First Search for Dyons with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions.

The MoEDAL trapping detector consists of approximately 800 kg of aluminum volumes. It was exposed during run 2 of the LHC program to 6.46 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point. Evidence for dyons (particles with electric and magnetic charge) captured in the trapping detector was sought by passing the aluminum volumes comprising the detector through a superconducting quantum interference device (SQUID) magnetometer. The presence of a trapped dyon would be signaled by a persistent current induced in the SQUID magnetometer. On the basis of a Drell-Yan production model, we exclude dyons with a magnetic charge ranging up to five Dirac charges (5g_{D}) and an electric charge up to 200 times the fundamental electric charge for mass limits in the range 870-3120 GeV and also monopoles with magnetic charge up to and including 5g_{D} with mass limits in the range 870-2040 GeV.

Magnetic Monopole Search with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions Interpreted in Photon-Fusion and Drell-Yan Production.

MoEDAL is designed to identify new physics in the form of stable or pseudostable highly ionizing particles produced in high-energy Large Hadron Collider (LHC) collisions. Here we update our previous search for magnetic monopoles in Run 2 using the full trapping detector with almost four times more material and almost twice more integrated luminosity. For the first time at the LHC, the data were interpreted in terms of photon-fusion monopole direct production in addition to the Drell-Yan-like mechanism. The MoEDAL trapping detector, consisting of 794 kg of aluminum samples installed in the forward and lateral regions, was exposed to 4.0 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to or above the Dirac charge are excluded in all samples. Monopole spins 0, ½, and 1 are considered and both velocity-independent and-dependent couplings are assumed. This search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.

Comparison of cheeses from goats fed 7 forages based on a new health index.

This study proposed the General Health Index of Cheese (GHIC) as an indicator for the presence of health-promoting compounds in cheese and compared the antioxidant capacity and phenolic and fatty acid contents of cheeses from goats consuming 7 forage species. Ninety-one homogeneous Red Syrian goats were randomly assigned to 1 of 7 feeding treatments (Festuca arundinacea, Hordeum vulgare, Triticosecale, Pisum sativum, Trifolium alexandrinum, Vicia sativa, and Vicia faba minor). The housed goat groups received the scheduled forage ad libitum. Forage species affected the antioxidant capacity, the phenolic and fatty acid contents, the Health Promoting Index, and the GHIC. Trifolium alexandrinum, Triticosecale, and Hordeum vulgare showed a clear advantage in terms of beneficial fatty acids content in goat cheese. Cheese from the Triticosecale group also showed a high antioxidant capacity value even if its polyphenol content was intermediate compared with others. Trifolium alexandrinum and Triticosecale had the highest value of the new index GHIC. This comparison suggests that there are important differences in fatty acid profile and polyphenol content among cheeses from goats fed grasses and legumes commonly used in the Mediterranean area. In this first approach, GHIC index, which combines the positive components found in cheese, seems to be a useful tool to provide an indication concerning the general health value of the product.

Search for Magnetic Monopoles with the MoEDAL Forward Trapping Detector in 13 TeV Proton-Proton Collisions at the LHC.

MoEDAL is designed to identify new physics in the form of long-lived highly ionizing particles produced in high-energy LHC collisions. Its arrays of plastic nuclear-track detectors and aluminium trapping volumes provide two independent passive detection techniques. We present here the results of a first search for magnetic monopole production in 13 TeV proton-proton collisions using the trapping technique, extending a previous publication with 8 TeV data during LHC Run 1. A total of 222 kg of MoEDAL trapping detector samples was exposed in the forward region and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges exceeding half the Dirac charge are excluded in all samples and limits are placed for the first time on the production of magnetic monopoles in 13 TeV pp collisions. The search probes mass ranges previously inaccessible to collider experiments for up to five times the Dirac charge.

Effects of Sulla forage (Sulla coronarium L.) on the oxidative status and milk polyphenol content in goats.

Twelve milking Girgentana goats were allocated into 3 groups and fed 3 diets ad libitum in a 3×3 Latin square design with 3 periods. The diets were Sulla fresh forage ad libitum (SUL), Sulla fresh forage ad libitum and 800g/d of barley meal (SULB), and mixed hay ad libitum and 800g/d of barley meal (HB). Changes were observed in total polyphenol intake, plasma oxidative status, plasma polyphenol content, metabolic status, milk polyphenol content, and total antioxidant capacity. The fresh forage diets (SUL and SULB) increased dry matter, total polyphenol, nontannic polyphenol and tannin intakes, and the milk total protein, casein, milk total polyphenols, and milk free polyphenols compared with the HB diet. The intake of condensed tannins was higher in the SUL than in the HB group, and an intermediate value was recorded for the SULB group. Plasma from the SUL- and SULB-fed goats exhibited greater total antioxidant capacity and greater total polyphenol and free polyphenol levels compared with the plasma from the HB group. Positive correlations between plasma total antioxidant capacity and condensed tannins intake (r=0.43), plasma total polyphenol and total polyphenol intake (r=0.61), and plasma free polyphenol and milk total polyphenols (r=0.38) were observed. The correlation between milk free polyphenols and whey total antioxidant capacity (r=0.42) highlights the role of free polyphenols in the determination of the antioxidant activity of milk. These results indicate that Sulla fresh forage exerts an antioxidant activity due to its secondary compounds that provide additional antioxidant value and that Sulla forage appears to be a promising strategy for improving product quality.

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30±10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Force and pressure distribution using Macintosh and GlideScope laryngoscopes in normal and difficult airways: a manikin study.

BACKGROUND: The forces applied to the soft tissues of the upper airway may have a deleterious effect. This study was designed to evaluate the performance of the GlideScope compared with the Macintosh laryngoscope. METHODS: Twenty anaesthetists and 20 trainees attempted tracheal intubation of a Laerdal SimMan manikin. Forces and pressure distribution applied by both laryngoscope blades onto the soft upper airway tissues were measured using film pressure transducers. The minimal force needed to achieve a successful intubation, in the same simulated scenario, was measured; additionally, we considered the visualization score achieved by using the Cormack-Lehane grades. RESULTS: All participants applied, on average, lower force with the GlideScope than with the Macintosh in each simulated scenario. Forces [mean (sd)] applied in the normal airway scenario [anaesthetists: Macintosh 39 (22) N and GlideScope 27 (15) N; trainees: Macintosh 45 (24) N and GlideScope 21 (15) N] were lower than forces applied in the difficult airway scenario [anaesthetists: Macintosh 95 (22) N and GlideScope 66 (20) N; trainees: Macintosh 100 (38) N and GlideScope 48 (16) N]. All the intubations using the GlideScope were successful, regardless of the scenario and previous intubation experience. The average pressure on the blades was 0.13 MPa for the Macintosh and 0.07 MPa for the GlideScope, showing a higher uniformity for the latter. CONCLUSIONS: The GlideScope allowed the participants to obtain a successful intubation applying a lower force. A flatter and more uniform pressure distribution, a higher successful rate, and a better glottic view were observed with the GlideScope.

Natural antibodies and their relationship with total immunoglobulins and acquired antibody response in goat kid (Capra hircus, L. 1758) serum.

Natural antibodies (NAb) are antibodies that can bind to a particular antigen without any apparent antigenic stimulation. In this paper, a careful analysis has been carried out on NAb levels in goat kid serum; possible correlations with the total immunoglobulin (tot-Ig) levels and specific antibody (SpAb) response were considered. Twenty randomly chosen kids were submitted to a first blood sampling (day 0). After 60 and 100 days, new blood samplings were carried out in the same animals. On day 0, after blood collection, all animals were immunized with a commercial vaccine; the immunization was repeated 30 days apart. Some exogenous antigens were tested to verify their immunoreactivity to NAb. Among them, the synthetic hapten 2,4,6-trinitrophenyl (TNP) conjugated with bovine serum albumin, resulted as the antigen with the higher immunoreactivity to NAb. Tot-Ig levels increased over time (p < 0.001). On the contrary, NAb levels, both IgG- and IgM-isotypes, significantly decreased during the experimental period (p < 0.001 and <0.05, respectively). Linear regression analyses showed a high correlation between IgM-NAb and tot-IgM levels (p < 0.001) at all the evaluated sampling times. However, a significant correlation between IgG-NAb and IgM-NAb was found only at the 1st (p < 0.01) and at the 2nd sampling (p < 0.05). No significant correlations were found between SpAb response and the other assessed humoral immune parameters. The obtained results are discussed in the light of the possible use of NAb assessment for the evaluation of the immune system activity in goat.

Toward exascale production of recombinant adeno-associated virus for gene transfer applications.

To gain acceptance as a medical treatment, adeno-associated virus (AAV) vectors require a scalable and economical production method. Recent developments indicate that recombinant AAV (rAAV) production in insect cells is compatible with current good manufacturing practice production on an industrial scale. This platform can fully support development of rAAV therapeutics from tissue culture to small animal models, to large animal models, to toxicology studies, to Phase I clinical trials and beyond. Efforts to characterize, optimize and develop insect cell-based rAAV production have culminated in successful bioreactor-scale production of rAAV, with total yields potentially capable of approaching the exa-(10(18)) scale. These advances in large-scale AAV production will allow us to address specific catastrophic, intractable human diseases such as Duchenne muscular dystrophy, for which large amounts of recombinant vector are essential for successful outcome.

Kinetic activity, membrane mitochondrial potential, lipid peroxidation, intracellular pH and calcium of frozen/thawed bovine spermatozoa treated with metabolic enhancers.

Owing to the progressive decline of sperm motility during storage there is a need to find substances capable of enhancing sperm energy metabolism and motility and/or preserving it from oxidative damage. The aim of this study was to evaluate in frozen/thawed bovine spermatozoa the effect of several compounds, such as myo-inositol, pentoxifylline, penicillamine + hypotaurine + epinephrine mixture (PHE), caffeine and coenzyme Q10+ zinc + d-aspartate mixture (CZA), on either kinetic or metabolic parameters. Sperm kinetics was evaluated by Sperm Class Analyser whereas specific fluorochromes were used to evaluated mitochondrial membrane potential (MMP), intracellular pH, intracellular calcium concentration and lipid peroxidation. Lipid peroxidation was also evaluated by TBARS analysis. Treatments significantly affected total and progressive motility with different dynamics in relation to the incubation time. After the first hour of incubation, CZA treatment produced the best performance in total and progressive sperm motility as well as in curvilinear velocity, average path velocity and amplitude of head displacement, whereas pentoxifylline stimulated the highest straight-line velocity. MMP showed higher values (p < 0.01) after treatment with pentoxifylline and PHE. Intracytoplasmic calcium concentration and lipid peroxidation were significantly (p < 0.05) affected by the incubation time rather than the treatments. Intracellular pH varied significantly (p < 0.01) in relation to either the incubation time or treatments. In particular, it showed a progressive increase throughout incubation with values in control group significantly higher than in myo-inositol, PHE, caffeine, pentoxifylline and CZA groups (7.37 ± 0.03 vs. 7.29 ± 0.03, 7.28 ± 0.03, 7.26 ± 0.03, 7.22 ± 0.03 and 7.00 ± 0.03, respectively; p < 0.01).; however, among treatments, CZA displayed the lowest values. Significant correlations were found between sperm kinetic and metabolic parameters. These findings provide new comparative information on the effects of putative metabolic enhancers on kinetics and metabolic activities of bovine spermatozoa. In this study, a rapid methodological approach for evaluating sperm quality is proposed.

Delayed onset infections after lower third molar germectomy could be related to the space distal to the second molar.

The onset of delayed infection after lower third molar germectomy is influenced by the amount of distal space. This retrospective study aimed to determine whether the incidence of delayed onset infection is related to the space distal to the second molar. The ratio between the distal space and the crown width, measured according to the Ganss protocol on panoramic radiographs, was obtained for 218 surgical germectomies performed for orthodontic reasons in 134 patients. A delayed onset infection occurred following 20 germectomies at between 2 and 8 weeks after surgery; purulent exudates from the alveolus and swelling were present. In 16 of the 20 cases of infection, a Ganss ratio of <0.5 showed the almost complete absence of space distal to the second molar. This study found that the distal space was significantly and inversely correlated with delayed onset infection (P=0.004). From a clinical point of view, it is important for the surgeon to be aware that a higher Ganss ratio may indicate that a delayed onset infection is less likely to occur and that a lower Ganss ratio could indicate a greater likelihood of this type of infection, so that the patient can be properly informed.

Gamma Knife Radiosurgery in the management of single and multiple brain metastases.

OBJECTIVES: To evaluate the efficacy and safety of Gamma Knife Radiosurgery (GKRS) in the treatment of single and multiple brain metastases. PATIENTS AND METHODS: From October 2012 to June 2014 106 patients were treated with Radiosurgery (RS) for brain metastases at University of Florence. 77 out of 106 patients had a radiological follow up and their data were analyzed. The target was defined as the enhancing lesion. The prescription dose was defined depending on tumor volume and tumor location. Each patient performed an MRI one month after GKRS for the first three months and every 3 months thereafter. Overall survival was calculated from the day of RS until death. Local recurrence (LR) was defined as radiologic growth of the irradiated lesion, while distant brain recurrence (DBR) was the evidence of brain lesion outside the previous irradiated field. Both the LR and DBR were calculated from the RS till the day of radiological evidence of relapse. The correlations within patient and disease characteristics and the outcomes of survival and disease control were analyzed. RESULTS: Mean follow up was 7.2 ± 4.8 months (range: 2.4-22.8 months). At the time of analysis 21 patients (27.3%) were dead. The overall survival (OS) at 1 year was 74%. On univariate Cox Regression analysis female gender (p=0.043, HR: 0.391, 95% CI: 0.157-0.972) and age >65 years (p=0.003 HR: 4.623, 95% CI: 1.687-12.663) were predictive for survival. On multivariate analysis, age older than 65 years (p=0.005HR: 4.254, 95% CI: 1.544-11.721) was confirmed as associated with worsened overall survival. 19 patients (24.7%) had recurrence in the radiosurgery field. The median time to local failure was 4.8 ± 2.0 months (range: 1.8-9.4 months) from GKRS. On Cox Regression univariate analysis, the only factor associated with higher risk of local failure was a number of treated lesions more than 4 (p=0.015, HR: 3.813, 95% CI: 1.298-11.202), no significant parameters were found at the multivariate analysis. The median time to develop distant brain failure was 6 ± 4.32 months (range: 1.08-21.6 months). Median distant brain control was 74% at 1 year. None of the factors analyzed was statistically significant for the distant brain relapse. The radiosurgery treatment was well tolerated. One patient treated for seven metastases developed seizures 8h after GKRS, he was treated with steroids and anticonvulsants. One patient had radiologic evidence of radionecrosis without any neurological symptoms. CONCLUSIONS: In well-performing patients with stable systemic disease radiosurgery can be performed as an exclusive treatment for brain metastases. Younger patients could have a greater benefit from the RS, on the other hand our finding confirm no correlation between the survival outcome and the number of lesions treated.

Trends in cervical cancer incidence in the district of Florence.

The trend in cervical cancer incidence in the District of Florence from 1975 to 1989 was investigated. Tuscany Cancer Registry data were available since 1985. Incidence data from 1975 to 1985 were obtained through a retrospective survey of all the Departments of Pathology and Gynaecology in the district. Cytological screening for cervical cancer has been available in the district since 1973, and since 1980 active invitation of residents aged 25 to 59 years has been in use. A significant trend in decreasing incidence was evident for the overall population (P = 0.003) and for 40-49 (P = 0.028), 50-59 (P < 0.001) and 60-69 (P = 0.002) year age groups, whereas no significant trend was observed for the age group 30-39 years. An association between attendance to screening and reduced incidence was evident, in that a greater reduction was evident for those cohorts (ages 50-59 and 60-69) who had a higher compliance to screening 10-15 years before. If the decrease in cervical cancer incidence was spontaneous, a parallel decrease of CIN3, which is commonly assumed to be the precursor of invasive carcinoma, would be expected. On the contrary, the detection rate of CIN3 at first Pap test showed a significant increase in the study period. All these findings suggest that the observed reduction in cervical cancer incidence was mostly due to the effect of screening, and stress the need for optimising the coverage of the invited population.

Referral policy and positive predictive value of call for surgical biopsy in the Florence Breast Cancer Screening Program.

The authors evaluate the referral rates and the predictive value (PV) of call for diagnostic work up or biopsy in a population based breast cancer screening program in the 1979-1986 period. The presence of mammographic abnormalities either benign or suspicious proved to be the only reliable referral criterion (recall rate = 7.9%, recall PV = 3.8%, biopsy call PV = 39%). When mammography was normal the presence of breast complaints other than pain or of a radiologically dense breast were aspecific referral criteria, and since the latter was abandoned, (a) referral rates dropped especially in younger women, (b) referral or biopsy PV improved, whereas (c) cancer detection rate was almost unaffected. Younger age was associated with higher referral rates and with lower PV of both referral or biopsy. Whenever comparison with previous examination was possible, mammography accuracy was higher; this explains the decrease in referral rates and the increased predictivity observed at further rounds with respect to first screening round.

Alteration of protein structure induced by low-energy (<18 eV) electrons. I. The peptide and disulfide bridges.

We present measurements of low-energy (<18 eV) electron-stimulated desorption of anions from acetamide (CH(3)CONH(2)) and dimethyl disulfide [DMDS: (CH(3)S)(2)] films. Electron irradiation of physisorbed CH(3)CONH(2) produces H(-), CH(3)(-) and O(-) anions, whereas the H(-), CH(2)(-), CH(3)(-), S(-), SH(-) and SCH(3)(-) anions are observed to desorb from the DMDS film. Below 12 eV, the dependence of the anion yields on the incident electron energy exhibits structures that indicate that a resonant process (i.e. dissociative electron attachment) is responsible for molecular fragmentation. Within the range of 1-18 eV, it is found that (1.7 and 1.4) x 10(7) H(-) ions/incident electron and (7.8 x 10(-11) and 4.3 x 10(-8)) of the other ions/incident electron are desorbed from acetamide and DMDS films, respectively. These results suggest that, within proteins, the disulfide bond is more sensitive to low-energy electron attack than the peptide bond. In biological cells, some proteins interact closely with nucleic acid. Therefore, the observed fragments, when produced from secondary low-energy electrons generated by high-energy radiation, not only may denature proteins, but may also induce reactions with the nearby nucleic acid and damage DNA.

Single-strand-specific radiosensitization of DNA by bromodeoxyuridine.

The effects of bromodeoxyuridine (BrdUrd) substitution for thymidine on gamma-ray-induced strand breakage were determined in single- and double-stranded oligonucleotides and double-stranded oligonucleotides containing a mismatched bubble region. BrdUrd does not sensitize complementary double-stranded DNA to gamma-ray-induced strand breakage, but it greatly sensitizes single-stranded DNA. However, when the BrdUrd is present in a single-stranded bubble of a double-stranded oligonucleotide, the non-base-paired nucleotides adjacent to the BrdUrd as well as several unpaired sites on the opposite unsubstituted strand are strongly sensitized. The radiosensitization properties of BrdUrd result primarily from the electrophilic nature of the bromine, making it a good leaving group and leading to the irreversible formation of the uridine-yl radical (dUrd(.)) or the uridine-yl anion (dUrd(-)) upon addition of an electron. The radiolytic loss of the bromine atom is greatly suppressed in double-stranded compared to single-stranded DNA. Thus we propose that the radiosensitization effects of bromouracil in vivo will likely be limited to single-strand regions such as found in transcription bubbles, replication forks, DNA bulges and the loop region of telomeres. Our results may have profound implications for the clinical use of bromodeoxyuridine (BrdUrd) as a radiosensitizer as well as for the development of targeted radiosensitizers.

Loop electrosurgical excision procedure of the transformation zone and colposcopically directed punch biopsy in the diagnosis of cervical lesions.

OBJECTIVE: To estimate the disagreement between the histologic reports at colposcopically directed punch biopsy of the cervix and subsequent loop excision of the transformation zone, and to assess the indications for loop excision in current practice. METHODS: The histologic diagnoses from loop electrosurgical excision procedures and concurrent colposcopically directed punch biopsies were compared in 337 consecutive women undergoing loop excision in a 5-year period. RESULTS: Disagreement between punch biopsy and loop excision was recorded in 190 cases (56.4%). The undercall and overcall rates for punch biopsy were 14 and 42.4%, respectively. Undercall at punch biopsy occurred in 24 of 46 cases of cervical intraepithelial neoplasia (CIN) III and in one microinvasive cancer diagnosed at loop excision, and disagreement was within one grade of CIN in 16 cases. CONCLUSIONS: Loop electrosurgical excision allows further and more accurate histologic examination of the transformation zone and should be the standard assessment procedure in all cases of CIN II detected at punch biopsy and whenever cytology or colposcopy suggests the risk of punch biopsy undercall. Immediate treatment by local destruction should not be performed, to avoid underestimation of the severity of the lesion.

Colposcopic survey of Papanicolaou test-negative cases with hyperkeratosis or parakeratosis.

A colposcopic survey was performed in 269 consecutive women with negative cytology showing hyperkeratosis or parakeratosis. A colposcopy-guided biopsy specimen of cervical abnormalities was taken in 88 cases, and human papillomavirus infection (HPV) was detected histologically in 25 cases. No cervical intraepithelial neoplasia (CIN) was detected. The detection rate of HPV was not significantly different from that observed in a consecutive series of 1073 Papanicolaou test-negative subjects self-referred for colposcopy. Colposcopic screening of subjects showing hyperkeratosis or parakeratosis with otherwise negative smears is not recommended because it does not allow detection of cytologically false-negative CIN.

A centralised cytology screening programme for cervical cancer in Florence.

STUDY OBJECTIVE: The aim of the study was to evaluate the effectiveness of a centralised population based cervical cytology screening programme. DESIGN: The study was a case-control investigation. SETTING: Cases and controls were confined to the province of Florence. PARTICIPANTS: 191 out of 208 cases of cervical cancer in women less than 75 years old at diagnosis in the period 1982-85 were interviewed. For each case three living controls were selected, strictly matched by year of birth and district of residence; in all 573 controls were eventually identified. Of these, 15 had had a hysterectomy (2.6%) and were excluded, and a further 18 (3.2%) did not take part for other reasons, leaving a total of 540 controls. MEASUREMENT AND RESULTS: Screening history was taken from a computerised archive for both cases and controls. A mail questionnaire was used to collect information on several potential confounding variables. For women screened only once in comparison with those never screened, the reduction in risk was about 70% (odds ratio 0.29. 95% confidence limits 0.15-0.55), while the reduction was even greater for those screened twice or more. No trend of increasing risk with increasing interval since last test was shown: considering separately women who had only had one test and those who had had two or more tests, the risk estimates were stable across different time intervals since the last test. CONCLUSIONS: There is a strong protective effect against developing invasive cervical cancer through participation in the screening programme.