A digital waveguide-based approach for Clavinet modeling and synthesis

The Clavinet is an electromechanical musical instrument produced in the mid-twentieth century. As is the case for other vintage instruments, it is subject to aging and requires great effort to be maintained or restored. This paper reports analyses conducted on a Hohner Clavinet D6 and proposes a computational model to faithfully reproduce the Clavinet sound in real time, from tone generation to the emulation of the electronic components. The string excitation signal model is physically inspired and represents a cheap solution in terms of both computational resources and especially memory requirements (compared, e.g., to sample playback systems). Pickups and amplifier models have been implemented which enhance the natural character of the sound with respect to previous work. A model has been implemented on a real-time software platform, Pure Data, capable of a 10-voice polyphony with low latency on an embedded device. Finally, subjective listening tests conducted using the current model are compared to previous tests showing slightly improved results

A Multicenter Retrospective Survey regarding Diabetic Ketoacidosis Management in Italian Children with Type 1 Diabetes

We conducted a retrospective survey in pediatric centers belonging to the Italian Society for Pediatric Diabetology and Endocrinology. The following data were collected for all new-onset diabetes patients aged 0-18 years: DKA (pH < 7.30), severe DKA (pH < 7.1), DKA in preschool children, DKA treatment according to ISPAD protocol, type of rehydrating solution used, bicarbonates use, and amount of insulin infused. Records (n = 2453) of children with newly diagnosed diabetes were collected from 68/77 centers (87%), 39 of which are tertiary referral centers, the majority of whom (n = 1536, 89.4%) were diagnosed in the tertiary referral centers. DKA was observed in 38.5% and severe DKA in 10.3%. Considering preschool children, DKA was observed in 72%, and severe DKA in 16.7%. Cerebral edema following DKA treatment was observed in 5 (0.5%). DKA treatment according to ISPAD guidelines was adopted in 68% of the centers. In the first 2 hours, rehydration was started with normal saline in all centers, but with different amount. Bicarbonate was quite never been used. Insulin was infused starting from third hour at the rate of 0.05-0.1 U/kg/h in 72% of centers. Despite prevention campaign, DKA is still observed in Italian children at onset, with significant variability in DKA treatment, underlying the need to share guidelines among centers

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR&nbsp;=&nbsp;2.05, 95%CI&nbsp;=&nbsp;1.39–3.02, p&nbsp;&lt;&nbsp;0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR&nbsp;=&nbsp;0.42, 95%CI&nbsp;=&nbsp;0.18–0.99, p&nbsp;=&nbsp;0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Joint hypermobility and its relationship to musculoskeletal pain in schoolchildren: a cross-sectional study.

OBJECTIVES: To determine if joint hypermobility is associated with musculoskeletal pain in a population of Italian schoolchildren. DESIGN: Cross-sectional, school-based study, using a pretested questionnaire administered to schoolchildren to enquire about musculoskeletal pain and Beighton criteria, with score of > or =5 as a cut-off, to test for hypermobility. SETTING: Eight primary schools in the town of Cesena, Italy. PARTICIPANTS: 1230 Italian schoolchildren aged 7 to 15 years representing an opportunistic sample of 10% of the schoolchildren in Cesena MAIN OUTCOME MEASURES: (1) The strength of association between hypermobiliy and musculoskeletal pain; (2) the impact of hypermobility on daily activities, using a subjective "disability score" and a "physical activity score." ANALYSIS: Sample size calculation for evaluating if hypermobility was associated with musculoskeletal pain was performed prior starting the study. Children experiencing pain at least once a week were used as cases, children experiencing pain seldom or never served as controls. RESULTS: A total of 1046 consenting Italian schoolchildren (mean age 10.8 years) were included. The prevalence of musculoskeletal pain reported by schoolchildren was 18%. 22% of children with musculoskeletal pain versus 23% of controls had hypermobility (OR 1.057, 95% CI 0.7 to 1.4). Functional limitations measured by a "disability score" correlated in a weak negative way with Beighton score (p = 0.03). The "physical activity score" correlated in a weak positive way with Beighton score (p = 0.012). CONCLUSIONS: No association was found between hypermobility and musculoskeletal pain. Hypermobile children did not experience functional limitations in daily activities, and they were slightly more active than non-hypermobile children

Increasing titres of anti-human-transglutaminase antibodies with age in healthy population

8nonenoneBaldas V; Not T; Città A; Ansaldi F; Bensa M; Marzari R; Sblattero D; Ventura ABaldas, V; Not, Tarcisio; Città, A; Ansaldi, F; Bensa, M; Marzari, Roberto; Sblattero, Daniele; Ventura, Alessandr

Augmented efficacy of nano-formulated docetaxel plus curcumin in orthotopic models of neuroblastoma

Neuroblastoma is a biologically heterogeneous extracranial tumor, derived from the sympathetic nervous system, that affects most often the pediatric population. Therapeutic strategies relying on aggressive chemotherapy, surgery, radiotherapy, and immunotherapy have a negative outcome in advanced or recurrent disease. Here, spherical polymeric nanomedicines (SPN) are engineered to co-deliver a potent combination therapy, including the cytotoxic docetaxel (DTXL) and the natural wide-spectrum anti-inflammatory curcumin (CURC). Using an oil-in-water emulsion/solvent evaporation technique, four SPN configurations were engineered depending on the therapeutic payload and characterized for their physico-chemical and pharmacological properties. All SPN configurations presented a hydrodynamic diameter of similar to 185 nm with a narrow size distribution. A biphasic release profile was observed for all the configurations, with almost 90 % of the total drug mass released within the first 24 h. SPN cytotoxic potential was assessed on a panel of human neuroblastoma cells, returning IC50 values in the order of 1 nM at 72 h and documenting a strong synergism between CURC and DTXL. Therapeutic efficacy was tested in a clinically relevant orthotopic model of neuroblastoma, following the injection of SH-SY5Y-Luc(+) cells in the left adrenal gland of athymic mice. Although -2 % of the injected SPN per mass tissue reached the tumor, the overall survival of mice treated with CURC/DTXL-SPN was extended by 50 % and 25 % as compared to the untreated control and the monotherapies, respectively. In conclusion, these results demonstrate that the therapeutic potential of the DTXL/CURC combination can be fully exploited only by reformulating these two compounds into systemically injectable nanoparticles