Laser surface alloying of 316L stainless steel coated with a bioactive hydroxyapatite-titanium oxide composite.

Laser surface alloying is a powerful technique for improving the mechanical and chemical properties of engineering components. In this study, laser surface irradiation process employed in the surface modification off 316L stainless steel substrate using hydroxyapatite-titanium oxide to provide a composite ceramic layer for the suitability of applying this technology to improve the biocompatibility of medical alloys and implants. Fusion of the metal surface incorporating hydroxyapatite-titania ceramic particles using a 30 W Nd:YAG laser at different laser powers, 40, 50 and 70% power and a scan speed of 40 mm s(-1) was observed to adopt the optimum condition of ceramic deposition. Coatings were evaluated in terms of microstructure, surface morphology, composition biocompatibility using XRD, ATR-FTIR, SEM and EDS. Evaluation of the in vitro bioactivity by soaking the treated metal in SBF for 10 days showed the deposition of biomimetic apatite

Accuracy of electron densities obtained via Koopmans-compliant hybrid functionals

We evaluate the accuracy of electron densities and quasiparticle energy gaps given by hybrid functionals by directly comparing these to the exact quantities obtained from solving the many-electron Schrodinger equation. We determine the admixture of Hartree-Fock exchange to approximate exchange-correlation in our hybrid functional via one of several physically justified constraints, including the generalized Koopmans' theorem. We find that hybrid functionals yield strikingly accurate electron densities and gaps in both exchange-dominated and correlated systems. We also discuss the role of the screened Fock operator in the success of hybrid functionals

Whole-genome methylation analysis of benign and malignant colorectal tumours

Changes in DNA methylation, whether hypo- or hypermethylation, have been shown to be associated with the progression of colorectal cancer. Methylation changes substantially in the progression from normal mucosa to adenoma and to carcinoma. This phenomenon has not been studied extensively and studies have been restricted to individual CpG islands, rather than taking a whole-genome approach. We aimed to study genome-wide methylation changes in colorectal cancer. We obtained 10 fresh-frozen normal tissue-cancer sample pairs, and five fresh-frozen adenoma samples. These were run on the lllumina HumanMethylation27 whole-genome methylation analysis system. Differential methylation between normal tissue, adenoma and carcinoma was analysed using Bayesian regression modelling, gene set enrichment analysis (GSEA) and hierarchical clustering (HC). The highest-rated individual gene for differential methylation in carcinomas versus normal tissue and adenomas versus normal tissue was GRASP (padjusted  = 1.59 × 10(-5) , BF = 12.62, padjusted  = 1.68 × 10(-6) , BF = 14.53). The highest-rated gene when comparing carcinomas versus adenomas was ATM (padjusted  = 2.0 × 10(-4) , BF = 10.17). Hierarchical clustering demonstrated poor clustering by the CIMP criteria for methylation. GSEA demonstrated methylation changes in the Netrin-DCC and SLIT-ROBO pathways. Widespread changes in DNA methylation are seen in the transition from adenoma to carcinoma. The finding that GRASP, which encodes the general receptor for phosphoinositide 1-associated scaffold protein, was differentially methylated in colorectal cancer is interesting. This may be a potential biomarker for colorectal cancer

The concavity of submarine canyon longitudinal profiles

Submarine canyons incise continental shelves and slopes, and are important conduits for the transport of sediment, nutrients, organic carbon and pollutants from continents to oceans. Submarine canyons bear morphological similarities to subaerial valleys, such as their longitudinal (long) profiles. Long profiles record the interaction between erosion and uplift, making their shape, or concavity, a record of environmental and tectonic processes. The processes that govern concavity of subaerial valleys and rivers are well documented on a global scale, however, the processes that control submarine canyon concavity are less well constrained. We address this problem by utilizing existing geomorphological, tectonic and climatic datasets to measure the long profiles and quantify the concavities of 377 modern submarine canyons. Key results show that: (1) the dominant control on submarine canyon concavity is tectonics, with forearcs and tectonically active margins hosting the least concave-up profiles; (2) present-day canyon position affects canyon concavity, with river-associated canyons being less concave than canyons currently dissociated from rivers on forearcs; (3) present-day onshore climate appears to have a more limited impact on submarine canyon concavity when compared to these factors. While significant local variation exists, these results indicate that tectonic processes are the dominant control on the concavity of submarine canyons on a global scale

A reference relative time-scale as an alternative to chronological age for cohorts with long follow-up

Background: Epidemiologists have debated the appropriate time-scale for cohort survival studies; chronological age or time-on-study being two such time-scales. Importantly, assessment of risk factors may depend on the choice of time-scale. Recently, chronological or attained age has gained support but a case can be made for a ‘reference relative time-scale’ as an alternative which circumvents difficulties that arise with this and other scales. The reference relative time of an individual participant is the integral of a reference population hazard function between time of entry and time of exit of the individual. The objective here is to describe the reference relative time-scale, illustrate its use, make comparison with attained age by simulation and explain its relationship to modern and traditional epidemiologic methods. Results: A comparison was made between two models; a stratified Cox model with age as the time-scale versus an un-stratified Cox model using the reference relative time-scale. The illustrative comparison used a UK cohort of cotton workers, with differing ages at entry to the study, with accrual over a time period and with long follow-up. Additionally, exponential and Weibull models were fitted since the reference relative time-scale analysis need not be restricted to the Cox model. A simulation study showed that analysis using the reference relative time-scale and analysis using chronological age had very similar power to detect a significant risk factor and both were equally unbiased. Further, the analysis using the reference relative time-scale supported fully-parametric survival modelling and allowed percentile predictions and mortality curves to be constructed. Conclusions: The reference relative time-scale was a viable alternative to chronological age, led to simplification of the modelling process and possessed the defined features of a good time-scale as defined in reliability theory. The reference relative time-scale has several interpretations and provides a unifying concept that links contemporary approaches in survival and reliability analysis to the traditional epidemiologic methods of Poisson regression and standardised mortality ratios. The community of practitioners has not previously made this connection

Enhancing in vitro biocompatibility and corrosion protection of organic-inorganic hybrid sol-gel films with nanocrystalline hydroxyapatite

Application of novel organic-inorganic hybrid sol-gel coatings containing dispersed hydroxyapatite (HAp) particles improves the biocompatibility, normal human osteoblast (NHOst) response in terms of osteoblast viability and adhesion of a Ti6Al4V alloy routinely used in medical implants. The incorporation of HAp particles additionally results in more effective barrier proprieties and improved corrosion protection of the Ti6Al4V alloy through higher degree of cross-linking in the organopolysiloxane matrix and enhanced film thickness

Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan.

The topoisomerase I (TOP1) inhibitor irinotecan triggers cell death by trapping TOP1 on DNA, generating cytotoxic protein-linked DNA breaks (PDBs). Despite its wide application in a variety of solid tumors, the mechanisms of cancer cell resistance to irinotecan remains poorly understood. Here, we generated colorectal cancer (CRC) cell models for irinotecan resistance and report that resistance is neither due to downregulation of the main cellular target of irinotecan TOP1 nor upregulation of the key TOP1 PDB repair factor TDP1. Instead, the faster repair of PDBs underlies resistance, which is associated with perturbed histone H4K16 acetylation. Subsequent treatment of irinotecan-resistant, but not parental, CRC cells with histone deacetylase (HDAC) inhibitors can effectively overcome resistance. Immunohistochemical analyses of CRC tissues further corroborate the importance of histone H4K16 acetylation in CRC. Finally, the resistant clones exhibit cross-resistance with oxaliplatin but not with ionising radiation or 5-fluoruracil, suggesting that the latter two could be employed following loss of irinotecan response. These findings identify perturbed chromatin acetylation in irinotecan resistance and establish HDAC inhibitors as potential therapeutic means to overcome resistance

Self-reported health and functional limitations among older people in the Kassena-Nankana District, Ghana

Background: Ghana is experiencing significant increases in its ageing population, yet research on the health and quality of life of older people is limited. Lack of data on the health and well-being of older people in the country makes it difficult to monitor trends in the health status of adults and the impact of social policies on their health and welfare. Research on ageing is urgently required to provide essential data for policy formulation and programme implementation. Objective: To describe the health status and identify factors associated with self-rated health (SRH) among older adults in a rural community in northern Ghana. Methods: The data come from a survey on Adult Health and Ageing in the Kassena-Nankana District involving 4,584 people aged 50 and over. Survey participants answered questions pertaining to their health status, including self-rated overall health, perceptions of well-being and quality of life, and self-reported assessment of functioning on a range of different health domains. Socio-demographic information such as age, sex, marital status and education were obtained from a demographic surveillance database. Results: The majority of older people rated their health status as good, with the oldest old reporting poorer health. Multivariate regression analysis showed that functional ability and sex are significant factors in SRH status. Adults with higher levels of functional limitations were much more likely to rate their health as being poorer compared with those having lower disabilities. Household wealth was significantly associated with SRH, with wealthier adults more likely to rate their health as good. Conclusion: The depreciation in health and daily functioning with increasing age is likely to increase people's demand for health care and other services as they grow older. There is a need for regular monitoring of the health status of older people to provide public health agencies with the data they need to assess, protect and promote the health and well-being of older people

Interactions between deep-water gravity flows and active salt tectonics

Behavior of sediment gravity flows can be influenced by seafloor topography associated with salt structures; this can modify the depositional architecture of deep-water sedimentary systems. Typically, salt-influenced deep-water successions are poorly imaged in seismic reflection data, and exhumed systems are rare, hence the detailed sedimentology and stratigraphic architecture of these systems remains poorly understood. The exhumed Triassic (Keuper) Bakio and Guernica salt bodies in the Basque–Cantabrian Basin, Spain, were active during deep-water sedimentation. The salt diapirs grew reactively, then passively, during the Aptian–Albian, and are flanked by deep-water carbonate (Aptian–earliest Albian Urgonian Group) and siliciclastic (middle Albian–Cenomanian Black Flysch Group) successions. The study compares the depositional systems in two salt-influenced minibasins, confined (Sollube basin) and partially confined (Jata basin) by actively growing salt diapirs, comparable to salt-influenced minibasins in the subsurface. The presence of a well-exposed halokinetic sequence, with progressive rotation of bedding, beds that pinch out towards topography, soft-sediment deformation, variable paleocurrents, and intercalated debrites indicate that salt grew during deposition. Overall, the Black Flysch Group coarsens and thickens upwards in response to regional axial progradation, which is modulated by laterally derived debrites from halokinetic slopes. The variation in type and number of debrites in the Sollube and Jata basins indicates that the basins had different tectonostratigraphic histories despite their proximity. In the Sollube basin, the routing systems were confined between the two salt structures, eventually depositing amalgamated sandstones in the basin axis. Different facies and architectures are observed in the Jata basin due to partial confinement. Exposed minibasins are individualized, and facies vary both spatially and temporally in agreement with observations from subsurface salt-influenced basins. Salt-related, active topography and the degree of confinement are shown to be important modifiers of depositional systems, resulting in facies variability, remobilization of deposits, and channelization of flows. The findings are directly applicable to the exploration and development of subsurface energy reservoirs in salt basins globally, enabling better prediction of depositional architecture in areas where seismic imaging is challenging