CALOCUBE: An approach to high-granularity and homogenous calorimetry for space based detectors

Future space experiments dedicated to the observation of high-energy gamma and cosmic rays will increasingly rely on a highly performing calorimetry apparatus, and their physics performance will be primarily determined by the geometrical dimensions and the energy resolution of the calorimeter deployed. Thus it is extremely important to optimize its geometrical acceptance, the granularity, and its absorption depth for the measurement of the particle energy with respect to the total mass of the apparatus which is the most important constraint for a space launch. The proposed design tries to satisfy these criteria while staying within a total mass budget of about 1.6 tons. Calocube is a homogeneous calorimeter instrumented with Cesium iodide (CsI) crystals, whose geometry is cubic and isotropic, so as to detect particles arriving from every direction in space, thus maximizing the acceptance; granularity is obtained by filling the cubic volume with small cubic CsI crystals. The total radiation length in any direction is more than adequate for optimal electromagnetic particle identification and energy measurement, whilst the interaction length is at least sufficient to allow a precise reconstruction of hadronic showers. Optimal values for the size of the crystals and spacing among them have been studied. The design forms the basis of a three-year R&D activity which has been approved and financed by INFN. An overall description of the system, as well as results from preliminary tests on particle beams will be described

The CALorimetric Electron Telescope (CALET) for high-energy astroparticle physics on the International Space Station

The CALorimetric Electron Telescope (CALET) is a space experiment, currently under development by Japan in collaboration with Italy and the United States, which will measure the flux of cosmic-ray electrons (and positrons) up to 20 TeV energy, of gamma rays up to 10 TeV, of nuclei with Z from 1 to 40 up to 1 PeV energy, and will detect gamma-ray bursts in the 7 keV to 20 MeV energy range during a 5 year mission. These measurements are essential to investigate possible nearby astrophysical sources of high energy electrons, study the details of galactic particle propagation and search for dark matter signatures. The main detector of CALET, the Calorimeter, consists of a module to identify the particle charge, followed by a thin imaging calorimeter (3 radiation lengths) with tungsten plates interleaving scintillating fibre planes, and a thick energy measuring calorimeter (27 radiation lengths) composed of lead tungstate logs. The Calorimeter has the depth, imaging capabilities and energy resolution necessary for excellent separation between hadrons, electrons and gamma rays. The instrument is currently being prepared for launch (expected in 2015) to the International Space Station ISS, for installation on the Japanese Experiment Module - Exposure Facility (JEM-EF)

Calet upper limits on X-RAY and GAMMA-RAY counterparts of GW151226

We present upper limits in the hard X-ray and gamma-ray bands at the time of the Laser Interferometer Gravitational-wave Observatory (LIGO) gravitational-wave event GW151226 derived from the CALorimetric Electron Telescope (CALET) observation. The main instrument of CALET, CALorimeter (CAL), observes gamma-rays from ∼1 GeV up to 10 TeV with a field of view of ∼2 sr. The CALET gamma-ray burst monitor (CGBM) views ∼3 sr and ∼2π sr of the sky in the 7 keV-1 MeV and the 40 keV-20 MeV bands, respectively, by using two different scintillator-based instruments. The CGBM covered 32.5% and 49.1% of the GW151226 sky localization probability in the 7 keV-1 MeV and 40 keV-20 MeV bands respectively. We place a 90% upper limit of 2 ×10-7 erg cm-2 s-1 in the 1-100 GeV band where CAL reaches 15% of the integrated LIGO probability (∼1.1 sr). The CGBM 7σ upper limits are 1.0 ×10-6 erg cm-2 s-1 (7-500 keV) and 1.8 ×10-6 erg cm-2 s-1 (50-1000 keV) for a 1 s exposure. Those upper limits correspond to the luminosity of 3-5 ×1049 erg s-1, which is significantly lower than typical short GRBs

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Energy calibration of CALET onboard the International Space Station

In August 2015, the CALorimetric Electron Telescope (CALET), designed for long exposure observations of high energy cosmic rays, docked with the International Space Station (ISS) and shortly thereafter began to collect data. CALET will measure the cosmic ray electron spectrum over the energy range of 1 GeV to 20 TeV with a very high resolution of 2% above 100 GeV, based on a dedicated instrument incorporating an exceptionally thick 30 radiation-length calorimeter with both total absorption and imaging (TASC and IMC) units. Each TASC readout channel must be carefully calibrated over the extremely wide dynamic range of CALET that spans six orders of magnitude in order to obtain a degree of calibration accuracy matching the resolution of energy measurements. These calibrations consist of calculating the conversion factors between ADC units and energy deposits, ensuring linearity over each gain range, and providing a seamless transition between neighboring gain ranges. This paper describes these calibration methods in detail, along with the resulting data and associated accuracies. The results presented in this paper show that a sufficient accuracy was achieved for the calibrations of each channel in order to obtain a suitable resolution over the entire dynamic range of the electron spectrum measurement

Device Orientation Independent Human Activity Recognition Model for Patient Monitoring Based on Triaxial Acceleration

Tracking a person’s activities is relevant in a variety of contexts, from health and group-specific assessments, such as elderly care, to fitness tracking and human–computer interaction. In a clinical context, sensor-based activity tracking could help monitor patients’ progress or deterioration during their hospitalization time. However, during routine hospital care, devices could face displacements in their position and orientation caused by incorrect device application, patients’ physical peculiarities, or patients’ day-to-day free movement. These aspects can significantly reduce algorithms’ performances. In this work, we investigated how shifts in orientation could impact Human Activity Recognition (HAR) classification. To reach this purpose, we propose an HAR model based on a single three-axis accelerometer that can be located anywhere on the participant’s trunk, capable of recognizing activities from multiple movement patterns, and, thanks to data augmentation, can deal with device displacement. Developed models were trained and validated using acceleration measurements acquired in fifteen participants, and tested on twenty-four participants, of which twenty were from a different study protocol for external validation. The obtained results highlight the impact of changes in device orientation on a HAR algorithm and the potential of simple wearable sensor data augmentation for tackling this challenge. When applying small rotations (0.85±0.11 against a baseline model f1-score equal to 0.49±0.12

Wrist-worn optical and chest strap heart rate comparison in a heterogeneous sample of healthy individuals and in coronary artery disease patients

Abstract Background The need for unobtrusive HR (heart rate) monitoring has led to the development of a new generation of strapless HR monitors. The aim of this study was to determine whether such an unobtrusive, wrist-worn optical HR monitor (OHRM) could be equivalent and therefore a valid alternative to a traditional chest strap during a broad range of activities in a heterogeneous healthy population and coronary artery disease (CAD) patients. Methods One hundred ninety-nine healthy volunteers, 84 males and 115 females, including 35 overweight-obese subjects, 53 pregnant women, and 20 CAD patients were tested in the present study. Second-by-second HR measured by the OHRM was concurrently evaluated against an ECG-based chest strap monitor during a broad range of activities (i.e., walking, running, cycling, gym, household, and sedentary activities). Results Data coverage, percentage of time the OHRM provides a HR not larger than 10 bpm from the reference, went from a minimum of 92% of the time in the least periodic activity (i.e., gym), to 95% during the most intense activity (i.e., running), and to a maximum of 98% for sedentary activities. The limits of agreement of the difference between the OHRM and the chest strap HR were within the range of ±15 bpm. The OHRM showed a concordance correlation coefficient of 0.98. Overall, the mean absolute error was not larger than 3 bpm, which can be considered clinically acceptable for a number of applications. A similar performance was found for CAD (94.2% coverage, 2.4 bpm error), but the small sample size does not allow any quantitative comparison. Conclusion Heart rate measured by OHRM at the wrist and ECG-based HR measured via a traditional chest strap are acceptably close in a broad range of activities in a heterogeneous, healthy population, and showed initial promising results also in CAD patients

Extraction of cardiac-related signals from a suprasternal pressure sensor during sleep

The accurate detection of respiratory effort during polysomnographyis a critical element in the diagnosis of sleep-disordered breathing conditions such as sleep apnea. Unfortunately, the sensors currently used to estimate respiratory effort are either indirect and ignore upper airway dynamics or are too obtrusive for patients. One promising alternative is the suprasternal notch pressure (SSP) sensor: a small element placed on the skin in the notch above the sternum within an airtight capsule that detects pressure swings in the trachea. Besides providing information on respiratory effort, the sensor is sensitive to small cardiac oscillations caused by pressure perturbations in the carotid arteries or the trachea. While current clinical research considers these as redundant noise, they may contain physiologically relevant information. We propose a method to separate the signal generated by cardiac activity from the one caused by breathing activity. Using only information available from the SSP sensor, we estimate the heart rate and track its variations, then use a set of tuned filters to process the original signal in the frequency domain and reconstruct the cardiac signal. We also include an overview of the technical and physiological factors that may affect the quality of heart rate estimation. The output of our method is then used as a reference to remove the cardiac signal from the original SSP pressure signal, to also optimize the assessment of respiratory activity. We provide a qualitative comparison against methods based on filters with fixed frequency cutoffs. In comparison with ECG-derived heart rate, we achieve an agreement error of 0.06±5.09bpm, with minimal bias drift across the measurement range, and only 6.36% of the estimates larger than 10bpm. Together with qualitative improvements in the characterization of respiratory effort, this opens the development of novel portable clinical devices for the detection and assessment of sleep disordered breathing

Sinus or not: a new beat detection algorithm based on a pulse morphology quality index to extract normal sinus rhythm beats from wrist-worn photoplethysmography recordings

OBJECTIVE: Wrist-worn photoplethysmography (PPG) can enable free-living physiological monitoring of people during diverse activities, ranging from sleep to physical exercise. In many applications, it is important to remove the pulses not related to sinus rhythm beats from the PPG signal before using it as a cardiovascular descriptor. In this manuscript, we propose an algorithm to assess the morphology of the PPG signal in order to reject non-sinus rhythm pulses, such as artefacts or pulses related to arrhythmic beats. APPROACH: The algorithm segments the PPG signal into individual pulses and dynamically evaluates their morphological likelihood of being normal sinus rhythm pulses via a template-matching approach that accounts for the physiological variability of the signal. The normal sinus rhythm likelihood of each pulse is expressed as a quality index that can be employed to reject artefacts and pulses related to arrhythmic beats. MAIN RESULTS: Thresholding the pulse quality index enables near-perfect detection of normal sinus rhythm beats by rejecting most of the non-sinus rhythm pulses (positive predictive value 98%-99%), both in healthy subjects and arrhythmic patients. The rejection of arrhythmic beats is almost complete (sensitivity to arrhythmic beats 7%-3%), while the sensitivity to sinus rhythm beats is not compromised (96%-91%). SIGNIFICANCE: The developed algorithm consistently detects normal sinus rhythm beats in a PPG signal by rejecting artefacts and, as a first of its kind, arrhythmic beats. This increases the reliability in the extraction of features which are adversely influenced by the presence of non-sinus pulses, whether related to inter-beat intervals or to pulse morphology, from wrist-worn PPG signals recorded in free-living conditions