48 research outputs found

    Orexin Receptor Activation Generates Gamma Band Input to Cholinergic and Serotonergic Arousal System Neurons and Drives an Intrinsic Ca(2+)-Dependent Resonance in LDT and PPT Cholinergic Neurons

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    A hallmark of the waking state is a shift in EEG power to higher frequencies with epochs of synchronized intracortical gamma activity (30-60 Hz) - a process associated with high-level cognitive functions. The ascending arousal system, including cholinergic laterodorsal (LDT) and pedunculopontine (PPT) tegmental neurons and serotonergic dorsal raphe (DR) neurons, promotes this state. Recently, this system has been proposed as a gamma wave generator, in part, because some neurons produce high-threshold, Ca(2+)-dependent oscillations at gamma frequencies. However, it is not known whether arousal-related inputs to these neurons generate such oscillations, or whether such oscillations are ever transmitted to neuronal targets. Since key arousal input arises from hypothalamic orexin (hypocretin) neurons, we investigated whether the unusually noisy, depolarizing orexin current could provide significant gamma input to cholinergic and serotonergic neurons, and whether such input could drive Ca(2+)-dependent oscillations. Whole-cell recordings in brain slices were obtained from mice expressing Cre-induced fluorescence in cholinergic LDT and PPT, and serotonergic DR neurons. After first quantifying reporter expression accuracy in cholinergic and serotonergic neurons, we found that the orexin current produced significant high frequency, including gamma, input to both cholinergic and serotonergic neurons. Then, by using a dynamic clamp, we found that adding a noisy orexin conductance to cholinergic neurons induced a Ca(2+)-dependent resonance that peaked in the theta and alpha frequency range (4-14 Hz) and extended up to 100 Hz. We propose that this orexin current noise and the Ca(2+) dependent resonance work synergistically to boost the encoding of high-frequency synaptic inputs into action potentials and to help ensure cholinergic neurons fire during EEG activation. This activity could reinforce thalamocortical states supporting arousal, REM sleep, and intracortical gamma

    A systematic review of participatory scenario planning to envision mountain social-ecological systems futures

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    Mountain social-ecological systems (MtSES) provide crucial ecosystem services to over half of humanity. However, populations living in these highly varied regions are now confronted by global change. It is critical that they are able to anticipate change to strategically manage resources and avoid potential conflict. Yet, planning for sustainable, equitable transitions for the future is a daunting task, considering the range of uncertainties and the unique character of MtSES. Participatory scenario planning (PSP) can help MtSES communities by critically reflecting on a wider array of innovative pathways for adaptive transformation. Although the design of effective approaches has been widely discussed, how PSP has been employed in MtSES has yet to be examined. Here, we present the first systematic global review of single- and multiscalar, multisectoral PSP undertaken in MtSES, in which we characterize the process, identify strengths and gaps, and suggest effective ways to apply PSP in MtSES. We used a nine-step process to help guide the analysis of 42 studies from 1989 screened articles. Our results indicate a steady increase in relevant studies since 2006, with 43% published between 2015 and 2017. These studies encompass 39 countries, with over 50% in Europe. PSP in MtSES is used predominantly to build cooperation, social learning, collaboration, and decision support, yet meeting these objectives is hindered by insufficient engagement with intended end users. MtSES PSP has focused largely on envisioning themes of governance, economy, land use change, and biodiversity, but has overlooked themes such as gender equality, public health, and sanitation. There are many avenues to expand and improve PSP in MtSES: to other regions, sectors, across a greater diversity of stakeholders, and with a specific focus on MtSES paradoxes. Communicating uncertainty, monitoring and evaluating impacts, and engendering more comparative approaches can further increase the utility of PSP for addressing MtSES challenges, with lessons for other complex social-ecological systems

    A systematic review of participatory scenario planning to envision mountain social-ecological systems futures

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    Mountain social-ecological systems (MtSES) provide crucial ecosystem services to over half of humanity. However, populations living in these highly varied regions are now confronted by global change. It is critical that they are able to anticipate change to strategically manage resources and avoid potential conflict. Yet, planning for sustainable, equitable transitions for the future is a daunting task, considering the range of uncertainties and the unique character of MtSES. Participatory scenario planning (PSP) can help MtSES communities by critically reflecting on a wider array of innovative pathways for adaptive transformation. Although the design of effective approaches has been widely discussed, how PSP has been employed in MtSES has yet to be examined. Here, we present the first systematic global review of single- and multiscalar, multisectoral PSP undertaken in MtSES, in which we characterize the process, identify strengths and gaps, and suggest effective ways to apply PSP in MtSES. We used a nine-step process to help guide the analysis of 42 studies from 1989 screened articles. Our results indicate a steady increase in relevant studies since 2006, with 43% published between 2015 and 2017. These studies encompass 39 countries, with over 50% in Europe. PSP in MtSES is used predominantly to build cooperation, social learning, collaboration, and decision support, yet meeting these objectives is hindered by insufficient engagement with intended end users. MtSES PSP has focused largely on envisioning themes of governance, economy, land use change, and biodiversity, but has overlooked themes such as gender equality, public health, and sanitation. There are many avenues to expand and improve PSP in MtSES: to other regions, sectors, across a greater diversity of stakeholders, and with a specific focus on MtSES paradoxes. Communicating uncertainty, monitoring and evaluating impacts, and engendering more comparative approaches can further increase the utility of PSP for addressing MtSES challenges, with lessons for other complex social-ecological systems. © 2020 by the author(s)

    Linking model design and application for transdisciplinary approaches in social-ecological systems

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    This work was supported by the US National Science Foundation through the Mountain Sentinels Research Coordination Network (NSF #1414106), the Swiss National Science Foundation through MtnPaths – Pathways for global change adaptation of mountain socio-ecological systems (#20521L_169916), and the Center for Collaborative Conservation at Colorado State University.As global environmental change continues to accelerate and intensify, science and society are turning to trans- disciplinary approaches to facilitate transitions to sustainability. Modeling is increasingly used as a technological tool to improve our understanding of social-ecological systems (SES), encourage collaboration and learning, and facilitate decision-making. This study improves our understanding of how SES models are designed and applied to address the rising challenges of global environmental change, using mountains as a representative system. We analyzed 74 peer-reviewed papers describing dynamic models of mountain SES, evaluating them according to characteristics such as the model purpose, data and model type, level of stakeholder involvement, and spatial extent/resolution. Slightly more than half the models in our analysis were participatory, yet only 21.6% of papers demonstrated any direct outreach to decision makers. We found that SES models tend to under-represent social datasets, with ethnographic data rarely incorporated. Modeling efforts in conditions of higher stakeholder diversity tend to have higher rates of decision support compared to situations where stakeholder diversity is absent or not addressed. We discuss our results through the lens of appropriate technology, drawing on the concepts of boundary objects and scalar devices from Science and Technology Studies. We propose four guiding principles to facilitate the development of SES models as appropriate technology for transdisciplinary applications: (1) increase diversity of stakeholders in SES model design and application for improved collaboration; (2) balance power dynamics among stakeholders by incorporating diverse knowledge and data types; (3) promote flexibility in model design; and (4) bridge gaps in decision support, learning, and communication. Creating SES models that are appropriate tech- nology for transdisciplinary applications will require advanced planning, increased funding for and attention to the role of diverse data and knowledge, and stronger partnerships across disciplinary divides. Highly contextualized participatory modeling that embraces diversity in both data and actors appears poised to make strong contributions to the world’s most pressing environmental challenges.PostprintPeer reviewe

    Labelling and Family Resemblance in the discrimination of polymorphous categories by pigeons

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    publication-status: Acceptedtypes: Article© 2011 Springer Verlag. This is a post print version of the article published in Animal Cognition, 2011, 14 (1), pp 21-34. The final publication is available at link.springer.comTwo experiments examined whether pigeons discriminate polymorphous categories on the basis of a single highly predictive feature or overall similarity. In the first experiment, pigeons were trained to discriminate between categories of photographs of complex real objects. Within these pictures, single features had been manipulated to produce a highly salient texture cue. Either the picture or the texture provided a reliable cue for discrimination during training, but in probe tests, the picture and texture cues were put into conflict. Some pigeons showed a significant tendency to discriminate on the basis of the picture cue (overall similarity or family resemblance), whereas others appeared to rely on the manipulated texture cue. The second experiment used artificial polymorphous categories in which one dimension of the stimulus provided a completely reliable cue to category membership, whereas three other dimensions provided cues that were individually unreliable but collectively provided a completely reliable basis for discrimination. Most pigeons came under the control of the reliable cue rather than the unreliable cues. A minority, however, came under the control of single dimensions from the unreliable set. We conclude that cue salience can be more important than cue reliability in determining what features will control behavior when multiple cues are available

    Reshaping ophthalmology training after COVID-19 pandemic

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    Background The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on practical activities and didactic teaching of residents and fellows. This survey aimed to propose long-term changes for ophthalmology training based on the changes experienced by trainees and their perception of new training opportunities. Methods An online survey was distributed to ophthalmology trainees in multiple countries. Descriptive statistics were used to analyse the data. Results A total of 504 analyzable responses were collected from 32 different countries. The current impact of COVID-19 pandemic was described as "severe" by most trainees (55.2%); however, the future perspective was more optimistic as demonstrated by the greater number of responses reporting a presumed "moderate" (37.3%), "mild" (14.1%) or "slight" (4.2%) long-term impact. The vast majority of trainees reported a decrease >= 50% of clinical activity (76.4%) and >75% of surgical activity (74.6%). Although an initial gap in didactic teaching has been experienced by many (55.4%), regular web-based teaching was reportedly attended by 67.7% of the respondents. A strong agreement was found regarding the worthwhile role of web-based case-presentations in clinical training (91.7%), web-based discussion of edited surgical videos (85.7%) and simulation-based practice (86.9%) in surgical training. Conclusions This survey, focusing on trainees' perspective, strongly reinforces the need to promptly include new technology-based training tools, such as web-based teaching, virtual surgical simulators, and telementoring, in long-term reorganisation of ophthalmology training to ensure its continuity and effectiveness, which would remain available even in the face of another unpredictable crisis within the health system

    Reshaping ophthalmology training after COVID-19 pandemic

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    Background: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on practical activities and didactic teaching of residents and fellows. This survey aimed to propose long-term changes for ophthalmology training based on the changes experienced by trainees and their perception of new training opportunities. Methods: An online survey was distributed to ophthalmology trainees in multiple countries. Descriptive statistics were used to analyse the data. Results: A total of 504 analyzable responses were collected from 32 different countries. The current impact of COVID-19 pandemic was described as “severe” by most trainees (55.2%); however, the future perspective was more optimistic as demonstrated by the greater number of responses reporting a presumed “moderate” (37.3%), “mild” (14.1%) or “slight” (4.2%) long-term impact. The vast majority of trainees reported a decrease ≥50% of clinical activity (76.4%) and >75% of surgical activity (74.6%). Although an initial gap in didactic teaching has been experienced by many (55.4%), regular web-based teaching was reportedly attended by 67.7% of the respondents. A strong agreement was found regarding the worthwhile role of web-based case-presentations in clinical training (91.7%), web-based discussion of edited surgical videos (85.7%) and simulation-based practice (86.9%) in surgical training. Conclusions: This survey, focusing on trainees’ perspective, strongly reinforces the need to promptly include new technology-based training tools, such as web-based teaching, virtual surgical simulators, and telementoring, in long-term reorganisation of ophthalmology training to ensure its continuity and effectiveness, which would remain available even in the face of another unpredictable crisis within the health systempublishersversionPeer reviewe

    Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials

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    A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

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    Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

    A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.

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    Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies
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