[Artificial intelligence for medical information departments : construction and evaluation of a decision-making tool to identify and prioritize stays of which the PMSI coding could be optimized, and to ensure the revenues generated by activity-based pricing]. / L'intelligence artificielle au service des départements d'information médicale : construction et évaluation d'un outil d'aide à la décision pour cibler et prioriser les séjours à contrôler et fiabiliser les recettes hospitalières générées par la tarification à l'activité.

BACKGROUND: Medical Information Departments help to optimize the hospital revenues generated by activity-based pricing. A review of medical files, selected after the targeting of coding summaries, is organized. The aim is to make any corrections to the diagnoses or coded procedures with a potential impact on the pricing of the stay. Targeting is of major importance as a means of concentrating resources on the files for which coding can be effectively improved. The tools available for targeting can be optimized. We have developed a decision-making support tool to make targeting more efficient. The objective of our study was to evaluate the performance of this tool. METHODS: The tool combines an artificial intelligence module with a rule-based expert module. A predictive score is assigned to each coding summary that reflects the probability of a revalued stay. Evaluation of the performance of this tool was based on a sample of 400 stays of at least 3 nights of patients hospitalized at the Paris Saint-Joseph Hospital from 1st November to 31st December 2019. Each stay was reviewed by a coding expert, without knowledge of the score assigned and without help from expert queries. Two main assessment criteria were used: area under the ROC curve and positive predictive value (PPV). RESULTS: The area under the ROC curve was 0.70 (CI 95% [0.64-0.76]). With a revalued coding rate of 32%, PPV was 41% for scores above 5, 65% for scores above 8, 88% for scores above 9. CONCLUSION: The study made it possible to validate the performance of the tool. The implementation of new variables could further increase its performance. This is an area of development to be considered, particularly with in view of generalizing individual invoicing in hospitals.

Near ground horizontal high resolution Cn2 profiling from Shack-Hartmann slopeand scintillation data.

Coupled slope and scintillation detection and ranging (CO-SLIDAR) is a very promising technique for the metrology of near ground Cn2 profiles. It exploits both phase and scintillation measurements obtained with a dedicated wavefront sensor and allows profiling on the full line of sight between pupil and sources. This technique is applied to an associated instrument based on a mid-IR Shack-Hartmann wavefront sensor coupled to a 0.35 m telescope, which observes two cooperative sources. This paper presents what we believe is the first comprehensive description of the CO-SLIDAR method in the context of near-ground optical turbulence metrology. It includes the presentation of the physics principles underlying the measurements of our unsupervised Cn2 profile reconstruction strategy together with the error bar estimation on the reconstructed values. The application to data acquired in a heterogeneous rural landscape during an experimental campaign in Lannemezan, France, demonstrates the ability to obtain profiles with a sampling pitch of about 220 m over a 2.7 km line of sight. The retrieved Cn2 profiles are presented and their variability in space and time is discussed.

Time location sampling in men who have sex with men in the HIV context: the importance of taking into account sampling weights and frequency of venue attendance.

Sex between men is the most frequent mode of HIV transmission in industrialised countries. Monitoring risk behaviours among men who have sex with men (MSM) is crucial, especially to understand the drivers of the epidemic. A cross-sectional survey (PREVAGAY), based on time-location sampling, was conducted in 2015 among MSM attending gay venues in 5 metropolitan cities in France. We applied the generalised weight share method (GWSM) to estimate HIV seroprevalence for the first time in this population, taking into account the frequency of venue attendance (FVA). Our objectives were to describe the implementation of the sampling design and to demonstrate the importance of taking into account sampling weights, including FVA by comparing results obtained by GWSM and by other methods which use sample weights not including FVA or no weight. We found a global prevalence of 14.3% (95% CI (12.0-16.9)) using GWSM and an unweighted prevalence of 16.4% (95% CI (14.9-17.8)). Variance in HIV prevalence estimates in each city was lower when we did not take into account either the sampling weights or the FVA. We also highlighted an association of FVA and serological status in the most of investigated cities.

[Factors associated with suicide attempts by sexual minorities: Results from the 2011 gay and lesbian survey]. / Facteurs associés aux tentatives de suicide chez les minorités sexuelles : résultats de l'enquête presse gays et lesbiennes 2011.

BACKGROUND: Since the 1990s, several studies have found higher rates of suicide attempts in homosexuals and bisexuals than in heterosexuals. The current challenge is to identify risk factors for targeting prevention. The aim of this paper was to determine, for the first time in France, the prevalence of suicide attempts over a 12-month period and associated factors in a population of men and women who self-identified as homosexuals or bisexuals. METHODS: A convenience sample cross-sectional survey was conducted in 2011 using an anonymous self-administered questionnaire made available in the gay press, and Internet sites targeting the gay or lesbian community. Among the persons completing the questionnaire, 10,100 men and 2963 women residing in France answered the questions on suicide attempts. The factors associated with suicide attempts during the previous 12 months were identified by logistic regression. RESULTS: Lifetime prevalence for suicide attempts was 16% in men and 18% in women; 12-month prevalence was 1.6% in men and 1.9% in women. Factors independently associated with suicide attempts in the past 12 months in men and women were lack of occupational activity, victim of sexual abuse, termination of a long-term relationship, excessive alcohol consumption in the past 12 months, depression, and in addition, in men, living in a small locality, victim of verbal or physical aggression and use of anxiolytics. CONCLUSION: According to our results, the fight against homophobia is an important element for the prevention of suicide attempts among homosexual and bisexual men. Indeed, in addition to traditional risk factors for suicide attempt, a significant association was also found with homophobic aggression in the past year.

Reorganization of large-scale cognitive networks during automation of imagination of a complex sequential movement.

We investigated the functional reconfiguration of the cerebral networks involved in imagination of sequential movements of the left foot, both performed at regular and fast speed after mental imagery training. Thirty-five volunteers were scanned with a 3T MRI while they imagined a sequence of ankle movements (dorsiflexion, plantar flexion, varus and valgus) before and after mental practice. Subjects were distributed in two groups: the first group executed regular movements whereas the second group made fast movements. We applied the general linear model (GLM) and model-free, exploratory tensorial independent component analytic (TICA) approaches to identify plastic post-training effects on brain activation. GLM showed that post-training imagination of movement was accompanied by a dual effect: a specific recruitment of a medial prefronto-cingulo-parietal circuit reminiscent of the default-mode network, with the left putamen, and a decreased activity of a lateral fronto-parietal network. Training-related subcortical changes only consisted in an increased activity in the left striatum. Unexpectedly, no difference was observed in the cerebellum. TICA also revealed involvement of the left executive network, and of the dorsal control executive network but no significant differences were found between pre- and post-training phases. Therefore, repetitive motor mental imagery induced specific putamen (motor rehearsal) recruitment that one previously observed during learning of overt movements, and, simultaneously, a specific shift of activity from the dorsolateral prefrontal cortex (attention, working memory) to the medial posterior parietal and cingulate cortices (mental imagery and memory rehearsal). Our data complement and confirm the notion that differential and coupled recruitment of cognitive networks can constitute a neural marker of training effects.

Brain areas involved in the control of speed during a motor sequence of the foot: real movement versus mental imagery.

We investigated the cerebral networks involved in execution and mental imagery of sequential movements of the left foot, both performed at slow and fast speed. Twelve volunteers were scanned with a 3T MRI during execution and imagination of a sequence of ankle movements. Overt movement execution and motor imagery shared a common network including the premotor, parietal and cingulate cortices, the striatum and the cerebellum. Motor imagery recruited specifically the prefrontal cortex, whereas motor execution recruited specifically the sensorimotor cortex. We also found that slow movements specifically recruited frontopolar and right dorsomedian prefrontal areas bilaterally, during both execution and mental imagery, whereas fast movements strongly activated the sensorimotor cerebral cortex. Finally, we noted that anterior vermis, lobules VI/VII and VIII of the cerebellum were specifically activated during fast movements, both in imagination and execution. We show that the selection of the neural networks underlying voluntary movement of the foot is depending on the speed strategy and is sensitive to execution versus imagery. Moreover, to the light of surprising recent findings in monkeys showing that the vermis should no longer be considered as entirely isolated from the cerebral cortex (Coffman et al., 2011 [2]), we suggest that the anterior vermis contributes to computational aspects of fast commands, whereas more lateral cerebellar superior lobe and lobule VIII would regulate patterning and sequencing of submovements in conjunction with movement rate. We also suggest that execution of overt slow movements, which strongly involves prefrontal executive cortex as during motor mental imagery, is associated with conscious mental representation of the ongoing movements.

A novel immunoassay using recombinant allergens simplifies peanut allergy diagnosis.

BACKGROUND: Double-blind placebo-controlled food challenge (DBPCFC) is currently considered the gold standard for peanut allergy diagnosis. However, this procedure that requires the hospitalization of patients, mostly children, in specialized centers for oral exposure to allergens may cause severe reactions requiring emergency measures. Thus, a simpler and safer diagnosis procedure is needed. The aim of this study was to evaluate the diagnostic performance of a new set of in vitro blood tests for peanut allergy. METHODS: The levels of IgE directed towards peanut extract and recombinant peanut allergens Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 7, and Ara h 8 were measured in 3 groups of patients enrolled at 2 independent centers: patients with proven peanut allergy (n=166); pollen-sensitized subjects without peanut allergy (n=61), and control subjects without allergic disease (n=10). RESULTS: Seventy-nine percent of the pollen-sensitized patients showed IgE binding to peanut, despite their tolerance to peanut. In contrast, combining the results of specific IgE to peanut extract and to recombinant Ara h 2 and Ara h 6 yielded a peanut allergy diagnosis with a 98% sensitivity and an 85% specificity at a positivity threshold of 0.10 kU/l. Use of a threshold of 0.23 kU/l for recombinant Ara h 2 increased specificity (96%) at the cost of sensitivity (93%). CONCLUSION: A simple blood test can be used to diagnose peanut allergy with a high level of precision. However, DBPCFC will remain useful for the few cases where immunological and clinical observations yield conflicting results.

QTL for resistance to summer mortality and OsHV-1 load in the Pacific oyster (Crassostrea gigas).

Summer mortality is a phenomenon severely affecting the aquaculture production of the Pacific oyster (Crassostrea gigas). Although its causal factors are complex, resistance to mortality has been described as a highly heritable trait, and several pathogens including the virus Ostreid Herpes virus type 1 (OsHV-1) have been associated with this phenomenon. A QTL analysis for survival of summer mortality and OsHV-1 load, estimated using real-time PCR, was performed using five F(2) full-sib families resulting from a divergent selection experiment for resistance to summer mortality. A consensus linkage map was built using 29 SNPs and 51 microsatellite markers. Five significant QTL were identified and assigned to linkage groups V, VI, VII and IX. Analysis of single full-sib families revealed differential QTL segregation between families. QTL for the two-recorded traits presented very similar locations, highlighting the interest of further study of their respective genetic controls. These QTL show substantial genetic variation in resistance to summer mortality, and present new opportunities for selection for resistance to OsHV-1.

Single Nucleotide polymorphisms and their relationship to codon usage bias in the Pacific oyster Crassostrea gigas.

DNA sequence polymorphism and codon usage bias were investigated in a set of 41 nuclear loci in the Pacific oyster Crassostrea gigas. Our results revealed a very high level of DNA polymorphism in oysters, in the order of magnitude of the highest levels reported in animals to date. A total of 290 single nucleotide polymorphisms (SNPs) were detected, 76 of which being localised in exons and 214 in non-coding regions. Average density of SNPs was estimated to be one SNP every 60 bp in coding regions and one every 40 bp in non-coding regions. Non-synonymous substitutions contributed substantially to the polymorphism observed in coding regions. The non-synonymous to silent diversity ratio was 0.16 on average, which is fairly higher to the ratio reported in other invertebrate species recognised to display large population sizes. Therefore, purifying selection does not appear to be as strong as it could have been expected for a species with a large effective population size. The level of non-synonymous diversity varied greatly from one gene to another, in accordance with varying selective constraints. We examined codon usage bias and its relationship with DNA polymorphism. The table of optimal codons was deduced from the analysis of an EST dataset, using EST counts as a rough assessment of gene expression. As recently observed in some other taxa, we found a strong and significant negative relationship between codon bias and non-synonymous diversity suggesting correlated selective constraints on synonymous and non-synonymous substitutions. Codon bias as measured by the frequency of optimal codons for expression might therefore provide a useful indicator of the level of constraint upon proteins in the oyster genome.

Unexpected thymic hyperplasia in transgenic mice harboring a neuronal promoter fused with simian virus 40 large T antigen.

The hypothalamic peptide growth hormone-releasing factor (GRF) regulates the secretion and production of growth hormone from the anterior pituitary (M. C. Gelato and G. R. Merriam, Annu. Rev. Physiol. 48:569-591). To study GRF gene regulation, transgenic mice were generated that harbor the human GRF promoter fused to the coding sequences from the simian virus 40 early region. These mice had normal hypothalamic functions but unexpectedly suffered from severe thymic hyperplasia. Immunohistochemical analysis revealed that large T antigen was expressed in the thymic epithelial cells. These cells have endocrine properties and are known to produce thymic hormones [corrected]. The thymic hyperplasia was the apparent consequence of inappropriate production of T-cell maturation factors by epithelial cells and could involve increased self renewal of apparently normal T stem cells in the thymus.

Effects of monoclonal antibodies that block transferrin receptor function on the in vivo growth of a syngeneic murine leukemia.

The ability of monoclonal antibodies (MAbs) against the murine transferrin receptor to inhibit the growth of transplanted syngeneic AKR/J SL-2 leukemic cells has been investigated. Two rat IgM antibodies, RI7 208 and REM 17.2, which both block transferrin receptor function, inhibited the growth of SL-2 leukemic cells in vitro at concentrations of 5-10 micrograms per ml. However, RI7 208 was more effective than REM 17.2 in prolonging survival of tumor-bearing mice. The antitumor effects of RI7 208 MAb were dependent on both the antibody dose and number of leukemic cells inoculated. The serum clearance of [75Se]methionine-labeled RI7 208 and REM 17.2 antibodies was similar and consisted of an initial rapid phase over the first 2 days followed by a slower phase. A single dose of 2 mg of antibody maintained a serum MAb concentration (greater than 10 micrograms/ml) sufficient to inhibit SL-2 leukemic cell growth in vitro for 2-3 days. The liver, kidney, and spleen were the major sites at which each of the antibodies accumulated regardless of whether trace or saturating amounts of antibody were administered. The specific activity of antibody found in s.c. SL-2 tumors was about 2-fold less than that of liver. It was shown that multiple doses of R17 208 MAb administered on a schedule aimed at maintaining a therapeutic serum level of MAb for 1-3 weeks were more effective than a single dose. Further, administration of RI7 208 MAb, in combination with the anti-Thy-1.1 MAb 19E12, was more effective than either antibody alone. SL-2 mutant cells were selected that were resistant to growth inhibitory effects of RI7 208 in vitro. The effects of RI7 208 MAb on the growth of these mutant cells in vivo suggests the major mechanism by which the MAb inhibits SL-2 tumor growth is by directly blocking receptor function. Acute toxicity associated with administration of the MAb was minimal. However, assays of myeloid and erythroid colony-forming units in bone marrow and spleen of mice given multiple doses of RI7 208 showed a depression of stem cell activity in bone marrow and elevated numbers of erythroid and cellular colony-forming units in the spleen.

Iron regulation and pathogenicity in Erwinia chrysanthemi 3937: role of the Fur repressor protein.

Low iron availability is a triggering signal for coordinated expression of the genes encoding pectate lyases PelB, PelC, PelD, and PelE, and chrysobactin iron transport functions, which are two main determinants of phytopathogenicity of the Erwinia chrysanthemi strain 3937. The possible implication of the ferric uptake regulation (Fur) protein in this process was investigated. The E. chrysanthemi fur gene was cloned by functional complementation of an Escherichia coli fur mutant and sequenced. The 444-bp open reading frame identified was found to code for a protein highly similar to the E. coli Fur regulator. An E. chrysanthemi fur null mutant was constructed by reverse genetics. This mutant showed altered growth capacity and reduced pathogenicity on African violets. In a fur background, transcriptional lacZ fusions to genes belonging to the E. chrysanthemi high affinity iron transport systems were constitutively expressed. Transcription of the pelA, pelD, and pelE genes was analyzed, using fusions to the uidA reporter gene. Iron availability and a fur mutation did not influence the expression of pelA. In the presence of iron, pelD and pelE transcription levels were higher in the fur mutant than in the parental strain. Furthermore, iron deficiency stimulated the expression of both fusions in the fur mutant. These findings indicate that, in E. chrysanthemi 3937, (i) Fur negatively controls iron transport and genes encoding PelD and PelE, and (ii) additional factor(s) mediate iron regulation of the pel genes.

Essential role of superoxide dismutase on the pathogenicity of Erwinia chrysanthemi strain 3937.

The sodA gene from Erwinia chrysanthemi strain 3937 was cloned by functional complementation of an Escherichia coli sodA sodB mutant and sequenced. We identified a 639-bp open reading frame, which encodes a protein that is 85% identical to the E. coli manganese-containing superoxide dismutase MnSOD. Promoter elements of this gene were identified by transcriptional mapping experiments. We constructed an E. chrysanthemi deltasodA mutant by reverse genetics. The deltasodA mutation resulted in the absence of a cytoplasmic SOD, which displays the same characteristics as those of MnSOD. The deltasodA mutant was more sensitive to paraquat than the wild-type strain. This mutant could macerate potato tubers, similar to the wild-type strain. In contrast, when inoculated on African violets, the mutant produced, at most, only small necrotic lesions. If the inoculum was supplemented with the superoxide anion-scavenging metalloporphyrin MnTMPyP or purified SOD and catalase, the deltasodA mutant was able to macerate the inoculated zone. Generation of superoxide anion by African violet leaves inoculated with E. chrysanthemi was demonstrated with nitroblue tetrazolium as an indicator. Therefore, at the onset of infection, E. chrysanthemi cells encounter an oxidative environment and require active protective systems against oxidative damages such as MnSOD to overcome these types of conditions.

The human leucocyte-common (LC) molecule: dissection of leukaemias using monoclonal antibodies directed against framework and restricted antigenic determinants.

Monoclonal antibodies have previously been raised against two separate antigenic determinants on the human LC molecule. One, F10.89.4, recognizes a 'framework' epitope on all LC molecules; these are found on the majority of leucocytes. The other, F8.11.13, recognizes only a 'restricted' epitope present on a subset of these molecules; this subset is found on B lymphocytes and a subpopulation of T lymphocytes. LC molecules on myeloid cells do not carry the 'restricted' antigenic determinant. We have investigated the differential expression of these LC epitopes on human leukaemias, using immunofluorescence on fresh leukaemic blasts and established cell lines. Our study shows that, as on normal haemopoietic cells, LC molecules on B leukaemias bear both 'framework' and 'restricted' epitopes, while the majority of T leukaemias bear only the 'framework' determinant. The small proportion of T cells that are F8.11.13+ ('restricted' epitope) are relatively mature, being of either OKT4+ or OKT8+ phenotype, and may be in an activated state (HLA-DR+). However, in contrast to normal haemopoietic cells, some myeloid leukaemias carry both 'framework' and 'restricted' epitopes (30% AML and AMML samples are F10.89.4+, F8.11.13+), and it is within this group that all TdT+ AML and AMML cases lie. Thus, these monoclonal antibodies should be useful for studying haemopoiesis in man and for analyzing human haemopoietic malignancies.

Preclinical profile of befloxatone, a new reversible MAO-A inhibitor.

Befloxatone, a novel oxazolidinone derivative, is a potent, selective and reversible monoamine oxidase A (MAO-A) inhibitor in vitro (K1A = 1.9-3.6 nM) and ex vivo (ED50 MAO-A = 0.02 mg/kg, p.o.). It does not interact with a large number of receptors, monoamine transporters or other amine oxidases. Binding studies with [3H]-befloxatone in rat brain sections show that it labels with high affinity (Kd = 1.3 nM) a single population of sites with the pharmacological characteristics and regional distribution of MAO-A. In the rat brain, befloxatone (0.75 mg/kg, i.p.) increases tissue levels of monoamines and decreases levels of their deaminated metabolites. Acute administration of befloxatone (0.75 mg/kg, i.p.) induces an increase in extracellular striatal dopamine and cortical norepinephrine but not cortical serotonin levels in the rat. Befloxatone (1 mg/kg, i.p.) potently inhibits the firing rate of serotonergic neurons, partially decreases the firing of noradrenergic neurons and has no effect on the firing of dopaminergic neurons (a mirror image of its effects on monoamine release in terminal regions), suggesting that the relative effects of befloxatone on monoamine release may be governed by autoreceptor-mediated control of monoaminergic neurons at the cell body level. Befloxatone (0.03-0.3 mg/kg, p.o.) exhibits potent activity in behavioural models predictive of antidepressant activity. Befloxatone (up to 1.5 mg/kg, p.o.) does not potentiate the pressor effects of orally administered tyramine at centrally active doses and duodenal [3H]-befloxatone binding is displaced by increasing doses of orally administered tyramine (0.1-40 mg/kg, i.p.). These results suggest that befloxatone is a potent reversible MAO-A inhibitor with antidepressant potential and a wide safety margin with regard to the potentiation of the pressor effect of tyramine.

Isepamicin once daily plus ceftriaxone versus amikacin plus ceftriaxone in febrile neutropenic patients.

Isepamicin is a new aminoglycoside with in-vitro activity superior to amikacin. It is a poor substrate for the 6'-aminoacetyltransferase-I enzyme which inactivates amikacin and therefore organisms possessing this enzyme are not resistant to isepamicin. The aim of this study was to compare the efficacy and safety of co-administration of isepamicin once daily plus ceftriaxone to amikacin twice daily plus ceftriaxone to amikacin twice daily plus ceftriaxone in febrile neutropenic cancer patients. Febrile episodes in 235 patients (156 in isepamicin group and 79 in amikacin group) were treated in this study. They occurred in 218 different patients. Fifteen patients were enrolled twice and one three times. Response rates to the two treatment regimens for microbiologically documented episodes, clinically documented episodes and further unexplained fever were similar. Tolerance of the treatment regimens, as measured by serum creatinine levels, hypoaccousia and cutaneous allergy was also similar in both treatment groups. In conclusion, isepamicin given once daily when combined with ceftriaxone in the treatment of febrile episodes in neutropenic cancer patients was as effective and no more toxic than amikacin.

Genome-wide patterns of divergence during speciation: the lake whitefish case study.

The nature, size and distribution of the genomic regions underlying divergence and promoting reproductive isolation remain largely unknown. Here, we summarize ongoing efforts using young (12 000 yr BP) species pairs of lake whitefish (Coregonus clupeaformis) to expand our understanding of the initial genomic patterns of divergence observed during speciation. Our results confirmed the predictions that: (i) on average, phenotypic quantitative trait loci (pQTL) show higher F(ST) values and are more likely to be outliers (and therefore candidates for being targets of divergent selection) than non-pQTL markers; (ii) large islands of divergence rather than small independent regions under selection characterize the early stages of adaptive divergence of lake whitefish; and (iii) there is a general trend towards an increase in terms of numbers and size of genomic regions of divergence from the least (East L.) to the most differentiated species pair (Cliff L.). This is consistent with previous estimates of reproductive isolation between these species pairs being driven by the same selective forces responsible for environment specialization. Altogether, dwarf and normal whitefish species pairs represent a continuum of both morphological and genomic differentiation contributing to ecological speciation. Admittedly, much progress is still required to more finely map and circumscribe genomic islands of speciation. This will be achieved through the use of next generation sequencing data but also through a better quantification of phenotypic traits moulded by selection as organisms adapt to new environmental conditions.