Dispersion of the surface phonons in semiconductor/topological insulator Si/Bi2Te3 heterostructure studied by high resolution Brillouin spectroscopy.

The dynamics and dispersion of surface phonons in heterostructure semiconductor/ topological insulator Si/Bi2Te3 was investigated using high resolution Brillouin light scattering method in the GHz frequency range. Both Rayleigh and Sezawa surface acoustic waves have been observed for wave vectors ranging from 0.006 to 0.023 nm-1. Anomaly in dispersion relations ω(q) for both surface waves were detected for the wave vector q = 0.016 nm-1. The finite element method (FEM) was used to simulate the observed shapes of ω(q) and to find the deformation profiles of surface acoustic waves. We attribute the observed changes to the coupling between low energy electrons and surface phonons. The coupling between helical Dirac states and surface phonons is discussed in the frame of accessible theoretical models.

Underprescription of medications in older adults: causes, consequences and solutions-a narrative review.

PURPOSE: Under-prescription is defined as the omission of a medication that is indicated for the treatment of a condition or a disease, without any valid reason for not prescribing it. The aim of this review is to provide an updated overview of under-prescription, summarizing the available evidence concerning its prevalence, causes, consequences and potential interventions to reduce it. METHODS: A PubMed search was performed, using the following keywords: under-prescription; under-treatment; prescribing omission; older adults; polypharmacy; cardiovascular drugs; osteoporosis; anticoagulant. The list of articles was evaluated by two authors who selected the most relevant of them. The reference lists of retrieved articles were screened for additional pertinent studies. RESULTS: Although several pharmacological therapies are safe and effective in older patients, under-prescription remains widespread in the older population, with a prevalence ranging from 22 to 70%. Several drugs are underused, including cardiovascular, oral anticoagulant and anti-osteoporotic drugs. Many factors are associated with under-prescription, e.g. multi-morbidity, polypharmacy, dementia, frailty, risk of adverse drug events, absence of specific clinical trials in older patients and economic factors. Under-prescription is associated with negative consequences, such as higher risk of cardiovascular events, worsening disability, hospitalization and death. The implementation of explicit criteria for under-prescription, the use of the comprehensive geriatric assessment by geriatricians, and the involvement of a clinical pharmacist seem to be promising options to reduce under-prescription. CONCLUSION: Under-prescription remains widespread in the older population. Further studies should be performed, to provide a better comprehension of this phenomenon and to confirm the efficacy of corrective interventions.

Correlation analysis of vibration modes in physical vapour deposited Bi2Se3 thin films probed by the Raman mapping technique.

In this work, the Raman spectroscopy mapping technique is used for the analysis of mechanical strain in Bi2Se3 thin films of various (3-400 nm) thicknesses synthesized by physical vapour deposition on amorphous quartz and single-layer graphene substrates. The evaluation of strain effects is based on the correlation analysis of in-plane (E2 g) and out-of-plane (A2 1g) Raman mode positions. For Bi2Se3 films deposited on quartz, experimental datapoints are scattered along the line with a slope of ∼0.85, related to the distribution of hydrostatic strain. In contrast to quartz/Bi2Se3 samples, for graphene/Bi2Se3 heterostructures with the same thicknesses, an additional negative slope of ∼-0.85, which can be associated with the distribution of the in-plane (a-b) biaxial tensile strain due to the film-substrate lattice mismatch, is observed. The algorithm of phonon deformation potential (PDP) calculation based on the proposed strain analysis for the 3 nm thick Bi2Se3 film deposited on the graphene substrate, where the strain is considered to be coherent across the thickness, is demonstrated. The PDPs for biaxial in-plane strain of the Bi2Se3 3 nm film in in-plane and out-of-plane modes are equal to -7.64 cm-1/% and -6.97 cm-1/%, respectively.

Transmitted drug resistance to NRTIs and risk of virological failure in naïve patients treated with integrase inhibitors.

OBJECTIVES: Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first-line integrase strand transfer inhibitor (InSTI)-based regimens. METHODS: Patients starting two NRTIs (lamivudine/emtricitabine plus abacavir/tenofovir) plus raltegravir or dolutegravir were selected from the EuResist cohort. The role of NRTI genotypic susceptibility score and of specific TDRMs in VF (i.e. two consecutive viral loads > 50 HIV-1 RNA copies/mL or a single viral load ≥ 200 copies/mL after 3 months from antiretroviral therapy start) was evaluated in the overall population and according to the InSTI employed. RESULTS: From 2008 to 2017, 1095 patients were eligible for the analysis (55.5% men, median age 39 years). In all, 207 VFs occurred over 1023 patient-years of follow-up. The genotypic susceptibility score (GSS) had no effect on the risk of VF in the overall population. However, the presence of M184V/I independently predicted VF of raltegravir- but not dolutegravir-based therapy when compared with a fully-active backbone [adjusted hazard ratio (aHR) = 3.09, P = 0.035], particularly when associated with other non-thymidine analogue mutations (aHR = 27.62, P = 0.004). Higher-zenith HIV-RNA and lower nadir CD4 counts independently predicted VF. CONCLUSIONS: NRTI backbone TDRMs increased the risk of VF with raltegravir-based but not dolutegravir-based regimens.

Dynamical charge density fluctuations pervading the phase diagram of a Cu-based high-T c superconductor.

Charge density modulations have been observed in all families of high-critical temperature (T c) superconducting cuprates. Although they are consistently found in the underdoped region of the phase diagram and at relatively low temperatures, it is still unclear to what extent they influence the unusual properties of these systems. Using resonant x-ray scattering, we carefully determined the temperature dependence of charge density modulations in YBa2Cu3O7-δ and Nd1+ x Ba2- x Cu3O7-δ for several doping levels. We isolated short-range dynamical charge density fluctuations in addition to the previously known quasi-critical charge density waves. They persist up to well above the pseudogap temperature T*, are characterized by energies of a few milli-electron volts, and pervade a large area of the phase diagram.

Low temperature hidden Fermi-liquid charge transport in under doped La x Sr1-x CuO2 infinite layer electron-doped thin films.

We have studied the low temperature electrical transport properties of La x Sr1-x CuO2 thin films grown by oxide molecular beam epitaxy on (1 1 0) GdScO3 and TbScO3 substrates. The transmission electron microscopy measurements and the x-ray diffraction analysis confirmed the epitaxy of the obtained films and the study of their normal state transport properties, removing the ambiguity regarding the truly conducting layer, allowed to highlight the presence of a robust hidden Fermi liquid charge transport in the low temperature properties of infinite layer electron doped cuprate superconductors. These results are in agreement with recent observations performed in other p  and n doped cuprate materials and point toward a general description of the superconducting and normal state properties in these compounds.

Lamivudine-based maintenance antiretroviral therapies in patients living with HIV-1 with suppressed HIV RNA: derivation of a predictive score for virological failure.

OBJECTIVES: Two-drug antiretroviral regimens based on lamivudine (3TC) plus either a protease inhibitor (PI) or dolutegravir (DTG) are becoming increasingly popular in switch strategies. Our goal was to derive a predictive score for virological failure (VF). METHODS: We retrospectively analysed data for a cohort of 587 virologically suppressed (HIV RNA < 37 HIV-1 RNA copies/mL), adult (≥ 18 years old) patients starting lamivudine plus either a boosted PI or dolutegravir. Predictors of VF (defined as a single HIV RNA measurement ≥ 1000 copies/mL or two consecutive HIV RNA measurements ≥ 50 copies/mL) were identified using a multivariate Cox regression model. A 'weighted' score was assigned to each variable associated with VF; the discriminative power of the score obtained was expressed as the area under the receiver-operator characteristic curve (ROC-AUC). RESULTS: During a median 2 years of follow-up time, 35 VFs occurred; predictors of VF were baseline residual HIV RNA between 20 and 36 copies/mL, African ethnicity, ≥ 10 therapeutic lines, the presence of at least one resistance-associated mutation (RAM) for resistance to current drugs (excluding M184V), a non-B viral subtype and a baseline CD4 count < 200 cells/µL. A score of 2 was assigned to non-B viral subtype, 3 to residual viraemia ≥ 20 copies/mL, ≥ 10 previous therapeutic lines and African ethnicity, 4 to baseline CD4 count < 200 cells/µL, and 7 to the presence of at least one RAM (excluding M184V). The ROC-AUC was 0.67 (95% confidence interval 0.57-0.77). CONCLUSIONS: The presence of at least one RAM, higher residual viraemia and African ethnicity were among the major predictors of VF in our cohort. Studies with larger sample sizes are warranted to improve the predictive value of the derived score.

Trends of hospitalisations rates in a cohort of HIV-infected persons followed in an Italian hospital from 1998 to 2016.

Here we evaluated hospitalisation rates and associated risk factors of human immunodeficiency virus (HIV)-infected individuals who were followed up in an Italian reference hospital from 1998 to 2016. Incidence rates (IR) of hospitalisations were calculated for five study periods from 1998 to 2016. The random-effects Poisson regression model was used to assess risk factors for hospitalisation including demographic and clinical characteristics. To consider that more events may occur for the same subject, multiple failure-time data analysis was also performed for selected causes using the Cox proportional hazards model. We evaluated 2031 patients. During 13 173 person-years (py) of follow-up, 3356 hospital admissions were carried out for 756 patients (IR: 255 per 1000 py). IR decreased significantly over the study period, from 634 in 1998-2000 to 126 per 1000 py in 2013-2016. Major declines were detected for AIDS-defining events, non-HIV/AIDS-related infections and neurological diseases. Older age, female sex, longer HIV duration and HCV coinfection were associated with a higher hospitalisation risk, whereas higher CD4 nadir and antiretroviral therapy were associated with a reduced risk. Influence of advanced HIV disease markers declined over time. Hospitalisation rates decreased during the study period in most causes. The relative weight of hospitalisations for non-AIDS-related tumours, cardiovascular, respiratory and kidney diseases increased during the study period, whereas those for AIDS-defining events declined.

Evidence-Based Medicine and Clinical Practice: the first Italian attempt to define the appropriateness of rehabilitation admission criteria through the application of the Delphi method.

BACKGROUND: One of the consequences of today's global economic crisis is the need to control healthcare spending, in particular by improving the level of appropriateness. Thus, admission to rehabilitation has become an issue, especially as regards inappropriateness of resource allocation. The scientific literature suggests that more attention should be paid to the problem of clinical appropriateness in order to better identify the patients' actual needs. For the first time in Italy, this study aims at defining the appropriateness of intensive rehabilitation admission criteria through use of the Delphi method involving a panel of national experts. MATERIAL AND METHODS: A three-round Delphi survey was conducted according to international guidelines. Electronic questionnaires were individually sent via e-mail to ensure the participants' anonymity throughout the process. Questions were mostly based on rehabilitation literature. RESULTS: During the Delphi process, a total of 79 items were submitted to a heterogenous panel of rehabilitation experts who were asked to express their level of agreement to the item contents on a five-point Likert scale. At the end of the survey, a list of 19 appropriate criteria for admission to intensive rehabilitation facilities and 21 reasons for inappropriateness was drawn up. CONCLUSION: This study represents the first attempt in Italy to define shared and objective appropriateness criteria for admission to intensive rehabilitation. Out of the total number of experts invited to participate (31), only 16 completed the entire survey. This poor participation rate unfortunately demonstrates the lack of awareness among Italian rehabilitation professionals, which is a further sign of both the scarcity of scientific evidence in this area and the need to reach consensus on admission criteria.

Prevalence and determinants of resistance mutations in HIV-1-infected patients exposed to integrase inhibitors in a large Italian cohort.

OBJECTIVES: The aim of the study was to analyse the prevalence of integrase resistance mutations in integrase strand transfer inhibitor (INSTI)-experienced HIV-1-infected patients and its predictors. METHODS: We selected HIV-1 integrase sequences from the Antiviral Response Cohort Analysis (ARCA) database, derived from INSTI-experienced patients between 2008 and 2017. Differences in the prevalence of resistance to raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG) were assessed by χ2 test and predictors of resistance were analysed by logistic regression. RESULTS: We included 462 genotypes from INSTI-exposed individuals: 356 'INSTI-failing' patients and 106 'previously INSTI-exposed' patients (obtained a median of 42 weeks after INSTI discontinuation [interquartile range (IQR) 17-110 weeks]). Overall, at least low-level resistance (LLR) to any INSTI (Stanford 8.5 algorithm) was detected in 198 (42.9%) cases. The most frequent INSTI resistance mutation was N155H, followed by Q148H/K/R, G140A/C/S, E138A/K/T and Y143C/H/R. Y143R and E138A were more prevalent in viral subtype B versus non-B [5.2 versus 1.5%, respectively (P = 0.04), and 3.1 versus 0%, respectively (P = 0.02)]. Overall, the Q148H/K/R plus G140A/C/S and/or E138A/K/T pattern, defining an intermediate level of resistance to DTG, was detected in 70 (15%) cases. Independent predictors of at least LLR to any INSTI were current use versus past use of INSTIs, a lower genotypic sensitivity score (GSS) for contemporary antiretroviral drugs used, and having an integrase sequence obtained in calendar year 2016 as compared to 2008-2009. CONCLUSIONS: The results support integrase resistance testing in INSTI-experienced patients. Emergence of INSTI resistance is facilitated by the reduced genetic barrier of the regimen as a consequence of resistance to companion drugs. However, INSTI resistance may become undetectable by standard population sequencing upon INSTI discontinuation.

SLC22A2 variants and dolutegravir levels correlate with psychiatric symptoms in persons with HIV.

BACKGROUND: Neuropsychiatric symptoms (NPs) have been reported with dolutegravir use. We hypothesized that increasing dolutegravir trough concentrations (Ctrough) and/or polymorphism in the SLC22A2 gene, encoding the organic cation transporter-2 (OCT2), which is involved in monoamine clearance in the CNS and is inhibited by dolutegravir, might be associated with NPs. METHODS: A cross-sectional cohort of HIV-positive patients treated with a dolutegravir-containing regimen underwent determination of allelic discrimination for SLC22A2 808 C → A polymorphism and dolutegravir Ctrough. The Symptom Checklist-90-R [investigating 10 psychiatric dimensions and reporting a general severity index (GSI)], a self-reported questionnaire and the Mini-International Neuropsychiatric Interview were offered to investigate current NPs. The effects of dolutegravir Ctrough and the SLC22A2 gene variant on NPs were explored by multivariable logistic regression. RESULTS: A cohort of 203 patients was analysed: 71.4% were male, with median age 51 years and 11 years of ART exposure. Median time on dolutegravir was 18 months. Dolutegravir was associated with different antiretroviral combinations (mainly lamivudine, 38.9%, and abacavir/lamivudine, 35.5%). SLC22A2 CA genotype was independently associated with an abnormal GSI [adjusted OR (aOR) 2.43; P = 0.072], anxiety (aOR 2.61; P = 0.044), hostility (aOR 3.76; P = 0.012) and with moderate to severe headache (aOR 5.55; P = 0.037), and dolutegravir Ctrough was associated with hostility (fourth versus first quartile aOR 6.70; P = 0.007) and psychoticism (fourth versus first quartile aOR 19.01; P = 0.008). Other NPs were not associated with SLC22A2 polymorphism or dolutegravir Ctrough. CONCLUSIONS: A variant of the OCT2-encoding gene, in addition to or in synergy with higher dolutegravir Ctrough, is associated with a set of NPs observed during dolutegravir therapy.

N-terminal pro B-Type natriuretic peptide is inversely correlated with low density lipoprotein cholesterol in the very elderly.

BACKGROUND AND AIMS: Laboratory studies on human adipose tissue and differentiated adipocytes indicate that natriuretic peptides (NPs) affect lipid metabolism and plasma cholesterol. Few previous clinical studies in non-elderly populations found associations between NPs in the physiological range and cholesterol. AIM: evaluate the association between NT-proBNP and lipid profile in very elderly hospitalized patients characterized by a wide range of NT-proBNP levels. METHODS AND RESULTS: Cross-sectional study on 288 very elderly patients hospitalized for medical conditions, in which increased NT-proBNP levels are very common. NT-proBNP, total cholesterol (TC), HDL cholesterol (HDLc) and triglycerides were collected just few days before discharge. Patients taking lipid-lowering drugs and patients with an admission diagnosis of acute heart failure were excluded. Calculated LDL-cholesterol (LDLc) was used for the analyses. Mean age: 87.7 ± 6.2 years; female prevalence (57.3%). Median NT-proBNP: 2949 (1005-7335) pg/ml; mean TC: 145.1 ± 40.3 mg/dl; mean HDLc: 38.4 ± 18.6 mg/dl; median triglycerides: 100 (75-129) mg/dl; mean LDLc: 84.0 ± 29.5 mg/dl. We found negative correlations between NT-proBNP and both TC and LDLc (Rho = -0.157; p = 0.008 and Rho = -0.166; p = 0.005, respectively), while no correlations emerged between NT-proBNP and HDLc (Rho = -0.065; p = 0.275) or triglycerides (Rho = -0.009; p = 0.874). These associations were confirmed considering NT-proBNP tertiles. The inverse association between NT-proBNP and LDLc was maintained even after adjusting for confounding factors. CONCLUSION: Our real-life clinical study supports the hypothesis that NPs play a role on cholesterol metabolism, given the association found between LDLc and NT-proBNP even in very elderly patients where NT-proBNP values are often in the pathological range.

Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicentre cohort of patients with suppressed HIV-1 replication.

OBJECTIVES: We evaluated the efficacy and tolerability of lamivudine + dolutegravir in a cohort of HIV-1 infected, treatment-experienced patients with undetectable HIV-RNA. METHODS: Time to treatment discontinuation (TD) and virological failure (VF) and their predictors were assessed in a multicenter cohort of HIV-1 infected patients, starting lamivudine + dolutegravir after reaching viral suppression. Secondary objective was the evaluation of changes in lipid profile, renal and immunological functions at week 48. RESULTS: We enrolled 206 patients (72.8% male, with 51 years median age), who mainly switched their antiretroviral therapy for simplification (32.5%) or drug toxicity (54.5%). The estimated probability of maintaining virological suppression at 48 and 96 weeks was 98.2% and 95.1%, respectively. VF was independently predicted by cumulative time on antiretroviral therapy. The estimated probability of remaining on lamivudine plus dolutegravir was 86.7% and 80.5% at week 48 and 96, respectively. A significant improvement in immunological function (CD4 count and CD4/CD8 ratio) was evidenced at week 48, as well as a decrease in total cholesterol/HDL ratio, triglycerides and estimated glomerular filtration rate. CONCLUSIONS: Lamivudine plus dolutegravir was effective in maintaining viral suppression in our cohort and led to an improvement in metabolic and immunologic functions.

An outbreak of acute hepatitis A among young adult men: clinical features and HIV coinfection rate from a large teaching hospital in Rome, Italy.

OBJECTIVES: Italy is a low-incidence region for hepatitis A; however, during the last 2 years an increase in the incidence of hepatitis A virus (HAV) infection was reported in Europe. The aim of this study was to describe this recent outbreak. METHODS: We retrospectively analysed all cases of acute hepatitis A diagnosed at our laboratory between January 2010 and June 2017. We evaluated the following variables at the time of diagnosis: sex, age, nationality, glutamic oxaloacetic transaminase (GOT/AST), glutamic pyruvic transaminase (GPT/ALT), bilirubin concentration, international normalized ratio (INR) and the presence or absence of anti-HIV-1/2 antibodies. Hospitalization was also considered. We analysed these parameters using the χ2 test and Mann-Whitney U-test. RESULTS: A total of 225 cases were analysed; 82.7% were in male patients, 94.2% were in Italians and the median age of the patients was 36.4 years. At diagnosis, the median GOT value was 306 U/L, the median GPT was 1389 U/L, and the median total bilirubin value was 5.88 mg/dL. Hospitalization was required for 142 patients, with a median duration of hospital stay of 8.5 days. In 2016-2017 we registered 141 cases, with a higher prevalence of male patients, higher GPT values and a higher prevalence of patients aged 20-39 years compared with older (2010-2015) cases. Homosexual intercourse was reported as the HAV risk factor in 70.2% of patients. HIV serology was available for 120 patients: 24 were HIV-positive, four of whom represented new diagnoses. HIV-positive patients showed lower bilirubin and GPT values and fewer hospitalizations than HIV-negative patients. CONCLUSIONS: In 2016-2017, we saw a rise in the number of hepatitis A cases, with a higher prevalence of adult male patients. No significant differences regarding the prevalence of HIV coinfection emerged.

The electron-phonon interaction at deep Bi 2 Te3-semiconductor interfaces from Brillouin light scattering.

It is shown that the electron-phonon interaction at a conducting interface between a topological insulator thin film and a semiconductor substrate can be directly probed by means of high-resolution Brillouin light scattering (BLS). The observation of Kohn anomalies in the surface phonon dispersion curves of a 50 nm thick Bi2Te3 film on GaAs, besides demonstrating important electron-phonon coupling effects in the GHz frequency domain, shows that information on deep interface electrons can be obtained by tuning the penetration depth of optically-generated surface phonons so as to selectively probe the interface region, as in a sort of quantum sonar.

NbN superconducting nanonetwork fabricated using porous silicon templates and high-resolution electron beam lithography.

Superconducting NbN nanonetworks with a very small number of interconnected nanowires, with diameter of the order of 4 nm, are fabricated combining a bottom-up (use of porous silicon nanotemplates) with a top-down technique (high-resolution electron beam lithography). The method is easy to control and allows the fabrication of devices, on a robust support, with electrical properties close to a one-dimensional superconductor that can be used fruitfully for novel applications.

Balance of excitation and inhibition determines 1/f power spectrum in neuronal networks.

The 1/f-like decay observed in the power spectrum of electro-physiological signals, along with scale-free statistics of the so-called neuronal avalanches, constitutes evidence of criticality in neuronal systems. Recent in vitro studies have shown that avalanche dynamics at criticality corresponds to some specific balance of excitation and inhibition, thus suggesting that this is a basic feature of the critical state of neuronal networks. In particular, a lack of inhibition significantly alters the temporal structure of the spontaneous avalanche activity and leads to an anomalous abundance of large avalanches. Here, we study the relationship between network inhibition and the scaling exponent ß of the power spectral density (PSD) of avalanche activity in a neuronal network model inspired in Self-Organized Criticality. We find that this scaling exponent depends on the percentage of inhibitory synapses and tends to the value ß = 1 for a percentage of about 30%. More specifically, ß is close to 2, namely, Brownian noise, for purely excitatory networks and decreases towards values in the interval [1, 1.4] as the percentage of inhibitory synapses ranges between 20% and 30%, in agreement with experimental findings. These results indicate that the level of inhibition affects the frequency spectrum of resting brain activity and suggest the analysis of the PSD scaling behavior as a possible tool to study pathological conditions.

Temporal correlations in neuronal avalanche occurrence.

Ongoing cortical activity consists of sequences of synchronized bursts, named neuronal avalanches, whose size and duration are power law distributed. These features have been observed in a variety of systems and conditions, at all spatial scales, supporting scale invariance, universality and therefore criticality. However, the mechanisms leading to burst triggering, as well as the relationship between bursts and quiescence, are still unclear. The analysis of temporal correlations constitutes a major step towards a deeper understanding of burst dynamics. Here, we investigate the relation between avalanche sizes and quiet times, as well as between sizes of consecutive avalanches recorded in cortex slice cultures. We show that quiet times depend on the size of preceding avalanches and, at the same time, influence the size of the following one. Moreover we evidence that sizes of consecutive avalanches are correlated. In particular, we show that an avalanche tends to be larger or smaller than the following one for short or long time separation, respectively. Our analysis represents the first attempt to provide a quantitative estimate of correlations between activity and quiescence in the framework of neuronal avalanches and will help to enlighten the mechanisms underlying spontaneous activity.

Test of Electric Charge Conservation with Borexino.

Borexino is a liquid scintillation detector located deep underground at the Laboratori Nazionali del Gran Sasso (LNGS, Italy). Thanks to the unmatched radio purity of the scintillator, and to the well understood detector response at low energy, a new limit on the stability of the electron for decay into a neutrino and a single monoenergetic photon was obtained. This new bound, τ≥6.6×10^{28} yr at 90% C.L., is 2 orders of magnitude better than the previous limit.