Optical Contactless Measurement of Electric Field-Induced Tensile Stress in Diamond Nanoscale Needles.

The application of a high electrostatic field at the apex of monocrystalline diamond nanoscale needles induces an energy splitting of the photoluminescence lines of color centers. In particular, the splitting of the zero-phonon line of the neutral nitrogen-vacancy complex (NV0) has been studied within a laser-assisted tomographic atom probe equipped with an in situ microphotoluminescence bench. The measured quadratic dependence of the energy splitting on the applied voltage corresponds to the stress generated on the metal-like apex surface by the electrostatic field. Tensile stress up to 7 GPa has thus been measured in the proximity of the needle apex. Furthermore, the stress scales along the needle shank inversely proportionally to its axial cross section. We demonstrate thus a method for contactless piezo-spectroscopy of nanoscale systems by electrostatic field regulation for the study of their mechanical properties. These results also provide an experimental confirmation to the models of dielectrics surface metallization under high electrostatic field.

Do dielectric nanostructures turn metallic in high-electric dc fields?

Three-dimensional dielectric nanostructures have been analyzed using field ion microscopy (FIM) to study the electric dc field penetration inside these structures. The field is proved to be screened within a few nanometers as theoretically calculated taking into account the high-field impact ionization process. Moreover, the strong dc field of the order of 0.1 V/Å at the surface inside a dielectric nanostructure modifies its band structure leading to a strong band gap shrinkage and thus to a strong metal-like optical absorption near the surface. This metal-like behavior was theoretically predicted using first-principle calculations and experimentally proved using laser-assisted atom probe tomography (APT). This work opens up interesting perspectives for the study of the performance of all field-effect nanodevices, such as nanotransistor or super capacitor, and for the understanding of the physical mechanisms of field evaporation of dielectric nanotips in APT.

A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study.

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.

[Bronchial and nonbronchial systemic artery embolization in managing haemoptysis: 31 years of experience]. / Embolizzaione delle arterie bronchiali e/o sistemiche non bronchiali nel controllo dell'emottisi: 31 anni d'esperienza.

PURPOSE: The authors report on 31 years of experience with bronchial (BAE) and/or nonbronchial (NBAE) systemic artery embolisation for managing haemoptysis. MATERIALS AND METHODS: A total of 534 patients who underwent bronchial artery angiography for haemoptysis between 1979 and 2010 were retrospectively evaluated. Of these patients, 477 (89%) had active bleeding and underwent BAE and/or NBAE (295 males and 182 females, aged between 12 and 71 years). Embolisation techniques, materials, major and minor complications and relapses were recorded. RESULTS: Complete resolution of haemoptysis was achieved within 24 h in 458/477 (96%) cases and within 48 h in 2% of cases. The aetiology of haemoptysis was as follows: cystic fibrosis (23%), bronchiectasis (13%), tuberculosis sequelae (8%), chronic obstructive pulmonary disease (COPD) (6%) and no apparent cause (21%). Major complications were recorded in 3/477 (0.6%): stroke (n=1), transient ischaemic attack (TIA) (n=1) and transient quadriplegia (n=1). Minor complications were recorded in 143/477 (30%): chest pain 86/143 (60%) and dysphagia 29/143 (20%). During a mean follow-up period of 14 (8-36) months, haemoptysis recurrence was observed in 42/110 cases (38%) of cystic fibrosis and in 77/367 cases of other diseases (21%). CONCLUSIONS: BAE and NBAE are effective and safe for acute treatment of haemoptysis, with low recurrence and complication rates. Interventional radiologist experience is crucial to the successful haemoptysis control and preventing complications.

Bright and ultrafast electron point source made of LaB6 nanotip.

The development of time-resolved transmission electron microscopy (TEM), ultrafast electron spectroscopy and pulsed X-ray sources relies on the realization of stable and high brightness sources of ultra-short electron bunches with a long service time. The flat photocathodes implanted in thermionic electron guns have been replaced by Schottky-type or cold-field emission sources driven by ultra-fast laser. Recently, lanthanum hexaboride (LaB6) nanoneedles have been reported to have high brightness and high emission stability when working in a continuous emission mode. Here, we prepare nano-field emitters from bulk LaB6 and we report on their use as ultra-fast electron sources. Using a high repetition rate laser in the infrared range, we present different field emission regimes as a function of the extraction voltage and laser intensity. The properties of the electron source (brightness, stability, energy spectrum and emission pattern) are determined for the different regimes. Our results show that LaB6 nanoneedles can be used as ultrafast and ultra-bright sources for time-resolved TEM, with better performances as compared to metallic ultra-fast field-emitters.

Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: stat6 is probably not required for the effect of IL-4.

Although much is known about the activation, proliferation, and function of CD4(+) T cells, little is known about how they survive as resting T cells in animals. Resting T cells have a half-life in animals of more than a week; however, when they are removed from animals and placed in tissue culture their half-life falls to approximately 24 h. In this paper, we show that the survival of resting T cells in vitro is promoted by two cytokines, interleukins 4 and 7 (IL-4, IL-7). They may do this in part by maintaining levels of survival-promoting proteins such as Bcl-2 in the cells, because the levels of Bcl-2 and Bcl-Xl in resting T cells fall rapidly after the cells are isolated from animals, and are maintained by culture in IL-4. Because the IL-4 receptor is known to signal through the JAK1 and JAK3/Stat6 pathway, we tested whether Stat6 was required for IL-4- dependent T cell survival. Surprisingly, we found that IL-4 rescued T cells from apoptosis in what appeared to be a Stat6-independent manner. These results demonstrate that the survival of resting T cells is an active process that can be affected by signals delivered by cytokines and also suggest that the IL-4 receptor on resting T cells may use a novel signaling pathway to facilitate T cell viability.

A photonic atom probe coupling 3D atomic scale analysis with in situ photoluminescence spectroscopy.

Laser enhanced field evaporation of surface atoms in laser-assisted Atom Probe Tomography (APT) can simultaneously excite photoluminescence in semiconductor or insulating specimens. An atom probe equipped with appropriate focalization and collection optics has been coupled with an in situ micro-photoluminescence (µPL) bench that can be operated during APT analysis. The photonic atom probe instrument we have developed operates at frequencies up to 500 kHz and is controlled by 150 fs laser pulses tunable in energy in a large spectral range (spanning from deep UV to near IR). Micro-PL spectroscopy is performed using a 320 mm focal length spectrometer equipped with a CCD camera for time-integrated and with a streak camera for time-resolved acquisitions. An example of application of this instrument on a multi-quantum well oxide heterostructure sample illustrates the potential of this new generation of tomographic atom probes.

Prospective multicentre study on azole resistance in Aspergillus isolates from surveillance cultures in haematological patients in Italy.

OBJECTIVES: This study was conducted to assess the prevalence of azole resistance in Aspergillus isolates from patients with haematological malignancies or who were undergoing haematopoietic stem cell transplantation and to identify the molecular mechanism of resistance. METHODS: In this 28-month prospective study involving 18 Italian centres, Aspergillus isolates from surveillance cultures were collected and screened for azole resistance, and mutations in the cyp51A gene were identified. Resistant isolates were genotyped by microsatellite analysis, and the allelic profiles were compared with those of resistant environmental and clinical isolates from the same geographical area that had been previously genotyped. RESULTS: There were 292 Aspergillus isolates collected from 228 patients. The isolates belonged mainly to the section Fumigati (45.9%), Nigri (20.9%), Flavi (16.8%) and Terrei (4.8%). Three isolates showed itraconazole resistance: Aspergillus fumigatus sensu stricto, Aspergillus lentulus (section Fumigati) and Aspergillus awamori (section Nigri). The itraconazole resistance rates were 1% and 1.48% considering all Aspergillus spp. isolates and the Aspergillus section Fumigati, respectively. The prevalence of azole resistance among all the patients was 1.3%. Among patients harbouring A. fumigatus sensu stricto isolates, the resistance rate was 0.79%. The A. fumigatus isolate, with the TR34/L98H mutation, was genotypically distant from the environmental and clinical strains previously genotyped. CONCLUSIONS: In this study, the Aspergillus azole resistance rate was 1% (3/292). In addition to A. fumigatus sensu stricto, A. lentulus and A. awamori azole-resistant isolates were identified. Therefore, it is important have a correct identification at the species level to address a rapid therapy better, quickly understand the shift towards cryptic species and have an updated knowledge of the local epidemiology.

Photoassisted and multiphoton emission from single-crystal diamond needles.

Practical realization of stable and high brightness sources of ultra-short electron pulses is an important issue in the development of time-resolved electron microscopy for the study of ultra-fast dynamics in materials. Here, we report on the experimental investigation of static (in the dark) and pulsed (under illumination by sub-picosecond laser pulses at 1040 nm) electron emission from single-crystal diamond needles. A significant increase of electron emission current was detected under laser illumination. The nonlinear dependence of the emission current on the laser intensity and on the angle between the needle and the laser beam polarization axis suggests multi-photon emission processes. This interpretation is in agreement with electron spectroscopy measurements performed for electrons emitted at different bias voltages and different laser power levels and repetition rates. The remarkable feature of the diamond emitters is their stability under high average power of laser radiation. This provides a new highly efficient source of photoemitted electrons based on single-crystal diamond.

Integrated Care Models for Managing and Preventing Frailty: A Systematic Review for the European Joint Action on Frailty Prevention (ADVANTAGE JA).

Frailty requires concerted integrated approaches to prevent functional decline. Although there is evidence that integrating care is effective for older people, there is insufficient data on outcomes from studies implementing integrated care to prevent and manage frailty. We systematically searched PubMed and Cochrane Library database for peer-reviewed medical literature on models of care for frailty, published from 2002 to 2017. We considered the effective and transferable components of the models of care and evidence of economic impact, where available. Information on European Union-funded projects or those registered with the European Innovation Partnership on Active and Healthy Ageing, and grey literature (including good practices) were also considered. We found 1,065 potential citations and 170 relevant abstracts. After excluding reports on specific diseases, processes or interventions and service models that did not report data, 42 full papers met the inclusion criteria. The evidence showed that few models of integrated care were specifically designed to prevent and tackle frailty in the community and at the interface between primary and secondary (hospital) care. Current evidence supports the case for a more holistic and salutogenic response to frailty, blending a chronic care approach with education, enablement and rehabilitation to optimise function, particularly at times of a sudden deterioration in health, or when transitioning between home, hospital or care home. In all care settings, these approaches should be supported by comprehensive assessment and multidimensional interventions tailored to modifiable physical, psychological, cognitive and social factors.

Laser-assisted atom probe tomography of semiconductors: The impact of the focused-ion beam specimen preparation.

This paper demonstrates the increased light absorption efficiency of semiconducting atom probe tips resulting from focused-ion-beam (FIB) preparation. We use transmission electron microscopy to show that semiconducting tips prepared with FIB are surrounded with an amorphized shell. Photomodulated optical reflectance measurements then provide evidence that FIB-induced damage leads to an increase in both sub- and supra-bandgap light absorption efficiency. Using laser-assisted atom probe tomography (La-APT) measurements, we finally show that, for a nanoscale tip geometry, the laser-induced heating of a tip during La-APT is enhanced by the FIB preparation. We conclude that, upon supra-bandgap illumination, the presence of a FIB-amorphized surface dramatically increases the light-induced heat generation inside semiconducting tips during La-APT. Furthermore, we also deduce that, in the intriguing case of sub-bandgap illumination, the amorphization plays a crucial role in the unexpected light absorption.

Microbiologic and clinical characteristics of biofilm-forming Candida parapsilosis isolates associated with fungaemia and their impact on mortality.

OBJECTIVES: Biofilm formation (BF) by fungal isolates may dramatically complicate infection. We determined the ability of Candida parapsilosis isolates from single fungaemia episodes to form biofilms and we analysed biofilm subgroups for antifungal susceptibility and pathogenic potential. We then correlated BF with clinical characteristics and outcomes of the episodes. METHODS: BF was measured using the crystal violet biomass assay. Antifungal susceptibility of preformed biofilms was assessed, and virulence was studied using the Galleria mellonella model. A retrospective analysis of patients' clinical records was performed. RESULTS: Of 190 patient-unique isolates, 84, 38 and 68 were identified as having high BF (HBF), moderate BF (MBF) or low BF (LBF), respectively. Among 30 randomly selected isolates, nine (eight HBF and one MBF), six (all HBF) and one (HBF) isolates had elevated sessile minimum inhibitory concentrations to fluconazole, anidulafungin or amphotericin B; all HBF and MBF isolates had elevated voriconazole sessile minimum inhibitory concentrations. G. mellonella killing rates of HBF isolates were significantly greater than MBF (or LBF) isolates (50% vs. 20%, 2 days from infection). By comparing HBF/MBF (106 patients) and LBF (84 patients) groups, we found that HBF/MBF patients had more central venous catheter-related fungaemias (62/106 (58.5%) vs. 29/84 (34.5%), p 0.001) and were more likely to die at 30 days from fungaemia onset (61/106 (57.5%) vs. 28/84 (33.3%), p 0.01). In the HBF/MBF group, azole antifungal therapy and central venous catheter removal were significantly associated with a higher and lower 30-day mortality rate, respectively. CONCLUSIONS: C. parapsilosis BF influences the clinical outcome in patients with fungaemia.

Safety and efficacy of pasireotide in dumping syndrome-results from a phase 2, multicentre study.

BACKGROUND: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. AIM: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. METHODS: A single-arm, open-label, multicentre, intrapatient dose-escalation, phase 2 study with 4 phases: screening, 3-month SC (subcutaneous), 3-month IM (intramuscular) and 6-month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3-month SC phase. A ≥50% response rate was considered clinically relevant. RESULTS: Forty-three patients with late dumping were enrolled; 33 completed the 3-month SC phase and 23 completed the 12-month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%-75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0-12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). CONCLUSION: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.

Femtosecond field ion emission by surface optical rectification.

We show that a model based on the surface optical rectification effect associated with the nonlinear response of free electrons may explain quantitatively, without adjustable parameters, all the observed features of the ultrafast laser-assisted field-ion emission from metal tips. Moreover, the same model provides also a plausible explanation for the low-fluence ultrafast laser ablation recently observed in metal surfaces and nanoparticles. We further test our model with experiments of ultrafast laser-assisted field-ion emission from tungsten tips in the tomographic atom probe.

Optical and thermal processes involved in ultrafast laser pulse interaction with a field emitter.

In the interaction between ultrafast laser pulses and a field emitter both optical and thermal processes are involved. In this paper, these physical process, and their timescales, are experimentally explored. Simple models are proposed to explain the observed experimental behaviour, and the influence of various parameters are investigated. In the case of optical processes, it is shown that the optical field is greatly enhanced at the tip apex, and that field evaporation could be induced by an optical non-linear effect called optical rectification. In the case of thermal processes, it is shown that the temperature rise because of light absorption can be determined and that the cooling process of the tip surface can be studied by pump probe measurements.

Some aspects of the silicon behaviour under femtosecond pulsed laser field evaporation.

Three dimension atom probe analysis of semiconductor materials requires the ability to bring high electric field at the specimen apex to remove atoms. It is shown that, if voltage pulses are used to evaporate doped silicon, the resistivity of the material has to be lower than about 10(2) Omega cm. To overcome this problem, voltage pulses have been replaced by femtosecond laser pulses. The laser pulses give rise to field evaporation by two processes. Both thermal and optical field evaporation have been observed. Thermal evaporation takes place at high laser intensities and with short wavelengths while the evaporation is assisted by the rectification of the optical field for lower intensities and in the infrared domain. Using the optical field evaporation, reproducible and good analyses in term of spatial and mass resolutions could be conducted.

Nonlinear dynamics induced in liquid crystals in the presence of the orbital and spin angular momentum of light.

We studied the dynamical effects induced in a homeotropic nematic film when a normally incident circularly polarized light beam with an elliptical intensity profile is used. A three-dimensional dynamical model shows that, besides the spin, the orbital angular momentum of photons also plays a role in the reorientation process. Our measurements fairly reproduce the main dynamical features predicted by the model in the near threshold region. The model, however, does not work, as it is, at higher incident laser power where chaotic director rotation was reported [A. Vella, A. Setaro, B. Piccirillo, E. Santamato, Phys. Rev. E 67, 051704 (2003)].