Vacuum ultraviolet silicon photomultipliers applied to BaF2cross-luminescence detection for high-rate ultrafast timing applications.

Inorganic scintillators are widely used for fast timing applications in high-energy physics (HEP) experiments, time-of-flight positron emission tomography and time tagging of soft and hard x-ray photons at advanced light sources. As the best coincidence time resolution (CTR) achievable is proportional to the square root of the scintillation decay time it is worth studying fast cross-luminescence, for example in BaF2which has an intrinsic yield of about 1400 photons/MeV. However, emission bands in BaF2are located in the deep-UV at 195 nm and 220 nm, which sets severe constraints on photodetector selection. Recent developments in dark matter and neutrinoless double beta decay searches have led to silicon photomultipliers (SiPMs) with photon detection efficiencies of 20%-25% at wavelengths of 200 nm. We tested state-of-the-art devices from Fondazione Bruno Kessler and measured a best CTR of 51 ± 5 ps full width at half maximum when coupling 2 mm × 2 mm × 3 mm BaF2crystals excited by 511 keV electron-positron annihilation gammas. Using these vacuum ultraviolet SiPMs we recorded the scintillation kinetics of samples from Epic Crystal under 511 keV excitation, confirming a fast decay time of 855 ps with 12.2% relative light yield and 805 ns with 84.0% abundance, together with a smaller rise time of 4 ps beyond the resolution of our setup. The total intrinsic light yield was determined to be 8500 photons/MeV. We also revealed a faster component with 136 ps decay time and 3.7% light yield contribution, which is extremely interesting for the fastest timing applications. Timing characteristics and CTR results on BaF2samples from different producers and with different dopants (yttrium, cadmium and lanthanum) are given, and clearly show that the the slow 800 ns emission can be effectively suppressed. Such results ultimately pave the way for high-rate ultrafast timing applications in medical diagnosis, range monitoring in proton or heavy ion therapy and HEP.

Penile cancer: prognostic and predictive factors in clinical decision-making.

Penile cancer (PC) is a typical tumor of non-industrialized countries. The incidence is 20-30 times higher in Africa and South America, considering the elevated prevalence of sexually transmitted diseases. Histologically, PC includes squamous cell carcinoma (SCPC), the most frequent, and nonsquamous carcinoma (NSCPC). Early diagnosis is the goal, whereas later diagnosis relates to poor functional outcomes and worse prognosis. The 5-year survival rate is 85% for patients with histologically regional negative lymph nodes, compared to 29%-40% for those with histologically regional positive lymph nodes. To date no new drugs are approved, and there are few new data about molecular mechanisms underlying tumorigenesis. The SCPC remains a rare tumor and the current therapeutic algorithm is based principally on retrospective analysis and less on prospective trials. In this review article, biomarkers of prognosis and efficacy of current treatments are summarized with a focus on those that have the potential to affect treatment decision-making in SCPC.

Advanced/metastatic bladder cancer: current status and future directions.

In 2015 bladder cancer was the fourth most frequent malignancy and the eighth cause of death for cancer. At diagnosis, about 30% of bladder cancer (BC) patients present a muscle-invasive bladder cancer (MIBC) and 5% a metastatic bladder carcinoma (MBC). For fit MBC patients, combination chemotherapy (CC) is the standard of care for first-line treatment. CC includes both the treatment with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) either the classical or the dose-dense MVAC regimen, and the doublet therapy with cisplatin and gemcitabine (CG). Median progression free survival (PFS) was 7 months and median overall survival (OS) was 15 months. The present review provides an update on the management of MBC, with focus on target therapies, immune checkpoint inhibition, looking for prognostic and predictive factors.

A very-high-energy component deep in the γ-ray burst afterglow.

Gamma-ray bursts (GRBs) are brief flashes of γ-rays and are considered to be the most energetic explosive phenomena in the Universe1. The emission from GRBs comprises a short (typically tens of seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed2. GRBs typically emit most of their energy via γ-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments3. However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive4. Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and γ-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.

Prognostic and predictive factors in testicular cancer.

OBJECTIVE: Testicular cancer is a relatively rare neoplasia, with an incidence of about 1,5% among male malignancies, usually in the third and fourth decade of life. Although several histological variants are known, with some histotypes affecting older patients (e.g., spermatocytic seminoma), there is a clear predominance (90-95%) of germ cell tumors among young adults patients1. Testicular Germ Cell Tumor (TGCT), undoubtedly the seminoma histological variant more than non-seminoma one, is definitely a highly curable disease, with a distinctive sensitivity to cisplatin-based therapy (and for seminomas to radiotherapy) and an outstanding cure rate of nearly 80% even for patients with advanced disease. So far, clinical and pathohistological features supported our efforts to choose the best treatment option for patients suffering from this malignancy, but we don't clearly enough know molecular and pathological features underlying different clinical behaviors, mostly in early-stage disease: by improving this knowledge, we should better "shape" therapeutic or surveillance programs for each patient, also in order to avoid unnecessary, if not harmful, treatments.

Search for γ-Ray Line Signals from Dark Matter Annihilations in the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy γ rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant γ-ray excess above the background is found. We derive upper limits on the annihilation cross section ⟨σv⟩ for monoenergetic DM lines at the level of 4×10^{-28} cm^{3} s^{-1} at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based γ-ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two γ-ray photons at the level expected from the thermal relic density for TeV DM particles.

Histological and immunohistochemical characterisation of uterine adenocarcinoma in an Asian elephant (Elephas Maximus).

A 56-year-old nulliparous female Asian elephant (Elephas maximus) living at the zoological garden of Naples (Italy), with a clinical history of recurrent colic, was found in agonal state and humane euthanasia was elected. At necropsy the uterine body was moderately increased in size and the lumen was reduced due to a poorly demarcated and infiltrative neoplasm. Furthermore, multiple, whitish, firm nodules were present in both lungs. Histological examination of the uterine mass revealed epithelial cells arranged in tubular or solid pattern infiltrating the endometrium and the muscular layer. Immunohistochemical examination showed immunoreactivity of neoplastic cells to oestrogen receptors antibody. Pulmonary lesions were histologically and immunohistochemically superimposable to the epithelial uterine neoplasm. A definitive diagnosis of uterine adenocarcinoma with pulmonary metastases was made.

H.E.S.S. Limits on Linelike Dark Matter Signatures in the 100 GeV to 2 TeV Energy Range Close to the Galactic Center.

A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l=-1.5°, b=0° and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. RESULTS: No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.

Search for Dark Matter Annihilations towards the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using γ-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant γ-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section ⟨σv⟩. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach ⟨σv⟩ values of 6×10^{-26} cm^{3} s^{-1} in the W^{+}W^{-} channel for a DM particle mass of 1.5 TeV, and 2×10^{-26} cm^{3} s^{-1} in the τ^{+}τ^{-} channel for a 1 TeV mass. For the first time, ground-based γ-ray observations have reached sufficient sensitivity to probe ⟨σv⟩ values expected from the thermal relic density for TeV DM particles.

CD55 is a HIF-2α marker with anti-adhesive and pro-invading properties in neuroblastoma.

CD55 has been revealed to have an important role in tumor genesis, and presence of small populations of cells with strong CD55 expression would be sufficient to predict poor prognosis of several tumors. In our study we revealed that CD55 is a novel target of hypoxia-inducible factor HIF-2α in neuroblastoma (NB) cells. We show that HIF-2α expression is sufficient to sustain stem-like features of NB cells, whereas CD55 protein upon HIF-2α expression contributes to growth of colonies and to invasion of cells, but not to stemness features. Interestingly, in NB tissues, CD55 expression is limited to quite a small population of cells that are HIF-2α positive, and the gene expression of CD55 in the NB data set reveals that the presence of CD55(high) affects prognosis of NB patients. The functional characterization of CD55-positive populations within heterogeneous NB monoclonal cell lines shows that CD55 has pro-invading and anti-adhesive properties that might provide the basis for the ability of solid tumors to survive as microscopic residual disease. The easy accessibility to CD55 membrane antigen will offer the possibility of a novel antibody approach in the treatment of recurrent tumors and will provide a ready target for antibody-based visualization in NB diagnosis and prognosis.

VITAMIN D AND BRONCHIAL INFLAMMATION IN ASTHMATIC CHILDREN.

The role of the vitamin D in calcium homeostasis and bone metabolism is well known. In recent years it has been recognized that in addition to the traditional functions, vitamin D modulates a variety of processes such as host defense, inflammation and immunity. Epidemiological data indicate that low levels of vitamin D in serum are associated with impaired lung function and increased incidence of inflammatory diseases, infectious diseases and cancer. The authors studied the correlation among vitamin D levels, allergic inflammation, lung function and control of asthma and found a significant decrease of FeNO values (p= 0.0018) in children with vitamin D levels>30 ng/ml. These findings confirm that vitamin D plays a major role in bronchial inflammation.

Dopamine transporter single-photon emission computerized tomography supports diagnosis of akinetic crisis of parkinsonism and of neuroleptic malignant syndrome.

Akinetic crisis (AC) is akin to neuroleptic malignant syndrome (NMS) and is the most severe and possibly lethal complication of parkinsonism. Diagnosis is today based only on clinical assessments yet is often marred by concomitant precipitating factors. Our purpose is to evidence that AC and NMS can be reliably evidenced by FP/CIT single-photon emission computerized tomography (SPECT) performed during the crisis. Prospective cohort evaluation in 6 patients. In 5 patients, affected by Parkinson disease or Lewy body dementia, the crisis was categorized as AC. One was diagnosed as having NMS because of exposure to risperidone. In all FP/CIT, SPECT was performed in the acute phase. SPECT was repeated 3 to 6 months after the acute event in 5 patients. Visual assessments and semiquantitative evaluations of binding potentials (BPs) were used. To exclude the interference of emergency treatments, FP/CIT BP was also evaluated in 4 patients currently treated with apomorphine. During AC or NMS, BP values in caudate and putamen were reduced by 95% to 80%, to noise level with a nearly complete loss of striatum dopamine transporter-binding, corresponding to the "burst striatum" pattern. The follow-up re-evaluation in surviving patients showed a recovery of values to the range expected for Parkinsonisms of same disease duration. No binding effects of apomorphine were observed. By showing the outstanding binding reduction, presynaptic dopamine transporter ligand can provide instrumental evidence of AC in Parkinsonism and NMS.

Inhaled hyaluronic acid as ancillary treatment in children with bacterial acute rhinopharyngitis.

Acute rhinopharyngitis (ARP) is the most common upper respiratory infection in children and represents a social problem for both the pharmaco-economic impact and a burden for the family. Topical antibiotic therapy is usually effective in bacterial ARP, but ancillary treatment might improve its efficacy. Hyaluronic acid (HA) is a promising molecule that has been recently proposed in upper respiratory disorders. Therefore, the purpose of this study was to evaluate the effects of ancillary HA treatment in children with bacterial ARP. Globally, 51 children (27 males, mean age 5.9 ± 2.1 years) with bacterial ARP were enrolled in the study. At baseline, children were randomly assigned to the treatment with: 125 mg of thiamphenicol diluted in 4 mL of saline isotonic solution twice daily (group A) or with 125 mg of thiamphenicol plus 4 ml of sodium hyaluronate 0.2% plus xylitol 5% (Aluneb, Sakura Italia) twice daily (group B) administered by the nasal device Rinowash (Airliquide Medical System, Italy) and connected to an aerosol nebulizer with pneumatic compressor (1.5 bar per 5 L/min) Nebula (Airliquide Medical System, Italy), for 10 days. sVAS, nasopharyngeal spotting, neutrophils and bacteria were assessed at baseline and after the treatment. Both treatments induced significant reduction of symptom perception, spotting, neutrophil and bacteria count. However, thiamphenicol plus HA was able to significantly induce a greater effect on sVAS (p=0.006), neutrophil count (p=0.01), and bacteria count (p=0.0003) than thiamphenicol alone. In conclusion, this study provides the first evidence that intranasal HA, as ancillary treatment, may be able to improve topical antibiotic efficacy in children with bacterial ARP.

FLOTAC for diagnosis of endo-parasites in pet squirrels in southern Italy.

The present study investigated the occurrence of endoparasites in pet squirrels in southern Italy. Fresh fecal samples were collected from 50 asymptomatic pet squirrels belonging to five different species (Callosciurus finlaysonii, n=6, C. prevosti, n=6; Tamias striatus, n=26, T. sibiricus, n=10; Sciurus carolinensis, n=2) housed both in pet shops and/or in private residences. All fecal samples were processed using the FLOTAC pellet technique to identify and count helminth eggs/larvae and protozoan cysts/oocysts. In addition, to detect Cryptosporidium spp. and Giardia spp. the samples were analyzed by the Remel Xpect(®) immunoassay. Helminth eggs were detected in 9 out of 50 squirrels. Specifically, eggs of Dicrocoelium dendriticum were found in 5 squirrels (C. finlaysonii, n=2; C. prevosti, n=2; T. striatus, n=1); eggs of the pinworm Syphacia spp. in 3 squirrels (C. prevosti, n=2; T. striatus, n=1); and eggs of gastrointestinal nematoda (Nippostrongylus-like) were found in 1 subject (C. prevosti). Finally, two squirrels (C. prevosti) had multiple parasitic infections with D. dendriticum and Capillaria hepatica, and with D. dendriticum and Strongyloides spp., respectively. None of the samples were positive for Cryptosporidium spp. or Giardia spp. or any other protozoa (e.g. Eimeria). To the authors' knowledge, this is the first report of a D. dendriticum natural infection in pet rodents.

Oral flora of Python regius kept as pets.

UNLABELLED: This study was aimed at evaluating the oral bacterial flora of 60 Python regius kept as pets by culture and biochemical methods. All isolates were also submitted to antimicrobial susceptibility testing using the disc diffusion method. The oral cavity of snakes sampled harboured a wide range of Gram-negative bacteria mainly constituted by Pseudomonas spp., Morganella morganii, Acinetobacter calcoaceticus, Aeromonas hydrophila, but also by Salmonella spp. Staphylococcus spp. was the commonest Gram-positive isolates, and various anaerobic Clostridium species were also found. The most effective antimicrobial agents were enrofloxacin and ciprofloxacin, followed by doxycycline and gentamicin. SIGNIFICANCE AND IMPACT OF THE STUDY: The oral cavity of snakes sampled harboured a wide range of bacteria. Our results suggest that people who come in contact with snakes could be at risk of infection and should follow proper hygiene practices when handling these reptiles.

Recurrent and fatal akinetic crisis in genetic-mitochondrial parkinsonisms.

BACKGROUND AND PURPOSE: Akinetic crisis (AC) is the most severe and possibly lethal complication of parkinsonism. It occurs with an incidence of 3‰ Parkinson's disease patients per year, but it is not known whether genetically determined parkinsonism is more or less susceptible to this complication. METHODS: In a cohort of 756 parkinsonian patients the incidence and outcome of AC was prospectively assessed. A total of 142 of the parkinsonian patients were tested for genetic mutations because of familial parkinsonism, and 20 patients resulted positive: in four the mutation definitely involved mitochondrial functions (POLG1, PINK1), two presented with LRRK2 mutation, nine presented with GBA mutation and five presented with Park 4 different mutations. RESULTS: Akinetic crisis occurred in 30 patients for an incidence of 2.8‰ persons/year and was lethal in seven (23%), not dissimilarly from known incidences of this complication. Yet six of 30 patients were carriers of genetic mutations, one GBA, one LRRK2, one POLG1 and three PINK1. In POLG1 and PINK1 carriers, the syndrome was recurrent and was fatal in three. Incidence of AC was 3.0‰ in familiar parkinsonism, 21.2‰ in genetic parkinsonisms. CONCLUSIONS: Our preliminary findings suggest that the incidence of AC is remarkably increased in carriers of these genetic mutations.

Salso-sulphide thermal water in the prevention of recurrent respiratory infections in children.

Recurrent respiratory infections (RRI) represent a social problem for both the pharmaco-economic impact and the burden on the family. Thermal water is popularly well accepted. However, there is no scientific evidence of its preventive activity on recurrent respiratory tract infections (RRI). Therefore, the purpose of this study was to evaluate the effects of Agnano thermal water nasal irrigation on RRI prevention in children.A total of 107 children (70 males, mean age 4.5 plus minus1.2 years) with RRI were enrolled in the study. At baseline, children were randomly assigned to the treatment with: A) inhaled crenotherapy with salso-sulphide water or B) isotonic saline (NaCl 0.9 percent). Inhaled therapy was performed using nasal washing by Rino-jet (ASEMA srl, Milan, Italy) b.i.d. for 12 days. Nasal washing lasted 2 minutes per nostril. Immediately before washing, children inhaled 1 l of water by stream inhalation per 2 minutes. Crenotherapy was capable of significantly reducing: the number of respiratory infections, nasal symptoms, neutrophil and bacteria count, turbinate and adenoidal hypertrophy, presence of biofilm, and blockage of ostiomeatal complex (OCM). In conclusion, this study provides the first evidence that Agnano crenotherapy may be capable of preventing RRI in children as it exerts some positive effects, such as reduction of nasal obstruction, OCM blockage, biofilm, and inflammatory events.

Recurrence of tako-tsubo syndrome, idiopathic dilated cardiomyopathy, and iterative ventricular tachycardia: just a fortuitous coincidence or a pathophysiological link?

We report the case of a 65-year-old woman with late recurrence of tako-tsubo syndrome, idiopathic dilated cardiomyopathy and prior iterative ventricular tachycardia. We hypothesize that the pathophysiological link among these clinical conditions could be the hyperactivity of the sympathetic nervous system.