| 1. |
- Fenstermacher, M.E., et al.
(författare)
-
DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
-
Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
|
|
| 2. |
- Callaway, EM, et al.
(författare)
-
A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
-
Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
|
|
| 3. |
- Tobias, Deirdre K, et al.
(författare)
-
Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
-
Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
-
Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
|
|
| 4. |
|
|
| 5. |
- Santangelo, James S., et al.
(författare)
-
Global urban environmental change drives adaptation in white clover
- 2022
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
-
Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
|
|
| 6. |
- Li, W, et al.
(författare)
-
Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL
- 2020
-
Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1, s. 63-
-
Tidskriftsartikel (refereegranskat)abstract
- Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.
|
|
| 7. |
|
|
| 8. |
- Gustafsson, Jenny K, 1981, et al.
(författare)
-
Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis
- 2021
-
Ingår i: eLife. - 2050-084X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Intestinal goblet cells maintain the protective epithelial barrier through mucus secretion and yet sample lumenal substances for immune processing through formation of goblet cell associated antigen passages (GAPs). The cellular biology of GAPs and how these divergent processes are balanced and regulated by goblet cells remains unknown. Using high-resolution light and electron microscopy, we found that in mice, GAPs were formed by an acetylcholine (ACh)-dependent endocytic event remarkable for delivery of fluid-phase cargo retrograde into the trans-golgi network and across the cell by transcytosis - in addition to the expected transport of fluid-phase cargo by endosomes to multi-vesicular bodies and lysosomes. While ACh also induced goblet cells to secrete mucins, ACh-induced GAP formation and mucin secretion were functionally independent and mediated by different receptors and signaling pathways, enabling goblet cells to differentially regulate these processes to accommodate the dynamically changing demands of the mucosal environment for barrier maintenance and sampling of lumenal substances. eLife digest Cells in the gut need to be protected against the many harmful microbes which inhabit this environment. Yet the immune system also needs to 'keep an eye' on intestinal contents to maintain tolerance to innocuous substances, such as those from the diet. The 'goblet cells' that are part of the gut lining do both: they create a mucus barrier that stops germs from invading the body, but they also can pass on molecules from the intestine to immune cells deep in the tissue to promote tolerance. This is achieved through a 'GAP' mechanism. A chemical messenger called acetylcholine can trigger both mucus release and the GAP process in goblet cells. Gustafsson et al. investigated how the cells could take on these two seemingly opposing roles in response to the same signal. A fluorescent molecule was introduced into the intestines of mice, and monitored as it pass through the goblet cells. This revealed how the GAP process took place: the cells were able to capture molecules from the intestines, wrap them in internal sack-like vesicles and then transport them across the entire cell. To explore the role of acetylcholine, Gustafsson et al. blocked the receptors that detect the messenger at the surface of goblet cells. Different receptors and therefore different cascades of molecular events were found to control mucus secretion and GAP formation; this explains how the two processes can be performed in parallel and independently from each other. Understanding how cells relay molecules to the immune system is relevant to other tissues in contact with the environment, such as the eyes, the airways, or the inside of the genital and urinary tracts. Understanding, and then ultimately harnessing this mechanism could help design of new ways to deliver drugs to the immune system and alter immune outcomes.
|
|
| 9. |
- Kong, Jeremy, et al.
(författare)
-
Incidence, Predictors, and Outcomes Associated With Worsening Renal Function in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.
- 2023
-
Ingår i: Journal of the American Heart Association. - 2047-9980. ; 12:14
-
Tidskriftsartikel (refereegranskat)abstract
- Background The incidence and implications of worsening renal function (WRF) after mitral valve transcatheter edge-to-edge repair (TEER) in patients with heart failure (HF) are unknown. Therefore, the aim of this study was to determine the proportion of patients with HF and secondary mitral regurgitation who develop persistent WRF within 30 days following TEER, and whether this development portends a worse prognosis. Methods and Results In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, 614 patients with HF and severe secondary mitral regurgitation were randomized to TEER with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone. WRF was defined as serum creatinine increase ≥1.5× or ≥0.3 mg/dL from baseline persisting to day 30 or requiring renal replacement therapy. All-cause death and HF hospitalization rates between 30 days and 2 years were compared in patients with and without WRF. WRF at 30 days was present in 11.3% of patients (9.7% in the TEER plus GDMT group and 13.1% in the GDMT alone group; P=0.23). WRF was associated with all-cause death (hazard ratio [HR], 1.98 [95% CI, 1.3-3.03]; P=0.001) but not HF hospitalization (HR, 1.47 [ 95% CI, 0.97-2.24]; P=0.07) between 30 days and 2 years. Compared with GDMT alone, TEER reduced both death and HF hospitalization consistently in patients with and without WRF (Pinteraction=0.53 and 0.57, respectively). Conclusions Among patients with HF and severe secondary mitral regurgitation, the incidence of WRF at 30 days was not increased after TEER compared with GDMT alone. WRF was associated with greater 2-year mortality but did not attenuate the treatment benefits of TEER in reducing death and HF hospitalization compared with GDMT alone. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.
|
|
| 10. |
|
|
| 11. |
- Buckley, Jeffrey, 1992-, et al.
(författare)
-
An assessment of the transparency of contemporary technology education research employing interview-based methodologies
- 2021
-
Ingår i: International journal of technology and design education. - : Springer Nature. - 0957-7572 .- 1573-1804.
-
Tidskriftsartikel (refereegranskat)abstract
- A high level of transparency in reported research is critical for several reasons, such as ensuring an acceptable level of trustworthiness and enabling replication. Transparency in qualitative research permits the identification of specific circumstances which are associated with findings and observations. Thus, transparency is important for the repeatability of original studies and for explorations of the transferability of original findings. There has been no investigation into levels of transparency in reported technology education research to date. With a position that increasing transparency would be beneficial, this article presents an analysis of levels of transparency in contemporary technology education research studies which employed interviews within their methodologies, and which were published within the International Journal of Technology and Design Education and Design and Technology Education: An International Journal (n = 38). The results indicate room for improvement, especially in terms of documenting researcher positionality, determinations of data saturation, and how power imbalances were managed. A discussion is presented on why it is important to improve levels of transparency in reported studies, and a guide on areas to make transparent is presented for qualitative and quantitative research.
|
|
| 12. |
- Khatri, Sumita B., et al.
(författare)
-
Use of fractional exhaled nitric oxide to guide the treatment of asthma an official american thoracic society clinical practice guideline
- 2021
-
Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 204:10, s. 97-109
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidencebased answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence.
|
|
| 13. |
- Lord, Edna, et al.
(författare)
-
Ancient DNA of Guinea Pigs (Cavia spp.) Indicates a Probable New Center of Domestication and Pathways of Global Distribution
- 2020
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Guinea pigs (Cavia spp.) have a long association with humans. From as early as 10,000 years ago they were a wild food source. Later, domesticated Cavia porcellus were dispersed well beyond their native range through pre-Columbian exchange networks and, more recently, widely across the globe. Here we present 46 complete mitogenomes of archaeological guinea pigs from sites in Peru, Bolivia, Colombia, the Caribbean, Belgium and the United States to elucidate their evolutionary history, origins and paths of dispersal. Our results indicate an independent centre of domestication of Cavia in the eastern Colombian Highlands. We identify a Peruvian origin for the initial introduction of domesticated guinea pigs (Cavia porcellus) beyond South America into the Caribbean. We also demonstrate that Peru was the probable source of the earliest known guinea pigs transported, as part of the exotic pet trade, to both Europe and the southeastern United States. Finally, we identify a modern reintroduction of guinea pigs to Puerto Rico, where local inhabitants use them for food. This research demonstrates that the natural and cultural history of guinea pigs is more complex than previously known and has implications for other studies regarding regional to global-scale studies of mammal domestication, translocation, and distribution.
|
|
| 14. |
- Patterson, Brooke E., et al.
(författare)
-
Evaluation of an injury prevention programme (Prep-to-Play) in women and girls playing Australian Football : design of a pragmatic, type III, hybrid implementation-effectiveness, stepped-wedge, cluster randomised controlled trial
- 2022
-
Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 12:9
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Due to the increase in participation and risk of anterior cruciate ligament (ACL) injuries and concussion in womens Australian Football, an injury prevention programme (Prep-to-Play) was codesigned with consumers (eg, coaches, players) and stakeholders (eg, the Australian Football League). The impact of supported and unsupported interventions on the use of Prep-to-Play (primary aim) and injury rates (secondary aim) will be evaluated in women and girls playing community Australian Football. Methods and analysis This stepped-wedge, cluster randomised controlled trial will include >= 140 teams from U16, U18 or senior womens competitions. All 10 geographically separated clusters (each containing >= 14 teams) will start in the control (unsupported) phase and be randomised to one of five dates (or wedges) during the 2021 or 2022 season to sequentially transition to the intervention (supported Prep-to-Play), until all teams receive the intervention. Prep-to-Play includes four elements: a neuromuscular training warm-up, contact-focussed football skills (eg, tackling), strength exercises and education (eg, technique cues). When transitioning to supported interventions, study physiotherapists will deliver a workshop to coaches and player leaders on how to use Prep-to-Play, attend team training at least two times and provide ongoing support. In the unsupported phase, team will continue usual routines and may freely access available Prep-to-Play resources online (eg, posters and videos about the four elements), but without additional face-to-face support. Outcomes will be evaluated throughout the 2021 and 2022 seasons (similar to 14 weeks per season). Primary outcome: use of Prep-to-Play will be reported via a team designate (weekly) and an independent observer (five visits over the two seasons) and defined as the team completing 75% of the programme, two-thirds (67%) of the time. Secondary outcomes: injuries will be reported by the team sports trainer and/or players. Injury definition: any injury occurring during a football match or training that results in: (1) being unable to return to the field of play for that match or (2) missing >= one match. Outcomes in the supported and unsupported phases will be compared using a generalised linear mixed model adjusting for clustering and time. Due to the type III hybrid implementation-effectiveness design, the study is powered to detect a improvement in use of Prep-to-Play and a reduction in ACL injuries. Ethics and dissemination La Trobe University Ethics Committee (HREC 20488) approved. Coaches provided informed consent to receive the supported intervention and players provided consent to be contacted if they sustained a head or knee injury. Results will be disseminated through partner organisations, peer-reviewed publications and scientific conferences.
|
|
| 15. |
- Pettersen, A. K., et al.
(författare)
-
Population divergence in maternal investment and embryo energy use and allocation suggests adaptive responses to cool climates
- 2023
-
Ingår i: Journal of Animal Ecology. - 0021-8790. ; 92:9, s. 1771-1785
-
Tidskriftsartikel (refereegranskat)abstract
- The thermal sensitivity of early life stages can play a fundamental role in constraining species distributions. For egg-laying ectotherms, cool temperatures often extend development time and exacerbate developmental energy cost. Despite these costs, egg laying is still observed at high latitudes and altitudes. How embryos overcome the developmental constraints posed by cool climates is crucial knowledge for explaining the persistence of oviparous species in such environments and for understanding thermal adaptation more broadly. Here, we studied maternal investment and embryo energy use and allocation in wall lizards spanning altitudinal regions, as potential mechanisms that enable successful development to hatching in cool climates. Specifically, we compared population-level differences in (1) investment from mothers (egg mass, embryo retention and thyroid yolk hormone concentration), (2) embryo energy expenditure during development, and (3) embryo energy allocation from yolk towards tissue. We found evidence that energy expenditure was greater under cool compared with warm incubation temperatures. Females from relatively cool regions did not compensate for this energetic cost of development by producing larger eggs or increasing thyroid hormone concentration in yolk. Instead, embryos from the high-altitude region used less energy to complete development, that is, they developed faster without a concomitant increase in metabolic rate, compared with those from the low-altitude region. Embryos from high altitudes also allocated relatively more energy towards tissue production, hatching with lower residual yolk: tissue ratios than low-altitude region embryos. These results are consistent with local adaptation to cool climate and suggest that this is underpinned by mechanisms that regulate embryonic utilisation of yolk reserves and its allocation towards tissue, rather than shifts in maternal investment of yolk content or composition.
|
|
| 16. |
- Simm, T. H., et al.
(författare)
-
The τ-plot, a multicomponent 1-D pole figure plot, to quantify the heterogeneity of plastic deformation
- 2020
-
Ingår i: Materials Characterization. - : Elsevier Inc.. - 1044-5803 .- 1873-4189. ; 160
-
Tidskriftsartikel (refereegranskat)abstract
- An approach is presented that allows multi-scale characterisations of heterogeneous deformation in crystalline materials by employing a range of characterisation techniques including: electron backscatter diffraction, digital image correlation and neutron diffraction powder measurements. The approach will be used to obtain critical information about the variations in parameters that characterise the deformed state in different crystallographic orientation texture components of a sample in a statistically significant way. These parameters include lattice strains, texture evolution, peak broadening, dislocation density, planar faults, phase changes and surface strain. This approach allows verification of models of plastic deformation to provide a more detailed view of plastic deformation heterogeneity at multiple length scales than obtained by other characterisation approaches. The approach demonstrated here is applied to two stainless steel alloys; an alloy that exhibits phase transformation during deformation and an alloy that remains the same phase all through deformation process.
|
|
| 17. |
- Ulrich, Roger, 1946, et al.
(författare)
-
ICU Patient Family Stress Recovery During Breaks in a Hospital Garden and Indoor Environments
- 2020
-
Ingår i: HERD. - : SAGE Publications. - 2167-5112 .- 1937-5867. ; 13:2, s. 83-102
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives : Measure the immediate change in intensive care unit (ICU) family members’ state stress levels from the beginning to the end of a person’s visit to a hospital garden and compare the changes produced by the garden with those associated with spending time in indoor hospital environments intended for respite and relaxation. Background : No previous research has compared the efficacy of different physical environments as interventions to foster stress reduction in family members of ICU patients, a group of hospital visitors known to experience high levels of distress. Method : A convenience sample of 42 ICU patient family (from 42 different families) completed the Present Functioning Visual Analogue Scales (PFVAS) before and after each visit (128 total visits) to a garden, an atrium/café, or ICU waiting room. Results : Stress scores significantly declined (i.e., improved) from the start to the end of a break on all PFVAS subscales (p <.0001) in both the garden and indoors locations. However, it is noteworthy that garden breaks resulted in significantly greater improvement in the “sadness” scale than breaks in indoor locations (p =.03), and changes in all five other PFVAS scores showed somewhat more reduction of stress for breaks spent in the garden than indoors, although these differences were not statistically significant. Conclusion : Creating an unlocked garden with abundant nature located close to an ICU can be an effective intervention for significantly mitigating state stress in family members of ICU patients and can be somewhat more effective than indoor areas expressly designed for family respite and relaxation.
|
|
