Geo-Neutrinos: from Theory to the KamLAND Results

Earth shines in antineutrinos produced from long-lived radioactive elements: detection of this signal can provide a direct test of the Bulk Silicate Earth (BSE) model and fix the radiogenic contribution to the terrestrial heat flow. In this paper we present a systematic approach to geo-neutrino production based on global mass balance, supplemented by a detailed geochemical and geophysical study of the region near the detector, in order to build theoretical constraints on the expected signal. We show that the prediction is weakly dependent on mantle modeling while it requires a good description of the crust composition in the region of the detector site. In 2005 the KamLAND experiment proved that the technique for exploiting geo-neutrinos in the investigation of the Earth's interior is now available. After performing an analysis of KamLAND data which includes recent high precision measurements of the 13C(α, n)16O cross section, we discuss the potential of future experiments for assessing the amount of uranium and thorium in different reservoirs (crust, mantle and core) of the Earth

Venous thrombo-embolism (VTE) prevention of patients undergoing total hip and knee replacement: budget impact analysis of apixaban in Italy

BACKGROUND: Venous thromboembolism (VTE) is a common and burdensome cardiovascular condition, frequently leading to severe complications and requiring high-cost healthcare interventions. New oral anticoagulants (nOACs) have demonstrated to be efficacious and safe in VTE prevention of patients undergoing total hip replacement (THR) and total knee replacement (TKR), a condition that is typically associated to cardiovascular disease. The Italian Healthcare Service (SSN) has recently approved the latest nOAC, apixaban. The present article aims to evaluate its economic impact in the perspective of the Italian SSN.METHODS: We conducted a budget impact analysis to estimate clinical outcomes and economic consequences associated to the reimbursement of apixaban, in the prevention of VTE as a consequence of major orthopedic surgery, over a three-year time horizon. In our analysis we compared two alternative scenarios, with apixaban either reimbursed (Scenario B) or not reimbursed (Scenario A) by the Italian SSN, and estimated the difference of healthcare costs between the two scenarios. Only direct healthcare costs have been considered.RESULTS: According to market assumptions, it is estimated that 1.2%, 3.7%, and 6.5% of THR patients, and 1.2%, 3.8% and 6.7% of TKR patients, would be treated with apixaban over the first three years since launch. At the estimated daily cost of apixaban (€2.48/die), this would translate into a budget impact of €14.3 mln, €45.5 mln, and €81.4 mln at years 1, 2 and 3 since launch, respectively. This expenditure would be more than offset by savings, due to: i) reduction of prescriptions of alternative treatment options (other nOACs, low-molecular weight heparins, fondaparinux); ii) reduction of the economic burden attributable of CV complications of VTE. Finally, Scenario B resulted slightly favourable compared to Scenario A, leading to economic savings for about €50 thousands over three years. Sensitivity analyses confirmed findings of the base-case analysis.CONCLUSIONS: Reimbursement of apixaban does not determine a budget impact increase for Italian SSN. Its usage may be considered fully sustainable from a pharmaco-economic viewpoint

NAFLD in Some Common Endocrine Diseases: Prevalence, Pathophysiology, and Principles of Diagnosis and Management

Secondary nonalcoholic fatty liver disease (NAFLD) defines those complex pathophysiological and clinical consequences that ensue when the liver becomes an ectopic site of lipid storage owing to reasons other than its mutual association with the metabolic syndrome. Disorders affecting gonadal hormones, thyroid hormones, or growth hormones (GH) may cause secondary forms of NAFLD, which exhibit specific pathophysiologic features and, in theory, the possibility to receive an effective treatment. Here, we critically discuss epidemiological and pathophysiological features, as well as principles of diagnosis and management of some common endocrine diseases, such as polycystic ovary syndrome (PCOS), hypothyroidism, hypogonadism, and GH deficiency. Collectively, these forms of NAFLD secondary to specific endocrine derangements may be envisaged as a naturally occurring disease model of NAFLD in humans. Improved understanding of such endocrine secondary forms of NAFLD promises to disclose novel clinical associations and innovative therapeutic approaches, which may potentially be applied also to selected cases of primary NAFLD

Universal divergenceless scaling between structural relaxation and caged dynamics in glass-forming systems

On approaching the glass transition, the microscopic kinetic unit spends increasing time rattling in the cage of the first neighbours whereas its average escape time, the structural relaxation time $\tau_\alpha$, increases from a few picoseconds up to thousands of seconds. A thorough study of the correlation between $\tau_\alpha$ and the rattling amplitude, expressed by the Debye-Waller factor (DW), was carried out. Molecular-dynamics (MD) simulations of both a model polymer system and a binary mixture were performed by varying the temperature, the density $\rho$, the potential and the polymer length to consider the structural relaxation as well as both the rotational and the translation diffusion. The simulations evidence the scaling between the $\tau_\alpha$ and the Debye-Waller factor. An analytic model of the master curve is developed in terms of two characteristic length scales pertaining to the distance to be covered by the kinetic unit to reach a transition state. The model does not imply $\tau_\alpha$ divergences. The comparison with the experiments supports the numerical evidence over a range of relaxation times as wide as about eighteen orders of magnitude. A comparison with other scaling and correlation procedures is presented. The study suggests that the equilibrium and the moderately supercooled states of the glassformers possess key information on the huge slowing-down of their relaxation close to the glass transition. The latter, according to the present simulations, exhibits features consistent with the Lindemann melting criterion and the free-volume model.Comment: 8 pages, 11 figure

Omission of dry period and effects on the subsequent lactation curve and on milk quality around calving in Italian Holstein cows

The aim of this study was to investigate the effect of dry period omission on subsequent milk production over a whole lactation and the effect on milk quality around calving. Seventeen Italian Friesian cows, homogeneous for milk yield and parity, were managed either with a traditional dry-off period of 55d (CTR group; n=8) or continuously milked up to parturition (CON group; n=9). Milk yield was recorded daily from 75±7 d before expected calving date to the end of subsequent lactation to fit the lactation curve. Before parturition milk samples were collected at -70 d, -60 d, and -55 d for CTR and CON groups and at -40 d, -30 d, and -7 d for CON cows. After calving, six milk samples were taken from 1d to 90 d from both groups and analyzed for fat, protein, lactose, MUN and somatic cells. Body weight (BW) and body condition (BCS) were obtained 7 times from -55 d before expected calving to 90 d after calving. The omission of the dry period modified the shape of lactation in CON cows that reached the peak 10 d earlier and producing - 5.5 kg/d than CTR. Over a 305 d period, the milk yield reduction was of -2241 kg in CON group. The higher amount of milk produced before calving, i.e., 560 kg of milk in 52 d of mean pre-partum period, did not compensate the milk yield reduction after a continuous lactation. Milk quality was unaffected by the omission of dry period after calving, and animals in both lactation groups showed a similar decreasing trends over time for fat and protein, and increasing trends for lactose and MUN. Somatic cell score remained higher (4.54 vs 3.40) in CON than in CTR cows after calving. No different BW or BCS changes were observed for both groups after calving. We conclude that despite the absence of great differences in milk quality, the complete omission of the dry period in cows reduce significantly the milk yield, suggesting no economical benefit from this management strategy

Type 2 diabetes mellitus and risk of hepatocellular carcinoma: spotlight on nonalcoholic fatty liver disease

The incidence of both type 2 diabetes mellitus (T2DM) and multiple cancer types are rapidly increasing worldwide. Several studies documented that T2DM is closely associated with an increased incidence of cancer. However, while some methodological considerations preclude a definitive association between T2DM and the risk of certain cancers, the relationship between T2DM and increased risk of incident hepatocellular carcinoma (HCC) remains significant even after adjustment for detection bias and reverse causation, indicating that such association is clinically reliable and robust. In addition, a number of observational studies also showed that T2DM is associated with higher mortality among persons with HCC. Some recent meta-analyses suggested that treatment with metformin may be associated with a lower risk of HCC, and may also beneficially influence HCC prognosis, whereas treatment with sulphonylureas or insulin seems to be related to a higher HCC risk. The underlying biological mechanisms linking T2DM and HCC are complex and difficult to elucidate, but the existence of close inter-connections among T2DM, obesity and nonalcoholic fatty liver disease (NAFLD) induces hepatic/systemic insulin resistance and causes the release of multiple pro-inflammatory cytokines, vasoactive factors and pro-oxidant molecules, which are all potentially implicated in the development and progression of HCC. In this clinical review, we discuss the epidemiological evidence linking T2DM to the risk of HCC. Moreover, we also briefly discuss the putative underlying mechanisms linking T2DM, NAFLD and HCC, and the potential effect of certain hypoglycemic agents on the risk of developing HCC

The Importance of Real-World Evidence in Understanding Influenza Vaccine Effectiveness

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Feeding dairy cows with full fat extruded or toasted soybean seeds as replacement of soybean meal and effects on milk yield, fatty acid profile and CLA content

The aim of this study was to evaluate the effects of the replacement of about 70% of soybean meal (SBM) with extruded(ES) or toasted (TS) full-fat soybean seeds in diets for lactating cows on milk quality, fatty acid profile, and conjugatedlinoleic acid (CLA) content. Eighteen lactating cows were assigned to 3 groups which received a basal diet, supplementedwith 1.8, 2.1 and 2.1 kg/head, respectively, of SBM, ES and TS. There was no significant effect on milk yield,calculated as the difference between daily yield during the experimental period and the mean of the last 5 days of adaptation(-1.65, -1.29 and -0.20 kg/d, respectively, for SBM, ES and TS; P>0.10) and milk quality parameters (fat, protein,urea and cheese making parameters) among treatments. In the ES group there was a decrease in the short chainFA content (from C4 to C13) in milk fat (9.2 vs 11.0 and 10.8 g/100 g lipids, respectively, for ES, SBM and TS; P<0.05).Medium chain FA (from C14 to C17) content in milk fat was lower for ES and TS groups compared with SBM (46.8 and48.0 vs 54.8 g/100 g lipids respectively; P<0.01), while long chain FA (C≥18) concentration in milk fat was lower in theSBM group compared to the others (34.3 vs 44.2 and 41.2 g/100 g lipids, respectively, for SBM, ES and TS; P<0.001).The replacement of SBM with ES enhanced oleic and linoleic acid and, particularly, CLA content. Intermediate values wereobserved for the TS group. CLA content (0.91, 0.62 and 0.56 g/100 g lipids, respectively, for ES, TS and SBM; P<0.05)increased throughout the trial in all groups. ES also reduced the proportion of SFA with respect to SBM (65.2, 68.2 and70.9 g/100 g lipids, respectively, for ES, TS and SBM; P<0.05), and increased MUFA (26.9, 24.5 and 23.1 g/100 g lipidsin the same order; P<0.05) and PUFA (7.4, 6.9 and 5.5 g/100 g lipids in the same order; P<0.05) of milk fat, thusimproving the health-quality of milk. The various soybean products did not affect either metabolic profile (protein, urea,glucose, cholesterol, NEFA, triglycerides, liver parameters and mineral serum content) or rumen parameters (pH, ammoniaand VFAs). The replacement of SBM with ES and TS permitted an improvement in the nutritional properties of milkwithout negatively affecting animal performances

The Long Pentraxin Ptx3 Is Synthesized in IgA Glomerulonephritis and Activates Mesangial Cells

Abstract The long pentraxin PTX3 has been recently involved in amplification of the inflammatory reactions and regulation of innate immunity. In the present study we evaluated the expression and role of PTX3 in glomerular inflammation. PTX3 expression was investigated in the IgA, type I membranoproliferative, and diffuse proliferative lupus glomerulonephritis, which are characterized by inflammatory and proliferative lesions mainly driven by resident mesangial cells, and in the membranous glomerulonephritis and the focal segmental glomerular sclerosis, where signs of glomerular inflammation are usually absent. We found an intense staining for PTX3 in the expanded mesangial areas of renal biopsies obtained from patients with IgA glomerulonephritis. The pattern of staining was on glomerular mesangial and endothelial cells. Scattered PTX3-positive cells were also detected in glomeruli of type I membranoproliferative glomerulonephritis. The concomitant expression of CD14 suggests an inflammatory origin of these cells. Normal renal tissue and biopsies from patients with the other glomerular nephropathies studied were mainly negative for PTX3 expression in glomeruli. However, PTX3-positive cells were detected in the interstitium of nephropathies showing inflammatory interstitial injury. In vitro, cultured human mesangial cells synthesized PTX3 when stimulated with TNF-α and IgA and exhibited specific binding for recombinant PTX3. Moreover, stimulation with exogenous PTX3 promoted mesangial cell contraction and synthesis of the proinflammatory lipid mediator platelet-activating factor. In conclusion, we provide the first evidence that mesangial cells may both produce and be a target for PTX3. The detection of this long pentraxin in the renal tissue of patients with glomerulonephritis suggests its potential role in the modulation of glomerular and tubular injury