Medulloblastoma has a global impact on health related quality of life: Findings from an international cohort

BACKGROUND: Understanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients. METHODS: Seventy-six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables on HRQL was considered-including molecular subgroup. RESULTS: The majority of patients reported having moderate or severe overall burden of morbidity for both the HUI2 and HUI3 (HUI2 = 60%; HUI3 = 72.1%) when proxy-assessed. Self-care in the HUI2 was rated as higher (ie better outcome) for patients from Western versus Eastern sites, P = .02. Patients with nonmetastatic status had higher values (ie better outcomes) for the HUI3 hearing, HUI3 pain, and HUI2 pain, all P \u3c .05. Patients treated with a gross total resection also had better outcomes for the HUI3 hearing (P = .04). However, those who underwent a gross total resection reported having worse outcomes on the HUI3 vision (P = .02). No differences in HRQL were evident as a function of subgroup. CONCLUSIONS: By examining an international sample of survivors, we characterized the worldwide impact of medulloblastoma. This is a critical first step in developing global standards for evaluating long-term outcomes

Planning with Information-Processing Constraints and Model Uncertainty in Markov Decision Processes

Information-theoretic principles for learning and acting have been proposed to solve particular classes of Markov Decision Problems. Mathematically, such approaches are governed by a variational free energy principle and allow solving MDP planning problems with information-processing constraints expressed in terms of a Kullback-Leibler divergence with respect to a reference distribution. Here we consider a generalization of such MDP planners by taking model uncertainty into account. As model uncertainty can also be formalized as an information-processing constraint, we can derive a unified solution from a single generalized variational principle. We provide a generalized value iteration scheme together with a convergence proof. As limit cases, this generalized scheme includes standard value iteration with a known model, Bayesian MDP planning, and robust planning. We demonstrate the benefits of this approach in a grid world simulation.Comment: 16 pages, 3 figure

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

Amicable pairs and aliquot cycles for elliptic curves

An amicable pair for an elliptic curve E/Q is a pair of primes (p,q) of good reduction for E satisfying #E(F_p) = q and #E(F_q) = p. In this paper we study elliptic amicable pairs and analogously defined longer elliptic aliquot cycles. We show that there exist elliptic curves with arbitrarily long aliqout cycles, but that CM elliptic curves (with j not 0) have no aliqout cycles of length greater than two. We give conjectural formulas for the frequency of amicable pairs. For CM curves, the derivation of precise conjectural formulas involves a detailed analysis of the values of the Grossencharacter evaluated at a prime ideal P in End(E) having the property that #E(F_P) is prime. This is especially intricate for the family of curves with j = 0.Comment: 53 page

Cost and performance of some carbon capture technology options for producing different quality CO₂ product streams

A techno-economic assessment of power plants with CO2 capture technologies with a focus on process scenarios that deliver different grades of CO2 product purity is presented. The three leading CO2 capture technologies are considered, namely; oxyfuel combustion, pre-combustion and post-combustion capture. The study uses a combination of process simulation of flue gas cleaning processes, modelling with a power plant cost and performance calculator and literature values of key performance criteria in order to evaluate the performance, cost and CO2 product purity of the considered CO2 capture options. For oxyfuel combustion capture plants, three raw CO2 flue gas processing strategies of compression and dehydration only, double flash system purification and distillation purification are considered. Analysis of pre-combustion capture options is based on integrated gasification combined cycle plants using physical solvent systems for capturing CO2 and sulfur species via three routes; co-capture of sulfur impurities with the CO2 stream using Selexol™ solvent, separate capture of CO2 and sulfur impurities using Selexol™, and Rectisol® solvent systems for separate capture of sulfur impurities and CO2. Analysis of post-combustion capture plants was made with and without some conventional pollution control devices. The results highlight the wide variation in CO2 product purity for different oxyfuel combustion capture scenarios and the wide cost variation for the pre-combustion capture scenarios. The post-combustion capture plant with conventional pollution control devices offers high CO2 purity (99.99 mol%) for average cost of considered technologies. The calculations performed will be of use in further analyses of whole chain CCS for the safe and economic capture, transport and storage of CO2

Risk of cardiovascular and all-cause mortality: impact of impaired health-related functioning and diabetes: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study.

OBJECTIVE: There is an established link between health-related functioning (HRF) and cardiovascular disease (CVD) mortality, and it is known that those with diabetes predominantly die of CVD. However, few studies have determined the combined impact of diabetes and impaired HRF on CVD mortality. We investigated whether this combination carries a higher CVD risk than either component alone. RESEARCH DESIGN AND METHODS: The Australian Diabetes, Obesity and Lifestyle (AusDiab) study included 11,247 adults aged ≥ 25 years from 42 randomly selected areas of Australia. At baseline (1999-2000), diabetes status was defined using the World Health Organization criteria and HRF was assessed using the SF-36 questionnaire. RESULTS: Overall, after 7.4 years of follow-up, 57 persons with diabetes and 105 without diabetes had died from CVD. In individuals with and without diabetes, HRF measures were significant predictors of increased CVD mortality. The CVD mortality risks among those with diabetes or impaired physical health component summary (PCS) alone were similar (diabetes only: hazard ratio 1.4 [95% CI 0.7-2.7]; impaired PCS alone: 1.5 [1.0-2.4]), while those with both diabetes and impaired PCS had a much higher CVD mortality (2.8 [1.6-4.7]) compared with those without diabetes and normal PCS (after adjustment for multiple covariates). Similar results were found for the mental health component summary. CONCLUSIONS: This study demonstrates that the combination of diabetes and impaired HRF is associated with substantially higher CVD mortality. This suggests that, among those with diabetes, impaired HRF is likely to be important in the identification of individuals at increased risk of CVD mortality

Bio‐Orthogonal Polymer Coatings for Co‐Presentation of Biomolecules

Controlled presentation of biomolecules on synthetic substrates is an important aspect for biomaterials development. If the immobilization of multiple biomolecules is required, highly efficient orthogonal surface chemistries are needed to ensure the precision of the immobilization. In this communication, chemical vapor deposition (CVD) copolymerization is used to fabricate polymer coatings with controlled ratio of alkyne and pentafluorophenyl ester (Pfp‐ester) groups. Cyclic argine‐glycine‐aspartic acid (cRGD) adhesion peptide and epidermal growth factor (EGF) are immobilized through alkyne–azide cycloaddtion (“click” chemistry) and active ester–amine reaction, respectively. Cell studies with human umbilical vein endothelial cells (HUVEC) and A431 cell lines demonstrate the biological activity of the coimmobilized biomolecules. Polymer coatings with bio‐orthogonal functional groups are developed for co‐immobilization of adhesion peptide and growth factor. The coatings are generated by chemical vapor deposition polymerization, with both alkyne and pentafluorophenyl ester which are used to covalently tether the biomolecules. The biological activity of the co‐immobilized biomolecules is demonstrated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91189/1/marc_201100819_sm_suppl.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91189/2/640_ftp.pd

Palaeoproterozoic magnesite: lithological and isotopic evidence for playa/sabkha environments

Magnesite forms a series of 1- to 15-m-thick beds within the approximate to2.0 Ga (Palaeoproterozoic) Tulomozerskaya Formation, NW Fennoscandian Shield, Russia. Drillcore material together with natural exposures reveal that the 680-m-thick formation is composed of a stromatolite-dolomite-'red bed' sequence formed in a complex combination of shallow-marine and non-marine, evaporitic environments. Dolomite-collapse breccia, stromatolitic and micritic dolostones and sparry allochemical dolostones are the principal rocks hosting the magnesite beds. All dolomite lithologies are marked by delta C-13 values from +7.1 parts per thousand to +11.6 parts per thousand (V-PDB) and delta O-18 ranging from 17.4 parts per thousand to 26.3 parts per thousand (V-SMOW). Magnesite occurs in different forms: finely laminated micritic; stromatolitic magnesite; and structureless micritic, crystalline and coarsely crystalline magnesite. All varieties exhibit anomalously high delta C-13 values ranging from +9.0 parts per thousand to +11.6 parts per thousand and delta O-18 values of 20.0-25.7 parts per thousand. Laminated and structureless micritic magnesite forms as a secondary phase replacing dolomite during early diagenesis, and replaced dolomite before the major phase of burial. Crystalline and coarsely crystalline magnesite replacing micritic magnesite formed late in the diagenetic/metamorphic history. Magnesite apparently precipitated from sea water-derived brine, diluted by meteoric fluids. Magnesitization was accomplished under evaporitic conditions (sabkha to playa lake environment) proposed to be similar to the Coorong or Lake Walyungup coastal playa magnesite. Magnesite and host dolostones formed in evaporative and partly restricted environments; consequently, extremely high delta C-13 values reflect a combined contribution from both global and local carbon reservoirs. A C- 13-rich global carbon reservoir (delta C-13 at around +5 parts per thousand) is related to the perturbation of the carbon cycle at 2.0 Ga, whereas the local enhancement in C-13 (up to +12 parts per thousand) is associated with evaporative and restricted environments with high bioproductivity

Marginalization of end-use technologies in energy innovation for climate protection

Mitigating climate change requires directed innovation efforts to develop and deploy energy technologies. Innovation activities are directed towards the outcome of climate protection by public institutions, policies and resources that in turn shape market behaviour. We analyse diverse indicators of activity throughout the innovation system to assess these efforts. We find efficient end-use technologies contribute large potential emission reductions and provide higher social returns on investment than energy-supply technologies. Yet public institutions, policies and financial resources pervasively privilege energy-supply technologies. Directed innovation efforts are strikingly misaligned with the needs of an emissions-constrained world. Significantly greater effort is needed to develop the full potential of efficient end-use technologies

Reconstruction of the Dark Energy equation of state

One of the main challenges of modern cosmology is to investigate the nature of dark energy in our Universe. The properties of such a component are normally summarised as a perfect fluid with a (potentially) time-dependent equation-of-state parameter $w(z)$. We investigate the evolution of this parameter with redshift by performing a Bayesian analysis of current cosmological observations. We model the temporal evolution as piecewise linear in redshift between `nodes', whose $w$-values and redshifts are allowed to vary. The optimal number of nodes is chosen by the Bayesian evidence. In this way, we can both determine the complexity supported by current data and locate any features present in $w(z)$. We compare this node-based reconstruction with some previously well-studied parameterisations: the Chevallier-Polarski-Linder (CPL), the Jassal-Bagla-Padmanabhan (JBP) and the Felice-Nesseris-Tsujikawa (FNT). By comparing the Bayesian evidence for all of these models we find an indication towards possible time-dependence in the dark energy equation-of-state. It is also worth noting that the CPL and JBP models are strongly disfavoured, whilst the FNT is just significantly disfavoured, when compared to a simple cosmological constant $w=-1$. We find that our node-based reconstruction model is slightly disfavoured with respect to the $\Lambda$CDM model.Comment: 17 pages, 5 figures, minor correction