For potentially acceptable manuscripts, the period between receipt of all reviews and when an editorial decision is made is usually

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Hence increase in LDL level selleck chemicals llc is

atheromatic. Our study demonstrated that CPAE treatment significantly increased HDL level while LDL level was unaffected in all experimental groups. The ALP, AST, ALT, TBIL, and TP are considered as sensitive indicator of liver injury.18 Rise in serum level of AST, ALT, ALP and total bilirubin have been attributed to the damaged structural integrity of the liver. The significant decrease in liver enzymes namely AST, ALT, ALP and total bilirubin levels were noticed after oral administration of CPAE as compared to diabetic animals. It implies the normal functioning and protective effect of liver and supports hepatoprotective claim of C. pareira. 4 The present study demonstrated increase in glucose metabolism and decrease in the gluconeogenesis as evidenced by increase in liver glycogen, serum lipids and creatinine levels. This affirms that other active ingredient(s) may impart for the in-vivo antihyperglycemic effect. This study unveils that the decrease in blood glucose level may be attributed to the stimulation of glucose

uptake by peripheral tissues and/or decrease FK228 solubility dmso in the gluconeogenesis. Hence, the antihyperglycemic effect may be probably due to an extrapancreatic mechanism and/or the regeneration of pancreatic β-cells. All authors have none to declare. The authors are highly thankful to Director, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India for providing research facilities for the completion of the present investigation. Authors are also thankful to JPR solutions for their partial funding to publish this research work. “
“Transgenic plants are the ones, whose DNA is modified using genetic engineering techniques. The aim is to introduce a new trait to the plant which does not occur naturally in the species. A transgenic plant contains a gene or genes that have been

artificially inserted. The inserted gene sequence is known as the transgene, it may come from an unrelated plant or from a completely different species. Adenylyl cyclase The purpose of inserting a combination of genes in a plant, is to make it as useful and productive as possible. This process provides advantages like improving shelf life, higher yield, improved quality, pest resistance, tolerant to heat, cold and drought resistance, against a variety of biotic and abiotic stresses. Transgenic plants can also be produced in such a way that they express foreign proteins with industrial and pharmaceutical value. Plants made up of vaccines or antibodies (Plantibodies) are especially stricing as plants are free of human diseases, thus reducing screening costs for viruses and bacterial toxins.1 The first transgenic plants were reported in 1983. Since then, many recombinant proteins have been expressed in several important agronomic species of plants including tobacco, corn, tomato, potato, banana, alfalfa and canola.

5 μg VLPs. This suggests that our VLP preparation induces sufficiently high titres of neutralising antibodies, even at low single vaccine doses of 0.03–0.3 μg VLP, to be protective in a stringent homologous and heterologous challenge. A contribution of virus-specific CD8+-cells to protection from infection might be redundant in this case. As the delivery route of VLPs was shown to influence the strengths of the humoral and cellular immune response [16] and [41], one might speculate whether the survival rate would have been higher in the study of Hemann Natural Product Library cost et al. [26], if an alternative to the intranasal vaccination route was chosen. Single immunisations with our vaccine could induce antibodies that were reactive

to all heterologous H7 subtypes tested (Fig. 2), in agreement with an earlier study [13]. We could also demonstrate significant reactivity to other members of group 2 HAs, such as the phylogenetically related H15 subtype and the more divergent H3 HA. Interestingly, cross-reactivity to H10, which is phylogenetically closer to H7 than H3, was only slightly above the background signal for the 3 μg dose group (Fig. 2), which is in agreement with results recently obtained by Muramatsu and colleagues [42]. It was previously shown that vaccination with different Akt cancer immunogens that vary only in their

globular head region, specifically could boost the stalk-reactive antibody response in mice [22] and [43]. However, both our immunisations for the prime-boost group were performed with the same immunogen and we assume that the boost in sero-reactivity primarily results from head-specific antibodies.

We therefore investigated the activity of the elicited antibodies by a hemagglutination inhibition assay with a panel of H7 strains. HI-active antibodies could be detected for the vaccine strains but also for a panel of divergent H7 viruses, which STK38 included representatives of the Eurasian and the North American lineage (Table 1). These results are in good agreement with those from Abbas et al. [44] obtained in chicken and Goff et al. [13] and Smith et al. [14] obtained in mice. We detected lower HI-activity for the PR8:SH1 virus than for PR8:AH1, even for the groups immunised with SH1-VLPs. This may be due to the utilisation of individual versus pooled sera in the assays. Although virus preparations were standardised, there still might have been slight variations in HA-activity of the viruses utilised. The second immunisation leads to a two-fold increase in HI titres for almost all tested virus strains. The observed HI crossreactivity might be the result of the completely conserved antigenic site A of Eurasian and North American lineage H7 viruses [13]. It is of note that even the group that received the lowest VLP dose of 0.03 μg and had only neglectable HI-activity was completely protected from challenge, suggesting that detectable levels of HI-active antibodies might not be required for protection.

Numerous practical resources have been developed to address these barriers and to help busy clinicians translate clinical evidence into patient management. These include pre-appraised resources such as clinical practice guidelines, critically appraised papers, and clinical commentaries on research papers. Various types of software have also been developed to assist in summarising answers to research

questions. For example, EBM Reports 3 helps organise, store, study and print health-related research reports obtained through internet searches, and EBM Calculator is free software that is designed to calculate statistics such as odds ratios and numbers needed to treat. Also, the Physiotherapy Evidence Database (PEDro) website provides a free index of high quality research BGB324 relevant to physiotherapists with ratings of the quality of the listed trials. Practical strategies to apply these resources in physiotherapy practice to improve patient care have been outlined elsewhere ( Herbert et al 2001, Herbert et al 2005). This editorial is not concerned with practical Veliparib in vitro barriers to evidence-based practice, but with conceptual barriers. We suggest that the original formulation of evidence-based practice has been lost in translation, resulting in misconceptions

about what this model of care is really about. These misconceptions may explain the reluctance of some physiotherapists to embrace the paradigm of evidence-based practice in

clinical care. Let’s examine some common beliefs about evidence-based practice. They include: (i) that it is a ‘cookbook’ approach to clinical practice, (ii) crotamiton that it devalues clinicians’ knowledge and expertise, and (iii) that it ignores patients’ values and preferences (Straus and McAlister 2000). According to the cookbook characterisation of evidence-based practice, treatment selection is dictated solely by evidence from randomised controlled trials. In a classic parody of this view, a 2003 British Medical Journal article reviewed what is known about the effectiveness of parachutes in preventing major trauma when jumping out of an aeroplane, concluding that, because there is no evidence from a randomised controlled trial, parachutes should not be used ( Smith and Pell, 2003). While clearly a mischievous piece of writing, it exposed a common misconception about evidence-based practice: that the double-blind randomised controlled trial is considered the holy grail, providing scientific evidence for clinical decision-making to the exclusion of clinicians’ professional expertise (and common sense) or an individual patient’s values.

MS (m/z): M+ calculated 499.02, found 498.94. Dark-brownish solid, M.P: 221–223 °C, Reaction time – 24 h, Yield – 39%, IR (KBr, cm−1): 3280 (N–H), 3126 (ArC–H), 2872 (AliC–H), 1672 (C O amide), 1584 (C C), MG-132 concentration 1246 (C–O), 1H NMR (DMSO-d6): d 2.03 (s, 3H, CH3), 3.39 (d, 5H, OC2H5), 5.46 (s, 1H, CH), 6.54 (d, 2H, ArH), 7.43 (m, 3H, ArH), 7.71 (d, 2H, ArH), 8.67 (s, 1H, NH), 9.38 (s, 1H, NH), 9.85 (s, 1H, NH). MS (m/z): MS (m/z): M+ calculated 472.02, found 471.97. Ash-colored solid, M.P: 236–238 °C, Reaction time – 23 h, Yield – 44%, IR (KBr, cm−1): 3254 (N–H), 3186(ArC–H), 2962 (AliC–H), 1672 (C O, amide), 1574 (C C), 1172 (O–C),1H NMR (DMSO-d6): d 2.02 (s, 3H, CH3), 3.68 (d, 5H, OC2H5), 5.43 (s, 1H, CH), 6.58 (d, 2H, ArH), 6.84 (d, 2H, ArH),7.43–7.86 (m, 3H, ArH), 9.37 (s, 1H, NH), 9.52 (s, 1H, NH), 9.88 (s, 1H, NH), MS (m/z): M+ calculated 488.00, found 488.05. Light-yellowish solid, M.P: 208–211 °C, Reaction time – 24 h, Yield – 41%, IR (KBr, cm−1): 3264 (N–H), 3182(ArC–H), 2948 (AliC–H), 1646 (C O, amide), Kinase Inhibitor Library concentration 1534 (C C), 1188 (O–C), 1H NMR (DMSO-d6): d 2.05 (s, 3H, CH3), 3.47 (d, 5H, OC2H5), 5.58 (s, 1H, CH), 6.35 (d, 2H, ArH), 7.48–7.64

(m, 4H, ArH), 8.87 (s, 1H, NH), 9.64 (s, 1H, NH), 9.73 (s, 1H, OH), 9.86 (s, 1H, NH). MS (m/z): M+ calculated 428.04, found 427.97. Light-greenish solid, M.P: 186–189 °C, Reaction time – 20 h, Yield – 51%, IR (KBr, cm−1): 3256 (N–H), 3148(ArC–H), 2952 (AliC–H), 1648 (C O, amide), 1576 (C C), 1168 (O–C), 1H NMR (DMSO-d6): d 2.02 (s, 3H, CH3), 3.85 (d, 5H, OC2H5), 5.63 (s, 1H, CH), 6.67 (d, 2H, ArH), 7.45–7.69 (m, 4H, ArH), 8.73 (s, 1H, NH), 9.45 (s, 1H, NH), 9.76 (s, 1H,

OH), 9.96 (s, 1H, NH). MS (m/z): M+ calculated 472.02, found 471.97. Light-greenish solid, M.P: 211–213 °C, Reaction time – 21 h, Yield – 54%, IR (KBr, cm−1): 3234 (N–H), 3160 (ArC–H), 2934 (AliC–H), 1656 (C O, amide), 1562 (C C), 1182 (O–C), 1H NMR (DMSO-d6): d 2.06 (s, 3H, CH3), 3.69 (d, 5H, OC2H5), 5.45 (s, 1H, CH), 6.57 (d, 2H, ArH), 7.52–7.66 (m, 4H, Oxymatrine ArH), 8.75 (s, 1H, NH), 9.47 (s, 1H, NH), 9.61 (s, 1H, OH), 9.79 (s, 1H, NH). MS (m/z): M+ calculated 488.00, found 488.08. Ash-colored solid, M.P: 256–259 °C, Reaction time – 19 h, Yield – 61%, IR (KBr, cm−1): 3258 (N–H), 3166(ArC–H), 2964 (AliC–H), 1672 (C O, amide), 1573 (C C), 1186 (O–C), 1H NMR (DMSO-d6): d 2.01 (s, 3H, CH3), 3.69 (d, 5H, OC2H5), 5.67 (s, 1H, CH), 6.37 (d, 2H, ArH), 7.45–7.71 (m, 4H, ArH), 8.85 (s, 1H, NH), 9.46 (s, 1H, NH), 9.75 (s, 1H, OH), 9.86 (s, 1H, NH).

Therefore, by fixing the homogenization time (30 min), stirring this website time (2 h) and sonication time (5 min), selected variables (A), (B), and (C) were studied at three different levels as low (−1), medium (0), and high (+1). The coded (factors) and actual values (responses) of the variables are given in Table 2. The following second-order polynomial equation can be used to draw conclusion after considering

the magnitude of coefficient and mathematical sign it carries i.e. positive or negative. Y=β0+β1A+β2B+β3C+β11A2+β22B2+β33C2+β12AB+β13AC+β23BCY=β0+β1A+β2B+β3C+β11A2+β22B2+β33C2+β12AB+β13AC+β23BCWhere Y was predicted response(s), β0 was an intercept, β1, β2, and β3 were linear coefficients, β11, β22, and β33 were squared coefficients and quadratic term, β12, β13, and β23 were interaction coefficients, and A, B,

and C were independent variables, which were selected based on the results from a preliminary study. To evaluate the fitness of the model, predicted R2 and adjusted R2 were evaluated. Different batches were prepared with different independent variables at different levels and responses, like particles size, % entrapment efficiency and % drug loading were obtained. The data was substituted to design expert software and polynomial equations were obtained. The models were evaluated in terms of statistically NVP-BEZ235 concentration significant coefficients and R2 values. 3-D surface plots were used to assess the relationship between the variables and the responses. The criterion for selection of optimum ALOX15 formulations was based on the highest possible

value of % entrapment efficiency (Y2), and % drug loading (Y3) and smallest value of particles size (Y1) ( Table 1). Finally, four optimized formulations were selected as check point to validate RSM. These formulations were again prepared and evaluated for responses. The resulting observed responses were compared with the predicted responses and percent error was calculated. A linear regression plots between actual and predicted responses were plotted. 7 All samples were diluted in 1:10 ratio with deionized water to get optimum counts. Average particle size, polydispersity index (PDI) and zeta potential were measured by photon correlation spectroscopy (PCS; Zetasizer, HAS 3000; Malvern Instruments, Malvern, UK). Measurements were carried out with an angle of 90° at 25 °C.8 A fixed quantity of SLNs dispersion (10 ml) was taken in a centrifuge tube and centrifuged at 18,000 rpm for 20 min at room temperature (Remi Instruments Pvt. Ltd, India), the lipid portion was isolated, and the absorbance of the drug in the supernatant was determined spectrophotometrically at λmax 247.5 nm (Shimadzu 1800, Japan).

The Phase I, double-blind, randomized study in 50 healthy adults aged 18–49 years (CTRI/2010/091/000082) compared see more the safety of two Al(OH)3 adjuvanted whole virion formulations (10 μg and 15 μg haemagglutinin (HA) per dose). Satisfactory

42-day follow-up data led to authorization for the Phase II/III double-blind, randomized study, carried out in 330 individuals (110 adults, 110 elderly and 110 adolescents and children ≥3 years) at five sites in India (CTRI/2010/091/000093). Following single dose of either 10 μg or 15 μg HA of the study vaccine given intramuscularly at 21 days apart, safety and immunogenicity were assessed and the vaccine found safe in all age groups. After 42 days of follow-up, no SAEs were reported and none of the few unsolicited events detected in each group was causally related to the study products. All solicited reactions reported in the groups were similar, mild in intensity and resolved without sequelae. Immunogenicity was assessed on Day click here 0 and 21 by

HAI assay. The vaccine-induced immune responses of both formulations were in line with published studies [6], [7] and [8]. Seroconversion and seroprotection (HI titres ≥1:40) rates met the requirements of the European Medicines Agency (EMEA) and the US Food and Drug Administration (FDA) for licensure in all three age groups. The DCG(I) granted the licence to market the 15 μg adjuvanted vaccine on 6 August 2010. As soon as six months of stability data are available, the 10 μg formulation will be registered and launched under the brand name Enzavac® in India. All the clinical studies were approved by the DCG(I), the Independent Review Board and the Institutional Ethics Committee. Additionally, all data were periodically reviewed and approved by an independent Data Safety Monitoring Board. Among other controls, an on-site regulatory audit for the manufacturing processes and quality control Calpain testing was carried out by an inspection team from WHO, the CDSCO/DCG(I), and local FDA in April 2010. During the entire clinical development and licensing of the IIV and

LAIV, SII was actively supported by the government agencies since the need for a pandemic vaccine in India was clear. As a result, they approved importation of the H1N1 vaccine strain, clinical trial protocols and finally licensure on a fast-track basis. In parallel, SII proactively apprised these agencies of developments at each stage of the project. For instance, while requirements for the production and use of IIV are long established, the WHO guidelines for the manufacture and evaluation of LAIV were being updated. Policy-makers and the scientific community were also apprehensive over issues such as potential reversion of attenuation to virulent phenotype, emergence of more pathogenic viruses from reassortant between vaccine strain and wild type strain, and limited safety data.

Five hours later, PBMCs were harvested and analyzed for CD107b and IFNγ by flow cytometry. There was a minimal background (<2%) in spontaneous CD107b cell surface mobilization and IFNγ expression (Fig. 2B). In contrast, 7.7% of CD8+ cells harvested before

surgery degranulated and elaborated IFNγ in response to autologous tumor cells, revealing a pre-existing CTL response against the tumor. The frequency of IFNγ+CD107b+ CTLs increased to 24.5% by 37 days following surgery and intracavitary IFNγ gene transfer. The frequency of tumor-reactive CTLs increased with subsequent vaccinations, peaking at a 38% IFNγ+/CD107b+ CTLs measured 14 days after the third vaccination (Fig. 2B). In contrast to the CTL response, selleck screening library vaccination was not associated with any clear trend in the

percentage of CD4+Fox3P+ regulatory T cells in the peripheral blood (Fig. 2C) [29]. The majority of GemA patients will ultimately develop GBM and succumb to their disease despite surgery and adjuvant therapy [4]. Compared to the more aggressive GBM that has a median time to progression of 6.9 months [2], we propose that GemA is an attractive target for immunological therapies that may work more slowly and, potentially, more effectively in this earlier and less aggressive form of astrocytoma to induce tumor regression and anti-tumor immunity. This case MI-773 ic50 report is not sufficient to make firm conclusions about the ability of the combination of IFNγ gene transfer and CpG/lysate vaccination to prevent progression of GemA to GBM, however the data do demonstrate that the therapy is feasible in a large animal model. Our results raise several interesting points that warrant attention. In the present study, the autologous tumor cells grew too slowly to generate adequate lysate after the first vaccination; therefore, we administered

allogeneic anaplastic astrocytoma lysate for the remaining four vaccinations. Interestingly, the first vaccination induced an IgG response ever specific to two antigens in the autologous tumor sample that were approximately 50–65 kDa in molecular weight, as seen at day 51 (Fig. 2A). Vaccination with allogeneic lysate apparently primed a polyclonal IgG response to several other autologous antigens. While the identity of these IgG epitopes (or the T cell epitopes) was not determined, our results demonstrate that CpG/lysate vaccination is a feasible method to break immunological tolerance to multiple glioma antigens. Although preliminary, our data indicate that autologous tumor cell lysate production may not always be feasible in WHO II grade gliomas, but allogeneic WHO III grade lysates could be used as a scalable “off the shelf” antigen source. We are currently treating additional dogs to better define the logistics, efficacy, and safety of this therapy.

2 Such biomolecular damage by selleck kinase inhibitor free radicals leads to many pathological diseases such as cancer, inflammation, and atherosclerosis.3 Antioxidants from various sources, especially those of plant origin, reduce the adverse effects of free radicals. They act as scavengers by donating one of their own electrons in order to replace the stolen electron from free radicals.4 Plant-derived bioactive compounds known as phytochemicals are rich in antioxidant and free radical scavenging properties.5 Many research studies have been carried out to identify plants with significant antioxidant and anticancer potential by analysing their cytotoxic, antiproliferative, apoptotic and radical scavenging

activities using both in vitro and in vivo systems. 6 Caesalpinia pulcherrima is one such candidate plant which blooms in three different colours (orange, pink and yellow) with unique long stamens. It is commonly known as peacock flower PI3K Inhibitor Library research buy or “Barbados pride” in English and as “Mayil kondrai” in Tamil and belongs to the family Fabaceae. The aerial parts of the plants have been used traditionally for the treatment of various diseases

including asthma, bronchitis, cholera, diarrhoea, dysentery and malarial infection. 7 The flowers of C. pulcherrima have been reported to possess antiviral activity. 8 In recent years, the use of animals in research, teaching and testing has become an important ethical and political issue. Alternative scientific tests are being developed, which are more efficient and reliable than animal tests. Several non-animal tests have been developed that are cost-effective, practical, and expedient.9 The major advantage of using organ slices as in vitro model is that they represent the multicellular, structural and functional features of in vivo tissue. Organ slices have been used extensively as a promising MycoClean Mycoplasma Removal Kit model for elucidating the mechanism of drug induced organ injury and for characterizing

species susceptibilities. 10 Precision-cut liver slices are widely used to elucidate the pharmacological metabolism and to investigate the toxicology and efficacy of novel substances on primary material under standardized conditions. 11 They also mimic the in vivo situation of the liver due to the presence of the physiological extracellular matrix. 12 Hence in the present study, the goat liver slices were selected as an in vitro model to determine the antioxidant potential of the methanolic extract of the three different flowers of C. pulcherrima (yellow, pink and orange) against H2O2 induced oxidative stress. Fresh flowers of C. pulcherrima ( Fig. 1) were collected from the local areas of Coimbatore. The three different flowers namely yellow, pink and orange were procured. The plant was identified and certified by the Botanical Survey of India, Tamil Nadu Agricultural University, Coimbatore. The voucher specimen was collected and maintained.

It is important to note that in all these studies, including ours, ‘recovery’ in ambulation and upper limb function does not necessarily imply complete recovery. Many patients deemed to have recovered motor function using our operational definitions may still have had significant limitations in higher levels of mobility or more complex upper limb functional tasks. Several acute stroke studies have considered age (Dallas et al 2008, de Weerdt et al 1987, Hu et al 2010, Loewen and Anderson 1990, Meldrum JAK inhibitor et al 2004, Veerbeek et al 2011, Wandel et

al 2000), and severity of stroke (Au-Yeung and Hui-Chan 2009, Dallas et al 2008, Hu et al 2010) in their multivariate analyses to identify predictors of ambulation or upper limb function.

Only one study has found age and severity of stroke as significant predictors of ambulation. This study recruited patients from a stroke intensive care unit. Patients were included in that study only if they were referred for rehabilitation (Hu et al 2010). Another study that investigated the benefits of constraint-induced movement therapy in people six months after stroke also reported that age was a predictor for upper limb function (Fritz et al 2006). In these two studies, the cohorts might not be representative of patients seen early AC220 after stroke. Age and NIHSS have previously been shown to be strong predictors of mortality (Konig et al 2008, Weimar et al 2004), disability (Johnston et al 2007), and independence with activities of daily living (Johnston et al 2007, Konig et al 2008, Weimar et al 2004) in acute stroke cohorts. Consequently these predictors appear to have broad predictive utility. Their routine use in acute stroke units will facilitate external validation of our prediction models in other cohorts. One limitation of the Idoxuridine NIHSS is that it is a complex assessment that requires training to administer (Reid et al 2010). This potentially undermines its clinical usefulness. However online training and access to the scale (Kasner 2006)

have overcome some of these problems. An advantage of the NIHSS is that it provides information on a variety of stroke-related impairments that can be used by various health professionals in the acute stroke setting (Kasner 2006). The NIHSS can also be administered to patients who do not have good cognition or language, whereas this can be problematic with the MAS. We therefore recommend the use of the NIHSS in future prediction models of ambulation and upper limb recovery after stroke. The strengths of our study include the consecutive recruitment of patients seen early after stroke, the minimal loss to follow-up, the low risk of over-fitting of the prediction model, and the strong performance of the prediction models (discrimination and calibration results).