Cu-Ag alloys are promising materials for electrical interconnections due to their combination of high conductivity and superior mechanical strength. In the present work, Cu-Ag alloys were ...electrodeposited from a cyanide-free electrolytic bath and different Ag percentages, ranging from 3 to 15 at.%, were obtained by controlling the deposition conditions. Electrochemical processes occurring during Cu-Ag deposition were investigated by means of cyclic voltammetry. Structural properties were examined by TEM and XRD and hardness was assessed by microindentation. TEM observations revealed the presence of nano-sized Ag precipitates at low Ag content, and the composition of the Cu-rich and Ag-rich phases in high-Ag alloys was deduced from XRD measurements. As-deposited alloys exhibited high hardness values and the contribution of solid-solution hardening was highlighted.
Observations in people with cerebral cavernous malformations, and in preclinical models of this disorder, suggest that the β-blocker propranolol might reduce the risk of intracerebral haemorrhage. We ...aimed to evaluate the safety and efficacy of prolonged treatment with propranolol to reduce the incidence of symptomatic intracerebral haemorrhage or focal neurological deficit in people with familial cerebral cavernous malformations.
We conducted a randomised, open-label, blinded-endpoint, phase 2 pilot trial (Treat_CCM) at six national reference centres for rare diseases in Italy. People aged 18 years or older with symptomatic familial cerebral cavernous malformation were eligible for enrolment. Participants were randomly assigned (2:1) to receive either oral propranolol (20-320 mg daily) plus standard care (intervention group), or standard care alone (control group), for 24 months. Participants, caregivers, and investigators were aware of treatment group assignment. Participants had clinical assessments and 3 T brain MRI at baseline and at 12 and 24 months. The primary outcome was new occurrence of symptomatic intracerebral haemorrhage or focal neurological deficit attributable to cerebral cavernous malformation over 24 months. Outcome assessors were masked to treatment group assignment. The primary analysis was done in the intention-to-treat population. Because of the pilot study design, we chose a one-sided 80% CI, which could either exclude a clinically meaningful effect or show a signal of efficacy. This trial is registered with EudraCT, 2017-003595-30, and ClinicalTrials.gov, NCT03589014, and is closed to recruitment.
Between April 11, 2018, and Dec 5, 2019, 95 people were assessed for eligibility and 83 were enrolled, of whom 57 were assigned to the propranolol plus standard care group and 26 to the standard care alone group. The mean age of participants was 46 years (SD 15); 48 (58%) were female and 35 (42%) were male. The incidence of symptomatic intracerebral haemorrhage or focal neurological deficit was 1·7 (95% CI 1·4-2·0) cases per 100 person-years (two 4% of 57 participants) in the propranolol plus standard care group and 3·9 (3·1-4·7) per 100 person-years (two 8% of 26) in the standard care alone group (univariable hazard ratio HR 0·43, 80% CI 0·18-0·98). The univariable HR showed a signal of efficacy, according to predefined criteria. The incidence of hospitalisation did not differ between groups (8·2 cases 95% CI 7·5-8·9 per 100 person-years in the propranolol plus standard care group vs 8·2 95% CI 7·1-9·3 per 100 person-years in the standard care alone group). One participant in the standard care alone group died of sepsis. Three participants in the propranolol plus standard care group discontinued propranolol due to side-effects (two reported hypotension and one reported weakness).
Propranolol was safe and well tolerated in this population. Propranolol might be beneficial for reducing the incidence of clinical events in people with symptomatic familial cerebral cavernous malformations, although this trial was not designed to be adequately powered to investigate efficacy. A definitive phase 3 trial of propranolol in people with symptomatic familial cerebral cavernous malformations is justified.
Italian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro, Swedish Science Council, Knut and Alice Wallenberg Foundation, CARIPLO Foundation, Italian Ministry of Health.
In the last few years, additive manufacturing has been investigated as a promising production methodology in the field of electro-mechanical devices thanks to the high process flexibility, the ...improved product customizability and the tridimensionality of the fabricated mechanical structures. Electro-mechanical devices are characterized by a dual nature, which combine mechanically moveable parts with electric components. For this reason, their production is particularly advantageous when different additive manufacturing technologies are employed in synergy. In this context, the present work aims at producing and experimentally verify the first functional accelerometer capable of piezoelectric signal readout fully fabricated through additive manufacturing techniques. A smart combination of 3D printing and inkjet materials deposition is here proposed: stereolithography of a photocurable resin is chosen to fabricate the structural components of the accelerometer, while inkjet printing is employed to pattern a P(VDF-TrFE) piezoelectric layer and the corresponding silver electrodes exploited for acceleration readout. The results achieved demonstrate that the proposed hybrid additive manufacturing technology is a very promising route for electro-mechanical sensors fabrication at the mesoscale.
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•The first fully additively manufactured piezoelectric accelerometer is described.•A hybrid production route that combines 3D printing and inkjet deposition is used.•Stereolithography is used to fabricated the structural part of the accelerometer.•Inkjet deposition is used to pattern a piezoelectric sensing gauge on the sensor.•The finished sensor shows capability to sense accelerations in the 0–10 g range.
Background Treatment with long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) can improve clinical outcomes in patients with heart failure (HF). Circulating levels of n-3 PUFA, an objective ...estimation of exposure, have never been measured in a large cohort of patients with HF. Methods We measured n-3 PUFA in plasma phospholipids at baseline and after 3 months in 1,203 patients with chronic HF enrolled in the GISSI-Heart Failure trial and randomized to n-3 PUFA 1 g/daily or placebo. N-3 PUFA levels were related to clinical characteristics, pharmacologic treatments, dietary habits, circulating biomarkers, and mortality. Results Baseline n-3 PUFA (5.1 ± 1.8 mol%) was associated with dietary fish intake, with an average difference of 43% between patients with the lowest and highest consumptions ( P < .0001). Baseline eicosapentaenoic acid (EPA) but not docosahexaenoic acid (DHA) was inversely related to C-reactive protein, pentraxin-3, adiponectin, natriuretic peptide, and troponin levels. Three-month treatment with n-3 PUFA raised their levels by 43%, independently of dietary fish consumption; increases in EPA levels were associated with decreased pentraxin-3. Low baseline levels of EPA but not DHA were no longer related to higher mortality after the addition of circulating biomarkers to multivariable models. Conclusion Before supplementation, circulating n-3 PUFA levels in patients with chronic HF mainly depend on dietary fish consumption and are inversely related to inflammatory markers and disease severity. Three-month treatment with n-3 PUFA markedly enriched circulating EPA and DHA, independently of fish intake, and lowered pentraxin-3. Low EPA levels are inversely related to total mortality in patients with chronic HF.
An intense systemic inflammatory response is observed following reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule protein released by neutrophils that intervenes in ...endothelial permeability regulation. In the present study, we investigated plasma levels of HBP in a large population of patients resuscitated from out-of-hospital cardiac arrest. We hypothesized that high circulating levels of HBP are associated with severity of post-cardiac arrest syndrome and poor outcome.
Plasma was obtained from 278 patients enrolled in a prospective multicenter observational study in 21 intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48 h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24 h Sequential Organ Failure Assessment (SOFA) score ≥ 12. ICU death and 12-month Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic regression tests and receiver operating characteristic curves with area under the curve (AUC) were performed.
Eighty-two percent of patients (229 of 278) survived to ICU discharge and 48 % (133 of 276) to 1 year with a favorable neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP were markedly elevated, 15.4 9.6-31.3 ng/mL, and persisted high 48 h later, 14.8 9.8-31.1 ng/mL. Admission levels of HBP were higher in patients who had higher 24 h SOFA and cardiovascular SOFA score (p < 0.0001) and in those who developed MODS compared to those who did not (29.3 13.7-60.1 ng/mL vs. 13.6 9.1-26.2 ng/mL, p < 0.0001; AUC = 0.70 ± 0.04, p = 0.0001). Admission levels of HBP were also higher in patients who died in ICU (31.0 17.7-78.2 ng/mL) compared to those who survived (13.5 9.1-25.5 ng/mL, p < 0.0001) and in those with an unfavorable 12-month neurological outcome compared to those with a favorable one (18.9 11.3-44.3 ng/mL vs. 12.8 8.6-30.4 ng/mL, p < 0.0001). Admission levels of HBP predicted early ICU death with an AUC of 0.74 ± 0.04 (p < 0.0001) and were independently associated with ICU death (OR 95 %CI 1.607 1.076-2.399, p = 0.020), but not with unfavorable 12-month neurological outcome (OR 95 %CI 1.154 0.834-1.596, p = 0.387).
Elevated plasma levels of HBP at ICU admission were independently associated with early death in ICU.
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