The Chapman Bone Algorithm: A Diagnostic Alternative for the Evaluation of Osteoporosis

Osteoporosis is the most common metabolic bone disease and goes largely undiagnosed throughout the world, due to the inaccessibility of DXA machines. Multivariate analyses of serum bone turnover markers were evaluated in 226 Orange County, California, residents with the intent to determine if serum osteocalcin and serum pyridinoline cross-links could be used to detect the onset of osteoporosis as effectively as a DXA scan. Descriptive analyses of the demographic and lab characteristics of the participants were performed through frequency, means and standard deviation estimations. We implemented logistic regression modeling to find the best classification algorithm for osteoporosis. All calculations and model building steps were carried out using R statistical language. Through these analyses, a mathematical algorithm with diagnostic potential was created. This algorithm showed a sensitivity of 1.0 and a specificity of 0.83, with an area under the Receiver Operating Characteristic curve of 0.93, thus demonstrating a high predictability for osteoporosis. Our intention is for this algorithm to be used to evaluate osteoporosis in locations where access to DXA scanning is scarce

Treat to Target: A Proposed New Paradigm for the Management of Crohn's Disease.

International audience: The traditional management of CD, based on progressive, step-wise treatment intensification with re-evaluation of response according to symptoms, does not improve long-term outcomes of CD and places patients at risk for bowel damage. The introduction of novel therapies and the development of new approaches to treatment in rheumatoid arthritis led to better outcomes for patients. Prominent among these is a "treat to target" strategy that is based on regular assessment of disease activity using objective clinical and biological outcome measures and the subsequent adjustment of treatments. This approach is complementary to the concept of early intervention in high risk patients. This review evaluates current literature on this topic and proposes a definition for the concept treating to targets for Crohn's disease

Independent replication of a melanoma subtype gene signature and evaluation of its prognostic value and biological correlates in a population cohort

Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3x10-4), Breslow thickness (P=5x10-10), ulceration (P=9.x10-8) and mitotic rate (P=3x10-7), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI 1.13-2.83), as previously reported. Furthermore, molecular subtypes were associated with season-adjusted serum vitamin D at diagnosis (P=0.04) and genetically predicted telomere length (P=0.03). Specifically, molecular high-grade tumors were more frequent in patients with lower vitamin D levels whereas high immune tumors came from patients with predicted shorter telomeres. Our data confirm the utility of molecular biomarkers in melanoma prognostic estimation using tiny archived specimens and shed light on biological mechanisms likely to impact on cancer initiation and progression

Electronic correlation in the quantum Hall regime

Two-dimensional interacting electron systems become strongly correlated if the electrons are subject to a perpendicular high magnetic field. After introducing the physics of the quantum Hall regime the incompressible many- particle ground state and its excitations are studied in detail at fractional filling factors for spin-polarized electrons. The spin degree of freedom whose importance was shown in recent experiments is considered by studying the thermodynamics at filling factor one and near one.Comment: 55 pages, 26 eps-figure

Unpaired and spin-singlet paired states of a two-dimensional electron gas in a perpendicular magnetic field

We present a variational study of both unpaired and spin-singlet paired states induced in a two-dimensional electron gas at low density by a perpendicular magnetic field. It is based on an improved circular-cell approximation which leads to a number of closed analytical results. The ground-state energy of the Wigner crystal containing a single electron per cell in the lowest Landau level is obtained as a function of the filling factor $\nu$: the results are in good agreement with those of earlier approaches and predict $\nu_{c} \approx 0.25$ for the upper filling factor at which the solid-liquid transition occurs. A novel localized state of spin-singlet electron pairs is examined and found to be a competitor of the unpaired state for filling factor $\nu >1$. The corresponding phase boundary is quantitatively displayed in the magnetic field-electron density plane.Comment: 19 pages, 8 figures, submitted to Phys. Rev. B on 7th April 2001. to appear in Phys. Rev.

Hamiltonian Description of Composite Fermions: Magnetoexciton Dispersions

A microscopic Hamiltonian theory of the FQHE, developed by Shankar and myself based on the fermionic Chern-Simons approach, has recently been quite successful in calculating gaps in Fractional Quantum Hall states, and in predicting approximate scaling relations between the gaps of different fractions. I now apply this formalism towards computing magnetoexciton dispersions (including spin-flip dispersions) in the $\nu=1/3$, 2/5, and 3/7 gapped fractions, and find approximate agreement with numerical results. I also analyse the evolution of these dispersions with increasing sample thickness, modelled by a potential soft at high momenta. New results are obtained for instabilities as a function of thickness for 2/5 and 3/7, and it is shown that the spin-polarized 2/5 state, in contrast to the spin-polarized 1/3 state, cannot be described as a simple quantum ferromagnet.Comment: 18 pages, 18 encapsulated ps figure

Transcriptional induction of cell wall remodelling genes is coupled to microtubule-driven growth isotropy at the shoot apex in Arabidopsis

The shoot apical meristem of higher plants continuously generates new tissues and organs through complex changes in growth rates and directions of its individual cells. Cell growth, which is driven by turgor pressure, largely depends on the cell walls, which allow cell expansion through synthesis and structural changes. A previous study revealed a major contribution of wall isotropy in organ emergence, through the disorganization of cortical microtubules. We show here that this disorganization is coupled with the transcriptional control of genes involved in wall remodelling. Some of these genes are induced when microtubules are disorganized and cells shift to isotropic growth. Mechanical modelling shows that this coupling has the potential to compensate for reduced cell expansion rates induced by the shift to isotropic growth. Reciprocally, cell wall loosening induced by different treatments or altered cell wall composition promotes a disruption of microtubule alignment. Our data thus indicate the existence of a regulatory module activated during organ outgrowth, linking microtubule arrangements to cell wall remodelling

Potential efficacy of mitochondrial genes for animal DNA barcoding: a case study using eutherian mammals

<p>Abstract</p> <p>Background</p> <p>A well-informed choice of genetic locus is central to the efficacy of DNA barcoding. Current DNA barcoding in animals involves the use of the 5' half of the mitochondrial cytochrome oxidase 1 gene (<it>CO1</it>) to diagnose and delimit species. However, there is no compelling <it>a priori </it>reason for the exclusive focus on this region, and it has been shown that it performs poorly for certain animal groups. To explore alternative mitochondrial barcoding regions, we compared the efficacy of the universal <it>CO1 </it>barcoding region with the other mitochondrial protein-coding genes in eutherian mammals. Four criteria were used for this comparison: the number of recovered species, sequence variability within and between species, resolution to taxonomic levels above that of species, and the degree of mutational saturation.</p> <p>Results</p> <p>Based on 1,179 mitochondrial genomes of eutherians, we found that the universal <it>CO1 </it>barcoding region is a good representative of mitochondrial genes as a whole because the high species-recovery rate (> 90%) was similar to that of other mitochondrial genes, and there were no significant differences in intra- or interspecific variability among genes. However, an overlap between intra- and interspecific variability was still problematic for all mitochondrial genes. Our results also demonstrated that any choice of mitochondrial gene for DNA barcoding failed to offer significant resolution at higher taxonomic levels.</p> <p>Conclusions</p> <p>We suggest that the <it>CO1 </it>barcoding region, the universal DNA barcode, is preferred among the mitochondrial protein-coding genes as a molecular diagnostic at least for eutherian species identification. Nevertheless, DNA barcoding with this marker may still be problematic for certain eutherian taxa and our approach can be used to test potential barcoding loci for such groups.</p

You've got a friend in me: how social networks and mobile phones facilitate healthcare access among marginalised groups in rural Thailand and Lao PDR

The seeming “ubiquity” of mobile phones has spawned a wave of interventions that use mobiles as platforms for health service delivery (mHealth). Operating in more than 100 countries, mHealth interventions commonly aspire to make healthcare more inclusive and efficient. Yet, mobile phone diffusion also stimulates locally emerging forms of health-related phone use that could create new digital inequalities among marginalised groups or compete with mHealth and other technology-based development interventions. We aim to inform this subject by asking, “How do mobile phone use and social support networks influence rural treatment-seeking behaviours among marginalised groups?” We hypothesise that (1) resource constraints drive marginalised groups towards informal healthcare access, and that (2) mobile phone use and social support networks facilitate access to formal healthcare with a bias towards private doctors. Analysing representative survey data from 2141 Thai and Lao villagers with descriptive statistics and multi-level regression models, we demonstrate that: (a) health-related phone use is concentrated among less marginalised groups, while social support networks are distributed more equitably; (b) marginalised villagers are more likely to utilise informal healthcare providers; and (c) mobile phones and social support networks are linked to increased yet delayed formal healthcare access that is directed towards public healthcare. We conclude that mobile phone diffusion has a mildly positive association with rural healthcare access, operating in a similar fashion but without (yet) appearing to crowd out social support. However encouraging, this is problematic news for mHealth and technology-based development interventions. The potential behavioural consequences of “informal mHealth” reinforce the notion that mobile phones are a non-neutral platform for mHealth and development interventions. The long-term implications require more research, but the literature suggests that increasing phone-aided healthcare facilitation could undermine local social support networks and leave already marginalised rural dwellers in yet more precarious circumstances

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog