| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 2. |
- Frykholm, Erik, 1985-
(författare)
-
The relevance and assessment of limb muscle function in individuals with chronic obstructive pulmonary disease
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic obstructive pulmonary disease (COPD) is a disease that is characterised by persistent respiratory symptoms and airflow limitation. Consequences beyond the airways and lungs are common, and include limb muscle dysfunction. Limb muscle dysfunction is treated with exercise training, and should be preceded by assessments to individualise prescriptions. Guidelines recommend assessment of quadriceps strength, but limb muscle dysfunction affects more than strength. Other less investigated assessments may be of interest. During training, direct physiological (cardiorespiratory, metabolic, and biomechanical) and symptomatic responses are important, since they can affect training effectivity, and they may differ depending on whether arms or legs are used. The main aims of this thesis were to investigate the relevance of assessments of quadriceps function, feasibility and reliability of methods to assess quadriceps endurance, and to compare the direct physiological and symptomatic responses during arm and leg activities in people with COPD.Method: This thesis is based on four papers. These include one systematic review with a meta-analysis of studies comparing direct physiological and symptomatic responses to activities performed with the arms versus the legs, and three papers based on an international cross-sectional multicentre study investigating reliability, feasibility, and relevance of three leg extension assessments of quadriceps endurance. Relative and absolute reliability were determined via interclass correlation coefficient (ICC), coefficient of variation (CV %), and limits of agreement (LoA %) for measures of isokinetic total work, isokinetic fatigue index, isometric time to exhaustion, and isotonic repetitions to exhaustion. The relevance of the measures of quadriceps endurance and other quadriceps functions were determined by the association to functional capacity and physical activity with Pearson correlation analyses (r) and multiple linear regression models (R2, adjusted R2, Δ R2, and Δ adjusted R2).Results: Results from the meta-analyses show that leg-cycle ergometer resulted in greater tidal volume (137 mL), minute ventilation (4.8 L/min), and oxygen consumption (164 mL/min) compared to arm cycle ergometer, while symptomatic responses were similar. Physiological responses (e.g., minute ventilation and oxygen consumption) during arm compared to leg resistance training exercises were similar. Results from studies on functional activities depend on the type and intensity of the activity performed. Isokinetic total work was the measurement with the highest relative reliability (ICC = 0.98) and the smallest absolute reliability (e.g., CV% = 6.5). Isokinetic fatigue index, isometric, and isotonic measures demonstrated low-to-high relative reliability (ICC = 0.64, 0.88, 0.91), and absolute reliability was larger (e.g., CV% = 20.3, 14.9, and 15.8%). Participants performed better on the retest for isokinetic total work and isometric measurements (4.8 and 10%, p < 0.001). The feasibility was similar across protocols, with an average time consumption of< 7.5 minutes, limited perceived dyspnoea compared to leg fatigue, and no major adverse advents. The measures of quadriceps function had mostly similar (r = +/- 0.07–0.45) levels of correlations to the functional capacity and physical activity. In multiple regression analyses improved quadriceps power the models to predict functional capacity the most (Δ adjusted R2= 0.10, 0.15, adjusted R2 = 0.60, 0.39). Isotonic endurance was the only muscle function that improved all physical activity models (ΔR2 = 0.04–0.07, p < 0.05, R2 = 0.38–0.49).Conclusions: The results indicate that if the goal of an activity is to maximise physiological responses such as minute ventilation and oxygen consumption, activities involving the legs should be preferred. Symptomatic responses seems task and intensity dependent, which suggest that strategies used to reduce symptoms should be based on relative intensity. In the assessment of quadriceps endurance, isokinetic, isometric and isotonic protocols present low to very high relative reliability. Differences in reliability and the better performance at retest might reflect differences in ability to detect true change. Quadriceps power seems to be more relevant to functional capacity, and isotonic quadriceps endurance seems to be more relevant to physical activity.
|
|
| 3. |
- Hibar, Derrek P., et al.
(författare)
-
Novel genetic loci associated with hippocampal volume
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
|
|
| 4. |
- Pattaro, Cristian, et al.
(författare)
-
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
|
|
| 5. |
- Satizabal, Claudia L., et al.
(författare)
-
Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
-
Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
|
|
| 6. |
- Artigas Soler, María, et al.
(författare)
-
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
-
Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
|
|
| 7. |
- Bergqvist, Matilda, et al.
(författare)
-
Dynamic and static quadriceps muscle endurance in people with COPD and healthy age and gender-matched controls
- 2019
-
Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 54:suppl 63
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: It is commonly known that quadriceps muscle endurance is decreased among people with COPD, however, whether static and dynamic quadriceps muscle endurance is affected to the same extent, remains to be determined. The latter of importance for the design of exercise modalities targeting quadriceps endurance in COPD.Methods: Static (isometric) and dynamic (isokinetic, isotonic) measurements of quadriceps muscle endurance was performed using a computerized dynamometer on 30 of individuals with COPD (FEV1 63% predicted) and 30 healthy age and gender-matched controls. Test order was randomized, separated by 30 min of rest. Comparisons between groups included both relative (seconds/repetitions) and absolute (total work [Nm]) measures of quadriceps endurance. Between-group results are presented as percentage difference (%) and effect sizes (ES).Results: When compared to healthy age and gender matched controls, people with COPD had significantly lower absolute measures of quadriceps endurance (isometric -32%, ES 0.66 [moderate]; isokinetic -29%, ES 0.94 [large], isotonic -38%, ES 0.89 [large], all p <0.05) as well as lower relative measures of dynamic quadriceps endurance (isotonic [repetitions] -20%, ES 0.50 [moderate], p = 0.02) while static quadriceps endurance did not differ between groups (isometric [seconds] -3%, ES 0.06 [trivial], p = 0.617).Conclusion: As evident by larger ES, dynamic quadriceps endurance seems to be reduced to a larger extent than static quadriceps endurance in people with COPD. Thus, exercise modalities that aim to improve quadriceps endurance should preferably be designed to increase dynamic quadriceps muscle enduranceFootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, OA3814.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
|
|
| 8. |
- Björklund, Martin, 1961-, et al.
(författare)
-
Office-cycling while working : An innovative concept to prevent and reduce musculoskeletal pain in office workers - a controlled feasibility study
- 2015
-
Konferensbidrag (refereegranskat)abstract
- Background: According to the World Health Organization, WHO, a sedentary lifestyle is the single largest health risk for a number of diseases including musculoskeletal disorders and metabolic diseases. The negative health effects of excessive sitting are not compensated for by shorter bouts of increased physical activity. However, evidence shows that increased physical activity reduces musculoskeletal pain, which is very prevalent in those who are inactive. About 50-70 % of those who work at a computer report musculoskeletal pain and spend on average about 5 hours/day with very low energy metabolism. Work places are therefore an important arena for prevention and intervention by means of reducing sedentary time and increasing physical activity both for general health benefits and effects on the musculoskeletal pain.Purpose: To test the feasibility of office-cycling in an office work place and explore its potential effects on musculoskeletal pain in office workers.Methods: Twenty office workers (ages 27-61, 5 males) with musculoskeletal pain participated in this three-week controlled pilot field study. The intervention group (n=10), had access to an innovative customized cycle ergometer (OfficeBiking®) at their regular office workstation whilst performing their usual work tasks. Offie-cycling was an alternative to sitting/standing by their height adjustable office desk; they were instructed to bike as often as comfortable. The control group (n=10) was instructed to continue to work as usual. The experiences of office-cycling and how it influenced work performance was studied with a questionnaire. Musculoskeletal pain was evaluated using pain drawings and pain ratings and participants' total pain was calculated by adding each individuals' self-reported pain from their three most painful areas (NRS 0-10).Results: Importantly, office-cycling did not reduce self-reported work performance; the majority (9/10) would like daily access; and made suggestions to improve the user-friendliness of the bike. Office-cycling was used regularly (median, 11/15 workdays; median active time 59 min/day IQR 39;91). There was no observed difference regarding either number of self-reported areas of pain (NSAP) or general musculoskeletal pain (GMP) between the intervention group and the control group at baseline. Self-reported GMP decreased in 8 persons in the intervention group which was one more than in the control group (n=7). NSAP decreased in the intervention group (n=7; md -1,0 IQR -2,3;0,0); and the control group (n=5; md -0,5 IQR -1,3;0,3). The difference in total pain (intervention end-baseline) revealed a clinically important change in the intervention group (NRS -2,5, IQR -8,8;4,0) but not in the control group (NRS 0,0 IQR -6,2;2,5).Conclusions: The results suggest that office-cycling is a feasible method for use in work place interventions with some promising results. Future research suggestions are: underlying mechanisms regarding effects of physical activity on pain in parallel with controlled studies in laboratory environments to investigate dose-effects for metabolic expenditure and optimal pain reduction whilst office-cycling.Implications: The results in this feasibility study indicate a promising potential of the innovative office-cycling concept to prevent and reduce musculoskeletal pain in sedentary office workers.
|
|
| 9. |
- Brinck, Tore, 1965-, et al.
(författare)
-
Electrostatics and polarization determine the strength of the halogen bond : a red card for charge transfer
- 2019
-
Ingår i: Journal of Molecular Modeling. - : Springer Nature. - 1610-2940 .- 0948-5023. ; 25:5
-
Tidskriftsartikel (refereegranskat)abstract
- A series of 20 halogen bonded complexes of the types R-Br center dot center dot center dot Br- (R is a substituted methyl group) and R '-CC-Br center dot center dot center dot Br- are investigated at the M06-2X/6-311+G(d,p) level of theory. Computations using a point-charge (PC) model, in which Br- is represented by a point charge in the electronic Hamiltonian, show that the halogen bond energy within this set of complexes is completely described by the interaction energy (E-PC) of the point charge. This is demonstrated by an excellent linear correlation between the quantum chemical interaction energy and E-PC with a slope of 0.88, a zero intercept, and a correlation coefficient of R-2=0.9995. Rigorous separation of E-PC into electrostatics and polarization shows the high importance of polarization for the strength of the halogen bond. Within the data set, the electrostatic interaction energy varies between 4 and-18kcal mol(-1), whereas the polarization energy varies between -4 and-10kcal mol(-1). The electrostatic interaction energy is correlated to the sum of the electron-withdrawing capacities of the substituents. The polarization energy generally decreases with increasing polarizability of the substituents, and polarization is mediated by the covalent bonds. The lower (more favorable) E-PC of CBr4---Br- compared to CF3Br center dot center dot center dot Br- is found to be determined by polarization as the electrostatic contribution is more favorable for CF3Br center dot center dot center dot Br-. The results of this study demonstrate that the halogen bond can be described accurately by electrostatics and polarization without any need to consider charge transfer.
|
|
| 10. |
- Brinck, Tore, Professor, 1965-, et al.
(författare)
-
The Importance of Electrostatics and Polarization for Noncovalent Interactions : Ionic Hydrogen Bonds vs Ionic Halogen Bonds
- 2022
-
Ingår i: Journal of Molecular Modeling. - : Springer Nature. - 1610-2940 .- 0948-5023. ; 28:9
-
Tidskriftsartikel (refereegranskat)abstract
- A series of 26 hydrogen-bonded complexes between Br- and halogen, oxygen and sulfur hydrogen-bond (HB) donors is investigated at the M06-2X/6-311 +G(2df,2p) level of theory. Analysis using a model in which Br- is replaced by a point charge shows that the interaction energy (Delta E-Int) of the complexes is accurately reproduced by the scaled interaction energy with the point charge (Delta E-Int(PC)). This is demonstrated by Delta E-Int = 0.86 Delta E-Int(PC) with a correlation coefficient, R-2=0.999. The only outlier is (Br-H-Br)(-), which generally is classified as a strong charge-transfer complex with covalent character rather than a HB complex. Delta E-Int(PC) can be divided rigorously into an electrostatic contribution (Delta E-ES(PC)) and a polarization contribution (Delta E-pol(PC)).Within the set of HB complexes investigated, the former varies between -7.2 and -32.7 kcal mol(-1), whereas the latter varies between -1.6 and -11.5 kcal mol(-1). Compared to our previous study of halogen-bonded (XB) complexes between Br and C-Br XB donors, the electrostatic contribution is generally stronger and the polarization contribution is generally weaker in the HB complexes. However, for both types of bonding, the variation in interaction strength can be reproduced accurately without invoking a charge-transfer term. For the Br-center dot center dot center dot HF complex, the importance of charge penetration on the variation of the interaction energy with intermolecular distance is investigated. It is shown that the repulsive character of Delta E-Int at short distances in this complex to a large extent can be attributed to charge penetration.
|
|
