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Health inequality and users' risk-taking: a longitudinal analysis in a French reproductive technology centre.

This article sets out to provide a demographic analysis of the production of social inequality through IVF trajectories in a reproductive technology centre of a French hospital. However specific this example may be, it reveals one of the paradoxes of social inequalities in health: lay experience of risk in reproductive technology shows profound inequalities related to social status, despite the fact that equality would seem to be guaranteed in France, since the social security system covers the full cost of the treatments. We will try to understand this paradox through a lifecourse approach. Thus, it will be shown that social inequality in reproductive health is deeply rooted in social scenarios of infertility that lead to differentiated medical experience: there is little benefit and even a worsening in the situation of lower class women, who were faced with unpredictable risks related to the collective testing of these new technologies. Conversely, the possibility of inventing new lifestories, which may or may not include motherhood, was given to upper class women who take calculated risks to delay the scheduling of their pregnancies. In short, this study confirms that the production of social inequality in reproductive health can only be understood in connection with the social dynamics of lifestyles, resulting in specific medical patterns. This paper also leads to the assumption that these social scenarios are related to attempts to enhance the different forms of capital: economic, cultural and social capital. In addition, the presence of risks aggravates this inequality process. This raises another question: do reproductive technologies result in reinforcing social inequality?

Adult↗

Dynamics of excitation pulses with attractive interaction: kinematic analysis and chemical wave experiments.

We present a theoretical analysis of stacking and destacking wave trains in excitable reaction-diffusion systems with anomalous velocity-wavelength dependence. For linearized dispersion relations, kinematic analysis yields an analytical function that rigorously describes front trajectories. The corresponding accelerations have exactly one extremum that slowly decays with increasing pulse number. For subsequent pulses these maxima occur with a lag time equal to the inverse slope of the linearized dispersion curve. These findings are reproduced in experiments with chemical waves in the 1,4-cyclohexanedione Belousov-Zhabotinsky reaction but should be also applicable to step bunching on crystal surfaces and certain traffic phenomena.

Journal Article↗

Historical introgression as a driver of diversification of diploid Picris (Compositae) in the Mediterranean Basin.

The Mediterranean Basin is recognized as one of the world's most prominent biodiversity hotspots, where past climatic changes have driven range shifts, secondary contact between populations, and gene exchange. This study investigates the impact of historical introgression on the diversification of diploid members of the genus Picris (Compositae). Using nuclear and plastid genome data obtained through the Hyb-Seq approach, we assess whether introgression contributed to the evolution of the Mediterranean Picris, potentially giving rise to multiple regional endemics. We also test whether introgression was associated with the transfer of traits such as life strategy and fruit morphology, which are involved in habitat-specific adaptation. Phylogenetic network analysis revealed two major introgression events that shaped evolutionary trajectories within the genus. The earliest and most complex events involved the Turkish endemic P. campylocarpa, which hybridized with the most recent common ancestor (MRCA) of the P. cyprica-P. pauciflora lineage and with the MRCA of the B1 subclade, comprising the P. hieracioides group and the P. scaberrima-P. strigosa lineage. The latter introgression preceded shifts from iteroparity to semelparity and from heterocarpy to homocarpy, ruling out an adaptive introgression origin for these traits. Nevertheless, all detected historical introgression events contributed to the diversification of diploid Picris taxa.

Diploidy↗

Frailty, fitness and late-life mortality in relation to chronological and biological age.

BACKGROUND: People age at remarkably different rates, but how to estimate trajectories of senescence is controversial. METHODS: In a secondary analysis of a representative cohort of Canadians aged 65 and over (n = 2914) we estimated a frailty index based on the proportion of 20 deficits observed in a structured clinical examination. The construct validity of the index was examined through its relationship to chronological age (CA). The criterion validity was examined in its ability to predict mortality, and in relation to other predictions about aging. From the frailty index, relative (to CA) fitness and frailty were estimated, as was an individual's biological age. RESULTS: The average value of the frailty index increased with age in a log-linear relationship (r = 0.91; p < 0.001). In a Cox regression analysis, biological age was significantly more highly associated with death than chronological age. The average increase in the frailty index (i.e. the average accumulation of deficits) amongst those with no cognitive impairment was 3 per cent per year. CONCLUSIONS: The frailty index is a sensitive predictor of survival. As the index includes items not traditionally related to adverse health outcomes, the finding is compatible with a view of frailty as the failure to integrate the complex responses required to maintain function.

Journal Article↗

Pax6 defines the di-mesencephalic boundary by repressing En1 and Pax2.

Transcriptional factors and signaling molecules are responsible for regionalization of the central nervous system. In the early stage of neural development, Pax6 is expressed in the prosencephalon, while En1 and Pax2 are expressed in the mesencephalon. Here, we misexpressed Pax6 in the mesencephalon to elucidate the mechanism of the di-mesencephalic boundary formation. Histological analysis, expression patterns of diencephalic marker genes, and fiber trajectory of the posterior commissure indicated that Pax6 misexpression caused a caudal shift of the di-mesencephalic boundary. Pax6 repressed En1, Pax2 and other tectum (mesencephalon)-related genes such as En2, Pax5, Pax7, but induced Tcf4, a diencephalon marker gene. To know how Pax6 represses En1 and Pax2, we ectopically expressed a dominant-active or negative form of Pax6. The dominant-active form of Pax6 showed a similar but more severe phenotype than Pax6, while the dominant-negative form showed an opposite phenotype, suggesting that Pax6 acts as a transcriptional activator. Thus Pax6 may repress tectum-related genes by activating an intervening repressor. The results of misexpression experiments, together with normal expression patterns of Pax6, En1 and Pax2, suggest that repressive interaction between Pax6 and En1/Pax2 defines the di-mesencephalic boundary.

Animals↗

The effect of body orientation on a point-to-point movement in healthy elderly persons.

OBJECTIVE: Upper limb retraining during the early phases of neurological rehabilitation often involves having individuals practice reaching in body orientations that reduce the effect of gravity on various joint motions (e.g., shoulder flexion, elbow extension). However, the efficacy of these training techniques has not been determined. The purpose of this study was to determine the effects of reducing gravity through a change in body orientation from sitting to side-lying on the kinematics of a point-to-point movement in healthy elderly persons. METHOD: Nine healthy, right-hand-dominant women 62 to 66 years of age pointed to a target in two different body orientations-sitting and side-lying. A 2-dimensional kinematic analysis of the movement was performed to compare the trajectory of the hand and the interjoint coordination under the two conditions. RESULTS: Regardless of body orientation relative to gravity, participants produced straight hand paths and smooth, bell-shaped velocity profiles. However, they moved slower in side-lying, and the pattern of interjoint coordination varied. The shoulder and elbow moved less, whereas the scapula made a greater contribution to the overall movement. Furthermore, the temporal coordination of the joints was modified as a consequence of body position. CONCLUSION: The results indicate that point-to-point arm movements made against gravity differ from those made in a gravity-reduced plane, particularly at the joint level, illustrating that movement organization is sensitive to this contextual difference. The effect of minimizing gravity on upper limb movement needs to be explored in patient populations to determine whether training patients in gravity-reduced orientations is efficacious.

Aged↗

Helping children adjust--a Tri-Ministry Study: I. Evaluation methodology.

This report describes the evaluation methodology of the Tri-Ministry Study--a school-based trial evaluating the effectiveness of three universal programs: (a) a classwide social skills program (SS), (b) a partner reading program (RE); and, (c) a combination of both (SS & RE), to reduce and prevent behavioural maladjustment among children in the primary division (up to grade 3) of Ontario schools. The trial was done between 1991 and 1995. Sixty schools in 11 boards of education took part and were assigned randomly to program(s) during the study. Contributing to the evaluation database are detailed follow-up assessments (observations, ratings, and standard tests) on 2439 children. Three-level growth trajectory models are used to evaluate program effects. The analysis presented for illustration in this report focuses on reading achievement measured by the Wide Range Achievement Test. A companion paper presents the results of the study and discusses important methodological and programmatic issues applicable to this and other prevention studies in the field.

Child↗

Examination of fragment dose contribution in heavy ion radiotherapy.

Heavy-ion radiotherapy is an efficient method for the treatment of deep-seated tumors, because the stopping of ions in a tissue delivers the maximal absorbed dose to the tumor-affected areas with minimal damage to the healthy tissues. However, heavy ions can undergo nuclear reactions, giving products with lower Z-values and hence a longer range in the tissue. This causes a dose increase beyond the mean range of the primary beam. The contribution of such reaction products was examined in an experiment where a stack of tissue-like targets interleaved with CR-39 etched track detectors (ETD) was irradiated with heavy ions. The analysis was performed using a recently developed technique of trajectory tracing, which enables the spectroscopy of fragments with different Z-values.

Carbon Isotopes↗

Race differences in depressive symptoms: a dynamic perspective on stress exposure and vulnerability.

The existence, nature, and strength of race differences in mental health remain unclear after several decades of research. In this research, we examine black-white differences in the relationship between acute stressors and depressive symptoms. We reframe the stress exposure and differential vulnerability hypotheses in the context of long-term trajectories of stress and depression, and we hypothesize that trajectories of stress growth will be associated with trajectories of depressive symptom growth. Using latent growth curve analysis of a sample of 1,972 older persons interviewed three times at three-year intervals, we test the hypotheses that (1) growth in exposure to loss-related events will predict growth in depressive symptoms, and (2) African Americans will experience greater stress growth than whites. Results support the hypotheses. Stress growth exhibited a linear increase for blacks but not for whites, and predicted depression growth for both races, but explained more variance for blacks than for whites.

Black or African American↗

Quantitative methodology of evaluating surgeon performance in laparoscopic surgery.

Quantitative performance and skill assessments are critical for evaluating the progress of surgical residents and the efficacy of different training programs. Current evaluation methods are subjective and potentially unreliable, so there is a need for objective methods to evaluate surgical performance. We identify a feasible method to measure kinematic data in the live operating room setting and to assess the repeatability of an analysis method based on a hierarchical decomposition of surgical tasks. We used an optoelectronic motion analysis system to acquire postural data and tool tip trajectories of one expert surgeon over a period of four months. To assess repeatability of performance measures, we created a hierarchical decomposition diagram describing the procedure in terms of surgical tasks, tool sequences and fundamental tool actions. From the kinematic data, we extracted characteristic measures of individual tool actions and compared these measured distributions using the Kolmogorov-Smirnov statistic. The comparisons of distributions show consistent performance over time by a trained surgeon and little effect from patient variability, and so are likely reliable measures of performance. An expanded set of reliable kinematic measures will form the basis for quantifying surgical skill and should be useful in validating surgical simulations for use in training, certifying surgeons and designing and evaluating new surgical tools.

Biomechanical Phenomena↗

Choosing the analysis population in non-inferiority studies: per protocol or intent-to-treat.

For superiority trials, the intent-to-treat population (ITT) is considered the primary analysis population because it tends to avoid the over-optimistic estimates of efficacy that results from a per-protocol (PP) population. However, the roles of the ITT population and PP population in non-inferiority studies are not clearly defined as in superiority trials. In this paper, a simulation study is conducted to systematically investigate the impact of different types of missingness and protocol violations on the conservatism or anticonservatism of analyses based on the ITT and the PP population in non-inferiority trials. We find that conservatism or anticonservatism of the PP or ITT analysis depends on many factors, including the type of protocol deviation and missingness, the treatment trajectory (for longitudinal study) and the method of handling missing data in ITT population. The requirement that non-inferiority be shown for both PP and ITT populations does not necessarily guarantee the validity of a non-inferiority conclusion and a sufficiently powered PP analysis is not necessarily powered for ITT analysis. It is important to assess the potential types and rates of protocol deviation and missingness that might occur in a non-inferiority trial and to obtain some prior knowledge regarding the treatment trajectory of the test treatment versus the active control at the design stage so that a proper analysis plan and appropriate power estimation can be carried out. In general, for the types of protocol violations and missingness considered, we find that hybrid ITT/PP analysis, which excludes non-compliant patients as in the PP analysis and properly addresses the impact of non-trivial missing data as in the MLE-based ITT analysis, is more promising by way of providing reliable non-inferiority tests.

Analysis of Variance↗

Muscle modes and synergies during voluntary body sway.

We studied the coordination of muscle activity during voluntary body sway performed by human subjects at different frequencies. Subjects stood on the force platform and performed cyclic shifts of the center of pressure (COP) while being paced by the metronome. A major question was: does the makeup of muscle synergies and their ability to assure reproducible sway trajectory vary with the speed of the sway? Principal component analysis was used to identify three muscle groups (M-modes) within the space of integrated indices of muscle activity. M-mode vectors were similar across both subjects and sway frequencies. There were also similar relations between changes in the magnitudes of all three M-modes and COP shifts (the Jacobians) across the sway frequencies. Variance in the M-mode space across sway cycles was partitioned into two components, one that did not affect the average value of COP shift ("good variance") and the other that did. An index (DeltaV) was computed reflecting the relative amount of the "good variance"; this index has been interpreted as reflecting a multi-M-mode synergy stabilizing the COP trajectory. The average value of DeltaV was similar across all sway frequencies; DeltaV showed a within-a-cycle modulation at low but not at high sway frequencies. The modulation was mostly due to variations in the "good variance". We conclude that muscle modes and their mapping on COP shifts are robust across a wide range of rates of COP shifts. Multi-M-mode synergies stabilize COP shifts (assure its reproducibility) within a wide range of its speeds, but only during cyclic COP changes. Taken together with earlier studies that showed weak or absent multi-M-mode synergies during fast discrete COP shifts, the results suggest a basic difference between the neural control assuring stability of steady-state processes (postural or oscillatory) and transient processes (such as discrete actions). Current results provide the most comprehensive support for the notion of multi-M-mode synergies stabilizing time profiles of important performance variables in motor tasks involving large muscle groups.

Adult↗

Molecular dynamics simulations of beta-turn forming tetra- and hexapeptides.

It was previously shown that the structural ensemble of model peptides DDKG and GKDG (H. Ishii et al. Biopolymers 24, 2045-2056, 1985), DEKS (A. Otter et al. J. Biomol. Struct. Dyn. 7, 455-476, 1989) NPGQ (F. R. Carbone et al. Int. J. Pept. Protein. Res. 26, 498-508, 1985), SALN (H. Santa et al. J. Biomol. Struct. Dyn. 16, 1033-1041, 1999), SYPFDV and SYPYDV (J. Yao et al. J. Mol. Biol. 243, 736-753, 1994), VP(D)AH and VP(D)SH (B. Imperiali et al. J. Am. Chem. Soc. 114, 3182-3188, 1992) in solution contains a significant - or in some cases dominant - proportion of beta-turn conformation. In this study, a protein database was searched for the above, unprotected sequences which incorporate only L-amino acid residues. Simulated annealing and 25 ns MD simulations of structures were also performed. The DSSP and STRIDE secondary structure-assigning algorithms and clustering were used to analyze trajectories and i, i+3 hydrogen bonds were also sought. The DSSP analysis showed a fluctuation between beta-turn and random meander structure, although bend structures were not detected because of the insufficient length of peptide chains. This alternating trend was confirmed when the STRIDE algorithm was used to analyze trajectories, but STRIDE assigned more turn structures. The population of the strongest clusters was above 40% and the middle structures adopted beta-turn structure for most sequences. These results are in good agreement with previous experimental results and support the idea of the ultra-marginal stability of turns in the absence of stabilizing long-range interactions of the neighboring segments of a polypeptide chain. However, interactions between the side-chains in tetrapeptides could also contribute to turn stability and result in unusual stability in some cases. Our observations suggest that such interactions are the consequence rather than the driving force of turn formation.

Amino Acid Sequence↗

Analysis of the ipsi- and contralateral location of the neurons of the nucleus reticularis tegmenti pontis projecting to the cerebellum and of the trajectory of their axons within the pons to the brachium pontis. An "in vivo" and "in vitro" study.

Using three different retrograde tracing techniques, we analysed the broad distribution of ipsi-, contra- and bilateral NRTP neurons projecting to the cerebellum in the adult rat. The placement of the tracers into the cerebellar peduncles allowed us to determine the overall pattern of the NRTP-cerebellar projection. At the same time, the HRP "in vitro" technique permitted the study of the axonal profiles of the NRTP neurons within the pons until reaching the brachium pontis. Our observations confirm: i) A symmetrical organization of the NRTP-cerebellar projection, the number and location of ipsi- and contralateral NRTP neurons being very similar in all cases; ii) The only exception is represented by the rostralmost portions of the NRTP, in which the neurons show a cluster-complementary pattern; iii) The axons of the NRTP neurons cross the pontine midline at the dorsalmost aspect of the BPN, occupying a medial location within the brachium pontis.

Animals↗

Stability and patterning of speech movement sequences in children and adults.

Children (aged 4 and 7 years) and young adults produced a six-syllable utterance 15 times. The displacement of the lower lip was recorded with an Optotrak system and analyzed in a number of ways. First, using a procedure recently developed in our laboratory, displacement records from the 15 repetitions were amplitude- and time-normalized, and the spatiotemporal index (the STI) was computed. The STI reflects the degree to which repeated performance of a task produces movement trajectories that converge on a single pattern. Children produced less stable movement trajectories, as reflected in higher values on the STI. In a second analysis, standard measurements of amplitude and peak velocity were made for two opening and two closing lip movements. These measures suggested that, relative to the size of their oral structures, children have large movement ranges in speech. Also, children tend to move with a lower peak velocity. This large-amplitude, low-velocity movement style may reflect different underlying control processes. Finally, another analysis focused on open-close movement sequences associated with two words of the utterance. A pattern-recognition algorithm applied to the normalized waveforms from the open-close sequences revealed that children and adults produced equally distinctive movement trajectories for the two syllables. Taken together, these preliminary results suggest that nonlinear and nonuniform changes occur in components of the speech motor system during development.

Adult↗

An exploration of a novel strategy for superposing several flexible molecules.

This paper describes a computational strategy for the superposition of a set of flexible molecules. The combinatorial problems of searching conformational space and molecular matching are reduced drastically by the combined use of simulated annealing methods and cluster analysis. For each molecule, the global minimum of the conformational energy is determined by annealing and the search trajectory is retained in a history file. All the significantly different low-energy conformations are extracted by cluster analysis of data in the history file. Each pair of molecules, in each of their significantly different conformations, is then matched by simulated annealing, using the difference-distance matrix as the objective function. A set of match statistics is then obtained, from which the best match taken from all different conformations can be found. The molecules are then superposed either by reference to a base molecule or by a consensus method. This strategy ensures that as wide a range of conformations as possible is considered, but at the same time that the smallest number of significantly different conformations is used. The method has been tested on a set of six angiotensin II antagonists with between 7-11 rotatable bonds.

Algorithms↗

Evolution of vertebrate genes related to prion and Shadoo proteins--clues from comparative genomic analysis.

Recent findings of new genes in fish related to the prion protein (PrP) gene PRNP, including our recent report of SPRN coding for Shadoo (Sho) protein found also in mammals, raise issues of their function and evolution. Here we report additional novel fish genes found in public databases, including a duplicated SPRN gene, SPRNB, in Fugu, Tetraodon, carp, and zebrafish encoding the Sho2 protein, and we use comparative genomic analysis to analyze the evolutionary relationships and to infer evolutionary trajectories of the complete data set. Phylogenetic footprinting performed on aligned human, mouse, and Fugu SPRN genes to define candidate regulatory promoter regions, detected 16 conserved motifs, three of which are known transcription factor-binding sites for a receptor and transcription factors specific to or associated with expression in brain. This result and other homology-based (VISTA global genomic alignment; protein sequence alignment and phylogenetics) and context-dependent (genomic context; relative gene order and orientation) criteria indicate fish and mammalian SPRN genes are orthologous and suggest a strongly conserved basic function in brain. Whereas tetrapod PRNPs share context with the analogous stPrP-2-coding gene in fish, their sequences are diverged, suggesting that the tetrapod and fish genes are likely to have significantly different functions. Phylogenetic analysis predicts the SPRN/SPRNB duplication occurred before divergence of fish from tetrapods, whereas that of stPrP-1 and stPrP-2 occurred in fish. Whereas Sho appears to have a conserved function in vertebrate brain, PrP seems to have an adaptive role fine-tuned in a lineage-specific fashion. An evolutionary model consistent with our findings and literature knowledge is proposed that has an ancestral prevertebrate SPRN-like gene leading to all vertebrate PrP-related and Sho-related genes. This provides a new framework for exploring the evolution of this unusual family of proteins and for searching for members in other fish branches and intermediate vertebrate groups.

Animals↗

Collective motions in proteins: a covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations.

A method is described for identifying collective motions in proteins from molecular dynamics trajectories or normal mode simulations. The method makes use of the covariances of atomic positional fluctuations. It is illustrated by an analysis of the bovine pancreatic trypsin inhibitor. Comparison of the covariance and cross-correlation matrices shows that the relative motions have many similar features in the different simulations. Many regions of the protein, especially regions of secondary structure, move in a correlated manner. Anharmonic effects, which are included in the molecular dynamics simulations but not in the normal analysis, are of some importance in determining the larger scale collective motions, but not the more local fluctuations. Comparisons of molecular dynamics simulations in the present and absence of solvent indicate that the environment is of significance for the long-range motions.

Algorithms↗