Evaluation of neodymium isotope analysis of human dental enamel as a provenance indicator using 1013â€¯Ω amplifiers (TIMS).

Human provenance studies employing isotopic analysis have become an essential tool in forensic and archaeological sciences, with multi-isotope approaches providing more specific location estimates compared to single isotope studies. This study reports on the human provenancing capability of neodymium isotopes (143Nd/144Nd), a relatively conservative tracer in the environment. Neodymium isotope ratios have only recently been determined on human remains due to low concentrations in human dental enamel (ppb range), requiring thermal ionisation mass spectrometry (TIMS) using 1013â€¯Ω resistors. Dental elements (third molars) from 20 individuals born and raised in the Netherlands were analysed for Nd concentration (n = 12) and Nd isotope ratios (n = 15). The geological control on Nd isotope composition was examined using coupled Nd-Sr isotope analysis of the same third molar. Teeth from different geological environments were also analysed (Caribbean, Columbian, and Icelandic, n = 5). Neodymium elemental concentrations in dental elements ranged between 0.1 and 7.9 ppb (median 0.5 ppb). The Dutch 143Nd/144Nd ratios of the provinces of Limburg and Friesland were between 0.5118 and 0.5121, with Dutch 87Sr/86Sr ratios in agreement with the previously established local range (0.708-0.710). The current findings were compared to previously published results on Nd concentration and composition from Dutch individuals. The concentration of Nd and 143Nd/144Nd ratios were weakly correlated (R2 = 0.47, n = 17) in Dutch human dental enamel. The majority (n = 25, 83.3%) of individuals had Nd and Sr isotope values isotopically indistinguishable from the geological environment in which their third molars formed and mineralised. However, the Nd isotope ratios of the Icelandic individual and several Dutch individuals (n = 4) suggested that Nd in enamel is not solely influenced by geological environment. In order for neodymium isotopes to be quantitatively applied in forensic and archaeological settings further analyses of individuals from various geographical regions with well-defined dietary Nd isotope data are required.

The influence of the location of the lesion on the absolute risk of the development of skin cancer in a patient with actinic keratosis.

The objective of this paper is to answer the clinical question whether the location of the lesion in an individual patient with actinic keratosis (AK) influences the absolute risk of the development of skin cancer. Between 0.025% and 16% of AK lesions advance towards squamous cell carcinoma per year. It is not well known whether this risk differs between locations on the body. A systematic search of available literature resulted in seven articles of which the two highest scoring on relevance and validity were selected. These two studies indicate that the absolute risk on the development of skin cancer in patients with AK differs between locations of the lesion and that time to progression from AK to squamous cell carcinoma is not different among the locations of the lesions. However, both studies have very limited sample sizes.

Understanding genes, environment and their interaction in attention-deficit hyperactivity disorder: is there a role for neuroimaging?

Attention-deficit hyperactivity disorder (ADHD) has an established heritable component, but identifying the genes involved has proven difficult. To date, the two most investigated risk genes in ADHD are the DRD4 and DAT1-genes. However, individual risk genes have only explained up to 1% of the variance in the phenotype, suggesting that they represent only relatively small risk factors for ADHD. As such, the role of environmental factors, gene-gene and gene-environment interactions are being investigated. However, studies have not always been able to address the neurobiological mechanisms by which environmental factors and interactions with genes exert their effect on the ADHD-phenotype. Neuroimaging is being used as a tool to investigate the neurobiological effects of individual risk genes. We suggest it could also be applied to investigate the mechanisms involved in environmental effects and interactions between genetic and environmental factors.

Kinetic analysis of the mass transport limited interaction between the tyrosine kinase lck SH2 domain and a phosphorylated peptide studied by a new cuvette-based surface plasmon resonance instrument.

We explored the use of a newly developed cuvette-based surface plasmon resonance (SPR) instrument (IBIS) to study peptide-protein interactions. We studied the interaction between the SH2 domain of lck and a phosphotyrosine peptide EPQY*EEIPIYL which was immobilized on a sensor chip. No indications for mass transport limitation (MTL) were observed when standard kinetic approaches were used. However, addition of competing peptide during dissociation revealed a high extent of rebinding. A dissociation rate constant (k(d)) of 0.6+/-0.1 s(-1) was obtained in the presence of large amounts of peptide. A simple bimolecular binding model, applying second-order kinetics for the cuvette system, could not adequately describe the data. Fits were improved upon including a step in the model which describes diffusion of the SH2 domain from the bulk to the sensor, especially for a surface with high binding capacity. From experiments in glycerol-containing buffers, it appeared that the diffusion rate decreased with higher viscosity. It is demonstrated that MTL during association and dissociation can be described by the same diffusion rate. A binding constant (K(D)) of 5.9+/-0.8 nM was obtained from the SPR equilibrium signals by fitting to a Langmuir binding isotherm, with correction for loss of free analyte due to binding. An association rate constant k(a) of 1.1(+/-0.2)x10(8) M(-1) x s(-1) was obtained from k(d)/K(D). The values for k(a) and k(d) obtained in this way were 2-3 orders larger than that from standard kinetic analysis, ignoring MTL. We conclude that in a cuvette the extent of MTL is comparable to that in a flow system.