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The HOLMES experiment aims to directly measure the ν mass studying the 163Ho electron capture decay spectrum developing arrays of TES-based microcalorimeters implanted with O(300 Bq/detector) Ho atoms. The embedding of the source inside detectors is a crucial step of the experiment. Because the 163Ho production process (neutron irradiation of a 162Er sample) is not perfectly free from impurities, Ho source must be separated from a lot of contaminants. A chemical processing removes every species other than Ho, but it is not sufficient to remove all isotope-related background sources: Indeed, 166mHo beta decay can produce fake signal in the region of interest. For this reason, a dedicated implantation system was set up. It is designed to achieve the separation power better than 5σ at 163/166 a.m.u. allowing an efficient Ho ions implantation inside microcalorimeter absorbers. Its main components are a 50 kV sputter-based ion source, a magnetic dipole and a target chamber. A specially designed co-evaporation system was designed to “grow” the gold microcalorimeter absorber during the implantation process, increasing the maximum achievable activity which can be implanted. The machine performances were evaluated by means of calibration runs using 63Cu/65Cu and Mo beams. A special care was given to the study of the more effective way to populate source plasma with Ho ions obtained from different Ho compounds by sputtering process. In this work, the machine development and commissioning are described.

Microdissection testicular sperm extraction (mTESE) has been proposed as a salvage treatment option for men with a previously failed classic TESE (cTESE), but data are scarce. We aimed to assess the outcome of and potential predictors of successful salvage mTESE in a cohort of men previously submitted to unfruitful cTESE. Data from 61 men who underwent mTESE after a failed cTESE between 01/2014 and 10/2020, at 6 tertiary-referral centres in Italy were analysed. All men were investigated with semen analyses, testicular ultrasound, hormonal and genetic blood testing. Pathological diagnosis from TESE was collected in every man. Descriptive statistics and logistic regression models were used to investigate potential predictors of positive sperm retrieval (SR+) after salvage mTESE. Baseline serum Follicle-Stimulating hormone (FSH) and total testosterone levels were 17.2 (8.6–30.1) mUI/mL and 4.7 (3.5-6.4) ng/mL, respectively. Sertoli-cell-only syndrome (SCOS), maturation arrest (MA) and hypospermatogenesis were found in 24 (39.3%), 21 (34.4%) and 16 (26.2%) men after cTESE, respectively. At mTESE, SR+ was found in 30 (49.2%) men. Patients with a diagnosis of hypospermatogenesis had a higher rate of SR+ (12/16 (75%)) compared to MA (12/21 (57.1%)) and SCOS (6/24 (25%)) patients at mTESE (p < 0.01). No clinical and laboratory differences were observed between SR+ and SR- patients at mTESE. There were no significant complications after mTESE. At multivariable logistic regression analysis, only hypospermatogenesis (OR 9.5; p < 0.01) was independently associated with SR+ at mTESE, after accounting for age and FSH. In conclusion, salvage mTESE in NOA men with previous negative cTESE was safe and promoted SR+ in almost 50%. A baseline pathology of hypospermatogenesis at cTESE emerged as the only independent predictor of positive outcomes at salvage mTESE.

In situations requiring high levels of customization and limited production volumes, additive manufacturing (AM) is a frequently utilized technique with several benefits. To properly configure all the parameters required to produce final goods of the utmost quality, AM calls for qualified designers and experienced operators. This research demonstrates how, in this scenario, artificial intelligence (AI) could significantly enable designers and operators to enhance additive manufacturing. Thus, 48 papers have been selected from the comprehensive collection of research using a systematic literature review to assess the possibilities that AI may bring to AM. This review aims to better understand the current state of AI methodologies that can be applied to optimize AM technologies and the potential future developments and applications of AI algorithms in AM. Through a detailed discussion, it emerges that AI might increase the efficiency of the procedures associated with AM, from simulation optimization to in-process monitoring.

Previous studies have shown discrepancies among countries in terms of treatment indications and patients' management due to different health care policies. Penile prosthesis implantation (PPI) is a highly effective treatment for erectile dysfunction (ED), which may have different accessibility according to the type of health system. We compared clinical characteristics of patients included in two national registries on PPI to investigate the influence of different health care systems on treatment indication and accessibility. The multicenter Italian Nationwide Systematic Inventarization of Surgical Treatment for ED (INSIST-ED) Registry and the multicenter Prospective Registry of Outcomes with Penile Prosthesis for Erectile Restoration (PROPPER), respectively for Italy and North America were considered. Clinical characteristics of patients included in both registries were compared using Wilcoxon Rank Sum test and the Pearson's Chi square test. Patients submitted to PPI in Italy are significantly younger (age: 61.2 vs. 63.8 years; p ≤ 0.001) compared with North America. The majority of patients are treated for post-radical prostatectomy ED in both registries (Italy: 31%; North America: 27%), although diabetes and cardiovascular diseases are more frequent reasons for PPI in the PROPPER registry (p ≤ 0.001), reflecting differences in disease prevalence among countries. In North America a non-hydraulic implant is considered only in 1% of cases as compared with 3% in Italy (p ≤ 0.001). In terms of postoperative management, a compressive surgical dressing (98% vs. 24%; p ≤ 0.001) is a more common strategy in North America. Finally, in Italy most surgeries are performed in a public hospital (82%), while the private setting (70.8%) is more common in North America (p ≤ 0.001). These findings suggest differences in health care systems between Italy and North America. A system like the American one would guarantee easier access to PPI in countries where the National Health System is mainly based on reimbursement to public hospital settings and where patients choosing private settings have to pay by themselves.

This article describes a model of supervision developed by Centro MIP in Santiago, Chile. This model is situated in the cultural history and legal context of psychotherapeutic practice in Chile, as well as in the unique pioneering spirit governing the institute since its founding in 1992. This psychotherapy-based model draws from constructivist and strategic orientations and includes elements of structural, solution-focused, and client-centered practice. The work has an overarching goal of serving the therapeutic growth of the supervisee and is guided by three primary principles: unwavering leadership (liderazgo irrenunciable), pursuing excellence (excelencia), and intervision (intervision). It is argued that enhancing supervisees’ therapeutic effectiveness and their own well-being is facilitated by eschewing within-session summative evaluation in favor of encouragement and bidirectional formative feedback. Several excerpts of supervisory sessions are provided to illustrate the method.

BackgroundFully adjustable articulators and pantographs record and reproduce individual mandibular movements. Although these instruments are accurate, they are operator-dependant and time-consuming. Pantographic recording is affected by inter and intra operator variability in the individuation of clinical reference points and afterwards in reading pantographic recording themselves. Finally only border movements can be reproduced.MethodsBionic Jaw Motion system is based on two components: a jaw movement analyzer and a robotic device that accurately reproduces recorded movements. The jaw movement analyzer uses an optoelectronic motion system technology made of a high frequency filming camera that acquires 140frames per second and a custom designed software that recognizes and determines the relative distance at each point in time of markers with known geometries connected to each jaw. Circumferential modified retainers connect markers and do not cover any occlusal surfaces neither obstruct occlusion. The recording process takes 5 to 10 s. Mandibular movement performance requires six degrees of freedom of movement, 3 rotations and 3 translations. Other robots are based on the so-called delta mechanics that use several parallel effectors to perform desired movements in order to decompose a complex trajectory into multiple more simple linear movements. However, each parallel effector introduces mechanical inter-component tolerances and mathematical transformations that are required to transform a recorded movement into the combination of movements to be performed by each effector. Bionic Jaw Motion Robot works differently, owing to three motors that perform translational movements and three other motors that perform rotations as a gyroscope. This configuration requires less mechanical components thus reducing mechanical tolerances and production costs. Both the jaw movement analyzer and the robot quantify the movement of the mandible as a rigid body with six degrees of freedom. This represents an additional advantage as no mathematical transformation is needed for the robot to reproduce recorded movements.ResultsBased on the described procedure, Bionic Jaw Motion provide accurate recording and reproduction of maxillomandibular relation in static and dynamic conditions.ConclusionThis robotic system represents an important advancement compared to available analogical and digital alternatives both in clinical and research contexts for cost reduction, precision and time saving opportunities.

Carboxypeptidase A (CPA) is a metalloexopeptidase that catalyzes the hydrolysis of the peptide bonds that are adjacent to the C-terminal end of a polypeptide chain. The enzyme preferentially cleaves over C-terminal L-amino acids with aromatic or branched side chains. This is of main importance for food industry because it can be employed for manufacturing functional foods from different protein sources with reduced hydrophobic amino acid content for patients with deficiencies in the absorption or digestion of the corresponding amino acids. In that way, strategies for effective multipoint covalent immobilization of CPA metalloenzyme on chitosan beads have been developed. The study of the ability to produce several chemical modifications on chitosan molecules before, during and after its coagulation to form carrier beads lead in a protective effect of the polymer matrix. The chemical modification of chitosan through the use of an N-alkylation strategy produced the best derivatives. N-alkyl chitosan derivative beads with D-fructose presented values of 0.86 for immobilization yield, 314.6 IU g−1 bead for initial activity of biocatalyst and were 5675.64-fold more stable than the free enzyme at 55 °C. Results have shown that these derivatives would present a potential technological application in hydrolytic processes due to both their physical properties, such as low swelling capacity, reduced metal chelation ability and bulk mesoporosity, and increased operational stability when compared with soluble enzyme. Fil: Manzo, Ricardo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Ceruti, Roberto Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Bonazza, Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Adriano, Wellington S.. Universidad Federal de Campina Grande; Brasil Fil: Sihufe, Guillermo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Mammarella, Enrique José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

The aim of this manuscript is to systematically review the current literature on surgical management of the short penis, focusing on surgical and functional outcomes and postoperative complications. Penile size still represents a major concern among a large proportion of men regardless of age and socio-cultural background. On the other hand, there is still no clear agreement on the definition of a short penis. Penile inadequacy can be secondary to a variety of clinical conditions, either organic or psychogenic; moreover, the causes of a short penis could be divided in congenital or acquired. A surgical intervention is often requested to address these conditions, with a variety of different techniques that reflect the vast heterogeneity of the etiologies of the disease. Surgical and patients’ satisfaction outcomes are extremely variable, as long as the different techniques are hardly comparable. As a general statement, a lack of objective data, mainly concerning postoperative lengthening results, must be emphasized. To date, penile lengthening procedures remain highly controversial. Recent evidences show better results in case of intrinsic or “false” penile shortness, while there is a lack of standardized studies concerning patients affected by penile dysmorphic disorder.

Oligodendrocyte precursor cells (OPCs, also called NG2 cells) are scattered throughout brain parenchyma, where they function as a reservoir to replace lost or damaged oligodendrocytes, the myelin-forming cells. The hypothesis that, under some circumstances, OPCs can actually behave as multipotent cells, thus generating astrocytes and neurons as well, has arisen from some in vitro and in vivo evidence, but the molecular pathways controlling this alternative fate of OPCs are not fully understood. Their identification would open new opportunities for neuronal replace strategies, by fostering the intrinsic ability of the brain to regenerate. Here, we show that the anti-epileptic epigenetic modulator valproic acid (VPA) can promote the generation of new neurons from NG2+ OPCs under neurogenic protocols in vitro, through their initial de-differentiation to a stem cell-like phenotype that then evolves to “hybrid” cell population, showing OPC morphology but expressing the neuronal marker βIII-tubulin and the GPR17 receptor, a key determinant in driving OPC transition towards myelinating oligodendrocytes. Under these conditions, the pharmacological blockade of the P2Y-like receptor GPR17 by cangrelor, a drug recently approved for human use, partially mimics the effects mediated by VPA thus accelerating cells’ neurogenic conversion. These data show a co-localization between neuronal markers and GPR17 in vitro, and suggest that, besides its involvement in oligodendrogenesis, GPR17 can drive the fate of neural precursor cells by instructing precursors towards the neuronal lineage. Being a membrane receptor, GPR17 represents an ideal “druggable” target to be exploited for innovative regenerative approaches to acute and chronic brain diseases.

The microcalorimeter array for a rhenium experiment (MARE) project aims at the direct and calorimetric measurement of the electron neutrino mass with sub-eV sensitivity. The design is based on large arrays of thermal detectors to study the beta decay of \(^{187}\)Re and the electron capture of \(^{163}\)Ho. One of the activities of the project, MARE 1 in Milan, has started in Milan using one array of 6 \(\times \) 6 silicon implanted thermistors equipped with AgReO\(_4\) absorbers. The purposes of MARE 1 in Milan are to achieve a sensitivity on the neutrino mass of a few eV and to investigate the systematics of \(^{187}\)Re neutrino mass measurements, focusing on those caused by the beta environmental fine structure and the beta spectrum theoretical shape. In parallel, the MARE collaboration is performing an R&D work for producing absorbers embedded with radioactive metal \(^{163}\)Ho. We report here the status of MARE using Re as beta source and the preliminary results obtained with \(^{163}\)Ho.

The present manuscript shows the importance of studying the isovector giant dipole resonance (IVGDR) to obtain information about the isospin-symmetry breaking and the shape evolution in excited nuclei. The $\gamma$ decay of the IVGDR was measured in the compound nuclei 80Zr and 81Rb formed at an excitation energy of $E^{\ast} = 54$ MeV and $ \langle J \rangle \approx 20\hbar$ . The reactions 40Ca+40Ca( $E_{beam} = 136$ MeV) and 37Cl+44Ca( $E_{beam} = 95$ MeV) were used to form the nuclei 80Zr and 81Rb, respectively. The experimental setup used for the $\gamma$ -rays detection was composed by the AGATA Demonstrator array coupled with large volume LaBr3:Ce detectors of the HECTOR+ array.

Class-A curves show very appreciable features in terms of smoothness and curvature trend that is commonly perceived as high quality profiles. These curves are commonly sketched by experienced operators, but at the present day no tools are available to transform a B-spline into a Class-A curve. The k-neigh-fast is an improved version of k-neighbours algorithm, described in Amati et al. (Comput Graph 30(3):345–352, 2006), aiming to transform a B-spline non-Class-A slope into a B-spline Class-A curve by manipulating a group of k geometric coefficients. Once the level of detail (LOD) representation of a curve has been computed, the k-neigh-fast algorithm, detects those control points representing non-Class-A imperfections. At each LOD, the algorithm individuates the detail coefficient maximizing the internal functional. Then k-neighbours has been modified applying filtering criteria. A control step starts to verify the transformation from a non-Class-A curve into a Class-A shape. This process is repeated until the chosen stopping condition is satisfied. The final shape with improved smoothness and monotonic curvature is achieved through manual procedure. This paper reports results dealing on an improved and faster wavelet-based LOD filtering implementation used to generate very smooth set of profiles that own to Class-A set. The LODs representation allows to divide curves into their coarser least-square approximations and details coefficients. The extraction and manipulation of details with multi-level filtering, allows to determine geometric imperfections. This method has been tested to the smoothing of the hull profile of ships: results are good since the non-A-curve are well converted in smoother lines. A more efficient implementation, based on a flexible LOD representation led to prove many benefits of this techniques; the tests performed exploiting a computer program implementation have demonstrated very good results in most of simulations considered.

The international project MARE (Microcalorimeter Array for a Rhenium Experiment) aims at the direct and calorimetric measurement of the electron neutrino mass with sub-eV sensitivity. Although the baseline of the MARE project consists in a large array of rhenium based thermal detectors, a different option for the isotope is also being considered. The different option is 163Ho. The potential of using 187Re for a calorimetric neutrino mass experiment has been already demonstrated. On the contrary, no calorimetric spectrum of 163Ho has been so far measured with the precision required to set a useful limit on the neutrino mass. The first phase of the project (MARE-1) is a collection of activities with the aim of sorting out both the best isotope and the most suited detector technology to be used for the final experiment. One of the MARE-1 activities is carried out in Milan by the group of Milano–Bicocca in collaboration with NASA/GSFC and Wisconsin groups. The Milan MARE-1 arrays are based on semiconductor thermistors, provided by the NASA/GSFC group, with dielectric silver perrhenate absorbers, AgReO4. The experiment, which is presently being assembled, is designed to host up to 8 arrays. With 288 detectors, a sensitivity of 3 eV at 90% CL on the neutrino mass can be reached within 3 years. This contribution gives an outlook for the MARE activities for the active isotope selection. In this contribution the status and the perspectives of the MARE-1 in Milan are also reported.

To evaluate the bias and precision of the respiratory muscle training device formulas to predict respiratory minute volume (RMV) and volume of the reservoir bag (BV) on a cohort of subjects with Cystic Fibrosis (CF). CF patients with available pulmonary function tests and maximal voluntary manoeuvres were included in the study. Vital capacity and maximal voluntary ventilation were extracted from subjects' records and then inserted to the manufacturer's formulas to obtain RMV and BV (measured setting). RMV and BV were compared according to standard and measured formulas in males and females. Sample was described and then processed using Bland-Altman analysis. Bland-Altman analysis for RMV revealed a bias and precision of 8.8 ± 29 L/min in males and 28.8 ± 16 L/min in females; 0.4 ± 0.5 L in males and 0.7 ± 0.4 L in females for BV. Concordance correlation coefficients for RMV were -0.03 in males and 0.02 in females; 0.22 in males and 0.03 in females for BV, reinforcing an unsatisfactory concordance between measured and manufacturer setting. This study shows considerable discrepancies between the two methods, making the degree of agreement not clinically acceptable. This might cause inappropriate setting and disservice to patients with CF.

Little is known about hemodynamic disturbances affecting cerebral hemispheres in traumatic brain injury (TBI) after cranioplasty. We prospectively investigated six stable TBI patients who underwent cranioplasty more than 90 days after effective decompressive craniectomy. Computerized tomography perfusion (CTP) studies and evaluation of clinical outcome were performed for each patient before cranioplasty and at 7 days and 3 months after surgery. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in multiple cortical circular regions positioned in cranioplasty-treated and contralateral hemispheres. Neither complications associated with cranioplasty nor changes in outcome were observed. On the treated side, CBF and CBV values were higher before and 7 days after cranioplasty than at 3 months after surgery, whereas MTT values were lower at 7 days than at 3 months after surgical treatment. Our results indicate that cortical perfusion progressively declines in the cranioplasty treated hemisphere but remains stable in the contralateral hemisphere after surgery and suggest that CTP can represent a promising tool for a longitudinal analysis of hemodynamic abnormalities occurring in TBI patients after cranioplasty. In addition, these data imply a possible role of cranioplasty in restoring flow to meet the prevailing metabolic demand.

A large worldwide collaboration is growing around the project of Micro-calorimeter Arrays for a Rhenium Experiment (MARE) for a direct calorimetric measurement of the neutrino mass. To validate the use of cryogenic detectors by checking the presence of unexpected systematic errors, two first experiments are planned using the available techniques composed of arrays of 300 detectors to measure 1010 events in a reasonable time of 3 years (step MARE-1) to reach a sensitivity on the neutrino mass of ∼2 eV/c2. Our experiment in Milan is based on compensated doped silicon implanted thermistor arrays made in NASA/GSFC and on AgReO4 crystals. We present here the design of the cryogenic system that integrates all the requirements for such experiment (electronics for high impedances, low parasitic capacitances, low micro-phonic noise).