Development of Silicon PhotoMultipliers at FBK-irst

We report on the development of Silicon PhotoMultipliers (SiPM) at the Fondazione Bruno Kessler (FBK)-irst (Trento, Italy) in the framework of a collaboration with INFN. Device geometry and technology are resumed, and selected results from the characterization of SiPM prototypes from three production batches are reported, including static, dynamic, and noise properties, as well as photodetection efficiency

First report in italy of the exotic mosquito species Aedes (Finlaya) koreicus, a potential vector of arboviruses and filariae

BACKGROUND: In the Veneto region (north-eastern Italy) an entomological surveillance system has been implemented since the introduction of the Asian tiger mosquito (Aedes albopictus) in 1991. During the routine monitoring activity in a tiger mosquito-free area, an unexpected mosquito was noticed, which clearly did not belong to the recorded Italian fauna. FINDINGS: At the end of May 2011, twelve larvae and pupae were collected in a small village in Belluno province (Veneto region) from a single manhole. Ten adults reared in the laboratory were morphologically and genetically identified as Aedes (Finlaya) koreicus (Edwards, 1917), a species native to Southeast Asia. The subsequent investigations carried out in the following months in the same village provided evidence that this species had become established locally. Entomological and epidemiological investigations are currently ongoing in the surrounding area, to verify the eventual extension of the species outside the village and to trace back the route of entry into Italy. CONCLUSIONS: This is the first report in Italy of the introduction of the exotic mosquito Ae. koreicus. This species has been shown experimentally to be competent in the transmission of the Japanese encephalitis virus and of the dog heartworm Dirofilaria immitis and is considered a potential vector of other arboviruses. Thus, the establishment of this species may increase the current risk or pose new potential threats, for human and animal health. This finding considerably complicates the entomological monitoring of the Asian tiger mosquito Ae. albopictus in Italy and stresses the importance of implementing the entomological surveillance for the early detection of and the rapid response against invasive mosquito species

Prospective longitudinal evaluation of treatment-related toxicity and health-related quality of life during the first year of treatment for pediatric acute lymphoblastic leukemia

Background: Pediatric acute lymphoblastic leukemia (ALL) therapy is accompanied by treatment-related toxicities (TRTs) and impaired quality of life. In Australia and New Zealand, children with ALL are treated with either Children’s Oncology Group (COG) or international Berlin-Frankfurt-Munster (iBFM) Study Group-based therapy. We conducted a prospective registry study to document symptomatic TRTs (venous thrombosis, neurotoxicity, pancreatitis and bone toxicity), compare TRT outcomes to retrospective TRT data, and measure the impact of TRTs on children’s general and cancer-related health-related quality of life (HRQoL) and parents’ emotional well-being. Methods: Parents of children with newly diagnosed ALL were invited to participate in the ASSET (Acute Lymphoblastic Leukaemia Subtypes and Side Effects from Treatment) study and a prospective, longitudinal HRQoL study. TRTs were reported prospectively and families completed questionnaires for general (Healthy Utility Index Mark 3) and cancer specific (Pediatric Quality of Life Inventory (PedsQL)-Cancer Module) health related quality of life as well the Emotion Thermometer to assess emotional well-being. Results: Beginning in 2016, 260 pediatric patients with ALL were enrolled on the TRT registry with a median age at diagnosis of 59 months (range 1–213 months), 144 males (55.4%), majority with Pre-B cell immunophenotype, n = 226 (86.9%), 173 patients (66.5%) treated according to COG platform with relatively equal distribution across risk classification sub-groups. From 2018, 79 families participated in the HRQoL study through the first year of treatment. There were 74 TRT recorded, reflecting a 28.5% risk of developing a TRT. Individual TRT incidence was consistent with previous studies, being 7.7% for symptomatic VTE, 11.9% neurotoxicity, 5.4% bone toxicity and 5.0% pancreatitis. Children’s HRQoL was significantly lower than population norms throughout the first year of treatment. An improvement in general HRQoL, measured by the HUI3, contrasted with the lack of improvement in cancer-related HRQoL measured by the PedsQL Cancer Module over the first 12 months. There were no persisting differences in the HRQoL impact of COG compared to iBFM therapy. Conclusions: It is feasible to prospectively monitor TRT incidence and longitudinal HRQoL impacts during ALL therapy. Early phases of ALL therapy, regardless of treatment platform, result in prolonged reductions in cancer-related HRQoL

Unique technique of surgery in an unusual variety of Scimitar syndrome: A Case Report

Scimitar syndrome is a rare congenital anomaly characterized by total or partial anomalous pulmonary venous drainage of the right lung to the inferior vena cava. We present a seven year old girl with a systolic murmur who was diagnosed as having a Scimitar syndrome with unusual drainage of the right pulmonary veins. The unique technique of surgery in this patient was appropriate to the unusual, previously not described anatomy

Prospective longitudinal evaluation of treatment-related toxicity and health-related quality of life during the first year of treatment for pediatric acute lymphoblastic leukemia

Background Pediatric acute lymphoblastic leukemia (ALL) therapy is accompanied by treatment-related toxicities (TRTs) and impaired quality of life. In Australia and New Zealand, children with ALL are treated with either Children's Oncology Group (COG) or international Berlin-Frankfurt-Munster (iBFM) Study Group-based therapy. We conducted a prospective registry study to document symptomatic TRTs (venous thrombosis, neurotoxicity, pancreatitis and bone toxicity), compare TRT outcomes to retrospective TRT data, and measure the impact of TRTs on children's general and cancer-related health-related quality of life (HRQoL) and parents' emotional well-being. Methods Parents of children with newly diagnosed ALL were invited to participate in the ASSET (Acute Lymphoblastic Leukaemia Subtypes and Side Effects from Treatment) study and a prospective, longitudinal HRQoL study. TRTs were reported prospectively and families completed questionnaires for general (Healthy Utility Index Mark 3) and cancer specific (Pediatric Quality of Life Inventory (PedsQL)-Cancer Module) health related quality of life as well the Emotion Thermometer to assess emotional well-being. Results Beginning in 2016, 260 pediatric patients with ALL were enrolled on the TRT registry with a median age at diagnosis of 59 months (range 1-213 months), 144 males (55.4%), majority with Pre-B cell immunophenotype, n = 226 (86.9%), 173 patients (66.5%) treated according to COG platform with relatively equal distribution across risk classification sub-groups. From 2018, 79 families participated in the HRQoL study through the first year of treatment. There were 74 TRT recorded, reflecting a 28.5% risk of developing a TRT. Individual TRT incidence was consistent with previous studies, being 7.7% for symptomatic VTE, 11.9% neurotoxicity, 5.4% bone toxicity and 5.0% pancreatitis. Children's HRQoL was significantly lower than population norms throughout the first year of treatment. An improvement in general HRQoL, measured by the HUI3, contrasted with the lack of improvement in cancer-related HRQoL measured by the PedsQL Cancer Module over the first 12 months. There were no persisting differences in the HRQoL impact of COG compared to iBFM therapy. Conclusions It is feasible to prospectively monitor TRT incidence and longitudinal HRQoL impacts during ALL therapy. Early phases of ALL therapy, regardless of treatment platform, result in prolonged reductions in cancer-related HRQoL.Clarissa E. Schilstra, Karen McCleary, Joanna E. Fardell, Mark W. Donoghoe, Emma McCormack, Rishi S. Kotecha, Richard De Abreu Lourenco, Shanti Ramachandran, Ruelleyn Cockcroft, Rachel Conyers, Siobhan Cross, Luciano Dalla, Pozza, Peter Downie, Tamas Revesz, Michael Osborn, Frank Alvaro, Claire E. Wakefield, Glenn M. Marshall, Marion K. Mateos, and Toby N. Trahai

Total Dose Dependence of Oxide Charge, Interstrip Capacitance and Breakdown Behavior of sLHC Prototype Silicon Strip Detectors and Test Structures of the SMART Collaboration

Abstract For the future luminosity upgrade proposed for the Large Hadron Collider (LHC) silicon strip detectors (SSD) and test structures were fabricated on various high-resistivity substrates (p-type MCz and FZ, n-type FZ) within the INFN funded SMART project. They were irradiated with 60 Co to test total dose (TID) effects, in order to study the impact of surface radiation damage on the detector properties (interstrip capacitance and resistance, break-down voltage). Selected results from the pre-rad and post-rad characterization of detectors and test structures are presented, in particular interstrip capacitance, breakdown voltage, flatband voltage and oxide charge. They show saturation at about 150 kRad. Annealing are performed both at room and at elevated temperature

Methotrexate-related central neurotoxicity: clinical characteristics, risk factors and genome-wide association study in children treated for acute lymphoblastic leukemia

Symptomatic methotrexate-related central neurotoxicity (MTX neurotoxicity) is a severe toxicity experienced during acute lymphoblastic leukemia (ALL) therapy with potential long-term neurologic complications. Risk factors and long-term outcomes require further study. We conducted a systematic, retrospective review of 1,251 consecutive Australian children enrolled on Berlin-Frankfurt-Münster or Children's Oncology Group-based protocols between 1998-2013. Clinical risk predictors for MTX neurotoxicity were analyzed using regression. A genome-wide association study (GWAS) was performed on 48 cases and 537 controls. The incidence of MTX neurotoxicity was 7.6% (n=95 of 1,251), at a median of 4 months from ALL diagnosis and 8 days after intravenous or intrathecal MTX. Grade 3 elevation of serum aspartate aminotransferase (P=0.005, odds ratio 2.31 [range, 1.28–4.16]) in induction/consolidation was associated with MTX neurotoxicity, after accounting for the only established risk factor, age ≥10 years. Cumulative incidence of CNS relapse was increased in children where intrathecal MTX was omitted following symptomatic MTX neurotoxicity (n=48) compared to where intrathecal MTX was continued throughout therapy (n=1,174) (P=0.047). Five-year central nervous system relapse-free survival was 89.2±4.6% when intrathecal MTX was ceased compared to 95.4±0.6% when intrathecal MTX was continued. Recurrence of MTX neurotoxicity was low (12.9%) for patients whose intrathecal MTX was continued after their first episode. The GWAS identified single-nucletide polymorphism associated with MTX neurotoxicity near genes regulating neuronal growth, neuronal differentiation and cytoskeletal organization (P<1x10-6). In conclusion, increased serum aspartate aminotransferase and age ≥10 years at diagnosis were independent risk factors for MTX neurotoxicity. Our data do not support cessation of intrathecal MTX after a first MTX neurotoxicity event.Marion K. Mateos, Glenn M Marshall, Pasquale M. Barbaro, Michael C.J. Quinn, Carly George, Chelsea Mayoh, Rosemary Sutton, Tamas Revesz, Jodie E Giles, Draga Barbaric, Frank Alvaro, Françoise Mechinaud, Daniel Catchpoole, John A. Lawson, Georgia Chenevix-Trench, Stuart MacGregor, Rishi S.Kotecha, Luciano Dalla-Pozza, and Toby N. Traha

Climatic Factors Driving Invasion of the Tiger Mosquito (Aedes albopictus) into New Areas of Trentino, Northern Italy

Background:The tiger mosquito (Aedes albopictus), vector of several emerging diseases, is expanding into more northerly latitudes as well as into higher altitudes in northern Italy. Changes in the pattern of distribution of the tiger mosquito may affect the potential spread of infectious diseases transmitted by this species in Europe. Therefore, predicting suitable areas of future establishment and spread is essential for planning early prevention and control strategies.Methodology/Principal Findings:To identify the areas currently most suitable for the occurrence of the tiger mosquito in the Province of Trento, we combined field entomological observations with analyses of satellite temperature data (MODIS Land Surface Temperature: LST) and human population data. We determine threshold conditions for the survival of overwintering eggs and for adult survival using both January mean temperatures and annual mean temperatures. We show that the 0°C LST threshold for January mean temperatures and the 11°C threshold for annual mean temperatures provide the best predictors for identifying the areas that could potentially support populations of this mosquito. In fact, human population density and distance to human settlements appear to be less important variables affecting mosquito distribution in this area. Finally, we evaluated the future establishment and spread of this species in relation to predicted climate warming by considering the A2 scenario for 2050 statistically downscaled at regional level in which winter and annual temperatures increase by 1.5 and 1°C, respectively.Conclusions/Significance:MODIS satellite LST data are useful for accurately predicting potential areas of tiger mosquito distribution and for revealing the range limits of this species in mountainous areas, predictions which could be extended to an European scale. We show that the observed trend of increasing temperatures due to climate change could facilitate further invasion of Ae. albopictus into new areas. © 2011 Roiz et al.Peer Reviewe

Outcome of children with multiply relapsed B-cell acute lymphoblastic leukemia: a therapeutic advances in childhood leukemia & lymphoma study.

The survival of pediatric patients with multiply relapsed and/or refractory (R/R) B-cell acute lymphoblastic leukemia has historically been very poor; however, data are limited in the current era. We conducted a retrospective study to determine the outcome of multiply R/R childhood B-ALL treated at 24 TACL institutions between 2005 and 2013. Patient information, treatment, and response were collected. Prognostic factors influencing the complete remission (CR) rate and event-free survival (EFS) were analyzed. The analytic set included 578 salvage treatment attempts among 325 patients. CR rates (mean ± SE) were 51 ± 4% for patients with bone marrow R/R B-ALL who underwent a second salvage attempt, 37 ± 6% for a third attempt, and 31 ± 6% for the fourth through eighth attempts combined. For patients achieving a CR after their second, third, and fourth through eighth attempts, the 2 year EFS was 41 ± 6%, 13 ± 7%, and 27 ± 13% respectively. Our results showed slight improvement when compared to previous studies. This is the largest and most recent study to date that evaluates the outcome of this patient population. Our data will provide detailed reference for the evaluation of new agents being developed for childhood B-ALL