| 1. |
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| 2. |
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| 3. |
- Bethlehem, RAI, et al.
(author)
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Brain charts for the human lifespan
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
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Journal article (peer-reviewed)abstract
- Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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| 4. |
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| 5. |
- Jakosky, B. M., et al.
(author)
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MAVEN observations of the response of Mars to an interplanetary coronal mass ejection
- 2015
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 350:6261
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Journal article (peer-reviewed)abstract
- Coupling between the lower and upper atmosphere, combined with loss of gas from the upper atmosphere to space, likely contributed to the thin, cold, dry atmosphere of modern Mars. To help understand ongoing ion loss to space, the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft made comprehensive measurements of the Mars upper atmosphere, ionosphere, and interactions with the Sun and solar wind during an interplanetary coronal mass ejection impact in March 2015. Responses include changes in the bow shock and magnetosheath, formation of widespread diffuse aurora, and enhancement of pick-up ions. Observations and models both show an enhancement in escape rate of ions to space during the event. Ion loss during solar events early in Mars history may have been a major contributor to the long-term evolution of the Mars atmosphere.
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| 6. |
- Jakosky, B. M., et al.
(author)
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The Mars Atmosphere and Volatile Evolution (MAVEN) Mission
- 2015
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In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 195:1-4, s. 3-48
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Research review (peer-reviewed)abstract
- The MAVEN spacecraft launched in November 2013, arrived at Mars in September 2014, and completed commissioning and began its one-Earth-year primary science mission in November 2014. The orbiter's science objectives are to explore the interactions of the Sun and the solar wind with the Mars magnetosphere and upper atmosphere, to determine the structure of the upper atmosphere and ionosphere and the processes controlling it, to determine the escape rates from the upper atmosphere to space at the present epoch, and to measure properties that allow us to extrapolate these escape rates into the past to determine the total loss of atmospheric gas to space through time. These results will allow us to determine the importance of loss to space in changing the Mars climate and atmosphere through time, thereby providing important boundary conditions on the history of the habitability of Mars. The MAVEN spacecraft contains eight science instruments (with nine sensors) that measure the energy and particle input from the Sun into the Mars upper atmosphere, the response of the upper atmosphere to that input, and the resulting escape of gas to space. In addition, it contains an Electra relay that will allow it to relay commands and data between spacecraft on the surface and Earth.
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| 7. |
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| 8. |
- Battisti, N. M. L., et al.
(author)
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Adapting care for older cancer patients during the COVID-19 pandemic: Recommendations from the International Society of Geriatric Oncology (SIOG) COVID-19 Working Group
- 2020
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In: Journal of Geriatric Oncology. - : Elsevier BV. - 1879-4068. ; 11:8, s. 1190-1198
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Journal article (peer-reviewed)abstract
- The COVID-19 pandemic poses a barrier to equal and evidence-based management of cancer in older adults. The International Society of Geriatric Oncology (SIOG) formed a panel of experts to develop consensus recommendations on the implications of the pandemic on several aspects of cancer care in this age group including geriatric assessment (GA), surgery, radiotherapy, systemic treatment, palliative care and research. Age and cancer diagnosis are significant predictors of adverse outcomes of the COVID-19 infection. In this setting, GA is particularly valuable to drive decision-making. GA may aid estimating physiologic reserve and adaptive capability, assessing risk-benefits of either providing or temporarily withholding treatments, and determining patient preferences to help inform treatment decisions. In a resource-constrained setting, geriatric screening tools may be administered remotely to identify patients requiring comprehensive GA. Tele-health is also crucial to ensure adequate continuity of care and minimize the risk of infection exposure. In general, therapeutic decisions should favor the most effective and least invasive approach with the lowest risk of adverse outcomes. In selected cases, this might require deferring or omitting surgery, radiotherapy or systemic treatments especially where benefits are marginal and alternative safe therapeutic options are available. Ongoing research is necessary to expand knowledge of the management of cancer in older adults. However, the pandemic presents a significant barrier and efforts should be made to ensure equitable access to clinical trials and prospective data collection to elucidate the outcomes of COVID-19 in this population. © 2020 Elsevier Inc.
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| 9. |
- Ring, A., et al.
(author)
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Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer
- 2021
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 125, s. 209-219
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Journal article (peer-reviewed)abstract
- Background: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. Methods: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. Results: Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed. Conclusions: Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. Trial Registration: ISRCTN 46099296. © 2021, The Author(s).
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| 11. |
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| 12. |
- Holmes, G. R., et al.
(author)
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Cost-Effectiveness Modeling of Surgery Plus Adjuvant Endocrine Therapy Versus Primary Endocrine Therapy Alone in UK Women Aged 70 and Over With Early Breast Cancer
- 2021
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In: Value in Health. - : Elsevier BV. - 1098-3015. ; 24:6, s. 770-779
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Journal article (peer-reviewed)abstract
- Objectives: Approximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective. Methods: Survival outcomes from a statistical model, and published data on recurrence, were combined with data from a large, multicenter, prospective cohort study of over 3400 UK women aged 70+ with early breast cancer and median 52-month follow-up, to populate a probabilistic economic model. This model evaluated the cost-effectiveness of surgery plus adjuvant therapies relative to PET for 24 illustrative subgroups: Age {70, 80, 90} × Nodal status {FALSE (F), TRUE (T)} × Comorbidity score {0, 1, 2, 3+}. Results: For a 70-year-old with no lymph node involvement and no comorbidities (70, F, 0), surgery plus adjuvant therapies was cheaper and more effective than PET. For other subgroups, surgery plus adjuvant therapies was more effective but more expensive. Surgery plus adjuvant therapies was not cost-effective for 4 of the 24 subgroups: (90, F, 2), (90, F, 3), (90, T, 2), (90, T, 3). Conclusion: From a UK perspective, surgery plus adjuvant therapies is clinically effective and cost-effective for most women aged 70+ with early breast cancer. Cost-effectiveness reduces with age and comorbidities, and for women over 90 with multiple comorbidities, there is little cost benefit and a negative impact on quality of life. © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research
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| 13. |
- Edberg, Niklas, et al.
(author)
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Rosetta and Mars Express observations of the influence of high solar wind pressure on the Martian plasma environment
- 2009
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In: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 27:12, s. 4533-4545
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Journal article (peer-reviewed)abstract
- We report on new simultaneous in-situ observations at Mars from Rosetta and Mars Express (MEX) on how the Martian plasma environment is affected by high pressure solar wind. A significant sharp increase in solar wind density, magnetic field strength and turbulence followed by a gradual increase in solar wind velocity is observed during similar to 24 h in the combined data set from both spacecraft after Rosetta's closest approach to Mars on 25 February 2007. The bow shock and magnetic pileup boundary are coincidently observed by MEX to become asymmetric in their shapes. The fortunate orbit of MEX at this time allows a study of the inbound boundary crossings on one side of the planet and the outbound crossings on almost the opposite side, both very close to the terminator plane. The solar wind and interplanetary magnetic field (IMF) downstream of Mars are monitored through simultaneous measurements provided by Rosetta. Possible explanations for the asymmetries are discussed, such as crustal magnetic fields and IMF direction. In the same interval, during the high solar wind pressure pulse, MEX observations show an increased amount of escaping planetary ions from the polar region of Mars. We link the high pressure solar wind with the observed simultaneous ion outflow and discuss how the pressure pulse could also be associated with the observed boundary shape asymmetry.
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| 14. |
- Wyld, L., et al.
(author)
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Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices
- 2021
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In: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 108:5, s. 499-510
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. METHODS: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. RESULTS: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P=0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P=0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P=0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P=0.013). Survival was similar in both arms. CONCLUSION: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com). © The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.
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| 15. |
- Wyld, L., et al.
(author)
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Improving outcomes for women aged 70 years or above with early breast cancer: Research programme including a cluster RCT
- 2022
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In: Programme Grants for Applied Research. - 2050-4322. ; 10:6
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Journal article (peer-reviewed)abstract
- Background: In breast cancer management, age-related practice variation is widespread, with older women having lower rates of surgery and chemotherapy than younger women, based on the premise of reduced treatment tolerance and benefit. This may contribute to inferior outcomes. There are currently no age-and fitness-stratified guidelines on which to base treatment recommendations. Aim: We aimed to optimise treatment choice and outcomes for older women (aged > 70 years) with operable breast cancer. Objectives: Our objectives were to (1) determine the age, comorbidity, frailty, disease stage and biology thresholds for endocrine therapy alone versus surgery plus adjuvant endocrine therapy, or adjuvant chemotherapy versus no chemotherapy, for older women with breast cancer; (2) optimise survival outcomes for older women by improving the quality of treatment decision-making; (3) develop and evaluate a decision support intervention to enhance shared decision-making; and (4) determine the degree and causes of treatment variation between UK breast units. Design: A prospective cohort study was used to determine age and fitness thresholds for treatment allocation. Mixed-methods research was used to determine the information needs of older women to develop a decision support intervention. A cluster-randomised trial was used to evaluate the impact of this decision support intervention on treatment choices and outcomes. Health economic analysis was used to evaluate the cost-benefit ratio of different treatment strategies according to age and fitness criteria. A mixed-methods study was used to determine the degree and causes of variation in treatment allocation. Main outcome measures: The main outcome measures were enhanced age-and fitness-specific decision support leading to improved quality-of-life outcomes in older women (aged > 70 years) with early breast cancer. Results: (1) Cohort study: The study recruited 3416 UK women aged > 70 years (median age 77 years). Follow-up was 52 months. (a) The surgery plus adjuvant endocrine therapy versus endocrine therapy alone comparison: 2854 out of 3416 (88%) women had oestrogen-receptor-positive breast cancer, 2354 of whom received surgery plus adjuvant endocrine therapy and 500 received endocrine therapy alone. Patients treated with endocrine therapy alone were older and frailer than patients treated with surgery plus adjuvant endocrine therapy. Unmatched overall survival and breast-cancer-specific survival were higher in the surgery plus adjuvant endocrine therapy group (overall survival: Hazard ratio 0.27, 95% confidence interval 0.23 to 0.33; p < 0.001; breast-cancer-specific survival: Hazard ratio 0.41, 95% confidence interval 0.29 to 0.58; p < 0.001) than in the endocrine therapy alone group. In matched analysis, surgery plus adjuvant endocrine therapy was still associated with better overall survival (hazard ratio 0.72, 95% confidence interval 0.53 to 0.98; p = 0.04) than endocrine therapy alone, but not with better breast-cancer-specific survival (hazard ratio 0.74, 95% confidence interval 0.40 to 1.37; p = 0.34) or progression-free-survival (hazard ratio 1.11, 95% confidence interval 0.55 to 2.26; p = 0.78). (b) The adjuvant chemotherapy versus no chemotherapy comparison: 2811 out of 3416 (82%) women received surgery plus adjuvant endocrine therapy, of whom 1520 (54%) had high-recurrence-risk breast cancer [grade 3, node positive, oestrogen receptor negative or human epidermal growth factor receptor-2 positive, or a high Oncotype DX® (Genomic Health, Inc., Redwood City, CA, USA) score of > 25]. In this high-risk population, there were no differences according to adjuvant chemotherapy use in overall survival or breast-cancer-specific survival after propensity matching. Adjuvant chemotherapy was associated with a lower risk of metastatic recurrence than no chemotherapy in the unmatched (adjusted hazard ratio 0.36, 95% confidence interval 0.19 to 0.68; p = 0.002) and propensity-matched patients (adjusted hazard ratio 0.43, 95% confidence interval 0.20 to 0.92; p = 0.03). Adjuva t chemotherapy improved the overall survival and breast-cancer-specific survival of patients with oestrogen-receptor-negative disease. (2) Mixed-methods research to develop a decision support intervention: An iterative process was used to develop two decision support interventions (each comprising a brief decision aid, a booklet and an online tool) specifically for older women facing treatment choices (endocrine therapy alone or surgery plus adjuvant endocrine therapy, and adjuvant chemotherapy or no chemotherapy) using several evidence sources (expert opinion, literature and patient interviews). The online tool was based on models developed using registry data from 23,842 patients and validated on an external data set of 14,526 patients. Mortality rates at 2 and 5 years differed by < 1% between predicted and observed values. (3) Cluster-randomised clinical trial of decision support tools: 46 UK breast units were randomised (intervention, n = 21; usual care, n = 25), recruiting 1339 women (intervention, n = 670; usual care, n = 669). There was no significant difference in global quality of life at 6 months post baseline (difference-0.20, 95% confidence interval-2.7 to 2.3; p = 0.90). In women offered a choice of endocrine therapy alone or surgery plus adjuvant endocrine therapy, knowledge about treatments was greater in the intervention arm than the usual care arm (94% vs. 74%; p = 0.003). Treatment choice was altered, with higher rates of endocrine therapy alone than of surgery in the intervention arm. Similarly, chemotherapy rates were lower in the intervention arm (endocrine therapy alone rate: Intervention sites 21% vs. usual-care sites 15%, difference 5.5%, 95% confidence interval 1.1% to 10.0%; p = 0.02; adjuvant chemotherapy rate: Intervention sites 10% vs. usual-care site 15%, difference 4.5%, 95% confidence interval 0.0% to 8.0%; p = 0.013). Survival was similar in both arms. (4) Health economic analysis: A probabilistic economic model was developed using registry and cohort study data. For most health and fitness strata, surgery plus adjuvant endocrine therapy had lower costs and returned more quality-adjusted life-years than endocrine therapy alone. However, for some women aged > 90 years, surgery plus adjuvant endocrine therapy was no longer cost-effective and generated fewer quality-adjusted life-years than endocrine therapy alone. The incremental benefit of surgery plus adjuvant endocrine therapy reduced with age and comorbidities. (5) Variation in practice: analysis of rates of surgery plus adjuvant endocrine therapy or endocrine therapy alone between the 56 breast units in the cohort study demonstrated significant variation in rates of endocrine therapy alone that persisted after adjustment for age, fitness and stage. Clinician preference was an important determinant of treatment choice. Conclusions: This study demonstrates that, for older women with oestrogen-receptor-positive breast cancer, there is a cohort of women with a life expectancy of < 4 years for whom surgery plus adjuvant endocrine therapy may offer little benefit and simply have a negative impact on quality of life. The Age Gap decision tool may help make this shared decision. Similarly, although adjuvant chemotherapy offers little benefit and has a negative impact on quality of life for the majority of older women with oestrogen-receptor-positive breast cancer, for women with oestrogen-receptor-negative breast cancer, adjuvant chemotherapy is beneficial. The negative impacts of adjuvant chemotherapy on quality of life, although significant, are transient. This implies that, for the majority of fitter women aged > 70 years, standard care should be offered. Limitations: As with any observational study, despite detailed propensity score matching, residual bias cannot be excluded. Follow-up was at median 52 months for the cohort analysis. Longer-term follow-up will be required to validate these findings owing to the slow time course of oestrogen-receptor-positive breast cancer. Future work: The online algorithm is now available (URL: Https://ag gap.shef.ac.uk/; accessed May 2022). There are plans to validate the tool and incorprate quality-of-life and 10-year survival outcomes.
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| 16. |
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| 17. |
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| 18. |
- Dieval, Catherine, et al.
(author)
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A case study of proton precipitation at Mars : Mars Express observations and hybrid simulations
- 2012
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117
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Journal article (peer-reviewed)abstract
- Using the data from the Analyzer of Space Plasma and Energetic Atoms (ASPERA-3) experiment on board Mars Express and hybrid simulations, we have investigated the entry of protons into the Martian induced magnetosphere. We discuss one orbit on the dayside with observations of significant proton fluxes at altitudes down to 260 km on 27 February 2004. The protons observed below the induced magnetosphere boundary at an altitude of less than 700 km have energies of a few keV, travel downward, and precipitate onto the atmosphere. The measured energy flux and particle flux are 108–109 eV cm−2 s−1 and 105–106 H+ cm−2 s−1, respectively. The proton precipitation occurs because the Martian magnetosheath is small with respect to the heated proton gyroradius in the subsolar region. The data suggest that the precipitation is not permanent but may occur when there are transient increases in the magnetosheath proton temperature. The higher-energy protons penetrate deeper because of their larger gyroradii. The proton entry into the induced magnetosphere is simulated using a hybrid code. A simulation using a fast solar wind as input can reproduce the high energies of the observed precipitating protons. The model shows that the precipitating protons originate from both the solar wind and the planetary exosphere. The precipitation extends over a few thousand kilometers along the orbit of the spacecraft. The proton precipitation does not necessarily correlate with the crustal magnetic anomalies.
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| 19. |
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| 20. |
- Morgan, J. L., et al.
(author)
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Observational cohort study to determine the degree and causes of variation in the rate of surgery or primary endocrine therapy in older women with operable breast cancer
- 2021
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983. ; 47:2, s. 261-268
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Journal article (peer-reviewed)abstract
- Background: In the UK there is variation in the treatment of older women with breast cancer, with up to 40% receiving primary endocrine therapy (PET), which is associated with inferior survival. Case mix and patient choice may explain some variation in practice but clinician preference may also be important. Methods: A multicentre prospective cohort study of women aged >70 with operable breast cancer. Patient characteristics (health status, age, tumour characteristics, treatment allocation and decision-making preference) were analysed to identify whether treatment variation persisted following case-mix adjustment. Expected case-mix adjusted surgery rates were derived by logistic regression using the variables age, co-morbidity, tumour stage and grade. Concordance between patients’ preferred and actual decision-making style was assessed and associations between age, treatment and decision-making style calculated. Results: Women (median age 77, range 70–102) were recruited from 56 UK breast units between 2013 and 2018. Of 2854/3369 eligible women with oestrogen receptor positive breast cancer, 2354 were treated with surgery and 500 with PET. Unadjusted surgery rates varied between hospitals, with 23/56 units falling outside the 95% confidence intervals on funnel plots. Adjusting for case mix reduced, but did not eliminate, this variation between hospitals (10/56 units had practice outside the 95% confidence intervals). Patients treated with PET had more patient-centred decisions compared to surgical patients (42.2% vs 28.4%, p < 0.001). Conclusions: This study demonstrates variation in treatment selection thresholds for older women with breast cancer. Health stratified guidelines on thresholds for PET would help reduce variation, although patient preference should still be respected. © 2020 The Authors
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| 21. |
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| 22. |
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| 23. |
- Allender, Chris J., et al.
(author)
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Preface
- 2001
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In: Analytica Chimica Acta. - 0003-2670 .- 1873-4324. ; 435:1, s. 1-2
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Journal article (other academic/artistic)
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| 24. |
- Berntsen, Peter, 1974, et al.
(author)
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Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells
- 2010
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In: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 7:Suppl 3
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Journal article (peer-reviewed)abstract
- The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40-100 nm and less than 44 mu m) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 mu m), although in none of these cases was cell viability impaired. Treatment with hydrogen peroxide up to 500 mu M did not alter viability or cell mechanics, suggesting that the particle effects are unlikely to be mediated by particle-generated reactive oxygen species. Our results highlight the susceptibility of cellular mechanical function to particulate exposures and suggest that direct exposure of the airway smooth muscle cells to particulates may initiate or aggravate respiratory diseases.
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| 25. |
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| 26. |
- Camara-Costa, H., et al.
(author)
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Quality of survival and cognitive performance in children treated for medulloblastoma in the PNET 4 randomized controlled trial
- 2017
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In: Neuro-Oncology Practice. - : Oxford University Press (OUP). - 2054-2577 .- 2054-2585. ; 4:3, s. 161-170
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Journal article (peer-reviewed)abstract
- Background. The relationship between direct assessments of cognitive performance and questionnaires assessing quality of survival (QoS) is reported to be weak-to-nonexistent. Conversely, the associations between questionnaires evaluating distinct domains of QoS tend to be strong. This pattern remains understudied. Methods. In the HIT-SIOP PNET4 randomized controlled trial, cognitive assessments, including Full Scale, Verbal and Performance IQ, Working Memory, and Processing Speed, were undertaken in 137 survivors of standard-risk medulloblastoma from 4 European countries. QoS questionnaires, including self-reports and/or parent reports of the Behavior Rating Inventory of Executive Function (BRIEF), the Health Utilities Index, the Strengths and Difficulties Questionnaire, and the Pediatric Quality of Life Inventory, were completed for 151 survivors. Correlations among direct cognitive assessments, QoS questionnaires, and clinical data were examined in participants with both assessments available (n = 86). Results. Correlations between direct measures of cognitive performance and QoS questionnaires were weak, except for moderate correlations between the BRIEF Metacognition Index (parent report) and working memory (r = .32) and between health status (self-report) and cognitive outcomes (r = .35-.44). Correlations among QoS questionnaires were moderate to strong both for parent and self-report (r = .39-.76). Principal Component Analysis demonstrated that questionnaires and cognitive assessments loaded on 2 separate factors. Conclusions. We hypothesize that the strong correlations among QoS questionnaires is partially attributable to the positive/negative polarity of all questions on the questionnaires, coupled with the relative absence of diseasespecific questions. These factors may be influenced by respondents' personality and emotional characteristics, unlike direct assessments of cognitive functioning, and should be taken into account in clinical trials.
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| 27. |
- Carlsson, Ella, et al.
(author)
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Influence of IMF draping direction and crustal magnetic field location on Martian ion beams
- 2008
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In: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 56:6, s. 861-867
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Journal article (peer-reviewed)abstract
- Data from the Ion Mass Analyzer (IMA) sensor of the ASPERA-3 instrument suite onboard Mars Express and data from the Magnetometer/Electron Reflectometer (MAG/ER) on Mars Global Surveyor have been analyzed to determine whether ion beam events (IBEs) are correlated with the direction of the draped interplanetary magnetic field (IMF) or the proximity of strong crustal magnetic fields to the subsolar point. We examined 150 IBEs and found that they are organized by IMF draping direction. However, no clear dependence on the subsolar longitude of the strongest magnetic anomaly is evident, making it uncertain whether crustal magnetic fields have an effect on the formation of the beams. We also examined data from the IMA sensor of the ASPERA-4 instrument suite on Venus Express and found that IBEs are observed at Venus as well, which indicates the morphology of the Martian and Venusian magnetotails are similar.
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| 28. |
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| 29. |
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| 31. |
- Fountain, M. T., et al.
(author)
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Design and deployment of semiochemical traps for capturing Anthonomus rubi Herbst (Coleoptera : Curculionidae) and Lygus rugulipennis Poppius (Hetereoptera: Miridae) in soft fruit crops
- 2017
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In: Crop Protection. - : Elsevier. - 0261-2194 .- 1873-6904. ; 99, s. 1-9
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Journal article (peer-reviewed)abstract
- Strawberry blossom weevil (SBW), Anthonomus rubi Herbst (Coleoptera: Curculionidae) and European tarnished plant bug (ETB), Lygus rugulipennis Poppius (Hetereoptera: Miridae), cause significant damage to strawberry and raspberry crops. Using the SBW aggregation pheromone and ETB sex pheromone we optimized and tested a single trap for both species. A series of field experiments in crops and semi-natural habitats in five European countries tested capture of the target pests and the ability to avoid captures of beneficial arthropods. A Unitrap containing a trapping agent of water and detergent and with a cross vane was more efficient at capturing both species compared to traps which incorporated glue as a trapping agent. Adding a green cross vane deterred attraction of non-pest species such as bees, but did not compromise catches of the target pests. The trap caught higher numbers of ETB and SBW if deployed at ground level and although a cross vane was not important for catches of ETB it was needed for significant captures of SBW. The potential for mass trapping SBW and ETB simultaneously in soft fruit crops is discussed including potential improvements to make this more effective and economic to deploy.
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| 32. |
- Gravesteijn, Benjamin Y., et al.
(author)
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Toward a New Multi-Dimensional Classification of Traumatic Brain Injury : A Collaborative European NeuroTrauma Effectiveness Research for Traumatic Brain Injury Study
- 2020
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:7, s. 1002-1010
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Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) is currently classified as mild, moderate, or severe TBI by trichotomizing the Glasgow Coma Scale (GCS). We aimed to explore directions for a more refined multidimensional classification system. For that purpose, we performed a hypothesis-free cluster analysis in the Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI) database: a European all-severity TBI cohort (n = 4509). The first building block consisted of key imaging characteristics, summarized using principal component analysis from 12 imaging characteristics. The other building blocks were demographics, clinical severity, secondary insults, and cause of injury. With these building blocks, the patients were clustered into four groups. We applied bootstrap resampling with replacement to study the stability of cluster allocation. The characteristics that predominantly defined the clusters were injury cause, major extracranial injury, and GCS. The clusters consisted of 1451, 1534, 1006, and 518 patients, respectively. The clustering method was quite stable: the proportion of patients staying in one cluster after resampling and reclustering was 97.4% (95% confidence interval [CI]: 85.6-99.9%). These clusters characterized groups of patients with different functional outcomes: from mild to severe, 12%, 19%, 36%, and 58% of patients had unfavorable 6 month outcome. Compared with the mild and the upper intermediate cluster, the lower intermediate and the severe cluster received more key interventions. To conclude, four types of TBI patients may be defined by injury mechanism, presence of major extracranial injury and GCS. Describing patients according to these three characteristics could potentially capture differences in etiology and care pathways better than with GCS only.
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| 33. |
- Jeffery, Adam J., et al.
(author)
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The pre-eruptive magma plumbing system of the 2007–2008 dome-forming eruption of Kelut volcano, East Java, Indonesia
- 2013
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In: Contributions to Mineralogy and Petrology. - : Springer Science and Business Media LLC. - 0010-7999 .- 1432-0967. ; 166:1, s. 275-308
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Journal article (peer-reviewed)abstract
- Kelut volcano, East Java, is an active volcanic complex hosting a summit crater lake that has been the source of some of Indonesia’s most destructive lahars. In November 2007, an effusive eruption lasting approximately 7 months led to the formation of a 260-m-high and 400-m-wide lava dome that displaced most of the crater lake. The 2007–2008 Kelut dome comprises crystal-rich basaltic andesite with a texturally complex crystal cargo of strongly zoned and in part resorbed plagioclase (An47–94), orthopyroxene (En64–72, Fs24–32, Wo2–4), clinopyroxene (En40–48, Fs14–19, Wo34–46), Ti-magnetite (Usp16–34) and trace amounts of apatite, as well as ubiquitous glomerocrysts of varying magmatic mineral assemblages. In addition, the notable occurrence of magmatic and crustal xenoliths (meta-basalts, amphibole-bearing cumulates, and skarn-type calc-silicates and meta-volcaniclastic rocks) is a distinct feature of the dome. New petrographical, whole rock major and trace element data, mineral chemistry as well as oxygen isotope data for both whole rocks and minerals indicate a complex regime of magma-mixing, decompression-driven resorption, degassing and crystallisation and crustal assimilation within the Kelut plumbing system prior to extrusion of the dome. Detailed investigation of plagioclase textures alongside crystal size distribution analyses provide evidence for magma mixing as a major pre-eruptive process that blends multiple crystal cargoes together. Distinct magma storage zones are postulated, with a deeper zone at lower crustal levels or near the crust-mantle boundary (>15 km depth), a second zone at mid-crustal levels (~10 km depth) and several magma storage zones distributed throughout the uppermost crust (<10 km depth). Plagioclase-melt and amphibole hygrometry indicate magmatic H2O contents ranging from ~8.1 to 8.6 wt.% in the lower crustal system to ~1.5 to 3.3 wt.% in the mid to upper crust. Pyroxene and plagioclase δ18O values range from 5.4 to 6.7 ‰, and 6.5 to 7.6 ‰, respectively. A single whole rock analysis of the 2007–2008 dome lava gave a δ18O value of 7.6 ‰, whereas meta-basaltic and calc-silicate xenoliths are characterised by δ18O values of 6.2 and 10.3 ‰, respectively. Magmatic δ18O values calculated from individual pyroxene and plagioclase analyses range from 5.7 to 7.0 ‰, and 6.2 to 7.4 ‰, respectively. This range in O-isotopic compositions is explained by crystallisation of pyroxenes in the lower to mid-crust, where crustal contamination is either absent or masked by assimilation of material having similar δ18O values to the ascending melts. This population is mixed with isotopically distinct plagioclase and pyroxenes that crystallised from a more contaminated magma in the upper crustal system. Binary bulk mixing models suggest that shallow-level, recycled volcaniclastic sedimentary rocks together with calc-silicates and/or limestones are the most likely contaminants of the 2007–2008 Kelut magma, with the volcaniclastic sediments being dominant.
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| 39. |
- Lillis, Robert J., et al.
(author)
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MOSAIC: A satellite constellation to enable groundbreaking mars climate system science and prepare for human exploration
- 2021
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In: Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 2:5
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Journal article (peer-reviewed)abstract
- The Martian climate system has been revealed to rival the complexity of Earth's. Over the last 20 yr, a fragmented and incomplete picture has emerged of its structure and variability; we remain largely ignorant of many of the physical processes driving matter and energy flow between and within Mars' diverse climate domains. Mars Orbiters for Surface, Atmosphere, and Ionosphere Connections (MOSAIC) is a constellation of ten platforms focused on understanding these climate connections, with orbits and instruments tailored to observe the Martian climate system from three complementary perspectives. First, low-circular near-polar Sun-synchronous orbits (a large mothership and three smallsats spaced in local time) enable vertical profiling of wind, aerosols, water, and temperature, as well as mapping of surface and subsurface ice. Second, elliptical orbits sampling all of Mars' plasma regions enable multipoint measurements necessary to understand mass/energy transport and ion-driven escape, also enabling, with the polar orbiters, dense radio occultation coverage. Last, longitudinally spaced areostationary orbits enable synoptic views of the lower atmosphere necessary to understand global and mesoscale dynamics, global views of the hydrogen and oxygen exospheres, and upstream measurements of space weather conditions. MOSAIC will characterize climate system variability diurnally and seasonally, on meso-, regional, and global scales, targeting the shallow subsurface all the way out to the solar wind, making many first-of-their-kind measurements. Importantly, these measurements will also prepare for human exploration and habitation of Mars by providing water resource prospecting, operational forecasting of dust and radiation hazards, and ionospheric communication/positioning disruptions.
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- Opgenoorth, Hermann J., et al.
(author)
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Day-side ionospheric conductivities at Mars
- 2010
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In: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 58:10, s. 1139-1151
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Journal article (peer-reviewed)abstract
- We present estimates of the day-side ionospheric conductivities at Mars based on magnetic field measurements by Mars Global Surveyor (MGS) at altitudes down to similar to 100 km during aerobraking orbits early in the mission. At Mars, the so-called ionospheric dynamo region, where plasma/neutral collisions permit electric currents perpendicular to the magnetic field, lies between 100 and 250 km altitude. We find that the ionosphere is highly conductive in this region, as expected, with peak Pedersen and Hall conductivities of 0.1-1.5 S/m depending on the solar illumination and induced magnetospheric conditions. Furthermore, we find a consistent double peak pattern in the altitude profile of the day-side Pedersen conductivity, similar to that on Titan found by Rosenqvist et al. (2009). A high altitude peak, located between 180 and 200 km, is equivalent to the terrestrial peak in the lower F-layer. A second and typically much stronger layer of Pedersen conductivity is observed between 120 and 130 km, which is below the Hall conductivity peak at about 130-140 km. In this altitude region, MGS finds a sharp decrease in induced magnetic field strength at the inner magnetospheric boundary, while the day-side electron density is known to remain high as far down as 100 km. We find that such Titan-like behaviour of the Pedersen conductivity is only observed under regions of strongly draped magnetospheric field-lines, and negligible crustal magnetic anomalies below the spacecraft. Above regions of strong crustal magnetic anomalies, the Pedersen conductivity profile becomes more Earth-like with one strong Pedersen peak above the Hall conductivity peak. Here, both conductivities are 1-2 orders of magnitude smaller than the above only weakly magnetised crustal regions, depending on the strength of the crustal anomaly field at ionospheric altitudes. This nature of the Pedersen conductivity together with the structured distribution of crustal anomalies all over the planet should give rise to strong conductivity gradients around such anomalies. Day-side ionospheric conductivities on Mars (in regions away from the crustal magnetic anomalies) and Titan seem to behave in a very similar manner when horizontally draped magnetic field-lines partially magnetise a sunlit ionosphere. Therefore, it appears that a similar double peak structure of strong Pedersen conductivity could be a more general feature of non-magnetised bodies with ionised upper atmospheres, and thus should be expected to occur also at other non-magnetised terrestrial planets like Venus or other planetary bodies within the host planet magnetospheres.
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| 43. |
- Richter, Sophie, et al.
(author)
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Serum biomarkers identify critically ill traumatic brain injury patients for MRI
- 2022
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In: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 26:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Magnetic resonance imaging (MRI) carries prognostic importance after traumatic brain injury (TBI), especially when computed tomography (CT) fails to fully explain the level of unconsciousness. However, in critically ill patients, the risk of deterioration during transfer needs to be balanced against the benefit of detecting prognostically relevant information on MRI. We therefore aimed to assess if day of injury serum protein biomarkers could identify critically ill TBI patients in whom the risks of transfer are compensated by the likelihood of detecting management-altering neuroimaging findings.METHODS: Data were obtained from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Eligibility criteria included: TBI patients aged ≥ 16 years, Glasgow Coma Score (GCS) < 13 or patient intubated with unrecorded pre-intubation GCS, CT with Marshall score < 3, serum biomarkers (GFAP, NFL, NSE, S100B, Tau, UCH-L1) sampled ≤ 24 h of injury, MRI < 30 days of injury. The degree of axonal injury on MRI was graded using the Adams-Gentry classification. The association between serum concentrations of biomarkers and Adams-Gentry stage was assessed and the optimum threshold concentration identified, assuming different minimum sensitivities for the detection of brainstem injury (Adams-Gentry stage 3). A cost-benefit analysis for the USA and UK health care settings was also performed. RESULTS: Among 65 included patients (30 moderate-severe, 35 unrecorded) axonal injury was detected in 54 (83%) and brainstem involvement in 33 (51%). In patients with moderate-severe TBI, brainstem injury was associated with higher concentrations of NSE, Tau, UCH-L1 and GFAP. If the clinician did not want to miss any brainstem injury, NSE could have avoided MRI transfers in up to 20% of patients. If a 94% sensitivity was accepted considering potential transfer-related complications, GFAP could have avoided 30% of transfers. There was no added net cost, with savings up to £99 (UK) or $612 (US). No associations between proteins and axonal injury were found in intubated patients without a recorded pre-intubation GCS.CONCLUSIONS: Serum protein biomarkers show potential to safely reduce the number of transfers to MRI in critically ill patients with moderate-severe TBI at no added cost.
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| 45. |
- Selstam, Eva, et al.
(author)
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Structural organisation of prolamellar bodies (PLB) isolated from Zea mays. Parallel TEM, SAXS and absorption spectra measurements on samples subjected to freeze-thaw, reduced pH and high-salt perturbation
- 2007
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In: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 0006-3002. ; 1768:9, s. 2235-2245
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Journal article (peer-reviewed)abstract
- Well-organised PLB gives rise to a X-ray diffraction pattern overlaid by a scattering pattern arising from individual tubules within less wellorganised regions of the lattice. TEM and SAXS measurements were used to characterise the structural changes in PLB subjected to perturbation by freeze-thaw, exposure to pH 6.5, or resuspension in high-salt media. Comparison of SAXS patterns measured, before and after structural perturbation allows the separation of the contributions from ordered and disordered PLB. The diffraction pattern is shown to be based on a diamond cubic (Fd3m) lattice of unit cell a= 78 nm. Freeze-thaw and high-salt disruption lead to the breakdown of ordered PLB into disordered tubules of similar dimensions to those making up the original PLB lattice. Their scattering patterns suggest that they are approximately 26 nm in diameter with a central lumen about 16 nm in diameter. The tubules formed at pH 6.5 are appreciably narrower, probably reflecting changes in the pattern of ionisation of charged groups at the membrane surface. Absorption spectra of PLB in media containing different concentrations of salts indicated that the structural and spectral changes are related. NADPH, have a significant role in the protection of POR-PChfide(650) but to have only a relatively small effect on the preservation of PLB organisation indicating that the retention of POR-PChlide(650) in isolated PLB preparations is a poor guide to their structural integrity.
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| 46. |
- Selstam, Eva, 1945-, et al.
(author)
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The relationship between different spectral forms of the protochlorophyllide oxidoreductase complex and the structural organisation of prolamellar bodies isolated from Zea mays
- 2011
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In: Photosynthesis Research. - : Springer Science and Business Media LLC. - 0166-8595 .- 1573-5079. ; 108:1, s. 47-59
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Journal article (peer-reviewed)abstract
- Incubation of prolamellar bodies (PLB) in high-salt media leads to changes in PLB structure and properties of their protochlorophyllide oxidoreductase-protochlorophyllide (POR-PChlide) complex. The paracrystalline organisation typical of PLB is disrupted and NADPH dissociates from photoconvertible POR-PChlide, with absorption maxima at 640 and 650 nm (POR-PChlide ( 640/650 )), and a non-photoconvertible form, with absorption maxima at 635 nm (POR-PChlide ( 635 )), is formed. These effects are strongly dependent on the valence of the cation of the perturbing salt, indicating that they involve surface double layers effects. They are also influenced by the nature of the anion and by high concentrations of non-electrolytes, suggesting the involvement of surface hydration effects. The structural changes are largely, if not entirely, independent of the presence of excess NADPH. Changes to the POR-PChlide complex, however, are strongly inhibited by excess NADPH suggesting that the two sets of changes may not be causally linked. As long as the disruption is not too great, the structural changes seen on incubation of PLB in high salt media lacking excess NADPH are reversed on removal of the high salt perturbation. This reversal is independent of the presence or absence of added NADPH. Reformation of photoconvertible POR-PChlide, however, requires the presence of NADPH. The reformation of paracrystalline PLB in the absence of NADPH strongly indicates that preservation of PLB structure, in isolated PLB preparations at least, is independent of the presence or absence of POR-PChlide ( 650 ).
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