Waveguide integrated hot electron bolometer for classical and quantum photonics.

The development of performant integrated detectors, which are sensitive to quantum fluctuations of coherent light, are strongly desired to realize a scalable and determinist photonic quantum processor based on continuous variables states of light. Here, we investigate the performance of hot electron bolometers (HEBs) fabricated on top of a silicon-on-insulator (SOI) photonic circuit showing responsivities up to 8600 V/W and a record noise equivalent temperature of 1.1 dB above the quantum limit. Thanks to a detailed analysis of the noise sources of the waveguide integrated HEB, we estimate 14.8 dBV clearance between the shot noise and electrical noise with just 1.1µW of local oscillator power. The full technology compatibility with superconducting nanowire single photon detectors (SNSPDs) opens the possibility of nonclassical state engineering and state tomography performed within the same platform, enabling a new class of optical quantum processors.

Single photon detection with superconducting nanowires on crystalline silicon carbide.

Silicon carbide (SiC) is among the most promising optical materials for the realization of classical and quantum photonics, due to the simultaneous presence of quantum emitters and a non-centrosymmetric crystal structure. In recent years, progress have been made in the development of SiC integrated optical components making this a mature platform for the implementation of quantum experiments on chip. Toward this scope, the fabrication of a single photon detector that can be implemented on top of a photonic circuit is essential to achieve a monolithic integration of all the fundamental building blocks required for photonic quantum technologies. Here we demonstrate for the first time single photon detection with superconducting nanowires on top of a bare 3C SiC layer using a novel approach for the fiber-to-detector coupling that allows the optical characterization of multiple detectors without the use of neither cryogenic positioners nor the micromachining of the substrate.

Clinical experience about an unexpected adverse event during nalmefene treatment in two patients with alcohol use disorder.

WHAT IS KNOWN AND OBJECTIVE: Nalmefene, a new opioid system regulator, has recently been approved for the treatment of alcohol dependence, primarily for reducing heavy drinking days. CASES DESCRIPTION: Two patients with a diagnosis of alcohol use disorder were treated with nalmefene. Both patients developed fatigue and deep sleepiness after 2 days of treatment. Only after 1 day of drug discontinuation, symptoms normalized. WHAT IS NEW AND CONCLUSION: We have analysed symptoms' development before and after treatment discontinuation and the possible association with nalmefene therapy. This case should pinpoint our attention on this adverse event for a careful choice of anticraving therapy in patients with severe alcohol use disorder.

Experimental test of theories of the detection mechanism in a nanowire superconducting single photon detector.

We report an experimental test of the photodetection mechanism in a nanowire superconducting single photon detector. Detector tomography allows us to explore the 0.8-8 eV energy range via multiphoton excitations. High accuracy results enable a detailed comparison of the experimental data with theories for the mechanism of photon detection. We show that the temperature dependence of the efficiency of the superconducting single photon detector is determined not by the critical current but by the current associated with vortex unbinding. We find that both quasiparticle diffusion and vortices play a role in the detection event.

The Rao's Brief Repeatable Battery version B: normative values with age, education and gender corrections in an Italian population.

The Brief Repeatable Battery (BRB) of Neuropsychological Tests is one of the most widely used instruments to assess cognitive functioning in multiple sclerosis patients. However, to date, normative data for the Italian population are available only for the version A, which limits the use of the battery in longitudinal evaluations. We administered the BRB version B to 132 healthy subjects to obtain normative values taking into account the influences of demographic factors on the test scores and calculating corrections for these relevant factors (age, gender and education). Higher age and educational level were associated with better performance on all the tests. The World List Generation was also influenced by gender, since women performed better than men. Moreover, some tests of the version B seem to be easier than those of version A. Our data can improve the applicability of the BRB for both clinical and research purposes in longitudinal assessments.

Modified detector tomography technique applied to a superconducting multiphoton nanodetector.

We present an experimental method to characterize multi-photon detectors with a small overall detection efficiency. We do this by separating the nonlinear action of the multiphoton detection event from linear losses in the detector. Such a characterization is a necessary step for quantum information protocols with single and multiphoton detectors and can provide quantitative information to understand the underlying physics of a given detector. This characterization is applied to a superconducting multiphoton nanodetector, consisting of an NbN nanowire with a bowtie-shaped subwavelength constriction. Depending on the bias current, this detector has regimes with single and multiphoton sensitivity. We present the first full experimental characterization of such a detector.

Heparin-induced acute adverse reaction--case report of a patient with acute trauma and a genetic predisposition to thrombotic events: a concurrence of events.

WHAT IS KNOWN AND OBJECTIVE: The most common complication of heparin therapy is bleeding. Allergic reactions to heparin are rare, and the mechanisms are poorly understood. We report on a case of acute systemic reaction after subcutaneous injections of a low-molecular-weight heparin (LMWH) in a patient with a genetic predisposition to thrombotic events and review the literature on heparin-induced acute adverse reaction. CASE SUMMARY: A 57-year-old diabetic, hypertriglyceridemic and hypercholesterolemic man was admitted with a fractured right malleolus sustained while driving. He was prescribed parnaparin sodium 4250 IU subcutaneously once a day. During the third injection, the patient developed widespread pain, sickness and facial rash, followed by a state of stupor (Glasgow Coma Scale 8) and was hospitalized in Neurological Unit. He was found to be a carrier of two genetic mutations (i.e. prothrombin G20210A and MTHFR mutation) associated with an increased risk of thrombotic events. Discontinuation of parnaparin and supportive care led to a sufficient recovery of the patient to be discharged 6 days after admission. WHAT IS NEW AND CONCLUSION: Treatment for heparin-related hypersensitivity reactions is largely supportive and symptomatic. Clinicians should be aware of these rare but potentially serious adverse events. Prothrombin gene mutations are quite common, and guidelines on anticoagulant therapy for affected patients are needed.

General intellectual impairment in chronic right hemisphere damaged patients with anosognosia: a group study.

The study evaluates the possible relations between cognitive impairment, persisting anosognosia for hemiplegia and peripersonal neglect. Thirty eight chronic right hemisphere stroke patients were divided in three age- and education-matched groups: A (n = 13) patients with left hemiparesis, peripersonal neglect, and anosognosia for hemiplegia; B (n = 12) patients with left hemiparesis and peripersonal neglect, and C (n = 13) patients with left hemiparesis only. We used MMSE and WAIS Verbal IQ and verbal subtests to assess cognitive impairment in patients, in order to avoid a bias due to visuospatial deficit, which is common in patients with neglect. VIQ, Information, Digit Span and Vocabulary WAIS subtests as well as MMSE were found to be significantly lower in group A versus group B. No difference was found in any test between groups B and C, indicating a general worse cognition in patients compared to those without anosognosia for hemiplegia. Patients with anosognosia for hemiplegia also showed larger brain lesions and, more frequently, frontal, parietal, temporal and basal ganglia involvement, particularly if they had low verbal IQ, indicating a relationship between cognitive impairment, persisting anosognosia for hemiplegia and large right hemisphere lesions.

A 1D CNN for high accuracy classification and transfer learning in motor imagery EEG-based brain-computer interface.

Objective.Brain-computer interface (BCI) aims to establish communication paths between the brain processes and external devices. Different methods have been used to extract human intentions from electroencephalography (EEG) recordings. Those based on motor imagery (MI) seem to have a great potential for future applications. These approaches rely on the extraction of EEG distinctive patterns during imagined movements. Techniques able to extract patterns from raw signals represent an important target for BCI as they do not need labor-intensive data pre-processing.Approach.We propose a new approach based on a 10-layer one-dimensional convolution neural network (1D-CNN) to classify five brain states (four MI classes plus a 'baseline' class) using a data augmentation algorithm and a limited number of EEG channels. In addition, we present a transfer learning method used to extract critical features from the EEG group dataset and then to customize the model to the single individual by training its late layers with only 12-min individual-related data.Main results.The model tested with the 'EEG Motor Movement/Imagery Dataset' outperforms the current state-of-the-art models by achieving a99.38%accuracy at the group level. In addition, the transfer learning approach we present achieves an average accuracy of99.46%.Significance.The proposed methods could foster the development of future BCI applications relying on few-channel portable recording devices and individual-based training.

The effect of tracheostomy on swallowing function in open partial horizontal laryngectomies: preliminary experience.

OBJECTIVE: Tracheostomy is required to ensure a safe airway in open partial horizontal laryngectomies. The presence of the tracheostomy tube can contribute to post-operative dysphagia. This study aimed to evaluate the effects of a circumferential tracheostomy technique on swallowing. METHODS: A retrospective study was conducted of patients who underwent open partial horizontal laryngectomies between April 2018 and June 2019. Patients were divided into two groups based on the tracheostomy technique: group 1 had two stitches from the inferior tracheal ring to the skin; group 2 had circumferential fixation of the trachea to the skin. Demographic information, surgical data, post-operative rehabilitation course and complication details were collected and analysed. RESULTS: Twenty-four patients were enrolled. Patients in group 2 had significant improvement in the initial phases of swallowing rehabilitation. CONCLUSION: Tracheostomy with anchorage of the trachea to the skin by circumferential stitches could allow early removal of the tracheal tube, with a better swallowing outcome.

Natalizumab efficacy on cognitive impairment in MS.

We report follow-up data on the efficacy of natalizumab therapy on neuropsychological impairment on an italian MS group of 39 patients at 1 year and of 11 patients at 2 years. Results show a significant reduction in relapse rate, in the number of impaired neuropsychological tests as well as in several single executive function and reasoning tests scores at 1 year. Improvement persisted at 2 years, including also memory and speed processing tasks. These data support the efficacy of natalizumab therapy in all the clinical domains, including cognitive deterioration, in multiple sclerosis patients.

Neuropsychological rehabilitation in adult multiple sclerosis.

Neuropsychological impairment affects 40-65% of multiple sclerosis patients, mainly involving speed in information processing, attention, executive functions and memory. Deterioration occurs over time independently from disability and seems to correlate particularly with magnetic resonance imaging (MRI) atrophy measures. Studies on therapies effective in controlling cognitive impairment are scanty. We found that intensive and specific training of attention, information processing and executive functions is significantly effective in ameliorating both neuropsychological treated functions and in reducing depression. Preliminary functional MRI data suggest that possible neural correlates of this neuropsychological training could be an exercise-induced activation of prefrontal and cingulate cortices.

High efficiency NbN nanowire superconducting single photon detectors fabricated on MgO substrates from a low temperature process.

We demonstrate high-performance nanowire superconducting single photon detectors (SSPDs) on bN thin films grown at a temperature compatible with monolithic integration. NbN films ranging from 150 nm to 3 nm in thickness were deposited by dc magnetron sputtering on MgO substrates at 400 degrees C SSPDs were fabricated on high quality NbN films of different thickness (7 to 3 nm) deposited under optimal conditions. Electrical and optical characterizations were performed on the SSPDs. The highest QE value measured at 4.2K is 20% at 1300 nm.

A case of syryngocystadenoma papilliferum (SCAP) involving middle ear, presenting with otomastoiditis and cerebral abscess.

Syryngocystadenoma papilliferum (SCAP) is an uncommon cutaneous adnexal neoplasm of apocrine gland origin. Until now, fewer than 200 cases have been reported in international literature, of which 12 cases involved the external ear. No cases of SCAP involving the middle ear have been reported. We describe a case of SCAP of external and middle ear, presenting with otomastoiditis and cerebral abscess; this aggressive behavior, never reported for a benign adenoma of the external or middle ear, could lead to a differential diagnosis with cholesteatoma or malignancies.

Dementia, delusions and seizures: storage disease or genetic AD?

We describe a case of a young patient suffering from a rapidly progressive cognitive decline, associated with delusions, myoclonus and seizures and with no family history for dementia. Clinical features, along with skin biopsy findings were overlapping storage disease; the genetic analysis, however, demonstrated a de novo presenilin 1 mutation. The present report suggests the usefulness of genetic determinations in early-onset cases of dementia, even without an autosomal dominant trait of inheritance; for these cases and their relatives an extensive genetic counselling should be recommended.

Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics.

BACKGROUND: Tumor recurrence is the most expected clinical event after the resection of non-muscle invasive bladder cancer, depending on histological findings of the initial lesion. In patients with low and intermediate risk of disease, the intravesical instillation of chemotherapy agents is recommended as a standard treatment to reduce recurrences. METHODS: A comprehensive review covering various aspects of different treatments with intravesical drugs is presented. RESULTS: Drugs may be instilled into the bladder starting with a single, 'early' postoperative administration or, after tumor resection with adjuvant intent or, before tumor resection under a neo-adjuvant regimen. Both latter protocols would consist of weekly treatments followed by monthly maintenance treatments. Different methods of administering drugs intravesically have been proposed to enhance the depth of drug penetration and its absorption into the bladder wall thus increasing the rate of drug-DNA reaction. These device-assisted therapies therefore have set a goal to potentiate the drug's effect and efficaciousness. The Radiofrequency-Induced Thermochemotherapeutic Effect (RITE) and the Electromotive-Drug Administration (EMDA) are the two most relevant modalities used to increase the activity of intravesical chemotherapy. Despite the widely adopted international guidelines' recommendations, and recent clinical trials of device-assisted chemotherapy instillations showing markedly enhanced recurrence-free survival compared even to the standard of care, clinicians and pharmacologists are not familiar with the in-depth physical aspects, pharmacokinetics and systemic absorption of chemotherapeutic drugs following their intravesical administration. CONCLUSION: Knowledge of drug diffusion mechanisms into the tissue and cellular cytoplasm following bladder instillation is a key to understand the safety profile and clinical activity of chemotherapy.

Approval rating and opinion of outpatients and general practitioners toward generic drugs: a questionnaire-based real-world study.

PURPOSE: Generic drugs use in the Liguria region is higher than the Italian average, but lower than in other European countries. No data exist about real-life prescription and level of awareness of generic drugs. In this study, we analyzed demographic, social, economic and cultural factors that may affect the level of awareness of generic drugs and their effective use. METHODS: We conducted a population survey using a structured questionnaire, administered to a sample of 8 outpatient clinics of general practitioners located in different districts of Genoa (Liguria, Italy). Multivariate logistic modeling was adopted to study the relationship between awareness/use of generic drugs and characteristics of subjects. RESULTS: Out of 2,000 outpatients surveyed, 95% were aware of generic drugs: these were mostly females (OR =2.2, 95% CI: 1.4-3.6), >35 years old (OR >6.0 vs 18-35 years), with a high level of education (OR >4.4 vs "elementary sch"), living in the west side of the city (OR =1.9 vs center); of these, only 59% declared that they effectively use generic drugs. Users were younger (OR =3.1, 18-35 years vs >65 years), with a high level of education (high school/university degree vs no title/elementary/secondary school OR =1.7), and were aware of the lower cost compared with branded drugs, and were mainly informed by pharmacists and physicians. CONCLUSIONS: Although subjects were substantially aware of the existence of generic drugs, ~40% still did not use them; doubts about their efficacy seem to be mainly driven by the idea that cheaper drugs lead to lower product quality, in terms of efficacy, safety and tolerability. New education policies on generic drugs are needed.

Analysis of risk factors for pharyngocutaneous fistula after total laryngectomy with particular focus on nutritional status.

Pharyngocutaneous fistula (PCF) is the most common complication following total laryngectomy and the most difficult to manage. It often causes increased morbidity, delays starting adjuvant therapy, prolongs hospitalisation, increases treatment costs and reduces the quality of life (QoL). The objective of this study is to analyse the predisposing factors and the most important nutritional parameters related to the development of PCF in patients undergoing total laryngectomy and to suggest medical alternatives that might improve results. We performed a retrospective study of 69 patients who underwent either primary or salvage total laryngectomy in our department between January 2008 and January 2012. Risk factors for fistula formation were analysed including tumour characteristics (histology, grading, AJCC stage), treatment (primary or salvage surgery, extent of resection, flap reconstruction, preoperative radiotherapy), comorbidity and nutritional status (preoperative haemoglobin, albumin and prealbumin levels and their changes during hospitalisation). Twenty-four patients developed a PCF (overall incidence 34.8%). Fistula formation was significantly higher in patients with diabetes, preoperative malnutrition (identified from low preoperative albumin and prealbumin levels). After specific nutritional evaluation and support, no patient developed a PCF. Risk factors for PCF formation are extensively treated in the literature but identification of high-risk patients is still controversial. Our study demonstrates that nutritional status of the patient, assessed by preoperative albumin, is also an important risk factor for PCF formation in addition to classical factors. Maintenance of a normal perioperative nutritional status can be helpful to avoid this complication.

Results of Early Versus Intermediate or Delayed Voice Therapy in Patients With Unilateral Vocal Fold Paralysis: Our Experience in 171 Patients.

OBJECTIVES: Vocal fold paralysis can have an important impact on a patient's quality of life. The goal of this study was to compare, in terms of vocal improvement and motility recovery, the post-vocal treatment results of our patients with unilateral vocal fold paralysis (UVFP) when treatment was started early (within 4 weeks from injury) versus intermediate (from 4 to 8 weeks) or delayed (at least 8 weeks after injury) treatment. STUDY DESIGN: An 11-year retrospective study of patients with UVFP who underwent multidimensional diagnostic-therapeutic assessment. METHODS: In total, 171 patients with UVFP were included in our study, divided into three groups who underwent early (first group), intermediate (second group), or delayed (third group) voice treatment. All patients underwent voice therapy based on forcible exercises supplemented by manipulations and maneuvers. RESULTS: Of the 171 patients with UVFP, 106 (62%) recovered vocal fold motility. Of these 106 patients, 51/78 (65%) were in the first group, 30/49 (61%) in the second group, and 25/44 (56%) in the third group. A significant (P < 0.0001) reduction in fundamental frequency (Fo) was present in the first group with a manifest improvement in the mean values of Jitter (Jitt%; P = 0.001), Shimmer (Shim%; P < 0.0001), and noise-to-harmonic ratio (NHR; P < 0.0001). A significant (P < 0.0001) reduction in Fo was found in the second group with a manifest improvement in Jitt% (P < 0.001), Shim% (P < 0.0001), and NHR (P < 0.0001). For the third group, no values were statistically significant apart from the improvement in NHR (P < 0.001). CONCLUSIONS: This study confirms the importance of early rehabilitation underlining the non-functional vocal recovery in patients who started treatment later than 8 weeks after injury.

Mu and kappa opioid system interactions in the expression of acute opioid dependence in isolated guinea-pig ileum.

In vivo studies have suggested that the kappa opioid system can partially inhibit the development of physical dependence to mu agonists. Vice versa, activation of mu receptors may inhibit the expression of physical dependence to kappa agonists. We studied mu-kappa interactions in the isolated guinea-pig ileum (GPI). In the isolated GPI briefly exposed to mu or kappa agonists the addition of the respective antagonists precipitated a withdrawal contracture. After a first withdrawal response, however, some tissues failed to exhibit subsequent mu or kappa withdrawal contractures. A withdrawal contracture to the selective mu antagonist, cyprodime, after repeated exposures to a selective mu agonist, dermorphin, was restored by nor-binaltorphimine (BNI), a selective kappa antagonist. Vice versa, after repeated exposures to the kappa agonist, U-50,488H, cyprodime restored tissue responsiveness to BNI. Tissues repeatedly exposed to dermorphin and washed after each exposure contracted to the addition of BNI. Tissues repeatedly exposed to U-50,488H contracted on the addition of cyprodime. These findings strongly suggest that exogenous agonist-elicited stimulation of the mu (or kappa) opioid system indirectly activates the endogenous kappa (or mu) system. The indirectly-activated endogenous system inhibits the withdrawal response to the exogenously-stimulated opioid system. In isolated GPI the mu and kappa opioid systems thus appear to interact, regulating each other.