Earth conductivity structures and their effects on geomagnetic induction in pipelines

Anomalous, large pipe-to-soil potentials (PSP) have been observed along a natural gas pipeline in eastern Ontario, Canada, where there is a major geological contact between the highly resistive rocks of the Precambrian Shield to the west and the more conductive Paleozoic sediments to the east. This study tested the hypothesis that large variations of PSP are related to lateral changes of Earth conductivity under the pipeline. Concurrent and co-located PSP and magnetotelluric (MT) geophysical data were acquired in the study area. Results from the MT survey were used to model PSP variations based on distributed-source transmission line theory, using a spatially-variant surface geoelectric field. Different models were built to investigate the impact of different subsurface features. Good agreement between modelled and observed PSP was reached when impedance peaks related to major changes of subsurface geological conditions were included. The large PSP could therefore be attributed to the presence of resistive intrusive bodies in the upper crust and/or boundaries between tectonic terranes. This study demonstrated that combined PSP-MT investigations are a useful tool in the identification of potential hazards caused by geomagnetically induced currents in pipelines

USO DE RECEPTORES GPS DE 100 HZ NA DETECÇÃO DE DEFLEXÕES VERTICAIS MILIMÉTRICAS DE PONTES DE CONCRETO DE PEQUENO PORTE

As últimas quatro décadas foram importantes para o desenvolvimento da malha rodoviária brasileira. O país recebeu incentivos financeiros para a sua expansão e diversas soluções estruturais para pontes e viadutos foram criadas. Em paralelo a este desenvolvimento, houve nos últimos anos um crescimento significativo dessas estruturas em estágio avançado de deterioração devido à ausência de programas de manutenção preventiva. Dessa maneira, este trabalho propõe o uso de receptores GPS num plano de monitoramento de curta duração para acompanhar o comportamento estrutural de uma ponte rodoviária curva de concreto armado já em serviço. E apresenta os primeiros resultados da pesquisa com a portadora L1 do sistema GPS e dados gravados com taxa de 100 Hz, no monitoramento do vão central de ponte de concreto de pequeno porte situada sobre o Rio Jaguari, na cidade de Extrema, divisa entre os Estados de Minas Gerais e São Paulo. O desafio reside no fato de que estruturas como estas - pontes de concreto de pequeno e médio porte - respondem pela grande maioria das obras de arte da malha rodoviária brasileira e por serem estruturas rígidas, apresentam deflexões verticais pequenas, de até 5mm. O experimento foi realizado por meio de sessões de observações com receptores GPS sobre a ponte, no vão instrumentado por equipamentos convencionais para posterior confrontação de resultados entre os receptores GPS e os métodos clássicos de monitoramento. A ferramenta de filtragem Continuos Wavelet Transform (CWT) foi utilizada para analisar as frequências de resposta da ponte a partir dos resíduos da dupla diferença de fase da portadora L1. A análise do espectro de energia da CWT gerado a partir dos dados coletados com os receptores GPS indicou alta concentração de energia nas mesmas faixas de frequência - de resposta do tabuleiro da ponte - apontadas pela Modelagem por Elementos Finitos e pela prova de carga dinâmica

Hospital discharges-based search of acute flaccid paralysis cases 2007-2016 in Italy and comparison with the National Surveillance System for monitoring the risk of polio reintroduction

Background: Acute flaccid paralysis (AFP) surveillance has been adopted globally as a key strategy for monitoring the progress of the polio eradication initiative. Hereby, to evaluate the completeness of the ascertainment of AFP cases in Italy, a hospital-discharges based search was carried out. Methods: AFP cases occurring between 2007 and 2016 among children under 15 years of age were searched in the Italian Hospital Discharge Records (HDR) database using specific ICD-9-CM diagnostic codes. AFP cases identified between 2015 and 2016 were then compared with those notified to the National Surveillance System (NSS). Results: Over a 10-year period, 4163 hospital discharges with diagnosis of AFP were reported in Italy. Among these, 956 (23.0%) were acute infective polyneuritis, 1803 (43.3%) myopathy, and 1408 (33.8%) encephalitis, myelitis and encephalomyelitis. During the study period, a decreasing trend was observed for all diagnoses and overall the annual incidence rate (IR) declined from 5.5 to 4.5 per 100,000 children. Comparing NSS with HDR data in 2015-2016, we found a remarkable underreporting, being AFP cases from NSS only 14% of those recorded in HDR. In particular, the acute infective polyneuritis cases reported to NSS accounted for 42.6% of those detected in HDR, while only 0.9% of myopathy cases and 13.1% of encephalitis/myelitis/encephalomyelitis cases have been notified to NSS. The highest AFP IRs per 100,000 children calculated on HDR data were identified in Liguria (17.4), Sicily (5.7), and Veneto (5.1) Regions; regarding the AFP notified to the NSS, 11 out of 21 Regions failed to reach the number of expected cases (based on 1/100,000 rate), and the highest discrepancies were observed in the Northern Regions. Overall, the national AFP rate was equal to 0.6, therefore did not reach the target value. Conclusions: AFP surveillance data are the final measure of a country's progress towards polio eradication. The historical data obtained by the HDR have been useful to assess the completeness of the notification data and to identify the Regions with a low AFP ascertainment rate in order to improve the national surveillance system

High-density neutrophils in MGUS and multiple myeloma are dysfunctional and immune-suppressive due to increased STAT3 downstream signaling

To understand neutrophil impairment in the progression from MGUS through active MM, we investigated the function of mature, high-density neutrophils (HDNs), isolated from peripheral blood. In 7 MM, 3 MGUS and 3 healthy subjects by gene expression profile, we identified a total of 551 upregulated and 343 downregulated genes in MM-HDN, involved in chemokine signaling pathway and FC-gamma receptor mediated phagocytosis conveying in the activation of STAT proteins. In a series of 60 newly diagnosed MM and 30 MGUS patients, by flow-cytometry we found that HDN from MM, and to a lesser extend MGUS, had an up-regulation of the inducible FcγRI (also known as CD64) and a down-regulation of the constitutive FcγRIIIa (also known as CD16) together with a reduced phagocytic activity and oxidative burst, associated to increased immune-suppression that could be reverted by arginase inhibitors in co-culture with lymphocytes. In 43 consecutive newly-diagnosed MM patients, who received first-line treatment based on bortezomib, thalidomide and dexamethasone, high CD64 could identify at diagnosis patients with inferior median overall survival (39.5 versus 86.7 months, p = 0.04). Thus, HDNs are significantly different among healthy, MGUS and MM subjects. In both MGUS and MM neutrophils may play a role in supporting both the increased susceptibility to infection and the immunological dysfunction that leads to tumor progression

Melflufen and dexamethasone in heavily pretreated relapsed and refractory multiple myeloma

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade $ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease

Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs\u27 therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy