Silent Phase of Johne’s Disease in Experimentally Infected Goats – A Study on New and Established Diagnostic Approaches Using Specific and Non-Specific Parameters

The current gold standard diagnostic test for Johne’s disease (JD) is detecting Mycobacterium avium subsp. paratuberculosis (MAP) from fecal samples via culture and/or PCR. Other commercially available JD diagnostic tests focus on the detection of specific antibodies within the serum or milk of infected ruminants. These tests have a high specificity but low their sensitivity and usually fail to diagnose the disease until later stages of the disease. The ideal diagnostic test should detect infected animals already during the silent phase. Here, we evaluate the use of new and established approaches to define the silent phase of JD in experimentally infected goats. None of the established diagnostic tests or new approaches for the detection of humoral and cellular immune responses were positive during the first year of infection. Only the characterization of various subsets of peripheral blood leukocytes and the weight development gave some indication for the presence of a chronic, but silent, infection. Weight differences were present throughout the first year. In addition, some of the subsets of leukocytes (WC1+ T cells, MHC class II+ leukocytes, CD1+ leukocytes, CD14+ granulocytes, and CD14+/MHC class II+ granulocytes) demonstrated significant differences, but only at certain time points

The power of evolutionary rescue is constrained by genetic load

International audienceThe risk of extinction faced by small isolated populations in changing environments can be reduced by rapid adaptation and subsequent growth to larger, less vulnerable sizes. Whether this process, called evolutionary rescue, is able to reduce extinction risk and sustain population growth over multiple generations is largely unknown. To understand the consequences of adaptive evolution as well as maladaptive processes in small isolated populations, we subjected experimental Tribolium castaneum populations founded with 10 or 40 individuals to novel environments, one more favorable, and one resource poor, and either allowed evolution, or constrained it by replacing individuals one-for-one each generation with those from a large population maintained in the natal environment. Replacement individuals spent one generation in the target novel environment before use to standardize effects due to the parental environment. After eight generations we mixed a subset of surviving populations to facilitate admixture, allowing us to estimate drift load by comparing performance of mixed to unmixed groups. Evolving populations had reduced extinction rates, and increased population sizes in the first four to five generations compared to populations where evolution was constrained. Performance of evolving populations subsequently declined. Admixture restored their performance, indicating high drift load that may have overwhelmed the beneficial effects of adaptation in evolving populations. Our results indicate that evolution may quickly reduce extinction risk and increase population sizes, but suggest that relying solely on adaptation from standing genetic variation may not provide long-term benefits to small isolated populations of diploid sexual species, and that active management facilitating gene flow may be necessary for longer term persistence

Data from: The power of evolutionary rescue is constrained by genetic load

Extinction risk of small isolated populations in changing environments can be reduced by rapid adaptation and subsequent growth to larger, less vulnerable sizes. Whether this process, called evolutionary rescue, is able to reduce extinction risk and sustain population growth over multiple generations is largely unknown. To understand the consequences of adaptive evolution as well as maladaptive processes in small isolated populations, we subjected experimental Tribolium castaneum populations founded with 10 or 40 individuals to novel environments, one more favorable, and one resource poor, and either allowed evolution, or constrained it by replacing individuals one-for-one each generation from a non-adapting large population to minimize both adaptive and non-adaptive evolutionary processes. Replacement individuals spent one generation in the target novel environment before use to standardize effects due to the parental environment. After 8 generations we mixed a subset of surviving populations to facilitate admixture, allowing us to estimate drift load by comparing performance of mixed to unmixed groups. Evolving populations had reduced extinction rates, and increased population sizes in the first four to five generations compared to populations where evolution was constrained. Performance of evolving populations subsequently declined. Admixture restored their performance, indicating high drift load that may have overwhelmed the beneficial effects of adaptation in evolving populations. Our results indicate that evolution may quickly reduce extinction risk and increase population sizes, but suggest that relying solely on adaptation from standing genetic variation may not provide long-term benefits to small isolated populations of diploid sexual species, and that active management facilitating gene flow may be necessary for longer-term persistence

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease