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Hepatitis E virus (HEV) is responsible for acute hepatitis in humans, through foodborne, zoonotic, and waterborne transmission routes. This study aimed to assess the prevalence of HEV in water matrices. Six categories were defined: untreated and treated wastewater, surface water (river, lake, and seawater), drinking water, groundwater, and other water environments (irrigation water, grey water, reservoir water, flood water, and effluent of pig slaughterhouse). We searched PubMed, Web of Science, Global Index Medicus, and Excerpta Medica Database. Study selection and data extraction were performed by at least two independent investigators. Heterogeneity (I2) was assessed using the χ2 test on the Cochran Q statistic and H parameter. Sources of heterogeneity were explored by subgroup analysis. This study is registered with PROSPERO, number CRD42021289116. We included 87 prevalence studies from 58 papers, 66.4% of which performed in Europe. The overall prevalence of HEV in water was 9.8% (95% CI 6.4–13.7). The prevalence was higher in untreated wastewater (15.1%) and lower in treated wastewater (3.8%) and in drinking water (4.7%). In surface water, prevalence was 7.4%, and in groundwater, the percentage of positive samples, from only one study available, was 8.3%. Overall, only 36.8% of the studies reported the genotype of HEV, with genotype 3 (HEV-3) prevalent (168 samples), followed by HEV-1 (148 sample), and HEV-4 (2 samples). High-income countries were the most represented with 59/87 studies (67.8%), while only 3/87 (3.5%) of the studies were performed in low-income countries. The overall prevalence obtained of this study was generally higher in industrialized countries. Risk of bias was low in 14.9% of the studies and moderate in 85.1%. The results of this review showed the occurrence of HEV in different waters environments also in industrialized countries with sanitation and safe water supplies. While HEV transmission to humans through water has been widely demonstrated in developing countries, it is an issue still pending in industrialized countries. Better knowledge on the source of pollution, occurrence, survival in water, and removal by water treatment is needed to unravel this transmission path. Graphical Abstract

Funding Acknowledgements Type of funding sources: None. Introduction From the beginning, the use of X-ray (XR) has been a critical component in both the guidance and development of arrhythmia ablation procedures. Despite the development of non-fluoroscopic navigators, the single-shot techniques for atrial fibrillation ablation procedures still rely almost exclusively on the use of XR. Recently, the Heliostar® irrigated radiofrequency balloon has been developed, which can be completely visualized on the Carto 3® navigation system. This special feature makes it possible to minimise the use of XR in this type of procedure or even suppress it. We present our first experience after the implementation of a "zero-XR" protocol for this procedure. Objectives The aim of this study was to demonstrate that "zero-XR" ablation of atrial fibrillation with Heliostar® radiofrequency balloon is possible and safe. Methods This is a single-centre study. Consecutively 22 patients with paroxysmal (63.6%) or persistent (36.4%) atrial fibrillation underwent pulmonary vein isolation by irrigated radiofrequency balloon (Heliostar®). Eight of the cases were performed without fluoroscopy, supported by the navigation system and intracardiac ultrasound, and the remaining 14 were performed without limitation of the use of XR. Clinical, echocardiographic and technical data were collected from all 22 patients. All cases were performed under general anaesthesia, with the Carto 3® navigation system. Mapping was performed in sinus rhythm whenever possible. Results 100% isolation of the veins was achieved, with 62.1% first pass isolation in the non-XR group versus 56.4% in the XR group (non-significant difference). The vein with the highest percentage of first pass isolations was the left inferior vein in both groups. There were no complications in either group. Procedure times were similar (left atrial dwell time of 32 minutes in the non-XR group and 40 minutes in the XR group, non-significant difference), although the mapping time was slightly shorter in the non-XR group (9,9±5 non-XR vs 16±6.9, p=0.04). There was also no difference in the mean time to isolation from the start of radiofrequency application in each vein (10.6 seconds in the non-XR group and 11 seconds in the XR group, p=0.75). The non-XR group had a higher number of patients with left main trunk, but the XR group had a higher percentage of patients with persistent forms of atrial fibrillation. Left atrial size was normal in most patients, and ventricular function was preserved, with no differences between the two groups. Conclusion Pulmonary vein isolation with the Heliostar® radiofrequency balloon without XR is possible and safe, with similar efficacy and first pass isolation rate, similar procedure time and no relevant complications in our series.

Perspective from Pathologic Characteristics of Cancers Detected in the Prostate Cancer Prevention Trial: Implications for Prostate Cancer Detection and Chemoprevention

Finasteride and Prostate Cancer: New York Times Article from Pathologic Characteristics of Cancers Detected in the Prostate Cancer Prevention Trial: Implications for Prostate Cancer Detection and Chemoprevention

This study adds insight regarding the occurrence and spread of SARS-CoV-2 Variants of Concern (VOCs) and Var-iants of Interest (VOIs) in Italy in October and November 2022, by testing urban wastewater collected through-out the country. A total of 332 wastewater samples were collected from 20 Italian Regions/Autonomous Provinces (APs) within the framework of national SARS-CoV-2 environmental surveillance. Of these, 164 were collected in the first week of October and 168 in the first week of November. A similar to 1600 bp fragment of the spike protein was sequenced by Sanger (for individual samples) and long-read nanopore sequencing (for pooled Region/AP samples).In October, mutations characteristic of Omicron BA.4/BA.5 were detected in the vast majority (91 %) of the samples amplified by Sanger sequencing. A fraction of these sequences (9 %) also displayed the R346T mutation. Despite the low prevalence documented in clinical cases at the time of sampling, amino acid substitutions characteristic of sublineages BQ.1 or BQ.1.1 were detected in 5 % of sequenced samples from four Regions/APs. A significantly higher variability of sequences and variants was documented in November 2022, when the rate of se-quences harbouring mutations of lineages BQ.1 and BQ1.1 increased to 43 %, and the number of Regions/APs positive for the new Omicron subvariant more than tripled (n = 13) compared to October. Moreover, an increase in the number of sequences with the mutation package BA.4/BA.5 + R346T (18 %), as well as the detection of variants never observed before in wastewater in Italy, such as BA.2.75 and XBB.1 (the latter in a Region where no clinical cases asso-ciated with this variant had ever been documented) was recorded.The results suggest that, as predicted by the ECDC, BQ.1/BQ.1.1 is rapidly becoming dominant in late 2022. Environ-mental surveillance proves to be a powerful tool for tracking the spread of SARS-CoV-2 variants/subvariants in the population.

The outbreak of coronavirus infectious disease-2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. Several studies have shown that detecting SARS-CoV-2 in untreated wastewater can be a useful tool to identify new outbreaks, establish outbreak trends, and assess the prevalence of infections. On 06 May 2021, over a year into the pandemic, we conducted a scoping review aiming to summarize research data on SARS-CoV-2 in sewage. Papers dealing with raw sewage collected at wastewater treatment plants, sewer networks, septic tanks, and sludge treatment facilities were included in this review. We also reviewed studies on sewage collected in community settings such as private or municipal hospitals, healthcare facilities, nursing homes, dormitories, campuses, airports, aircraft, and cruise ships. The literature search was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded 1090 results, 66 of which met the inclusion criteria and are discussed in this review. Studies from 26 countries worldwide have investigated the occurrence of SARS-CoV-2 in sewage of different origin. The percentage of positive samples in sewage ranged from 11.6 to 100%, with viral concentrations ranging from ˂LOD to 4.6 × 108 genome copies/L. This review outlines the evidence currently available on wastewater surveillance: (i) as an early warning system capable of predicting COVID-19 outbreaks days or weeks before clinical cases; (ii) as a tool capable of establishing trends in current outbreaks; (iii) estimating the prevalence of infections; and (iv) studying SARS-CoV-2 genetic diversity. In conclusion, as a cost-effective, rapid, and reliable source of information on the spread of SARS-CoV-2 and its variants in the population, wastewater surveillance can enhance genomic and epidemiological surveillance with independent and complementary data to inform public health decision-making during the ongoing pandemic. Graphic Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s12560-021-09498-6.

Introduction From the outset, the use of Xray (XR) has been a critical component in both the guidance and development of arrhythmia ablation procedures. At present however, due to the complex nature of electrophysiology procedures, the use of XR in isolation is not sufficient to ensure procedural success. Subsequently, the use of non-fluoroscopic virtual mapping systems is essential. Currently, given the evolution of this technology and its essential nature for procedural guidance, it is worth asking whether the use of XR is indeed still necessary in the modern era. The objective of this study was to demonstrate that “zero-XR” ablation of complex arrhythmias such as atrial fibrillation is both possible and safe. Methods Between 2020 and 2021, a total of 116 patients admitted for pulmonary vein ablation were included in the study. Amongst these, 41 patients were prospectively included at our centre, in a protocol for point-by-point ablation of pulmonary veins without fluoroscopy, “zero-XR”. In addition to the non-fluoroscopic mapping system, the transseptal puncture was monitored by intracardiac ultrasound in all cases. The objective of the ablation was the complete isolation of the pulmonary veins. In some patients, at the discretion of the operator, the ablation of other substrates was added. For the remaining 75 patients in the study, the ablation was performed using conventional techniques without the limitation of the use of XR. The mean follow up was 12 months. Results The baseline characteristics of the patients, as well as the description of the procedure, are shown in the Table. There were no differences in the acute success rate or procedure time between the two groups. There was only one complication related to the procedure in the non-XR group consisting of pericardial effusion without cardiac tamponade. Regarding the recurrence rate at 12 months, it was higher in the group with fluoroscopy, without reaching statistical significance [n=0 in the group without fluoroscopy, n=2 (2.7%) in the group with fluoroscopy, p=0.15]. Conclusion In our series, point-by-point ablation of atrial fibrillation without fluoroscopy proved to be a safe and feasible technique, with similar success rates when compared to conventional procedures using XR. Funding Acknowledgement Type of funding sources: None.

Since May 2022, monkeypox cases have been reported in non-endemic countries, and the disease was declared a Public Health Emergency of International Concern. Rapid identification of new cases is critical for outbreak control. Environmental surveillance can be used as a complementary tool for detecting pathogens circulating in communities. This study aimed to investigate whether Monkeypox DNA can be detected in wastewater from a transportation hub.Twenty samples were collected in Italy’s first airport in Rome and tested using published and modified real-time PCR assays targeting the G2R region (TFN gene), F3L, and N3R genes. Nested PCR assays were also used for confirmation by sequencing. Three samples tested positive by real-time PCR and/or by nested PCR, confirming the occurrence of the virus in the airport’s wastewater.Wastewater surveillance can be quickly adapted to investigate emerging threats and can be used to track the introduction and/or the diffusion of the Monkeypox virus in communities.

Pepper mild mottle virus (PMMoV), a plant pathogenic virus belonging to the family Virgoviridae, has been proposed as a potential viral indicator for human faecal pollution in aquatic environments. The present study investigated the occurrence, amount and diversity of PMMoV in water environments in Italy. A total of 254 water samples, collected between 2017 and 2019 from different types of water, were analysed. In detail, 92 raw sewage, 32 treated sewage, 16 river samples, 9 estuarine waters, 20 bathing waters, 67 groundwater samples and 18 drinking waters were tested. PMMoV was detected in 79% and 75% of untreated and treated sewage samples, respectively, 75% of river samples, 67% and 25% of estuarine and bathing waters and 13% of groundwater samples. No positive was detected in drinking water. The geometric mean of viral concentrations (genome copies/L) was ranked as follows: raw sewage (2.2 × 106) > treated sewage (2.9 × 105) > river waters (6.1 × 102) > estuarine waters (4.8 × 102) > bathing waters (8.5 × 101) > groundwater (5.9 × 101). A statistically significant variation of viral loads could be observed between raw and treated sewage and between these and all the other water matrices. PMMoV occurrence and viral loads did not display seasonal variation in raw sewage nor correlation with faecal indicator bacteria in marine waters and groundwater. This study represents the first report on the occurrence and quantification PMMoV in different water environments in Italy. Further studies are required to evaluate the suitability of PMMoV as a viral indicator for human faecal pollution and for viral pathogens in waters.

The characteristics of superelasticity and shape-memory of the NiTi make endodontic rotary files suitably flexible and resistant while operating within curved canals. However, continuous rotation within accentuated curvatures causes stresses that can lead to intraoperative fracture by torsional shear or flexural cyclic fatigue. The aim of this paper is to design and build a rotary bending testing machine able to estimate reproducibly the fatigue life of endodontic instruments. The main innovation of this apparatus consists in ensuring that the file rotates freely, not being forced within a suitable shaped housing, and this provides both advantages of reducing the influence of the friction phenomena and maintaining unchanged geometric parameters. A further element of novelty is the real-time measurement of the bending force during the test up to the failure. Moreover, such a machine makes it possible to perform predictive thermographic tests of the file fatigue life and to monitor the energetic trend of the static and rotary bending while testing.

Very-high Energy (VHE) gamma-ray astroparticle physics is a relatively young field, and observations over the past decade have surprisingly revealed almost two hundred VHE emitters which appear to act as cosmic particle accelerators. These sources are an important component of the Universe, influencing the evolution of stars and galaxies. At the same time, they also act as a probe of physics in the most extreme environments known - such as in supernova explosions, and around or after the merging of black holes and neutron stars. However, the existing experiments have provided exciting glimpses, but often falling short of supplying the full answer. A deeper understanding of the TeV sky requires a significant improvement in sensitivity at TeV energies, a wider energy coverage from tens of GeV to hundreds of TeV and a much better angular and energy resolution with respect to the currently running facilities. The next generation gamma-ray observatory, the Cherenkov Telescope Array Observatory (CTAO), is the answer to this need. In this talk I will present this upcoming observatory from its design to the construction, and its potential science exploitation. CTAO will allow the entire astronomical community to explore a new discovery space that will likely lead to paradigm-changing breakthroughs. In particular, CTA has an unprecedented sensitivity to short (sub-minute) timescale phenomena, placing it as a key instrument in the future of multi-messenger and multi-wavelength time domain astronomy. I will conclude the talk presenting the first scientific results obtained by the LST-1, the prototype of one CTAO telescope type - the Large-Sized Telescope, that is currently under commission., PoS: Proceedings of Science, 395, ISSN:1824-8039, Proceedings of 37th International Cosmic Ray Conference (ICRC2021)

Saffold virus (SAFV) is an emerging human cardiovirus associated with respiratory and gastrointestinal infection, and, more recently, to symptoms related to the endocrine, cardiovascular, and neurological systems. Information about SAFV circulation in Italy is scarce. In order to provide insights into the epidemiology of SAFV in Italy, 141 raw sewage samples collected throughout Italy were tested using broad-range nested RT-PCR primers targeting the 5'-NC region. Seven samples (5·0%) were confirmed as SAFV in samples collected in North, Centre and Southern Italy. Typing was attempted through amplification of the VP1 coding region, using both published and newly designed primers, and one sample was characterized as SAFV-2. SIGNIFICANCE AND IMPACT OF THE STUDY: Prevalence, genetic diversity and geographic distribution of SAFV in Italy is currently unknown. This study represents the first detection of SAFV in sewage samples in Italy, suggesting that it is circulating in the population despite lack of clinical reporting. Whether the virus is associated with asymptomatic cases or with undetected gastroenteritis or respiratory illness is unknown. Further studies are needed to investigate on the occurrence and persistence of SAFV in water environments and its waterborne transmission potential.

Background Genotype-phenotype correlations in dilated cardiomyopathy (DCM) and, in particular, the effects of gene variants on clinical outcomes remain poorly understood. Objectives The purpose of this study was to investigate the prognostic role of genetic variant carrier status in a large cohort of DCM patients. Methods A total of 487 DCM patients were analyzed by next-generation sequencing and categorized the disease genes into functional gene groups. The following composite outcome measures were assessed: 1) all-cause mortality; 2) heart failure–related death, heart transplantation, or destination left ventricular assist device implantation (DHF/HTx/VAD); and 3) sudden cardiac death/sustained ventricular tachycardia/ventricular fibrillation (SCD/VT/VF). Results A total of 183 pathogenic/likely pathogenic variants were found in 178 patients (37%): 54 (11%) Titin; 19 (4%) Lamin A/C (LMNA); 24 (5%) structural cytoskeleton-Z disk genes; 16 (3.5%) desmosomal genes; 46 (9.5%) sarcomeric genes; 8 (1.6%) ion channel genes; and 11 (2.5%) other genes. All-cause mortality was no different between variant carriers and noncarriers (p = 0.99). A trend toward worse SCD/VT/VF (p = 0.062) and DHF/HTx/VAD (p = 0.061) was found in carriers. Carriers of desmosomal and LMNA variants experienced the highest rate of SCD/VT/VF, which was independent of the left ventricular ejection fraction. Conclusions Desmosomal and LMNA gene variants identify the subset of DCM patients who are at greatest risk for SCD and life-threatening ventricular arrhythmias, regardless of the left ventricular ejection fraction.

Purpose:We sought to determine the minimum number of transperineal prostate mapping biopsies needed to optimize the prostate cancer detection rate.Materials and Methods:A total of 436 men underwent...

Aims The diversity and the geographical distribution of swine papillomaviruses (PVs) are virtually unknown. The occurrence and the diversity of swine PV were therefore investigated in pig slurry collected in Italy, to contribute towards filling this gap in knowledge. Methods and Results Twenty‐two slurry samples underwent analysis by nested PCR and DNA sequencing using published and newly designed specific primer pairs for Sus scrofa papillomavirus (SsPV) type 1 and 2 (SsPV1 and 2), along with degenerate PV‐specific primers targeting the major coat protein L1 and the helicase protein E1. Overall, three samples (13·6%) were positive for SsPV1 by specific primers, and nucleotide (nt) sequences showed 99–100% nt identity with SsPV1 variant a (EF395818), while SsPV2 was not found in any sample. Using generic primers, eight samples (36·4%) were tested positive for human papillomavirus (HPV), and were characterized as follows: β1‐HPV8, β1‐HPV14, β1‐HPV206, β2‐HPV113, β2‐HPV120 and γ1‐HPV173. Moreover, one unclassified γ‐type was detected. Conclusions Both swine and human PVs were detected in pig slurry in this study. The unexpected presence of HPV in pig waste could be explained as the result of an improper use of the sewage collection pits and/or with improper procedures of the operators. Significance and Impact of the Study This study reports the first detection of SsPV1 in Italy, along with the first detection of HPVs in pig slurry samples in Italy, and expands our knowledge about PV diversity and geographic distribution.

Key points Wild-type mice and mice with hepatocyte-specific or whole-body deletions of perilipin-2 (Plin2) were used to define hepatocyte and extra-hepatocyte effects of altered cellular lipid storage on obesity and non-alcoholic fatty liver disease (NAFLD) pathophysiology in a Western-diet (WD) model of these disorders. Extra-hepatocyte actions of Plin2 are responsible for obesity, adipose inflammation and glucose clearance abnormalities in WD-fed mice. Hepatocyte and extra-hepatic actions of Plin2 mediate fatty liver formation in WD-fed mice through distinct mechanisms. Hepatocyte-specific actions of Plin2 are primary mediators of immune cell infiltration and fibrotic injury in livers of obese mice. Abstract Non-alcoholic fatty liver disease (NAFLD) is an obesity- and insulin resistance-related metabolic disorder with progressive pathology. Perilipin-2 (Plin2), a ubiquitously expressed cytoplasmic lipid droplet scaffolding protein, is hypothesized to contribute to NAFLD in humans and rodent models through effects on cellular lipid metabolism. In this study, we delineate hepatocyte-specific and extra-hepatocyte Plin2 mechanisms regulating the effects of obesity and insulin resistance on NAFLD pathophysiology in mice fed an obesogenic Western-style diet (WD). Total Plin2 deletion (Plin2-Null) fully protected WD-fed mice from obesity, insulin resistance, adipose inflammation, steatohepatitis (NASH) and liver fibrosis found in WT animals. Hepatocyte-specific Plin2 deletion (Plin2-HepKO) largely protected against NASH and fibrosis and partially protected against steatosis in WD-fed animals, but it did not protect against obesity, insulin resistance, or adipose inflammation. Significantly, total or hepatocyte-specific Plin2 deletion impaired WD-induced monocyte recruitment and pro-inflammatory macrophage polarization found in livers of WT mice. Analyses of the molecular and cellular processes mediating steatosis, inflammation and fibrosis identified differences in total and hepatocyte-specific actions of Plin2 on the mechanisms promoting NAFLD pathophysiology. Our results demonstrate that hepatocyte-specific actions of Plin2 are central to the initiation and pathological progression of NAFLD in obese and insulin-resistant mice through effects on immune cell recruitment and fibrogenesis. Conversely, extra-hepatocyte Plin2 actions promote NAFLD pathophysiology through effects on obesity, inflammation and insulin resistance. Our findings provide new insight into hepatocyte and extra-hepatocyte mechanisms underlying NAFLD development and progression.

In the degenerative disc disease, the traditional treatment consists in a removal of the intervertebral disc followed by the fusion of the two adjacent vertebral bodies (arthrodesis). An alternative treatment is the use of an artificial intervertebral disc. The advantage of an artificial intervertebral disc is that the mobility of the vertebral column will be restored. Aim of this paper consists in the definition of a prosthetic device for insertion in the intervertebral zone. Different types of artificial bone prostheses have been proposed, seldom based on similarity with physiological discs, then made with a central part (nucleus) consisting of hydrogel and an outer containment belt (annulus) consisting of a plastic material of greater stiffness. Upper and lower containment plates allow realizing a closed structure to be inserted in place of the original disc. Then, in our solution, the external parts (annulus and plates) were modeled by HDPE and the inner part (nucleus) by hydrogel. Both the materials are highly biocompatible. Both materials were modeled by the Ogden parameters related to elastomers. In fact, under the action of near-bending and twisting forces, the disc is subject to large deformations that the materials are able to withstand in elastic conditions. In order to assign the correct Ogden parameters to the materials, a procedure was used to fit the curves acquired by literature. The discs were subjected to compressive load as well as to forward and back bending (flexion and extension), lateral bending, torsion and combined loading.

Many solutions were adopted to substitute the intervertebral disc when it is damaged and has to be removed, in order to assure stability of the spine as well as some degree of freedom of the spine segment. The disc prostheses currently on the market, however, are frequently subject to failure due to wear and degeneration of the material or stress shielding. Aim of the present research is the design a new solution for the artificial intervertebral disc and to perform a numerical-experimental analysis on them. Starting from the tests performed on the hyperelastic materials considered to substitute the intervertebral disc, numerical models were carried out on the new devices. The paper prosecutes with the experimental analysis, under simple static compression tests. Finally, numerical and experimental comparison was made in order to evaluate the best prosthesis among the different adopted models.

The International Trichinella Reference Centre (ITRC) is the official laboratory of the International Commission on Trichinellosis, of the World Organization for Animal Health and of the European Union Reference Laboratory for Parasites. The ITRC was established in 1988 as a repository of

Many mouse models of rheumatoid arthritis have been identified, but only a limited number are present for axial spondyloarthritis (AxSpA). Collagen Ab-induced arthritis (CAIA) is one of the most widely used mouse models of arthritis, and it is complement-dependent. We found that mice developing CAIA also developed spinal lesions similar to those found in AxSpA. To induce CAIA, mice were injected intraperitoneally at day 0 with anti-collagen Abs, followed by LPS injection at day 3. CAIA mice demonstrated a significant kyphosis through the spine, as well as hypertrophic cartilage and osseous damage of the intravertebral joints. Immunohistochemical staining of the kyphotic area revealed increased complement C3 deposition and macrophage infiltration, with localization to the intravertebral joint margins. Near Infrared (NIR) in vivo imaging showed that anti-collagen Abs conjugated with IRDye® 800CW not only localized to cartilage surface in the joints but also to the spine in arthritic mice. We report here a novel preclinical mouse model in which, associated with the induction of CAIA, mice also exhibited salient features of AxSpA; this new experimental model of AxSpA may allow investigators to shed light on the local causal mechanisms of AxSpA bone and soft tissue changes as well as treatment.

The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires the detection of viral RNA by reverse transcription–polymerase chain reaction (RT-qPCR) performed mainly using nasopharyngeal swabs. However, this procedure requires separate analysis per each individual, performed in advanced centralized laboratory facilities with specialized medical personnel. In this study, an alternative approach termed “solid waste-based surveillance (SWBS)” was explored, in order to investigate SARS-CoV-2 infection in small communities through the indirect sampling of saliva left on waste. Sampling was performed at 20 different sites in Italy during the second peak of COVID-19. Three swabs were positive for SARS-CoV-2 using a published RT-qPCR protocol targeting the non-structural protein 14 region, and the viral load ranged 4.8 × 103–4.0 × 106 genome copies/swab. Amino acid substitutions already reported in SARS-CoV-2 sequences circulating in Italy (A222V and P521S) were detected in two positive samples. These findings confirmed the effectiveness of SWBS for non-invasive and dynamic SARS-CoV-2 surveillance., Graphical abstract Unlabelled Image

Background Pepper mild mottle virus (PMMoV), a plant virus belonging to Virgoviridae, has recently been suggested as a potential viral indicator for faecal pollution in aquatic environments, since it has been found to be abundantly excreted from healthy human subjects. Methods The occurrence, amount and diversity of PMMoV was investigated in water environments by nested RT-PCR and TaqMan based quantitative PCR. During 2017-2019, 251 water samples (92 urban wastewaters, 32 treated effluents, 16 surface water samples, 9 estuarine samples, 20 seawater samples, 67 groundwater samples, and 15 drinking waters) were analysed. Results PMMoV was detected in 73/92 (79%) wastewater samples, 22/32 (69%) treated sewages, 11/16 (69%) river samples, 6/9 (67%) estuarine samples, 5/20 (25%) bathing waters, and 9/67 (13%) groundwaters, whilst drinking water samples tested always negative. Mean viral concentrations (genome copies/L) were: raw sewage 4.2 × 106, treated sewage 7.4 × 105, river 3.2 × 103, estuarine waters 9.6 × 102, seawaters 3.0 × 102, groundwaters 7.7 × 101. Conclusions This study highlights the significant occurrence of PMMoV in aquatic environment in Italy, and a clear gradient of viral prevalence and concentrations from polluted to clean waters (wastewaters to drinking waters). Key messages PMMoV is ubiquitous throughout the water cycle in Italy with different concentrations. Studies are needed to evaluate the suitability of PMMoV as a viral indicator for human fecal pollution in waters.

INTRODUCTION AND OBJECTIVE:mpMRI is known to miss clinically significant prostate cancer (csPC) in up to 30% of men. These lesions are usually smaller than 1 cc and are not easily identified when 1...

To identify patients at risk of high-grade prostate cancer using prostate cancer biomarkers.A total of 601 men were screened for prostate cancer in 2012, 2015, and 2016 using prostate cancer biomarkers: prostate health index (phi), 4KScore, and SelectMDx. The first two are blood tests that incorporate several PSA isoforms; SelectMDx measures mRNA levels of homeobox C6 and distal-less homeobox 1 in post-digital rectal examination urine samples. The performance of each biomarker was evaluated using cut off values based on published literature. Gleason Grade Group (GG) ≥ 2 is considered as high-grade prostate cancer.For patients with PSA1.5 ng/mL, none were at risk for GG ≥ 2 cancer based on SelectMDx0%, whereas 17.1% were at intermediate to high risk of finding GG ≥ 2 cancer with 4KScore ≥ 7.5%, and 3.5% were at risk of finding any prostate cancer with phi ≥ 36 at biopsy. For cut offs revised for finding men at high risk for GG ≥ 2 cancer at biopsy, only one patient with PSA1.5 ng/mL would be at risk with 4KScore ≥ 20% and none with phi ≥ 52.7. For patients with PSA 1.5 to 3.99 ng/mL, 2%, 8%, and 1% were at high risk for finding GG ≥ 2 cancer at biopsy based on phi, 4KScore, and SelectMDx, respectively.Men with PSA1.5 ng/mL are at very low risk of finding high-grade prostate cancer at biopsy. However, some men with PSA between 1.5 to 3.99 ng/mL may be at intermediate to high risk for high-grade prostate cancer. Thus, primary care physicians could run biomarkers test and refer those with positive biomarker results to a specialist for further evaluation.

The HERMES-TP/SP mission, based on a nanosatellite constellation, has very stringent constraints of sensitivity and compactness, and requires an innovative wide energy range instrument. The instrument technology is based on the "siswich" concept, in which custom-designed, low-noise Silicon Drift Detectors are used to simultaneously detect soft X-rays and to readout the optical light produced by the interaction of higher energy photons in GAGG:Ce scintillators. To preserve the inherent excellent spectroscopic performances of SDDs, advanced readout electronics is necessary. In this paper, the HERMES detector architecture concept will be described in detail, as well as the specifically developed front-end ASICs (LYRA-FE and LYRA-BE) and integration solutions. The experimental performance of the integrated system composed by scintillator+SDD+LYRA ASIC will be discussed, demonstrating that the requirements of a wide energy range sensitivity, from 2 keV up to 2 MeV, are met in a compact instrument., Comment: 12 pages, 10 figures. Proceedings of SPIE "Astronomical Telescopes and Instrumentation" 2020

The High Energy Rapid Modular Ensemble of Satellites (HERMES) Technological and Scientific pathfinder is a space borne mission based on a constellation of LEO nanosatellites. The payloads of these CubeSats consist of miniaturized detectors designed for bright high-energy transients such as Gamma-Ray Bursts (GRBs). This platform aims to impact Gamma Ray Burst (GRB) science and enhance the detection of Gravitational Wave (GW) electromagnetic counterparts. This goal will be achieved with a field of view of several steradians, arcmin precision and state of the art timing accuracy. The localization performance for the whole constellation is proportional to the number of components and inversely proportional to the average baseline between them, and therefore is expected to increase as more. In this paper we describe the Payload Data Handling Unit (PDHU) for the HERMES-TP and HERMES SP mission. The PDHU is the main interface between the payload and the satellite bus. The PDHU is also in charge of the on-board control and monitoring of the scintillating crystal detectors. We will explain the TM/TC design and the distinct modes of operation. We also discuss the on-board data processing carried out by the PDHU and its impact on the output data of the detector., Comment: 11 pages, 10 figures. Proceedings of SPIE "Astronomical Telescopes and Instrumentation" 2020

Space Telescopes and Instrumentation 2020: Ultraviolet to Gamma Ray; Virtual, Online; United States; 14 December 2020 through 18 December 2020; Code 166330.--Proceedings of SPIE - The International Society for Optical Engineering Volume 11444, 2020, Article number 114442K.--Full list of authors: Labanti, C.; Amati, L.; Frontera, F.; Mereghetti, S.; Gasent-Blesa, J. L.; Tenzer, C.; Orleanski, P.; Kuvvetli, I.; Campana, R.; Fuschino, F.; Terenzi, L.; Virgilli, E.; Morgante, G.; Orlandini, M.; Butler, R. C.; Stephen, J. B.; Auricchio, N.; De Rosa, A.; Da Ronco, V.; Evangelisti, F. Melchiorri, M.; Squerzanti, S.; Fiorini, M.; Bertuccio, G.; Mele, F.; Gandola, M.; Malcovati, P.; Grassi, M.; Bellutti, P.; Borghi, G.; Ficorella, F.; Picciotto, A.; Zanini, V.; Zorzi, N.; Demenev, E.; Rashevskaya, I.; Rachevski, A.; Zampa, G.; Vacchi, A.; Zampa, N.; Baldazzi, G.; La Rosa, G.; Sottile, G.; Volpe, A.; Winkler, M.; Reglero, V.; Connell, P. H.; Pinazo-Herrero, B.; Navarro-González, J.; Rodríguez-Martínez, P.; Castro-Tirado, A. J.; Santangelo, A.; Hedderman, P.; Lorenzi, P.; Sarra, P.; Pedersen, S. M.; Tcherniak, D.; Guidorzi, C.; Rosati, P.; Trois, A.; Piazzolla, R., THESEUS (Transient High Energy Sky and Early Universe Surveyor) is one of the three missions selected by ESA as fifth medium class mission (M5) candidates in its Cosmic Vision science program, currently under assessment in a phase A study with a planned launch date in 2032. THESEUS is designed to carry on-board two wide and deep sky monitoring instruments for X/gamma-ray transients detection: a wide-field soft X-ray monitor with imaging capability (Soft X-ray Imager, SXI, 0.3 - 5 keV), a hard X-ray, partially-imaging spectroscopic instrument (X and Gamma Imaging Spectrometer, XGIS, 2 keV - 10 MeV), and an optical/near-IR telescope with both imaging and spectroscopic capability (InfraRed Telescope, IRT, 0.7 - 1.8 µm). The spacecraft will be capable of performing fast repointing of the IRT to the error region provided by the monitors, thus allowing it to detect and localize the transient sources down to a few arcsec accuracy, for immediate identification and redshift determination. The prime goal of the XGIS will be to detect transient sources, with monitoring timescales down to milliseconds, both independently of, or following up, SXI detections, and identify the sources performing localisation at, The Phase A study of the THESEUS/XGIS instrument is supported by ASI-INAF Agreement n. 2018-29-HH.0, OHB Italia/ - INAF-OASBo Agreement n.2331/2020/01, by the European Space Agency ESA through the M5/NPMC Programme and by the AHEAD2020 project funded by UE through H2020-INFRAIA-2018-2020. By the Spanish Ministerio de Ciencia e Innovación, PID2019-109269RB-C41. By Polish National Science Center, Project 2019/35/B/ST9/03944 and Foundation for Polish Science, Project POIR.04.04.00-00-5C65/17-00.

The X and Gamma Imaging Spectrometer instrument on-board the THESEUS mission (selected by ESA in the framework of the Cosmic Vision M5 launch opportunity, currently in phase A) is based on a detection plane composed of several thousands of single active elements. Each element comprises a 4.5x4.5x30 mm 3 CsI(Tl) scintillator bar, optically coupled at both ends to Silicon Drift Detectors (SDDs). The SDDs acts both as photodetectors for the scintillation light and as direct X-ray sensors. In this paper the design of the XGIS detection plane is reviewed, outlining the strategic choices in terms of modularity and redundancy of the system. Results on detector-electronics prototypes are also described. Moreover, the design and development of the low-noise front-end electronics is presented, emphasizing the innovative architectural design based on custom-designed Application-Specific Integrated Circuits (ASICs)., Comment: Proceedings of the SPIE 2020, paper 11444-277

In this paper, an ultrasound measurement method was applied to bulge test on carbon black-filled SBR specimens, in order to determine their thickness at the top of the dome. This method consists in measuring first the variation in the ultrasonic velocity as a function of the deformation in the uniaxial state and subsequently obtaining the thickness value in the equibiaxial state, assuming the congruence of velocity in uniaxial and equibiaxial stress states, respectively. The comparison between experimental data and the thickness values deriving from the most reliable theoretical criteria for both metallic and rubbers-like materials was shown. A new theoretical approach taking into account the slight compressibility of elastomers to estimate the thickness at the dome apex was proposed. Such an approach provided a general equation to define the thickness of the dome in bulge-tested SBR+20%CB as a function of the Poisson ratio.

We report on the first detection of very high-energy (VHE) gamma-ray emission from the Crab Nebula by a Cherenkov telescope in dual-mirror Schwarzschild-Couder (SC) configuration. The result has been achieved by means of the 4 m size ASTRI-Horn telescope, operated on Mt. Etna (Italy) and developed in the context of the Cherenkov Telescope Array Observatory preparatory phase. The dual-mirror SC design is aplanatic and characterized by a small plate scale, allowing us to implement large field of view cameras with small-size pixel sensors and a high compactness. The curved focal plane of the ASTRI camera is covered by silicon photo-multipliers (SiPMs), managed by an unconventional front-end electronics based on a customized peak-sensing detector mode. The system includes internal and external calibration systems, hardware and software for control and acquisition, and the complete data archiving and processing chain. The observations of the Crab Nebula were carried out in December 2018, during the telescope verification phase, for a total observation time (after data selection) of 24.4 h, equally divided into on- and off-axis source exposure. The camera system was still under commissioning and its functionality was not yet completely exploited. Furthermore, due to recent eruptions of the Etna Volcano, the mirror reflection efficiency was reduced. Nevertheless, the observations led to the detection of the source with a statistical significance of 5.4 sigma above an energy threshold of ~3 TeV. This result provides an important step towards the use of dual-mirror systems in Cherenkov gamma-ray astronomy. A pathfinder mini-array based on nine large field-of-view ASTRI-like telescopes is under implementation., 6 pages, 2 figures

Purpose of this paper is to perform an energetic analysis on metal specimens under fatigue testing using the simultaneous application of different non-destructive techniques: thermography (TH), acoustic emission (AE) and digital image correlation (DIC). They assure the better evaluation, being contactless methods, usable in real time and, even if TH and DIC are related to the specimen surface, representative of the inside state of the materials. In particular, the cascade of hits and the acoustic energy were recorded to assess the parameters linked to the fracture of the materials. At the same time, the surface temperature, detected by a thermocamera, and the displacements induced on the specimen, using the DIC on the free zone of the specimens, were recorded. The DIC analysis allows the evaluation of the correct displacement by a pattern realized on the opposite face respect to TH. AE data and hysteresis curves (derived by DIC) were compared with the measures acquired by TH and reveal a reliable correlation between them in terms of fatigue limit.

Human Cosavirus (HCoSV) is a newly discovered virus whose role in human enteric diseases is still unknown. In Italy, the prevalence and genetic diversity of HCoSV are unexplored. One hundred forty-one raw sewage samples collected throughout Italy were screened for HCoSV by RT-nested PCR. HCoSV was detected in 25.5% of samples. Species A, C, and D, and a potentially new species were detected. Our results show a significant circulation and heterogeneity of HCoSV in Italy.

Recurrent self-mating can result in nearly clonal propagation of biological lineages, but even occasional outcrossing can serve to redistribute variation in future generations, providing cohesion among regional populations. The zoonotic parasite Trichinella spiralis has been suspected to undergo frequent inbreeding, resulting in genetically uniform larval cohorts which differ markedly from one another. Here, we explored the extent of inbreeding for this parasite by determining how genetic variation (at variable microsatellite markers) is distributed among 1379 larvae derived from 41 wild boars in Extremadura, Spain. In particular, we sought to determine how much of the genetic variation in this region's parasites occurs among the larvae of any given wild boar, and whether each derives from one, or more, parental lineages. We found strong evidence for inbreeding, resulting in genetically distinct parasite subpopulations among the parasites derived from many pairs of wild boar. Fully two-thirds of these parasite cohorts appear to derive from inbred parents; in 10% of the wild boars, parasites were so inbred as to become absolutely fixed in all of the assayed genetic loci. In spite of this, more than one pair of parents appear to have given rise to the infections in one-third of the sampled wild boars, resulting in mixed infections. These mixed infections should slow losses of heterozygosity and multi-locus polymorphism in any given parasite lineage. Such outcrossing should limit distinctions that would otherwise accumulate among transmission chains, thereby enforcing cohesion through the region's population in spite of its marked departure from panmixia. Conditions of transmission may differ in other regions, where such epidemiological features may engender different evolutionary outcomes.

NiTi endodontic rotary instruments have increased flexibility and strength compared with stainless steel instruments, but they seem to be vulnerable to fracture in clinical situations. Heat treatment (thermal processing) is one of the most fundamental approaches toward adjusting the transition temperatures of NiTi alloys and affecting the fatigue and torsional resistance of NiTi endodontic files. In recent years, novel thermo-mechanical processing and manufacturing technologies such as controlled memory wire (CM-wire), M-Wire and electrical discharge machining (EDM) have been developed to optimize the microstructure of NiTi alloys and their mechanical properties. Aim of this work was to investigate the torsional resistance (maximum torque load, and angular rotation) of NiTi instruments made by different thermo-mechanical and manufacturing processes. For this purpose, a torque device able to perform static and dynamic tests of Ni-Ti instruments for root canal treatment was designed and realized, by performing this device through the design and optimization of the single components and on the system globally.

We describe a new method of identifying night-time clouds over the Pierre Auger Observatory using infrared data from the Imager instruments on the GOES-12 and GOES-13 satellites. We compare cloud. identifications resulting from our method to those obtained by the Central Laser Facility of the Auger Observatory. Using our new method we can now develop cloud probability maps for the 3000 km(2) of the Pierre Auger Observatory twice per hour with a spatial resolution of similar to 2.4 km by similar to 5.5 km. Our method could also be applied to monitor cloud cover for other ground-based observatories and for space-based observatories. (C) 2013 Elsevier B.V. All rights reserved., The successful installation, commissioning, and operation of the Pierre Auger Observatory would not have been possible without the strong commitment and effort from the technical and adminis- trative staff in Malargüe. We are very grateful to the following agencies and organiza- tions for financial support: Comisión Nacional de Energía Atómica, Fundación Antorchas, Gobierno De La Provincia de Mendoza, Municipalidad de Malargüe, NDM Holdings and Valle Las Leñas, in gratitude for their continuing cooperation over land access, Argentina; the Australian Research Council; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Projetos (FINEP), Fundação de Amparo à Pesquisa do Estado de Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Ministério de Ciência e Tecnolo- gia (MCT), Brazil; AVCR AV0Z10100502 and AV0Z10100522, GAAV KJB100100904, MSMT-CR LA08016, LG11044, MEB111003, MSM0021620859, LA08015, TACR TA01010517 and GA UK 119810, Czech Republic; Centre de Calcul IN2P3/CNRS, Centre Na- tional de la Recherche Scientifique (CNRS), Conseil Régional Ile-de- France, Département Physique Nucléaire et Corpusculaire (PNC- IN2P3/CNRS), Département Sciences de l’Univers (SDU-INSU/ CNRS), France; Bundesministerium für Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), Finanzministeri- um Baden-Württemberg, Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF), Ministerium für Wissenschaft und Forschung, Nordrhein-Westfalen, Ministerium für Wissenschaft, Forschung und Kunst, Baden-Württemberg, Germany; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), Italy; Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico; Ministerie van Ond- erwijs, Cultuur en Wetenschap, Nederlandse Organisatie voor Wet- enschappelijk Onderzoek (NWO), Stichting voor Fundamenteel Onderzoek der Materie (FOM), Netherlands; Ministry of Science and Higher Education, Grant Nos. N N202 200239 and N N202 207238, Poland; Portuguese national funds and FEDER funds with- in COMPETE - Programa Operacional Factores de Competitividade through Fundação para a Ciência e a Tecnologia, Portugal; Roma- nian Authority for Scientific Research ANCS, CNDI-UEFISCDI part- nership projects nr.20/2012 and nr.194/2012, project nr.1/ ASPERA2/2012 ERA-NET and PN-II-RU-PD-2011-3-0145-17, Roma- nia; Ministry for Higher Education, Science, and Technology, Slove- nian Research Agency, Slovenia; Comunidad de Madrid, FEDER funds, Ministerio de Ciencia e Innovación and Consolider-Ingenio 2010 (CPAN), Xunta de Galicia, Spain; The Leverhulme Foundation, Science and Technology Facilities Council, United Kingdom; Department of Energy, Contract Nos. DE-AC02-07CH11359, DE- FR02-04ER41300, DE-FG02-99ER41107, National Science Founda- tion, Grant No. 0450696, The Grainger Foundation USA; NAFO- STED, Vietnam; Marie Curie-IRSES/EPLANET, European Particle Physics Latin American Network, European Union 7th Framework Program, Grant No. PIRSES-2009-GA-246806; and UNESCO. We would like to thank the former Michigan Tech students: Nathan Kelley-Hoskins, Kyle Luck and Arin Nelson for their impor- tant contribution to the development of this paper. We would like to thank NOAA for the GOES satellite data that we freely down- loaded from their website. Also, we would like to mention in these acknowledgments Dr. Steve Ackerman and Dr. Tony Schreiner for very valuable conversations

Noroviruses (NoV) are a major cause of gastroenteritis worldwide. Recently, a novel variant of NoV GII.17 (GII.P17_GII.17 NoV), termed Kawasaki 2014, has been increasingly reported in NoV outbreaks in Asia, and has also been described in Europe and North America. In this study, sewage samples were investigated to study the occurrence and genetic diversity of NoV genogroup II (GII) along a 6-year period. Moreover, the spread of GII.17 strains (first appearance and occurrence along time) was specifically assessed. A total of 122 sewage samples collected from 2011 to 2016 from four wastewater treatment plants in Rome (Italy) were initially tested using real-time RT-(q)PCR for GII NoV. Positive samples were subsequently subjected to genotypic characterization by RT-nested PCRs using broad-range primes targeting the region C of the capsid gene of GII NoV, and specific primers targeting the same region of GII.17 NoV. In total, eight different genotypes were detected with the broad-range assay: GII.1 (n = 6), GII.2 (n = 8), GII.3 (n = 3), GII.4 (n = 13), GII.6 (n = 3), GII.7 (n = 2), GII.13 (n = 2), and GII.17 (n = 3), with the latter two genotypes detected only in 2016. Specific amplification of GII.17 NoV was successful in 14 out of 110 positive samples, spanned over the years 2013-2016. The amplicons of the broad-range PCR, pooled per year, were further analyzed by next-generation sequencing (NGS) for a deeper analysis of the genotypes circulating in the study period. NGS confirmed the circulation of GII.17 NoV since 2013 and detected, beyond the eight genotypes identified by Sanger sequencing, three additional genotypes regarded as globally uncommon: GII.5, GII.16, and GII.21. This study provides evidence that GII.17 NoV Kawasaki has been circulating in the Italian population before its appearance and identification in clinical cases, and has become a major genotype in 2016. Our results confirm the usefulness of wastewater surveillance coupled with NGS to study the molecular epidemiology of NoV and to monitor the emergence of NoV strains.

Among the considerable number of studies that can be carried out using muons, we pay specific attention to the radiography of volcanoes based on the same principle of the X-ray radiography of human body. Thanks to their high penetration capability, cosmic-ray muons can be used to reconstruct the density distribution of the interior of huge structures by measuring the attenuation induced by the material on the muon flux. In particular, the quantitative understanding of the inner structure of volcanoes is a key-point to forecast the dangerous stages of activity and mitigate volcanic hazards. The instrumental approach is currently based on the detection of muons crossing hodoscopes made up of scintillator planes. Unfortunately, these detectors are affected by a strong background comprised by accidental coincidence of vertical shower particles, horizontal high-energy electrons and upward going particles. We propose an alternative technique based on the detection of the Cherenkov light produced by muons. This can be achieved with an imaging atmospheric Cherenkov telescope composed of a high reflectivity optical system that focus the Cherenkov light onto a multi-pixel focal camera with fast read-out electronics. The Cherenkov light emitted by a muon is imaged on the camera as an annular pattern which contains information to reconstruct the direction of the incident muon. We have estimated that using the Cherenkov imaging technique for muon radiography of volcanoes gives the advantage of a negligible background and improved spatial resolution, compared to the majority of the particle detectors. We present results of simulations based on a telescope with a positioning resolution of 13.5 m which corresponds to an acceptance of 9 cm2 sr. The telescope is located 1500 m far from a toy-model volcano, namely, a cone with a base diameter of 500 m and a height of 240 m. We test the feasibility of the proposed method by estimating the minimum number of observation nights needed to resolve inner empty conduits of different diameter.

The main purpose of this paper is defining a procedure that allows the tracking of the measuring point in notched specimens under static testing, investigated by full field experimental methodologies. One of the main problems is the motion of the measuring zone, associated with its compliance under increasing load. A procedure based on Digital Image Correlation (D.I.C.) aiming to define the stress concentration factor in a dynamic way has been developed. Furthermore, numerous revealing tests based on Thermographic Analysis (T.A.) have been carried out on flat plastics specimens with different hole diameters. The assessed and final tracking procedure could be used to better define the trend of temperature changes during the static tensile test, as well as measuring the stress concentration factors in notched specimens.

Human adenoviruses (HAdVs) are of major public health importance and are associated with a variety of clinical manifestations, including gastroenteritis, respiratory, ocular and urinary tract infections. To study the occurrence, prevalence and diversity of HAdV species and types circulating in Italy, we conducted a large-scale molecular-epidemiological investigation, a yearlong monitoring of 22 wastewater treatment plants, covering 10 Italian regions, representative of northern, central, and southern Italy. A total of 141 raw sewage samples were collected from January to December 2013, and processed to detect and characterize by phylogenetic analysis a fragment of the hexon coding region of HAdVs. Nested PCR results showed the presence of HAdVs in 85 out of 141 samples (60% of samples). Fifty-nine samples were characterized by conventional Sanger sequencing as belonging to four HAdV species and four types: A (type 12, 5 samples), B (type 3, 8 samples), C (type 5, 1 sample) and F (type 41, 45 samples). The remaining 26 samples could not be characterized because of uninterpretable (mixed) electropherograms suggesting the presence of multiple species and/or types. Pools of characterized and uncharacterized PCR amplicons were further analyzed by next-generation sequencing (NGS). NGS results revealed a marked HAdV diversity with 16 additional types detected beyond the four types found by Sanger sequencing. Overall, 19 types were identified, belonging to HAdV species A-F: types 12 and 31 (species A), type 3 (species B), types 1, 2, and 5 (species C), types 9, 17, 24, 26, 37, 38, 42, 44, 48, and 70 (species D), type 4 (species E), and types 40 and 41(species F). An untypeable HAdV was also detected, showing similar percentages of identity with more than one prototype (types 15, 30, 56, and 59). Our findings documented the circulation of a wide variety of species and types in raw sewage, potentially able to affect other surface water environments and hence human health. Next-generation sequencing proved to be an effective strategy for HAdV genotyping in wastewater samples. It was able to detect a wide range of "less prevalent" types unidentified by conventional Sanger sequencing, confirming that studies based on conventional technologies may grossly underestimate the existence of some, possibly less common, types. Knowledge of the distribution of HAdV species and types would improve our understanding of waterborne HAdV-related health risks.

Background Gold nanoparticles treated with near infrared (NIR) light can be heated preferentially, allowing for thermal ablation of targeted cells. The use of novel intravesical nanoparticle-directed therapy in conjunction with laser irradiation via a fiber optic cystoscope, represents a potential ablative treatment approach in patients with superficial bladder cancer. Objective To examine the thermal ablative effect of epidermal growth factor receptor (EGFR)-directed gold nanorods irradiated with NIR light in an orthotopic urinary bladder cancer model. Methods Gold nanorods linked to an anti-EGFR antibody (Conjugated gold NanoRods - CNR) were instilled into the bladder cavity of an orthotopic murine xenograft model with T24 bladder cancer cells expressing luciferase. NIR light was externally administered via an 808 nm diode laser. This treatment was repeated weekly for 4 weeks. The anti-cancer effect was monitored by an in vivo imaging system in a non-invasive manner, which was the primary outcome of our study. Results The optimal approach for an individual treatment was 2.1 W/cm2 laser power for 30 seconds. Using this in vivo model, NIR light combined with CNR demonstrated a statistically significant reduction in tumor-associated bioluminescent activity (n = 16) compared to mice treated with laser alone (n = 14) at the end of the study (p = 0.035). Furthermore, the CNR+NIR light treatment significantly abrogated bioluminescence signals over a 6-week observation period, compared to pre-treatment levels (p = 0.045). Conclusions Photothermal tumor ablation with EGFR-directed gold nanorods and NIR light proved effective and well tolerated in a murine in vivo model of urinary bladder cancer.

// Thomas W. Flaig 1 , Maren Salzmann-Sullivan 1 , Lih-Jen Su 1 , Zhiyong Zhang 1 , Molishree Joshi 2 , Miguel A. Gijon 2 , Jihye Kim 1 , John J. Arcaroli 1 , Adrie Van Bokhoven 3 , M. Scott Lucia 3 , Francisco G. La Rosa 3 and Isabel R. Schlaepfer 1 1 Division of Medical Oncology, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA 2 Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA 3 Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA Correspondence to: Isabel R. Schlaepfer, email: // Keywords : CPT1A, prostate cancer, enzalutamide, ranolazine, INPP5K Received : February 27, 2017 Accepted : April 10, 2017 Published : April 21, 2017 Abstract Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. We have found that deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid oxidation to fuel PCa growth. Using immunohistochemistry we have found that the CPT1A isoform is abundant in PCa compared to benign tissue (n=39, p