Analyzing Temperature Effects on Mortality Within the R Environment: The Constrained Segmented Distributed Lag Parameterization

Here we present and discuss the R package modTempEff including a set of functions aimed at modelling temperature effects on mortality with time series data. The functions fit a particular log linear model which allows to capture the two main features of mortality- temperature relationships: nonlinearity and distributed lag effect. Penalized splines and segmented regression constitute the core of the modelling framework. We briefly review the model and illustrate the functions throughout a simulated dataset.

Analyzing Temperature Effects on Mortality Within the R Environment: The Constrained Segmented Distributed Lag Parameterization

Here we present and discuss the R package modTempEff including a set of functions aimed at modelling temperature effects on mortality with time series data. The functions fit a particular log linear model which allows to capture the two main features of mortality- temperature relationships: nonlinearity and distributed lag effect. Penalized splines and segmented regression constitute the core of the modelling framework. We briefly review the model and illustrate the functions throughout a simulated dataset

Extinctions of aculeate pollinators in Britain and the role of large-scale agricultural changes

Pollinators are fundamental to maintaining both biodiversity and agricultural productivity, but habitat destruction, loss of flower resources, and increased use of pesticides are causing declines in their abundance and diversity. Using historical records we assessed the rate of extinction of bee and flower-visiting wasp species in Britain, from the mid 19th century to the present. The most rapid phase of extinction appears to be related to changes in agricultural policy and practice beginning in the 1920s, before the agricultural intensification prompted by the Second World War, often cited as the most important driver of biodiversity loss in Britain. Slowing of the extinction rate from the 1960s onwards may be due to prior loss of the most sensitive species and/or effective conservation programs

Global trends in infectious diseases at the wildlife–livestock interface

The role and significance of wildlife–livestock interfaces in disease ecology has largely been neglected, despite recent interest in animals as origins of emerging diseases in humans. Scoping review methods were applied to objectively assess the relative interest by the scientific community in infectious diseases at interfaces between wildlife and livestock, to characterize animal species and regions involved, as well as to identify trends over time. An extensive literature search combining wildlife, livestock, disease, and geographical search terms yielded 78,861 publications, of which 15,998 were included in the analysis. Publications dated from 1912 to 2013 and showed a continuous increasing trend, including a shift from parasitic to viral diseases over time. In particular there was a significant increase in publications on the artiodactyls–cattle and bird–poultry interface after 2002 and 2003, respectively. These trends could be traced to key disease events that stimulated public interest and research funding. Among the top 10 diseases identified by this review, the majority were zoonoses. Prominent wildlife–livestock interfaces resulted largely from interaction between phylogenetically closely related and/or sympatric species. The bird–poultry interface was the most frequently cited wildlife–livestock interface worldwide with other interfaces reflecting regional circumstances. This review provides the most comprehensive overview of research on infectious diseases at the wildlife–livestock interface to date

Necrotizing fasciitis of the lower limbs

We report an uncommon severe soft-tissue infection of the thighs in a male child with acute lymphoblastic leukemia. Early and aggressive medical treatment and the conservative surgical approach were successful. Necrotizing fasciitis should be suspected in any soft-tissue infection until it can be definitely ruled out, since prompt deliver of medical and surgical intervention is essential

A STEP-BY-STEP PROCESS TO GENERATE FUNCTIONAL OSTEOCLASTS FROM SITE SPECIFIC GENE-CORRECTED INDUCED PLURIPOTENT STEM CELLS: AN AUTOLOGOUS CELL THERAPY APPROACH TO TREAT AUTOSOMAL RECESSIVE OSTEOPETROSIS.

Autosomal recessive osteopetrosis (ARO) is a human severe inherited disorder leading to increased bone mass, decreased bone strength with risk of multiple fractures and progressive narrowing of the medullary cavity. Among the heterogeneous group of osteopetrosis, ARO shows the most severe phenotype, leading to death early in life if not treated. The most frequently mutated gene is the T-cell immune regulator 1 (TCIRG1), encoding the a3 subunit of the vacuolar-type proton transporting ATPase pump, which mediates the acidification of the bone/osteoclast interface, causing defects in the resorbing activity of osteoclasts. The spontaneous mouse model oc/oc well recapitulates the disease features. Hematopoietic stem cell (HSC) transplantation is the only treatment so far available to cure the disease, due to the hematopoietic origin of osteoclasts, however its success is limited to the restricted number of available matched donors. Thus, the transplant of autologous corrected hematopoietic cells represents a valid alternative therapeutic option. In particular, due to the limitations in performing gene targeting of primary cells, induced pluripotent stem cells (iPSc) obtained from patients could represent an unlimited source of autologous cells in which it is possible to perform target gene correction. They can be subsequently differentiated towards hematopoietic progenitors to perform an autologous transplantation. In the present thesis, I have exploited murine iPSc as a potential source of cells to be differentiated into functional osteoclasts able to resorb bone. To this end, I have pursued the following strategy: (a) generation of vector-free iPSc from wild type (wt) and oc/oc mice employing a third generation Cre-excisable lentiviral vector carrying the reprogramming genes Oct4, Sox2, Klf4; (b) correction of oc/oc iPSc replacing the entire mutated Tcirg1 gene through homologous recombination, by using a BAC engineered vector; (c) set up a protocol for the differentiation of wt, uncorrected and corrected oc/oc iPSc into the hematopoietic lineage, generating both mature cells and high proliferative potential colony-forming progenitors; (d) further differentiation of obtained myeloid precursors into osteoclasts with rescued bone resorbing activity upon gene-correction. The process is aimed at generating transplantable hematopoietic cells, including osteoclast precursors, with the final goal of transplanting them in the ARO mouse model oc/oc to revert the phenotype, thus providing a proof of principle for an autologous cell therapy approach to treat ARO