Simultaneous Measurement of the Half-Life and Spectral Shape of

Current bounds on the neutrino Majorana mass are affected by significant uncertainties in the nuclear calculations for neutrinoless double-beta decay. A key issue for a data-driven improvement of the nuclear theory is the actual value of the axial coupling constant g_{A}, which can be investigated through forbidden ß decays. We present the first measurement of the 4th-forbidden ß decay of ^{115}In with a cryogenic calorimeter based on indium iodide. Exploiting the enhanced spectrum-shape method for the first time to this isotope, our study accurately determines simultaneously spectral shape, g_{A}, and half-life. The interacting shell model, which best fits our data, indicates a half-life for this decay at T_{1/2}=(5.26±0.06)×10^{14} yr.

A phase 2, randomized, blinded, dose-finding, controlled clinical trial to evaluate the safety, tolerability, and immunogenicity of a 24-valent pneumococcal conjugate vaccine (VAX-24) in healthy adults 65 years and older.

Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578.

Isolation and identification of Legionella spp. from non-hospital facilities: a preliminary one-year surveillance study in the urban area of Pesaro-Urbino (Central Italy).

BACKGROUND: Legionella is considered one of the most important causes of potentially preventable morbid-ity and mortality. These microorganisms are ubiquitous, but incomplete information is available on the geographic distribution of Legionella species in our region. STUDY DESIGN: For the mentioned reasons, in this work the distribution of Legionella spp. in non-hospital facilities of the urban area of Pesaro-Urbino (Central Italy), including public fountains, residential build-ings, public and private offices and retirement homes, was investigated. METHODS: A total of 298 water samples were collected from the different facilities and subjected to standard Legionella isolation and identification protocols. RESULTS: As reported, 17.8% of the collected water samples resulted positive for Legionella spp. (28.6% from retirement homes, 21.3% from residential buildings, 15.3% from private and public offices). The highest per-centage of positive samples (14.4%) was found in hot water from retirements homes (58.8%) and residential buildings (31.8%); the most frequent isolated serogroups were L. pneumophila 2-14 (71.7%). CONCLUSIONS: This work is the first describing the distribution of Legionella spp. in non-hospital facilities in the province of Pesaro-Urbino, and highlights a condition of potential risk for susceptible categories. From our data, we can point that a regular and constant control to prevent microbiological risk from legionellosis, particularly in facilities housing the elderly, is recommended.

Asynchrony in Peritumoral Resting-State Blood Oxygen Level-Dependent fMRI Predicts Meningioma Grade and Invasion.

BACKGROUND AND PURPOSE: Meningioma grade is determined by histologic analysis, with detectable brain invasion resulting in a diagnosis of grade II or III tumor. However, tissue undersampling is a common problem, and invasive parts of the tumor can be missed, resulting in the incorrect assignment of a lower grade. Radiographic biomarkers may be able to improve the diagnosis of grade and identify targets for biopsy. Prior work in patients with gliomas has shown that the resting-state blood oxygen level-dependent fMRI signal within these tumors is not synchronous with normal brain. We hypothesized that blood oxygen level-dependent asynchrony, a functional marker of vascular dysregulation, could predict meningioma grade. MATERIALS AND METHODS: We identified 25 patients with grade I and 11 patients with grade II or III meningiomas. Blood oxygen level-dependent time-series were extracted from the tumor and the radiographically normal control hemisphere and were included as predictors in a multiple linear regression to generate a blood oxygen level-dependent asynchrony map, in which negative values signify synchronous and positive values signify asynchronous activity relative to healthy brain. Masks of blood oxygen level-dependent asynchrony were created for each patient, and the fraction of the mask that extended beyond the contrast-enhancing tumor was computed. RESULTS: The spatial extent of blood oxygen level-dependent asynchrony was greater in high (grades II and III) than in low (I) grade tumors (P < 0.001) and could discriminate grade with high accuracy (area under the curve = 0.88). CONCLUSIONS: Blood oxygen level-dependent asynchrony radiographically discriminates meningioma grade and may provide targets for biopsy collection to aid in histologic diagnosis.

Prevalence and characteristics of positional plagiocephaly in healthy full-term infants at 8-12 weeks of life.

Positional plagiocephaly (PP) denotes flattening of the skull that occurs frequently in healthy infants. Aim of this study was to estimate the prevalence of positional plagiocephaly and to identify the risk factors in a cohort of healthy infants in order to help prevention of PP. In a prospective design, all healthy full-term infants, ranging from 8 to 12 weeks of age, who presented at the public immunization clinic in Ferrara, were eligible for the study. After obtaining informed consent, we interviewed the parents and examined the infants using the Argenta's assessment tool. Of 283 infants examined, 107 (37.8%) were found to have PP at 8-12 weeks of age. In 64.5%, PP was on the right side, 50.5% were male and 15% presented also with brachycephaly. Risk factors significantly associated were lower head circumference, advanced maternal age, Italian compared to African, and supine sleep position, in particular for infants born at 37 weeks, preference for one side of the head. In logistic regression, risk factors significantly associated were lower birth weight, advanced maternal age, and supine sleep position. CONCLUSIONS: Positional plagiocephaly is a common issue faced by pediatricians; our results reinforce the need of improving prevention both of sudden infant death and positional plagiocephaly, through uniform messages provided prenatally and postnatally by different health professionals. "What is Known:" •The incidence of positional plagiocephaly varies due to population studied and measuring methods. •Different factors are considered in the literature as being associated to positional plagiocephaly (infant factors, obstetric factors, infant care practices, sociodemographic factors). "What is New:" •This is one of the few European studies quantifying positional plagiocephaly prevalence in a population of unselected healthy infants. •In this study, positional plagiocephaly is confirmed as a common issue, related to some factor (as supine sleep position and positional head prevalence) that should be addressed in pre and postnatal counseling. •The prone sleepers rate in our population highlight the need to improve parental awareness regarding SIDS prevention, in particular in borderline gestational age.

A Multiparametric Model for Mapping Cellularity in Glioblastoma Using Radiographically Localized Biopsies.

BACKGROUND AND PURPOSE: The complex MR imaging appearance of glioblastoma is a function of underlying histopathologic heterogeneity. A better understanding of these correlations, particularly the influence of infiltrating glioma cells and vasogenic edema on T2 and diffusivity signal in nonenhancing areas, has important implications in the management of these patients. With localized biopsies, the objective of this study was to generate a model capable of predicting cellularity at each voxel within an entire tumor volume as a function of signal intensity, thus providing a means of quantifying tumor infiltration into surrounding brain tissue. MATERIALS AND METHODS: Ninety-one localized biopsies were obtained from 36 patients with glioblastoma. Signal intensities corresponding to these samples were derived from T1-postcontrast subtraction, T2-FLAIR, and ADC sequences by using an automated coregistration algorithm. Cell density was calculated for each specimen by using an automated cell-counting algorithm. Signal intensity was plotted against cell density for each MR image. RESULTS: T2-FLAIR (r = -0.61) and ADC (r = -0.63) sequences were inversely correlated with cell density. T1-postcontrast (r = 0.69) subtraction was directly correlated with cell density. Combining these relationships yielded a multiparametric model with improved correlation (r = 0.74), suggesting that each sequence offers different and complementary information. CONCLUSIONS: Using localized biopsies, we have generated a model that illustrates a quantitative and significant relationship between MR signal and cell density. Projecting this relationship over the entire tumor volume allows mapping of the intratumoral heterogeneity in both the contrast-enhancing tumor core and nonenhancing margins of glioblastoma and may be used to guide extended surgical resection, localized biopsies, and radiation field mapping.

Ultraviolet germicidal irradiation in tap water contaminated by Aspergillus spp.

We investigated the effect of ultraviolet germicidal irradiation (UVI) from a low-pressure mercury lamp on several pathogenic Aspergillus spp. including A. flavipes, A. flavus, A. fumigatus, A. glaucus, A. nidulans, A. niger, A. terreus, A. ustus and A. versicolor suspended in tap water under laboratory-scale conditions. It was shown that within 10 s of exposure, time species such as A. glaucus, A. niudulans and A. ustus were completely inactivated, while 40 s were needed for the elimination of all the species tested. A. flavus and A. niger were found to be less susceptible than other species. Based on these results we conclude that UV disinfection could effectively inactivate Aspergillus spp. in tap water. Such disinfection could be used to reduce potential exposure of high-risk patients to fungal aerosols, particularly in hospital settings, where point-of-use (POU) UV light devices could be installed to provide safe water at a very low cost.

HOLMES: The electron capture decay of [Formula: see text]Ho to measure the electron neutrino mass with sub-eV sensitivity.

The European Research Council has recently funded HOLMES, a new experiment to directly measure the neutrino mass. HOLMES will perform a calorimetric measurement of the energy released in the decay of [Formula: see text]Ho. The calorimetric measurement eliminates systematic uncertainties arising from the use of external beta sources, as in experiments with beta spectrometers. This measurement was proposed in 1982 by A. De Rujula and M. Lusignoli, but only recently the detector technological progress allowed to design a sensitive experiment. HOLMES will deploy a large array of low temperature microcalorimeters with implanted [Formula: see text]Ho nuclei. The resulting mass sensitivity will be as low as 0.4 eV. HOLMES will be an important step forward in the direct neutrino mass measurement with a calorimetric approach as an alternative to spectrometry. It will also establish the potential of this approach to extend the sensitivity down to 0.1 eV. We outline here the project with its technical challenges and perspectives.

Occurrence of fungi in dialysis water and dialysate from eight haemodialysis units in central Italy.

BACKGROUND: Fungal contamination of dialysis fluids may be a serious problem in therapy, particularly due to the debilitated immune system of haemodialysis patients. AIM: To investigate the occurrence, distribution, and diversity of fungi in dialysis water and dialysis solution of eight haemodialysis units in a region of central Italy. METHODS: Samples were collected over a one-year period from different points of the haemodialysis circuits in accordance with the guidelines of the Italian Society of Nephrology. Isolation and identification of fungi was performed according to the ISTISAN method Reports (2007/05 and 2008/10). FINDINGS: Of the 976 samples analysed, 96 grew filamentous fungi, 28 were positive for yeast, and six samples contained both mould and yeast. A wide variety of filamentous fungi (26 genera, of which 15 identified at species level, and 'mycelia sterilia') were recovered, many of which are known as opportunistic pathogens. Cladosporium spp. were most frequently found (39%), followed by Alternaria spp. and Tricophyton spp. Fungal counts in treated water and standard dialysate solution were always below the threshold (<10 cfu/mL), and thus are in agreement with the Italian guidelines for dialysis fluid quality, whereas 10.9% of the samples of ultrapure dialysate solution were contaminated by one or several fungi types, in contravention of the guidelines. CONCLUSION: The large variety of opportunistic fungi recovered in the haemodialysis circuits proves the importance of including an analysis of fungi to check the microbial quality of dialysis water and dialysate.

Nuclear lipid droplets: a novel nuclear domain.

We investigated nuclear neutral-lipid (NL) composition and organization, as NL may represent an alternative source for providing fatty acids and cholesterol (C) to membranes, signaling paths, and transcription factors in the nucleus. We show here that nuclear NL were organized into nonpolar domains in the form of nuclear-lipid droplets (nLD). By fluorescent confocal microscopy, representative nLD were observed in situ within the nuclei of rat hepatocytes in vivo and HepG2 cells, maintained under standard conditions in culture, and within nuclei isolated from rat liver. nLD were resistant to Triton X-100 and became stained with Sudan Red, OsO4, and BODIPY493/503. nLD and control cytosolic-lipid droplets (cLD) were isolated from rat-liver nuclei and from homogenates, respectively, by sucrose-gradient sedimentation. Lipids were extracted, separated by thin-layer chromatography, and quantified. nLD were composed of 37% lipids and 63% proteins. The nLD lipid composition was as follows: 19% triacylglycerols (TAG), 39% cholesteryl esters, 27% C, and 15% polar lipids; whereas the cLD composition contained different proportions of these same lipid classes, in particular 91% TAG. The TAG fatty acids from both lipid droplets were enriched in oleic, linoleic, and palmitic acids. The TAG from the nLD corresponded to a small pool, whereas the TAG from the cLD constituted the main cellular pool (at about 100% yield from the total homogenate). In conclusion, nLD are a domain within the nucleus where NL are stored and organized and may be involved in nuclear lipid homeostasis.

First measurement of the partial widths of 209Bi decay to the ground and to the first excited states.

209Bi alpha decay to the ground and to the first excited state have been recently observed for the first time with a large BGO scintillating bolometer. The half-life of 209Bi is determined to be τ(1/2)=(2.01±0.08)×10(19) yr while the branching ratio for the ground-state to ground-state transition is (98.8±0.3)%.

Aminophosphonic acids and derivatives. Synthesis and biological applications.

In recent years, phosphonic acids and their derivatives have received increasing attention as analogues of a series of naturally occurring phosphates and as "bio-isosteric phosphorus analogues" of amino acids. Unlike a phosphate group, the phosphonate moiety is not readily hydrolyzed, in a biological environment, by the enzymes involved in the phosphate cleavage. This feature makes these compounds extremely useful in several applications, in metabolic regulation, in enhancement or inhibition studies, in the development of potential drugs against several metabolic disorders. The great potential of these compounds in biological applications resulted in an intense effort directed to the development of efficient synthetic methods for their preparation, with particular attention to stereoselective synthesis. The purpose of this review is to give an up-to-date account of the chemistry, the synthesis and the biological activity of aminophosphonic acids and their derivatives.

[Disinfection efficiency of peracetic acid, alone and in combination with hypochlorite, against Mycobacterium avium in drinking water]. / Efficacia disinfettante dell'acido peracetico (PAA), da solo o in combinazione con il cloro, nei confronti di Mycobacterium avium in acqua destinata al consumo umano.

Peracetic acid (PAA) is a disinfectant with a wide spectrum of antimicrobial activity, but little is known about the feasibility of using it in the field of drinking water treatment. The aim of this study has been assess disinfectant efficacy of PAA, alone or in combination with hypochlorite, against M. avium in drinking water M. avium is a common opportunistic pathogen in immunocompromised subjects that is able to survive and grow in drinking water distribution systems. In this study PAA did not show appreciable activity against the greater number of tested strains (16/21) up to 5 ppm of PAA, a weak activity was seen on 4 strains, while a significant reduction in viable cells (about 50%) was seen only on 1 strain after 48 h of treatment with 5 ppm of PAA. We also evidenced that M. avium was unaffected by chlorine concentration usually present in drinking water distribution system. Finally, the combination of PAA and sodium hypochlorite did not promote enhanced antimicrobial efficacy respect to the single disinfectants. In conclusion, our result would indicate that PAA is an unlikely candidate for the disinfection of drinking water from M. avium and further strategies are required to eliminate M. avium from drinking water system.

Measurement of the p to s wave branching ratio of 187Re beta decay from beta environmental fine structure.

The mixed occurrence of s-wave and p-wave contributions in a first forbidden unique Gamow-Teller beta decay has been investigated for the first time by measuring the beta environmental fine structure (BEFS) in a 187Re crystalline compound. The experiment has been carried out with an array of eight AgReO4 thermal detectors operating at a temperature of approximately 100 mK. A fit of the observed BEFS spectrum indicates the p-wave electron emission as the dominant channel. The complete understanding of the BEFS distortion of the 187Re beta decay spectrum is crucial for future experiments aiming at the precise calorimetric measurement of the antineutrino mass.

New limit on the neutrinoless betabeta decay of 130Te.

We report the present results of CUORICINO, a search for neutrinoless double-beta (0nu betabeta) decay of 130Te. The detector is an array of 62 TeO2 bolometers with a total active mass of 40.7 kg. The array is cooled by a dilution refrigerator shielded from environmental radioactivity and energetic neutrons, operated at approximately 8 mK in the Gran Sasso Underground Laboratory. No evidence for (0nu betabeta) decay was found and a new lower limit, T(1/2)(0nu) > or = 1.8 x 10(24) yr (90% C.L.) is set, corresponding to [m(nu)] < or = 0.2 to 1.1 eV, depending on the theoretical nuclear matrix elements used in the analysis.

Bolometric bounds on the antineutrino mass.

High statistics calorimetric measurements of the beta spectrum of 187Re are being performed with arrays of silver perrhenate crystals operated at low temperature. After a substantial modification of the experimental setup, a new measurement with ten silver perrhenate microbolometers has been running since July 2002. The crystals have masses around 300 microg and their average FWHM energy resolution is of 28.3 eV at the beta end point. The Kurie plot collected during 4485 h x mg effective running time has an end-point energy of 2466.1+/-0.8(stat)+/-1.5(syst) eV, while the half lifetime of the decay is found to be 43.2+/-0.2(stat)+/-0.1(syst) Gy. These values are the most precise obtained so far for 187Re. The best fit value for m(2)(nu(e)) is 147+/-237(stat)+/-90(syst) eV(2), which corresponds to an upper limit for the electron antineutrino mass m(nu(e))< or =21.7 eV at 90% C.L.

Antifungal activity of Brassica oleracea var. botrytis fresh aqueous juice.

The antifungal activity of fresh, aqueous Brassica oleracea var. botrytis juice against Candida albicans and other pathogenic fungi was investigated. The juice was found to be effective both in inhibiting the growth of blastoconidia and reducing the appearance of C. albicans germ tubes. Furthermore, the juice inhibited the growth of some pathogenic, filamentous fungi.

Azomethine ylide cycloaddition/reductive heterocyclization approach to oxindole alkaloids: asymmetric synthesis of (-)-horsfiline.

The intermolecular [3 + 2] annulation of azomethine ylides with 2(2-nitrophenyl)acrylate dienophiles followed by reductive heterocyclization affords the spiro(indole-pyrrolidine) ring system. Hence, this enable us to accomplish a concise and highly enantioselective synthesis of (-)-horsfiline 1, based on chiral auxiliary-directed pi-face discrimination in the 1,3-dipolar cycloaddition of (1S,2R)-2-phenyl-1-cyclohexyl ester 4f with N-methylazomethine ylide.

Efficacy of macrolides used in combination with ethambutol, with or without other drugs, against Mycobacterium avium within human macrophages.

The activities of clarithromycin or roxithromicin used in combination with other antimicrobial drugs were tested in human macrophages experimentally infected with 23 strains of Mycobacterium avium. Overall, clarithromycin-ethambutol-rifampicin was the most active combination tested. The reduction in intracellular viable bacilli was found to be more than 1 log(10) for 95% and more than 2 logs(10) for 65% of the strains. The second most active combination was roxithromycin-ethambutol-rifampicin, which was found to be bactericidal for about 80% and highly bactericidal for 20% of the strains. Others combinations were only bacteriostatic or weakly bactericidal for many of the strains. The addition of a third drug did not necessarily promote enhanced bacterial killing inside the macrophage.

Radiosurgery for the treatment of recurrent central neurocytomas.

OBJECTIVE: Central neurocytomas are benign neoplasms with neuronal differentiation typically located in the lateral ventricles of young adults. Although the treatment of choice is complete surgical excision, patients may experience local recurrence. Adjuvant therapy for patients with residual or recurrent tumor has included reoperation, radiotherapy, or chemotherapy. To avoid the side effects of conventional radiotherapy in young patients, we present a series of patients with clear evidence of tumor progression who were treated with gamma knife radiosurgery. METHODS: Four patients (ages 20-49 yr; mean, 28 yr) who presented with an intraventricular mass on magnetic resonance imaging scans and underwent craniotomy for tumor resection were reviewed retrospectively. Histopathological analysis confirmed central neurocytoma in all cases. Each patient was followed up clinically and radiographically with serial magnetic resonance imaging. When radiographic signs of tumor progression were evident, patients were treated with radiosurgery. RESULTS: Complete radiographic tumor resection was achieved in all patients. There were no major postoperative complications. Local tumor progression was detected on magnetic resonance imaging scans 9 to 25 months after surgery (median, 17.5 mo). All patients achieved complete response to radiosurgery with reduction in tumor size. There have been no complications from radiosurgery. Follow-up ranged from 12 to 28 months (mean, 16.5 mo) after radiosurgery, and from 24 to 84 months (mean, 54.5 mo) after initial presentation. CONCLUSION: Radiosurgery with the gamma knife unit provides safe and effective adjuvant therapy after surgical resection of central neurocytomas. Radiosurgery may eliminate the need for reoperation and avoid the possible long-term side effects from conventional radiotherapy in young patients.