| 1. |
|
|
| 2. |
- Bice, Annie R., et al.
(author)
-
Homotopic contralesional excitation suppresses spontaneous circuit repair and global network reconnections following ischemic stroke
- 2022
-
In: eLife. - 2050-084X. ; 11
-
Journal article (peer-reviewed)abstract
- Understanding circuit-level manipulations that affect the brain’s capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g. use of the unaffected limb) can negatively influence recovery, but it is unknown which specific neural connections exert this influence, and to what extent increased contralesional activity affects systems-and molecular-level biomarkers of recovery. Here, we combine optogenetic photostimulation with optical intrinsic signal imaging (OISI) to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice either recovered spontaneously or received chronic optogenetic excitation of right S1FP over the course of 4 weeks. Contralesional excitation suppressed perilesional S1FP remapping and was associated with abnormal patterns of stimulus-evoked activity in the unaffected limb. This maneuver also prevented the restoration of resting-state functional connectivity (RSFC) within the S1FP network, RSFC in several networks functionally-distinct from somatomotor regions, and resulted in persistent limb-use asymmetry. In stimulated mice, perilesional tissue exhibited transcriptional changes in several genes relevant for recovery. Our results suggest that contralesional excitation impedes local and global circuit reconnection through suppression of cortical activity and several neuroplasticity-related genes after stroke, and highlight the importance of site selection for therapeutic intervention after focal ischemia.
|
|
| 3. |
- Fenstermacher, M.E., et al.
(author)
-
DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
-
In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
-
Journal article (peer-reviewed)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.
|
|
| 4. |
- Holmqvist, Anna Sällfors, et al.
(author)
-
Assessment of Late Mortality Risk after Allogeneic Blood or Marrow Transplantation Performed in Childhood
- 2018
-
In: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437. ; 4:12
-
Journal article (peer-reviewed)abstract
- Importance: Allogeneic blood or marrow transplantation (BMT) is a curative option for malignant and nonmalignant diseases of childhood. However, little is known about trends in cause-specific late mortality in this population during the past 3 decades. Objectives: To examine cause-specific late mortality among individuals who have lived 2 years or more after allogeneic BMT performed in childhood and whether rates of late mortality have changed over time. Design, Setting, and Participants: A retrospective cohort study was conducted of individuals who lived 2 years or more after undergoing allogeneic BMT performed in childhood between January 1, 1974, and December 31, 2010. The end of follow-up was December 31, 2016. Exposure: Allogeneic BMT performed in childhood. Main Outcomes and Measures: All-cause mortality, relapse-related mortality, and non-relapse-related mortality. Data on vital status and causes of death were collected using medical records, the National Death Index Plus Program, and Accurint databases. Results: Among 1388 individuals (559 females and 829 males) who lived 2 years or more after allogeneic BMT performed in childhood, the median age at transplantation was 14.6 years (range, 0-21 years). In this cohort, there was a total of 295 deaths, yielding an overall survival rate of 79.3% at 20 years after BMT. The leading causes of death were infection and/or chronic graft-vs-host disease (121 of 244 [49.6%]), primary disease (60 of 244 [24.6%]), and subsequent malignant neoplasms (45 of 244 [18.4%]). Overall, the cohort had a 14.4-fold increased risk for death (95% CI, 12.8-16.1) compared with the general population (292 deaths observed; 20.3 deaths expected). Relative mortality remained elevated at 25 years or more after BMT (standardized mortality ratio, 2.9; 95% CI, 2.0-4.1). The absolute excess risk for death from any cause was 12.0 per 1000 person-years (95% CI, 10.5-13.5). The cumulative incidence of non-relapse-related mortality exceeded that of relapse-related mortality throughout follow-up. The 10-year cumulative incidence of late mortality decreased over time (before 1990, 18.9%; 1990-1999, 12.8%; 2000-2010, 10.9%; P =.002); this decrease remained statistically significant after adjusting for demographic and clinical factors (referent group: <1990; 1990-1999: hazard ratio, 0.64; 95% CI, 0.47-0.89; P =.007; 2000-2010: hazard ratio, 0.49; 95% CI, 0.31-0.76; P =.002; P <.001 for trend). Conclusions and Relevance: Late mortality among children undergoing allogeneic BMT has decreased during the past 3 decades. However, these patients remain at an elevated risk of late mortality even 25 years or more after transplantation when compared with the general population, necessitating lifelong follow-up.
|
|
| 5. |
- Holmqvist, Anna Sällfors, et al.
(author)
-
Late morbidity and mortality after autologous blood or marrow transplantation for lymphoma in children, adolescents and young adults—a BMTSS report
- 2024
-
In: Leukemia. - 0887-6924. ; 38:3, s. 601-609
-
Journal article (peer-reviewed)abstract
- We determined the risk of late morbidity and mortality after autologous blood or marrow transplantation (BMT) for lymphoma performed before age 40. The cohort included autologous BMT recipients who had survived ≥2 years after transplantation (N = 583 [HL = 59.9%; NHL = 40.1%]) and a comparison cohort (N = 1070). Participants self-reported sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life threatening] or 5 [fatal]) was assigned to the conditions using CTCAE v5.0. Logistic regression estimated the odds of grade 3–4 conditions in survivors vs. comparison subjects. Proportional subdistribution hazards models identified predictors of grade 3–5 conditions among BMT recipients. Median age at BMT was 30.0 years (range: 2.0–40.0) and median follow-up was 9.8 years (2.0–32.1). Survivors were at a 3-fold higher adjusted odds for grade 3–4 conditions (95% CI = 2.3–4.1) vs. comparison subjects. Factors associated with grade 3–5 conditions among BMT recipients included age at BMT (>30 years: adjusted hazard ratio [aHR] = 2.31; 95% CI = 1.27–4.19; reference: ≤21 years), pre-BMT radiation (aHR = 1.52; 95% CI = 1.13–2.03; reference: non-irradiated), and year of BMT (≥2000: aHR = 0.54; 95% CI = 0.34–0.85; reference: <1990). The 25 years cumulative incidence of relapse-related and non-relapse-related mortality was 18.2% and 25.9%, respectively. The high risk for late morbidity and mortality after autologous BMT for lymphoma performed at age <40 calls for long-term anticipatory risk-based follow-up.
|
|
| 6. |
|
|
| 7. |
- Holmqvist, Anna Sällfors, et al.
(author)
-
Late Mortality after Allogeneic Bone Marrow Transplantation in Childhood for Bone Marrow Failure Syndromes and Severe Aplastic Anemia
- 2019
-
In: Biology of Blood and Marrow Transplantation. - : Elsevier BV. - 1083-8791. ; 25:4, s. 749-755
-
Journal article (peer-reviewed)abstract
- Children with bone marrow failure syndromes and severe aplastic anemia (SAA) are treated with allogeneic blood or marrow transplantation (BMT). However, there is a paucity of studies examining late mortality risk after allogeneic BMT performed in childhood for bone marrow failure syndromes and SAA and evaluating how this risk differs between these diseases. We investigated cause-specific late mortality in 2-year survivors of allogeneic BMT for bone marrow failure syndromes and SAA performed before age 22 years between 1974 and 2010 at 2 US transplantation centers. Vital status information was collected from medical records, the National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. The standardized mortality ratio (SMR) was calculated using age- sex-, and calendar-specific mortality rates from the Centers for Disease Control and Prevention. Among the 2-year survivors of bone marrow failure syndromes (n = 120) and SAA (n = 147), there were 15 and 19 deaths, respectively, yielding an overall survival of 86.4% for bone marrow failure syndromes and 93.1% for SAA at 15 years post-BMT. Compared with the general population, patients with bone marrow failure syndromes were at a higher risk for premature death (SMR, 22.7; 95% CI, 13.1 to 36.2) compared with those with SAA (SMR, 4.5; 95% CI, 2.8 to 7.0) (P <.0001). The elevated relative risk persisted at ≥15 years after BMT for both diseases. The hazard of all-cause late mortality was 2.9-fold (95% CI, 1.1 to 7.3) higher in patients with bone marrow failure syndromes compared with those with SAA. The high late mortality risk in recipients of allogeneic BMT in childhood for bone marrow failure syndromes calls for intensified life-long follow-up.
|
|
| 8. |
- Holmqvist, Anna Sällfors, et al.
(author)
-
Late mortality after autologous blood or marrow transplantation in childhood : A Blood or Marrow Transplant Survivor Study-2 report
- 2018
-
In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 131:24, s. 2720-2729
-
Journal article (peer-reviewed)abstract
- Autologous blood or marrow transplantation (BMT) is a curative option for several types of childhood cancer. However, there is little information regarding the risk of late mortality. We examined all-cause mortality, relapse-related mortality (RRM), and nonrelapse-related mortality (NRM) in 2-year survivors of autologous BMT performed before age 22 between 1980 and 2010 at 1 of 2 US transplant centers. Vital status information was collected using medical records, National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. Cumulative incidence of mortality used competing risk methods. Standardized mortality ratio (SMR) was calculated using age-, sex-, and calendar-specific mortality rates from Centers for Disease Control and Prevention. Cox regression analysis was used to determine predictors of all-cause late mortality. Among the 345 2-year survivors, 103 deaths were observed, yielding an overall survival of 70.3% 15 years post-BMT. The leading causes of death included primary disease (50.0%), subsequent neoplasm (21.4%), and infection (18.2%). Overall, the cohort was at a 22-fold increased risk of late mortality (SMR, 21.8; 95% CI, 17.9-26.3), compared with the general population. Mortality rates remained elevated among the 10-year survivors (SMR, 20.6; 95% CI, 9.9-37.2) but approached those of the general population ≥15 years post-BMT. The 10-year cumulative incidence of RRM (14.3%) exceeded that of NRM (10.4%). The 10-year cumulative mortality rate declined over time (<1990, 35.1%; 1990-1999, 25.6%; 2000-2010, 21.8%; P 5 .05). In conclusion, childhood autologous BMT recipients have an increased risk of late mortality, compared with the general population. The late mortality rates have declined over the past 3 decades.
|
|
| 9. |
- Holmqvist, Anna Sällfors, et al.
(author)
-
Severe, life-threatening, and fatal chronic health conditions after allogeneic blood or marrow transplantation in childhood
- 2023
-
In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 129:4, s. 624-633
-
Journal article (peer-reviewed)abstract
- Background: A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied. Methods: Seven hundred eighty-nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age <22 years and 690 siblings completed a 255-item survey self-reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life-threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3–5 conditions. Logistic regression was used to estimate the risk of grade 3–4 conditions in BMT recipients who were alive at the time of this study compared with siblings. Results: The median age at transplantation was 11.3 years (range, 0.4–22.0 years), and the median length of follow-up was 11.7 years (range, 2.0–45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3–4 condition was 53.8% (95% CI, 46.7%–60.3%). The adjusted odds ratio of a grade 3–4 condition was 15.1 in survivors (95% CI, 9.5–24.0) compared with siblings. The risk of a grade 3–5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01–1.05) and was higher among females (HR, 1.27; 95% CI, 1.02–1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27–2.31), and those reporting chronic graft-versus-host disease (HR, 1.38; 95% CI, 1.09–1.74). Conclusions: Two-year survivors of allogeneic BMT in childhood have an increased risk of grade 3–4 chronic health conditions compared with siblings, suggesting the need for long-term follow-up.
|
|
| 10. |
- Kanoni, Stavroula, et al.
(author)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 11. |
- Klug, Stefanie J, et al.
(author)
-
TP53 codon 72 polymorphism and cervical cancer : a pooled analysis of individual data from 49 studies
- 2009
-
In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 10:8, s. 772-784
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.
|
|
| 12. |
- Sartelli, Massimo, et al.
(author)
-
Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
-
In: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
-
Research review (peer-reviewed)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
|
|
| 13. |
|
|
| 14. |
- Aad, G., et al.
(author)
-
- 2011
-
swepub:Mat__t (peer-reviewed)
|
|
| 15. |
- Aad, G., et al.
(author)
-
- 2011
-
Journal article (peer-reviewed)
|
|
| 16. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 17. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 18. |
- Aad, G., et al.
(author)
-
- 2013
-
swepub:Mat__t (peer-reviewed)
|
|
| 19. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 20. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 21. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 22. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 23. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 24. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 25. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 26. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 27. |
- Aad, G., et al.
(author)
-
- 2011
-
swepub:Mat__t (peer-reviewed)
|
|
| 28. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 29. |
- Aad, G., et al.
(author)
-
- 2012
-
Journal article (peer-reviewed)
|
|
| 30. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 31. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 32. |
- Aad, G., et al.
(author)
-
- 2013
-
swepub:Mat__t (peer-reviewed)
|
|
| 33. |
- Aad, G., et al.
(author)
-
- 2012
-
Journal article (peer-reviewed)
|
|
| 34. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 35. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 36. |
- Aad, G., et al.
(author)
-
- 2011
-
Journal article (peer-reviewed)
|
|
| 37. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 38. |
- Aad, G., et al.
(author)
-
- 2012
-
Journal article (peer-reviewed)
|
|
| 39. |
- Aad, G., et al.
(author)
-
- 2011
-
swepub:Mat__t (peer-reviewed)
|
|
| 40. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 41. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 42. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 43. |
- Aad, G., et al.
(author)
-
- 2011
-
Journal article (peer-reviewed)
|
|
| 44. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 45. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t
|
|
| 46. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 47. |
- Aad, G., et al.
(author)
-
- 2012
-
Journal article (peer-reviewed)
|
|
| 48. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 49. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 50. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
