Tau PET and relative cerebral blood flow in Dementia with Lewy bodies: A PET study

Purpose: Alpha-synuclein often co-occurs with Alzheimer’s disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. / Methods: Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology(DLB-AD+). Receptor parametric mapping(cerebellar gray matter reference region) was used to extract regional binding potential (BPND) and R1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [18F]flortaucipir BPND and R1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [18F]flortaucipir BPND, R1 and performance on ten neuropsychological tests. / Results: Regional [18F]flortaucipir BPND in DLB was comparable with tau binding in controls (p>0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p<0.05). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p<0.01). Lower frontal R1 was associated with impaired performance on digit span forward (standardized beta, stβ=0.72) and category fluency (stβ=0.69) tests. Lower parietal R1 was related to lower delayed (stβ=0.50) and immediate (stβ=0.48) recall, VOSP number location (stβ=0.70) and fragmented letters (stβ=0.59) scores. Lower occipital R1 was associated to worse performance on VOSP fragmented letters (stβ=0.61), all p<0.05. / Conclusion: The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET

Head-and-neck paragangliomas are associated with sleep-related complaints, especially in the presence of carotid body tumors

Item does not contain fulltextOBJECTIVES: The carotid body functions as a chemoreceptor. We hypothesized that head-and-neck paragangliomas (HNP) may disturb the function of these peripheral chemoreceptors and play a role in sleep-disordered breathing. DESIGN: This is a case-control study. SETTING: This study was conducted in a tertiary referral center. PARTICIPANTS AND MAIN OUTCOME MEASURES: We assessed fatigue, sleep, and exercise capacity in 74 HNP patients using three questionnaires (Epworth Sleepiness Scale, St. George Respiratory Questionnaire, and a standard clinical sleep assessment questionnaire). Outcomes were compared to those of age- and sex-matched controls. RESULTS AND CONCLUSIONS: Activity, disturbance of psychosocial function, and total score were worse compared to controls (15.4 +/- 18.5 vs. 7.2 +/- 9.9, P = 0.007; 5.3 +/- 10.5 vs. 1.2 +/- 2.6, P = 0.008; and 10.4 +/- 12.9 vs. 5.0 +/- 4.8, P = 0.006, respectively). Patients reported more daytime fatigue, concentration difficulties, and depression (51% vs. 24%, P = 0.006; 31% vs. 10%, P = 0.010; and 19% vs. 2%, P = 0.012). Waking up was reported to be less refreshing in HNP patients (53% vs. 73%, P = 0.038). Dysphonia was a predictor of symptoms, activity, disturbance of psychosocial function, and total scores. Remarkably, the presence of a carotid body tumor was an independent predictor of increased daytime sleepiness (beta = 0.287, P = 0.029). In conclusion, patients with HNP have remarkable sleep-related complaints. Especially the presence of carotid body tumors appears to be associated with increased daytime somnolence.1 juni 201

Coupled-Channel Effects in Collisions between Heavy Ions near the Coulomb Barrier

With the recent availability of state-of-the-art heavy-ion stable and radioactive beams, there has been a renew interest in the investigation of nuclear reactions with heavy ions. I first present the role of inelastic and transfer channel couplings in fusion reactions induced by stable heavy ions. Analysis of experimental fusion cross sections by using standard coupled-channel calculations is discussed. The role of multi-neutron transfer is investigated in the fusion process below the Coulomb barrier by analyzing $^{32}$S+$^{90,96}$Zr as benchmark reactions. The enhancement of fusion cross sections for $^{32}$S+$^{96}$Zr is well reproduced at sub-barrier energies by NTFus code calculations including the coupling of the neutron-transfer channels following the Zagrebaev semi-classical model. Similar effects for $^{40}$Ca+$^{90}$Zr and $^{40}$Ca+$^{96}$Zr fusion excitation functions are found. The breakup coupling in both the elastic scattering and in the fusion process induced by weakly bound stable projectiles is also shown to be crucial. In this lecture, full coupled-channel calculations of the fusion excitation functions are performed by using the breakup coupling for the more neutron-rich reaction and for the more weakly bound projectiles. I clearly demonstrate that Continuum-Discretized Coupled-Channel calculations are capable to reproduce the fusion enhancement from the breakup coupling in $^{6}$Li+$^{59}$Co.Comment: 14 pages. 6 figure

Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis

The ADA and the EASD recently published a consensus statement for the medical management of hyperglycaemia in patients with type 2 diabetes. The authors advocate initial treatment with metformin monotherapy and lifestyle modification, followed by addition of basal insulin or a sulfonylurea if glycaemic goals are not met (tier 1 recommendations). All other glucose-lowering therapies are relegated to a secondary (tier 2) status and only recommended for selected clinical settings. In our view, this algorithm does not offer physicians and patients the appropriate selection of options to individualise and optimise care with a view to sustained control of blood glucose and reduction both of diabetes complications and cardiovascular risk. This paper critically assesses the basis of the ADA/EASD algorithm and the resulting tiers of treatment options

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Intensive care organisation: Should there be a separate intensive care unit for critically injured patients?

In the last two decennia, the mixed population general intensive care unit (ICU) with a “closed format” setting has gained in favour compared to the specialized critical care units with an “open format” setting. However, there are still questions whether surgical patients benefit from a general mixed ICU. Trauma is a significant cause of morbidity and mortality throughout the world. Major or severe trauma requiring immediate surgical intervention and/or intensive care treatment. The role and type of the ICU has received very little attention in the literature when analyzing outcomes from critical injuries. Severely injured patients require the years of experience in complex trauma care that only a surgery/trauma ICU can provide. Should a trauma center have the capability of a separate specialized ICU for trauma patients (“closed format”) next to its standard general mixed IC

High performance work practices in small firms: a resource-poverty and strategic decision-making perspective

Contains fulltext : 116515.pdf (publisher's version ) (Open Access)High performance work practices (HPWPs) are human resource management practices aimed at stimulating employee and organisational performance. The application of HPWPs is not widespread in small organisations. We examine whether the implementation of coherent bundles of HPWPs (aimed at employee ability, employee motivation or at the opportunity to perform) depends on the scarcity of resources, as reflected in the size of the company, and on strategic decision-making in small firms related to the owner’s expertise and attitudes. In our research, a total of 211 employees from 45 small organisations were asked to rate the presence of HPWPs in their organisation. These averaged perceptions were linked to information provided by the owner–managers on the size of their firm and their own expertise and attitudes. The findings support that smaller but coherent bundles of HPWPs can be found in small organisations and that the implementation of these bundles depends on available resources, strategic decision-making and the combination of the two. These findings highlight the need to integrate the notions of resource poverty and strategic decision-making to understand the uptake of bundles of HPWPs within small firms