Updating beliefs beyond the here-and-now: the counter-factual self in anosognosia for hemiplegia.

The syndrome of anosognosia for hemiplegia, or the lack of awareness for one's paralysis following right hemisphere stroke, can provide unique insights into the neurocognitive mechanisms of self-awareness. Yet it remains unclear whether anosognosia for hemiplegia is a modality-specific deficit of sensorimotor monitoring, or whether domain-general processes of attention and belief-updating converge to cause anosognosia for hemiplegia. Using a Bayesian learning framework, we formalized and empirically investigated the hypothesis that failures to update anosognosic beliefs can be explained by abnormalities in the relative uncertainty (i.e. precision) ascribed to prior beliefs versus sensory information in different contexts. We designed a new motor belief-updating task that manipulated both the temporal (prospective and retrospective) and spatial (hemispace most affected by inattention and hemispace less affected by inattention) conditions in which beliefs had to be updated, and we validated its sensitivity to anosognosia for hemiplegia in 26 patients with right hemisphere stroke. We then computed and empirically tested two different Bayesian predictors of prospective beliefs using two proxies for precision in anosognosia for hemiplegia patients: (i) standardized, neuropsychological measures of objective attention abilities, i.e. visuospatial neglect scores and (ii) subjective uncertainty reports, i.e. confidence ratings. Our results suggest that while neglect does not affect local, sensorimotor error monitoring, it does seem to affect the degree to which observed errors are used to update more general, prospective beliefs about counterfactual motor abilities in anosognosia for hemiplegia. Difficulties in such 'counterfactual' belief-updating were associated with disruptions in tracts of the ventral attentional network (i.e. superior longitudinal fasciculus connecting the temporo-parietal junction and ventral frontal cortex) and associated lesions to the insula, inferior parietal cortex and superior temporal regions. These results suggest that self-awareness extends beyond local, retrospective monitoring, requiring also salience-based, convergence of beliefs about the self that go beyond the 'here-and-now' of sensorimotor experience.

River restoration is prone to failure unless pre-optimized within a mechanistic ecological framework | Insights from a model-based case study.

River restoration with the use of in-stream structures has been widely implemented to maintain/improve physical habitats. However, the response of aquatic biota has often been too weak to justify the high costs of restoration projects. The ecological effectiveness of river restoration has thus been much debated over claims that large-scale environmental drivers often overshadow the potential positive ecological effects of locally placed in-stream structures. In this study, we used a two-dimensional hydrodynamic-habitat model to evaluate the ecological effectiveness of habitat restoration with the use of in-stream structures in various water discharges, ranging from near-dry to environmental flows. The habitat suitability of benthic macroinvertebrates and of three cyprinid fish species was simulated for six restoration schemes and at four discharge scenarios, and was compared with a reference model, without in-stream structures. We found that the ecological response to habitat restoration varied by species and life stages, it strongly depended on the reach-scale flow conditions, it was often negative at near-environmental flows, and when positive, mostly at near-dry flows, it was too low to justify the high costs of river restoration. Flow variation was the major environmental driver that our local habitat restoration schemes attempted -but mostly failed-to fine-tune. We conclude that traditional river restoration, based on trial and error, will likely fail and should be ecologically pre-optimized before field implementation. Widespread use of in-stream structures for ecological restoration is not recommended. However, at near-dry flows, the response of all biotic elements except for macroinvertebrates, was positive. In combination with the small habitat-suitability differences observed among structure types and densities, we suggest that sparse/moderate in-stream structure placement can be used for cost-effective river restoration, but it will only be ecologically effective -thus justifying the high implementation costs-when linked to very specific purposes: (i) to conserve endangered species and (ii) to increase/improve habitat availability/suitability during dry periods, thus proactively preventing/reducing the current and future ecological impacts of climate change.

Damage to the right insula disrupts the perception of affective touch.

Specific, peripheral C-tactile afferents contribute to the perception of tactile pleasure, but the brain areas involved in their processing remain debated. We report the first human lesion study on the perception of C-tactile touch in right hemisphere stroke patients (N = 59), revealing that right posterior and anterior insula lesions reduce tactile, contralateral and ipsilateral pleasantness sensitivity, respectively. These findings corroborate previous imaging studies regarding the role of the posterior insula in the perception of affective touch. However, our findings about the crucial role of the anterior insula for ipsilateral affective touch perception open new avenues of enquiry regarding the cortical organization of this tactile system.

Effectiveness and Safety of Micafungin in Managing Invasive Fungal Infections among Patients in Greece with Hematologic Disorders: The ASPIRE Study.

INTRODUCTION: Invasive candidiasis (IC) can be a life-threatening infection in immunocompromised patients, particularly those with cancer, hematologic diseases and/or hematopoietic stem cell transplantation (HSCT) recipients. The objective of this study was to evaluate the effectiveness of micafungin in patients with hematologic malignancies or HSCT recipients, relevant to clinical presentation of IC, in real-life practice in Greece. METHODS: ASPIRE was a phase IV, multicenter, non-interventional, prospective cohort study, conducted at ten tertiary hospitals in Greece, in adults with hematologic disease. Micafungin treatment for IC or prophylaxis for Candida infection was administered per standard clinical practice until a clinical outcome (success or failure) was reached. Treatment success was defined by the EORTC/MSG criteria for invasive fungal infections (IFI) and was assessed by the investigator. Treatment discontinuation and safety were also evaluated. RESULTS: One hundred forty-three patients were enrolled. Median age was 62; 85 (59.4%) patients were male, and 133 (93.0%) had Greek ethnicity. One hundred twenty-six (88.1%) patients had hematologic malignancies, and 21 (14.7%) had received HSCT. Prophylaxis was administered to 74 (51.7%) patients [median (range) dose: 50 (50-150) mg/day] with no signs of IFI. Overall, 52 (36.4%) patients with possible IFI at baseline received micafungin treatment [100 (50-125) mg/day] versus 12 (17.2%) with probable [100 (75-150) mg/day] and 5 (3.5%) with confirmed [125 (100-150) mg/day] IFI. Treatment success was 91.6% (95% CI 85.80-95.59; n = 131) overall and 90.5% (n = 67) in patients receiving prophylaxis. Median time on treatment was 13 days. Treatment discontinuation (n = 26; 18.2%) was not related to adverse events. No treatment-related serious adverse events were reported. CONCLUSION: Micafungin treatment for IC or prophylaxis for Candida infection was effective and well tolerated in patients with hematologic disorders in clinical practice in Greece. These results demonstrate that micafungin could be used more widely for prophylaxis. Further work is required to determine the efficacy and safety of micafungin for the management of IFIs in hematologic settings. FUNDING: Astellas Pharma Inc.

Comparative Assessment of Environmental Flow Estimation Methods in a Mediterranean Mountain River.

The ecological integrity of rivers ultimately depends on flow regime. Flow degradation is especially prominent in Mediterranean systems and assessing environmental flows in modified rivers is difficult, especially in environments with poor hydrologic monitoring and data availability. In many Mediterranean countries, which are characterized by pronounced natural variability and low summer flows, water management actions usually focus on prescribing minimum acceptable flows estimated by hydrologic methods. In this study, a comparative assessment of environmental flow estimation methods is developed in a river with poorly monitored flows and limited understanding of past reference conditions. This assessment incorporates both a hydrologic and a fish habitat simulation effort that takes into consideration hydrologic seasonality in a Greek mountainous river. The results of this study indicate that especially in data scarce regions the utilization of biotic indicators through habitat models, may provide valuable information, beyond that achievable with hydrologic methods, for developing regional environmental flow criteria. Despite the widespread use of the method, challenges in transferability of fish habitat simulation provide undefined levels of uncertainty and may require the concurrent use of different assessment tools and site-specific study.

Potential impacts of climate change on flow regime and fish habitat in mountain rivers of the south-western Balkans.

The climate change in the Mediterranean area is expected to have significant impacts on the aquatic ecosystems and particular in the mountain rivers and streams that often host important species such as the Salmo farioides, Karaman 1938. These impacts will most possibly affect the habitat availability for various aquatic species resulting to an essential alteration of the water requirements, either for dams or other water abstractions, in order to maintain the essential levels of ecological flow for the rivers. The main scope of this study was to assess potential climate change impacts on the hydrological patterns and typical biota for a south-western Balkan mountain river, the Acheloos. The altered flow regimes under different emission scenarios of the Intergovernmental Panel on Climate Change (IPCC) were estimated using a hydrological model and based on regional climate simulations over the study area. The Indicators of Hydrologic Alteration (IHA) methodology was then used to assess the potential streamflow alterations in the studied river due to predicted climate change conditions. A fish habitat simulation method integrating univariate habitat suitability curves and hydraulic modeling techniques were used to assess the impacts on the relationships between the aquatic biota and hydrological status utilizing a sentinel species, the West Balkan trout. The most prominent effects of the climate change scenarios depict severe flow reductions that are likely to occur especially during the summer flows, changing the duration and depressing the magnitude of the natural low flow conditions. Weighted Usable Area-flow curves indicated the limitation of suitable habitat for the native trout. Finally, this preliminary application highlighted the potential of science-based hydrological and habitat simulation approaches that are relevant to both biological quality elements (fish) and current EU Water policy to serve as efficient tools for the estimation of possible climate change impacts on the south-western Balkan river ecosystems.

Monitoring minimal residual disease in acute myeloid leukaemia with NPM1 mutations by quantitative PCR: clonal evolution is a limiting factor.

Nucleophosmin (NPM1) mutations in exon 12 represent the most frequent molecular aberrations in adult patients with acute myeloid leukaemia (AML). Molecular detection of NPM1 mutation A could be a useful marker for routine monitoring of minimal residual disease (MRD). We established a calibrator-normalized relative quantification real-time polymerase chain reaction (PCR) assay for NPM1 mutation A. ABL1 was used as a reference housekeeping gene and the NPM1 mutation A-containing OCI/AML3 cell line as a calibrator. Relative quantification was performed by calculating the NPM1 mutation A/ABL1 ratio which was normalized to the NPM1 mutation A/ABL1 ratio of OCI/AML3 calibrator cDNA. The assay showed a sensitivity of 10(-5). The clinical usefulness was evaluated by monitoring MRD in 51 AML patients with NPM1 mutation A. In 27 patients analysed at diagnosis and after induction treatment, NPM1 mutation A ratios showed a median log(10) reduction of 2.48, which correlated with response to therapy. Among the 51 patients, 21 relapsed and two lost the mutation. We established a sensitive, specific and reproducible assay for routine quantification and monitoring of NPM1 mutation A levels. However, clonal evolution was observed in 9.5% limiting the usefulness of the NPM1 mutation A mutation as a molecular marker in these patients.