Simulating high-pressure surface reactions with molecular beams.

Using a reactive molecular beam with high kinetic energy (Ekin), it is possible to speed gas-surface reactions involving high activation barriers (Eact), which would require elevated pressures (P0) if a random gas with a Maxwell-Boltzmann distribution is used. By simply computing the number of molecules that overcome the activation barrier in a random gas at P0 and in a molecular beam at Ekin = Eact, we establish an Ekin-P0 equivalence curve, through which we postulate that molecular beams are ideal tools to investigate gas-surface reactions that involve high activation energies. In particular, we foresee the use of molecular beams to simulate gas surface reactions within the industrial-range (>10 bar) using surface-sensitive ultra-high vacuum (UHV) techniques, such as X-ray photoemission spectroscopy (XPS). To test this idea, we revisit the oxidation of the Cu(111) surface combining O2 molecular beams and XPS experiments. By tuning the kinetic energy of the O2 beam in the range of 0.24-1 eV, we achieve the same sequence of surface oxides obtained in ambient pressure photoemission (AP-XPS) experiments, in which the Cu(111) surface was exposed to a random O2 gas up to 1 mbar. We observe the same surface oxidation kinetics as in the random gas, but with a much lower dose, close to the expected value derived from the equivalence curve.

Physical and functional performance assessment in pediatric oncology: a systematic review.

BACKGROUND: Research indicates reduced physical performance from diagnosis into survivorship of pediatric cancer patients. However, there is no systematic information or guideline available on the methods to assess physical performance and function in this population. The purpose was to systematically compile and describe assessments of physical performance and function in patients and survivors of pediatric cancer, including cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait and motor performance test batteries. METHODS: We searched the databases PubMed, SPORTDiscus, and Cochrane Database and performed abstract and full-text selection of 2619 articles according to the Cochrane Handbook of Systematic Reviews. Information on patients characteristics, assessments, information on validity and reliability, and relevant references was extracted. RESULTS: In summary, 63 different assessments were found in 149 studies including 11639 participants. Most studies evaluated cardiorespiratory fitness and muscle strength with the majority conducted off treatment. Some outcomes (e.g. speed) and diagnoses (e.g. neuroblastoma) were severely underrepresented. With the exception of gait, leukemia patients represented the largest group of individuals tested. CONCLUSIONS: Insufficient data and patient heterogeneity complicate uniform recommendations for assessments. Our results support researchers and practitioners in selecting appropriate assessment to meet their specific research questions or individual daily practice needs. IMPACT: This systematic review includes 149 studies and provides a comprehensive summary of 63 assessments to evaluate cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait or motor performance test batteries in patients and survivors of pediatric cancer. We present the most studied fields within the pediatric cancer population, which are cardiorespiratory fitness and muscle strength, off treatment phase, and leukemia patients. We propose research priorities by identification of subgroups in terms of cancer type, phase of treatment, and outcome of interest that are underrepresented in studies currently available.

Scaling Platinum-Catalyzed Hydrogen Dissociation on Corrugated Surfaces.

We determine absolute reactivities for dissociation at low coordinated Pt sites. Two curved Pt(111) single-crystal surfaces allow us to probe either straight or highly kinked step edges with molecules impinging at a low impact energy. A model extracts the average reactivity of inner and outer kink atoms, which is compared to the reactivity of straight A- and B-type steps. Local surface coordination numbers do not adequately capture reactivity trends for H2 dissociation. We utilize the increase of reactivity with step density to determine the area over which a step causes increased dissociation. This step-type specific reactive area extends beyond the step edge onto the (111) terrace. It defines the reaction cross-section for H2 dissociation at the step, bypassing assumptions about contributions of individual types of surface atoms. Our results stress the non-local nature of H2 interaction with a surface and provide insight into reactivity differences for nearly identical step sites.

Survival and therapeutic response in patients with melanoma of unknown and known primary: a single-centre retrospective analysis.

BACKGROUND: The survival of patients with melanoma of unknown primary (MUP) is proposed to be more favourable than that for melanoma of known primary (MKP). This may be due to an enhanced initial immune response in patients with MUP, which could also affect the efficacy of immunotherapy in advanced disease. OBJECTIVES: The present study compared therapeutic outcome and survival in Stage III and IV MUP and MKP. RESULTS: Medical records of 67 MUP and 536 MKP patients were reviewed. Median overall survival (OS) in Stage III patients was 77 months versus 54 months in patients with MUP and MKP, respectively (p = 0.11). Median OS was prolonged in MUP patients receiving adjuvant first-line ipilimumab (p = 0.14). In contrast, OS tended to be more favourable in patients with MKP after palliative first-line ipilimumab treatment (p = 0.16). Yet, no statistically significant differences in OS were detected between the groups. Moreover, survival after anti-PD-1-antibody treatment was similar in patients with MUP and MKP. CONCLUSION: Overall, we observed similar survival outcomes after immunotherapy in patients with MUP and MKP. These findings provide no evidence of difference in responsiveness to immunotherapy between patients with MUP and MKP.

It's not just the defects - a curved crystal study of H2O desorption from Ag.

We investigate water desorption from hydrophobic surfaces using two curved Ag single crystals centered at (111) and (001) apices. On these types of crystals the step density gradually increases along the curvature, allowing us to probe large ranges of surface structures in between the (001), (111) and (110) planes. Subtle differences in desorption of submonolayer water coverages point toward structure dependencies in water cluster nucleation. The B-type step on hydrophobic Ag binds water structures more strongly than adjacent (111) planes, leading to preferred desorption from steps. This driving force is smaller for A-type steps on (111) terraces. The A'-type step flanked by (001) terraces shows no indication of preferred desorption from steps. Extrapolation to the (311) surface, not contained within either curved surface, demonstrates that both A- and A'-type steps can be regarded chemically identical for water desorption. The different trends in desorption temperature on the two crystals can thus be attributed to stronger water adsorption at (001) planes than at (111) planes and identical to adsorption at the step. These results show that our approach to studying the structure dependence of water desorption is sensitive to variations in desorption energy smaller than 'chemical accuracy', i.e. 1 kcal mol-1.

Site-specific reactivity of molecules with surface defects-the case of H2 dissociation on Pt.

The classic system that describes weakly activated dissociation in heterogeneous catalysis has been explained by two dynamical models that are fundamentally at odds. Whereas one model for hydrogen dissociation on platinum(111) invokes a preequilibrium and diffusion toward defects, the other is based on direct and local reaction. We resolve this dispute by quantifying site-specific reactivity using a curved platinum single-crystal surface. Reactivity is step-type dependent and varies linearly with step density. Only the model that relies on localized dissociation is consistent with our results. Our approach provides absolute, site-specific reaction cross sections.

KRAS Mutations in Canine and Feline Pancreatic Acinar Cell Carcinoma.

Companion animals may serve as valuable models for studying human cancers. Although KRAS is the most commonly mutated gene in human ductal pancreatic cancers (57%), with mutations frequently occurring at codons 12, 13 and 61, human pancreatic acinar cell carcinomas (ACCs) lack activating KRAS mutations. In the present study, 32 pancreatic ACC samples obtained from 14 dogs and 18 cats, including seven metastases, were analyzed for six common activating KRAS mutations located in codons 12 (n = 5) and 13 (n = 1) using Sequenom MassARRAY. No KRAS mutations were found, suggesting that, similar to human pancreatic ACC, KRAS mutations do not play a critical role in feline or canine pancreatic ACC. Due to the similarity of the clinical disease in dogs and cats to that of man, this study confirms that companion animals offer potential as a suitable model for investigating this rare subtype of pancreatic carcinoma.

One in Four Questioned Children Faces Problems Regarding Reintegration Into Physical Education at School After Treatment for Pediatric Cancer.

Resumption of physical activity and reintegration into social surroundings after treatment for pediatric cancer is of high importance to recover from the burden of disease and treatment and to positively influence long-term health outcomes. Eighty-three children who had completed intensive treatment for pediatric cancer were surveyed regarding their participation in physical education at school (PES). The results show a concerning low rate of participation, particularly in children treated for pediatric bone tumors, and associated barriers. Reported reasons for quitting PES seem to be conquerable by individual and entity-related support to enable participation according to the children's desire.

Motor Performance After Treatment for Pediatric Bone Tumors.

BACKGROUND: Reduced motor performance can negatively affect physical activity and social partake after childhood cancer. Especially in bone tumor patients, who are at risk of physical limitations due to surgical interventions, motor performance has not yet been sufficiently investigated. Therefore, this study aimed at assessing motor performance in pediatric bone tumor patients. PROCEDURE: Motor performance was measured within 2 years posttreatment using the MOON (test for MOtor performance in pediatric ONcology) test. This instrument enables quantitative data collection even in physically impaired patients for comparison with age-matched and sex-matched reference values. RESULTS: Twenty-one patients (13 male) ages 15.2±2.1 years (median: 15 y, 10 to 19 y) and 9.4±7.4 months posttreatment (median: 6 mo, 2 to 24 mo) were tested. Motor performance was slightly reduced in muscular endurance of the legs; significantly reduced in speed, flexibility, eye-hand coordination, and muscular explosive strength (P<0.001), whereas patients' hand grip strength and static balance were superior to the reference values. Follow-up duration, body mass index, and tumor localization apparently affected motor performance. CONCLUSIONS: These findings show serious reductions in motor performance within 2 years after bone tumor treatment and highlight the need for interventions to improve motor performance. The results should be used to advise and support patients to engage in suitable physical and sports activities.

Telehealth on heart failure: results of the Recap project.

Telehealth has become a very important tool that allows the monitoring of heart failure patients in a home environment. However, little is known about the effect that such monitoring systems have on patients' compliance, evolution and self-care behaviour. In particular, the effect that the selected user interface has on these factors is unknown. This study aims to investigate this, and to determine some practicalities that must be considered when designing and implementing a telehealth programme for heart failure. To achieve this, daily measurements of blood pressure, pulse, SpO2 and weight were collected from 534 patients suffering from heart failure. In addition, they were asked to fill in the European heart failure self-care behaviour scale questionnaire and the EQ-5D quality of life questionnaire, before and after the monitoring period. Two telehealth systems were used, the Motiva platform provided by Philips and the standalone unit provided by Docobo, the Doc@Home system. Significant differences were found between both systems concerning the compliance and adherence of patients. Moreover, a general, positive effect of telehealth was identified due to the fact that patients showed an increased self-awareness when managing their condition. These findings are supported by behavioural changes and a better understanding of heart failure from the patients' perspective.

Motor performance in children and adolescents with cancer at the end of acute treatment phase.

UNLABELLED: Reduced motor performance may particularly limit reintegration into normal life after cessation of treatment in pediatric cancer patients. This study aimed at analyzing motor performance at the end of the acute treatment phase and reveals potential risk factors for motor deficits. A childhood cancer population with different tumor entities was assessed with the MOON test, which allows for comparison with age- and gender-matched reference values of healthy children, at the end of the acute treatment phase. Forty-seven patients were tested at 7.0 ± 2.6 months after diagnosis. Significant reductions of motor performance affected muscular explosive strength (P < 0.001), handgrip strength (P < 0.001), muscular endurance of legs (P = 0.035), hand-eye coordination (P < 0.001), static balance (P = 0.003), speed (P = 0.012), and flexibility (P < 0.001). Loss of upper extremity coordination did not achieve statistical significance. Associations between single motor deficits and the tumor entity, age, body mass index, and inactivity during treatment were revealed, whereas no associations were found for gender and vincristine application. CONCLUSION: Overall, motor performance was low in the patient group studied. We recommend that individualized exercise interventions to attenuate motor deficits and promote physical activity are needed during cancer treatment in order to enhance motor performance and improve social participation during and after cancer therapy.

The mammalian target of rapamycin inhibitor everolimus (RAD001) in early breast cancer: results of a pre-operative study.

mTOR plays a key role in tumor cell cycle control, proliferation, and survival. RAD001 (everolimus) is a novel macrolide that inhibits mTOR and thus downstream signaling pathways. 31 post-menopausal women with early breast cancer were given 5 mg RAD001 once daily for 14 days prior to surgery. Biopsies were taken at diagnosis and at surgery (post 14 days of treatment) and assessed for immunohistochemical changes in proliferation (Ki67), apoptosis (active caspase-3), p-AKT (s473), p-S6 (s235/236 and s240/244), p-mTOR (s2448), ER, and PR. Five patients did not complete the 2-week treatment period due to adverse events. All adverse events were grade 1 or 2 (NCIC-CTC scale). RAD001 treatment significantly decreased proliferation (geometric mean reduction 74% from baseline (p = 0.019)), particularly in HER-2 positive tumors. High Ki67 pre-treatment correlated with reduction in Ki67, an increase in apoptosis, a reduction in p-AKT (cytoplasmic) and reduction in p-mTOR following treatment. Nuclear expression of p-AKT was significantly reduced with treatment. Tumors that had a reduction in Ki67 with treatment exhibited a significant reduction in cytoplasmic p-AKT. p-S6 staining was significantly reduced independently of Ki67 (p < 0.001 for two sites of phosphorylation). RAD001 5 mg/daily is safe and tolerable in postmenopausal early breast cancer patients and inhibits the mTOR pathway and its downstream effectors, significantly reducing tumor cell proliferation. Tumors with high Ki67, high p-AKT, and HER-2 positivity may be more responsive to mTOR inhibition with RAD001. This is the first study to report results of RAD001 5 mg as a single agent in early breast cancer.

A Comprehensive Profile of Decoding and Comprehension in Autism Spectrum Disorders.

The present study examined intake data from 384 participants with autism spectrum disorders (ASD) and a comparison group of 100 participants with dyslexia on nine standardized measures of decoding and comprehension. Although diagnostic groups were based on parental reports and could not be verified independently, we were able to observe significant distinctions between subject groups. Overall findings confirm previous results of a disassociation between decoding and comprehension in ASD. Using a larger sample than previous studies and a greater variety of measures, a pattern of relatively intact decoding skills paired with low comprehension was found in autism, PDD-NOS, and Asperger's. In contrast, the dyslexic group showed the opposite pattern of stronger comprehension and weaker decoding.

Hepatic transcriptomic profiles of European flounder (Platichthys flesus) from field sites and computational approaches to predict site from stress gene responses following exposure to model toxicants.

Genomic technologies offer opportunities to gain a more global assessment of the health status of an organism through an understanding of the functional pathways that are responding to pollutant exposure. We have developed a 13,000 clone cDNA toxicogenomics microarray for Platichthys flesus, the European flounder (EU-GENIPOL Project). We aimed to distinguish the origins of flounder taken from six sampling sites of different pollution status in Northern Europe according to their hepatic gene expression profile using bioinformatic approaches. To determine which gene expression differences may relate to pollutant impact, we have completed complementary laboratory exposures of flounder to selected toxicants and determined the associated gene expression profiles. Using multivariate variable selection coupled with a statistical modelling procedure (GALGO) we can predict geographical site but the accuracy is limited to specific sites. The search space for a combination of genes that effectively predicts class membership is very large, however, by combining the signatures derived from acute laboratory exposure to individual chemicals to limit the search space, a very accurate model for classification of all the different environmental sites was achieved. The final model utilised the expression profiles of 16 clones and validation with a qPCR array comprising these genes correctly assigned the site of origin for fish obtained from three of the sites in an independent sampling. These data would imply that the gene expression fingerprints obtained with these arrays are primarily attributable to variations in chemical pollutant responses at the different sites, indicating their potential utility in environmental impact assessment.

A comparison of pollutant biomarker responses with transcriptional responses in European flounders (Platicthys flesus) subjected to estuarine pollution.

European flounders from two UK estuaries with different contaminant profiles were sampled and analysed for impacts of PAHs, heavy metals and estrogenic compounds by currently adopted measurement procedures used in statutory monitoring programs. These showed that fish from the polluted Tyne estuary had responded to all three classes of pollutants with elevations in hepatic EROD, MT and plasma VTG and that there was considerable interanimal variation in the magnitude of the response. Analysis of PAH metabolites in bile showed recent uptake of low molecular weight PAHs. The pollutant response was also apparent when hepatic levels of cytochrome P450 1A (CYP1A), metallothionein (MT) and vitellogenin (VTG) mRNAs were quantified by real time PCR. Whilst there did not appear to be a direct correlation between levels of gene transcripts and their protein products on an individual basis, these results demonstrate that measurements of mRNA levels of specific genes, or their protein products both demonstrate induction in polluted environments and are thus valid measures in biomonitoring studies. Procedurally, the use of the single generic technology of Q-PCR was much simpler and is worth pursuing in future studies.