TBS (Trabecular Bone Score) is More Sensitive Than BMD to Diabetes-Related Fracture Risk

Background:Type 2 diabetes (T2D) is associated with increased fracture risk but paradoxically greater BMD. TBS (trabecular bone score), a novel grey-level texture measurement extracted from DXA images, correlates with 3D parameters of bone micro-architecture. We evaluated the ability of lumbar spine (LS) TBS to account for the increased fracture risk in diabetes. Methods:29,407 women ≥50 years at the time of baseline hip and spine DXA were identified from a database containing all clinical BMD results for the Province of Manitoba, Canada. 2,356 of the women satisfied a well-validated definition for diabetes, the vast majority of whom (>90%) would have T2D. LS L14 TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Health service records were assessed for incident non-traumatic major osteoporotic fracture codes (mean follow-up 4.7 years). Results:In linear regression adjusted for FRAX risk factors (age,BMI, glucocorticoids, prior major fracture, rheumatoid arthritis, COPD as a smoking proxy, alcohol abuse) and osteoporosis therapy, diabetes was associated with higher BMD for LS, femoral neck and total hip but lower LS TBS (all p<0.001). Similar results were seen after excluding obese subjects withBMI>30. In logistic regression (Figure), the adjusted odds ratio (OR) for a skeletal measurement in the lowest vs highest tertile was less than 1 for all BMD measurements but increased for LS TBS (adjusted OR 2.61, 95%CI 2.30-2.97). Major osteoporotic fractures were identified in 175 (7.4%) with and 1,493 (5.5%) without diabetes (p < 0.001). LS TBS predicted fractures in those with diabetes (adjusted HR 1.27, 95%CI 1.10-1.46) and without diabetes (HR 1.31, 95%CI 1.24-1.38). LS TBS was an independent predictor of fracture (p<0.05) when further adjusted for BMD (LS, femoral neck or total hip). The explanatory effect of diabetes in the fracture prediction model was greatly reduced when LS TBS was added to the model (indicating that TBS captured a large portion of the diabetes-associated risk), but was paradoxically increased from adding any of the BMD measurements. Conclusions:Lumbar spine TBS is sensitive to skeletal deterioration in postmenopausal women with diabetes, whereas BMD is paradoxically greater. LS TBS predicts osteoporotic fractures in those with diabetes, and captures a large portion of the diabetes-associated fracture risk. Combining LS TBS with BMD incrementally improves fracture prediction.

Patients' sibling history was sensitive for hypertension and specific for diabetes.

OBJECTIVE: We examined the analytic validity of reported family history of hypertension and diabetes among siblings in the Seychelles. STUDY DESIGN AND SETTING: Four hundred four siblings from 73 families with at least two hypertensive persons were identified through a national hypertension register. Two gold standards were used prospectively. Sensitivity was the proportion of respondents who indicated the presence of disease in a sibling, given that the sibling reported to be affected (personal history gold standard) or was clinically affected (clinical status gold standard). Specificity was the proportion of respondents who reported an unaffected sibling, given that the sibling reported to be unaffected or was clinically unaffected. Respondents gave information on the disease status in their siblings in approximately two-thirds of instances. RESULTS: When sibling history could be obtained (n=348 for hypertension, n=404 for diabetes), the sensitivity and the specificity of the sibling history were, respectively, 90 and 55% for hypertension, and 61 and 98% for diabetes, using clinical status and, respectively, 89 and 78% for hypertension, and 53 and 98% for diabetes, using personal history. CONCLUSION: The sibling history, when available, is a useful screening test to detect hypertension, but it is less useful to detect diabetes.

Determinação do volume de madeira em povoamento de eucalipto por escâner a laser aerotransportado

O objetivo deste trabalho foi avaliar a possibilidade de se estimar o diâmetro à altura do peito (DAP) com os dados de altura e de número de árvores derivados do escâner a laser aerotransportado (LiDAR, "light detection and ranging"), e determinar o volume de madeira de talhão de Eucalyptus sp. a partir dessas variáveis. O número total de árvores detectadas foi obtido com uso da filtragem de máxima local. A altura de plantas estimada pelo LiDAR apresentou tendência não significativa à subestimativa. A estimativa do DAP foi coerente com os valores encontrados no inventário florestal; porém, também mostrou tendência à subestimativa, em razão do comportamento observado quanto à altura. A variável número de fustes apresentou valores próximos aos observados nas parcelas do inventário. O LiDAR subestimou o volume total de madeira do talhão em 11,4%, em comparação ao volume posto na fábrica. A tendência de subestimação da altura das árvores (em média, cerca de 5%) impactou a estimativa do volume individual de árvores e, consequentemente, a do volume do talhão. No entanto, é possível gerar equações de regressão que estimam o DAP com boa precisão, a partir de dados de altura de plantas obtidos pelo LiDAR. O modelo parabólico é o que possibilita as melhores estimativas da produção volumétrica dos talhões de eucalipto.

Computer-aided volume measurement of posttraumatic orbits reconstructed with AO titanium mesh plates: accuracy and reliability

PURPOSE: To prospectively evaluate the accuracy and reliability of "freehand" posttraumatic orbital wall reconstruction with AO (Arbeitsgemeinschaft Osteosynthese) titanium mesh plates by using computer-aided volumetric measurement of the bony orbits. METHODS: Bony orbital volume was measured in 12 patients from coronal CT scan slices using OsiriX Medical Image software. After defining the volumetric limits of the orbit, the segmentation of the bony orbital region of interest of each single slice was performed. At the end of the segmentation process, all regions of interest were grouped and the volume was computed. The same procedure was performed on both orbits, and thereafter the volume of the contralateral uninjured orbit was used as a control for comparison. RESULTS: In all patients, the volume data of the reconstructed orbit fitted that of the contralateral uninjured orbit with accuracy to within 1.85 cm3 (7%). CONCLUSIONS: This preliminary study has demonstrated that posttraumatic orbital wall reconstruction using "freehand" bending and placement of AO titanium mesh plates results in a high success rate in re-establishing preoperative bony volume, which closely approximates that of the contralateral uninjured orbit.

Redes neurais artificiais para a modelagem do volume de madeira e biomassa do cerradão com dados de satélite

Resumo:O objetivo deste trabalho foi avaliar a eficácia da aplicação de modelos de análise de regressão e redes neurais artificiais (RNAs) na predição do volume de madeira e da biomassa acima do solo, da vegetação arbórea em área de cerradão. Volume de madeira e biomassa foram estimados com equações alométricas desenvolvidas para a área de estudo. Os índices de vegetação, como variáveis preditoras, foram estimados a partir de imagens do sensor LISS-III, e a área basal foi determinada por medições na floresta. A precisão das equações foi verificada pela correlação entre os valores estimados e observados (r), erro-padrão da estimativa (Syx) e gráfico residual. As equações de regressão para o volume de madeira total e do fuste (0,96 e 0,97 para r, e 11,92 e 9,72% para Syx, respectivamente) e para a biomassa (0,91 e 0,92 para r, e 22,73 e 16,80% para Syx, respectivamente) apresentaram bons ajustes. As redes neurais também apresentaram bom ajuste com o volume de madeira (0,99 e 0,99 para r, e 4,93 e 4,83% para Syx) e a biomassa (0,97 e 0,98 r, e 8,92 e 7,96% para Syx, respectivamente). A área basal e os índices de vegetação foram eficazes na estimativa do volume de madeira e biomassa para o cerradão. Os valores reais de volume de madeira e biomassa não diferiram estatisticamente dos valores estimados pelos modelos de regressão e redes neurais (χ2ns); contudo, as RNAs são mais acuradas.

Ultra-performance liquid chromatography mass spectrometry and sensitive bioassay methods for quantification of posaconazole plasma concentrations after oral dosing.

Posaconazole (POS) is a new antifungal agent for prevention and therapy of mycoses in immunocompromised patients. Variable POS pharmacokinetics after oral dosing may influence efficacy: a trough threshold of 0.5 ?g/ml has been recently proposed. Measurement of POS plasma concentrations by complex chromatographic techniques may thus contribute to optimize prevention and management of life-threatening infections. No microbiological analytical method is available. The objective of this study was to develop and validate a new simplified ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method and a sensitive bioassay for quantification of POS over the clinical plasma concentration range. The UPLC-MS/MS equipment consisted of a triple quadrupole mass spectrometer, an electrospray ionization (ESI) source, and a C(18) analytical column. The Candida albicans POS-hypersusceptible mutant (MIC of 0.002 ?g/ml) ?cdr1 ?cdr2 ?flu ?mdr1 ?can constructed by targeted deletion of multidrug efflux transporters and calcineurin genes was used for the bioassay. POS was extracted from plasma by protein precipitation with acetonitrile-methanol (75%/25%, vol/vol). Reproducible standard curves were obtained over the range 0.014 to 12 (UPLC-MS/MS) and 0.028 to 12 ?g/ml (bioassay). Intra- and interrun accuracy levels were 106% ± 2% and 103% ± 4% for UPLC-MS/MS and 102% ± 8% and 104% ± 1% for bioassay, respectively. The intra- and interrun coefficients of variation were 7% ± 4% and 7% ± 3% for UPLC-MS/MS and 5% ± 3% and 4% ± 2% for bioassay, respectively. An excellent correlation between POS plasma concentrations measured by UPLC-MS/MS and bioassay was found (concordance, 0.96). In 26 hemato-oncological patients receiving oral POS, 27/69 (39%) trough plasma concentrations were lower than 0.5 ?g/ml. The UPLC-MS/MS method and sensitive bioassay offer alternative tools for accurate and precise quantification of the plasma concentrations in patients receiving oral posaconazole.

The epithelial sodium channel and the control of sodium balance.

Studies aiming at the elucidation of the genetic basis of rare monogenic forms of hypertension have identified mutations in genes coding for the epithelial sodium channel ENaC, for the mineralocorticoid receptor, or for enzymes crucial for the synthesis of aldosterone. These genetic studies clearly demonstrate the importance of the regulation of Na(+) absorption in the aldosterone-sensitive distal nephron (ASDN), for the maintenance of the extracellular fluid volume and blood pressure. Recent studies aiming at a better understanding of the cellular and molecular basis of ENaC-mediated Na(+) absorption in the distal part of nephron, have essentially focused on the regulation ENaC activity and on the aldosterone-signaling cascade. ENaC is a constitutively open channel, and factors controlling the number of active channels at the cell surface are likely to have profound effects on Na(+) absorption in the ASDN, and in the amount of Na(+) that is excreted in the final urine. A number of membrane-bound proteases, kinases, have recently been identified that increase ENaC activity at the cell surface in heterologous expressions systems. Ubiquitylation is a general process that regulates the stability of a variety of target proteins that include ENaC. Recently, deubiquitylating enzymes have been shown to increase ENaC activity in heterologous expressions systems. These regulatory mechanisms are likely to be nephron specific, since in vivo studies indicate that the adaptation of the renal excretion of Na(+) in response to Na(+) diet occurs predominantly in the early part (the connecting tubule) of the ASDN. An important work is presently done to determine in vivo the physiological relevance of these cellular and molecular mechanisms in regulation of ENaC activity. The contribution of the protease-dependent ENaC regulation in mediating Na(+) absorption in the ASDN is still not clearly understood. The signaling pathway that involves ubiquitylation of ENaC does not seem to be absolutely required for the aldosterone-mediated control of ENaC. These in vivo physiological studies presently constitute a major challenge for our understanding of the regulation of ENaC to maintain the Na(+) balance.

Evolution of the epithelial sodium channel and the sodium pump as limiting factors of aldosterone action on sodium transport.

Despite large changes in salt intake, the mammalian kidney is able to maintain the extracellular sodium concentration and osmolarity within very narrow margins, thereby controlling blood volume and blood pressure. In the aldosterone-sensitive distal nephron (ASDN), aldosterone tightly controls the activities of epithelial sodium channel (ENaC) and Na,K-ATPase, the two limiting factors in establishing transepithelial sodium transport. It has been proposed that the ENaC/degenerin gene family is restricted to Metazoans, whereas the α- and β-subunits of Na,K-ATPase have homologous genes in prokaryotes. This raises the question of the emergence of osmolarity control. By exploring recent genomic data of diverse organisms, we found that: 1) ENaC/degenerin exists in all of the Metazoans screened, including nonbilaterians and, by extension, was already present in ancestors of Metazoa; 2) ENaC/degenerin is also present in Naegleria gruberi, an eukaryotic microbe, consistent with either a vertical inheritance from the last common ancestor of Eukaryotes or a lateral transfer between Naegleria and Metazoan ancestors; and 3) The Na,K-ATPase β-subunit is restricted to Holozoa, the taxon that includes animals and their closest single-cell relatives. Since the β-subunit of Na,K-ATPase plays a key role in targeting the α-subunit to the plasma membrane and has an additional function in the formation of cell junctions, we propose that the emergence of Na,K-ATPase, together with ENaC/degenerin, is linked to the development of multicellularity in the Metazoan kingdom. The establishment of multicellularity and the associated extracellular compartment ("internal milieu") precedes the emergence of other key elements of the aldosterone signaling pathway.

Analysis of a finite volume method for a cross-diffusion model in population dynamics

The main goal of this paper is to propose a convergent finite volume method for a reactionâeuro"diffusion system with cross-diffusion. First, we sketch an existence proof for a class of cross-diffusion systems. Then the standard two-point finite volume fluxes are used in combination with a nonlinear positivity-preserving approximation of the cross-diffusion coefficients. Existence and uniqueness of the approximate solution are addressed, and it is also shown that the scheme converges to the corresponding weak solution for the studied model. Furthermore, we provide a stability analysis to study pattern-formation phenomena, and we perform two-dimensional numerical examples which exhibit formation of nonuniform spatial patterns. From the simulations it is also found that experimental rates of convergence are slightly below second order. The convergence proof uses two ingredients of interest for various applications, namely the discrete Sobolev embedding inequalities with general boundary conditions and a space-time $L^1$ compactness argument that mimics the compactness lemma due to Kruzhkov. The proofs of these results are given in the Appendix.

Connexin 43 expression in human hypertrophied heart due to pressure and volume overload.

Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution.