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Purpose: Anti-Xa peak level monitoring is recommended during LMWH treatment in renal impairment or obesity. The trough level has been proposed as marker for bleeding. We studied the influence of renal impairment and obesity on anti-Xa levels. Methods: Peak and trough levels were collected during therapeutic nadroparin treatment in patients with renal impairment, obese patients, and controls. 27 patients (n = 68 samples) were evaluated and combined with published data (n = 319 samples from 35 patients) using population pharmacokinetic (popPK) modelling. Results: Median peak level was 0.44 and 0.95 IU/mL in renal impairment with and without dose reduction and 0.60 and 0.43 IU/mL in obesity and controls, respectively. Trough levels were < 0.5 IU/mL in all patients with renal impairment with dose reduction and in 5/6 control patients. In the popPK model, total body weight and eGFR were covariates for clearance and lean body weight for distribution volume. Model-based evaluations demonstrated peak levels below the therapeutic window in controls and increased levels in renal impairment. Dose reductions resulted in a different effect on peak and trough levels. Obese patients (BMI up to 32 kg/m2) had similar levels upon weight-based dosing. Conclusion: In renal impairment, anti-Xa peak levels after dose reduction are comparable to those in controls. Weight-based dosing is suitable for obese patients. Aiming for peak levels between 0.6 and 1.0 IU/mL in these patients would result in overexposure compared to controls. Considering the association of trough levels and bleeding risk and our findings, trough monitoring seems to be a suitable parameter to identify nadroparin accumulation. [ABSTRACT FROM AUTHOR]

Explanations about differences in drinking and smoking rates between educational tracks have so far mainly focused on factors outside the classroom. The extent to which these behaviors are rewarded with popularity within a classroom—so called popularity norms—and their interaction with individual characteristics could explain the observed differences in risk behavior. 1860 adolescents (Mage = 13.04; 50% girls) from 81 different classrooms reported three times during one academic year about their own and their classmates behavior. Overall, in vocational tracks popularity norms for alcohol and smoking were more positive and predicted classroom differences in alcohol and smoking. Knowledge about classroom processes can advance the field in unraveling the functional aspects of risk behavior in adolescence. Preregistration: The hypotheses and the analytical plan of this study were preregistered under number #39136 (https://aspredicted.org/blind.php?x=gx77p6). [ABSTRACT FROM AUTHOR]

A dynamic load and stress analysis of a wind turbine is carried out using transient fluid-structure interaction simulations. On the structural side, the three 50 m long commercial glass-fiber epoxy blades are modelled using shell elements, accurately including the properties of the composite materials. On the fluid side, a hexahedral mesh is obtained for every blade and for the hub of the machine. These meshes are then overlaid to a structured background mesh through an overset technique. The displacements prescribed by the structural solver are imposed on top of the rigid rotation of the turbine. The atmospheric boundary layer (ABL) is included using the k-epsilon turbulence model. The computational fluid dynamics (CFD) and computational solid mechanics (CSM) solvers are strongly coupled using an in-house code. The transient evolution of loads, stresses and displacements on each blade is monitored throughout the simulated time. The ABL induces oscillating axial displacements in the outboard region of the blade. Furthermore, the influence of gravity on the structure is accounted for and investigated, showing that it largely affects the tangential displacement of the blade. The oscillating deformations lead to sensible differences in the torque provided by each blade during its rotation. • The atmospheric boundary layer leads to oscillating torque and loads on each blade. • The oscillatory deformation of the blade sensibly affects its performance. • The inner structures of the blades experience periodical bending solicitation. • Gravity sensibly affects the tangential deformation of the blades. [ABSTRACT FROM AUTHOR]

Domain-wall (DW) motion in magnetic nanostrips is intensively studied, in particular because of the possible applications in data storage. In this work, we will investigate a novel method of DWmotion using magnetic field pulses, with the precession torque as the driving mechanism. We use a one dimensional (1D) model to show that it is possible to drive DWs in out-of-plane materials using the precession torque, and we identify the key parameters that influence this motion. Because the DW moves back to its initial position at the end of the field pulse, thereby severely complicating direct detection of the DW motion, depinning experiments are used to indirectly observe the effect of the precession torque. The 1D model is extended to include an energy landscape in order to predict the influence of the precession torque in the depinning experiments. Although preliminary experiments did not yet show an effect of the precession torque, our calculations indicate that depinning experiments can be used to demonstrate this novel method of DW motion in out-of-plane materials, which even allows for coherent motion of multiple domains when the Dzyaloshinskii-Moriya interaction is taken into account. [ABSTRACT FROM AUTHOR]

Minor international differences [ABSTRACT FROM AUTHOR]

Background: Social causation as well as health-related selection may contribute to educational gradients in adolescents’ attention problems (AP) and externalizing behaviour (EB). From past studies it is unclear which of these mechanisms predominates, as AP and EB have the potential to disrupt adolescents’ educational careers, but may also be affected by differences in their social environment. Furthermore, gradients in AP and EB may reflect ‘third variables’ already present in childhood, such as parental socioeconomic status (SES) and IQ. We investigated social causation and healthrelated selection in the development of educational differences in EB and AP. Methods: We used data from a Dutch population-based cohort (TRAILS Study; n = 2,229), including measurements of educational level, EB, and AP at ages around 14, 16, 19, 22, and 26 years. First, we evaluated the directionality in longitudinal associations between education, EB, and AP with cross-lagged panel models, with and without adjusting for pre-existing individual differences using fixed effects. Second, we assessed the role of parental SES and IQ in childhood both as confounders in longitudinal associations, and as predictors of AP, EB, and educational level around age 14. Results: In fixed effects models, AP, but not EB, consistently predicted decreases in educational level throughout all of adolescence and young adulthood. Regarding social causation, differences in parental SES contributed to increases in EB amongst the lower educational tracks in mid-adolescence. Childhood IQ and parental SES strongly predicted education around age 14. Parental SES, but not IQ, also predicted early adolescent AP and EB. Conclusions: We found health-related selection attributable to AP throughout all phases of adolescence and young adulthood. Further, our results highlight the role of social causation from parental SES in determining adolescent educational level, AP, and EB. Key messages: • AP have the potential to negatively impact adolescents’ educational careers and may trigger downward mobility in the educational system in all phases of adolescence and young adulthood. • The results of this study call for actions to reduce the impact of AP on education. Further, it is essential to address the effects of insufficient economic resources on education and mental health. [ABSTRACT FROM AUTHOR]

Background The use of epidermal growth factor receptor inhibitors to treat metastatic colorectal cancer (mCRC) patients requires prior confirmation of tumour wild type (WT) RAS mutation status (exons 2/3/4 for KRAS or NRAS ). This retrospective pooled analysis aims to robustly estimate RAS mutation prevalence and individual variation patterns in mCRC patients. Method Individual patient data from five randomised, controlled panitumumab studies (three phase III, one phase II and one phase Ib/II) were pooled for this analysis. The phase III studies included mCRC patients independent of RAS mutation status; the phase II and Ib/II studies included mCRC patients with confirmed WT KRAS exon 2 status. Four studies conducted RAS testing using Sanger sequencing; one study used a combination of next-generation sequencing and Sanger sequencing. In order to assign overall RAS status, the mutation status of all exons 2/3/4 KRAS or NRAS was required to be known. Results Data from 3196 mCRC patients from 36 countries were included in the analysis. The overall unadjusted RAS mutation prevalence in mCRC patients was 55.9% (95% confidence interval (CI): [53.9–57.9%]), with the following distribution observed: KRAS exon 2 (prevalence 42.6% [40.7–44.5%]); KRAS exon 3 (3.8% [2.9–4.9%]); KRAS exon 4 (6.2% [5.0–7.6%]); NRAS exon 2 (2.9% [2.1–3.9%]); NRAS exon 3 (4.2% [3.2–5.4%]); NRAS exon 4 (0.3% [0.1–0.7%]). Differences in RAS mutation prevalence estimates were observed by study ( p = 0.001), gender ( p = 0.030), and by country ( p = 0.028). Conclusions This analysis provides robust estimates of overall RAS mutation prevalence and individual variation patterns in mCRC patients. [ABSTRACT FROM AUTHOR]

This article deals with the questions what the benefits and limitations are of the instruments and strategies that patient organisations use to influence quality of care. The advocacy of patients' interests has become more important for patient organisations in recent years, which is partly due to Dutch health care policy reform. Thirty state funded quality improvement projects run by patient organisations between 2009 and 2012 have been analysed. The quality improvement instruments developed and used in these projects are concerned with: standardization and standard setting (What is good care?); consultation, comparison and checking (What is the state of the care given?); and negotiating and advising (How can quality of care be improved?). The choice for these instruments is partly based on patient organisations' strategies of scientization, valuing institutionalized methods and valuing good relationships. We see that the development and use of these quality improvement instruments do strengthen patient organisation and therefore have internal identity and organisational effects. However, the external effects patient organisations can have by using these instruments and strategies is limited or at least insecure by lack of economic capital after the development phase and lack of negotiating power. The external effects of these instruments and strategies depend largely on a patient organisation's network and the willingness, degree of openness and policy of other stakeholders to cooperate. Therefore, these forms of patient participation remain vulnerable. [ABSTRACT FROM AUTHOR]

This paper reports the final results from a prespecified descriptive analysis (conducted 30 months after the last patient was enrolled) that confirms the PFS benefit with panitumumab + FOLFIRI versus FOLFIRI alone in previously treated patients with wild-type KRAS metastatic colorectal cancer. New analyses in this manuscript include efficacy by skin toxicity severity and by prior bevacizumab and oxaliplatin therapy, of which this is the first report of this type. The results by prior therapy show that the addition of panitumumab in patients treated with prior oxaliplatin–bevacizumab improved PFS (median 6.4 versus 3.7 months; HR 0.58 [95% CI 0.37 0.90]; P = 0.014) with trends to improved survival (median 16.1 versus 12.1 months; HR 0.69 [95% CI 0.45, 1.08]; P = 0.10); to our knowledge, the first observation of the efficacy of an anti-EGFR in combination with chemotherapy in the second-line compared with chemotherapy alone following a bevacizumab-containing regimen in the first-line treatment in patients with wild-type KRAS mCRC.Background The study 20050181 demonstrated significant improvements in progression-free survival (PFS), objective response, and a nonsignificant trend toward increased overall survival (OS) with panitumumab–FOLFIRI versus FOLFIRI alone for second-line wild-type (WT) KRAS metastatic colorectal cancer (mCRC). Updated long-term data from a prespecified descriptive analysis are reported. Patients and methods Patients receiving one prior mCRC treatment were randomly assigned (1:1) to panitumumab (6.0 mg/kg)–FOLFIRI versus FOLFIRI every 2 weeks. Co-primary end points (PFS and OS) were prospectively analyzed by tumor KRAS status. Results One thousand one hundred and eighty-six patients were randomly assigned. In patients with WT KRAS tumors, panitumumab–FOLFIRI significantly improved PFS versus FOLFIRI [median 6.7 versus 4.9 months; hazard ratio (HR) 0.82 [95% confidence interval (CI) 0.69, 0.97]; P = 0.023]. A trend toward longer OS was observed (median 14.5 versus 12.5 months; HR 0.92 [95% CI 0.78, 1.10]; P = 0.37). Response rates improved from 10% to 36% (P < 0.0001). From post hoc analyses in patients receiving prior oxaliplatin–bevacizumab, panitumumab–FOLFIRI improved PFS (median 6.4 versus 3.7 months; HR 0.58 [95% CI 0.37, 0.90]; P = 0.014). PFS and OS appeared longer for worst-grade skin toxicity of 2–4, versus 0–1 or FOLFIRI. Safety results were as previously reported and consistent with the known toxicities with anti-epidermal growth factor receptor therapy. Conclusions These data confirm the primary efficacy and safety findings of this trial and support panitumumab–FOLFIRI as a second-line treatment of WT KRAS mCRC. [ABSTRACT FROM AUTHOR]

Nonlinear normal modes, which are defined as a nonlinear extension of the concept of linear normal modes, are a rigorous tool for nonlinear modal analysis. The objective of this paper is to demonstrate that the computation of nonlinear normal modes and of their oscillation frequencies can now be achieved for complex, real-world aerospace structures. The application considered in this study is the airframe of the Morane-Saulnier Paris aircraft. Ground vibration tests of this aircraft exhibited softening nonlinearities in the connection between the external fuel tanks and the wing tips. The nonlinear normal modes of this aircraft are computed from a reduced-order nonlinear finite element model using a numerical algorithm combining shooting and pseudo-arclength continuation. Several nonlinear normal modes, involving, e.g., wing bending, wing torsion, and tail bending, are presented, which highlights that the aircraft can exhibit very interesting nonlinear phenomena. Specifically, it is shown that modes with distinct linear frequencies can interact and generate additional nonlinear modes with no linear counterpart. [ABSTRACT FROM AUTHOR]

In this work, we will present a novel approach for the detection of small molecules with molecularly imprinted polymer (MIP)-type receptors. This heat-transfer method (HTM) is based on the change in heat-transfer resistance imposed upon binding of target molecules to the MIP nanocavities. Simultaneously with that technique, the impedance is measured to validate the results. For proof-of-principle purposes, aluminum electrodes are functionalized with MIP particles, and l-nicotine measurements are performed in phosphate-buffered saline solutions. To determine if this could be extended to other templates, histamine and serotonin samples in buffer solutions are also studied. The developed sensor platform is proven to be specific for a variety of target molecules, which is in agreement with impedance spectroscopy reference tests. In addition, detection limits in the nanomolar range could be achieved, which is well within the physiologically relevant concentration regime. These limits are comparable to impedance spectroscopy, which is considered one of the state-of-the-art techniques for the analysis of small molecules with MIPs. As a first demonstration of the applicability in biological samples, measurements are performed on saliva samples spiked with l-nicotine. In summary, the combination of MIPs with HTM as a novel readout technique enables fast and low-cost measurements in buffer solutions with the possibility of extending to biological samples. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Background:This phase 2 study evaluated trebananib (AMG 386), an investigational peptide-Fc fusion protein that neutralises the interaction between angiopoietins-1/2 and the Tie2 receptor, plus FOLFIRI as second-line treatment for patients with metastatic colorectal cancer.Methods:Patients had adenocarcinoma of the colon or rectum with progression within 6 months of receiving only one prior fluoropyrimidine/oxaliplatin-based chemotherapy regimen for metastatic disease. All patients received FOLFIRI and were randomised 2 : 1 to also receive intravenous trebananib 10 mg kg−1 once weekly (QW) (Arm A) or placebo QW (Arm B). The primary end point was investigator-assessed progression-free survival (PFS).Results:One hundred and forty-four patients were randomised (Arms A/B, n=95/49). Median PFS in Arms A and B was 3.5 and 5.2 months (hazard ratio (HR) 1.23; 95% CI, 0.81-1.86; P=0.33) and median overall survival (OS) was 11.9 and 8.8 months, respectively (HR 0.90; 95% CI; 0.53-1.54; P=0.70). Objective response rate (ORR) was 14% and 0% in Arms A and B, respectively. Incidence of grade 3 adverse events was similar between treatment arms (Arm A, 61%; Arm B, 65%) and included pulmonary embolism (1%/4%), deep vein thrombosis (5%/2%), and hypertension (1%/0%).Conclusion:Administration of trebananib plus FOLFIRI did not prolong PFS compared with placebo plus FOLFIRI. Toxicities were manageable and consistent with those known for FOLFIRI and trebananib. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the association of primary tumour F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake. Methods: PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses. Results: In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV. Conclusion: Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT. [ABSTRACT FROM AUTHOR]

Abstract: Serotonin is an important signaling molecule in the human body. The detection of serotonin is commonly performed by high performance liquid chromatography (HPLC), which is costly and time consuming due to extensive sample preparation. We will show that these problems can be overcome by using molecularly imprinted polymers (MIPs) as synthetic receptors in combination with impedance spectroscopy as readout technique. The MIPs were prepared with several blends of the underlying monomers and the best performing MIP material was selected by optical batch-rebinding experiments. MIP microparticles were then integrated in an impedimetric sensor cell and dose–response curves were measured in PBS buffer and in non-diluted blood plasma. The sensor provides reliable data in the physiologically relevant concentration regime as an independent validation by HPLC measurements demonstrates. Finally, we show that the impedimetric response upon serotonin binding can be attributed to a capacitive effect at the interface between the MIP particles and the plasma. [Copyright &y& Elsevier]

Clin Microbiol Infect 2012; 18: 514-520 Abstract It is now well established that simian immunodeficiency viruses (SIVs) from chimpanzees (SIVcpz) and gorillas (SIVgor) from west Central Africa are at the origin of HIV-1/AIDS. Apes are also infected with other retroviruses, notably simian T-cell lymphotropic viruses (STLVs) and simian foamy viruses (SFVs), that can be transmitted to humans. We discuss the actual knowledge on SIV, STLV and SFV infections in chimpanzees, gorillas, and bonobos. We especially elaborate on how the recent development of non-invasive methods has allowed us to identify the reservoirs of the HIV-1 ancestors in chimpanzees and gorillas, and increased our knowledge of the natural history of SIV infections in chimpanzees. Multiple cross-species events with retroviruses from apes to humans have occurred, but only one transmission of SIVcpz from chimpanzees in south-eastern Cameroon spread worldwide, and is responsible for the actual HIV pandemic. Frequent SFV transmissions have been recently reported, but no human-to-human transmission has been documented yet. Because humans are still in contact with apes, identification of pathogens in wild ape populations can signal which pathogens may be cause risk for humans, and allow the development of serological and molecular assays with which to detect transmissions to humans. Finally, non-invasive sampling also allows the study of the impact of retroviruses and other pathogens on the health and survival of endangered species such as chimpanzees, gorillas, and bonobos. [ABSTRACT FROM AUTHOR]

This contribution comments on Directive 2011/24, providing a legal framework for cross border healthcare 13 years after the famous Kohll and Decker case law. The Directive contains provisions concerning the reimbursement of costs, the responsibilities of the Member States and their mutual cooperation in healthcare. Analysing the (potential) impact of the Directive 2011/24 on EU healthcare systems, patients and healthcare providers, it becomes clear that the impact of the Directives reaches far beyond patient mobility. The Directive creates patients' rights, pays attention to the quality and safety of healthcare services and creates an excessive structure of cooperation in the field of healthcare. The European Union seems ready to use its economies of scale to improve healthcare for all European patients. [ABSTRACT FROM AUTHOR]

Objective: To compare field methods for measuring body composition, ie bioelectrical impedance analysis (BIA) and skin fold thicknesses (SFT), to reference methods, such as air-displacement plethysmography (ADP), in order to validate their use in anorexia nervosa (AN) patients. Method: Fat mass (FM), fat-free mass (FFM) and percent body fat (PBF) of 27 AN patients (24.6±8.5 yrs) were assessed using BIA, SFT and ADP. Results: PBF and FM measured by SFT (PBFSFT and FMSFT) were significantly higher compared to PBFADP and FMADP (14.4±3.8% and 6.1±1.9 kg versus 11.3±6.6% and 4.8±3.0 kg); fat-free mass (FFMSFT) was significantly lower compared to FFMADP (35.5±3.3kg versus 36.7±3.8kg). There was a trend in bias related to the degree of fatness for PBFSFT and PBFBIA versus PBFADP: at lower PBFADP, PBFSFT and PBFBIA were overestimated compared with PBFADP; PBFSFT and PBFBIA were slightly underestimated compared with PBFADP at higher PBFADP. Conclusion: It is suggested that ADP and SFT or BIA cannot be used interchangeably in AN patients at group level and certainly not at an individual level. [ABSTRACT FROM AUTHOR]

Abstract: Realizing that nonlinearity is a frequent occurrence in engineering structures and that linear experimental modal analysis (EMA) is of limited usefulness in this context, the present paper is an attempt to develop nonlinear EMA by targeting the extraction of nonlinear normal modes (NNMs) from time series of nonlinear mechanical systems. Based on a nonlinear extension of phase resonance testing, the proposed methodology excites the structure to isolate a single NNM during the experiments. Thanks to the invariance principle, the energy dependence of that nonlinear mode (i.e., the NNM modal curves and their oscillation frequencies) can be extracted from the resulting free decay response using time–frequency analysis. This paper is devoted to the experimental demonstration and robustness of this procedure. To this end, an experimental cantilever beam with a geometrical nonlinearity is considered, and the ability of the proposed methodology to extract its NNMs from the measured responses is assessed. [Copyright &y& Elsevier]

Abstract: Modal testing and analysis is well-established for linear systems. The objective of this paper is to progress toward a practical experimental modal analysis (EMA) methodology of nonlinear mechanical structures. In this context, nonlinear normal modes (NNMs) offer a solid theoretical and mathematical tool for interpreting a wide class of nonlinear dynamical phenomena, yet they have a clear and simple conceptual relation to the classical linear normal modes (LNMs). A nonlinear extension of force appropriation techniques is developed in this study in order to isolate one single NNM during the experiments. With the help of time–frequency analysis, the energy dependence of NNM modal curves and their frequencies of oscillation are then extracted from the time series. The proposed methodology is demonstrated using two numerical benchmarks, a two-degree-of-freedom system and a planar cantilever beam with a cubic spring at its free end. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2010; 16: 1525-1531 Abstract The tremendous diversity of human immunodeficiency virus (HIV)-1 strains circulating worldwide has an important impact on almost all aspects of the management of this infection, from the identification of infected persons, through treatment efficacy and monitoring, and prevention strategies such as vaccine design. The areas where HIV-1 genetic diversity is highest are those where the majority of patients in need of treatment and biological monitoring live. With increased access to treatment in these areas, it is expected that the demand for monitoring tools such as viral load assays and resistance tests will also increase, and their reliability will be critical. Regular updates of these assays during the last two decades have aimed at improving their performances in different ways that include their reliability with different HIV-1 strains. We here review to what extent HIV-1 genetic diversity still limits or not the use of currently available viral load and resistance tests. [ABSTRACT FROM AUTHOR]

The purpose of this study was to further document the extent of the effect of wearing deviating clothing schemes on the accuracy of body composition measurement using air-displacement plethysmography (ADP) compared to the clothing prescribed by the manufacturer. Thirty-one men (21.9±1.7 yrs) and 31 women (20.7±1.8 yrs) were measured in the reference (REF) condition, wearing an extra t-shirt (TS), wearing an extra t-shirt + long track-suit trousers (TT), and again in the REF condition respectively. Technical error of test-retest under REF conditions was excellent for percentage body fat (0.57%) (PF). Both deviating conditions resulted in significantly lower mean PF estimations (P<0.05) compared to the REF condition in men (REF:11.8±6.9%; TS:7.7±7.3%; TT: 0.1±8.2%) and women (REF:25.4±6.0%; TS:22.5±6.0%; TT: 15.2±6.7%). Variance tended to increase as more clothing was worn, and a significant trend in bias was found for body density in the TT condition with underestimations increasing with increasing body density. Together with the existing literature the present study clearly demonstrates that mean bias increases as the amount of non-standard clothing worn in the BOD-POD increases, together with measurement variation. The observed mean bias, increased variance and significant trend in bias as body density increases, result in faulty results that are of little if any practical use to the health professional and his client when assessing body composition status. It is therefore not recommended to use ADP to assess body composition if for any reason clients are unable or unwilling to adhere to the prescribed clothing conditions. [ABSTRACT FROM AUTHOR]

Background For pre-school children, the home literacy environment (HLE) plays an important role in the development of language and literacy skills. As there is little known about the HLE of children with intellectual disabilities (ID), the aim of the present study was to investigate the HLE of children with ID in comparison with children without disabilities. Method Parent questionnaires concerning aspects of the HLE were used to investigate differences between 48 children with ID, 107 children without disabilities of the same chronological age and 36 children without disabilities of the same mental age (MA). Furthermore, for the children with ID, correlations were computed between aspects of the HLE and children's non-verbal intelligence, speech intelligibility, language and early literacy skills. Results and conclusions From the results of the multivariate analyses of variance it could be concluded that the HLE of children with ID differed from that of children in the chronological age group on almost all aspects. When compared with children in the MA group, differences in the HLE remained. However, differences mainly concerned child-initiated activities and not parent-initiated activities. Correlation analyses showed that children's activities with literacy materials were positively related with MA, productive syntax and vocabulary age, and book orientation skills. Also, children's involvement during storybook reading was related with their MA, receptive language age, productive syntax and vocabulary age, book orientation and rapid naming of pictures. The amount of literacy materials parents provided was related to a higher productive syntax age and level of book orientation of the children. Parent play activities were also positively related to children's speech intelligibility. The cognitive disabilities of the children were the main cause of the differences found in the HLE between children with ID and children without disabilities. Parents also adapt their level to the developmental level of their child, which may not always be the most stimulating for the children. [ABSTRACT FROM AUTHOR]

Abstract: The concept of nonlinear normal modes (NNMs) is discussed in the present paper and its companion, Part I. One reason of the still limited use of NNMs in structural dynamics is that their computation is often regarded as impractical. However, when resorting to numerical algorithms, we show that the NNM computation is possible with limited implementation effort, which paves the way to a practical method for determining the NNMs of nonlinear mechanical systems. The proposed algorithm relies on two main techniques, namely a shooting procedure and a method for the continuation of NNM motions. The algorithm is demonstrated using four different mechanical systems, a weakly and a strongly nonlinear two-degree-of-freedom system, a simplified discrete model of a nonlinear bladed disk and a nonlinear cantilever beam discretized by the finite element method. [Copyright &y& Elsevier]

Abstract: The concept of nonlinear normal modes (NNMs) is discussed in the present paper and its companion, Part II. Because there is virtually no application of the NNMs to large-scale engineering structures, these papers are an attempt to highlight several aspects that might drive their development in the future. Specifically, we support that (i) numerical methods for the continuation of periodic solutions pave the way for an effective and practical computation of NNMs, and (ii) time–frequency analysis is particularly suitable for the analysis of the resulting dynamics. Another objective of the present paper is to describe, in simple terms, and to illustrate the fundamental properties of NNMs. This is achieved to convince the structural dynamicist not necessarily acquainted with them that they are a useful framework for the analysis of nonlinear vibrating structures. [Copyright &y& Elsevier]

Background Panitumumab is a fully human monoclonal IgG2 antibody targeting the epidermal growth factor receptor (EGFR). Aim To review the efficacy of panitumumab in the treatment of metastatic colorectal cancer (mCRC). Methods Available literature identified from PubMed and conference websites was reviewed. Results In phase 2–3 studies, panitumumab monotherapy achieved objective response rates (ORRs) of 8–13% in relapsed/refractory EGFR-expressing mCRC. In a randomized phase 3 study (463 patients), panitumumab almost halved the risk of disease progression/death vs. a control group receiving only best supportive care (hazard ratio 0.54; 95% CI: 0.44–0.66; P < 0.0001). Objective response was achieved in 22/231 (10%) patients randomized to panitumumab – and also in 20/176 (11%) patients assigned to the control group who received panitumumab in a separate crossover protocol after disease progression. Response was confined to patients with tumours harbouring wild-type KRAS (ORR ≈20%). Panitumumab is also being evaluated in earlier lines of treatment. Panitumumab monotherapy is generally well tolerated; the most common toxicities are skin toxicity (≈90%) and diarrhoea (<30%). Development of anti-panitumumab antibodies (0.3% by ELISA) and grade 3–4 infusion reactions (<1%) are rare. Conclusion Panitumumab is an effective monotherapy option for patients with relapsed/refractory EGFR-expressing mCRC harbouring wild-type KRAS. [ABSTRACT FROM AUTHOR]

Background and Purpose: The involvement of the neuropeptide oxytocin in the control of male sexual responses is documented although its exact mechanisms of action, and especially the site(s) of action, are not fully delineated. In order to clarify this issue, we tested the effects of a peptide oxytocin antagonist delivered through different routes on sexual responses elicited, in anaesthetized male rats, by i.c.v. 7-hydroxy-2-(di-N-propylamino) tetralin (7-OH-DPAT), a dopamine agonist, preferentially active on D3 receptors.Experimental Approach: Seminal vesicle pressure (SVP) and bulbospongiosus muscle (BS) electromyograms were recorded as physiological markers of emission and expulsion phases of ejaculation respectively and intracavernosal pressure (ICP) was monitored as a physiological marker of erection.Key Results: When injected i.v., the oxytocin antagonist did not impair 7-OH-DPAT-induced SVP and ICP responses while BS burst frequency was diminished. When delivered i.c.v., the oxytocin antagonist dose-dependently inhibited occurrence of 7-OH-DPAT-induced sexual responses. When delivered intrathecally (i.t.) at the level of the 6th lumbar (L6) segment, but not the 13th thoracic (T13) segment, the oxytocin antagonist reduced the duration of BS responses and the occurrence of ejaculation without impairing ICP responses.Conclusions and Implications: Brain oxytocin receptors mediate male sexual responses elicited by i.c.v. 7-OH-DPAT in anaesthetized rats whereas L6 spinal oxytocin receptors only impair the occurrence of ejaculation. Peripheral oxytocin receptors are marginally involved in 7-OH-DPAT-induced sexual responses. These findings should be considered for the development of potential pharmacological treatment of premature ejaculation in man. [ABSTRACT FROM AUTHOR]

BACKGROUND: Children with cerebral palsy (CP) and accompanying disabilities are prone to reading difficulties. The aim of the present study was to examine the foundations of phonological awareness in pre-school children with CP in comparison with a normally developing control group. Rhyme perception was regarded as an early indicator of phonological awareness, whereas non-verbal reasoning, speech ability, auditory perception, auditory short-term memory and vocabulary were regarded as foundation measures. METHODS: A number of tasks were administrated to examine group differences in rhyme perception and its foundation measures. Correlations between the tasks were analysed for both groups followed by multiple regression analyses wherein rhyme perception was predicted by its foundation measures. RESULTS: Children with CP scored below their normally developing peers on emergent phonological awareness and its foundation measures. Regarding the prediction of phonological awareness, non-verbal reasoning followed by pseudoword articulation, were found to predict phonological awareness, i.e. rhyme perception, in the group of children with CP. In the control group, auditory perception was a significant predictor of emergent phonological awareness. The CP group was further split up into two groups according to the children's non-verbal reasoning skills, i.e. general IQ. The below-average IQ group scored below the average IQ group on phonological awareness and on most foundation measures. In addition, the average IQ group of the children with CP scored lower than the control group. CONCLUSION: The results of this study indicate that general intelligence and speech ability (i.e. pseudoword articulation) can be seen as important facilitators of emergent phonological awareness in children with CP. These findings support the role of intelligence in the emergence of phonological awareness in children with CP. Children with CP with intellectual disabilities seem to have a disadvantage in acquiring phonological awareness, especially when their speech abilities are also impaired. However, general intelligence is not enough to predict phonological awareness as other foundation measures are also important for phonological awareness independent of general intelligence. [ABSTRACT FROM AUTHOR]

Background Children with cerebral palsy (CP) and accompanying disabilities are prone to reading difficulties. The aim of the present study was to examine the foundations of phonological awareness in pre-school children with CP in comparison with a normally developing control group. Rhyme perception was regarded as an early indicator of phonological awareness, whereas non-verbal reasoning, speech ability, auditory perception, auditory short-term memory and vocabulary were regarded as foundation measures. Methods A number of tasks were administrated to examine group differences in rhyme perception and its foundation measures. Correlations between the tasks were analysed for both groups followed by multiple regression analyses wherein rhyme perception was predicted by its foundation measures. Results Children with CP scored below their normally developing peers on emergent phonological awareness and its foundation measures. Regarding the prediction of phonological awareness, non-verbal reasoning followed by pseudoword articulation, were found to predict phonological awareness, i.e. rhyme perception, in the group of children with CP. In the control group, auditory perception was a significant predictor of emergent phonological awareness. The CP group was further split up into two groups according to the children's non-verbal reasoning skills, i.e. general IQ. The below-average IQ group scored below the average IQ group on phonological awareness and on most foundation measures. In addition, the average IQ group of the children with CP scored lower than the control group. Conclusion The results of this study indicate that general intelligence and speech ability (i.e. pseudoword articulation) can be seen as important facilitators of emergent phonological awareness in children with CP. These findings support the role of intelligence in the emergence of phonological awareness in children with CP. Children with CP with intellectual disabilities seem to have a disadvantage in acquiring phonological awareness, especially when their speech abilities are also impaired. However, general intelligence is not enough to predict phonological awareness as other foundation measures are also important for phonological awareness independent of general intelligence. [ABSTRACT FROM AUTHOR]

In a randomised phase 3 trial, panitumumab significantly improved progression-free survival (PFS) in patients with refractory metastatic colorectal cancer (mCRC). This analysis characterises the association of PFS with CRC symptoms, health-related quality of life (HRQoL), and overall survival (OS). CRC symptoms (NCCN/FACT CRC symptom index, FCSI) and HRQoL (EQ-5D) were assessed for 207 panitumumab patients and 184 best supportive care (BSC) patients who had at least one post-baseline patient-reported outcome (PRO) assessment. Patients alive at week 8 were included in the PRO and OS analyses and categorised by their week 8 progression status as follows: no progressive disease (no PD; best response of at least stable disease) vs progressive disease (PD). Standard imputation methods were used to assign missing values. Significantly more patients were progression free at weeks 8-24 with panitumumab vs BSC. After excluding responders, a significant difference in PFS remained favouring panitumumab (HR=0.63, 95% CI=0.52-0.77; P<0.0001). At week 8, lack of disease progression was associated with significantly and clinically meaningful lower CRC symptomatology for both treatment groups and higher HRQoL for panitumumab patients only. Overall survival favoured no PD patients vs PD patients alive at week 8. Lack of disease progression was associated with better symptom control, HRQoL, and OS. [ABSTRACT FROM AUTHOR]

Background: To document covariates which contribute to inter-individual variability in propofol pharmacokinetics in preterm and term neonates.Methods: Population pharmacokinetics were estimated (non-linear mixed effect modelling) based on the arterial blood samples collected in (pre)term neonates after i.v. bolus administration of propofol (3 mg kg(-1), 10 s). Covariate analysis included postmenstrual age (PMA), postnatal age (PNA), gestational age, weight, and serum creatinine.Results: Two hundred and thirty-five arterial concentration-time points were collected in 25 neonates. Median weight was 2930 (range 680-4030) g, PMA 38 (27-43) weeks, and PNA 8 (1-25) days. In a three-compartment model, PMA was the most predictive covariate for clearance (P<0.001) when parameterized as [CL(std).(PMA/38)(11.5)]. Standardized propofol clearance (CL(std)) at 38 weeks PMA was 0.029 litre min(-1). The addition of a fixed value in neonates with a PNA of >/=10 days further improved the model (P<0.001) and resulted in the equation [CL(std).(PMA/38)(11.5) +0.03] for neonates >/=10 days. Values for central volume (1.32 litre), peripheral volume 1 (15.4 litre), and peripheral volume 2 (1.29 litre) were not significantly influenced by any of the covariates (P>0.001).Conclusions: PMA and PNA contribute to the inter-individual variability of propofol clearance with very fast maturation of clearance in neonatal life. This implicates that preterm neonates and neonates in the first week of postnatal life are at an increased risk for accumulation during either intermittent bolus or continuous administration of propofol. [ABSTRACT FROM AUTHOR]

Objective:To study the genetic and environmental determination of variation in Heath–Carter somatotype (ST) components (endomorphy, mesomorphy and ectomorphy).Design:Multivariate path analysis on twin data.Subjects:Eight hundred and three members of 424 adult Flemish twin pairs (18–34 years of age).Results:The results indicate the significance of sex differences and the significance of the covariation between the three ST components. After age-regression, variation of the population in ST components and their covariation is explained by additive genetic sources of variance (A), shared (familial) environment (C) and unique environment (E). In men, additive genetic sources of variance explain 28.0% (CI 8.7–50.8%), 86.3% (71.6–90.2%) and 66.5% (37.4–85.1%) for endomorphy, mesomorphy and ectomorphy, respectively. For women, corresponding values are 32.3% (8.9–55.6%), 82.0% (67.7–87.7%) and 70.1% (48.9–81.8%). For all components in men and women, more than 70% of the total variation was explained by sources of variance shared between the three components, emphasising the importance of analysing the ST in a multivariate way.Conclusions:The findings suggest that the high heritabilities for mesomorphy and ectomorphy reported in earlier twin studies in adolescence are maintained in adulthood. For endomorphy, which represents a relative measure of subcutaneous adipose tissue, however, the results suggest heritability may be considerably lower than most values reported in earlier studies on adolescent twins. The heritability is also lower than values reported for, for example, body mass index (BMI), which next to the weight of organs and adipose tissue also includes muscle and bone tissue. Considering the differences in heritability between musculoskeletal robustness (mesomorphy) and subcutaneous adipose tissue (endomorphy) it may be questioned whether studying the genetics of BMI will eventually lead to a better understanding of the genetics of fatness, obesity and overweight.International Journal of Obesity (2007) 31, 1295–1301; doi:10.1038/sj.ijo.0803575; published online 6 March 2007 [ABSTRACT FROM AUTHOR]

Gemcitabine and oxaliplatin (GEMOX) are active as first-line therapy against advanced pancreatic cancer. This study aims to evaluate the activity and tolerability of this combination in patients refractory to standard gemcitabine (GEM). A total of 33 patients (median age of 57) were included with locally advanced and metastatic evaluable diseases, who had progressed during or following GEM therapy. The GEMOX regimen consisted of 1000 mg m−2 of GEM at a 100-min infusion on day 1, followed on day 2 by 100 mg m−2 of oxaliplatin at a 2-h infusion; a cycle that was given every 2 weeks. All patients received at least one cycle of GEMOX (median 5; range 1–29). Response by 31 evaluable patients was as follows: PR: 7/31(22.6%), s.d. 8 weeks: 11/31(35.5%), s.d. <8 weeks: 1/31(3.2%), PD: 12/31(38.7%). Median duration of response and TTP were 4.5 and 4.2 months, respectively. Median survival was 6 months (range 0.5–21). Clinical benefit response was observed in 17/31 patients (54.8%). Grade III/IV non-neurologic toxicities occurred in 12/33 patients (36.3%), and grade I, II, and III neuropathy in 17(51%), 3(9%), and 4(12%) patients, respectively. GEMOX is a well-tolerated, active regimen that may provide a benefit to patients with advanced pancreatic cancer after progression following standard gemcitabine treatment.British Journal of Cancer (2006) 94, 481–485. doi:10.1038/sj.bjc.6602966 www.bjcancer.com Published online 24 January 2006 [ABSTRACT FROM AUTHOR]

Background : Several studies with different designs have attempted to estimate the heritability of somatotype components. However they often ignore the covariation between the three components as well as possible sex and age effects. Shared environmental factors are not always controlled for. Aim : This study explores the pattern of genetic and environmental determination of the variation in Heath-Carter somatotype components from early adolescence into young adulthood. Subjects and methods : Data from the Leuven Longitudinal Twin Study, a longitudinal sample of Belgian same-aged twins followed from 10 to 18 years ( n = 105 pairs, equally divided over five zygosity groups), is entered into a multivariate path analysis. Thus the covariation between the somatotype components is taken into account, gender heterogeneity can be tested, common environmental influences can be distinguished from genetic effects and age effects are controlled for. Results : Heritability estimates from 10 to 18 years range from 0.21 to 0.88, 0.46 to 0.76 and 0.16 to 0.73 for endomorphy, mesomorphy and ectomorphy in boys. In girls, heritability estimates range from 0.76 to 0.89, 0.36 to 0.57 and 0.57 to 0.76 for the respective somatotype components. Sex differences are significant from 14 years onwards. More than half of the variance in all somatotype components for both sexes at all time points is explained by factors the three components have in common. Conclusions : The finding of substantial genetic influence on the variability of somatotype components is further supported. The need to consider somatotype as a whole is stressed as well as the need for sex- and perhaps age-specific analyses. Further multivariate analyses are needed to confirm the present findings. [ABSTRACT FROM AUTHOR]

Background/Aims: Postoperative mortality after colon surgery is relatively infrequent. In order to evaluate the quality of colon surgery, post-mortem evaluation is useful. This study was performed to determine the value of a mortality register used at the Department of Surgery of the Red Cross Hospital. Methods: From 1991 to 2000, 882 colon resections were performed for both malignant and benign disorders, including elective and emergency surgery. Permission for autopsy was asked routinely. All cases were reviewed and categorized in a multidisciplinary meeting. Any discrepancy between the clinical and post-mortem diagnosis was determined by a pathologist. Results: The mortality rate of colon surgery was 8.0% (n = 71), 23% for emergency surgery and 6% for elective surgery (p < 0.001). For patients under 70 years of age the mortality rate was 4.3%, for patients over 70 years of age 11.2% (p < 0.001). Autopsy was performed in 62% (n = 44) of the patients. Discrepancy between clinical and post-mortem findings was documented in 14%. Conclusion: Postoperative mortality after colon surgery is influenced by the timing of surgery (elective or emergency procedure) and the age of the patient. A discrepancy of 14% between clinical cause of death and postmortem cause of death justifies the need for obtaining autopsy in this type of surgery. [ABSTRACT FROM AUTHOR]

There is considerable evidence that the activity of the neuronal dopamine transporter (DAT) is dynamically regulated and a putative implication of its phosphorylation in this process has been proposed. However, there is little information available regarding the nature of physiological stimuli that contribute to the endogenous control of the DAT function. Based on the close relationship between glutamatergic and dopaminergic systems in the striatum, we investigated the modulation of the DAT activity by metabotropic glutamate receptors (mGluRs). Short-term incubations of rat striatal synaptosomes with micromolar concentrations of the group I mGluR selective agonist (S)-3,5-dihydroxyphenylglycine were found to significantly decrease the DAT capacity and efficiency. This alteration was completely prevented by a highly selective mGluR5 antagonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). The effect of (S)-3,5-dihydroxyphenylglycine was also inhibited by staurosporine and by selective inhibitors of protein kinase C and calcium calmodulin-dependent protein kinase II. Co-application of okadaic acid prolonged the transient effect of the agonist, supporting a critical role for phosphorylation in the modulation of the DAT activity by mGluRs. In conclusion, we propose that striatal mGluR5 contribute to the control of the DAT activity through concomitant activation of both protein kinase C and calcium calmodulin-dependent protein kinase II. [ABSTRACT FROM AUTHOR]

Examines the tumor necrosis factor (TNF) gene-308 SBP polymorphism in several Crohn's disease (CD) patients. Production of TNF-α by colonic mucosa of CD patients; Extraction of the genomic DNA; Culture of colonic biopsies.

Changes in nucleolar size and nucleolar vacuolation at early stages of fiber development and final fiber dimensions were determined for cotton of different species: Gossypium hirsutum L. cv. B49, Gossypium barbadense L. cv. Menoufi and Gossypium arboreum L. cv. Virnar. Size of the nucleolus in combination with its vacuolation at an early stage of development was found to be clearly associated with the final result of fiber development. [ABSTRACT FROM AUTHOR]

Food and nutrition studies in animals and human beings often meet with technical difficulties and sometimes with ethical questions. An alternative to research in living animals is the dynamic multicompartmental in vitro model for the gastrointestinal tract described by Minekus et al. (1995) and Havenaar & Minekus (1996). The dynamic conditions that are simulated in this model are peristaltic movements, transit times, pH responses, secretion of enzymes and electrolytes and absorption of nutrients and water. To obtain data for an in vitro model of the dog gastrointestinal tract, the literature was surveyed for physiological responses to different types of dog food. These included: values of enzyme activities, electrolyte concentrations, gastric emptying and intestinal transit times, pH values, secretion and composition of bile and absorption rates in different parts of the dog gastrointestinal tract. The review focuses on research carried out on healthy, adult dogs of 10-20 kg and on parameters related to the oral cavity, stomach and small intestine. This literature research gives sufficient data on the physiology of the canine digestive tract for the development of an in vitro dynamic model that adequately simulates the functions of the stomach and small intestine of the dog. [ABSTRACT FROM AUTHOR]

Background: In low- and middle-income countries, surveillance of antimicrobial resistance (AMR) is mostly hospital-based and, in view of poor access to clinical microbiology, biased to more resistant pathogens. We aimed to assess AMR among Escherichia coli isolates obtained from urine cultures of pregnant women as an indicator for community AMR and compared the AMR results with those from E. coli isolates obtained from febrile patients in previously published clinical surveillance studies conducted within the same population in Nanoro, rural Burkina Faso. We furthermore explored feasibility of adding urine culture to standard antenatal care in a rural sub-Saharan African setting. Methods: Between October 2016–September 2018, midstream urine samples collected as part of routine antenatal care in Nanoro district were cultured by a dipslide method and screened for antibiotic residues. Significant growth was defined as a pure culture of Enterobacterales at counts of ≥ 104 colony forming units/ml. Results: Significant growth was observed in 202/5934 (3.4%) cultures; E. coli represented 155 (76.7%) of isolates. Among E. coli isolates, resistance rates to ampicillin, cotrimoxazole and ciprofloxacin were respectively 65.8%, 64.4% 16.2%, compared to 89.5%, 89.5% and 62.5% among E. coli from clinical isolates (n = 48 of which 45 from blood cultures). Proportions of extended spectrum beta-lactamase producers and multidrug resistance were 3.2% and 5.2% among E. coli isolates from urine in pregnant women versus 35.4%, and 60.4% respectively among clinical isolates. Conclusions: The E. coli isolates obtained from healthy pregnant women had significantly lower AMR rates compared to clinical E. coli isolates, probably reflecting the lower antibiotic pressure in the pregnant women population. Adding urine culture to the routine urine analysis (dipstick) of antenatal care was feasible. The dipslide culture method was affordable and user-friendly and allowed on-site inoculation and easy transport; challenges were contamination (midstream urine sampling) and the semi-quantitative reading. Provided confirmation of the present findings in other settings, E. coli from urine samples in pregnant women may be a potential indicator for benchmarking, comparing, and monitoring community AMR rates across populations over different countries and regions. [ABSTRACT FROM AUTHOR]

This study evaluated a new immunochromatographic assay (SAS Legionella Test) for its ability to detect Legionella pneumophila serogroup 1 antigen in urine. Results were compared with those obtained using the Binax Now urinary antigen test. Sensitivity and specificity were estimated as 82.9% and 99.0%, respectively, for the SAS Legionella Test, and 91.4% and 100%, respectively, for the Binax Now urinary antigen test. The sensitivity of both tests increased to 97.1% (p 0.009) and 94.2% (p 0.7), respectively, if the tests were examined after 1 h. [ABSTRACT FROM AUTHOR]

The data generated in buildings are used for all types of purposes. The quality of information used in assisting people to escape an emergency situation is of importance. In practice today, none of the data-generating systems that aid in the escape from emergency situations is validated on a regular basis. This study is based on the smart building concept. The rationale behind this concept is to provide information about a building and the usage of that building at each moment in time. An experiment was conducted to measure the impact of different types of information on participants' choice of exit, exit time and distance travelled. Seven identical floors of one building were used with different setups to see if the choice of exit is influenced by the type of information provided at the moment of an alarm. It was found that the information does have a significant impact on the choice of exit, escape speed and distance travelled. Furthermore, it was shown that false information can increase the time it takes to leave the building and the distance travelled, impacting the survival rate. The more imperative information is visualised, the stronger its influence is on the choices made. • Fire drill experiment in a student house to determine impact of given information. • The information impacts the time to escape, distance travelled and choice of exit. • False information negatively impacts the escape. • Visualisation influences information comprehension. [ABSTRACT FROM AUTHOR]

The article presents a brief report on the evaluation of Rapid U Legionella Plus Test, an immunochromatographic assay for detection of Legionella pneumophila serogroup 1 antigen in urine. The study evaluated the antigen test to detect Legionnaires' disease in well-described sample of patients. Results of the study indicated that Rapid U Legionella Plus Test showed the same high degree of sensitivity with that of the widely used Binax NOW test when used with non-concentrated urine samples.

Background: KRAS mutations in metastatic colorectal cancer (mCRC) are used as predictive biomarkers to select therapy with EGFR monoclonal antibodies (mAbs). Other factors may be significant determinants of benefit. Methods: Individual patient data from randomised trials with a head-to-head comparison between EGFR mAb versus no EGFR mAb (chemotherapy alone or best supportive care) in mCRC, across all lines of therapy, were pooled. Overall survival (OS) and progression-free survival (PFS) were compared between groups. Treatment effects within the predefined KRAS biomarker subsets were estimated by adjusted hazard ratio (HRadj) and 95% confidence interval (CI). EGFR mAb efficacy was measured within the KRAS wild-type subgroup according to BRAF and NRAS mutation status. In both KRAS wild-type and mutant subgroups, additional factors that could impact EGFR mAb efficacy were explored including the type of chemotherapy, line of therapy, age, sex, tumour sidedness and site of metastasis. Results: 5675 patients from 8 studies were included, all with known mCRC KRAS mutation status. OS (HRadj 0.90, 95% CI 0.84–0.98, p = 0.01) and PFS benefit (HRadj 0.73, 95% CI 0.68–0.79, p < 0.001) from EGFR mAbs was observed in the KRAS wild-type group. PFS benefit was seen in patients treated with fluorouracil (HRadj 0.75, 95% CI 0.68–0.82) but not with capecitabine-containing regimens (HRadj 1.04, 95% CI 0.86–1.26) (pinteraction = 0.002). Sidedness also interacted with EGFR mAb efficacy, with survival benefit restricted to left-sided disease (pinteraction = 0.038). PFS benefits differed according to age, with benefits greater in those under 70 (pinteraction = 0.001). The survival benefit was not demonstrated in those patients with mutations found in the KRAS, NRAS or BRAF genes. The presence of liver metastases interacted with EGFR mAb efficacy in patients with KRAS mutant mCRC (pinteraction = 0.004). Conclusion: The benefit provided by EGFR mAbs in KRAS WT mCRC is associated with left-sided primary tumour location, younger patient age and absence of NRAS or BRAF mutations. Survival benefit is observed with fluorouracil but not capecitabine. Exploratory results support further research in KRAS mutant mCRC without liver metastases. [ABSTRACT FROM AUTHOR]

We experimentally demonstrate single-pulse all-optical switching in Pt/Co/Gd stacks using linearly polarized laser pulses. This shows that thermal single-pulse switching is not limited to ferrimagnetic alloys, but is also possible in ferrimagnetic multilayers that are highly suitable for future applications due to easy fabrication and (interface) engineering. Moreover, it is shown that the threshold fluence needed for the optical switch strongly depends on the thickness of the Co layer, with a remarkable low threshold fluence of ≈1.2 mJ/cm² for a Co thickness of 0.8 nm. Lastly, helicity-dependent measurements showed no significant effect of the magnetic circular dichroism in these thin magnetic layers. [ABSTRACT FROM AUTHOR]

We evaluated a new immunochromatographic assay (Legionella V-TesT, Coris BioConcept, Gembloux, Belgium) for its ability to detect Legionella pneumophila serogroup 1 antigen in urine. Test devices were read at various time points to determine the optimum incubation time regarding performance. The results were compared with those obtained with the BinaxNOW urinary antigen test. The sensitivity and specificity were 82.2% and 98.6%, respectively, for the Legionella V-TesT and 83.9% and 100%, respectively, for the BinaxNOW urinary antigen test after 15 min of incubation. When tests were examined after 60 min, the sensitivity for both tests increased to 91.5%. [ABSTRACT FROM AUTHOR]

Peritoneal carcinomatosis carries a dismal prognosis. Recently, extensive surgery followed by hyperthermic intraperitoneal chemoperfusion (HIPEC) has been proposed in the management of these patients. Elegible patients suffered from peritoneal carcinomatosis without evidence of systemic disease. Following extensive cytoreduction, HIPEC was performed with a closed technique at 42-43°C using mitomycine C, cisplatinum, mitoxantrone, or paclitaxel administered with a closed perfusion circuit during 90 min. All patients were followed closely and survival data