Artificial barriers prevent genetic recovery of small isolated populations of a low-mobility freshwater fish.

Habitat loss and fragmentation often result in small, isolated populations vulnerable to environmental disturbance and loss of genetic diversity. Low genetic diversity can increase extinction risk of small populations by elevating inbreeding and inbreeding depression, and reducing adaptive potential. Due to their linear nature and extensive use by humans, freshwater ecosystems are especially vulnerable to habitat loss and fragmentation. Although the effects of fragmentation on genetic structure have been extensively studied in migratory fishes, they are less understood in low-mobility species. We estimated impacts of instream barriers on genetic structure and diversity of the low-mobility river blackfish (Gadopsis marmoratus) within five streams separated by weirs or dams constructed 45-120 years ago. We found evidence of small-scale (<13 km) genetic structure within reaches unimpeded by barriers, as expected for a fish with low mobility. Genetic diversity was lower above barriers in small streams only, regardless of barrier age. In particular, one isolated population showed evidence of a recent bottleneck and inbreeding. Differentiation above and below the barrier (FST = 0.13) was greatest in this stream, but in other streams did not differ from background levels. Spatially explicit simulations suggest that short-term barrier effects would not be detected with our data set unless effective population sizes were very small (<100). Our study highlights that, in structured populations, the ability to detect short-term genetic effects from barriers is reduced and requires more genetic markers compared to panmictic populations. We also demonstrate the importance of accounting for natural population genetic structure in fragmentation studies.

Thermal plasticity in Drosophila melanogaster populations from eastern Australia: quantitative traits to transcripts.

The flexibility afforded to genotypes in different environments by phenotypic plasticity is of interest to biologists studying thermal adaptation because of the thermal lability of many traits. Differences in thermal performance and reaction norms can provide insight into the evolution of thermal adaptation to explore broader questions such as species distributions and persistence under climate change. One approach is to study the effects of temperature on fitness, morphological and more recently gene expression traits in populations from different climatic origins. The diverse climatic conditions experienced by Drosophila melanogaster along the eastern Australian temperate-tropical gradient are ideal given the high degree of continuous trait differentiation, but reaction norm variation has not been well studied in this system. Here, we reared a tropical and temperate population from the ends of the gradient over six developmental temperatures and examined reaction norm variation for five quantitative traits including thermal performance for fecundity, and reaction norms for thermotolerance, body size, viability and 23 transcript-level traits. Despite genetic variation for some quantitative traits, we found no differentiation between the populations for fecundity thermal optima and breadth, and the reaction norms for the other traits were largely parallel, supporting previous work suggesting that thermal evolution occurs by changes in trait means rather than by reaction norm shifts. We examined reaction norm variation in our expanded thermal regime for a gene set shown to previously exhibit GxE for expression plasticity in east Australian flies, as well as key heat-shock genes. Although there were differences in curvature between the populations suggesting a higher degree of thermal plasticity in expression patterns than for the quantitative traits, we found little evidence to support a role for genetic variation in maintaining expression plasticity.

[Cost comparison of two reprocessing procedures of flexible ureteroscopes at the University Hospital of Dijon]. / Comparaison de coûts de deux modalités de retraitement des urétéroscopes souples au CHU de Dijon.

INTRODUCTION: The University Hospital of Dijon has selected sterilization for some of its flexible endoscopes. The decision came as part of an acquisition of a low-temperature sterilizer. The objective is to compare the actual cost of reprocessing a heat-sensitive ureteroscope by sterilization to a high-level disinfection (HLD) in semi-automatic bench. MATERIAL AND METHODS: From June 1 to December 31, 2013, the ureteroscope has been exclusively reprocessed by low-temperature sterilization (LTS). In parallel, the theorical number of peracetic acid disinfection that should have been made was simulated. An observational study of actual costs by micro-costing technique allowed us to determine the set of resources consumed by each of these strategies. Specific costs of sterilization were from the billing terms provided with the central sterile services department. RESULTS: During the 7 months of study, the ureteroscope was used and sterilized 11 times. Thirty-two chemical disinfection procedures would have been necessary. Comparing these two strategies, a cost difference is highlighted for the LTS with a real economy of 43.8% compared with HLD (1154.77 € versus 649.40 €). CONCLUSION: All in all, this micro-economic study confirms and strengthens our previous decision for selecting LTS for heat-sensitive ureteroscopes. On top of better micro-economic outcomes, it also provides benefits in theoretical risk analysis of transmission of infection.

No patterns in thermal plasticity along a latitudinal gradient in Drosophila simulans from eastern Australia.

Phenotypic plasticity may be an important initial mechanism to counter environmental change, yet we know relatively little about the evolution of plasticity in nature. Species with widespread distributions are expected to have evolved higher levels of plasticity compared with those with more restricted, tropical distributions. At the intraspecific level, temperate populations are expected to have evolved higher levels of plasticity than their tropical counterparts. However, empirical support for these expectations is limited. In addition, no studies have comprehensively examined the evolution of thermal plasticity across life stages. Using populations of Drosophila simulans collected from a latitudinal cline spanning the entire east coast of Australia, we assessed thermal plasticity, measured as hardening capacity (the difference between basal and hardened thermal tolerance) for multiple measures of heat and cold tolerance across both adult and larval stages of development. This allowed us to explicitly ask whether the evolution of thermal plasticity is favoured in more variable, temperate environments. We found no relationship between thermal plasticity and latitude, providing little support for the hypothesis that temperate populations have evolved higher levels of thermal plasticity than their tropical counterparts. With the exception of adult heat survival, we also found no association between plasticity and ten climatic variables, indicating that the evolution of thermal plasticity is not easily predicted by the type of environment that a particular population occupies. We discuss these results in the context of the role of plasticity in a warming climate.

Frequency of dosage prescribing medication errors associated with manual prescriptions for very preterm infants.

WHAT IS KNOWN AND OBJECTIVE: The risk of dosage Prescription Medication Error (PME) among manually written prescriptions within 'mixed' prescribing system (computerized physician order entry (CPOE) + manual prescriptions) has not been previously assessed in neonatology. This study aimed to evaluate the rate of dosage PME related to manual prescriptions in the high-risk population of very preterm infants (GA < 33 weeks) in a mixed prescription system. METHODS: The study was based on a retrospective review of a random sample of manual daily prescriptions in two neonatal intensive care units (NICU) A and B, located in different French University hospitals (Dijon and La Reunion island). Daily prescription was defined as the set of all drugs manually prescribed on a single day for one patient. Dosage error was defined as a deviation of at least ±10% from the weight-appropriate recommended dose. RESULTS AND DISCUSSION: The analyses were based on the assessment of 676 manually prescribed drugs from NICU A (58 different drugs from 93 newborns and 240 daily prescriptions) and 354 manually prescribed drugs from NICU B (73 different drugs from 131 newborns and 241 daily prescriptions). The dosage error rate per 100 manually prescribed drugs was similar in both NICU: 3·8% (95% CI: 2·5-5·6%) in NICU A and 3·1% (95% CI: 1·6-5·5%) in NICU B (P = 0·54). Among all the 37 identified dosage errors, the over-dosing was almost as frequent as the under-dosing (17 and 20 errors, respectively). Potentially severe dosage errors occurred in a total of seven drug prescriptions. None of the dosage PME was recorded in the corresponding medical files and information on clinical outcome was not sufficient to identify clinical conditions related to dosage PME. Overall, 46·8% of manually prescribed drugs were off label or unlicensed, with no significant differences between prescriptions with or without dosage error. The risk of a dosage PME increased significantly if the drug was included in the CPOE system but was manually prescribed (OR = 3·3; 95% CI: 1·6-7·0, P < 0·001). WHAT IS NEW AND CONCLUSION: The presence of dosage PME in the manual prescriptions written within mixed prescription systems suggests that manual prescriptions should be totally avoided in neonatal units.

Generic vancomycin products: Analysis of serum concentrations in patients with acute myeloid leukemia.

UNLABELLED: Concerns have recently emerged about the quality of generic vancomycin products. Our aim is to analyze serum vancomycin concentrations measured 48 hours after the start of an empirical treatment regimen in patients with acute myeloid leukemia (AML) who received one of the two generic vancomycin products available in France. PATIENTS AND METHODS: Seventy-nine AML patients treated with vancomycin during two study periods were included in the study. Our vancomycin dosing regimen was based on the patients' total body weight adjusted for renal clearance. RESULTS: A total of 93 serum vancomycin concentrations were collected: 31 in period 1 and 62 in period 2. In bivariate analysis, the mean serum vancomycin concentrations were not significantly different (19.9 ± 11.2 mg/L in period 1 vs 18.9 ± 6.0 mg/L in period 2, P=0.64). In the final generalized estimating equations model, serum vancomycin concentrations correlated statistically with a positive coefficient for age (P<0.001) and with negative coefficients for male sex (P=0.001) and hemoglobin level (P=0.021). CONCLUSION: Serum vancomycin concentrations measured 48 hours after the start of an empirical treatment were not influenced by the nature of the generic product but correlated with age, sex and hemoglobin level in AML patients.

Multivariate analysis of adaptive capacity for upper thermal limits in Drosophila simulans.

Thermal tolerance is an important factor influencing the distribution of ectotherms, but our understanding of the ability of species to evolve different thermal limits is limited. Based on univariate measures of adaptive capacity, it has recently been suggested that species may have limited evolutionary potential to extend their upper thermal limits under ramping temperature conditions that better reflect heat stress in nature. To test these findings more broadly, we used a paternal half-sibling breeding design to estimate the multivariate evolutionary potential for upper thermal limits in Drosophila simulans. We assessed heat tolerance using static (basal and hardened) and ramping assays. Our analyses revealed significant evolutionary potential for all three measures of heat tolerance. Additive genetic variances were significantly different from zero for all three traits. Our G matrix analysis revealed that all three traits would contribute to a response to selection for increased heat tolerance. Significant additive genetic covariances and additive genetic correlations between static basal and hardened heat-knockdown time, marginally nonsignificant between static basal and ramping heat-knockdown time, indicate that direct and correlated responses to selection for increased upper thermal limits are possible. Thus, combinations of all three traits will contribute to the evolution of upper thermal limits in response to selection imposed by a warming climate. Reliance on univariate estimates of evolutionary potential may not provide accurate insight into the ability of organisms to evolve upper thermal limits in nature.

[Admissions to a coronary care unit for severe iatrogenic conditions: a prospective study of 7244 patients]. / Les admissions pour iatrogénie sévère en unité de soins intensifs de cardiologie: étude prospective sur 7244 patients.

INTRODUCTION: Iatrogenic complications are defined as adverse drug reactions or complications induced by non-drug interventions, such as cardiac devices or stimulation techniques. Iatrogenic complications occurring during hospital stay are known to be associated with increased hospital length of stay and mortality. Only few data are available on iatrogenic as cause of hospital admission, particularly in coronary care unit. In patient admitted in coronary care unit for iatrogenic, we aimed: (a) to analyse their prevalence, type and characteristics, (b) to analyse their in-hospital length of stay and mortality and (c) to evaluate the predictive factors of severity and mortality. METHODS: From 1st April 2008 to 31 January 2012, all the consecutive admissions caused by iatrogenic complications at the coronary care unit were prospectively included and classified in two groups: (1) pharmacological iatrogenic (beta-blockers, digoxin, calcium channel blockers, cordarone, several antiarrhythmic , anticoagulants, antiplatelets and others), (2) non-pharmacological iatrogenic (pacemaker, cardioverter-defibrillator, radiofrequency, coronary angiography and cardiac surgery including valve surgery). We excluded patients with intentional overdose. We also compared patients according to the severity (group 1: patients who just need a monitoring; and group 2: patients for whom there was invasive procedure or for whom we used vasoactive amine). RESULTS: Among 7244 patients admitted in coronary care unit during the inclusion period, 250 (3.4%) were admitted for iatrogenic complication, 136 in pharmacological group and 114 in non-pharmacological group. In non-pharmacological group, there was more men: 73.7% vs. 47.8% (P < 0.001), patients are younger: 67.3 ± 13.2 vs. 75.4 ± 15.8 (P < 0.001) and are more severe: 80.4% in group 2 vs. 69.4% (P = 0.05). The mortality in this group tends to be more important. According to the severity, there is no difference about drugs: 7.4 ± 3.4 vs. 6.8 ± 2.9 (P = 0.184) and are staying longer in hospital: 4.7 ± 3.2 days vs. 3.4 ± 2.4 (P = 0.009) for coronary care unit length of stay and 15 ± 13.7 vs. 10 ± 9.8 (P = 0.003) for total length of stay. CONCLUSION: Iatrogenic represent a non-negligible cause of admission in coronary care unit, which associated with significant mortality (8.8%) and with a trend toward a higher length of stay. Further studies are needed to determinate the origin of mortality and to better characterize patients at risk of iatrogenic.

[Medication errors in neonatal medicine: from prescription to administration]. / Prévention des erreurs médicamenteuses en néonatologie : de la prescription à l'administration.

Neonatal units have the highest incidence of medication errors (approximately 5%) compared to adult and pediatric wards. Medication errors include prescribing errors, transcription errors, dispensing errors, medication administration errors, and monitoring. Dosing error is the most common prescribing error. Prevention of medication error must be global. The implementation of a computerized physician order entry significantly reduces prescribing errors but other preventive measures remain necessary.

Complex patterns of local adaptation in heat tolerance in Drosophila simulans from eastern Australia.

Latitudinal clines are considered a powerful means of investigating evolutionary responses to climatic selection in nature. However, most clinal studies of climatic adaptation in Drosophila have involved species that contain cosmopolitan inversion polymorphisms that show clinal patterns themselves, making it difficult to determine whether the traits or inversions are under selection. Further, although climatic selection is unlikely to act on only one life stage in metamorphic organisms, a few studies have examined clinal patterns across life stages. Finally, clinal patterns of heat tolerance may also depend on the assay used. To unravel these potentially confounding effects on clinal patterns of thermal tolerance, we examined adult and larval heat tolerance traits in populations of Drosophila simulans from eastern Australia using static and dynamic (ramping 0.06 °C min(-1)) assays. We also used microsatellites markers to clarify whether demographic factors or selection are responsible for population differentiation along clines. Significant cubic clinal patterns were observed for adult static basal, hardened and dynamic heat knockdown time and static basal heat survival in larvae. In contrast, static, hardened larval heat survival increased linearly with latitude whereas no clinal association was found for larval ramping survival. Significant associations between adult and larval traits and climatic variables, and low population differentiation at microsatellite loci, suggest a role for climatic selection, rather than demographic processes, in generating these clinal patterns. Our results suggest that adaptation to thermal stress may be species and life-stage specific, complicating our efforts to understand the evolutionary responses to selection for increasing thermotolerance.

A multivariate test of evolutionary constraints for thermal tolerance in Drosophila melanogaster.

Exposure to extreme temperatures is increasingly likely to impose strong selection on many organisms in their natural environments. The ability of organisms to adapt to such selective pressures will be determined by patterns of genetic variation and covariation. Despite increasing interest in thermal adaptation, few studies have examined the extent to which the genetic covariance between traits might constrain thermal responses. Furthermore, it remains unknown whether sex-specific genetic architectures will constrain responses to climatic selection. We used a paternal half-sibling breeding design to examine whether sex-specific genetic architectures and genetic covariances between traits might constrain evolutionary responses to warming climates in a population of Drosophila melanogaster. Our results suggest that the sexes share a common genetic underpinning for heat tolerance as indicated by a strong positive inter-sexual genetic correlation. Further, we found no evidence in either of the sexes that genetic trade-offs between heat tolerance and fitness will constrain responses to thermal selection. Our results suggest that neither trade-offs, nor sex-specific genetics, will significantly constrain an evolutionary response to climatic warming, at least in this population of D. melanogaster.

A comprehensive assessment of geographic variation in heat tolerance and hardening capacity in populations of Drosophila melanogaster from eastern Australia.

We examined latitudinal variation in adult and larval heat tolerance in Drosophila melanogaster from eastern Australia. Adults were assessed using static and ramping assays. Basal and hardened static heat knockdown time showed significant linear clines; heat tolerance increased towards the tropics, particularly for hardened flies, suggesting that tropical populations have a greater hardening response. A similar pattern was evident for ramping heat knockdown time at 0.06°C min(-1) increase. There was no cline for ramping heat knockdown temperature (CT(max) ) at 0.1°C min(-1) increase. Acute (static) heat knockdown temperature increased towards temperate latitudes, probably reflecting a greater capacity of temperate flies to withstand sudden temperature increases during summer in temperate Australia. Larval viability showed a quadratic association with latitude under heat stress. Thus, patterns of heat resistance depend on assay methods. Genetic correlations in thermotolerance across life stages and evolutionary potential for critical thermal limits should be the focus of future studies.

Investigating latitudinal clines for life history and stress resistance traits in Drosophila simulans from eastern Australia.

Latitudinal clines have been demonstrated for many quantitative traits in Drosophila and are assumed to be due to climatic selection. However, clinal studies are often performed in species of Drosophila that contain common cosmopolitan inversion polymorphisms that also show clinal patterns. These inversion polymorphisms may be responsible for much of the observed clinal variation. Here, we consider latitudinal clines for quantitative traits in Drosophila simulans from eastern Australia. Drosophila simulans does not contain cosmopolitan inversion polymorphisms, so allows the study of clinal selection on quantitative traits that are not confounded by associations with inversions. Body size showed a strong linear cline for both females and males. Starvation resistance exhibited a weak linear cline in females, whereas chill-coma recovery exhibited a significant nonlinear cline in females only. No clinal pattern was evident for development time, male chill-coma recovery, desiccation or heat resistance. We discuss these results with reference to the role inversion polymorphisms play in generating clines in quantitative traits of Drosophila.

Nucleotide diversity in the Hsp90 gene in natural populations of Drosophila melanogaster from Australia.

Hsp90 is regarded as one of the best candidates for an evolved mechanism that regulates the expression of genetic and phenotypic variability. We examined nucleotide diversity in both the promoter and coding regions of Hsp90, the gene which encodes Hsp90 in Drosophila, in natural populations of Drosophila melanogaster from eastern Australia. We found that Hsp90 is polymorphic for only two nonsynonymous changes in the coding region, both of which are deletions of a lysine residue. One of these lysine deletions was in complete linkage disequilibrium with the inversion In(3L)P, and showed a significant association with latitude. The other lysine deletion reported here for the first time varied from 0 to 15% in natural populations, but did not show a clinal pattern. The regulatory and coding regions of Hsp90 showed very low nucleotide diversity compared to other nuclear genes, and chromosomes containing In(3L)P had lower levels of nucleotide diversity than the standard arrangements. Non-neutral evolution of Hsp90 was not supported by analyses of either the regulatory or coding regions of the gene. These results are discussed within the context of Hsp90 variation being involved in thermotolerance as well as the expression of genetic and phenotypic variability.

Antagonistic selection between adult thorax and wing size in field released Drosophila melanogaster independent of thermal conditions.

Attempts to explain size variation in Drosophila and other small insects often focus on the larval stage and association between development time and size, but patterns are also influenced by direct selection on size-related traits in the adults. Here we use multiple field releases of Drosophila melanogaster to test the association between size and one component of field fitness, the ability of Drosophila to locate resources for feeding and breeding. We find antagonistic selection between wing length and thorax length in both males and females, such that capture at baits is higher for flies with relatively larger thorax lengths and smaller wings. However flies with large wings relative to thoraces disperse further as reflected in the longer distances moved to baits. These patterns did not depend strongly on weather conditions, suggesting that selection on adult size is at least partly independent of temperature. Antagonistic selection between size traits can generate changes in size along gradients if the distribution of resources in the environment varies and selects for different dispersal patterns, particularly as dispersal is relatively higher under warmer conditions.

The association between inversion In(3R)Payne and clinally varying traits in Drosophila melanogaster.

In Drosophila melanogaster, inversion In(3R)Payne increases in frequency towards low latitudes and has been putatively associated with variation in size and thermal resistance, traits that also vary clinally. To assess the association between size and inversion, we obtained isofemale lines of inverted and standard karyotype of In(3R)Payne from the ends of the Australian D. melanogaster east coast cline. In the northern population, there was a significant association between In(3R)Payne and body size, with standard lines from this population being relatively larger than inverted lines. In contrast, the inversion had no influence on development time or cold resistance. We strengthened our findings further in a separate study with flies from populations from the middle of the cline as well as from the cline ends. These flies were scored for wing size and the presence of In(3R)Payne using a molecular marker. In females, the inversion accounted for around 30% of the size difference between cline ends, while in males the equivalent figure was 60%. Adaptive shifts in size but not in the other traits are therefore likely to have involved genes closely associated with In(3R)Payne. Because the size difference between karyotypes was similar in different populations, there was no evidence for coadaptation within populations.

[Acute nonalcoholic nonbiliary pancreatitis. Difficulties in diagnosis and possibility of nicotine toxicity]. / Pancréatite aiguë non alcoolique non biliaire. Difficultés du diagnostic etiologique et toxicité possible de la nicotine.

INTRODUCTION: The possibility of nicotine toxicity, although rare, should be considered in cases of acute edematous pancreatitis. CASE: A 30-year-old woman was hospitalized to identify the cause of an initial episode of acute edematous pancreatitis. The observation of native anti-DNA and antiphospholipid antibodies suggested lupus pancreatitis and/or an antiphospholipid syndrome, both subsequently ruled out. The final diagnosis was nicotine poisoning induced by the combination of a nicotine patch and tobacco smoking. CONCLUSION: Although a nicotine patch has never been reported in connection with an episode of acute pancreatitis before, this case suggests that such an event might be a rare complication of an overdose of nicotine.

Genetic correlations, tradeoffs and environmental variation.

Negative genetic correlations among traits are often used as evidence for tradeoffs that can influence evolutionary trajectories in populations. While there may be evidence for negative correlations within a particular environment, genetic correlations can shift when populations encounter different environmental conditions. Here we review the evidence for these shifts by focusing on experiments that have examined genetic correlations in more than one environment. In many studies, there are significant changes in correlations and these can even switch sign across environments. This raises questions about the validity of deducing genetic constraints from studies in one environment and suggests that the interaction between environmental conditions and the expression of genetic covariation is an important avenue for future work.