| 1. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 4. |
- Ikuta, K. S., et al.
(författare)
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Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 400:10369, s. 2221-2248
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Tidskriftsartikel (refereegranskat)abstract
- Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 5. |
- Bryazka, D., et al.
(författare)
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Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020
- 2022
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Ingår i: Lancet. - 0140-6736. ; 400:10347, s. 185-235
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Tidskriftsartikel (refereegranskat)abstract
- Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0.603 (0.400-1.00) standard drinks per day, and the NDE varied between 0.002 (0-0) and 1.75 (0.698-4.30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0.114 (0-0.403) to 1.87 (0.500-3.30) standard drinks per day and an NDE that ranged between 0.193 (0-0.900) and 6.94 (3.40-8.30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59.1% (54.3-65.4) were aged 15-39 years and 76.9% (7.0-81.3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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| 6. |
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| 8. |
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| 9. |
- Alahamami, Mastour A., et al.
(författare)
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Comparison of cysts in red and green images for diabetic macular edema
- 2014
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Konferensbidrag (refereegranskat)abstract
- Purpose: To improve the detection of macular cyst with photoscreening, we tested whether in a population of largely minority patients the red channel image from a color fundus camera visualizes cysts in diabetic macular edema better than the green channel image. In assessing diabetic retinas for clinically significant macular edema, the presence of cysts must be judged with respect to the central macula. Some grading programs use red free images, often derived from green channel images, to enhance visualization of retinal vessel damage or macular pigment, but some red and near infrared instruments have detected cysts better than short wavelength techniques. Methods: We evaluated macular cysts in 13 diabetic patients diagnosed with clinically significant macular edema, age range 33-68 years. Diabetic patients were selected from the screening study of >2000 underserved patients seen at Eastmont Wellness Center, Oakland, CA. Patients underwent photoscreening with a nonmydriatic color fundus camera (Canon Cr-DGi, Tokyo, Japan) and SD-OCT (iVue, Optovue Inc, Fremont, CA). The color fundus images for those patients were transformed into red and green channels to evaluate the appearance of macular cysts in red channel images and green channel images. The region of each cyst was compared SD-OCT scans (Adobe Photoshop CS5.1, San Jose, CA). Only cysts touching the central 1 mm around the fixation from the SD-OCT scans were sampled. Results: The average size of retinal cysts in red channel images, 124.57 µm (±106.96), was significantly greater than in green channel, 59.44 µm (±76.6), (p<0.006). Entire cysts could not be seen in 5 eyes in the green channel images. Conclusions: Our results indicate that the grading of cysts in the central macular might be improved by incorporating red channel images. There are a number of potential factors that could make cysts less visible in the green channel images, including poorer light penetration through to the deeper retina or macular pigment. Anterior segment issues impact more on green channel images. This population includes mostly minority patients who have dark fundi, and darker images.
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| 10. |
- Arthur, Edmund, et al.
(författare)
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Central Macular Thickness in Diabetic Patients : A Sex-based Analysis
- 2019
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Ingår i: Optometry and Vision Science. - : American Academy of Optometry. - 1040-5488 .- 1538-9235. ; 96:4, s. 266-275
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Tidskriftsartikel (refereegranskat)abstract
- SIGNIFICANCE The pathological changes in clinically significant diabetic macular edema lead to greater retinal thickening in men than in women. Therefore, male sex should be considered a potential risk factor for identifying individuals with the most severe pathological changes. Understanding this excessive retinal thickening in men may help preserve vision. PURPOSE The purpose of this study was to investigate the sex differences in retinal thickness in diabetic patients. We tested whether men with clinically significant macular edema had even greater central macular thickness than expected from sex differences without significant pathological changes. This study also aimed to determine which retinal layers contribute to abnormal retinal thickness. METHODS From 2047 underserved adult diabetic patients from Alameda County, CA, 142 patients with clinically significant macular edema were identified by EyePACS-certified graders using color fundus images (Canon CR6-45NM). First, central macular thickness from spectral domain optical coherence tomography (iVue; Optovue Inc.) was compared in 21 men versus 21 women without clinically significant macular edema. Then, a planned comparison contrasted the greater values of central macular thickness in men versus women with clinically significant macular edema as compared with those without. Mean retinal thickness and variability of central macular layers were compared in men versus women. RESULTS Men without clinically significant macular edema had a 12-μm greater central macular thickness than did women (245 ± 21.3 and 233 ± 13.4 μm, respectively; t40 = −2.18, P = .04). Men with clinically significant macular edema had a 67-μm greater central macular thickness than did women (383 ± 48.7 and 316 ± 60.4 μm, P < .001); that is, men had 55 μm or more than five times more (t20 = 2.35, P = .02). In men, the outer-nuclear-layer thickness was more variable, F10,10 = 9.34. CONCLUSIONS Underserved diabetic men had thicker retinas than did women, exacerbated by clinically significant macular edema.
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| 11. |
- Arthur, Edmund, et al.
(författare)
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Individual Retinal Layer Thickness in Diabetic Patients with Clinically Significant Macular Edema : A Gender Based Analysis
- 2016
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Konferensbidrag (refereegranskat)abstract
- Purpose: To compare segmented retinal layer thicknesses between male and female diabetics with clinically significant macular edema (CSME). This study expands our earlier analysis of central macular thickness (CMT) measurements in diabetic males vs. females. Methods: Diabetic retinopathy screening of 2080 diabetics from Alameda County, CA, indicated 142 patients with CSME, as judged by EyePACS certified graders using color fundus images (Canon CR6-45NM). Of the 2080 diabetics, 1784 were imaged with SD-OCT (Optovue iVue). From the 142 patients, we selected 11 males with good fixation, CMT > 300 µm, and no other ocular complications, along with 11 females with the greatest values of CMT while controlling for age, HbA1c and diabetes duration. Manual segmentation of retinal layers using custom software (Mathworks Matlab) of the SD-OCT images of these subjects was done. We analyzed thicknesses for regions 1 deg - 2 deg for nasal and temporal retina in a B-scan centered on the fovea. A 2 X 2 ANOVA probed the differences in thickness for gender, meridian, and their interaction. We also analyzed the central 1 mm of the outer retinal layers, and performed t-tests. Results: Males had significantly thicker nerve fiber layer (NFL) (13.30 ± 2.85 µm) than females (10.13 ± 6.13 µm) and ganglion cell layer-inner plexiform layer (GCL-IPL) (62.54 ± 21.18 µm) than females (48.07 ± 25.91 µm), p < 0.05. There was no effect of meridian and no interaction (p > 0.05). All other layers except the retinal pigment epithelium (RPE) were thicker for males than females even though these were not significant (p > 0.05). There were no significant differences for the layers of the outer retina, which were highly variable and distorted by cysts. Conclusion: Outside the fovea, NFL and GCL-IPL thicknesses were significantly higher in males than females.
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| 12. |
- Baskaran, Karthikeyan, et al.
(författare)
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Benefit of Adaptive Optics Aberration Correction at Preferred Retinal Locus
- 2012
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Ingår i: Optometry and Vision Science. - 1040-5488 .- 1538-9235. ; 89:9, s. 1417-1423
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE.: To investigate the effect of eccentric refractive correction and full aberration correction on both high- and low-contrast grating resolution at the preferred retinal locus (PRL) of a single low-vision subject with a long-standing central scotoma. METHODS.: The subject was a 68-year-old women with bilateral absolute central scotoma due to Stargardt disease. She developed a single PRL located 25 degrees nasally of the damaged macula in her left eye, this being the better of the two eyes. High- (100%) and low-contrast (25 and 10%) grating resolution acuity was evaluated using four different correction conditions. The first two corrections were solely refractive error corrections, namely, habitual spectacle correction and full spherocylindrical correction. The latter two corrections were two versions of adaptive optics corrections of all aberrations, namely, habitual spectacle correction with aberration correction and full spherocylindrical refractive correction with aberration correction. RESULTS.: The mean high-contrast (100%) resolution acuity with her habitual correction was 1.06 logMAR, which improved to 1.00 logMAR with full spherocylindrical correction. Under the same conditions, low-contrast (25%) acuity improved from 1.30 to 1.14 logMAR. With adaptive optics aberration correction, the high-contrast resolution acuities improved to 0.89/0.92 logMAR and the low-contrast acuities improved to 1.04/1.06 logMAR under both correction modalities. The low-contrast (10%) resolution acuity was 1.34 logMAR with adaptive optics aberration correction; however, with purely refractive error corrections, she was unable to identify the orientation of the gratings. CONCLUSIONS.: Correction of all aberrations using adaptive optics improves both high- and low-contrast resolution acuity at the PRL of a single low-vision subject with long-standing absolute central scotoma
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| 13. |
- Baskaran, Karthikeyan, et al.
(författare)
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Stability of fixation in diabetes patients with and without clinically significant macular edema
- 2014
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Konferensbidrag (refereegranskat)abstract
- Purpose - Eye diseases affecting central vision impair fixation and interfere with day-to-day tasks such as reading. Diabetic retinopathy and clinically significant macular edema (CSME) are leading causes of visual impairment in diabetes patients. The aim of this study is to find whether diabetic patients with CSME have poorer fixation stability compared to patients without CSME, by analyzing the fundus images obtained from the Laser Scanning Digital Camera (LSDC).Methods - Two hundred underserved, diabetic patients were screened for diabetic retinopathy at the Eastmont Wellness Center within the EyePACS telemedicine network, using LSDC. One eye of each patient who had diabetic retinopathy was included in this study. Non-mydriatic color fundus photos were classified for presence of CSME by two independent, certified EyePACS graders. The first 50 patients (25 males & 25 females) with CSME were selected and 50 (27 males & 23 females) diabetic patients without CSME were selected as controls. Mean age was 59 (±9) years for patients with CSME and was 55 (±10) years for patients without CSME. The subjects included 53% Hispanics, 26% African Americans and 21% other. A series of 20 images (36 deg field, 1024 X 1024 pixels, and 850 nm) were acquired at 11 fps. Eye positions were obtained by selecting a region of interest in the first image of each series and aligning the remaining images to that region by cross-correlation. The bi-contour ellipse area (BCEA) and the standard deviation of the Euclidean distance (SDED) were used to quantify fixation stability.Results - The fixation stability for patients with CSME was significantly worse than for those without CSME (t test: p < 0.001, 0.007 for BCEA and SDED, respectively). The mean fixation stability obtained by the BCEA metric was 2.74 (±0.40) log(minArc2) and 2.34 (±0.42) log(minArc2) for patients with and without CSME, respectively. For SDED the mean was 48.4 (±28.8) microns and 34.6 (±20.4) microns for patients with and without CSME, respectively. The correlation with age was not significant for either group (R2 = 0.052, 0.011).Conclusions - Diabetic patients with CSME had poorer fixation stability than patients without CSME for both metrics. Fixation stability is a potential tool for assessing macular function and could be used for tracking the treatment and progression of macular edema.The LSDC images provide one method to quantify fixation stability rapidly.
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| 14. |
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| 15. |
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| 16. |
- Green, Jason J. A., et al.
(författare)
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Retina Artery to Vein Intensity Ratio as a Function of Wavelength and Dark-Field Offset With Low Cost Ophthalmoscope
- 2014
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Konferensbidrag (refereegranskat)abstract
- PurposeTo quantify light return from retinal vessels for oxygenation status. To use a low-cost Digital Light Ophthalmoscope (DLO) based on a novel structured light pattern Digital Light Projector for quantitative retinal imaging. MethodsFive normal subjects of ages 27-63 and various eye colors were imaged without mydriasis. The DLO produced a progressively scanning 6 pixel wide stripe, 96 stripe illumination pattern (85 μm stripe width at retina) with LEDs at 635 +/- 25nm (Red) and 535 +/- 70nm (Green) with a constant fixation target location across tests. The illumination was synchronized to a 13.2 Hz rolling shutter CMOS sensor (11 μm resolution at retina). To collect the light return from the retina at varying light multiply scattered levels, aperture offset was varied in position with respect to the illumination centerline: dark-field mode was obtained with large offsets and confocal mode had small offsets, where offset was varied from -517 μm (row start 30) to 1353 μm (row start 200). Multiple images of 12 bit dynamic range were captured in sequence, aligned with translational cross correlation, then time averaged to reduce noise. The artery and vein gray scale intensity level was measured at vessel centers for: 1) both vessels over background retina and 2) artery over the optic disc and vein over background. Mean-to-mean intensity ratios were then compared. ResultsWith an aperture width of 704 μm, intensity varied by 2.60 bits (a factor of 4.5) for each subject per condition: red, green, artery, and vein, 3.39 bits if same subject and condition (2.3% Red A/V ratio CoV σ/μ), and by 5.07 bits over all tests. Yet, the ratio (Red/Green Artery)/(Red/Green Vein) was close to unity across offsets and linear fits had an R^2 regression of, for case 1: 0.72, 0.06, 0.25, 0.18, and 0.49, and case 2: 0.0005, 0.89, 0.75, 0.50, and 0.18. The Artery/Vein ratio trend slopes, intercept points, and inversions varied between subjects, i.e. contrast reversals were observed. ConclusionsThe DLO can be utilized electronically to effectively perform quantitative fundus imaging at both Red and Green wavelengths, which is a step towards performing oximetry. 77 is zero offset
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| 17. |
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| 18. |
- Johansson, Patrik, et al.
(författare)
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A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 32:2
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) is a malignant brain tumor with few therapeutic options. The disease presents with a complex spectrum of genomic aberrations, but the pharmacological consequences of these aberrations are partly unknown. Here, we report an integrated pharmacogenomic analysis of 100 patient-derived GBM cell cultures from the human glioma cell culture (HGCC) cohort. Exploring 1,544 drugs, we find that GBM has two main pharmacological subgroups, marked by differential response to proteasome inhibitors and mutually exclusive aberrations in TP53 and CDKN2A/B. We confirm this trend in cell and in xenotransplantation models, and identify both Bcl-2 family inhibitors and p53 activators as potentiators of proteasome inhibitors in GBM cells, We can further predict the responses of individual cell cultures to several existing drug classes, presenting opportunities for drug repurposing and design of stratified trials. Our functionally profiled biobank provides a valuable resource for the discovery of new treatments for GBM.
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| 19. |
- Lundström, Linda, et al.
(författare)
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Symmetries in peripheral ocular aberrations
- 2011
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Ingår i: Journal of Modern Optics. - : Informa UK Limited. - 0950-0340 .- 1362-3044. ; 58:19-20, s. 1690-1695
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Tidskriftsartikel (refereegranskat)abstract
- A mirror symmetry in the aberrations between the left and right eyes has previously been found foveally, but while a similar symmetry for the peripheral visual field is likely, it has not been investigated. Nevertheless, the peripheral optical quality is often evaluated in only one eye, because it is more time efficient than analyzing the whole visual field of both eyes. This study investigates the correctness of such an approach by measuring the peripheral wavefront aberrations in both eyes of 22 subjects out to +/- 40 degrees horizontally. The largest aberrations (defocus, astigmatism, and coma) were found to be significantly correlated between the left and right eyes when comparing the same temporal or nasal angle. The slope of the regression line was close to +/- 1 (within 0.05) for these aberrations, with a negative slope for the horizontally odd aberrations, i.e. the left and right eyes are mirror symmetric. These findings justify that the average result, sampled in one of the two eyes of many subjects, can be generalized to the other eye as well.
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| 20. |
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| 21. |
- Porcelli, D., et al.
(författare)
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The importance of colloids and mires for the transport of uranium isotopes through the Kalix River watershed and Baltic Sea
- 1997
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Ingår i: Geochimica et Cosmochimica Acta. - 0016-7037 .- 1872-9533. ; 61:19, s. 4095-4113
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Tidskriftsartikel (refereegranskat)abstract
- The importance of colloids and organic deposits for the transport of uranium isotopes from continental source regions and through the estuarine environment was investigated in the mire-rich Kalix River drainage basin in northern Sweden and the Baltic Sea. Ultrafiltration techniques were used to separate uranium and other elements associated with colloids > 10 kD and >3 kD from "solute" uranium and provided consistent results and high recovery rates for uranium as well as for other elements from large volume samples. Uranium concentrations in 0.45 μm-filtered Kalix River water samples increased by a factor of 3 from near the headwaters in the Caledonides to the river mouth while major cation concentrations were relatively constant. 234U/238U ratios were high (δ234U = 770-1500) throughout the basin, without showing any simple pattern, and required a supply of 234U-rich water. Throughout the Kalix River, a large fraction (30-90%) of the uranium is carried by >10 kD colloids, which is compatible with uranium complexation with humic acids. No isotopic differences were found between colloid-associated and solute uranium. Within the Baltic Sea, about half of the uranium is removed at low salinities. The proportion that is lost is equivalent to that of river-derived colloid-bound uranium, suggesting that while solute uranium behaves conservatively during estuarine mixing, colloid-bound uranium is lost due to rapid flocculation of colloidal material. The association of uranium with colloids therefore may be an important parameter in determining uranium estuarine behavior. Mire peats in the Kalix River highly concentrate uranium and are potentially a significant source of recoil 234U to the mirewaters and river waters. However, mirewater data clearly demonstrate that only small 234U/238U shifts are generated relative to inflowing groundwater. A simple box model of uranium accumulation in peat and transport through the mire that is compatible with the mire data demonstrates that with efficient removal of uranium from solution, only small shifts in 234U/238U ratios can be generated in mirewater uranium. The measurements and model calculations show that mirewaters are not the primary source of the uranium in the river. Bedrock groundwaters with high 234U/238U ratios and uranium concentrations must be the dominant source of riverine uranium.
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| 22. |
- Vinsland, E, et al.
(författare)
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The zinc finger/RING domain protein Unkempt regulates cognitive flexibility
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 16299-
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Tidskriftsartikel (refereegranskat)abstract
- Correct orchestration of nervous system development is a profound challenge that involves coordination of complex molecular and cellular processes. Mechanistic target of rapamycin (mTOR) signaling is a key regulator of nervous system development and synaptic function. The mTOR kinase is a hub for sensing inputs including growth factor signaling, nutrients and energy levels. Activation of mTOR signaling causes diseases with severe neurological manifestations, such as tuberous sclerosis complex and focal cortical dysplasia. However, the molecular mechanisms by which mTOR signaling regulates nervous system development and function are poorly understood. Unkempt is a conserved zinc finger/RING domain protein that regulates neurogenesis downstream of mTOR signaling in Drosophila. Unkempt also directly interacts with the mTOR complex I component Raptor. Here we describe the generation and characterisation of mice with a conditional knockout of Unkempt (UnkcKO) in the nervous system. Loss of Unkempt reduces Raptor protein levels in the embryonic nervous system but does not affect downstream mTORC1 targets. We also show that nervous system development occurs normally in UnkcKO mice. However, we find that Unkempt is expressed in the adult cerebellum and hippocampus and behavioural analyses show that UnkcKO mice have improved memory formation and cognitive flexibility to re-learn. Further understanding of the role of Unkempt in the nervous system will provide novel mechanistic insight into the role of mTOR signaling in learning and memory.
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