Estimation of whole body muscle, adipose/fat mass, validation in health and during weight loss. Development of prediction equations using MRI as reference method

Background: Body composition is affected by diseases, and affects responses to medical treatments, dosage of medicines, etc., while an abnormal body composition contributes to the causation of many chronic diseases. While we have reliable biochemical tests for certain nutritional parameters of body composition, such as iron or iodine status, and we have harnessed nuclear physics to estimate the body’s content of trace elements, the very basic quantification of body fat content and muscle mass remains highly problematic. Both body fat and muscle mass are vitally important, as they have opposing influences on chronic disease, but they have seldom been estimated as part of population health surveillance. Instead, most national surveys have merely reported BMI and waist, or sometimes the waist/hip ratio; these indices are convenient but do not have any specific biological meaning. Anthropometry offers a practical and inexpensive method for muscle and fat estimation in clinical and epidemiological settings; however, its use is imperfect due to many limitations, such as a shortage of reference data, misuse of terminology, unclear assumptions, and the absence of properly validated anthropometric equations. To date, anthropometric methods are not sensitive enough to detect muscle and fat loss. Aims: The aim of this thesis is to estimate Adipose/fat and muscle mass in health disease and during weight loss through; 1. evaluating and critiquing the literature, to identify the best-published prediction equations for adipose/fat and muscle mass estimation; 2. to derive and validate adipose tissue and muscle mass prediction equations; and 3.to evaluate the prediction equations along with anthropometric indices and the best equations retrieved from the literature in health, metabolic illness and during weight loss. Methods: a Systematic review using Cochrane Review method was used for reviewing muscle mass estimation papers that used MRI as the reference method. Fat mass estimation papers were critically reviewed. Mixed ethnic, age and body mass data that underwent whole body magnetic resonance imaging to quantify adipose tissue and muscle mass (dependent variable) and anthropometry (independent variable) were used in the derivation/validation analysis. Multiple regression and Bland-Altman plot were applied to evaluate the prediction equations. To determine how well the equations identify metabolic illness, English and Scottish health surveys were studied. Statistical analysis using multiple regression and binary logistic regression were applied to assess model fit and associations. Also, populations were divided into quintiles and relative risk was analysed. Finally, the prediction equations were evaluated by applying them to a pilot study of 10 subjects who underwent whole-body MRI, anthropometric measurements and muscle strength before and after weight loss to determine how well the equations identify adipose/fat mass and muscle mass change. Results: The estimation of fat mass has serious problems. Despite advances in technology and science, prediction equations for the estimation of fat mass depend on limited historical reference data and remain dependent upon assumptions that have not yet been properly validated for different population groups. Muscle mass does not have the same conceptual problems; however, its measurement is still problematic and reference data are scarce. The derivation and validation analysis in this thesis was satisfactory, compared to prediction equations in the literature they were similar or even better. Applying the prediction equations in metabolic illness and during weight loss presented an understanding on how well the equations identify metabolic illness showing significant associations with diabetes, hypertension, HbA1c and blood pressure. And moderate to high correlations with MRI-measured adipose tissue and muscle mass before and after weight loss. Conclusion: Adipose tissue mass and to an extent muscle mass can now be estimated for many purposes as population or groups means. However, these equations must not be used for assessing fatness and categorising individuals. Further exploration in different populations and health surveys would be valuable.

Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies

International audience

Unpolarized transverse momentum dependent parton distribution and fragmentation functions at next-to-next-to-leading order

The transverse momentum dependent parton distribution/fragmentation functions (TMDs) are essential in the factorization of a number of processes like Drell-Yan scattering, vector boson production, semi-inclusive deep inelastic scattering, etc. We provide a comprehensive study of unpolarized TMDs at next-to-next-to-leading order, which includes an explicit calculation of these TMDs and an extraction of their matching coefficients onto their integrated analogues, for all flavor combinations. The obtained matching coefficients are important for any kind of phenomenology involving TMDs. In the present study each individual TMD is calculated without any reference to a specific process. We recover the known results for parton distribution functions and provide new results for the fragmentation functions. The results for the gluon transverse momentum dependent fragmentation functions are presented for the first time at one and two loops. We also discuss the structure of singularities of TMD operators and TMD matrix elements, crossing relations between TMD parton distribution functions and TMD fragmentation functions, and renormalization group equations. In addition, we consider the behavior of the matching coefficients at threshold and make a conjecture on their structure to all orders in perturbation theory.

Glue ear, hearing loss and IQ:an association moderated by the child's home environment

BACKGROUND: Glue ear or otitis media with effusion (OME) is common in children and may be associated with hearing loss (HL). For most children it has no long lasting effects on cognitive development but it is unclear whether there are subgroups at higher risk of sequelae. OBJECTIVES: To examine the association between a score comprising the number of times a child had OME and HL (OME/HL score) in the first four/five years of life and IQ at age 4 and 8. To examine whether any association between OME/HL and IQ is moderated by socioeconomic, child or family factors. METHODS: Prospective, longitudinal cohort study: the Avon Longitudinal Study of Parents and Children (ALSPAC). 1155 children tested using tympanometry on up to nine occasions and hearing for speech (word recognition) on up to three occasions between age 8 months and 5 years. An OME/HL score was created and associations with IQ at ages 4 and 8 were examined. Potential moderators included a measure of the child's cognitive stimulation at home (HOME score). RESULTS: For the whole sample at age 4 the group with the highest 10% OME/HL scores had performance IQ 5 points lower [95% CI -9, -1] and verbal IQ 6 points lower [95% CI -10, -3] than the unaffected group. By age 8 the evidence for group differences was weak. There were significant interactions between OME/HL and the HOME score: those with high OME/HL scores and low 18 month HOME scores had lower IQ at age 4 and 8 than those with high OME/HL scores and high HOME scores. Adjusted mean differences ranged from 5 to 8 IQ points at age 4 and 8. CONCLUSIONS: The cognitive development of children from homes with lower levels of cognitive stimulation is susceptible to the effects of glue ear and hearing loss.

The actinin family of actin crosslinking proteins: natural functions and potential applications in synthetic biology

Actinin and spectrin proteins are members of the Spectrin Family of Actin Crosslinking Proteins. The importance of these proteins in the cytoskeleton is demonstrated by the fact that they are common targets for disease causing mutations. In their most prominent roles, actinin and spectrin are responsible for stabilising and maintaining the muscle architecture during contraction, and providing shape and elasticity to the red blood cell in circulation, respectively. To carry out such roles, actinin and spectrin must possess important mechanical and physical properties. These attributes are desirable when choosing a building block for protein-based nanoconstruction. In this study, I assess the contribution of several disease-associated mutations in the actinin-1 actin binding domain that have recently been linked to a rare platelet disorder, congenital macrothrombocytopenia. I investigate the suitability of both actinin and spectrin proteins as potential building blocks for nanoscale structures, and I evaluate a fusion-based assembly strategy to bring about self-assembly of protein nanostructures. I report that the actinin-1 mutant proteins display increased actin binding compared to WT actinin-1 proteins. I find that both actinin and spectrin proteins exhibit enormous potential as nano-building blocks in terms of their stability and ability to self-assemble, and I successfully design and create homodimeric and heterodimeric bivalent building blocks using the fusion-based assembly strategy. Overall, this study has gathered helpful information that will contribute to furthering the advancement of actinin and spectrin knowledge in terms of their natural functions, and potential unnatural functions in protein nanotechnology.

On the effect of confounding in linear regression models: an approach based on the theory of quadratic forms

The main topic of this thesis is confounding in linear regression models. It arises when a relationship between an observed process, the covariate, and an outcome process, the response, is influenced by an unmeasured process, the confounder, associated with both. Consequently, the estimators for the regression coefficients of the measured covariates might be severely biased, less efficient and characterized by misleading interpretations. Confounding is an issue when the primary target of the work is the estimation of the regression parameters. The central point of the dissertation is the evaluation of the sampling properties of parameter estimators. This work aims to extend the spatial confounding framework to general structured settings and to understand the behaviour of confounding as a function of the data generating process structure parameters in several scenarios focusing on the joint covariate-confounder structure. In line with the spatial statistics literature, our purpose is to quantify the sampling properties of the regression coefficient estimators and, in turn, to identify the most prominent quantities depending on the generative mechanism impacting confounding. Once the sampling properties of the estimator conditionally on the covariate process are derived as ratios of dependent quadratic forms in Gaussian random variables, we provide an analytic expression of the marginal sampling properties of the estimator using Carlson’s R function. Additionally, we propose a representative quantity for the magnitude of confounding as a proxy of the bias, its first-order Laplace approximation. To conclude, we work under several frameworks considering spatial and temporal data with specific assumptions regarding the covariance and cross-covariance functions used to generate the processes involved. This study allows us to claim that the variability of the confounder-covariate interaction and of the covariate plays the most relevant role in determining the principal marker of the magnitude of confounding.

Interplay Between Cell Growth And Cell Cycle In Plants.

The growth of organs and whole plants depends on both cell growth and cell-cycle progression, but the interaction between both processes is poorly understood. In plants, the balance between growth and cell-cycle progression requires coordinated regulation of four different processes: macromolecular synthesis (cytoplasmic growth), turgor-driven cell-wall extension, mitotic cycle, and endocycle. Potential feedbacks between these processes include a cell-size checkpoint operating before DNA synthesis and a link between DNA contents and maximum cell size. In addition, key intercellular signals and growth regulatory genes appear to target at the same time cell-cycle and cell-growth functions. For example, auxin, gibberellin, and brassinosteroid all have parallel links to cell-cycle progression (through S-phase Cyclin D-CDK and the anaphase-promoting complex) and cell-wall functions (through cell-wall extensibility or microtubule dynamics). Another intercellular signal mediated by microtubule dynamics is the mechanical stress caused by growth of interconnected cells. Superimposed on developmental controls, sugar signalling through the TOR pathway has recently emerged as a central control point linking cytoplasmic growth, cell-cycle and cell-wall functions. Recent progress in quantitative imaging and computational modelling will facilitate analysis of the multiple interconnections between plant cell growth and cell cycle and ultimately will be required for the predictive manipulation of plant growth.

Effect of triiodothyronine on the maxilla and masseter muscles of the rat stomatognathic system

The maxilla and masseter muscles are components of the stomatognathic system involved in chewing, which is frequently affected by physical forces such as gravity, and by dental, orthodontic and orthopedic procedures. Thyroid hormones (TH) are known to regulate the expression of genes that control bone mass and the oxidative properties of muscles; however, little is known about the effects of TH on the stomatognathic system. This study investigated this issue by evaluating: i) osteoprotegerin (OPG) and osteopontine (OPN) mRNA expression in the maxilla and ii) myoglobin (Mb) mRNA and protein expression, as well as fiber composition of the masseter. Male Wistar rats (~250 g) were divided into thyroidectomized (Tx) and sham-operated (SO) groups (N = 24/group) treated with T3 or saline (0.9%) for 15 days. Thyroidectomy increased OPG (~40%) and OPN (~75%) mRNA expression, while T3 treatment reduced OPG (~40%) and OPN (~75%) in Tx, and both (~50%) in SO rats. Masseter Mb mRNA expression and fiber type composition remained unchanged, despite the induction of hypo- and hyperthyroidism. However, Mb content was decreased in Tx rats even after T3 treatment. Since OPG and OPN are key proteins involved in the osteoclastogenesis inhibition and bone mineralization, respectively, and that Mb functions as a muscle store of O2 allowing muscles to be more resistant to fatigue, the present data indicate that TH also interfere with maxilla remodeling and the oxidative properties of the masseter, influencing the function of the stomatognathic system, which may require attention during dental, orthodontic and orthopedic procedures in patients with thyroid diseases.

Transmission potential, skin inflammatory response, and parasitism of symptomatic and asymptomatic dogs with visceral leishmaniasis

Background: Visceral leishmaniasis in Brazil is caused by the protozoan Leishmania (Leishmania) chagasi and it is transmitted by sandfly of the genus Lutzomyia. Dogs are an important domestic reservoir, and control of the transmission of visceral leishmaniasis (VL) to humans includes the elimination of infected dogs. However, though dogs are considered to be an important element in the transmission cycle of Leishmania, the identification of infected dogs representing an immediate risk for transmission has not been properly evaluated. Since it is not possible to treat infected dogs, they are sacrificed when a diagnosis of VL is established, a measure that is difficult to accomplish in highly endemic areas. In such areas, parameters that allow for easy identification of reservoirs that represents an immediate risk for transmission is of great importance for the control of VL transmission. In this study we aimed to identify clinical parameters, reinforced by pathological parameters that characterize dogs with potential to transmit the parasite to the vector. Results: The major clinical manifestations of visceral leishmaniasis in dogs from an endemic area were onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. The transmission potential of these dogs was assessed by xenodiagnosis using Lutzomyia longipalpis. Six of nine symptomatic dogs were infective to Lutzomyia longipalpis while none of the five asymptomatic dogs were infective to the sandfly. Leishmania amastigotes were present in the skin of all clinically symptomatic dogs, but absent in asymptomatic dogs. Higher parasite loads were observed in the ear and ungueal region, and lower in abdomen. The inflammatory infiltrate was more intense in the ears and ungueal regions of both symptomatic and asymptomatic dogs. In clinically affected dogs in which few or none Leishmania amastigotes were observed, the inflammatory infiltrate was constituted mainly of lymphocytes and macrophages. When many parasites were present, the infiltrate was also comprised of lymphocytes and macrophages, as well as a larger quantity of polymorphonuclear neutrophils (PMNs). Conclusion: Dogs that represent an immediate risk for transmission of Leishmania in endemic areas present clinical manifestations that include onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. Lymphadenopathy in particular was a positive clinical hallmark since it was closely related to the positive xenodiagnosis.

Multi-trait and random regression mature weight heritability and breeding value estimates in Nelore cattle

Mature weight breeding values were estimated using a multi-trait animal model (MM) and a random regression animal model (RRM). Data consisted of 82 064 weight records from 8 145 animals, recorded from birth to eight years of age. Weights at standard ages were considered in the MM. All models included contemporary groups as fixed effects, and age of dam (linear and quadratic effects) and animal age as covariates. In the RRM, mean trends were modelled through a cubic regression on orthogonal polynomials of animal age and genetic maternal and direct and maternal permanent environmental effects were also included as random. Legendre polynomials of orders 4, 3, 6 and 3 were used for animal and maternal genetic and permanent environmental effects, respectively, considering five classes of residual variances. Mature weight (five years) direct heritability estimates were 0.35 (MM) and 0.38 (RRM). Rank correlation between sires' breeding values estimated by MM and RRM was 0.82. However, selecting the top 2% (12) or 10% (62) of the young sires based on the MM predicted breeding values, respectively 71% and 80% of the same sires would be selected if RRM estimates were used instead. The RRM modelled the changes in the (co) variances with age adequately and larger breeding value accuracies can be expected using this model.

Effect of Nd:YAG Laser and Acidulated Phosphate Fluoride on Bovine and Human Enamel Submitted to Erosion/Abrasion or Erosion Only: An in Vitro Preliminary Study

Objective: The aim of the present in vitro study was to evaluate, using two different methodologies, the effectiveness of pulsed Nd:YAG laser irradiation associated with topical acidulated phosphate fluoride (APF) for preventing enamel erosion and structure loss under regimes of erosion and abrasion or erosion only. Background Data: An increased incidence of noncarious lesions (erosion and abrasion) has been observed, consequently new preventative therapies have been proposed. Materials and Methods: Two different methodologies were performed. For the first, 100 bovine crowns were submitted to four different treatments (n = 25): no treatment (control), 4 min application of APF, Nd:YAG laser irradiation (1 W, 100 mJ, 10 Hz, 141.5 J/cm(2)), and Nd:YAG laser irradiation+4 min of APF. After the specimens were exposed to citric acid (2% w/v; 30 min), they were submitted to 5000 brushing cycles. Specimen mass was measured before and after the treatments. For the second methodology, 20 human crowns were embedded in acrylic resin and cut surfaces were exposed and polished. The specimens were divided into four groups (n = 10): no treatment (control), APF for 4 min, Nd:YAG laser irradiation (1 W, 100 mJ, 10 Hz, 125 J/cm(2)), and Nd:YAG laser irradiation+APF. The samples were then immersed in citric acid (2% w/v; 90 min). Vickers hardness was obtained before and after the treatments. Results: The Nd:YAG laser irradiation+APF (bovine and human enamel) was more effective and yielded statistically significant results for surface microhardness and enamel wear. Conclusion: Nd:YAG laser irradiation associated with APF reduced bovine enamel wear and human enamel softening when samples were submitted to a regime of erosion and abrasion or erosion only in vitro.

Effect of Titanium Tetrafluoride and Amine Fluoride Treatment Combined with Carbon Dioxide Laser Irradiation on Enamel and Dentin Erosion

Objective: This in vitro study aimed to analyze the influence of carbon dioxide (CO(2)) laser irradiation on the efficacy of titanium tetrafluoride (TiF(4)) and amine fluoride (AmF) in protecting enamel and dentin against erosion. Methods: Bovine enamel and dentin samples were pretreated with carbon dioxide (CO(2)) laser irradiation only (group I), TiF(4) only (1% F, group II), CO(2) laser irradiation before (group III) or through (group IV) TiF(4) application, AmF only (1% F, group V), or CO(2) laser irradiation before (group VI) or through (group VII) AmF application. Controls remained untreated. Ten samples of each group were then subjected to an erosive demineralization and remineralization cycling for 5 days. Enamel and dentin loss were measured profilometrically after pretreatment, 4 cycles (1 day), and 20 cycles (5 days) and statistically analyzed using analysis of variance and Scheffe's post hoc tests. Scanning electron microscopy (SEM) analysis was performed in pretreated but not cycled samples (two samples each group). Results: After 20 cycles, there was significantly less enamel loss in groups V and IV and significantly less dentin loss in group V only. All other groups were not significantly different from the controls. Lased surfaces (group I) appeared unchanged in the SEM images, although SEM images of enamel but not of dentin showed that CO(2) laser irradiation affected the formation of fluoride precipitates. Conclusion: AmF decreased enamel and dentin erosion, but CO(2) laser irradiation did not improve its efficacy. TiF(4) showed only a limited capacity to prevent erosion, but CO(2) laser irradiation significantly enhanced its ability to reduce enamel erosion.

Chemical similarities between Galactic bulge and local thick disk red giant stars

Context. The evolution of the Milky Way bulge and its relationship with the other Galactic populations is still poorly understood. The bulge has been suggested to be either a merger-driven classical bulge or the product of a dynamical instability of the inner disk. Aims. To probe the star formation history, the initial mass function and stellar nucleosynthesis of the bulge, we performed an elemental abundance analysis of bulge red giant stars. We also completed an identical study of local thin disk, thick disk and halo giants to establish the chemical differences and similarities between the various populations. Methods. High-resolution infrared spectra of 19 bulge giants and 49 comparison giants in the solar neighborhood were acquired with Gemini/Phoenix. All stars have similar stellar parameters but cover a broad range in metallicity. A standard 1D local thermodynamic equilibrium analysis yielded the abundances of C, N, O and Fe. A homogeneous and differential analysis of the bulge, halo, thin disk and thick disk stars ensured that systematic errors were minimized. Results. We confirm the well-established differences for [O/Fe] (at a given metallicity) between the local thin and thick disks. For the elements investigated, we find no chemical distinction between the bulge and the local thick disk, which is in contrast to previous studies relying on literature values for disk dwarf stars in the solar neighborhood. Conclusions. Our findings suggest that the bulge and local thick disk experienced similar, but not necessarily shared, chemical evolution histories. We argue that their formation timescales, star formation rates and initial mass functions were similar.

Kinematic parameters and membership probabilities of open clusters in the Bordeaux PM2000 catalogue

Aims. We derive lists of proper-motions and kinematic membership probabilities for 49 open clusters and possible open clusters in the zone of the Bordeaux PM2000 proper motion catalogue (+ 11 degrees <= delta <= + 18 degrees). We test different parametrisations of the proper motion and position distribution functions and select the most successful one. In the light of those results, we analyse some objects individually. Methods. We differenciate between cluster and field member stars, and assign membership probabilities, by applying a new and fully automated method based on both parametrisations of the proper motion and position distribution functions, and genetic algorithm optimization heuristics associated with a derivative-based hill climbing algorithm for the likelihood optimization. Results. We present a catalogue comprising kinematic parameters and associated membership probability lists for 49 open clusters and possible open clusters in the Bordeaux PM2000 catalogue region. We note that this is the first determination of proper motions for five open clusters. We confirm the non-existence of two kinematic populations in the region of 15 previously suspected non-existent objects.

Chemical similarities between Galactic bulge and local thick disk red giants: O, Na, Mg, Al, Si, Ca, and Ti

Context. The formation and evolution of the Galactic bulge and its relationship with the other Galactic populations is still poorly understood. Aims. To establish the chemical differences and similarities between the bulge and other stellar populations, we performed an elemental abundance analysis of alpha- (O, Mg, Si, Ca, and Ti) and Z-odd (Na and Al) elements of red giant stars in the bulge as well as of local thin disk, thick disk and halo giants. Methods. We use high-resolution optical spectra of 25 bulge giants in Baade's window and 55 comparison giants (4 halo, 29 thin disk and 22 thick disk giants) in the solar neighborhood. All stars have similar stellar parameters but cover a broad range in metallicity (-1.5 < [Fe/H] < +0.5). A standard 1D local thermodynamic equilibrium analysis using both Kurucz and MARCS models yielded the abundances of O, Na, Mg, Al, Si, Ca, Ti and Fe. Our homogeneous and differential analysis of the Galactic stellar populations ensured that systematic errors were minimized. Results. We confirm the well-established differences for [alpha/Fe] at a given metallicity between the local thin and thick disks. For all the elements investigated, we find no chemical distinction between the bulge and the local thick disk, in agreement with our previous study of C, N and O but in contrast to other groups relying on literature values for nearby disk dwarf stars. For -1.5 < [Fe/H] < -0.3 exactly the same trend is followed by both the bulge and thick disk stars, with a star-to-star scatter of only 0.03 dex. Furthermore, both populations share the location of the knee in the [alpha/Fe] vs. [Fe/H] diagram. It still remains to be confirmed that the local thick disk extends to super-solar metallicities as is the case for the bulge. These are the most stringent constraints to date on the chemical similarity of these stellar populations. Conclusions. Our findings suggest that the bulge and local thick disk stars experienced similar formation timescales, star formation rates and initial mass functions, confirming thus the main outcomes of our previous homogeneous analysis of [O/Fe] from infrared spectra for nearly the same sample. The identical a-enhancements of thick disk and bulge stars may reflect a rapid chemical evolution taking place before the bulge and thick disk structures we see today were formed, or it may reflect Galactic orbital migration of inner disk/bulge stars resulting in stars in the solar neighborhood with thick-disk kinematics.