| 1. |
- Saxena, Richa, et al.
(författare)
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Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
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| 2. |
- Hardy, J., et al.
(författare)
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Pathways to Alzheimer's disease
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 275:3, s. 296-303
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Tidskriftsartikel (refereegranskat)abstract
- Recent trials of anti-amyloid agents have not produced convincing improvements in clinical outcome in Alzheimer's disease; however, the reason for these poor or inconclusive results remains unclear. Recent genetic data continue to support the amyloid hypothesis of Alzheimer's disease with protective variants being found in the amyloid gene and both common low-risk and rare high-risk variants for disease being discovered in genes that are part of the amyloid response pathways. These data support the view that genetic variability in how the brain responds to amyloid deposition is a potential therapeutic target for the disease, and are consistent with the notion that anti-amyloid therapies should be initiated early in the disease process. © 2014 The Association for the Publication of the Journal of Internal Medicine.
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| 3. |
- Hasan, A, et al.
(författare)
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World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia : Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance.
- 2012
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Ingår i: The World Journal of Biological Psychiatry. - : Informa UK Limited. - 1562-2975 .- 1814-1412. ; 13:5, s. 318-378
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Tidskriftsartikel (refereegranskat)abstract
- These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A–F; Bandelow et al. 2008b, World J Biol Psychiatry 9:242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.
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| 4. |
- Parnetti, L, et al.
(författare)
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Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer's disease.
- 2011
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 124:2, s. 122-129
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Tidskriftsartikel (refereegranskat)abstract
- Objectives - To measure cerebrospinal fluid (CSF) activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in patients with Alzheimer's disease (AD) participating in randomized clinical trials from three European centers, before and after long-term treatment with different AChE inhibitors (AChEIs). Materials and methods - Of the 144 patients included in the study, 104 were treated with donepezil, 15 with galantamine, 16 with rivastigmine, and nine with placebo. CSF AChE and BChE activities were measured at baseline and after 1-year treatment. Results - Donepezil and galantamine groups showed a significant increase in CSF AChE activity at follow-up, while no changes for BChE activity were observed; in donepezil group, a positive correlation between plasma concentration and AChE activity was documented. Conversely, in rivastigmine group, a decrease in CSF activity of both enzymes was observed. CSF AChE and BChE activities were not correlated with the clinical outcome in any group considered. CSF biomarkers did not show any change after treatment. Conclusions - AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.
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| 5. |
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| 6. |
- Blennow, Kaj, 1958, et al.
(författare)
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No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.
- 2011
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 123, s. 245-51
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Tidskriftsartikel (refereegranskat)abstract
- Blennow K, Jonsson M, Andreasen N, Rosengren L, Wallin A, Hellström PA, Zetterberg H. No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01408.x .(c) 2010 John Wiley & Sons A/S. Background - Psychiatric and neurological symptoms are common among soldiers exposed to blast without suffering a direct head injury. It is not known whether such symptoms are direct consequences of blast overpressure. Objective - To examine if repeated detonating explosions or firing if of heavy weapons is associated with neurochemical evidence of brain damage. Materials and methods - Three controlled experimental studies. In the first, army officers were exposed to repeated firing of a FH77B howitzer or a bazooka. Cerebrospinal fluid (CSF) was taken post-exposure to measure biomarkers for brain damage. In the second, officers were exposed for up to 150 blasts by firing a bazooka, and in the third to 100 charges of detonating explosives of 180 dB. Serial serum samples were taken after exposure. Results were compared with a control group consisting of 19 unexposed age-matched healthy volunteers. Results - The CSF biomarkers for neuronal/axonal damage (tau and neurofilament protein), glial cell injury (GFAP and S-100b), blood-brain barrier damage (CSF/serum albumin ratio) and hemorrhages (hemoglobin and bilirubin) and the serum GFAP and S-100b showed normal and stable levels in all exposed officers. Discussion - Repeated exposure to high-impact blast does not result in any neurochemical evidence of brain damage. These findings are of importance for soldiers regularly exposed to high-impact blast when firing artillery shells or other types of heavy weapons.
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| 7. |
- Boudreau, Shellie A., et al.
(författare)
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Features of cortical neuroplasticity associated with multidirectional novel motor skill training: a TMS mapping study
- 2013
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 225:4, s. 513-526
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Tidskriftsartikel (refereegranskat)abstract
- Given the evidence that the primary motor cortex (MI) consists of subpopulations of upper motor neurons tuned to different directional parameters of a motor movement, this study hypothesized that novel motor skill training involving either a bidirectional or more complex multidirectional tongue-typing movement should produce distinct training-related features of tongue MI neuroplasticity in humans. Novel motor skill training consisted of tongue typing using custom-made intra-oral keypads for 30-min over two consecutive days. The bidirectional keypad consisted of three sensors positioned along the upper palatal midline as a 3 x 1 array, whereas the multidirectional keypad consisted of nine sensors arranged as a 3 x 3 array that was centred along the upper palatal midline. Each sensor corresponded to one letter and participants were asked to type sequences of letters by accurately placing the tongue over the correct sensor. Before and after each training session, excitability of the tongue MI was assessed with transcranial magnetic stimulation (TMS)-motor evoked potentials (MEPs) over 13 motor map sites and TMS-MEP stimulus-response curves were constructed for the first dorsal interosseous (FDI, as an internal control). Tongue-typing performance improved within and across training days for both groups; although bidirectional training displayed greater success. Bidirectional and multidirectional training were associated with increases and decreases in a number of cortical motor map sites from where tongue activity could be evoked, however; multidirectional training was associated with a greater number of cortical motor map sites with increased excitability and a shift in the centre of gravity of the motor map. No effects of training were found on the FDI TMS-MEP stimulus-response curves. This study revealed distinct training-related features of tongue MI neuroplasticity and proposes that a greater amount of functionally related neuronal populations may be 'trained' by the inclusion of different and more complex directional parameters within a novel motor task.
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| 8. |
- Caltenco, Héctor, et al.
(författare)
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On the tip of the tongue: Learning typing and pointing with an intra-oral interface
- 2014
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Ingår i: Disability and Rehabilitation: Assistive Technology. - : Informa UK Limited. - 1748-3115 .- 1748-3107. ; 9:4, s. 307-317
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate typing and pointing performance and improvement over time of four able-bodied participants using an intra-oral tongue-computer interface for computer control. Background: A physically disabled individual may lack the ability to efficiently control standard computer input devices. There have been several efforts to produce and evaluate interfaces that provide individuals with physical disabilities the possibility to control personal computers. Method: Training with the intra-oral tongue-computer interface was performed by playing games over 18 sessions. Skill improvement was measured through typing and pointing exercises at the end of each training session. Results: Typing throughput improved from averages of 2.36 to 5.43 correct words per minute. Pointing throughput improved from averages of 0.47 to 0.85 bits/s. Target tracking performance, measured as relative time on target, improved from averages of 36% to 47%. Path following throughput improved from averages of 0.31 to 0.83 bits/s and decreased to 0.53 bits/s with more difficult tasks. Conclusions: Learning curves support the notion that the tongue can rapidly learn novel motor tasks. Typing and pointing performance of the tongue-computer interface is comparable to performances of other proficient assistive devices, which makes the tongue a feasible input organ for computer control.
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| 9. |
- Caltenco, Héctor, et al.
(författare)
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The Impact of Function Location on Typing and Pointing Tasks With an Intraoral Tongue-Computer Interface
- 2014
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Ingår i: International Journal of Human-Computer Interaction. - : Informa UK Limited. - 1532-7590 .- 1044-7318. ; 30:4, s. 267-277
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Tidskriftsartikel (refereegranskat)abstract
- Intraoral target (typing) and on-screen target (pointing/tracking) selection tasks were performed by 10 participants during 3 consecutive day sessions. Tasks were performed using 2 different intraoral sensor layouts. Reduction of undesired sensor activations while speaking as well as the influence of intraoral temperature variation on the signals of the intraoral interface was investigated. Results showed that intraoral target selection tasks were performed better when the respective sensor was located in the anterior area of the palate, reaching 78 and 16 activations per minute for repetitive and "unordered" sequences, respectively. Virtual target pointing and tracking tasks, of circles of 50, 70, and 100 pixels diameter, showed no significant difference in performance, reaching average pointing throughputs of 0.62 to 0.72 bits per second and relative time on target of 34% to 60%. Speaking tasks caused an average of 10 to 31 involuntary activations per minute in the anterior part of the palate. Intraoral temperature variation between 11.87 degrees C and 51.37 degrees C affected the sensor signal baseline in a range from -25.34% to 48.31%. Results from this study provide key design considerations to further increase the efficiency of tongue-computer interfaces for individuals with upper-limb mobility impairments.
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| 10. |
- Caltenco, Héctor, et al.
(författare)
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TongueWise : tongue-computer interface software for people with tetraplegia
- 2010
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Ingår i: International Conference of the IEEE Engineering in Medicine and Biology Society. - 1557-170X. - 9781424441235 ; 32, s. 4534-4537
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Konferensbidrag (refereegranskat)abstract
- Many computer interfaces and assistive devices for people with motor disabilities limit the input dimensionality from user to system, in many cases leading to single switch interfaces where the user can only press one button. This can, either limit the level of direct access to the functionalities of the operating system, or slow down speed of interaction. In this paper we present TongueWise: a software developed for a tongue computer interface that can be activated with the tip of the tongue and that provides direct input that covers most of the standard keyboard and mouse commands.
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