Observation of the effect of gravity on the motion of antimatter.

Einstein's general theory of relativity from 19151 remains the most successful description of gravitation. From the 1919 solar eclipse2 to the observation of gravitational waves3, the theory has passed many crucial experimental tests. However, the evolving concepts of dark matter and dark energy illustrate that there is much to be learned about the gravitating content of the universe. Singularities in the general theory of relativity and the lack of a quantum theory of gravity suggest that our picture is incomplete. It is thus prudent to explore gravity in exotic physical systems. Antimatter was unknown to Einstein in 1915. Dirac's theory4 appeared in 1928; the positron was observed5 in 1932. There has since been much speculation about gravity and antimatter. The theoretical consensus is that any laboratory mass must be attracted6 by the Earth, although some authors have considered the cosmological consequences if antimatter should be repelled by matter7-10. In the general theory of relativity, the weak equivalence principle (WEP) requires that all masses react identically to gravity, independent of their internal structure. Here we show that antihydrogen atoms, released from magnetic confinement in the ALPHA-g apparatus, behave in a way consistent with gravitational attraction to the Earth. Repulsive 'antigravity' is ruled out in this case. This experiment paves the way for precision studies of the magnitude of the gravitational acceleration between anti-atoms and the Earth to test the WEP.

Sympathetic cooling of positrons to cryogenic temperatures for antihydrogen production.

The positron, the antiparticle of the electron, predicted by Dirac in 1931 and discovered by Anderson in 1933, plays a key role in many scientific and everyday endeavours. Notably, the positron is a constituent of antihydrogen, the only long-lived neutral antimatter bound state that can currently be synthesized at low energy, presenting a prominent system for testing fundamental symmetries with high precision. Here, we report on the use of laser cooled Be+ ions to sympathetically cool a large and dense plasma of positrons to directly measured temperatures below 7 K in a Penning trap for antihydrogen synthesis. This will likely herald a significant increase in the amount of antihydrogen available for experimentation, thus facilitating further improvements in studies of fundamental symmetries.

Prevalence and co-occurrence of unhealthy lifestyle habits and behaviours among secondary school students in Tuscany, central Italy.

OBJECTIVES: Unhealthy habits acquired during adolescence may persist in adulthood and eventually increase the risk of chronic illnesses. STUDY DESIGN: We reported on a survey conducted in 2013-2015 among secondary school students in Tuscany, central Italy. METHODS: We compared the prevalence of self-reported lifestyle characteristics and overweight/obesity between genders and age groups (14-16 vs 17-21 years). We partitioned each gender- and age-specific stratum into groups based on cigarette smoking and engagement in sport activities, and compared the prevalence of other unhealthy lifestyles across groups using Poisson regression. RESULTS: Overall, 2167 students (53.3% males, mean age 16.8 years) were included. Males were more frequently overweight/obese than females. Cigarette smoking increased with age and did not differ by gender. Males were more likely to engage in sport activities, drink alcoholic beverages and adopt other unhealthy lifestyle habits, whereas females reported a more frequent use of painkillers. Cigarette smoking was the single lifestyle characteristic most consistently associated with other unhealthy habits. CONCLUSIONS: The prevalence and patterns of co-occurrence of unhealthy lifestyle habits varied by gender and age group among secondary school students in Italy. Our findings should be taken into account when planning public health initiatives aiming to combat obesity and tackle unhealthy lifestyles among secondary school students in Italy.

Demonstration of Cascaded Modulator-Chicane Microbunching of a Relativistic Electron Beam.

We present results of an experiment showing the first successful demonstration of a cascaded microbunching scheme. Two modulator-chicane prebunchers arranged in series and a high power mid-IR laser seed are used to modulate a 52 MeV electron beam into a train of sharp microbunches phase locked to the external drive laser. This configuration is shown to greatly improve matching of the beam into the small longitudinal phase space acceptance of short-wavelength accelerators. We demonstrate trapping of nearly all (96%) of the electrons in a strongly tapered inverse free-electron laser accelerator, with an order-of-magnitude reduction in injection losses compared to the classical single-buncher scheme. These results represent a critical advance in laser-based longitudinal phase space manipulations and find application in high gradient advanced acceleration as well as in high peak and average power coherent radiation sources.

Meter-Scale Terahertz-Driven Acceleration of a Relativistic Beam.

Terahertz (THz) radiation promises breakthrough advances in compact advanced accelerators due to the gigavolts-per-meter fields achievable, but the challenge of maintaining overlap and synchronism between beams and short laser-generated THz pulses has so far limited interactions to the few-millimeter scale. We implement a novel scheme for simultaneous group and phase velocity matching of nearly single-cycle THz radiation with a relativistic electron beam for meter-scale inverse free-electron laser interaction in a magnetic undulator, resulting in energy modulations of up to 150 keV using modest THz pulse energies (≤1 µJ). Using this scheme, we demonstrate for the first time the use of a laser-based THz source for bunch-length compression and time-stamping of a relativistic electron beam.

High-Velocity Microsprays Enhance Antimicrobial Activity in Streptococcus mutans Biofilms.

Streptococcus mutans in dental plaque biofilms play a role in caries development. The biofilm's complex structure enhances the resistance to antimicrobial agents by limiting the transport of active agents inside the biofilm. The authors assessed the ability of high-velocity water microsprays to enhance delivery of antimicrobials into 3-d-old S. mutans biofilms. Biofilms were exposed to a 90° or 30° impact, first using a 1-µm tracer bead solution (109 beads/mL) and, second, a 0.2% chlorhexidine (CHX) or 0.085% cetylpyridinium chloride (CPC) solution. For comparison, a 30-s diffusive transport and simulated mouthwash were also performed. Confocal microscopy was used to determine number and relative bead penetration depth into the biofilm. Assessment of antimicrobial penetration was determined by calculating the killing depth detected by live/dead viability staining. The authors first demonstrated that the microspray was able to deliver significantly more microbeads deeper in the biofilm compared with diffusion and mouthwashing exposures. Next, these experiments revealed that the microspray yielded better antimicrobial penetration evidenced by deeper killing inside the biofilm and a wider killing zone around the zone of clearance than diffusion alone. Interestingly the 30° impact in the distal position delivered approximately 16 times more microbeads and yielded approximately 20% more bacteria killing (for both CHX and CPC) than the 90° impact. These data suggest that high-velocity water microsprays can be used as an effective mechanism to deliver microparticles and antimicrobials inside S. mutans biofilms. High shear stresses generated at the biofilm-burst interface might have enhanced bead and antimicrobial delivery inside the remaining biofilm by combining forced advection into the biofilm matrix and physical restructuring of the biofilm itself. Further, the impact angle has potential to be optimized both for biofilm removal and active agents' delivery inside biofilm in those protected areas where some biofilm might remain.

QPSK 3R regenerator using a phase sensitive amplifier.

A black box phase sensitive amplifier based 3R regeneration scheme is proposed for non-return to zero quadrature phase shift keyed formatted signals. Performance improvements of more than 2 dB are achieved at the presence of input phase distortion.

Streptococcus mutans biofilm transient viscoelastic fluid behaviour during high-velocity microsprays.

Using high-speed imaging we assessed Streptococcus mutans biofilm-fluid interactions during exposure to a 60-ms microspray burst with a maximum exit velocity of 51m/s. S. mutans UA159 biofilms were grown for 72h on 10mm-length glass slides pre-conditioned with porcine gastric mucin. Biofilm stiffness was measured by performing uniaxial-compression tests. We developed an in-vitro interproximal model which allowed the parallel insertion of two biofilm-colonized slides separated by a distance of 1mm and enabled high-speed imaging of the removal process at the surface. S. mutans biofilms were exposed to either a water microspray or an air-only microburst. High-speed videos provided further insight into the mechanical behaviour of biofilms as complex liquids and into high-shear fluid-biofilm interaction. We documented biofilms extremely transient fluid behaviour when exposed to the high-velocity microsprays. The presence of time-dependent recoil and residual deformation confirmed the pivotal role of viscoelasticity in biofilm removal. The air-only microburst was effective enough to remove some of the biofilm but created a smaller clearance zone underlying the importance of water and the air-water interface of drops moving over the solid surface in the removal process. Confocal and COMSTAT analysis showed the high-velocity water microspray caused up to a 99.9% reduction in biofilm thickness, biomass and area coverage, within the impact area.

In Vitro Effects of Strontium on Proliferation and Osteoinduction of Human Preadipocytes.

Development of tools to be used for in vivo bone tissue regeneration focuses on cellular models and differentiation processes. In searching for all the optimal sources, adipose tissue-derived mesenchymal stem cells (hADSCs or preadipocytes) are able to differentiate into osteoblasts with analogous characteristics to bone marrow mesenchymal stem cells, producing alkaline phosphatase (ALP), collagen, osteocalcin, and calcified nodules, mainly composed of hydroxyapatite (HA). The possibility to influence bone differentiation of stem cells encompasses local and systemic methods, including the use of drugs administered systemically. Among the latter, strontium ranelate (SR) represents an interesting compound, acting as an uncoupling factor that stimulates bone formation and inhibits bone resorption. The aim of our study was to evaluate the in vitro effects of a wide range of strontium (Sr(2+)) concentrations on proliferation, ALP activity, and mineralization of a novel finite clonal hADSCs cell line, named PA20-h5. Sr(2+) promoted PA20-h5 cell proliferation while inducing the increase of ALP activity and gene expression as well as HA production during in vitro osteoinduction. These findings indicate a role for Sr(2+) in supporting bone regeneration during the process of skeletal repair in general, and, more specifically, when cell therapies are applied.

Removal of Dental Biofilms with an Ultrasonically Activated Water Stream.

Acidogenic bacteria within dental plaque biofilms are the causative agents of caries. Consequently, maintenance of a healthy oral environment with efficient biofilm removal strategies is important to limit caries, as well as halt progression to gingivitis and periodontitis. Recently, a novel cleaning device has been described using an ultrasonically activated stream (UAS) to generate a cavitation cloud of bubbles in a freely flowing water stream that has demonstrated the capacity to be effective at biofilm removal. In this study, UAS was evaluated for its ability to remove biofilms of the cariogenic pathogen Streptococcus mutans UA159, as well as Actinomyces naeslundii ATCC 12104 and Streptococcus oralis ATCC 9811, grown on machine-etched glass slides to generate a reproducible complex surface and artificial teeth from a typodont training model. Biofilm removal was assessed both visually and microscopically using high-speed videography, confocal scanning laser microscopy (CSLM), and scanning electron microscopy (SEM). Analysis by CSLM demonstrated a statistically significant 99.9% removal of S. mutans biofilms exposed to the UAS for 10 s, relative to both untreated control biofilms and biofilms exposed to the water stream alone without ultrasonic activation (P < 0.05). The water stream alone showed no statistically significant difference in removal compared with the untreated control (P = 0.24). High-speed videography demonstrated a rapid rate (151 mm(2) in 1 s) of biofilm removal. The UAS was also highly effective at S. mutans, A. naeslundii, and S. oralis biofilm removal from machine-etched glass and S. mutans from typodont surfaces with complex topography. Consequently, UAS technology represents a potentially effective method for biofilm removal and improved oral hygiene.

The calcium-sensing receptor in bone metabolism: from bench to bedside and back.

UNLABELLED: The calcium-sensing receptor (CaSR), a key player in the maintenance of calcium homeostasis, can influence bone modeling and remodeling by directly acting on bone cells, as demonstrated by in vivo and in vitro evidence. The modulation of CaSR signaling can play a role in bone anabolism. INTRODUCTION: The calcium-sensing receptor (CaSR) is a key player in the maintenance of calcium homeostasis through the regulation of PTH secretion and calcium homeostasis, thus indirectly influencing bone metabolism. In addition to this role, in vitro and in vivo evidence points to direct effects of CaSR in bone modeling and remodeling. In addition, the activation of the CaSR is one of the anabolic mechanisms implicated in the action of strontium ranelate, to reduce fracture risk. METHODS: This review is based upon the acquisition of data from a PubMed enquiry using the terms "calcium sensing receptor," "CaSR" AND "bone remodeling," "bone modeling," "bone turnover," "osteoblast," "osteoclast," "osteocyte," "chondrocyte," "bone marrow," "calcilytics," "calcimimetics," "strontium," "osteoporosis," "skeletal homeostasis," and "bone metabolism." RESULTS: A fully functional CaSR is expressed in osteoblasts and osteoclasts, so that these cells are able to sense changes in the extracellular calcium and as a result modulate their behavior. CaSR agonists (calcimimetics) or antagonists (calcilytics) have the potential to indirectly influence skeletal homeostasis through the modulation of PTH secretion by the parathyroid glands. The bone anabolic effect of strontium ranelate, a divalent cation used as a treatment for postmenopausal and male osteoporosis, might be explained, at least in part, by the activation of CaSR in bone cells. CONCLUSIONS: Calcium released in the bone microenvironment during remodeling is a major factor in regulating bone cells. Osteoblast and osteoclast proliferation, differentiation, and apoptosis are influenced by local extracellular calcium concentration. Thus, the calcium-sensing properties of skeletal cells can be exploited in order to modulate bone turnover and can explain the bone anabolic effects of agents developed and employed to revert osteoporosis.

Numerical investigation of all-optical add-drop multiplexing for spectrally overlapping OFDM signals.

We propose a novel architecture for all-optical add-drop multiplexing of OFDM signals. Sub-channel extraction is achieved by means of waveform replication and coherent subtraction from the OFDM super-channel. Numerical simulations have been carried out to benchmark the performance of the architecture against critical design parameters.

Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin.

BACKGROUND: The different perception and assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) between healthcare providers and patients has not yet been fully addressed, although these two approaches might eventually lead to inconsistent, possibly conflicting interpretation, especially regarding sensory impairment. PATIENTS AND METHODS: A cohort of 281 subjects with stable CIPN was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC v. 2.0) sensory scale, the clinical Total Neuropathy Score (TNSc©), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sumscore (mISS) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). RESULTS: Patients' probability estimates showed that the EORTC QLQ-CIPN20 sensory score was overall more highly related to the NCI-CTC sensory score. However, the vibration perception item of the TNSc had a higher probability to be scored 0 for EORTC QLQ-CIPN20 scores lower than 35, as vibration score 2 for EORTC QLQ-CIPN20 scores between 35 and 50 and as grade 3 or 4 for EORTC QLQ-CIPN20 scores higher than 50. The linear models showed a significant trend between each mISS item and increasing EORTC QLQ-CIPN20 sensory scores. CONCLUSION: None of the clinical items had a perfect relationship with patients' perception, and most of the discrepancies stood in the intermediate levels of CIPN severity. Our data indicate that to achieve a comprehensive knowledge of CIPN including a reliable assessment of both the severity and the quality of CIPN-related sensory impairment, clinical and PRO measures should be always combined.

Rasch-built Overall Disability Scale for patients with chemotherapy-induced peripheral neuropathy (CIPN-R-ODS).

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-R-ODS) comprising 146 items was assessed twice (interval: 2-3 weeks; test-retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-R-ODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS). The preliminary R-ODS did not meet Rasch model's expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-R-ODS consisting of 28 items fulfilled all the model's expectations with proper validity and reliability, and was unidimensional. The final CIPN-R-ODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinal-based measures. Its use is recommended in future clinical trials in CIPN.

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS: After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION: Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

A practical method for the estimation of therapeutic activity in the treatment of Graves' hyperthyroidism.

AIM: To test the efficacy of a practical method which allows the calculation of personalized activity in Graves' disease. METHODS: The method is based on International Commission of Radiological Protection (ICRP) 53 data. The model allows the prediction of the activity administered in order to release 300 Gy to the thyroid, once its iodine uptake and mass are known. We applied it to 289 patients investigated by clinical examination, biochemical assessment and neck ultrasonography. The method was applied considering the thyroid 131I uptake and the ultrasound mass. The patients were followed by check of TSH, FT3, FT4 and clinical examination. Finally, we evaluated the difference between our dosimetric method and the hypothetic administration of a fix amount of 131I (185, 370 and 600 Mbq respectively) in term of adsorbed dose. RESULTS: The average activity administered was 403.3+92.5 MBq with an average dose released to thyroid of 304.9+24.8 Gy. From a statistical point of view the administration of standard activities (185 and 600 MBq) would represent respectively a wrong estimate of the optimal dose (meanly 140.8+44.7 Gy and 473.6+142.6 Gy respectively). The administration of a standard activity (370 MBq) would release a dose close to that prescribed (291.2 Gy) with a standard deviation (86.9 Gy), which is considerably higher than the one obtained with the dosimetric model (24.8 Gy). Twenty four months after radioiodine treatment, 57.8% of patients presented hypothyroidism, 23.2% euthyroidism and 19% of hyperthyroidism. The overall therapeutic efficiency was of 81%. CONCLUSION: The dosimetric method based on IRCP 53 data, is effective in controlling Graves' hyperthyroidism. Advantages in adopting this method are: dose optimization to patient, easy implementation in the clinical practice, low budget impact.

Cellular response in semi-intensively cultured sea bream gills to Ergasilus sieboldi (Copepoda) with emphasis on the distribution, histochemistry and fine structure of mucous cells.

Light and ultrastructure studies were carried out on gill of sea bream, Sparus aurata L., naturally infected with Ergasilus sieboldi (Copepoda) to assess pathology and host cell responses. Thirty S. aurata were examined, and 23 (74%) were infected, the intensity of infection ranging from 3 to 50 parasites per host. The copepod encircled gill lamellae with its second antennae, occluded arteries, compressed the epithelium, provoked hyperplasia and haemorrhage, and often caused tissue disruption. Adjacent to the site of attachment, rodlet cells (RCs), mast cells (MCs) and mucous cells were observed. In parasitized fish, mucous cells were more abundant in infected gills than in uninfected (t-test, P<0.01), while no significant differences were encountered in the numbers of RCs and MCs between gill of infected and uninfected fish (t-test, P>0.01). In both infected and uninfected gill, the RCs were within the primary lamella and also sometimes occurred in secondary lamella. In healthy and infected gill, MCs were free within the connective tissue inside and outside the blood vessels of the primary lamellae and made close contact with vascular endothelial cells. Infected and uninfected gill mucous cells stained positively for neutral muco-substances (PAS positive). In all sea bream, gill mucous cells presented a central or eccentric electron-dense core within the mucus granules.

Dual-energy imaging in full-field digital mammography: a phantom study.

A dual-energy technique which employs the basis decomposition method is being investigated for application to digital mammography. A three-component phantom, made up of plexiglas, polyethylene, and water, was doubly exposed with the full-field digital mammography system manufactured by General Electric. The 'low' and 'high' energy images were recorded with a Mo/Mo anode-filter combination and a Rh/Rh combination, respectively. The total dose was kept within the acceptable levels of conventional mammography. The first hybrid images obtained with the dual-energy algorithm are presented in comparison with a conventional radiograph of the phantom. Image-quality characteristics at contrast cancellation angles between plexiglas and water are discussed. Preliminary results show that a combination of a standard Mo-anode 28 kV radiograph with a Rh-anode 49 kV radiograph provides the best compromise between image-quality and dose in the hybrid image.

Signal-to-noise ratio evaluation in dual-energy radiography with synchrotron radiation.

Dual-energy radiography is an effective technique that allows removal of contrast between pairs of materials in order to display details of interest on a uniform background. In mammographic images the detection of small nodules is often impeded by obscuring background 'clutter' resulting from the contrast between normal tissues (glandular and adipose) in their neighbourhood. We consider whether it could be possible to apply dual-energy radiography to the breast, which is hypothetically principally composed of three tissues, glandular, adipose and cancerous, in order to remove the contrast due to the distribution of normal tissues and, as a consequence, to enhance the intrinsic contrast of the pathology. The purpose of this work is to test the limitations of dual-energy radiography on a three-component phantom under optimum conditions of the source and detector. We use a synchrotron monochromatic beam, produced at the ELETTRA synchrotron facility (Trieste, Italy), and an imaging plate detector, in order to acquire two images at low and high energies of a phantom composed of polyethylene, plexiglas and water. For evaluation of the potential of this procedure we studied the signal-to-noise ratio (SNR) of polyethylene and water on a set of images obtained by applying the dual-energy procedure. We found that the SNR of polyethylene and water is around the detectability threshold (according to Rose's criteria) at the contrast cancellation angles. Finally we evaluated the air entrance dose required for this double exposure, resulting in 0.81 mGy for the low-energy image and 0.01 mGy for the high-energy image. To obtain the same image quality for a standard breast of 5.5 cm, mean glandular doses of 3.50 mGy and 0.03 mGy at 17 keV and at 34 keV, respectively, are required.