Variable opportunities for outcrossing result in hotspots of novel genetic variation in a pathogen metapopulation

Many pathogens possess the capacity for sex through outcrossing, despite being able to reproduce also asexually and/or via selfing. Given that sex is assumed to come at a cost, these mixed reproductive strategies typical of pathogens have remained puzzling. While the ecological and evolutionary benefits of outcrossing are theoretically well-supported, support for such benefits in pathogen populations are still scarce. Here, we analyze the epidemiology and genetic structure of natural populations of an obligate fungal pathogen, Podosphaera plantaginis. We find that the opportunities for outcrossing vary spatially. Populations supporting high levels of coinfection -a prerequisite of sex - result in hotspots of novel genetic diversity. Pathogen populations supporting coinfection also have a higher probability of surviving winter. Jointly our results show that outcrossing has direct epidemiological consequences as well as a major impact on pathogen population genetic diversity, thereby providing evidence of ecological and evolutionary benefits of outcrossing in pathogens.Peer reviewe

Radiological score of computed tomography scans predicts revision surgery for chronic rhinosinusitis

Objective. Evaluate computed tomography (CT) signs that predict need for revision endoscopic sinus surgery (ESS) of chronic rhinosinusitis (CRS). Methods. CRS patients (n = 48) underwent routine sinus CT scans and baseline ESS in 2006-2011. Lund-Mackay (LM) scores and 43 other CT signs were analysed blinded from both sides. Patients filled in a questionnaire during the day of CT scanning. Follow-up data were collected from hospital records until January 2018. Associations were analysed by Fisher's exact, Mann Whitney U, Kaplan-Meier method with logrank test and Cox's proportional hazard model. Results. Total LM score was not significantly associated with the need for revision ESS. The best predictive model was a sum of CT signs of non-detectable anatomy of inferior/middle turbinates, obstructed frontal recess, and previous sinus surgery. Using these CT findings, we formed a Radiological Score (RS) (min-max, 0-3 points). Having at least one RS point was significantly associated with the need for revision ESS during the average follow-up of 10.7 years (p = 0.008, Logrank test). Conclusion. We identified a radiologic score that was able to predict the need for revision ESS, which is probably useful in predicting CRS outcomes.Peer reviewe

Assessing Cut-off Points of Eosinophils, Nasal Polyp, and Lund-Mackay Scores to Predict Surgery in Nasal Polyposis : A Real-World Study

Background: Developing tools to identify chronic rhinosinusitis with nasal polyps (CRSwNP) patients requiring surgical treatment would help clinicians treat patients more effectively. The aim of this retrospective cross-sectional study was to identify cut-off values for eosinophil percentage, nasal polyps (NP), and Lund-Mackay (LM) scores that may predict the need for surgical treatment in Finnish CRSwNP patients. Methods: Data of CRSwNP patients (N = 378) undergoing consultation for ESS in 2001-19 were used. Data was collected from patient records and Lund-Mackay scores were determined from sinus computed tomography scans. The percentage of eosinophils was microscopically evaluated from the polyp samples available (n = 81). Associations were analyzed by Mann Whitney U test, and cut-off values by the area under the receiver operating characteristic curve (AUROC). Results: ESS was performed to 293 (77.5%) of patients. Polyp eosinophilia was associated significantly with ESS (p = 0.001), whereas peripheral blood eosinophil count, LM- score and endoscopic NP- score were not (p > 0.05). AUROC values (95% CI) for detecting those needing ESS were for polyp eosinophilia 0.71 (0.60-0.83), p = 0.001, for LM score 0.59 (0.50-0.67), p = 0.054; for NP score 0.56 (0.48-0.64), p = 0.17, and for blood eosinophil count 0.68 (0.46-0.90), p = 0.08. With the threshold value of polyp eosinophilia (>25%), the sensitivity and specificity were optimal for detecting the group needing ESS from the group not undergoing ESS. The cut-off value of blood eosinophil count (>0.26 x 10(9)/L) had relatively good, yet statistically insignificant (underpowered), predictive potential. Moderate cut-off values were found for endoscopic LM score (>= 14/24) and NP score (>= 4/8). Conclusions: Polyp eosinophilia (>25%) predicted ESS among Finnish hospital-level CRSwNP patients. A future challenge would be to find less invasive and cost-effective clinical factors predicting uncontrolled CRSwNP.Peer reviewe

The impact of host metapopulation structure on the population genetics of colonizing bacteria

Many key bacterial pathogens are frequently carried asymptomatically, and the emergence and spread of these opportunistic pathogens can be driven, or mitigated, via demographic changes within the host population. These inter-host transmission dynamics combine with basic evolutionary parameters such as rates of mutation and recombination, population size and selection, to shape the genetic diversity within bacterial populations. Whilst many studies have focused on how molecular processes underpin bacterial population structure, the impact of host migration and the connectivity of the local populations has received far less attention. A stochastic neutral model incorporating heightened local transmission has been previously shown to fit closely with genetic data for several bacterial species. However, this model did not incorporate transmission limiting population stratification, nor the possibility of migration of strains between subpopulations, which we address here by presenting an extended model. We study the consequences of migration in terms of shared genetic variation and show by simulation that the previously used summary statistic, the allelic mismatch distribution, can be insensitive to even large changes in microepidemic and migration rates. Using likelihood-free inference with genotype network topological summaries we fit a simpler model to commensal and hospital samples from the common nosocomial pathogens Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Enterococcus faecium. Only the hospital data for E. faecium display clearly marked deviations from the model predictions which may be attributable to its adaptation to the hospital environment

Factors influencing the practice of new graduate nurses : a focused ethnography of acute care settings

Aim: To explore the influence of an acute care setting on competency deployment of new graduate nurses (NGNs) from a competency -based undergraduate programme . Background: In the last 15 years, nursing education has shifted to competency -based education (CBE). Few studies have focused on how NGNs from these reformed programmes use the competencies they have developed. To be paradigmatically coherent with the nature of a competence, studies should also examine how context influences nursing practice and competency deployment. Design: A focused ethnography of three acute care units from one academic hospital in Canada. Methods: Purposive and snowball sampling strategies were used to recruit 19 participants: NGNs (n = 4), nurse preceptors (n = 2), clinical nurse specialists (n = 9) , and nurse managers (n = 4). Data were collected through individual interviews, focus groups , observation and documentation. Data were analysed according to Roper and Shapira’s (2000) ethnographic nursing analysis framework. Results: Organizational and individual factors were identified as influencing NGNs ’ competenc y deployment. Organizational factors are orientation, stability, workload, and the scientific culture of the unit. Personal factors have been linked to groups of professionals: for NGNs, personality and clinical placements during their initial education; for nurses working with NGNs, to be role models, to promote integration and to denounce bullying; and for other health professionals, to recognize nursing expertise. Conclusion: One way to s mooth the transition from academic to clinical settings for NGNs is by offering transition or orientation programmes that will provide them with stability and a reduced workload, allowing them to progressively deploy their competencies. Relevance to clinical practice: Organizational and individual factors influence how new graduate nurses deploy their competencies. Clinical educators and nurse managers can help new nurses by acting on these factors

Analysis of graduating nursing students’ moral courage in six European countries

Background: Moral courage is defined as courage to act according to one's own ethical values and principles even at the risk of negative consequences for the individual. In a complex nursing practice, ethical considerations are integral. Moral courage is needed throughout nurses' career.Aim: To analyse graduating nursing students' moral courage and the factors associated with it in six European countries.Research design: A cross-sectional design, using a structured questionnaire, as part of a larger international ProCompNurse study. In the questionnaire, moral courage was assessed with a single question (visual analogue scale 0-100), the questionnaire also covered several background variables.Participants and research context: The sample comprised graduating nursing students (n = 1796) from all participating countries. To get a comprehensive view about graduating nursing students' moral courage, the views of nurse managers (n = 538) and patients (n = 1327) from the same units in which the graduating nursing students practised were also explored, with parallel questionnaires.Ethical considerations: Ethical approvals and research permissions were obtained according to national standards in every country and all participants gave their informed consent.Results: The mean of graduating nursing students' self-assessed moral courage was 77.8 (standard deviation 17.0; on a 0-100 scale), with statistically significant differences between countries. Higher moral courage was associated with many factors, especially the level of professional competence. The managers assessed the graduating nursing students' moral courage lower (66.5; standard deviation 18.4) and the patients slightly higher (80.6; standard deviation 19.4) than the graduating nursing students themselves.Discussion and conclusions: In all countries, the graduating nursing students' moral courage was assessed as rather high, with differences between countries and populations. These differences and associations between moral courage and ethics education require further research.</p

Finnish flow diverter study: 8 years of experience in the treatment of acutely ruptured intracranial aneurysms

Background: Flow diversion of acutely ruptured intracranial aneurysms (IAs) is controversial due to high treatment-related complication rates and a lack of supporting evidence. We present clinical and radiological results of the largest series to date.Methods: This is a nationwide retrospective study of acutely ruptured IAs treated with flow diverters (FDs). The primary outcome was the modified Rankin Scale (mRS) score at the last available follow-up time. Secondary outcomes were treatment-related complications and the aneurysm occlusion rate.Results: 110 patients (64 females; mean age 55.7 years; range 12-82 years) with acutely ruptured IAs were treated with FDs between 2012 and 2020 in five centers. 70 acutely ruptured IAs (64%) were located in anterior circulation, and 47 acutely ruptured IAs (43%) were blister-like. A favorable functional outcome (mRS 0-2) was seen in 73% of patients (74/102). Treatment-related complications were seen in 45% of patients (n=49). Rebleeding was observed in 3 patients (3%). The data from radiological follow-ups were available for 80% of patients (n=88), and complete occlusion was seen in 90% of aneurysms (79/88). The data from clinical follow-ups were available for 93% of patients (n=102). The overall mortality rate was 18% (18/102).Conclusions: FD treatment yields high occlusion for acutely ruptured IAs but is associated with a high risk of complications. Considering the high mortality rate of aneurysmal subarachnoid hemorrhage, the prevention of rebleeding is crucial. Thus, FD treatment may be justified as a last resort option.</p

Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback

<p>Abstract</p> <p>Background</p> <p>The motor-driven predictions about expected sensory feedback (efference copies) have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs) were recorded in response to upward pitch shift stimuli (PSS) with five different magnitudes (0, +50, +100, +200 and +400 cents) at voice onset during active vocal production and passive listening to the playback.</p> <p>Results</p> <p>Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents), became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli.</p> <p>Conclusions</p> <p>Findings of the present study suggest that the brain utilizes the motor predictions (efference copies) to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds.</p

Human Auditory Cortical Activation during Self-Vocalization

During speaking, auditory feedback is used to adjust vocalizations. The brain systems mediating this integrative ability have been investigated using a wide range of experimental strategies. In this report we examined how vocalization alters speech-sound processing within auditory cortex by directly recording evoked responses to vocalizations and playback stimuli using intracranial electrodes implanted in neurosurgery patients. Several new findings resulted from these high-resolution invasive recordings in human subjects. Suppressive effects of vocalization were found to occur only within circumscribed areas of auditory cortex. In addition, at a smaller number of sites, the opposite pattern was seen; cortical responses were enhanced during vocalization. This increase in activity was reflected in high gamma power changes, but was not evident in the averaged evoked potential waveforms. These new findings support forward models for vocal control in which efference copies of premotor cortex activity modulate sub-regions of auditory cortex