Regulating altruistic agents

Altruism or `regard for others' can encourage self-restraint among generators of negative externalities, thereby mitigating the externality problem. We explore how introducing impure altruism into standard regulatory settings alters regulatory prescriptions. We show that the optimal calibration of both quantitative controls and externality taxes are affected. It also leads to surprising results on the comparative performance of instruments. Under quantity-based regulation welfare is increasing in the propensity for altruism in the population; under price-based regulation the relationship is non-monotonic. Price-based regulation is preferred when the population is either predominantly altruistic or predominantly selfish, quantity-based regulation for cases in between

Evaluation of a kDNA-Based qPCR Assay for the Detection and Quantification of Old World Leishmania Species

none10noThe parasite protozoan Leishmania, the causative agent of leishmaniasis, includes two subgenera of medical interest: Leishmania (Leishmania) and Leishmania (Viannia). Parasite species detection and characterization is crucial to choose treatment protocols and to monitor the disease evolution. Molecular approaches can speed up and simplify the diagnostic process. In particular, several molecular assays target the mitochondrial DNA minicircle network (kDNA) that characterizes the Leishmania genus. We previously proposed a qPCR assay targeting kDNA, followed by high resolution melt (HRM) analysis (qPCR-ML) to distinguish L. (L.) infantum and L. (L.) amazonensis from L. Viannia species. Successively, this assay has been integrated with other qPCR assays, to differentiate L. (L.) infantum, L. (L.) amazonensis and L. (L.) mexicana. In this work, we tested the applicability of our qPCR-ML assay on L. (L.) donovani, L. (L.) major, L. (L.) tropica and L. (L.) aethiopica, showing that the qPCR-ML assay can also amplify Old World species, different from L. (L.) infantum, with good quantification limits (1 × 10-4-1 × 10-6 ng/pcr tube). Moreover, we evaluated 11 L. (L.) infantum strains/isolates, evidencing the variability of the kDNA minicircle target molecules among the strains/isolates of the same species, and pointing out the possibility of quantification using different strains as reference. Taken together, these data account for the consideration of qPCR-ML as a quantitative pan-Leishmania assay.openCeccarelli, Marcello; Buffi, Gloria; Diotallevi, Aurora; Andreoni, Francesca; Bencardino, Daniela; Vitale, Fabrizio; Castelli, Germano; Bruno, Federica; Magnani, Mauro; Galluzzi, LucaCeccarelli, Marcello; Buffi, Gloria; Diotallevi, Aurora; Andreoni, Francesca; Bencardino, Daniela; Vitale, Fabrizio; Castelli, Germano; Bruno, Federica; Magnani, Mauro; Galluzzi, Luc

Cranial radiotherapy predisposes to abdominal adiposity in survivors of childhood acute lymphocytic leukemia

Background: Advances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in this process. the aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia.Methods: A comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance.Results: Cranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance.Conclusions: Adolescent and young adult survivors of childhood acute lymphocytic leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Div Pediat Endocrinol, Dept Pediat, UNIFESP EPM, São Paulo, BrazilIOP GRAACC, Pediat Oncol Inst, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Prevent & Social Med, Div Biostat, UNIFESP EPM, São Paulo, BrazilUniv Estadual Campinas, Lab Invest Metab & Diabet LIMED, Fac Med Sci, UNICAMP, Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imaging, UNIFESP EPM, São Paulo, BrazilUniv Estadual Campinas, Dept Pediat, Div Pediat Endocrinol, Fac Med Sci,UNICAMP, Campinas, SP, BrazilUniversidade Federal de São Paulo, Div Pediat Endocrinol, Dept Pediat, UNIFESP EPM, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Prevent & Social Med, Div Biostat, UNIFESP EPM, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imaging, UNIFESP EPM, São Paulo, BrazilFAPESP: 06/06162-9Web of Scienc

Development and Application of a High Resolution Melt (HRM) based test for the Rapid Screening of Leishmania infantum Genotypes

INTRODUCTION Leishmaniasis includes anthropo zoonotic infectious diseases caused by a protozoan of the Leishmania genus, associated with different clinical manifestations, affecting both humans and other vertebrates, including dogs The Mediterranean basin, including Italy, is considered an endemic area for both visceral and cutaneous leishmaniasis caused by L infantum The multi locus enzyme electrophoresis ( based on the electrophoretic mobility of several enzymes from promastigotes cultures, is considered the reference method for parasite typing Through this method, about 45 L infantum zymodemes (also termed MON) have been identified in humans in the Mediterranean basin 1 Among these, L infantum MON 1 is the most widespread, representing about 70 of all identified strains In Italy, canine infections showed a high prevalence of MON 1 91 with the remaining composed almost exclusively of MON 72 2 Since MLEE technique is cumbersome, time consuming and requires parasites isolation, several biomolecular approaches have been developed In particular, we identified the SNP 390 T>G in malic enzyme ( gene as a potential marker to differentiate the most common L infantum genotype, i e 390 T (corresponding to zymodemes MON 1 72 201 from all others. AIMS This study aimed to develop a Rapid Genotype Screening ( assay for L infantum genetic characterization in clinical samples using high resolution melt ( analysis, exploiting the polymorphism 390 T>G in the ME gene

Development and application of a MLST panel for the identification of informative polymorphisms in Leishmania infantum strains in the Mediterranean region

Background. Leishmaniasis is a zoonotic disease endemic in the Mediterranean region, where the causative agent of human and canine infection is Leishmania infantum. The spread of leishmaniasis is associated with population movements, ecology of phlebotomine vectors, and reservoir host. We used multilocus sequence typing (MLST) to explore the genetic variability of L. infantum strains in the Mediterranean region, including the borderline territory of Pantelleria island, and identify informative polymorphisms for rapid identification of genotypes through high-resolution melt (HRM)-based assays. Material and Methods. A customized sequencing panel targeting 14 housekeeping genes was designed and MLST analysis was performed using the Ion Torrent S5 on 9 L. infantum strains/isolates: 5 canine isolates (3 from Pantelleria Island and 2 from central Italy), and 4 human isolates/strains from Tunisia, France, central and southern Italy. MLST results and in silico analysis of sequences available in Genbank allowed to select two informative polymorphisms on ME and GPI genes (390T/G and 1834A/G, respectively) used to develop two HRM-based assays for fast screening of 28 clinical samples. Results. The MLST analysis identified a single L. infantum clonal complex regardless of the geographic origin or host (human or canine), except for the human isolate from central Italy that showed polymorphisms in 11 out of 14 housekeeping genes, and clustered independently in a molecular phylogenetic analysis. Successively, the screening through HRM-based assays of 28 clinical samples from central/south Italy and Pantelleria island allowed to identify 6 diploid sequence types (DSTs). Interestingly, the sequence type 390T/1834A was found only in Pantelleria island (prevalence 75%). Conclusion. This study represents a description of the genetic variability of L. infantum through a first approach based on MLST and then by HRM analysis on selected polymorphisms. The HRM assays could be used as fast and cheap tools for epidemiological surveillance of L. infantum

Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir with or without Ribavirin in Patients with HIV-HCV Coinfection. Real Life Interim Analysis of an Italian Multicentre Compassionate Use Program

Background and Aims: An HCV cure is now possible in a large proportion of HIV-HCV patient. We present real life results of a compassionate use program promoted by SIMIT (Infectious and Tropical Diseases Italian Society) of Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir ± Ribavirin for 12 weeks in 213 HIV-HCV genotype 1 patients. Data on efficacy and tolerability of this strategy in HIV patients have been reported until now only in 43 non cirrhotic HIV subjects

Multi-messenger prospects for black hole - neutron star mergers in the O4 and O5 runs

The existence of merging black hole-neutron star (BHNS) binaries has been ascertained through the observation of their gravitational wave (GW) signals. However, to date, no definitive electromagnetic (EM) emission has been confidently associated with these mergers. Such an association could help unravel crucial information on these systems, for example, their BH spin distribution, the equation of state (EoS) of NS and the rate of heavy element production. We model the multi-messenger (MM) emission from BHNS mergers detectable during the fourth (O4) and fifth (O5) observing runs of the LIGO-Virgo-KAGRA GW detector network, in order to provide detailed predictions that can help enhance the effectiveness of observational efforts and extract the highest possible scientific information from such remarkable events. Our methodology is based on a population synthesis-approach, which includes the modelling of the signal-to-noise ratio of the GW signal in the detectors, the GW-inferred sky localization of the source, the kilonova (KN) optical and near-infrared light curves, the relativistic jet gamma-ray burst (GRB) prompt emission peak photon flux, and the GRB afterglow light curves in the radio, optical and X-ray bands. The resulting prospects for BHNS MM detections during O4 are not promising, with a GW detection rate of $15.0^{+15.4}_{-8.8}$ yr$^{-1}$, but joint MM rates of $\sim 10^{-1}$ yr$^{-1}$ for the KN and $\sim 10^{-2}$ yr$^{-1}$ for the jet-related emission. In O5 we find an overall increase in expected detection rates by around an order of magnitude, owing to both the enhanced sensitivity of the GW detector network, and the coming online of future EM facilities. Finally, we discuss direct searches for the GRB radio afterglow with large-field-of-view instruments as a new possible follow-up strategy in the context of ever-dimming prospects for KN detection.Comment: Submitted to A&A. 17 pages, 11 figures, 2 tables. Comments are welcome

Trichphyton violaceum and T. soudanese: re-emerging pathogens in Italy, 2005-2013

Dermatomycoses due to Trichophyton violaceum are described in Mediterranean Countries, North Africa and in the Horn of Africa where T. soudanense is present too, but it was rare until few years ago in Italy. Aim of the present study was to evaluate an Italian multicenter 9 year (2005-2013) experience concerning these re-emerging pathogens. Fifty three fungal strains were sent from clinical laboratories to the Medical Mycology Committee (CoSM) - Italian Association of Clinical Microbiology (AMCLI) for mycological confirmation. Strains were identified as T. violaceum (23) and T. soudanense (30) by phenotypic and genotypic methods. These dermatophytes present epidemiological (high rate of inter-human transmission, high risk among adopted children coming from countries of either the Horn of Africa or Sub-Saharan Africa also in outbreaks of tinea capitis) and clinical peculiarities (reduced alopecia, presence of exudative lesions) confirming the originality of these \u201cimported\u201d dermatophyte infection

From current status to optimization of HCV treatment: Recommendations from an expert panel

Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens. For such reason interferon-free regimens are now the treatments of choice for all patients. Successful anti-HCV treatment can stop liver disease progression and can solve the HCV-related extra hepatic manifestations, eventually reducing both liver-related and overall mortality. Together with the rapidly accumulating data about the evolution of treatment landscape, different guidelines from national and international Liver Scientific Societies have been published until today. However, these recommendations may not be applied worldwide as, due to high treatment costs, most of them identify as priority groups only patients with advanced liver disease. Moreover some types of patients pose clinical management problems for which even the guidelines do not always provide useful answers. With the aim of treatment optimization by filling some of the gaps of the current guidelines and addressing the remaining unmet needs in practice, a group of Italian experts, experienced on treatment of HCV infection, met in Stresa in February 2016. The summary of all the considerations arising from this two-day meeting and the final statements are reported in this position paper

Preoperative bi-fractionated accelerated radiation therapy for combined treatment of locally advanced rectal cancer in a consectutive series of unselected patients

Background: although preoperative RT (Radiation Therapy) is becoming the preferred approach for combined treatment of locally advanced rectal adenocarcinoma, no regimen can be now considered as a standard. Since the toxicity of preoperative RT isn't yet completely known, and the advantages of preoperative RT could be counterbalanced by increased postoperative morbidity and mortality, a monocentre series of preoperative bifractionated accelerated RT was retrospectively reviewed to clarify toxicity and outcomes after a prolonged follow up. Methods: patients were screened following these eligibility criteria: histology-proven adenocarcinoma of the rectum; distal tumour extent at 12 cm or less from the anal verge; clinical stage T3-4/anyN, or anyT/ N1-2; ECOG Performance Status 0-2. A total dose of 41.6 Gy (26 twice daily fractions of 1.6 Gy) was delivered. Surgery was carried out 17 \ub1 2 days after RT completion, adopting the total mesorectal excision technique. Results: 24 men and 23 women were enrolled; median age was 55 years (r.: 39-77). Twenty-eight patients were stage II and 19 stage III. 9 patients suffered from a recurrent tumour. 2 patients experienced a severe grade 4 gastrointestinal toxicity (a colo-vaginal fistula and an intestinal obstruction, both successfully treated). Operative mortality was nil; postoperative early complications occurred in 13 cases; mean length of hospital stay was 15 days. After a mean follow up of 44 months (r.: 18-84) 8 patients had deceased for recurrent disease, 15 were alive with a disease progression (2 pelvic recurrences and 13 pure distant deposits) and 24 were alive, without disease. The 5-year actuarial overall survival was 74.2%, the disease-free survival 62.9% and the regional control rate 84.7%. Long-term complications included 1 case of radiation enteritis requiring surgery, 2 cases of anastomotic stricture and 3 cases of bladder incontinence. Conclusion: bifractionated accelerated RT administered in the preoperative setting to patients bearing locally advanced rectal cancer is reliable and safe, as its immediate and late toxicity (mainly infectious) is acceptably low and long-term survivals are achievable. These findings support the increasing use of preoperative RT for treatment of this malignancy in experienced centres. Ongoing multicentric trials are expected to address still unsolved issues, including the benefit of CT adjunct to preoperative RT