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Our aim was to analyse, on a population level, the year-long decline in cancer diagnoses in the region of Lombardy (Italy), and to characterise the tumours with the greatest reduction in diagnosis by patient age, sex and tumour stage at diagnosis. We used the health care utilisation databases of the Lombardy region to identify cancer patients' characteristics (eg, sex, age) and cancer-related information (eg, cancer site, stage at diagnosis). The frequency of new cancer diagnoses in 2019 and 2020 were compared in terms of percentage differences in undiagnosed cases. We observed two peaks in the decline in cancer diagnoses: March to May 2020 (-37%) and October to December 2020 (-19%). The decline persisted over the course of 2020 and was higher in males and patients aged 74+. Diagnoses of all four common cancers analysed (female breast, lung, colorectal and prostate) remained below pre-pandemic levels. For breast and colorectal cancers, the decline in diagnoses was high in the age groups targeted by population-based screening programmes. We observed a reduction in localised stage cancer diagnoses for all four cancers. Our data confirm that timely monitoring of cancer diagnoses and interventions to prevent disruption of routine diagnostic services are needed to mitigate the impact of emergencies on cancer patients.

Objective Seropositive rheumatoid arthritis (RA) is a chronic autoimmune disease that is rarely "cured." Human mesenchymal stem cells (hMSCs) are known to reduce inflammation and restore immune homeostasis. However, methods for predicting therapeutic hMSC potency have not been established. The goal of these studies was to use and refine an ex vivo functional assay that determines potency of hMSCs and can then be validated in clinical trials as a potency measure of hMSCs used therapeutically to treat RA. Methods Allogeneic hMSCs were cytokine-stimulated, and a conditioned medium (CM) was harvested. The CM was tested for the potential to attenuate RA CD4+ T cell proliferation using suppression assays. Indoleamine 2, 3-dioxygenase (IDO) mRNA, and protein were quantified in hMSCs as a measure to compare hMSCs across (prior) studies. Results To mimic a proinflammatory environment that resembles that in RA, interleukin-1(IL1β), tumor necrosis factor α (TNFα) , and interferon γ (IFNγ) (alone or in combination) were used to precondition hMSCs. Treating hMSCs with a combination of these cytokines generated a CM "secretome" that suppressed T cell proliferation between 70 and 83%. Forty-eight hours of cytokine preconditioning hMSCs was required to maximize this effect. T cell suppression positively correlated with increases in hMSC cellular IDO mRNA and protein. Conclusion By standardizing assays to measure hMSC effects, their potency on T cell suppression can be quantified. These studies demonstrate that hMSCs can be compared functionally to identify optimal preparation(s) for therapeutic use in RA and that the potency of hMSC-dependent T cell suppression may differ between hMSC donors. Clinical studies are warranted to validate the hypothesis that ex vivo potency in suppressing T cells will positively correlate with a reduction in RA disease activity and increase in immunological quiescence.

Over the last two decades, many studies have contributed to improving our understanding of the brittle failure mechanisms of boron carbide and provided a road map for inhibiting the underlying mechanisms and improving the mechanical response of boron carbide. This paper provides a review of the design and processing approaches utilized to address the amorphization and transgranular fracture of boron carbide, which are mainly based on what we have found through 9 years of work in the field of boron carbides as armor ceramics.

PURPOSE The response of human cells to applied electrical signals depends on the cellular health status, because it is influenced by the composition and structure of the main cellular components. Therefore, electrical impedance-based techniques can be considered as sensitive tools to investigate healthy or disease state at cellular level. The goal of this study is to show that different types of in vitro cellular lines, related to different health status, can be differentiated using impedance spectra analysis. METHODS Three different types of human breast cell line, corresponding to healthy, cancerous, and metastatic adenocarcinoma cells, were measured by means of electrical impedance spectroscopy. By modeling the investigated cells with proper resistive and capacitive circuital elements, the magnitude of the cell electrical components and spectra of real and imaginary part of dielectric permittivity were obtained. The latter were subsequently examined with a commonly adopted mathematical model, in order to estimate the values of specific dielectric parameters for the three different cellular lines. RESULTS The relative variation of cellular capacitance with respect to that of the culture medium, estimated at 100 Hz, has a larger value for the two types of cancerous cells with respect to the noncancerous type. Furthermore, the ratio between the real and imaginary part of the dielectric permittivity function has larger values for metastatic cells with respect to the normal and nonmetastatic ones. Therefore, the mentioned relative capacitance allows to discriminate between normal and cancerous cells, whereas the results obtained for the dielectric function can discriminate between metastatic and nonmetastatic cells. CONCLUSIONS This study can be considered as an exploratory investigation of evaluating in vitro the health status of humans cells using selected electrical impedance parameters as potential markers. The obtained results highlight that a standard cultureware system, provided with interdigitated electrodes and appropriate impedance parameters, that is, cellular capacitance and the ratio between the imaginary and real part of cellular dielectric function, can be used to discriminate between healthy and cancerous breast cell lines, as well as different malignancy degrees.

Aims There is a strong interest in identifying the biological mechanisms involved in the genetic risk for psychotic disorders. In this study, we evaluated the correlation between serum concentrations of specific molecular markers and the genetic component for schizophrenia and bipolar disorder. Methods We analysed the association between the polygenic risk score (PRS) and the serum levels of different inflammatory/metabolic markers in a sample of 81 first-episode psychosis patients (FEP) with a diagnosis of schizophrenia or bipolar disorder and 33 controls. Results A positive correlation of schizophrenia and bipolar disorder PRS with the inflammatory marker C-C Motif Chemokine Ligand 4 serum concentration (ρ = 0.42, P = 1.56 × 10-04 and ρ = 0.40, P = 1.65 × 10-03 , respectively) and a negative correlation with the serum ghrelin content (ρ = - 0.35, P = 4.27 × 10-03 and ρ = - 0.45, P = 6.05 × 10-04 , respectively) were observed. Conclusion These findings provide new insight into the biological underpinnings of the PRS component, thus supporting a role of the genetic liability on the inflammatory and metabolic alterations that characterize psychosis onset.

High-temperature annealing, known as Tabula Rasa (TR), proves to be an effective method for dissolving oxygen precipitate nuclei in n-Cz silicon and makes this material resistant to temperature-induced and process-induced lifetime degradation. Tabula Rasa is especially effective in n-Cz wafers with oxygen concentration >15 ppma. Vacancies, self-interstitials, and their aggregates result from TR as a metastable side effect. Temperature-dependent lifetime spectroscopy reveals that these metastable defects have shallow energy levels ~0.12 eV. Their concentrations strongly depend on the ambient gases during TR because of an offset of the thermal equilibrium between vacancies and self-interstitials. However, these metastable defects anneal out at typical cell processing temperatures ≥850°C and have little effect on the bulk lifetime of the processed cell structures. Without dissolving built-in oxygen precipitate nuclei, high-temperature solar cell processing severely degrades the minority carrier lifetimes to below 0.1 millisecond, while TR-treated n-Cz wafers after the cell processing steps exhibit carrier lifetimes above 2.2 milliseconds.

We report vibrational spectra of two types of eumelanin samples: a synthetic one, produced by oxidation of tyrosine with hydrogen peroxide, and a natural one, extracted from Sepia officinalis, with the aim of pointing out the differences between the main vibrational properties of such two pigments. Fourier transform infrared, Raman and surface-enhanced Raman scattering spectra allow the identification of several vibrational modes involving specific monomeric units. The main differences between the spectra of the two types of eumelanin are related to (i) a larger amount of carboxylic acid in the synthetic than in the natural sample; (ii) a shift of spectral position of corresponding peaks; and (iii) a contribution of residual proteins to the signals from the natural sample. Such results suggest that vibrational techniques may be helpful for non-destructively determining the composition of various eumelanin pigments, with potential applications in biomedical, electronic and cultural heritage fields. © 2016 Society of Chemical Industry

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the effectiveness of intratracheal administration of synthetic protein‐free pulmonary surfactant in neonates at risk of developing RDS or with established RDS. Comparison 1: Does intratracheal administration of synthetic protein‐free pulmonary surfactant compared to air placebo or normal saline or no treatment reduce mortality and other complications of preterm birth in preterm infants at risk of developing RDS? Comparison 2: Does intratracheal administration of synthetic protein‐free pulmonary surfactant compared to air placebo or normal saline or no treatment reduce mortality and other complications of preterm birth in preterm infants with clinical and/or radiologic evidence of respiratory distress syndrome requiring assisted ventilation?

The indentation-size effect (ISE) in a commercial SiAlON was investigated by conducting Knoop indentation between 0.1 and 20 kg. The resulting ISE was analyzed utilizing Meyer's Law, Proportional Specimen Resistance (PSR) model, and a Multifractal Scaling Law (MFSL). Meyer's law and the PSR model fits to the hardness–load data were not excellent. Further analysis based on the PSR model and MFSL revealed three piecewise linear fits corresponding to load regimes 0.1–0.3, 0.5–2, and 5–20 kg. Physical inference of MFSL fit parameters suggested that these three load regimes correspond to where indentation behavior is governed by deformation mechanisms limited to single grains, grain boundaries, and multiple grains, respectively. Independent of the ISE analysis results, comprehensive examination of indents by scanning electron microscopy revealed that changes in deformation mechanisms could also be grouped into these three load regimes. Corresponding changes in deformation mechanisms were microcleavage cracking, grain-boundary cracking, and macrocracking, respectively. These observations are consistent with the findings of both the PSR model and MFSL with respect to the physical aspects of the governing mechanisms. It is concluded that these mechanisms are responsible for the observed ISE in this commercial SiAlON.

Objective To examine in a sample of hematopoietic stem cell transplant patients assessed throughout protective isolation (i) levels of anxiety and depression and (ii) pre-isolation factors (socio-demographics, biomedical variables and personality traits), which might predict higher levels of anxiety and depression during isolation. Methods The study used a longitudinal prospective design. Anxiety and depression were assessed in 107 participants by the State-Trait Anxiety Inventory and Self-rating Depression Scale at admission and weekly at fixed time points throughout isolation. Among pre-isolation factors, patients' psychological status was evaluated by the Cognitive Behavioral Assessment (2.0). Predictors were explored by random-effects models. Results One-tenth of the patients suffered from clinically significant anxiety and depressive symptoms at admission. Although the percentage of depressed patients increased more than twofold after 2 weeks of isolation, that of anxious patients did not significantly change over time. Female gender, higher anxiety and obsessive–compulsive symptoms, intratensive personality traits and lower performance status predicted higher depression during isolation. Conclusions Anxiety and depression represent a relevant problem for hematopoietic stem cell transplant patients during isolation. Early detection of predictors, such as anxiety levels, obsessive–compulsive symptoms and performance status, could help prevent depression via targeted psychological intervention. Copyright © 2012 John Wiley & Sons, Ltd.

In Tabor's classical studies of the deformation of metals, the yield stress (Y) and hardness (H) were shown to be related according to H/Y {approx} 3 for complete or fully plastic deformation. Since then it has been anecdotally shown for ceramics that this ratio is

Summary Morphological changes of normal human keratinocyte cellshave been monitored by means of atomic force microscopyafter the exposure at a mercury solution containing HgCl 2 at10 −7 M. The measurements have been carried out in contactmode in a thermostated liquid cell, to reproduce a cellularenvironment similar to the physiologic one. Remarkablealterations of the cellular morphology and volume havebeen revealed after few minutes from starting the exposureexperiment, although the HgCl 2 concentration is severalordersofmagnitudeslowerthanthecytotoxicvalue(10 −4 M).The atomic force microscopy technique results to be apowerful mean to investigate modifications induced in thecellmorphologybyexternalchemicalagents. Introduction The toxic effects of mercury and its compounds for humansand animals have been verified in several studies (Langford& Ferner, 1999; Magos & Clarkson, 2006). They aredue to its high affinity to sulphydryl groups contained inproteins. Recently, the European Union established to castoff some common mercury-containing clinical instruments,as thermometers and sphygmomanometers, because ofpoisoning risk (European Council Directive 2007/51/CE).Mercury is naturally present in the earth’s crust. It isalso present in the atmosphere either derived naturallyfrom the degassing of the earth’s crust, emissions fromvolcanoes,evaporationfromtheworld’sseasorfromindustrialpollution. In addition, several human activities involve

Raman micro-spectroscopy can be used to investigate biological single cells exposed to different chemicals. Since chronic exposure at low doses of pesticides can promote several diseases, the investigation of cellular changes induced by exposure to non-cytotoxic doses of pesticides is of increasing interest. The efficiency of Raman micro-spectroscopy to detect chemical modification in normal human keratinocytes induced by exposure to non-cytotoxic doses of chlorpyriphos, an organophosphate pesticide present in many plant-protection products, was investigated. Such modification affects mainly proteineous components (both single amino acids and amide linkages between amino acids) of the nucleus, cellular membranes and cytoplasm as well as the nucleic acid component of the nucleus. Chemical modifications are already detectable after 24 h exposure of keratinocytes at a chlorpyriphos concentration of 10−6M, which is three orders of magnitude lower than the cytotoxic concentration (10−3M). Heavy damage to the lipid component occurs after exposure to the nearly cytotoxic concentration (10−4M). Atomic force microscopy images of keratinocyte cells exposed for 24 h to various chlorpyriphos concentrations show a progressive deterioration of the morphology of cellular membrane as the chlorpyriphos concentration increases. The results of this work may have wide applications in the monitoring of molecular changes in single human cells exposed to toxic agents. Copyright © 2010 John Wiley & Sons, Ltd.

Quasi-static Weibull strength-size scaling of hot-pressed silicon carbide is described. Two surface conditions (uniaxial ground and uniaxial ground followed by grit blasting) were explored. Strength test coupons sampled effective areas from the very small (4 × 10−3 mm2) to the very large (4 × 104 mm2). Equibiaxial flexure and Hertzian ring crack initiation were used for the strength tests, and characteristic strengths for several different specimen geometries were analyzed as a function of effective area. Characteristic strength was found to substantially increase with decreased effective area for both surface conditions. Weibull moduli of 9.4- and 11.7 well-represented strength-size scaling for the two ground conditions between an effective area range of 10−1 and 4 × 104 mm2. Machining damage was observed to be the dominant flaw type over this range. However, for effective areas

The inelastic deformation mechanisms and damage features observed in structural ceramics subjected to nonpenetrating, high-velocity impacts are similar to those seen in quasistatic Hertzian indentation, albeit more severe. For impacts on large ceramic bodies (relative to impactor diameter), cone cracking is the primary mechanism in regions of high tensile stresses. In regions of nonhydrostatic compressive stresses, depending on the material characteristics, elasticity, grain-boundary microcracking, or plasticity are the primary mechanisms, and depending on their associated energetics, may be able to compete with the initiation and growth of cone cracks. In this regard, a new model is presented that examines the effect of grain-boundary microcracking on cone cracking through shear-induced dilatancy (i.e., bulking) within the quasiplastic zone that forms just underneath the impact site. Depending on the size of the quasiplastic zone and bulking pressure, it is shown that the bulking phenomenon has the potential to suppress cone cracking. Lastly, examples of other shear-driven inelastic deformation mechanisms are presented.

Objective: The aims of this study were: i) to determine changes in symptoms and social disability, and ii) to explore predictors of clinical and social outcome in patients receiving community-based mental health care. Method: A total of 354 patients treated in the South-Verona Community Mental Health Service were followed up over 6 years (with assessments made at baseline, 2 and 6 years) by using a set of standardized measures exploring psychopathology (Brief Psychiatric Rating Scale) and social disability (Disability Assessment Schedule). Generalized linear latent and mixed models were used to explore longitudinal predictors of clinical and social outcome. Results: Psychotic patients displayed clinical and social outcome characterized by complex patterns of exacerbation and remission over time; however, a clear trend towards a deteriorating course was not found, thus challenging the notion that psychotics are fatally prone to a destiny of chronicity. Non-psychotics reported a significant reduction in the core symptom of depression and in the observable physical and motor manifestations of tension and agitation, and a parallel increase in complaints about their physical health. Clinical and social dimensions of outcome are influenced by specific and different set of predictors. Conclusion: The results of this study confirm the need to implement naturalistic outcome studies conducted in the ‘real world’ services to inform decisions and strategies to be adopted in routine clinical practice.

Objective: To describe the main characteristics of the South-Verona Outcome Project (SVOP) and to focus on its overall conceptual framework, with specific reference to the following perspectives: i) integrating evidence-based and practice-based approaches; ii) involving service professionals in routine outcome assessment; and iii) involving service users in mental health outcome assessment. Method: A selective literature review of methodological and empirical papers addressing the relevance and usefulness of outcome research to routine clinical practice was performed. Results: Reviewed literature shows the need to integrate evidence-based and practice-based approaches and to involve service professionals in routine outcome assessment, by adopting a multiple perspective paradigm. Studies conducted in ‘real world’ health services indicate that the outcome of care is multifaceted and it can be perceived differently when different perspectives are taken into account. Such a complex picture can provide more comprehensive information on the effectiveness of care provided, to feed back positively into clinical practice. Conclusion: The SVOP design and its methodological background were demonstrated to be appropriate for a detailed and routine assessment of outcome in the ‘real world’ of mental health services.

There is evidence suggesting that Dysbindin (DTNBP1) is a susceptibility gene for schizophrenia in Caucasian, Chinese, and Japanese populations. We sought to determine if dysbindin was associated with schizophrenia and its symptoms in a representative group of schizophrenic patients from a Community-Based Mental Health Service (CMHS) in Verona, Italy. A prevalence cohort of schizophrenic patients (n = 141) was assessed at baseline and then 3 and 6 years later. Eighty patients and 106 healthy controls were genotyped for polymorphisms in dysbindin. We tested if diagnosis, clinical symptoms as measured by the Brief Psychiatric Rating Scale (BPRS), and functioning as measured by the Global Assessment of Functioning Scale (GAF), were associated with the presence of certain dysbindin polymorphisms. Finally, using the longitudinal clinical data, we tested if patients carrying dysbindin high-risk haplotypes had a more unfavorable longitudinal clinical outcome. A trend towards statistical association (P = 0.058) between schizophrenia and rs2619538 was found. Using GENECOUNTING software, we found that rs2619538-P1583 (P = 0.048), P1320-P1757 (P = 0.034), and rs2619538-P1583-P1578 (P = 0.040) haplotypes occurred more often in cases compared to controls before correction for multiple testing. The rs2619538-P1583 haplotype was more likely to be transmitted to subjects with more severe and persistent psychopathology. These preliminary results are compatible with the view that DTNBP1 is a susceptibility factor for schizophrenia, and is associated with worse psychopathology. © 2007 Wiley-Liss, Inc.