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Measurements of the gravitational constant G are notoriously difficult. Individual state-of-the-art experiments have managed to determine the value of G with high precision: although, when considered collectively, the range in the measured values of G far exceeds individual uncertainties, suggesting the presence of unaccounted for systematic effects. Here, we propose a Bayesian framework to account for the presence of systematic errors in the various measurement of G while proposing a consensus value, following two paths: a parametric approach, based on the maximum entropy principle, and a non-parametric one, the latter being a very flexible approach not committed to any specific functional form. With both our methods, we find that the uncertainty on this fundamental constant, once systematics are included, is significantly larger than what quoted in CODATA 2018. Moreover, the morphology of the non-parametric distribution hints towards the presence of several sources of unaccounted for systematics. In light of this, we recommend a consensus value for the gravitational constant G = 6. 6740 - 0.0015 + 0.0015 × 10 - 11 m 3 kg - 1 s - 2 . [ABSTRACT FROM AUTHOR]

Background: Reconstruction options following nipple-sparing mastectomy (NSM) are diverse and not yet investigated with level IA evidence. The analysis of surgical and oncological outcomes of NSM from the Italian National Registry shows its safety and wide acceptance both for prophylactic and therapeutic cases. A further in-depth analysis of the reconstructive approaches with their trend over time and their failures is the aim of this study. Methods: Data extraction from the National Database was performed restricting cases to the 2009-2014 period. Different reconstruction procedures were analyzed in terms of their distribution over time and with respect to specific indications. A 1-year minimum follow-up was conducted to assess reconstructive unsuccessful events. Univariate and multivariate analyses were performed to investigate the causes of both prosthetic and autologous failures. Results: 913 patients, for a total of 1006 procedures, are included in the analysis. A prosthetic only reconstruction is accomplished in 92.2 % of cases, while pure autologous tissues are employed in 4.2 % and a hybrid (prosthetic plus autologous) in 3.6 %. Direct-to-implant (DTI) reaches 48.7 % of all reconstructions in the year 2014. Prophylactic NSMs have a DTI reconstruction in 35.6 % of cases and an autologous tissue flap in 12.9 % of cases. Failures are 2.7 % overall: 0 % in pure autologous flaps and 9.1 % in hybrid cases. Significant risk factors for failures are diabetes and the previous radiation therapy on the operated breast. Conclusions: Reconstruction following NSM is mostly prosthetic in Italy, with DTI gaining large acceptance over time. Failures are low and occurring in diabetic and irradiated patients at the multivariate analysis. [ABSTRACT FROM AUTHOR]

Background: In the field of kidney transplantation, identifying early signatures of humoral rejection is a key challenge. Methods: We investigated the presence of anti-HLA antibodies and the distribution of lymphocyte subpopulations in 77 kidney-transplanted children and young adults compared to 23 healthy controls. Moreover, we tested whether the presence of anti-HLA antibodies could be related to modification in lymphocyte phenotype. Finally, we correlated the presence of anti-HLA antibodies and specific alteration of lymphocyte subsets with clinical outcomes. Results: In kidney-transplanted children who developed anti-HLA antibodies, we observed an expansion of double-negative B cells (CD19 + CD27-IgD-), indicating premature aging of this compartment. Moreover, we reported signs of impaired B cell regulation, indicated by a higher IL-21R+ B cell frequency associated with an abnormal increase of follicular helper T cells. Finally, a considerable reduction in CD8+ effector T and invariant Natural killer T (NKT) cells was observed. The stability of graft function over time is significantly correlated with the frequency of peripheral effector CD4+ and CD8+ T cells and invariant NKT cells. Conclusions: This study supports the usefulness of lymphocyte subset as one of a spectrum of early diagnostic tools required to identify patients at risk of developing donor alloimmune response. [ABSTRACT FROM AUTHOR]

Cyclosporin A (CsA) is an effective therapy for children with long-lasting nephrotic syndrome (NS). Long-term treatment can result in chronic CsA nephropathy (CsAN) and there is controversy concerning its incidence and severity. Trough levels are commonly used to monitor the drug concentration. We report a retrospective clinical and histological analysis of 18 children (12 males, 6 females) with steroid-dependent nephrotic syndrome (15 patients) and partially steroid-sensitive nephrotic syndrome (3 patients) treated with CsA for a long-term period (mean 4.9 years, range 2.2-6.9). Before CsA treatment all patients had normal creatinine clearance. CsA was started at a dose of 5 mg/kg per day administered orally in two divided doses and adjusted to maintain the mean CsA blood concentration between 250 and 350 ng/ml obtained from abbreviated area under the curve (AUC). A renal biopsy was performed after a mean period of 3.9 years (range 2.2-6.2) from the start of CsA treatment. Tubular, interstitial, and arteriolar lesions were evaluated in order to assess CsAN. The mean CsA dose and the mean CsA blood concentration were 4.4 mg/kg per day (range 3.6-5.8) and 276.6 ng/ml (range 162-346), respectively. No child had a worsening creatinine clearance during CsA treatment and follow-up after CsA discontinuation. If compared with the year before the start of CsA treatment, NS relapses and prednisone (PDN) dose significantly decreased during CsA treatment, 4/year versus 0.8/year (P<0.0001) and 0.9 mg/kg per day versus 0.2 mg/kg per day (P<0.0001), respectively. Histological analysis showed 15 patients with minimal change disease and 3 with focal segmental glomerulosclerosis. Clear-cut lesions diagnostic of CsAN were never found and only mild lesions were observed in 5 children (suggestive of CsAN in 2 patients and consistent with CsAN in 3 patients). Long-term CsA treatment is confirmed to be effective in preventing NS relapses and reducing PDN dose. Renal function is not a reliable indicator of CsAN. With the mean CsA blood concentrations used in our patients CsAN presented a low incidence (28%) and was generally mild. Renal biopsy should be performed 2-3 years from the start of long-term CsA treatment, especially if the mean CsA blood concentrations are not regularly monitored. [ABSTRACT FROM AUTHOR]

In this study we compared patient and technique survival of 163 new hemodialysis (HD) patients (age 11.4±3.1 years) and 295 peritoneal dialysis patients (7.7±4.8 years. P< 0.001), treated in 23 dialysis centers participating in the Italian Registry of Pediatric Chronic Peritoneal Dialysis (CPD) during the years 1989–2000. Three HD (1.8%) and 17 CPD (5.8%) patients died; the overall average death rate was 9.8/1,000 patient-years in HD and 29.8/1,000 patient-years in CPD patients. No statistically significant difference in patient survival between CPD and HD was found, while the survival of 102 CPD children younger than 5 years at the start of dialysis was lower (P=0.0001) than that of 193 CPD and 160 HD patients aged 5–15 years. We registered 12 modality failures among HD (7.4%) patients and 44 among CPD (14.9%) patients. The main causes were vascular access failure and patient choice in HD, and infection in CPD patients. Technique survival was lower (P=0.007) in CPD than in HD patients; a statistically significant difference (P=0.01) was also observed between both the 0- to 5- and the 5- to 15-year-old CPD patients and the HD patients aged 5–15 years. Logistic regression analysis confirmed age at initiation of dialysis to be a predictor of patient death (P=0.0001) in the whole patient population, and of technique failure in HD (P=0.006) but not in CPD patients (P=0.16). [ABSTRACT FROM AUTHOR]

Glomerulocystic kidney disease (GCKD) is a rare congenital condition that is usually reported in infants and young children. Only five cases of acquired GCKD after an acquired renal disease have been reported. Among these, two patients have developed cystic glomerular lesions following hemolytic uremic syndrome (HUS). We report a third case in a 2-year-old patient with this association. Common features between these three cases include atypical HUS, development of GCKD after prolonged peritoneal dialysis treatment, severe hypertension, and normal-sized kidneys without development of macroscopic cysts. Pathology findings in our patient include heavy expression of epidermal growth factor receptor in proximal tubules and evidence of obstruction of the glomerular outflow. We speculate that cystic dilatation of the Bowman's capsule may be secondary to ischemic lesions leading to proximal tubular obstruction. [ABSTRACT FROM AUTHOR]

The results of the first 3 year' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986-1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1:20.8 dialysis-months); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. The incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%. [ABSTRACT FROM AUTHOR]

Memory B cells (MBC) respond to secondary antigen challenge to protect against infection and to boost immunity following vaccinations. Despite effective treatment, chronic HIV infection disturbs MBCs by reducing numbers and altering functionality due to hyper-activation and increased apoptosis leading to suboptimal antibody responses against common infectious agents. We used single cell gene expression analysis to evaluate antigen-specific memory B cells in peripheral blood of virally-suppressed HIV-infected individuals and healthy controls stratified by serum H1N1 antibody response 3 weeks post-administration of the seasonal trivalent inactivated influenza vaccine. We used a fluorescent probe to isolate influenza H1N1-specific B cells and a multiplexed and targeted RT-PCR approach to measure expression levels of 96 genes involved in B cell activation and function. Gene profiling revealed a 4-gene predictive signature containing the phosphoinositide-3 kinase (PI3K) inhibitor, PTEN, for identifying antigen-specific MBC from HIV-infected individuals compared to healthy controls. Gene co-expression analysis showed that in addition to overexpression of PTEN, there was increased co-expression of type I interferon-associated genes with PTEN on single cell level in HIV compared to controls. This study highlights the persistent defects in MBC from HIV-infected individuals and points to the PI3K signaling pathway as a target for potential immune intervention. [ABSTRACT FROM AUTHOR]

A 10-year-old female with relapsing gross haematuria and Münchausen syndrome is reported, emphasizing the rarity of this situation in children and the difficult diagnostic pathway. A careful personality study of the patient and family members is absolutely necessary in order to proceed with diagnosis and successful treatment. [ABSTRACT FROM AUTHOR]