biomass production of hybrid poplar clones. SREG addresses the issue of clonal recommendation in multi‐environment trials through a biplot representation that visually identifies superior genotypes. Factorial regression, alternatively, involves a description of clonal reaction to the environment in terms of physical variables that directly affect productivity. Initially, SREG aided in identifying cross‐over interactions that often involved hybrids of different taxonomic background. Factorial regression then selected latitude, mean temperature of the vegetative period (MTVP) and soil sand content as main site factors responsible for differential clonal adaptation. Genotypic responses depended strongly on taxonomic background: P. deltoides Bartr. ex Marsh. × P. nigra L. clones showed an overall positive sensitivity to increased MTVP and negative sensitivity to increased sand content, whereas the opposite occurred for P. trichocarpa Torr. & Gray × P. deltoides clones; the three‐cross hybrid [(P. deltoides × P. trichocarpa) × P. nigra] often displayed an intermediate performance. This information can contribute toward the identification and biological understanding of adaptive characteristics relevant for poplar breeding in Mediterranean conditions and facilitate clonal recommendation at eco‐regional level.This research was funded by MINECO (Spain) throughout the project RTA2008-00025-C02-01 and RTA2011-00006-00-00. We also acknowledge the collaboration of project AGL2009-11006. We would like to thank the public company SOMACYL for hosting one of the experimental plots. We are also grateful to Juan Pablo de la Iglesia and Ana Parras for their technical support throughout the experiment

Accuracy of Malaria Rapid Diagnostic Tests in Community Studies and their Impact on Treatment of Malaria in an Area with Declining Malaria Burden in North-Eastern Tanzania.

Despite some problems related to accuracy and applicability of malaria rapid diagnostic tests (RDTs), they are currently the best option in areas with limited laboratory services for improving case management through parasitological diagnosis and reducing over-treatment. This study was conducted in areas with declining malaria burden to assess; 1) the accuracy of RDTs when used at different community settings, 2) the impact of using RDTs on anti-malarial dispensing by community-owned resource persons (CORPs) and 3) adherence of CORPs to treatment guidelines by providing treatment based on RDT results. Data were obtained from: 1) a longitudinal study of passive case detection of fevers using CORPs in six villages in Korogwe; and 2) cross-sectional surveys (CSS) in six villages of Korogwe and Muheza districts, north-eastern, Tanzania. Performance of RDTs was compared with microscopy as a gold standard, and factors affecting their accuracy were explored using a multivariate logistic regression model. Overall sensitivity and specificity of RDTs in the longitudinal study (of 23,793 febrile cases; 18,154 with microscopy and RDTs results) were 88.6% and 88.2%, respectively. In the CSS, the sensitivity was significantly lower (63.4%; χ2=367.7, p<0.001), while the specificity was significantly higher (94.3%; χ2=143.1, p<0.001) when compared to the longitudinal study. As determinants of sensitivity of RDTs in both studies, parasite density of<200 asexual parasites/μl was significantly associated with high risk of false negative RDTs (OR≥16.60, p<0.001), while the risk of false negative test was significantly lower among cases with fever (axillary temperature ≥37.5 °C) (OR≤0.63, p≤0.027). The risk of false positive RDT (as a determinant of specificity) was significantly higher in cases with fever compared to afebrile cases (OR≥2.40, p<0.001). Using RDTs reduced anti-malarials dispensing from 98.9% to 32.1% in cases aged ≥5 years. Although RDTs had low sensitivity and specificity, which varied widely depending on fever and parasite density, using RDTs reduced over-treatment with anti-malarials significantly. Thus, with declining malaria prevalence, RDTs will potentially identify majority of febrile cases with parasites and lead to improved management of malaria and non-malaria fevers

The impact of an intervention to introduce malaria rapid diagnostic tests on fever case management in a high transmission setting in Uganda: A mixed-methods cluster-randomized trial (PRIME).

Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 95\% CI: 0.56, 1.17 p = 0.24). Most children (76.0\%) tested positive by reference mRDT, but many were not prescribed AL (22.5\% intervention versus 25.9\% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3\% invention vs 42.4\% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management

The usefulness of rapid diagnostic tests in the new context of low malaria transmission in zanzibar.

BACKGROUND\ud \ud We assessed if histidine-rich-protein-2 (HRP2) based rapid diagnostic test (RDT) remains an efficient tool for Plasmodium falciparum case detection among fever patients in Zanzibar and if primary health care workers continue to adhere to RDT results in the new epidemiological context of low malaria transmission. Further, we evaluated the performance of RDT within the newly adopted integrated management of childhood illness (IMCI) algorithm in Zanzibar.\ud \ud METHODS AND FINDINGS\ud \ud We enrolled 3890 patients aged ≥2 months with uncomplicated febrile illness in this health facility based observational study conducted in 12 primary health care facilities in Zanzibar, between May-July 2010. One patient had an inconclusive RDT result. Overall 121/3889 (3.1%) patients were RDT positive. The highest RDT positivity rate, 32/528 (6.1%), was found in children aged 5-14 years. RDT sensitivity and specificity against PCR was 76.5% (95% CI 69.0-83.9%) and 99.9% (95% CI 99.7-100%), and against blood smear microscopy 78.6% (95% CI 70.8-85.1%) and 99.7% (95% CI 99.6-99.9%), respectively. All RDT positive, but only 3/3768 RDT negative patients received anti-malarial treatment. Adherence to RDT results was thus 3887/3889 (99.9%). RDT performed well in the IMCI algorithm with equally high adherence among children <5 years as compared with other age groups.\ud \ud CONCLUSIONS\ud \ud The sensitivity of HRP-2 based RDT in the hands of health care workers compared with both PCR and microscopy for P. falciparum case detection was relatively low, whereas adherence to test results with anti-malarial treatment was excellent. Moreover, the results provide evidence that RDT can be reliably integrated in IMCI as a tool for improved childhood fever management. However, the relatively low RDT sensitivity highlights the need for improved quality control of RDT use in primary health care facilities, but also for more sensitive point-of-care malaria diagnostic tools in the new epidemiological context of low malaria transmission in Zanzibar.\ud \ud TRIAL REGISTRATION\ud \ud ClinicalTrials.gov NCT01002066