Macaca sylvanus Linnaeus 1758 from the Middle Pleistocene of Quecchia Quarry (Brescia, Northern Italy)

During the Plio-Pleistocene the Barbary macaque, Macaca sylvanus Linnaeus, 1758 was widely distributed throughout Europe and North Africa (Szalay and Delson, 1979; Delson, 1980; Rook et al., 2001), and it became extinct in Europe during the Late Pleistocene (Elton and O’Regan, 2014). Nowadays this primate is still present in North Africa and a small population has been reintroduced at Gibraltar (Modolo et al., 2005). The taxonomy of the Plio-Pleistocene European macaques is still debated but many authors agree in considering all the fossils as belonging to the M. sylvanus lineage, while the Pleistocene endemic M. majori Azzaroli, 1946 from Sardinia (Italy) has been considered a distinct valid species (Rook and O’Higgins, 2005). The occurrence of this species is documented from Late Pliocene to Late Pleistocene sites located in Northern and Central Italy. Here we describe unpublished dentognathic remains of Macaca sylvanus from the Middle Pleistocene site of Quecchia Quarry (Botticino, Brescia, North Italy)

A new journal... on spindle cells

Welcome to Clinical Sarcoma Research a new open access, online medical journal providing a forum for clinical knowledge on rare solid cancers - sarcomas. We believe there is a vacuum, which this effort may hope to fill at least in part. Indeed, we ought to share first-hand medical experience and clinically meaningful translational ideas much more within the sarcoma community worldwide. This journal is intended to be one of the many tools we need for this purpose

Long-term disease stability with bicalutamide in a man with aggressive angiomyxoma: case report and state of art

Aggressive angiomyxoma (AA) is a rare mesenchymal neoplasm, which is commonly diagnosed in females and located in the perineal and pelvic region. Tissue specimens of AA patients often show positivity for estrogen (ER) and progesterone receptors (PgR), while some cases of androgen receptor (AR) positivity have been reported in males. When feasible, surgical excision represent the most effective treatment of AA; however, when experiencing advanced or recurrent disease, local disease control could be achieved with systemic hormonal treatment. To date, evidence regarding AA management in male patients is scarce, and only a few cases have been reported in literature. Hereby, we describe the case of a 59-year-old-man suffering from perineal AA with positivity for androgen receptors (AR) showing a long-lasting disease stability during the treatment with an AR-blocking drug (bicalutamide). A literature review regarding the state of art of AA management with a particular look to male patients is also provided

Protection estimates for the 13 kA bus bars interconnections at 3.5 - 4.5 TeV

This memorandum provides alternate estimates of the critical additional resistance Radd of the 13 kA superconducting bus bars interconnections (IC), both for the LHC main bending (MB) dipole and main quadrupole (MQ) magnets. The calculations are performed using the 1-D thermo-electrical model described in [1], based on the definition of transverse local heat transfer coefficient towards the cooling helium bath established from the analysis of short sample tests performed in 2009 and 2010. Details on the model and its validation are not discussed here. The most pessimistic (adiabatic), most optimistic (full cooling) and most likely (partial cooling) critical additional resistances are provided, depending on the bus-bar and cable RRR, dump time constant, and space distribution of the defect, for beam energy between 3.5 and 4.5 TeV

EBV-Encoded Latent Membrane Protein 1 Cooperates with BAFF/BLyS and APRIL to Induce T Cell-Independent Ig Heavy Chain Class Switching

By substituting the H chain C region of IgM with that of IgG, IgA, or IgE, class switching enables Abs to acquire new effector functions that are crucial for the neutralization of invading pathogens. Class switching occurs through class switch DNA recombination (CSR) and usually requires engagement of CD40 on B cells by CD40 ligand on Ag-activated CD4+ T cells. CSR must be tightly regulated because abnormal IgG and IgA production favors the onset of autoimmunity, whereas increased switching to IgE leads to atopy. These inflammatory disorders can be triggered or exacerbated by EBV infection. In this study, we show that EBV induces CD40-independent CSR from Cµ to multiple downstream Cγ, Cα, and C∊ genes through latent membrane protein 1 (LMP1), a CD40-like viral protein that signals in a ligand-independent fashion. LMP1-induced CSR is associated with transcriptional activation of germline Cγ, Cα, and C∊ genes and triggers the up-regulation of activation-induced cytidine deaminase, a crucial component of the CSR machinery. In addition, LMP1 induces B cells to express B cell-activating factor of the TNF family and a proliferation-inducing ligand, two molecules that mediate B cell survival and T cell-independent Ab production. B cell-activating factor of the TNF family and a proliferation-inducing ligand cooperate with LMP1 to induce Ig class switching because their neutralization by appropriate soluble decoy receptors attenuates CSR in LMP1-expressing B cells. By showing that LMP1 triggers T cell-independent CSR, our findings suggest that EBV could play an important role in the pathogenesis of disorders with aberrant IgG, IgA, and/or IgE production

Stability analysis of the Interconnection of the LHC Main Superconducting Bus Bars

The operation of the Large Hadron Collider calls for a thorough analysis of the thermo-electric behavior of the 13 kA superconducting bus-bars connecting its dipole and quadrupole main magnets. This presentation reports a synthesis of the work performed jointly by researchers and students at CERN and at the University of Bologna as a contribution to the understanding of the LHC incident occurred on September 19th 2008. This work is complementary to the analyses carried out at CERN by the MPE group. The aim of the work is to analyze the stability of the interconnections as far as the quality of manufacturing, operating conditions and protection system parameters are concerned. A first part of the work is devoted to the development of a numerical model suitable for the analysis of the faulty interconnections. The main type of defect analyzed is the lack of solder among the superconducting cable and the copper stabilizer components at the interface between bus bar and splice. The evaluation of the critical defect length limiting the maximum safe current for powering the magnets without risk of thermal runaway is provided, as a function of the RRR of cable and stabilizer, decay time constant of the LHC circuit, spatial distribution of the defect and cooling conditions. A second part of the work is related to the modeling of the heat transfer mechanism between the main superconducting bus bar and the surrounding helium bath. This study is aimed to analyze a set of experimental measurements on the heat transfer coefficient of the main bending dipole bus bars performed at CERN. The final part of the work consists in a preliminary analysis of the heat transfer mechanisms involved in the stability experiments of defective interconnections performed in the FRESCA facility

Rechallenge of denosumab in advanced giant cell tumor of the bone after atypical femur fracture: A case report and review of literature

Giant cell tumor of the bone (GCTB) is a locally aggressive neoplasm where surgery is often curative. However, it can rarely give rise to distant metastases. Currently, the only available active therapeutic option for unresectable GCTB is denosumab, an anti-RANKL monoclonal antibody that dampens the aggressive osteolysis typically seen in this disease. For advanced/metastatic GCTB, denosumab should be continued lifelong, and although it is usually well tolerated, important questions may arise about the long-term safety of this drug. In fact, uncommon but severe toxicities can occur and eventually lead to denosumab discontinuation, such as atypical fracture of the femur (AFF). The optimal management of treatment-related AFF is a matter of debate, and to date, it is unknown whether reintroduction of denosumab at disease progression is a clinically feasible option, as no reports have been provided so far. Hereinafter, we present a case of a patient with metastatic GCTB who suffered from AFF after several years of denosumab; we describe the clinical features, orthopedic treatment, and oncological outcomes, finally providing the first evidence that denosumab rechallenge after AFF occurrence may be a safe and viable option at GCTB progression

Latitude variation in the prevalence of asthma and allergic rhinitis in Italy: results from the GEIRD study

BACKGROUND: Earlier studies have pointed out a great variability in the prevalence of asthma and asthma-like symptoms in different geo-climatic areas. AIM: To test the association between latitude and prevalence of asthma and allergic rhinitis in Italian young adults. METHODS: In the frame of Gene-Environment Interaction in Respiratory Diseases study, a postal screening questionnaire on respiratory health and exposure to environmental factors was administered to 18,357 randomly selected subjects aged 20-44 years in 7 centres: 3 in Northern (Torino, Pavia, Verona), 2 in Central (Ancona, Perugia) and 2 in Southern Italy (Salerno, Sassari). RESULTS: 10,494 (57.2%) subjects responded to the questionnaire. The prevalence of self-reported doctor-diagnosed asthma and allergic rhinitis in the lifespan was 10.2% and 26.9%, respectively, and was significantly different across the centres (p<0.05). After adjusting for sex, age, potential risk factors for respiratory diseases and design confounders, the prevalence of asthma (OR: 1.07 per 1°latitude decrease, p<0.001), asthma-like symptoms (wheezing, chest tightness, asthma attacks: OR ranging from 1.04 to 1.06, p<0.05) and allergic rhinitis (OR: 1.03, p=0.04) showed a significant north-to-south trend. Similarly, a 1°C increment in temperature was significantly associated with asthma (OR: 1.10, p<0.001) and asthma-like symptoms (OR from 1.07 to 1.10, p<0.05), but not with allergic rhinitis (OR=1.02, p=0.190). CONCLUSION: The prevalence of asthma and allergic rhinitis increased moving southwards in Italy, suggesting that prolonged exposure to different geo-climatic conditions may affect the onset of asthma and allergic respiratory diseases

Long-term survival in elderly patients with a do-not-intubate order treated with noninvasive mechanical ventilation

Paolo Scarpazza1, Cristoforo Incorvaia2, Paolo Amboni3, Giuseppe di Franco1, Stefania Raschi1, Pierfranco Usai1, Monica Bernareggi1, Cristiano Bonacina1, Chiara Melacini1, Roberta Cattaneo1, Serena Bencini1, Chiara Pravettoni2, Gian Galeazzo Riario-Sforza2, Gianni Passalacqua4, Walter Casali11Divisione di Broncopneumotisiologia, Ospedale Civile, Vimercate, Italy; 2Pulmonary Rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy; 3Clinical Chemistry Laboratory, Ospedali Riuniti, Bergamo, Italy; 4Allergy and Respiratory Diseases, University Of Genoa, Genoa, ItalyBackground: Noninvasive mechanical ventilation (NIMV) is an effective tool in treating patients with acute respiratory failure (ARF), since it reduces both the need for endotracheal intubation and the mortality in comparison with nonventilated patients. A particular issue is represented by the outcome of NIMV in patients referred to the emergency department for ARF and with a do-not-intubate (DNI) status because of advanced age or excessively critical conditions. This study evaluated long-term survival in a group of elderly patients with acute hypercapnic ARF who had a DNI order and who were successfully treated by NIMV.Methods: The population consisted of 54 patients with a favorable outcome after NIMV for ARF. They were followed up for 3 years by regular control visits, with at least one visit every 4 months, or as needed according to the patient’s condition. Of these, 31 continued NIMV at home and 23 were on long-term oxygen therapy (LTOT) alone.Results: A total of 16 of the 52 patients had not survived at the 1-year follow-up, and another eight patients died during the 3-year observation, with an overall mortality rate of 30.8% after 1 year and 46.2% after 3 years. Comparing patients who continued NIMV at home with those who were on LTOT alone, 9 of the 29 patients on home NIMV died (6 after 1 year and 3 after 3 years) and 15 of the 23 patients on LTOT alone died (10 after 1 year and 5 after 3 years).Conclusion: These results show that elderly patients with ARF successfully treated by NIMV following a DNI order have a satisfactory long-term survival.Keywords: COPD, acute respiratory failure, mortality rate, respiratory failur