| 1. |
|
|
| 2. |
- Adam, A, et al.
(författare)
-
Abstracts from Hydrocephalus 2016.
- 2017
-
Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
|
|
| 4. |
- Hibar, D. P., et al.
(författare)
-
Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
- 2018
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:4, s. 932-942
-
Tidskriftsartikel (refereegranskat)abstract
- Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d='0.293; P=1.71 × 10 '21), left fusiform gyrus (d='0.288; P=8.25 × 10 '21) and left rostral middle frontal cortex (d='0.276; P=2.99 × 10 '19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
|
|
| 5. |
|
|
| 6. |
- Curigliano, G, et al.
(författare)
-
De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.
- 2017
-
Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 28:8, s. 1700-1712
-
Tidskriftsartikel (refereegranskat)abstract
- The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.
|
|
| 7. |
|
|
| 8. |
- Hibar, D. P., et al.
(författare)
-
Subcortical volumetric abnormalities in bipolar disorder
- 2016
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:12, s. 1710-1716
-
Tidskriftsartikel (refereegranskat)abstract
- Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10 -7) and thalamus (d=-0.148; P=4.27 × 10 -3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10 -5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons. © 2016 Macmillan Publishers Limited, part of Springer Nature.
|
|
| 9. |
- Alam, Syed Bahauddin, et al.
(författare)
-
Small modular reactor core design for civil marine propulsion using micro-heterogeneous duplex fuel. Part I: Assembly-level analysis
- 2019
-
Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 346, s. 157-175
-
Tidskriftsartikel (refereegranskat)abstract
- In an effort to de-carbonise commercial freight shipping, there is growing interest in the possibility of using nuclear propulsion systems. In this reactor physics study, we seek to design a soluble-boron-free (SBF) and low-enriched uranium (LEU) (<20% U-235 enrichment) civil nuclear marine propulsion small modular reactor (SMR) core that provides at least 15 effective full-power-years (EFPY) life at 333 MWth using 18% U-235 enriched micro-heterogeneous ThO2-UO2 duplex fuel and 15% U-235 enriched homogeneously mixed all-UO2 fuel. We use WIMS to develop subassembly designs and PANTHER to examine whole-core arrangements.The assembly-level behaviours of candidate burnable poison (BP) materials and control rods are investigated. We examine gadolinia (Gd2O3), erbia (Er2O3) and ZrB2 integral fuel burnable absorber (IFBA) as BPs. We arrive at a design with the candidate fuels loaded into 13 x 13 assemblies using IFBA pins for reactivity control. Taking advantage of self-shielding effects, this design maintains low and stable assembly reactivity with relatively little burnup penalty. Thorium-based duplex fuel offers better performance than all-UO2 fuel with all BP options considered. Duplex fuel has similar to 20% lower reactivity swing and, in consequence, lower initial reactivity than all-UO2 fuel. The lower initial reactivity and smaller reactivity swing make the task of reactivity control through BP design easier in the thorium-rich duplex core. For control rod design, we examine boron carbide (B4C), hafnium, and Ag-In-Cd alloy. All the candidate materials exhibit greater rod worth for the duplex design. For both fuels, B4C has the highest rod worth. In particular, one of the major objectives of this study is to offer/explore a thorium-based candidate alternative fuel platform for the proposed marine core. It is proven by literature reviews that the ability of the duplex fuel was never explored in the context of a single-batch, LEU, SBF, long-life SMR core. In this regard, the motivation of this paper is to observe the neutronic performance of the proposed duplex fuel with respect to the UO2 fuel and 'open the option' of designing the functional cores with both the duplex and UO2 fuel cores.
|
|
| 10. |
- Castell, A, et al.
(författare)
-
A selective high affinity MYC-binding compound inhibits MYC:MAX interaction and MYC-dependent tumor cell proliferation
- 2018
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 10064-
-
Tidskriftsartikel (refereegranskat)abstract
- MYC is a key player in tumor development, but unfortunately no specific MYC-targeting drugs are clinically available. MYC is strictly dependent on heterodimerization with MAX for transcription activation. Aiming at targeting this interaction, we identified MYCMI-6 in a cell-based protein interaction screen for small inhibitory molecules. MYCMI-6 exhibits strong selective inhibition of MYC:MAX interaction in cells and in vitro at single-digit micromolar concentrations, as validated by split Gaussia luciferase, in situ proximity ligation, microscale thermophoresis and surface plasmon resonance (SPR) assays. Further, MYCMI-6 blocks MYC-driven transcription and binds selectively to the MYC bHLHZip domain with a KD of 1.6 ± 0.5 μM as demonstrated by SPR. MYCMI-6 inhibits tumor cell growth in a MYC-dependent manner with IC50 concentrations as low as 0.5 μM, while sparing normal cells. The response to MYCMI-6 correlates with MYC expression based on data from 60 human tumor cell lines and is abrogated by MYC depletion. Further, it inhibits MYC:MAX interaction, reduces proliferation and induces massive apoptosis in tumor tissue from a MYC-driven xenograft tumor model without severe side effects. Since MYCMI-6 does not affect MYC expression, it is a unique molecular tool to specifically target MYC:MAX pharmacologically and it has good potential for drug development.
|
|
