Asexual reproduction in introduced and native populations of the ant Cerapachys biroi.

Asexual reproduction is particularly common among introduced species, probably because it helps to overcome the negative effects associated with low population densities during colonization. The ant Cerapachys biroi has been introduced to tropical and subtropical islands around the world since the beginning of the last century. In this species, workers can reproduce via thelytokous parthenogenesis. Here, we use genetic markers to reconstruct the history of anthropogenic introductions of C. biroi, and to address the prevalence of female parthenogenesis in introduced and native populations. We show that at least four genetically distinct lineages have been introduced from continental Asia and have led to the species' circumtropical establishment. Our analyses demonstrate that asexual reproduction dominates in the introduced range and is also common in the native range. Given that C. biroi is the only dorylomorph ant that has successfully become established outside of its native range, this unusual mode of reproduction probably facilitated the species' worldwide spread. On the other hand, the rare occurrence of haploid males and at least one clear case of sexual recombination in the introduced range show that C. biroi has not lost the potential for sex. Finally, we show that thelytoky in C. biroi probably has a genetic rather than an infectious origin, and that automixis with central fusion is the most likely underlying cytological mechanism. This is in accordance with what is known for other thelytokous eusocial Hymenoptera.

Combining chromosomal arm status and significantly aberrant genomic locations reveals new cancer subtypes.

Many types of tumors exhibit characteristic chromosomal losses or gains, as well as local amplifications and deletions. Within any given tumor type, sample specific amplifications and deletions are also observed. Typically, a region that is aberrant in more tumors, or whose copy number change is stronger, would be considered as a more promising candidate to be biologically relevant to cancer. We sought for an intuitive method to define such aberrations and prioritize them. We define V, the "volume" associated with an aberration, as the product of three factors: (a) fraction of patients with the aberration, (b) the aberration's length and (c) its amplitude. Our algorithm compares the values of V derived from the real data to a null distribution obtained by permutations, and yields the statistical significance (p-value) of the measured value of V. We detected genetic locations that were significantly aberrant, and combine them with chromosomal arm status (gain/loss) to create a succinct fingerprint of the tumor genome. This genomic fingerprint is used to visualize the tumors, highlighting events that are co-occurring or mutually exclusive. We apply the method on three different public array CGH datasets of Medulloblastoma and Neuroblastoma, and demonstrate its ability to detect chromosomal regions that were known to be altered in the tested cancer types, as well as to suggest new genomic locations to be tested. We identified a potential new subtype of Medulloblastoma, which is analogous to Neuroblastoma type 1.

Diverging Cave- and River-Dwelling Newts Exert the Same Mate Preference in their Native Light Conditions

When colonizing a new habitat, populations must adapt their sexual behaviour to new ecological constraints. Because caves display drastically different conditions from surface habitats and cave animals are deprived from visual information, hypogean populations are expected to have modified their mate preference and signalling behaviour after cave colonization. Here, we experimentally examined the female preference and the sexual behaviour of brook newts Calotriton asper from different cave and river populations, either in light or in darkness. Our results suggest that females prefer large individuals in both hypogean and epigean populations, but that this preference is only expressed in the light conditions of their native habitat. Hence, some mate choice criteria would be maintained across genetically divergent populations and throughout dissimilar habitats. However, this sexual behaviour is likely to be expressed via a different sensory pathway in the different habitats, suggesting that a sensory shift has occurred in cave populations, enabling animals to communicate through a non-visual channel.

Treatment Options in the Management of Status Epilepticus

Status epilepticus treatment involves the use of several pharmacologic compounds, which are conceptually divided into three successive and additional lines of action. Because of their rapid onset of action, benzodiazepines represent the first approach; these are followed by classic antiepileptic drugs that are administered intravenously. In refractory episodes, pharmacologic coma induction with an appropriate anesthetic is advocated. Apart from first-line compounds, the level of evidence for medications used in status epilepticus is extremely limited. It is important to specifically address etiology in order to maximize the impact of the antiepileptic therapy. Fine-tuning of the treatment strategy, mainly regarding the choice of whether to induce coma, should be approached by balancing the benefits of rapid control of the status epilepticus with the risks of adverse effects. Although each status epilepticus episode should be treated as rapidly as possible, it appears advisable to reserve coma induction for those forms, such as generalized convulsive status, that have been shown to present a consistent risk of neurologic sequelae.

Effects of usual nutrient intake and vitamin D status on markers of bone turnover in Swiss adolescents.

OBJECTIVE: To evaluate the effects of nutrient intake and vitamin D status on markers of type I collagen formation and degradation in adolescent boys and girls. DESIGN: Cross-sectional study. SETTING: Canton of Vaud, West Switzerland. SUBJECTS: A total of 92 boys and 104 girls, aged 11-16 y. Data were collected on height, weight, pubertal status (self-assessment of Tanner stage), nutrient intake (3-day dietary record) and fasting serum concentration of 25-hydroxyvitamin D (25OHD), and markers of collagen formation (P1NP) and degradation (serum C-terminal telopeptides: S-CTX). RESULTS: Tanner stage was a significant determinant of P1NP in boys and girls and S-CTX in girls. Of the nutrients examined, only the ratio of calcium to phosphorus (Ca/P) was positively associated with P1NP in boys, after adjustment for pubertal status. 25OHD decreased significantly at each Tanner stage in boys. Overall, 15% of boys and 17% of girls were identified as being vitamin D insufficient (serum 25OHD <30 nmol/l), with the highest proportion of insufficiency at Tanner stage 4-5 (29%) in boys and at Tanner stage 3 (24%) in girls. A significant association was not found between 25OHD and either bone turnover marker, nor was 25OHD insufficiency associated with higher concentrations of the bone turnover markers. CONCLUSIONS: The marked effects of puberty on bone metabolism may have obscured any possible effects of diet and vitamin D status on markers of bone metabolism. The mechanistic basis for the positive association between dietary Ca/P ratio and P1NP in boys is not clear and may be attributable to a higher Ca intake per se, a critical balance between Ca and P intake or higher dairy product consumption. A higher incidence of vitamin D insufficiency in older adolescents may reflect a more sedentary lifestyle or increased utilisation of 25OHD, and suggests that further research is needed to define their requirements. SPONSORSHIP: Nestec Ltd and The Swiss Foundation for Research in Osteoporosis.

Parenteral anticoagulants in heart disease: Current status and perspectives (Section II). Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease.

Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.

Newer antiepileptic drugs in the treatment of status epilepticus: Impact on prognosis.

Newer antiepileptic drugs (AEDs) are increasingly prescribed and seem to have a comparable efficacy as the classical AEDs; however, their impact on status epilepticus (SE) prognosis has received little attention. In our prospective SE database (2006-2010), we assessed the use of older versus newer AEDs (levetiracetam, pregabalin, topiramate, lacosamide) over time and its relationship to outcome (return to clinical baseline conditions, new handicap, or death). Newer AEDs were used more often toward the end of the study period (42% of episodes versus 30%). After adjustment for SE etiology, SE severity score, and number of compounds needed to terminate SE, newer AEDs were independently related to a reduced likelihood of return to baseline (p<0.001) but not to increased mortality. These findings seem in line with recent findings on refractory epilepsy. Also, in view of the higher price of the newer AEDs, well-designed, prospective assessments analyzing the impact of newer AEDs on efficacy and tolerability in patients with SE appear mandatory.

Beta-catenin Status in P?aediatric Medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics.

Medulloblastoma is the most frequent malignant paediatric brain tumour. The activation of the Wnt/beta-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favourable patient outcome. We report a series of 72 paediatric medulloblastomas evaluated for beta-catenin protein expression, CTNNB1 mutations, and comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of beta-catenin showed extensive nuclear staining (>50% of the tumour cells) in six cases and focal nuclear staining (<10% of cells) in three cases. The other cases either exhibited a signal strictly limited to the cytoplasm (58 cases) or were negative (five cases). CTNNB1 mutations were detected in all beta-catenin extensively nucleopositive cases. The expression profiles of these cases documented strong activation of the Wnt/beta-catenin pathway. Remarkably, five out of these six tumours showed a complete loss of chromosome 6. In contrast, cases with focal nuclear beta-catenin staining, as well as tumours with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/beta-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5-121.2 months) from diagnosis. All three patients with focal nuclear staining of beta-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumours represent a distinct molecular subgroup of medulloblastomas with favourable outcome, indicating that therapy de-escalation should be considered. International consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved.

Second-line status epilepticus treatment: comparison of phenytoin, valproate, and levetiracetam.

Purpose:  Phenytoin (PHT), valproic acid (VPA), or levetiracetam (LEV) are commonly used as second-line treatment of status epilepticus (SE), but comparative studies are not available. Methods:  Among 279 adult SE episodes identified prospectively in our tertiary care hospital over 4 years, we retrospectively identified 187 episodes in which PHT, VPA, or LEV were given after benzodiazepines. Patients with postanoxic SE were not included. Demographics, clinical SE features, failure of second-line treatment to control SE, new handicap, and mortality at hospital discharge were assessed. Uni- and multivariable statistical analyses were applied to compare the three agents. Key Findings:  Each compound was used in about one third of SE episodes. VPA failed to control SE in 25.4%, PHT in 41.4%, and LEV in 48.3% of episodes in which these were prescribed. A deadly etiology was more frequent in the VPA group, whereas SE episodes tended to be more severe in the PHT group. After adjustment for these known SE outcome predictors, LEV failed more often than VPA [odds ratio (OR) 2.69; 95% confidence interval (CI) 1.19-6.08]; 16.8% (95% CI: 6.0-31.4%) of second-line treatment failures could be attributed to LEV. PHT was not statistically different from the other two compounds. Second-line treatment did not seem to influence new handicap and mortality, whereas etiology and the SE Severity Score (STESS) were robust independent predictors. Significance:  Even without significant differences on outcome at discharge, LEV seems less efficient than VPA to control SE after benzodiazepines. A prospective comparative trial is needed to address this potentially concerning finding.

Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab in the trial SAKK 50/07.

The O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical trials with temozolomide plus bevacizumab therapy in metastatic melanoma patients are ongoing, although the predictive value of the MGMT promoter methylation status in this setting remains unclear. We assessed MGMT promoter methylation in formalin-fixed, primary tumor tissue of metastatic melanoma patients treated with first-line temozolomide and bevacizumab from the trial SAKK 50/07 by methylation-specific polymerase chain reaction. In addition, the MGMT expression levels were also analyzed by MGMT immunohistochemistry. Eleven of 42 primary melanomas (26%) revealed a methylated MGMT promoter. Promoter methylation was significantly associated with response rates CR + PR versus SD + PD according to RECIST (response evaluation criteria in solid tumors) (p<0.05) with a trend to prolonged median progression-free survival (8.1 versus 3.4 months, p>0.05). Immunohistochemically different protein expression patterns with heterogeneous and homogeneous nuclear MGMT expression were identified. Negative MGMT expression levels were associated with overall disease stabilization CR + PR + SD versus PD (p=0.05). There was only a poor correlation between MGMT methylation and lack of MGMT expression. A significant proportion of melanomas have a methylated MGMT promoter. The MGMT promoter methylation status may be a promising predictive marker for temozolomide therapy in metastatic melanoma patients. Larger sample sizes may help to validate significant differences in survival type endpoints.

Population genetic structure in the native and introduced range of the Argentine ant/

SUMMARY : The evolution of animal societies, where some individuals forego their own reproductive opportunities to help others to reproduce, poses an evolutionary paradox that can be traced back to Darwin. Altruism may evolve through kin selection when the donor and recipient of altruistic acts are related to each other. In social insects, workers are generally highly related to the brood they rear when colonies are headed by a single queen. Yet some ants have an extraordinary social organization, called unicoloniality, whereby individuals from separate nests mix freely to form large supercolonies, which in some cases extend over hundreds of km. These supercolonies are characterised by a high number of queens (polygyny) and an absence of clear colony boundaries. This type of social organization represents an evolutionary paradox because relatedness between nestmates is effectively zero. In such conditions, kin selection cannot account for the evolution of reproductive altruism. Moreover, unicoloniality is thought to be unstable over time, because workers that can no longer aid close relatives may evolve more selfish strategies. The Argentine ant (Linepithema humile) is a highly invasive species listed among the hundred world's worst invaders by the UICN. Native from South America, L. humile has been accidentally introduced throughout the world. Native populations have been described as noninvasive with a family-based organization. In contrast, within its introduction range, they form unicolonial supercolonies that contain numerous nests without intraspecific aggression. The development of such unicolonial populations has been explained as a direct consequence of the ant's introduction into a new habitat, favouring a transition from family-based to open colonies. To determine if the social structure of the Argentine ant is fundamentally different between the native and the introduced range, we studied genetically and behaviourally native and introduced populations of L. humile over different geographic scales. Our results clearly indicated that there are no fundamental differences in the social organisation of the Argentine ant between the two ranges. Our investigations revealed that, contrary to previous claims, native populations have a unicolonial social organisation very similar to that observed in the introduced range. Consequently, the unicolonial social structure of the Argentine ant does not stem from a shift in social organization associated with introduction into new habitats but evolved in the native range and is likely a stable, evolutionarily ancient adaptation to the local environment. Our study on native populations of L. humile also gave important insight in the comprehension of the evolution of unicoloniality in the Argentine ant. Native supercolonies are relatively small compared to introduced ones and may co-habit in a same population. These supercolonies are genetically highly differentiated leading to a significant relatedness among nestmate workers when the different supercolonies of a population are taken as a reference population. This provides the necessary conditions for loin selection to operate. Furthermore, we examined a native population over time, which revealed a high supercolony extinction rate. If more competitive supercolonies are more likely to survive or replace other supercolonies, a subtle dynamical process between the spread of selfish traits within supercolony and the selective elimination of supercolonies with such traits may allow a stable equilibrium and the persistence of unicoloniality over time. Finally, a worldwide study of the Argentine ant showed that the introduced supercolonies originate from numerous independent introduction events. In conclusion, the success of the Argentine ant does not stem from a shift in social organization associated with its introduction into new habitats, but is most probably explained by the intrinsic characteristics developed in its native range. RESUME : L'altruisme de reproduction où certains individus renoncent à leur propre reproduction pour aider d'autres individus à se reproduire constitue l'un des plus grand paradoxe de l'évolution. En effet, comment expliquer l'évolution de comportements qui tendent à augmenter les chances de survie et le succès reproductif d'autres individus, alors que ces actes diminuent l'aptitude de leurs auteurs ? La théorie de la sélection de parentèle permet de résoudre ce problème. Cette théorie stipule qu'en aidant de proches parents à se reproduire, les individus peuvent promouvoir indirectement la transmission de copies de leurs propres gènes à la génération suivante. Chez les insectes sociaux, l'altruisme des ouvrières s'explique par la théorie de sélection de parentèle lorsque les colonies sont monogynes (constituées d'une seule reine) puisque les ouvrières sont fortement apparentées aux couvains dont elles s'occupent. Par contre, les espèces dites unicoloniales, dont les colonies forment des réseaux de nids appelés supercolonies, représentent toujours un paradoxe pour les théories de l'évolution puisque l'apparentement entre les différents individus d'un nid est nulle. De plus, l'unicolonialité ne devrait pas être stable sur le long terme parce que les ouvrières qui ne s'occupent plus de leur apparentés devraient développer des stratégies plus égoïstes au cours du temps. La fourmi d'Argentine (Linepithema humile) est une espèce invasive ayant un impact considérable sur son environnement. Originaire d'Amérique du Sud, elle a été introduite dans pratiquement toutes les régions du monde dont le climat est de type méditerranéen. Son incroyable succès invasif s'explique par sa structure sociale unicoloniale observée dans chacun des pays où elle a été introduite. Par contre, les rares études effectuées en Argentine ont suggéré que la fourmi d'Argentine n'était pas unicoloniale dans son aire native. L'unicolonialité chez la fourmi d'Argentine était donc considéré comme une conséquence de son introduction dans de nouveaux environnements. Durant cette thèse, nous avons vérifié si la structure sociale de cette espèce différait fondamentalement entre l'aire native et introduite. Pour cela, nous avons étudié, à différentes échelles géographiques, des populations introduites et argentines avec une approche génétique et comportementale. L'ensemble de nos résultats montrent que les différences entre les deux structure sociales ne sont pas aussi importantes que ce que l'on imaginait. Les populations natives sont aussi constituées de réseaux de nids coopérants. La taille de ses supercolonies est toutefois bien moins importante en Argentine et il n'est pas rare de trouver plusieurs supercolonies cohabitantes dans une même population. Nous avons démontré que ces réseaux de nids étaient constitués d'individus qui sont plus apparentés entre eux qu'ils ne le sont avec les individus d'autres supercolonies, ainsi l'unicolonialité dans son aire d'origine ne représente pas un réel paradoxe pour les théories de l'évolution. Finalement nous avons étudié la même population en Argentine à six ans d'intervalle et avons constaté que les supercolonies avaient un taux de survie très faible ce qui pourrait expliquer la stabilité de l'unicolonialité au cours du temps. Si les supercolonies les plus compétitives survivent mieux que les supercolonies dans lesquelles apparaissent des traits égoïstes, on devrait alors observer une dynamique entre l'apparition de traits égoïstes et l'élimination des supercolonies dans lesquelles ces traits égoïstes évolueraient. Finalement, une étude mondiale nous a montré que les supercolonies étaient originaires de nombreux événements d'introductions indépendants. En conclusion, le succès invasif de la fourmi d'Argentine n'est donc pas dû à un changement de comportement associé à son introduction mais est lié aux caractéristiques qu'elle a développées en Argentine.

Falls efficacy predicts functional status on month after discharge in elderly patients undergoing post-accute rehabilitation

Objective: To investigate the relationship between falls efficacy at admission and functional status reported one month after discharge from post-acute rehabilitation in a cohort of elderly patients. Methods: Participants were elderly patients admitted to postacute rehabilitation in an academic geriatric facility. Data on demographics and affective status were collected upon admission; functional status and gait speed were measured at admission and at discharge; self-reported functional status and history of falls since discharge were collected one month after discharge (follow-up). Falls efficacy was measured using the Fall Efficacy Scale, that assesses confidence in performing 12 activities of daily living without falling (range 0 to 100, higher score indicating higher confidence). Patients were classified using the median FES score at baseline (95) as cut-off to divide the population into "confident" and "fearful" groups. Results: Participants' (N=180, mean age 81.3±7.1 years, 75.6% women) mean FES score was 92.3±8.7 at baseline (range 60-100). Basic ADL score averaged 3.5±1.6 at baseline, 4.7±1.3 at discharge, and 5.5±0.7 at follow-up (self-reported). Baseline FES score was positively correlated with basic ADL at follow-up (rho=0.35, p<.001). At follow-up, 58.7% of the patients were fully independent in basic ADL, this proportion being significantly higher in confident than fearful patients (70.7% vs 42.4%, p<.001). Compared to confident patients, those fearful had significantly lower odds (OR 0.3, 95%CI 0.2-0.6, p<.001) to report full independence at follow-up. This relationship remained (adjOR = 0.4, 95%CI 0.2-0.8, p=.01) after controlling for demographics, baseline gait speed, depressive symptoms, functional status at discharge, and history of falls since discharge. Conclusion: In this cohort of older rehab patients, poor falls efficacy at admission was associated with lower function reported one month after discharge even after controlling for initial mobility performance and functional status at discharge. Further studies should determine whether interventions aiming at falls efficacy improvement will also result in improved function in fearful subjects undergoing rehabilitation.