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We evaluate an adaptive optimisation methodology, Bayesian optimisation (BO), for designing a minimum weight explosive reactive armour (ERA) for protection against a surrogate medium calibre kinetic energy (KE) long rod projectile and surrogate shaped charge (SC) warhead. We perform the optimisation using a conventional BO methodology and compare it with a conventional trial-and-error approach from a human expert. A third approach, utilising a novel human-machine teaming framework for BO is also evaluated. Data for the optimisation is generated using numerical simulations that are demonstrated to provide reasonable qualitative agreement with reference experiments. The human-machine teaming methodology is shown to identify the optimum ERA design in the fewest number of evaluations, outperforming both the stand-alone human and stand-alone BO methodologies. From a design space of almost 1800 configurations the human-machine teaming approach identifies the minimum weight ERA design in 10 samples.

AbstractWhen did the ‘modern garden’ appear? Studying the origin of this form of landscape design not only contributes to theory but also highlights the practical value of garden projects and, for the first time, recognizes the landscape architect as a professional. Identifying, analysing and critically interpreting the principles of the modern garden thus recognizes the importance of the professional skills of the landscape architect in contemporary times, and helps to communicate, highlight and reinforce the strategic contribution that he or she makes to our landscapes and cities. This article aims to demonstrate that the origin of the modern garden, generally attributed to the twentieth century, can be observed in the second half of the nineteenth century, when a new paradigm, the jardin paysager moderne, introduced by Jean-Pierre Barillet-Deschamps (1824-1873) and subsequently applied by the scholars of his école(E. Deny, A. and P. Péan, J. Vacherot), came to the fore in France. Based on innovative and revolutionary principles, such as the rationalization of the design process or the adoption of a comprehensive approach to the project, the new model laid the foundations for the modern garden and landscape art.

Évaluer l’impact économique des futures prescriptions de biosimilaires d’étanercept et d’adalimumab à l’échelle des territoires de santé couverts par le groupement de commandes des produits de santé PharmAlp’Ain.

Intradialytic hypotension (IDH) has a dramatic impact on the main outcomes of dialysis patients. Early warning of hemodynamic worsening during dialysis would enable preventive measures to be taken. Blood oxygen saturation (SO2) is used for hemodynamic monitoring in the critical care setting and may provide useful information about IDH onset. To evaluate whether short- and medium-term variations in the SO2signal (ST-SO2var, MT-SO2var,) during dialysis are a predictor of IDH. In this 3-month observational cohort study, 51 hypotension-prone chronic hemodialysis (HD) patients, with vascular access by arteriovenous fistula (AVF) or central venous catheter (CVC), were enrolled. Continuous non-invasive blood SO2was monitored (fc = 0.2 Hz) by an optical sensor on the arterial line of the extracorporeal circulation; blood pressure (every 30 min), symptoms and their time of appearance were noted. Predictive power of IDH was expressed by the area under curve (AUC) sensitivity and specificity based on intradialytic variations in SO2. A total of 1290 HD sessions were analyzed. Overall, off-line ST-SO2varanalysis proved able to correctly predict IDH in 67 % of the sessions where IDH occurred. The best predictive performance was found in the presence of highly arterialized AVF (SO2> 95 %) (75 % sensitivity; AUC 0.825; p < 0.05). On the contrary, in sessions with CVC, IDH prediction proved more efficient by MT-SO2var(AUC 0.575; p = 0.01). Intradialytic SO2variability could be a valid parameter to detect in advance the hemodynamic worsening that precedes IDH. Appropriate timely intervention could help prevent IDH onset.

The purpose of this study is to introduce a new approach of high speed cutting numerical modelling. A lagrangian Smoothed Particle Hydrodynamics (SPH) based model is carried out using the Ls-Dyna software. SPH is a meshless method, thus large material distortions that occur in the cutting problem are easily managed and SPH contact control permits a “natural” workpiece/chip separation. Estimated chip morphology and cutting forces are compared to machining dedicated code results and experimental data. The developed SPH model proved its ability to account for continuous and shear localized chip formation and also correctly estimates the cutting forces, as illustrated in some orthogonal cutting examples.

The Central Limit Theorem is presented showing how a uniform distribution, generated with a dice, tends to converge to a normal distribution when the number of thrown dices becomes large enough.

The paper presents a very simple introduction to the concept of confidence interval for both a proportion and a mean. The confidence interval is useful when analyzing data that refer to a sample extracted from a target population. The confidence interval defines the upper and lower values of the interval of the variable we are studying; in other words, it defines the interval that one should expect, with a predefined level of confidence, to contain the true value of the proportion or the mean value of the population.

Relative survival, a methodology previously used in epidemiologic studies of cancer, compares the observed survival of a patient cohort with expected survival derived from general population life tables. We examined relative survival in patients treated by long-term dialysis in the Italian Dialysis and Transplantation Registry in order to determine the prognosis of dialysis patients.

Angiogenesis is a key event in the natural progression of gliomas. Nestin, a marker for multipotential neuroepithelial stem cells, is detected in neuroepithelial tumors and in proliferating endothelial cells (ECs) and is involved in the early stages of lineage commitment, proliferation and differentiation. Nestin expression is correlated with proangiogenic chemokines (CXCL12 and its receptor CXCR4) and growth factors (VEGF, PDGF-B and its receptor PDGFR-β). VEGF expression upregulates CXCR4 on endothelial cells, binding the chemokine SDF1/CXCL12 (Stromal Derived Factor) that has a role on angiogenesis and chemotaxis of endothelial cells; PDGF (platelet-derived growth factor) and PDGFR-β are also crucial by increasing the expression of VEGF. We performed a retrospective study on the presence and role of nestin-expressing cells in 102 patients with glioma, relating the findings to VEGF, CXCL12, PDGFR-β expression and to clinical outcome (time to tumor progression-TTP and survival time-ST). Our results suggest that in gliomas the detection of proliferating ECs expressing nestin correlates to histological malignancy grade and clinical outcome. Also, the expression of CXCL12 in low-grade gliomas was the only factor associated with a significantly shorter TTP, suggesting a role of this chemokine in angiogenic shift and/or disease progression.

Background Numerous investigations have reported that viral hepatitis is associated with significant hepatocellular damage, as expressed by raised aminotransferases in serum, in dialysis population. However, scarce information exists on the activity of gamma glutamyltranspeptidase (GGTP) in dialysis patients with infection by hepatotropic viruses.Objectives We measured serum GGTP values in a large cohort (n=757) of patients receiving long-term dialysis; healthy controls were also included. The relationship between GGTP values and a series of demographic, clinical, and biochemical parameters was analyzed.Methods Serum GGTP levels were tested by spectrophotometry. A subset (n=333) of dialysis patients was tested by molecular technology (branched-chain DNA (bDNA) assay) to evaluate the relationship between serum GGTP and HCV viremia. A subgroup (n=78) of dialysis patients was analyzed by an ultrasound scan of gallbladder and biliary tract to assess the presence of gallstone disease. Multivariate analyses were made using regression models; serum GGTP values were included as a dependent variable. The usefulness of serum GGTP levels in detecting HBsAg and anti-HCV positivity was evaluated using receiver operating characteristics (ROC) curve analysis.Results Univariate analysis showed that serum GGTP levels were significantly higher in HBsAg positive and/or anti-HCV positive patients than in HBsAg negative/anti-HCV negative patients on dialysis; 85.1±184.1 versus 25.86±23.9 IU/l (P=0.0001). The frequency of raised GGTP levels was 22.2% (41/184) among dialysis patients with chronic viral hepatitis. Multivariate analysis showed a significant and independent association between serum GGTP values and positive HBsAg (P=0.005) and anti-HCV antibody (P=0.0001) status. Mean GGTP values were significantly higher in study patients than controls, 32.32±60.02 versus 23.5±16.92 IU/L (P=0.01); however, no significant difference with regard to GGTP between study and healthy cohorts persisted after correction for age, gender, race, and viral markers. No relationship between gallstone disease and serum GGTP was found (NS). An independent and significant association (P=0.0291) between raised GGTP levels and detectable HCV RNA in serum was noted among patients tested by biology molecular techniques. ROC technology demonstrated that GGTP was equally useful for detecting HBV (P=0.0004) and HCV (P=0.0005) among dialysis patients.Conclusions We found an independent and significant association between serum GGTP values and HBsAg and/or anti-HCV antibody in dialysis population. Twenty-two percent of dialysis patients with chronic viral hepatitis had elevated GGTP. No difference in GGTP between HBsAg- negative/anti-HCV-negative dialysis patients and healthy individuals was found. Routine testing for serum GGTP levels to assess liver disease induced by hepatotropic viruses or other agents in dialysis population is suggested.

ABSTRACTDialysis patients remain a high-risk group for hepatitis C virus (HCV) infection. The current diagnosis of HCV infection among dialysis patients includes serological assays and nucleic acid amplification technology (NAT) for assessing serum anti-HCV antibody and HCV viremia, respectively. However, current NAT techniques are expensive and labor-intensive and often lack standardization. An assay prototype designed to detect and quantify total HCV core antigen (total HCV core Ag) protein in serum and plasma in the presence or absence of anti-HCV antibodies has been recently developed. A comparison between a total anti-HCV core Ag enzyme-linked immunosorbent assay (ELISA) and a quantitative HCV RNA assay based on reverse transcription-PCR (RT-PCR) (Amplicor HCV Monitor test) was performed using a large (n= 305) cohort of ELISA HCV 3.0 HCV-negative and -positive patients on maintenance dialysis. The concentrations of HCV core Ag and HCV RNA levels (measured by RT-PCR) were significantly correlated (r= 0.471, P= 0.0001) over a wide range of HCV RNA levels and were maintained among different HCV genotypes (HCV genotype 1, r= 0.862, P= 0.0001; HCV genotype 2, r= 0.691, P= 0.0001). We estimated that 1 pg of total HCV core Ag per ml is equivalent to approximately 19.952 IU of HCV RNA per ml, even if the wide range in the ratio of core Ag to HCV RNA (95% confidence intervals, 2.8 × 103to 1.6 × 105IU/ml) precluded definitive conclusions. In summary, total HCV core Ag proved to be useful for performing HCV RNA measurement among dialysis patients in routine laboratories without the need for special equipment or training. The present study supports the use of the total anti-HCV core Ag ELISA for assessing viral load among dialysis patients with HCV infection.

The authors investigated two unrelated patients with Creutzfeldt-Jakob disease (CJD) with clinical features of sporadic CJD (sCJD) carrying one extra octapeptide repeat in the prion protein (PrP) gene (PRNP). A synaptic type PrP distribution throughout the cerebral gray matter and plaque-like PrP deposits in the subcortical gray structures were detected immunocytochemically. The different patterns of PrP deposition were associated with distinct types of protease-resistant PrP, similar to type 1 and type 2 of sCJD. The features suggest that this insertion is a pathogenic mutation.

Control of the spread of hepatitis B virus (HBV) infection in dialysis units has been one of major advances in the management of end-stage renal disease. However, the natural history of HBV in dialysis patients remains unclear. The aim of this study is to measure monthly HBV viral load (HBV DNA) in a large cohort (n = 29) of hepatitis B surface antigen (HBsAg)-positive chronic dialysis patients during 12 months.

The growing proportion of elderly patients largely accounts for the striking increase in number of patients admitted to renal replacement treatment (RRT) in recent years. Most of them are treated with haemodialysis, which involves various problems connected with vascular access. A survey was therefore conducted amongst the Dialysis Units of Lombardy. The aim was to evaluate how vascular access surgery for elderly patients is organized, and which techniques are used to monitor surgical access as well as the central catheters (CVCs). A questionnaire was sent to the 43 Lombardy Units, 79.1% of which replied. The results of a previous study analyzing the same topics in all patients on RRT in Lombardy were considered as “controls”. In this way it was possible to compare the strategy used for elderly patients with that of the general dialysis population.Forty-one percent (41%) of elderly patients in Lombardy were started on RRT using acute CVCs. This percentage is quite similar to that documented (39%) in the general dialysis population. The distribution is quite different when we consider the patients alive on RRT at 31 December 1999, when a permanent vascular access (distal AVF, proximal AVF or AV graft) was used in about 70% of cases.For elderly patients, as for the general RRT population, first choice access is mainly (79%) distal arterio-venous fistula (AVF) with end-to-end, side-to-side with distal ligature of the vein or side-to-end anastomosis. As a second choice, proximal AVF is more widely used than AV grafts, which are implanted only when all native vessels and related surgical procedures are exhausted.CVCs are valid solutions not only as temporary access, but also as an alternative permanent solution to the problems related to elderly dialysis patients. In the elderly, the jugular vein is the most frequent site of insertion for chronic tunnelled devices (91%) and the femoral vein for acute CVCs (40%). Despite the documented incidence of related episodes of stenosis/obstruction, the subclavian vein is used as a temporary access in quite a high percentage of cases (22% in the elderly and 32% in the general RRT population).Only in selected cases diagnostic procedures (mainly Venography and Doppler studies) are performed prior to permanent access choice. Similarly, vascular access is monitored mainly using a recirculation test, albeit not routinely. As in the general dialysis population, in the cases of vascular access thrombosis and stenosis, surgical revision is the most common approach.

To evaluate the organisation of vascular access surgery, the techniques used to monitor surgical access and the central catheters, a survey was conducted amongst dialysis Units of Lombardy. A questionnaire was sent out to the 43 dialysis centres in Lombardy, 96% of which replied.In almost 90% of dialysis units nephrologists perform vascular access albeit in close cooperation with vascular surgeons for the more complex cases.First choice access is by distal arteriovenous fistula (AVF): 36% end-to-end, 31.7% side-to-end, and 19.5% side-to-side with distal ligature of the vein.As second choice proximal AVF is more widely used than AV grafts, which are implanted only when all native vessels and related surgical procedures are exhausted.Central venous catheters offer valid solutions not only as temporary access, but also as an alternative permanent one. In both cases the jugular vein is the most frequent site of insertion. Despite the documented incidence of related episodes of stenosis/obstruction, the subclavian vein is used as a temporary access in quite a high percentage of cases.Only in selected cases are diagnostic procedures (mainly Venography and Doppler studies) performed prior to permanent access choice. Similarly vascular access is monitored mainly using a recirculation test albeit not routinely. In case of vascular access thrombosis, surgical revision is the most common approach.

Our objective was to analyze the survival of diabetic patients on renal replacement therapy and to compare their survival on extracorporeal and on peritoneal dialysis. All data regarding diabetic patients admitted to dialysis between 1 January 1983 and 31 December 1993 were collected by means of individual patient questionnaires sent to all of the 44 regional Renal Units (100% answers) of Lombardy, Italy. Cox proportional hazards model, stepwise procedure, was applied in order to select the covariates significantly associated with survival. Age (at baseline), sex, type of diabetes, initial modality of treatment (hemodialysis or peritoneal dialysis), and initial clinical risk factors (malignancies, serious heart disease, vascular disease, cirrhosis of the liver, cachexia) were considered. Descriptive analysis of survival was performed using the Kaplan-Meier technique. The survival of all diabetic patients (895) was 86.5% at one year, 52% at three years, an d 34% at five years. The main causes of the 488 deaths of diabetic patients were cardiovascular diseases (56%), cachexia (18%), and infections (11%). The relative death risk of patients on peritoneal dialysis versus those on hemodialysis, after taking into account the main comorbid conditions, did not significantly differ from 1, as estimated by the Cox proportional hazards regression model. Five-year survival of diabetic patients was 34%, and no differences were found between peritoneal dialysis and hemodialysis as far as mortality is concerned.

The aim of this study is to evaluate the relationship between two different procedures for potassium removal during hemodialysis (HD) and cardiac arrhythmias. Cell excitability and the transmission of impulses may be influenced by variations of resting membrane potential (RMP). The rapid decrease of plasma potassium during the first two hours of standard HD causes a membrane hyperpolarization. A different K+ kinetic, with a gradual and constant elimination of K+ during HD, may reduce this further unphysiological aspect and its clinical consequences. This can be obtained keeping blood-dialysate K+ gradient as constant as possible with the use of a dialysate K+ concentration (Kd) decreasing during HD. Our experimental studies on various K+ intradialytic gradients seem to indicate as optimal to this purpose K+ gradients of 1.5 mEq/l at the beginning of dialysis, esponentially decreasing during treatment to Kd values of 2.5 mEq/l at the end of dialysis (variable Kd). Patients included in the trial will be submitted to two different methods of treatment with Kd 2 mEq/l and variable Kd, and to a 24 hours ECG the day of dialysis. We will compare the number of intra and interdialytic premature ventricular complexes to evaluate the impact of two different models of potassium removal on arrhythmias.

This 1993 report of the Lombardy Regional Dialysis and Transplant Registry refers to all the data collected between January 1, 1983, and December, 31, 1992, by means of individual patient questionnaires sent to all of Lombardy's 44 renal units (100% replies). The number of patients recorded by the Registry as being alive progressively increased; by the end of 1992, the number was 6,014 (655 patients per million population); 4,770 patients were on dialysis treatment (515 patients per million population, 79.3%) and 1,244 patients (140 patients per million population, 20.7%) had received a kidney graft. The acceptance rate for dialysis increased from 64 per million population in 1983 to 102 per million population in 1992; the increase in the transplant rate was much lower (from 18.7 to 21.3 per million population). The percentage of primary nephropathies in the new patients accepted for dialysis treatment were 22.0% glomerulonephritis, 13.8% interstitial nephritis, 15.2% vascular diseases, 10.1% cystic kidney, and 10.6% diabetes. The use of acetate hemodialysis declined over the 10-year period from 72.4% to 17.5%; that of bicarbonate hemodialysis increased from 8.8% to 50.1% and that of hemodiafiltration increased from 0.2% to 11.1%. The prevalence of hospital hemodialysis was stable, ranging from 55.4% to 52.2%; home hemodialysis decreased from 15.7% to 5.3%, continuous ambulatory peritoneal dialysis increased from 13.3% to 19.6%, and limited care increased from 13.7% to 22.4%. The crude death rate increased from 7.5% in 1983 to 10.5% in 1992. The survival rate (Kaplan-Meier) of all patients on dialysis was 78.8% at 2 years, 62.2% at 4 years, and 40% at 8 years; for transplanted patients, the survival and graft survival rate at 2 years was, respectively, 95% and 86%. The relative death risk of the patients on peritoneal dialysis with respect to those on hemodialysis was 1.419, as estimated by the Cox proportional hazard regression model. The main causes of deaths of patients on dialysis treatment during the year 1992 were cardiovascular diseases (47.0%) and cachexia (19.5%); in transplanted patients, they were cardiovascular diseases (36.6%) and infections (34%). Registries are not only important for planning health care but are also very useful instruments for clinical research.

The creatinine measure obtained in 300 healthy males is presented as an example of normal distribution, together with the concept of standardized Gaussian curve.

The Gaussian function is presented as one of the first possible options to describe the distribution of data that have a high frequency in their middle values and a low frequency in their extreme values. The Euler's number e and its derivation are also here presented.

The paper presents a brief exposition about the false and potentially dangerous results which may arise from a wrong sample choice or a biased interpretation of even a single question, in particular when the privacy of the patient is involved.

The relationship between the probability of realization of an event and the information obtained from the evnt itself is presented.The discussed example refers to codon and amino acids.