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  • Eliasson, A. C., et al. (författare)
  • The Manual Ability Classification System (MACS) for children with cerebral palsy: scale development and evidence of validity and reliability
  • 2006
  • Ingår i: Dev Med Child Neurol. - : John Wiley and Sons. - 0012-1622 .- 1469-8749. ; 48:7, s. 549-54
  • Tidskriftsartikel (refereegranskat)abstract
    • The Manual Ability Classification System (MACS) has been developed to classify how children with cerebral palsy (CP) use their hands when handling objects in daily activities. The classification is designed to reflect the child's typical manual performance, not the child's maximal capacity. It classifies the collaborative use of both hands together. Validation was based on the experience within an expert group, a review of the literature, and thorough analysis of children across a spectrum of function. Discussions continued until consensus was reached, first about the constructs, then about the content of the five levels. Parents and therapists were interviewed about the content and the description of levels. Reliability was tested between pairs of therapists for 168 children (70 females, 98 males; with hemiplegia [n=52], diplegia [n=70], tetraplegia [n=19], ataxia [n=6], dyskinesia [n=19], and unspecified CP [n=2]) between 4 and 18 years and between 25 parents and their children's therapists. The results demonstrated that MACS has good validity and reliability. The intraclass correlation coefficient between therapists was 0.97 (95% confidence interval 0.96-0.98), and between parents and therapist was 0.96 (0.89-0.98), indicating excellent agreement.
  • Ek, Linda, et al. (författare)
  • Hand Assessment for Infants : normative reference values
  • 2019
  • Ingår i: Developmental Medicine & Child Neurology. - : Mac Keith Press. - 0012-1622 .- 1469-8749. ; 61:9, s. 1087-1092
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To create normative reference values for unilateral and bilateral use of the hands, using the Hand Assessment for Infants (HAI), a newly developed criterion-referenced assessment measuring hand use in infants aged 3 months to 12 months at risk of cerebral palsy (CP).METHOD: In total, 489 HAI assessments of typically developing infants (243 females, 246 males), aged 3 months to 10 months (mean 6mo 14d [SD 2mo 5d]), were collected in Italy and Sweden. Normative growth curves based on mean and SDs were created, as well as skill acquisition curves for each test item. Correlation to age and differences between groups based on sex and nationality, as well as differences between the right and the left hand, were investigated.RESULTS: The growth curves showed a steady increase in mean value and a decrease in SD over age. There were no differences between groups based on sex or nationality. There was a negligible mean difference (0.1 raw score) between the right and left hands.INTERPRETATION: HAI normative reference values are now available, which can assist in identifying deviating hand use for each month of age, as well as a side difference between hands in infants at risk of CP.WHAT THIS PAPER ADDS: A Hand Assessment for Infants (HAI) result greater than 2SD below the mean indicates atypical hand use. Skill acquisition curves describe the age at which typically developing infants master the HAI items. Most typically developing infants do not demonstrate asymmetry in hand use.
  • Eliasson, Ann-Christin, 1950-, et al. (författare)
  • Efficacy of baby-CIMT : study protocol for a randomised controlled trial on infants below age 12 months, with clinical signs of unilateral CP
  • 2014
  • Ingår i: BMC Pediatrics. - : BioMed Central. - 1471-2431 .- 1471-2431. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Infants with unilateral brain lesions are at high risk of developing unilateral cerebral palsy (CP). Given the great plasticity of the young brain, possible interventions for infants at risk of unilateral CP deserve exploration. Constraint-induced movement therapy (CIMT) is known to be effective for older children with unilateral CP but is not systematically used for infants. The development of CIMT for infants (baby-CIMT) is described here, as is the methodology of an RCT comparing the effects on manual ability development of baby-CIMT versus baby-massage. The main hypothesis is that infants receiving baby-CIMT will develop manual ability in the involved hand faster than will infants receiving baby-massage in the first year of life.METHOD AND DESIGN: The study will be a randomised, controlled, prospective parallel-group trial. Invited infants will be to be randomised to either the baby-CIMT or the baby-massage group if they: 1) are at risk of developing unilateral CP due to a known neonatal event affecting the brain or 2) have been referred to Astrid Lindgren Children's Hospital due to asymmetric hand function. The inclusion criteria are age 3-8 months and established asymmetric hand use. Infants in both groups will receive two 6-weeks training periods separated by a 6-week pause, for 12 weeks in total of treatment. The primary outcome measure will be the new Hand Assessment for Infants (HAI) for evaluating manual ability. In addition, the Parenting Sense of Competence scale and Alberta Infant Motor Scale will be used. Clinical neuroimaging will be utilized to characterise the brain lesion type. To compare outcomes between treatment groups generalised linear models will be used.DISCUSSION: The model of early intensive intervention for hand function, baby-CIMT evaluated by the Hand Assessment for Infants (HAI) will have the potential to significantly increase our understanding of how early intervention of upper limb function in infants at risk of developing unilateral CP can be performed and measured.TRIAL REGISTRATION: SFO-V4072/2012, 05/22/2013.
  • Eliasson, Jonas, et al. (författare)
  • The Stockholm congestion - charging trial 2006 : Overview of effects
  • 2009
  • Ingår i: Transportation Research Part A. - Amsterdam : Elsevier. - 0965-8564 .- 1879-2375. ; 43:3, s. 240-250
  • Tidskriftsartikel (refereegranskat)abstract
    • The Stockholm congestion charging trial in 2006 demonstrated the effects of a full-scale time-differentiated urban road toll scheme. Improvements in travel times were large enough to be perceived by the general public. This was pivotal to the radical change of public attitudes that occurred during the trial and that resulted in a positive outcome of a subsequent referendum on a proposal for making the system permanent. This paper summarises the effects of the trial and analyses to what extent targets were met. Effects on congestion reduction were larger than anticipated, which also resulted in favourable economic and environmental effects. The trial showed that a single-cordon toll could affect traffic within a large area, i.e., not just close to the zone limits.
  • Krumlinde-Sundholm, Lena, et al. (författare)
  • Development of the Hand Assessment for Infants : evidence of internal scale validity
  • 2017
  • Ingår i: Developmental Medicine & Child Neurology. - : Mac Keith Press. - 0012-1622 .- 1469-8749. ; 59:12, s. 1276-1283
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The aim of this study was to develop a descriptive and evaluative assessment of upper limb function for infants aged 3 to 12 months and to investigate its internal scale validity for use with infants at risk of unilateral cerebral palsy.METHOD: The concepts of the test items and scoring criteria were developed. Internal scale validity and aspects of reliability were investigated on the basis of 156 assessments of infants at 3 to 12 months corrected age (mean 7.2mo, SD 2.5) with signs of asymmetric hand use. Rasch measurement model analysis and non-parametric statistics were used.RESULTS: The new test, the Hand Assessment for Infants (HAI), consists of 12 unimanual and five bimanual items, each scored on a 3-point rating scale. It demonstrated a unidimensional construct and good fit to the Rasch model requirements. The excellent person reliability enabled person separation to six significant ability strata. The HAI produced an interval-level measure of bilateral hand use as well as unimanual scores of each hand, allowing a quantification of possible asymmetry expressed as an asymmetry index.INTERPRETATION: The HAI can be considered a valid assessment tool for measuring bilateral hand use and quantifying side difference between hands among infants at risk of developing unilateral cerebral palsy.WHAT THIS PAPER ADDS: The Hand Assessment for Infants (HAI) measures the use of both hands and quantifies a possible asymmetry of hand use. HAI is valid for infants at 3 to 12 months corrected age at risk of unilateral cerebral palsy.
  • Rosengren, A. H., et al. (författare)
  • Overexpression of alpha2A-adrenergic receptors contributes to type 2 diabetes
  • 2010
  • Ingår i: Science. - : American Association for the Advancement of Science. - 1095-9203. ; 327:5962, s. 217-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Several common genetic variations have been associated with type 2 diabetes, but the exact disease mechanisms are still poorly elucidated. Using congenic strains from the diabetic Goto-Kakizaki rat, we identified a 1.4-megabase genomic locus that was linked to impaired insulin granule docking at the plasma membrane and reduced beta cell exocytosis. In this locus, Adra2a, encoding the alpha2A-adrenergic receptor [alpha(2A)AR], was significantly overexpressed. Alpha(2A)AR mediates adrenergic suppression of insulin secretion. Pharmacological receptor antagonism, silencing of receptor expression, or blockade of downstream effectors rescued insulin secretion in congenic islets. Furthermore, we identified a single-nucleotide polymorphism in the human ADRA2A gene for which risk allele carriers exhibited overexpression of alpha(2A)AR, reduced insulin secretion, and increased type 2 diabetes risk. Human pancreatic islets from risk allele carriers exhibited reduced granule docking and secreted less insulin in response to glucose; both effects were counteracted by pharmacological alpha(2A)AR antagonists.
  • Barg, Sebastian, et al. (författare)
  • The stimulatory action of tolbutamide on Ca2+-dependent exocytosis in pancreatic beta cells is mediated by a 65-kDa mdr-like P-glycoprotein
  • 1999
  • Ingår i: Proceedings of the National Academy of Sciences. - : National Acad Sciences. - 1091-6490 .- 0027-8424. ; 96:10, s. 5539-5544
  • Tidskriftsartikel (refereegranskat)abstract
    • Intracellular application of the sulfonylurea tolbutamide during whole-cell patch-clamp recordings stimulated exocytosis >5-fold when applied at a cytoplasmic Ca2+ concentration of 0.17 microM. This effect was not detectable in the complete absence of cytoplasmic Ca2+ and when exocytosis was elicited by guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). The stimulatory action could be antagonized by the sulfonamide diazoxide, by the Cl--channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), by intracellular application of the antibody JSB1 [originally raised against a 170-kDa multidrug resistance (mdr) protein], and by tamoxifen (an inhibitor of the mdr- and volume-regulated Cl- channels). Immunocytochemistry and Western blot analyses revealed that JSB1 recognizes a 65-kDa protein in the secretory granules. This protein exhibited no detectable binding of sulfonylureas and is distinct from the 140-kDa sulfonylurea high-affinity sulfonylurea receptors also present in the granules. We conclude that (i) tolbutamide stimulates Ca2+-dependent exocytosis secondary to its binding to a 140-kDa high-affinity sulfonylurea receptor in the secretory granules; and (ii) a granular 65-kDa mdr-like protein mediates the action. The processes thus initiated culminate in the activation of a granular Cl- conductance. We speculate that the activation of granular Cl- fluxes promotes exocytosis (possibly by providing the energy required for membrane fusion) by inducing water uptake and an increased intragranular hydrostatic pressure.
  • Barg, Sebastian, et al. (författare)
  • Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells
  • 2000
  • Ingår i: Diabetes. - : American Diabetes Association Inc.. - 1939-327X .- 0012-1797. ; 49:9, s. 1500-1510
  • Tidskriftsartikel (refereegranskat)abstract
    • alpha-Cells were identified in preparations of dispersed mouse islets by immunofluorescence microscopy. A high fraction of alpha-cells correlated with a small cell size measured as the average cell diameter (10 microm) and whole-cell capacitance (<4 pF). The alpha-cells generated action potentials at a low frequency (1 Hz) in the absence of glucose. These action potentials were reversibly inhibited by elevation of the glucose concentration to 20 mmol/l. The action potentials originated from a membrane potential more negative than -50 mV, had a maximal upstroke velocity of 5 V/s, and peaked at +1 mV. Voltage-clamp experiments revealed the ionic conductances underlying the generation of action potentials. alpha-Cells are equipped with a delayed tetraethyl-ammonium-blockable outward current (activating at voltages above -20 mV), a large tetrodotoxin-sensitive Na+ current (above -30 mV; peak current 200 pA at +10 mV), and a small Ca2+ current (above -50 mV; peak current 30 pA at +10 mV). The latter flowed through omega-conotoxin GVIA (25%)- and nifedipine-sensitive (50%) Ca(2+)-channels. Mouse alpha-cells contained, on average, 7,300 granules, which undergo Ca(2+)-induced exocytosis when the alpha-cell is depolarized. Three functional subsets of granules were identified, and the size of the immediately releasable pool was estimated as 80 granules, or 1% of the total granule number. The maximal rate of exocytosis (1.5 pF/s) was observed 21 ms after the onset of the voltage-clamp depolarization, which is precisely the duration of Ca(2+)-influx during an action potential. Our results suggest that the secretory machinery of the alpha-cell is optimized for maximal efficiency in the use of Ca2+ for exocytosis.
  • Collins, S. C., et al. (författare)
  • Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon
  • 2008
  • Ingår i: Diabetologia. - : Springer. - 1432-0428 .- 0012-186X. ; 51:9, s. 1689-1693
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis Long-term exposure to NEFAs leads to inhibition of glucose-induced insulin secretion. We tested whether the release of somatostatin and glucagon, the two other major islet hormones, is also affected. Methods Mouse pancreatic islets were cultured for 72 h at 4.5 or 15 mmol/l glucose with or without 0.5 mmol/l oleate or palmitate. The release of glucagon and somatostatin during subsequent 1 h incubations at 1 or 20 mmol/l glucose as well as the islet content of the two hormones were determined. Lipid-induced changes in islet cell ultrastructure were assessed by electron microscopy. Results Culture at 15 mmol/l glucose increased islet glucagon content by similar to 50% relative to that observed following culture at 4.5 mmol/l glucose. Inclusion of oleate or palmitate reduced islet glucagon content by 25% (at 4.5 mmol/l glucose) to 50% (at 15 mmol/l glucose). Long-term exposure to the NEFA increased glucagon secretion at 1 mmol/l glucose by 50% (when islets had been cultured at 15 mmol/l glucose) to 100% (with 4.5 mmol/l glucose in the culture medium) and abolished the inhibitory effect of 20 mmol/l glucose on glucagon secretion. Somatostatin content was unaffected by glucose and lipids, but glucose-induced somatostatin secretion was reduced by similar to 50% following long-term exposure to either of the NEFA, regardless of whether the culture medium contained 4.5 or 15 mmol/l glucose. Ultrastructural evidence of lipid deposition was seen in < 10% of non-beta cells but in > 80% of the beta cells. Conclusions/interpretation Long-term exposure to high glucose and/or NEFA affects the release of somatostatin and glucagon. The effects on glucagon secretion are very pronounced and in type 2 diabetes in vivo may aggravate the hyperglycaemic effects due to lack of insulin.
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