Time-resolved single-photon detection module based on silicon photomultiplier: A novel building block for time-correlated measurement systems

We present the design and preliminary characterization of the first detection module based on Silicon Photomultiplier (SiPM) tailored for single-photon timing applications. The aim of this work is to demonstrate, thanks to the design of a suitable module, the possibility to easily exploit SiPM in many applications as an interesting detector featuring large active area, similarly to photomultipliers tubes, but keeping the advantages of solid state detectors (high quantum efficiency, low cost, compactness, robustness, low bias voltage, and insensitiveness to magnetic field). The module integrates a cooled SiPM with a total photosensitive area of 1 mm2 together with the suitable avalanche signal read-out circuit, the signal conditioning, the biasing electronics, and a Peltier cooler driver for thermal stabilization. It is able to extract the single-photon timing information with resolution better than 100 ps full-width at half maximum. We verified the effective stabilization in response to external thermal perturbations, thus proving the complete insensitivity of the module to environment temperature variations, which represents a fundamental parameter to profitably use the instrument for real-field applications. We also characterized the single-photon timing resolution, the background noise due to both primary dark count generation and afterpulsing, the single-photon detection efficiency, and the instrument response function shape. The proposed module can become a reliable and cost-effective building block for time-correlated single-photon counting instruments in applications requiring high collection capability of isotropic light and detection efficiency (e.g., fluorescence decay measurements or time-domain diffuse optics systems)

Genetic screening of Fabry patients with EcoTILLING and HRM technology

<p>Abstract</p> <p>Background</p> <p>Anderson-Fabry disease (FD) is caused by a deficit of the α-galactosidase A enzyme which leads to the accumulation of complex sphingolipids, especially globotriaosylceramide (Gb3), in all the cells of the body, causing the onset of a multi-systemic disease with poor prognosis in adulthood. In this article, we describe two alternative methods for screening the <it>GLA </it>gene which codes for the α-galactosidase A enzyme in subjects with probable FD in order to test analysis strategies which include or rely on initial pre-screening.</p> <p>Findings</p> <p>We analyzed 740 samples using EcoTILLING, comparing two mismatch-specific<ul/>endonucleases, CEL I and ENDO-1, while conducting a parallel screening of the same samples using HRM (High Resolution Melting). Afterwards, all samples were subjected to direct sequencing. Overall, we identified 12 different genetic variations: -10C>T, -12G>A, -30G>A, IVS2-76_80del5, D165H, C172Y, IVS4+16A>G, IVS4 +68 A>G, c.718_719delAA, D313Y, IVS6-22C>T, G395A. This was consistent with the high genetic heterogeneity found in FD patients and carriers. All of the mutations were detected by HRM, whereas 17% of the mutations were not found by EcoTILLING. The results obtained by EcoTILLING comparing the CEL I and ENDO-1 endonucleases were perfectly overlapping.</p> <p>Conclusion</p> <p>On the basis of its simplicity, flexibility, repeatability, and sensitivity, we believe that<ul/>HRM analysis of the <it>GLA </it>gene is a reliable presequencing screening tool. This method can be applied to any genomic feature to identify known and unknown genetic alterations, and it is ideal for conducting screening and population studies.</p

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

SPAD-based asynchronous-readout array detectors for image-scanning microscopy

Fluorescence microscopy and derived techniques are continuously looking for photodetectors able to guarantee increased sensitivity, high spatial and temporal resolution, and ease of integration into modern microscopy architectures. Recent advances in single-photon avalanche diodes (SPADs) fabricated with industry-standard microelectronic processes allow the development of new detection systems tailored to address the requirements of advanced imaging techniques (such as image-scanning microscopy). To this aim, we present the complete design and characterization of two bidimensional SPAD arrays composed of 25 fully independent and asynchronously operated pixels, both having fill factor of about 50% and specifically designed for being integrated into existing laser scanning microscopes. We used two different microelectronics technologies to fabricate our detectors: the first technology exhibiting very low noise (roughly 200 dark counts per second at room temperature) and the second one showing enhanced detection efficiency (more than 60% at a wavelength of 500 nm). Starting from the silicon-level device structures and moving towards the in-pixel and readout electronics description, we present performance assessments and comparisons between the two detectors. Images of a biological sample acquired after their integration into our custom image-scanning microscope finally demonstrate their exquisite on-field performance in terms of spatial resolution and contrast enhancement. We envisage that this work can trigger the development of a new class of SPAD-based detector arrays able to substitute the typical single-element sensor used in fluorescence laser scanning microscopy

SPAD-based asynchronous-readout array detectors for image-scanning microscopy

Fluorescence microscopy and derived techniques are continuously looking for photodetectors able to guarantee increased sensitivity, high spatial and temporal resolution, and ease of integration into modern microscopy architectures. Recent advances in single-photon avalanche diodes (SPADs) fabricated with industry-standard microelectronic processes allow the development of new detection systems tailored to address the requirements of advanced imaging techniques (such as image-scanning microscopy). To this aim, we present the complete design and characterization of two bidimensional SPAD arrays composed of 25 fully independent and asynchronously operated pixels, both having fill factor of about 50% and specifically designed for being integrated into existing laser scanning microscopes. We used two different microelectronics technologies to fabricate our detectors: the first technology exhibiting very low noise (roughly 200 dark counts per second at room temperature) and the second one showing enhanced detection efficiency (more than 60% at a wavelength of 500 nm). Starting from the silicon-level device structures and moving towards the in-pixel and readout electronics description, we present performance assessments and comparisons between the two detectors. Images of a biological sample acquired after their integration into our custom image-scanning microscope finally demonstrate their exquisite on-field performance in terms of spatial resolution and contrast enhancement. We envisage that this work can trigger the development of a new class of SPAD-based detector arrays able to substitute the typical single-element sensor used in fluorescence laser scanning microscopy

Nanostructured TiO2 Grown by Low-Temperature Reactive Sputtering for Planar Perovskite Solar Cells

Low-temperature nanostructured electron-transporting layers (ETLs) for perovskite solar cells are grown by reactive sputtering at 160 degrees C with thickness in the range 22-76 nm and further stabilization in air at 180 degrees C to improve the lattice structure and to consequently reduce charge recombination during solar cell operation. In addition, the post-deposition treatment aims at leveling differences among samples to ensure material reproducibility. Nanostructured TiO2 has a further added value in promoting the structural coupling with the perovskite layer and establishing conformal interfaces in favor of the charge extraction from the active material. Nanostructuring of the ETLs also allows the shaping of the band gap width and position with a beneficial impact on the electrical parameters, as tested in standard architecture containing methylammonium lead iodide perovskites. A balance among parameters is achieved using a 40-nm-thick TiO2 ETL with a maximum efficiency of similar to 5% reached without surface treatments or additional layers. The proposed growth methodology would be compatible with the use of flexible substrates after appropriated ETL structural adaptation. It can be likewise applied in perovskite/silicon-heterojunction tandem solar cells to fulfill the industrial demand for clean, solvent-free, reproducible, reliable, and high-throughput processes

Clinical variables associated with treatment changes in Parkinson's disease: results from the longitudinal phase of the REASON study

To assess over a period of 9 months in a sample of Italian Parkinson's disease (PD) patients reasons leading the neurologist to modify dopaminergic treatment and patients' causes of dissatisfaction with ongoing therapy. To evaluate the influence of disease severity on therapy persistence. A disease severity balanced sample of PD patients with stable anti-parkinsonian drugs (APD) treatment was enrolled and evaluated every 3 months. Patients requiring APD treatment modifications were discontinued from the study. The probability to modify APD treatment is greater for higher motor (UPDRS scores) and non-motor symptoms (NMSS score) severity. Both from neurologist's and patient's perspective, motor symptoms were the main determinants underlying APD treatment modifications. Non-motor symptoms were cause of dissatisfaction with ongoing APD treatment for 52 % of the patients, while only 36 % of the neurologists considered these as valid reasons for therapy change. REASON is the first study in PD patients that prospectively examined reasons driving APD treatment changes. Results show that the disease severity significantly increases the probability of APD treatment change. Patients attribute greater relevance than neurologists to non-motor symptoms as reason requiring treatment changes. This confirms that patient and neurologist perceptions only partially overlap