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ObjectiveThe impact of a screening programme on colorectal cancer (CRC) incidence in its target population depends on several variables, including coverage with invitations, participation rate, positivity rate of the screening test, compliance with an invitation to second-level assessment and endoscopists’ sensitivity. We propose a synthetic indicator that may account for all the variables influencing the potential impact of a screening programme on CRC incidence.DesignWe defined the ‘rate of advanced adenoma on the target population’ (AA-TAP) as the rate of patients who received a diagnosis of advanced adenoma within a screening programme, divided by the programme target population. We computed the AA-TAP for the CRC Italian screening programmes (biennial faecal immunochemical test, target population 50–69 year olds) using the data of the Italian National Survey from 2003 to 2016, overall and by region, and assessed the association between AA-TAP and CRC incidence fitting a linear regression between the trend of regional CRC incidence rates in 50–74 year old subjects and the cumulative AA-TAP.ResultsIn 2016, the AA-TAP at a national level was 105×100 000, whereas significant differences were observed between the northern and central regions (respectively 126 and 149×100 000) and the South and Islands (36×100 000). The cumulative AA-TAP from 2004 to 2012 was significantly correlated with the difference between CRC incidence rates in 2013–2014 and those in 2003–2004 (p=0.009).ConclusionThe AA-TAP summarises into a single indicator the potential impact of a screening programme in reducing CRC incidence rates.

The microfluidic technique has emerged as a promising tool to accelerate the clinical translation of nanoparticles, and its application affects several aspects, such as the production of nanoparticles and the in vitro characterization in the microenvironment, mimicking in vivo conditions. This review covers the general aspects of the microfluidic technique and its application in several fields, such as the synthesis, recovering, and samples analysis of nanoparticles, and in vitro characterization and their in vivo application. Among these, advantages in the production of polymeric nanoparticles in a well-controlled, reproducible, and high-throughput manner have been highlighted, and detailed descriptions of microfluidic devices broadly used for the synthesis of polysaccharide nanoparticles have been provided. These nanoparticulate systems have drawn attention as drug delivery vehicles over many years; nevertheless, their synthesis using the microfluidic technique is still largely unexplored. This review deals with the use of the microfluidic technique for the synthesis of polysaccharide nanoparticles; evaluating features of the most studied polysaccharide drug carriers, such as chitosan, hyaluronic acid, and alginate polymers. The critical assessment of the most recent research published in literature allows us to assume that microfluidics will play an important role in the discovery and clinical translation of nanoplatforms.

BackgroundCognitive deficits are associated with poor quality of life and increased risk of development of dementia in patients with Parkinson’s disease (PD) psychosis. The trajectory of cognitive decline in PD psychosis remains however unclear.ObjectiveWe examined this using data from the Parkinson’s Progression Markers Initiative study.MethodsWe analysed data from patients with drug-naïve PD (n=676) and healthy controls (HC, n=187) over 5 years, and examined all cognitive measures assessed at each time point. We classified patients with PD into those who developed psychosis over the course of the study (PDP) and those without psychosis throughout (PDnP) using the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part I hallucinations/psychosis item. We used linear mixed-effect models with restricted maximum likelihood. Age, sex, ethnicity, education and neuropsychiatric and PD-specific symptoms were entered as covariates of interest.FindingsThere were no baseline cognitive differences between PD patient groups. There were differences in cognitive performance between PD and HC across the majority of the assessments.Patients with PDP exhibited greater cognitive decline over 5 years compared with PDnP across most domains even after controlling for sociodemographics, depression, sleepiness, rapid eye movement sleep behaviour disorder and motor symptom severity (immediate recall, b=−0.288, p=0.003; delayed recall, b=−0.146, p=0.003; global cognition, Montreal Cognitive Assessment, b=−0.206, p<0.001; visuospatial, b=−0.178, p=0.012; semantic fluency, b=−0.704, p=0.002; processing speed, b=−0.337, p=0.029).ConclusionsPatients with PD psychosis exhibited decline in semantic aspects of language, processing speed, global cognition, visuospatial abilities and memory, regardless of sociodemographic characteristics, neuropsychiatric and motor symptoms. These cognitive domains, particularly semantic aspects of language may therefore play an important role in PD psychosis and warrant further investigation.Trial registration number NCT01141023.

BackgroundCognitive deficits and reduced dopamine transporter (DAT) binding ratio have been reported in Parkinson’s disease psychosis (PDP). However, it remains unclear whether DAT striatal binding ratio (SBR) may contribute to worsening cognitive performance in PDP.ObjectivesWe examined this using data from the Parkinson’s Progression Markers Initiative.MethodsWe analysed data from 392 PD patients, from baseline to year 4 follow-up, and classified patients into PD with psychosis (PDP) and without psychosis (PDnP). DAT SBR was available from 123I-FP-CIT-SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging. We examined all cognitive measures assessed at each time point; sociodemographic characteristics, neuropsychiatric and PD-specific symptoms were entered as covariates of interest.FindingsPDP patients had lower DAT SBR compared with PDnP patients (b=−0.092, p=0.035) over all time points, which remained significant after controlling for age, sex and ethnicity. PDP patients also reported worse trajectory of task performance on the Montreal Cognitive Assessment (MoCA) (b=−0.238, p=0.001) and symbol digit modality (b=−0.534, p=0.016) compared with PDnP patients. Declining performance in symbol digit modality (Group×Time×DAT SBR interaction, b=0.683, p=0.028) but not MoCA was differentially associated with the decline in DAT SBR over time. MoCA scores declined more in PDP compared with PDnP patients over all timepoints (Group×Time interaction, b=−0.284, p=0.016).ConclusionsDecline in striatal presynaptic dopamine function may specifically underlie longitudinal decline in performance in the symbol digit modality task that engages processing speed, associative learning and working memory in PD psychosis. Whether striatal presynaptic dopamine changes explain accelerated longitudinal decline in other cognitive domains in people with PDP remains to be tested.

Purpose To determine associations between red blood cell (RBC) transfusion and early and late clinical outcomes in massively transfused adult trauma patients. Methods A retrospective cohort study (1992–2001) including 260 patients receiving ≥10 RBC units ≤24 hr after admission to a university-affiliated trauma centre. We extracted demographic and clinical data and used multivariable regression to determine independent effects of RBC transfusion on clinical outcomes. Results Patients had a high (mean [standard deviation]) injury severity score (ISS) (42.5 [15.1]), a high admission sequential organ failure assessment (SOFA) score (8.4 [3.8]), and a high hospital mortality (58.5%). They received 38 (25–64) (median [interquartile range]) blood components within 48 hr, including 19 (14–28) RBC units. For 143 patients surviving ≥48 hr, the maximum SOFA score was associated with RBC units transfused before 48 hr (linear regression beta coefficient 0.075, P  < 0.0001), lower nadir hemoglobin before 48 hr (0.034, P  = 0.03), age (0.032, P  = 0.015), and admission SOFA (0.59, P  < 0.0001). The RBC units transfused by 48 hr were not associated with either hospital mortality ( n  = 35) among patients surviving ≥48 hr (independent predictors, age [logistic regression odds ratio (OR) 1.06, 95% confidence interval 1.03–1.10], ISS [OR 1.07, 1.02–1.13], and maximum SOFA score [OR 1.56, 1.27–1.93]) or 48-hr mortality ( n  = 117) (independent predictors, admission SOFA [1.65, 1.45–1.88] and later year of hospital admission [OR 1.15, 1.02–1.29]). Conclusions Hospital mortality is high among massively transfused trauma patients. Among early survivors, 48-hr RBC transfusion volume is associated with increased organ dysfunction, but not hospital mortality. Also, it is not associated with 48-hr mortality. Future research should continue to explore methods to improve hemostasis and minimize the need for RBC transfusion.

The experimental identification of transversal dispersivity in the laboratory is not a very developed subject; the authors herein propose two methods for identifying transversal dispersivity in laboratory experiments, based on the analytical solution of a continuous, point‐like, injection of a nonreactive solute in a flow tank packed with a homogeneous porous medium. The solute transport is supposedly two‐dimensional, whereas the hydraulic flow is monodimensional with a uniform velocity. Each identification method is based on the measurement of concentration in pairs of points. In the first method the points are taken along lines normal to the direction of the fluid flow, with one of the two points set on the central axis of the flow tank. In the second method the two measurement points are placed on lines passing through the solute injection point. The stability of the two methods, with respect to concentration measurement errors, is analyzed to assess the reliability of the transversal dispersivity estimate. Furthermore, the two methods are found to be sensitive to variations of the concentrations.

The inhibitory effect of bovine lactoferrin (BLf) saturated with ferric, manganese or zinc ions, on the infection of Vero cells by human herpes simplex virus type 1 (HSV1) and 2 (HSV2) was investigated. Viral infectivity determined by intracellular antigen synthesis and plaque formation was efficiently inhibited by metal saturated lactoferrins in a dose-dependent manner. Effective BLf concentrations which reduced the infection by 50% ranged from 5.2 to 31 micrograms ml-1 and were far below the cytotoxicity threshold. Fe3+BLf and Mn2+BLf exhibited selectivity indexes higher than Zn2+BLf and apoBLf for both viruses and the effect was mainly directed towards the early steps of infection. The slight viral inhibition shown by the citrate complexes of the different metals could indicate that the antiviral effect was not significantly influenced by Fe3+, Mn2+ or Zn2+ ions delivered by BLf into the cells.

A measure of human development, which is not affected by some relevant drawbacks of the commonly utilized measures, is constructed. It is a function of several attributes associated with various factors - economic, social, environmental - and also includes non-homogeneous attributes. It is non-linear in its variables, so that it includes possible interactions among the attributes. Furthermore, it takes into account public opinion about human development through a well-defined procedure of assessment elicitation. The formulation of the human development function constituting the measure is described when considering just one attribute and then several attributes, and the difference between independence and dependence in assessment is shown. Such a procedure is applied to the measurement of human development in 9 countries of the EU, by using thirteen attributes related to the economic, social and environmental fields as well as to the quality of life.