A program of nurse algorithm-guided care for adult patients with acute minor illnesses in primary care

Background: Attention to patients with acute minor-illnesses requesting same-day consultation represents a major burden in primary care. The workload is assumed by general practitioners in many countries. A number of reports suggest that care to these patients may be provided, at in least in part, by nurses. However, there is scarce information with respect to the applicability of a program of nurse management for adult patients with acute minor-illnesses in large areas. The aim of this study is to assess the effectiveness of a program of nurse algorithm-guided care for adult patients with acute minor illnesses requesting same-day consultation in primary care in a largely populated area. Methods: A cross-sectional study of all adult patients seeking same day consultation for 16 common acute minor illnesses in a large geographical area with 284 primary care practices. Patients were included in a program of nurse case management using management algorithms. The main outcome measure was case resolution, defined as completion of the algorithm by the nurse without need of referral of the patient to the general practitioner. The secondary outcome measure was return to consultation, defined as requirement of new consultation for the same reason as the first one, in primary care within a 7-day period. Results: During a two year period (April 2009-April 2011), a total of 1,209,669 consultations were performed in the program. Case resolution was achieved by nurses in 62.5% of consultations. The remaining cases were referred to a general practitioner. Resolution rates ranged from 94.2% in patients with burns to 42% in patients with upper respiratory symptoms. None of the 16 minor illnesses had a resolution rate below 40%. Return to consultation during a 7-day period was low, only 4.6%. Conclusions: A program of algorithms-guided care is effective for nurse case management of patients requesting same day consultation for minor illnesses in primary care.

Evolutionary and ecological significance of non-shivering thermogenesis in the common vole

La production endogène à long terme de chaleur, même au repos, est une adaptation que l'on retrouve chez les animaux à sang chaud (les oiseaux et les mammifères). Cette production de chaleur a comme but le maintien d'une température constante du corps indépendamment de la température extérieure. A cette fin, les mammifères ont développé une forme de tissu spécialisé nommé tissu adipeux brun (BAT). Ce tissu est responsable de la conversion de nourriture en chaleur, procédé appelé thermogenèse sans frisson (NST = non-shivering thermogenesis). Durant ce procédé la uncoupling protein 1 (UCP1) convertit, au sein des mitochondries, la nourriture en chaleur au lieu de produire de l'ATP, molécule utilisée comme énergie cellulaire. On suppose que cette inefficacité de la conversion de la nourriture en ATP dans le BAT influence l'homéostasie de l'énergie, l'allocation des ressources ainsi que la régulation de processus gourmant en énergie comme la croissance et la reproduction. Afin de maintenir une température du corps constante, les mammifères doivent ajuster leur NST en fonction de la température ambiante. La NST devrait être donc plus importante que la croissance et la reproduction durant l'hiver que lors l'été/à haute altitude qu'à basse altitude. En effet, plusieurs études ont déjà démontré la dépendance de la NST aux divers paramètres environnementaux. Par contre, l'héritabilité de la NST ainsi que sa relation avec d'autres traits de caractère, ne sont que très peu connus, ceci malgré l'importance d'une telle information afin de pouvoir comprendre son potentiel évolutif. L'étude de l'importance évolutive et écologique sur la NST chez les campagnols des champs (Microtus arvalis) fut donc le but cette thèse de doctorat. Grâce aux informations collectées sur 4 générations de campagnols (chapitre 1), une dépendance saisonnière et journalière de la NST a été démontrée: elle augmente lors des périodes froides et diminue lors de la lactation. On a démontré que bien qu'étant plastique, la variation de la NST a une composante génétique significative. Elle est corrélée avec le taux d'activité métabolique au repos indiquant des contraintes intrinsèques. A l'aide d'une expérience de jardin commune, on a pu démontrer dans le chapitre 2 que les campagnols habitant en altitude ont une capacité génétique de thermogenèse sans frisson plus haute que celles de basse altitude. Ils produisent des portées plus petites et leur descendance grandit moins vite, surtout à partir du 10ème jour ce qui coïncide avec le début de la production de chaleur endogène. En choisissant artificiellement des campagnols avec une NST faible ou grande, on a pu démontrer une relation entre la NST et la développement de la masse corporelle. Les campagnols avec une haute NST grandissent plus lentement et sont plus légères à l'âge adulte que celles ayant une basse NST. A l'aide d'un croisement interligne entre les campagnols sélectionnés (avec basse et haute NST), on a pu montrer dans le chapitre 3 des effets « parent-of-origin >> du développement massique de la descendance, indiquant une empreinte génétique parentale. Cela veut dire que l'expression d'un allele dépend de l'origine parentale. De plus, des effets « parent-of-origin » des taux de base de norépinephrine et d'irisine ont pu être trouvés. Ces hormones sont connues pour influencer non seulement la TSF mais aussi d'autres caractéristiques. Ces influences ouvrent la voie à de nouvelles études sur la relation entre la TSF et l'histoire de vie. Dans le chapitre 4 on a démontré des effets à long terme de l'allocation des ressources en manipulant la taille des portées qui ont abouti à des différences dans l'investissement dans la reproduction et de la croissance de la descendance à la fois dans le cas de la reproduction manipulé et aussi dans le non - manipulée entre les femelles avec portées agrandies et réduites. Ensemble, ces résultats mettent en évidence le rôle central de la NST dans l'allocation des ressources sur la base d'un compromis entre le maintien et la croissance et ainsi transforme l'histoire de vie des mammifères. Ces études montrent comment les mammifères peuvent répondre rapidement à court et à long terme (c'est-à-dire par des réponses génétiques ou plastiques) à un changement rapide du climat. On montre aussi qu'il y a probablement une corrélation entre l'histoire de vie et des changements du comportement. Finalement mes résultats ont montré un lien étroit entre la NST et la croissance et les dimensions du corps. Ces résultats indiquent que le tissu adipeux brun et la NST pourraient être une cible thérapeutique intéressante pour traiter l'obésité.

A program of nurse algorithm-guided care for adult patients with acute minor illnesses in primary care

Background: Attention to patients with acute minor-illnesses requesting same-day consultation represents a major burden in primary care. The workload is assumed by general practitioners in many countries. A number of reports suggest that care to these patients may be provided, at in least in part, by nurses. However, there is scarce information with respect to the applicability of a program of nurse management for adult patients with acute minor-illnesses in large areas. The aim of this study is to assess the effectiveness of a program of nurse algorithm-guided care for adult patients with acute minor illnesses requesting same-day consultation in primary care in a largely populated area. Methods: A cross-sectional study of all adult patients seeking same day consultation for 16 common acute minor illnesses in a large geographical area with 284 primary care practices. Patients were included in a program of nurse case management using management algorithms. The main outcome measure was case resolution, defined as completion of the algorithm by the nurse without need of referral of the patient to the general practitioner. The secondary outcome measure was return to consultation, defined as requirement of new consultation for the same reason as the first one, in primary care within a 7-day period. Results: During a two year period (April 2009-April 2011), a total of 1,209,669 consultations were performed in the program. Case resolution was achieved by nurses in 62.5% of consultations. The remaining cases were referred to a general practitioner. Resolution rates ranged from 94.2% in patients with burns to 42% in patients with upper respiratory symptoms. None of the 16 minor illnesses had a resolution rate below 40%. Return to consultation during a 7-day period was low, only 4.6%. Conclusions: A program of algorithms-guided care is effective for nurse case management of patients requesting same day consultation for minor illnesses in primary care.

Mutual trust and cooperation in the evolutionary hawks-doves game

Using a new dynamical network model of society in which pairwise interactions are weighted according to mutual satisfaction, we show that cooperation is the norm in the hawks-doves game when individuals are allowed to break ties with undesirable neighbors and to make new acquaintances in their extended neighborhood. Moreover, cooperation is robust with respect to rather strong strategy perturbations. We also discuss the empirical structure of the emerging networks, and the reasons that allow cooperators to thrive in the population. Given the metaphorical importance of this game for social interaction, this is an encouraging positive result as standard theory for large mixing populations prescribes that a certain fraction of defectors must always exist at equilibrium.

Chromosomal versus mitochondrial DNA evolution: tracking the evolutionary history of the southwestern european populations of the Sorex araneus group (Mammalia Insectivora)

The shrews of the Sorer araneus group have undergone a spectacular chromosome evolution. The karyotype of Sorer granarius is generally considered ancestral to those of Sorer coronatus and S. araneus. However, a sequence of 777 base pairs of the cytochrome b gene of the mitochondrial DNA (mtDNA) produces a quite different picture: S. granarius is closely related to the populations of S. araneus from the Pyrenees and from the northwestern Alps, whereas S. coronatus and S. araneus from Italy and the southern Alps represent two well-separated lineages. It is suggested that mtDNA and chromosomal evolution are in this case largely independant processes. Whereas mtDNA haplotypes are closely linked to the geographical history of the populations, chromosomal mutations were probably transmitted from one population to another. Available data suggest that the impressive chromosome polymorphism of this group is quite a recent phenomenon.

A program of nurse algorithm-guided care for adult patients with acute minor illnesses in primary care

Background: Attention to patients with acute minor-illnesses requesting same-day consultation represents a major burden in primary care. The workload is assumed by general practitioners in many countries. A number of reports suggest that care to these patients may be provided, at in least in part, by nurses. However, there is scarce information with respect to the applicability of a program of nurse management for adult patients with acute minor-illnesses in large areas. The aim of this study is to assess the effectiveness of a program of nurse algorithm-guided care for adult patients with acute minor illnesses requesting same-day consultation in primary care in a largely populated area. Methods: A cross-sectional study of all adult patients seeking same day consultation for 16 common acute minor illnesses in a large geographical area with 284 primary care practices. Patients were included in a program of nurse case management using management algorithms. The main outcome measure was case resolution, defined as completion of the algorithm by the nurse without need of referral of the patient to the general practitioner. The secondary outcome measure was return to consultation, defined as requirement of new consultation for the same reason as the first one, in primary care within a 7-day period. Results: During a two year period (April 2009-April 2011), a total of 1,209,669 consultations were performed in the program. Case resolution was achieved by nurses in 62.5% of consultations. The remaining cases were referred to a general practitioner. Resolution rates ranged from 94.2% in patients with burns to 42% in patients with upper respiratory symptoms. None of the 16 minor illnesses had a resolution rate below 40%. Return to consultation during a 7-day period was low, only 4.6%. Conclusions: A program of algorithms-guided care is effective for nurse case management of patients requesting same day consultation for minor illnesses in primary care.

Efficient total variation algorithm for fetal brain MRI reconstruction.

Fetal MRI reconstruction aims at finding a high-resolution image given a small set of low-resolution images. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has considered several regularization terms s.a. Dirichlet/Laplacian energy, Total Variation (TV)- based energies and more recently non-local means. Although TV energies are quite attractive because of their ability in edge preservation, standard explicit steepest gradient techniques have been applied to optimize fetal-based TV energies. The main contribution of this work lies in the introduction of a well-posed TV algorithm from the point of view of convex optimization. Specifically, our proposed TV optimization algorithm or fetal reconstruction is optimal w.r.t. the asymptotic and iterative convergence speeds O(1/n2) and O(1/√ε), while existing techniques are in O(1/n2) and O(1/√ε). We apply our algorithm to (1) clinical newborn data, considered as ground truth, and (2) clinical fetal acquisitions. Our algorithm compares favorably with the literature in terms of speed and accuracy.

Reproductive bribing and policing as evolutionary mechanisms for the suppression of within-group selfishness.

We show that a new, simple, and robust general mechanism for the social suppression of within-group selfishness follows from Hamilton's rule applied in a multilevel selection approach to asymmetrical, two-person groups: If it pays a group member to behave selfishly (i.e., increase its share of the group's reproduction, at the expense of group productivity), then its partner will virtually always be favored to provide a reproductive "bribe" sufficient to remove the incentive for the selfish behavior. The magnitude of the bribe will vary directly with the number of offspring (or other close kin) potentially gained by the selfish individual and inversely with both the relatedness r between the interactants and the loss in group productivity because of selfishness. This bribe principle greatly extends the scope for cooperation within groups. Reproductive bribing is more likely to be favored over social policing for dominants rather than subordinates and as intragroup relatedness increases. Finally, analysis of the difference between the group optimum for an individual's behavior and the individual's inclusive fitness optimum reveals a paradoxical feedback loop by which bribing and policing, while nullifying particular selfish acts, automatically widen the separation of individual and group optima for other behaviors (i.e., resolution of one conflict intensifies others).

A new perspective on the evolutionary history of western European Sorex araneus group revealed by paternal and maternal molecular markers.

The species of the common shrew (Sorex araneus) group are morphologically very similar, but have undergone a spectacular chromosomal evolution. We investigate here the evolutionary history of the Sorex araneus group distributed in western Europe. In particular, we clarify the position of a difficult species, S. granarius, using sex-specific (mtDNA and Y-chromosome) markers. The karyotype of S. granarius is generally considered similar to the common ancestor of the restricted group considered here. The mtDNA data (1.4 kb) confirms the close relationship between S. granarius and S. araneus sensu stricto (hereafter S. araneus s.s.), but the Y-chromosome (3.4 kb) produces a quite different picture: S. granarius is closely related to another species, S. coronatus. Comparison of mtDNA and Y-chromosome phylogenies suggests that the genetic and chromosomal evolution in this group are disconnected processes. The evolutionary history of the south-western European populations of the S. araneus group can only be understood considering secondary contacts between taxa after their divergence, implying genetic exchanges by means of hybridization and/or introgression.

Evolutionary comparison provides evidence for pathogenicity of RMRP mutations.

Cartilage-hair hypoplasia (CHH) is a pleiotropic disease caused by recessive mutations in the RMRP gene that result in a wide spectrum of manifestations including short stature, sparse hair, metaphyseal dysplasia, anemia, immune deficiency, and increased incidence of cancer. Molecular diagnosis of CHH has implications for management, prognosis, follow-up, and genetic counseling of affected patients and their families. We report 20 novel mutations in 36 patients with CHH and describe the associated phenotypic spectrum. Given the high mutational heterogeneity (62 mutations reported to date), the high frequency of variations in the region (eight single nucleotide polymorphisms in and around RMRP), and the fact that RMRP is not translated into protein, prediction of mutation pathogenicity is difficult. We addressed this issue by a comparative genomic approach and aligned the genomic sequences of RMRP gene in the entire class of mammals. We found that putative pathogenic mutations are located in highly conserved nucleotides, whereas polymorphisms are located in non-conserved positions. We conclude that the abundance of variations in this small gene is remarkable and at odds with its high conservation through species; it is unclear whether these variations are caused by a high local mutation rate, a failure of repair mechanisms, or a relaxed selective pressure. The marked diversity of mutations in RMRP and the low homozygosity rate in our patient population indicate that CHH is more common than previously estimated, but may go unrecognized because of its variable clinical presentation. Thus, RMRP molecular testing may be indicated in individuals with isolated metaphyseal dysplasia, anemia, or immune dysregulation.

A system-level, molecular evolutionary analysis of mammalian phototransduction

Visual perception is initiated in the photoreceptor cells of the retina via the phototransduction system.This system has shown marked evolution during mammalian divergence in such complex attributes as activation time and recovery time. We have performed a molecular evolutionary analysis of proteins involved in mammalianphototransduction in order to unravel how the action of natural selection has been distributed throughout thesystem to evolve such traits. We found selective pressures to be non-randomly distributed according to both a simple protein classification scheme and a protein-interaction network representation of the signaling pathway. Proteins which are topologically central in the signaling pathway, such as the G proteins, as well as retinoid cycle chaperones and proteins involved in photoreceptor cell-type determination, were found to be more constrained in their evolution. Proteins peripheral to the pathway, such as ion channels and exchangers, as well as the retinoid cycle enzymes, have experienced a relaxation of selective pressures. Furthermore, signals of positive selection were detected in two genes: the short-wave (blue) opsin (OPN1SW) in hominids and the rod-specific Na+/Ca2+,K+ ion exchanger (SLC24A1) in rodents. The functions of the proteins involved in phototransduction and the topology of the interactions between them have imposed non-random constraints on their evolution. Thus, in shaping or conserving system-level phototransduction traits, natural selection has targeted the underlying proteins in a concerted manner.

Differences in the evolutionary history of disease genes affected by dominant or recessive mutations

Background: Global analyses of human disease genes by computational methods have yielded important advances in the understanding of human diseases. Generally these studies have treated the group of disease genes uniformly, thus ignoring the type of disease-causing mutations (dominant or recessive). In this report we present a comprehensive study of the evolutionary history of autosomal disease genes separated by mode of inheritance.Results: We examine differences in protein and coding sequence conservation between dominant and recessive human disease genes. Our analysis shows that disease genes affected by dominant mutations are more conserved than those affected by recessive mutations. This could be a consequence of the fact that recessive mutations remain hidden from selection while heterozygous. Furthermore, we employ functional annotation analysis and investigations into disease severity to support this hypothesis. Conclusion: This study elucidates important differences between dominantly- and recessively-acting disease genes in terms of protein and DNA sequence conservation, paralogy and essentiality. We propose that the division of disease genes by mode of inheritance will enhance both understanding of the disease process and prediction of candidate disease genes in the future.

Migrated foreign body liver abscess: illustrative case report, systematic review, and proposed diagnostic algorithm.

Pyogenic liver abscess is a severe condition and a therapeutic challenge. Treatment failure may be due to an unrecognized ingested foreign body that migrated from the gastrointestinal tract. There has recently been a marked increase in the number of reported cases of this condition, but initial misdiagnosis as cryptogenic liver abscess still occurs in the majority of cases. We conducted the current study to characterize this entity and provide a diagnostic strategy applicable worldwide. To this end, data were collected from our case and from a systematic review that identified 59 well-described cases. Another systematic review identified series of cryptogenic-and Asian Klebsiella-liver abscess; these data were pooled and compared with the data from the cases of migrated foreign body liver abscess. The review points out the low diagnostic accuracy of history taking, modern imaging, and even surgical exploration. A fistula found through imaging procedures or endoscopy warrants surgical exploration. Findings suggestive of foreign body migration are symptoms of gastrointestinal perforation, computed tomography demonstration of a thickened gastrointestinal wall in continuity with the abscess, and adhesions seen during surgery. Treatment failure, left lobe location, unique location (that is, only 1 abscess location within the liver), and absence of underlying conditions also point to the diagnosis, as shown by comparison with the cryptogenic liver abscess series. This study demonstrates that migrated foreign body liver abscess is a specific entity, increasingly reported. It usually is not cured when unrecognized, and diagnosis is mainly delayed. This study provides what we consider the best available evidence for timely diagnosis with worldwide applicability. Increased awareness is required to treat this underestimated condition effectively, and further studies are needed.