| 1. |
- Huth, Cornelia, et al.
(författare)
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IL6 gene promoter polymorphisms and type 2 diabetes - Joint analysis of individual participants' data from 21 studies
- 2006
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Ingår i: DIABETES. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:10, s. 2915-2921
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Tidskriftsartikel (refereegranskat)abstract
- Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, −174G>C (rs1800795) and −573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 −174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 −573G>C and type 2 diabetes. The observed association of the IL6 −174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Conde, Lucia, et al.
(författare)
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Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:8, s. 661-664
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
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| 4. |
- Day, Louise T., et al.
(författare)
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"Every Newborn-BIRTH" protocol : observational study validating indicators for coverage and quality of maternal and newborn health care in Bangladesh, Nepal and Tanzania
- 2019
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Ingår i: Journal of Global Health. - : International Global Health Society. - 2047-2978 .- 2047-2986. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: To achieve Sustainable Development Goals and Universal Health Coverage, programmatic data are essential. The Every Newborn Action Plan, agreed by all United Nations member states and >80 development partners, includes an ambitious Measurement Improvement Roadmap. Quality of care at birth is prioritised by both Every Newborn and Ending Preventable Maternal Mortality strategies, hence metrics need to advance from health service contact alone, to content of care. As facility births increase, monitoring using routine facility data in DHIS2 has potential, yet validation research has mainly focussed on maternal recall surveys. The Every Newborn - Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study aims to validate selected newborn and maternal indicators for routine tracking of coverage and quality of facility-based care for use at district, national and global levels.Methods: EN-BIRTH is an observational study including >20000 facility births in three countries (Tanzania, Bangladesh and Nepal) to validate selected indicators. Direct clinical observation will be compared with facility register data and a pre-discharge maternal recall survey for indicators including: uterotonic administration, immediate newborn care, neonatal resuscitation and Kangaroo mother care. Indicators including neonatal infection management and antenatal corticosteroid administration, which cannot be easily observed, will be validated using inpatient records. Trained clinical observers in Labour/Delivery ward, Operation theatre, and Kangaroo mother care ward/areas will collect data using a tablet-based customised data capturing application. Sensitivity will be calculated for numerators of all indicators and specificity for those numerators with adequate information. Other objectives include comparison of denominator options (ie, true target population or surrogates) and quality of care analyses, especially regarding intervention timing. Barriers and enablers to routine recording and data usage will be assessed by data flow assessments, quantitative and qualitative analyses.Conclusions: To our knowledge, this is the first large, multi-country study validating facility-based routine data compared to direct observation for maternal and newborn care, designed to provide evidence to inform selection of a core list of indicators recommended for inclusion in national DHIS2. Availability and use of such data are fundamental to drive progress towards ending the annual 5.5 million preventable stillbirths, maternal and newborn deaths.
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| 5. |
- Day, Louise T, et al.
(författare)
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"Every Newborn-BIRTH" protocol: observational study validating indicators for coverage and quality of maternal and newborn health care in Bangladesh, Nepal and Tanzania.
- 2019
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Ingår i: Journal of global health. - : International Global Health Society. - 2047-2986 .- 2047-2978. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- To achieve Sustainable Development Goals and Universal Health Coverage, programmatic data are essential. The Every Newborn Action Plan, agreed by all United Nations member states and >80 development partners, includes an ambitious Measurement Improvement Roadmap. Quality of care at birth is prioritised by both Every Newborn and Ending Preventable Maternal Mortality strategies, hence metrics need to advance from health service contact alone, to content of care. As facility births increase, monitoring using routine facility data in DHIS2 has potential, yet validation research has mainly focussed on maternal recall surveys. The Every Newborn - Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study aims to validate selected newborn and maternal indicators for routine tracking of coverage and quality of facility-based care for use at district, national and global levels.EN-BIRTH is an observational study including >20 000 facility births in three countries (Tanzania, Bangladesh and Nepal) to validate selected indicators. Direct clinical observation will be compared with facility register data and a pre-discharge maternal recall survey for indicators including: uterotonic administration, immediate newborn care, neonatal resuscitation and Kangaroo mother care. Indicators including neonatal infection management and antenatal corticosteroid administration, which cannot be easily observed, will be validated using inpatient records. Trained clinical observers in Labour/Delivery ward, Operation theatre, and Kangaroo mother care ward/areas will collect data using a tablet-based customised data capturing application. Sensitivity will be calculated for numerators of all indicators and specificity for those numerators with adequate information. Other objectives include comparison of denominator options (ie, true target population or surrogates) and quality of care analyses, especially regarding intervention timing. Barriers and enablers to routine recording and data usage will be assessed by data flow assessments, quantitative and qualitative analyses.To our knowledge, this is the first large, multi-country study validating facility-based routine data compared to direct observation for maternal and newborn care, designed to provide evidence to inform selection of a core list of indicators recommended for inclusion in national DHIS2. Availability and use of such data are fundamental to drive progress towards ending the annual 5.5 million preventable stillbirths, maternal and newborn deaths.
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| 6. |
- Hanson, Angela, et al.
(författare)
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Lung aeration during ventilation after recruitment guided by tidal elimination of carbon dioxide and dynamic compliance was better than after end-tidal carbon dioxide targeted ventilation : A computed tomography study in surfactant-depleted piglets
- 2011
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Ingår i: Pediatric Critical Care Medicine. - 1529-7535 .- 1947-3893. ; 12:6, s. E362-E368
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To test the hypothesis that tidal elimination of carbon dioxide and dynamic compliance guided lung recruitment and positive end-expiratory pressure titration in surfactant-depleted piglets result in improved aeration (repeated computed tomography scans) and reduced ventilation pressures compared to those of a control group with conventional end-tidal carbon dioxide targeted ventilation. Design: Prospective animal investigation. Setting: Clinical physiology research laboratory. Subjects: Seventeen saline-lavaged piglets. Interventions: The piglets were initially ventilated at an end-inspiratory pressure of 20 cm H(2)O, a positive end-expiratory pressure of 5 cm H(2)O, and a tidal volume of 10 mL kg(-1) for an end-tidal carbon dioxide target of 30-45 torr followed by 5 mins of ventilation without positive end-expiratory pressure. After this, the control group was ventilated for the same end-tidal carbon dioxide target during the study period. In the recruitment group, the protocol started with an increase of the positive end-expiratory pressure to 15 cm H(2)O. The end-inspiratory pressure was then increased in steps of 3 cm H(2)O to a tidal elimination of carbon dioxide peak/plateau in one recruitment group and further increased in two steps in a second recruitment group. A downward positive end-expiratory pressure titration was followed by continuous dynamic compliance monitoring. The "open lung positive end-expiratory pressure" was set 2 cm H(2)O above the positive end-expiratory pressure at the first dynamic compliance decline and used for a final "open lung ventilation" period. Measurements and Main Results: The recruitment groups showed better aeration, lower ventilatory pressure amplitude, and better dynamic compliance than the control group at the end of the study. Recruitment using airway pressures above the tidal elimination of carbon dioxide peak/plateau did not improve aeration. Using end-tidal carbon dioxide targeted ventilation in the control group restored aeration after the ventilation without positive end-expiratory pressure, but no recruitment or improvement of dynamic compliance was measured. Conclusions: Aeration was significantly better after recruitment and positive end-expiratory pressure titration than in a control group managed by "conventional" end-tidal carbon dioxide targeted ventilation. An increase of the end-inspiratory pressure above the tidal elimination of carbon dioxide peak/plateau did not result in an increased amount of normally aerated lung. A recruitment maneuver resulted in a lower ventilatory amplitude for achieving a target tidal volume and better dynamic compliance at the end of the study period compared to those of the control group.
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| 7. |
- Hanson, Angela, et al.
(författare)
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Recruitment and PEEP level influences long-time aeration in saline-lavaged piglets: an experimental model.
- 2012
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Ingår i: Paediatric anaesthesia. - : Wiley. - 1460-9592 .- 1155-5645. ; 22:11, s. 1072-1079
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate aeration/ventilation in saline-lavaged piglets during a 3-h follow-up after a recruitment maneuver (RM)/PEEP titration compared with PEEP 10cmH(2) O without a RM. Background: Lung recruitment and PEEP titration are used to find a PEEP preventing repetitive opening/collapsing of lung. Methods: Twenty-one lung-lavaged piglets, mean age 7weeks and mean weight 10kg; a RM-group and a PEEP10-group, were ventilated at PEEP 5cmH(2) O (baseline) followed by zero PEEP ventilation. In the RM-group, tidal elimination of CO(2) and dynamic compliance (Cdyn) guided recruitment and PEEP titration, respectively. A final 3-h ventilation followed using PEEP 2cmH(2) O above the first decline of Cdyn and end-inspiratory pressure (EIP) for a target tidal volume (V(T) ) of 10ml·kg(-1) . In the PEEP10-group, PEEP 10cmH(2) O without a RM was used during the final 3-h ventilation. CT scans and blood gases were repeated every 30min. Airway pressures, Cdyn and hemodynamics were continuously recorded. Results: Aeration improved without differences between groups. The RM-group PEEP level of 10±0.6cmH(2) O did not differ from the PEEP10-group. Compared to baseline EIP was lower in the RM-group after 3-h ventilation. In both groups, driving pressure (DP) was lower and Cdyn higher than baseline. In the RM-group, final EIP and DP were lower and Cdyn higher than in the PEEP10-group. Conclusions: Both RM/PEEP titration and PEEP elevation resulted in improved aeration without differences between groups at the end point. Lung aeration was achieved at lower EIP and DP and higher Cdyn in the RM-group than in the PEEP10-group.
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| 8. |
- Hanson, Angela
(författare)
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Recruitment of small size lungs - experimental studies
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients - both children and adults - undergoing anesthesia and mechanical ventilation rapidly develop atelectasis. Even more severe problems occur in patients with acute lung injury/acute respiratory distress syndrome. To prevent the lung from further injury use of lung protective ventilation including a recruitment maneuver (RM) and a positive end-expiratory pressure (PEEP) titration are parts of the treatment. Children differ from adults not only in size but also in physiology. Studies in pediatric size animals should precede clinical studies. Methods: 52 pediatric size piglets, weighing about 10 kg were surfactant depleted using a lung injury model with saline lavage. In the first two of four studies tidal elimination of CO2 (VTCO2) was evaluated as a marker of optimal recruitment and dynamic compliance (Cdyn) was evaluated as a marker of incipient collapse during a RM and downward PEEP titration respectively. In all four studies the titrated PEEP was used during different follow-up-ventilation periods. Aeration, airway pressures including driving pressure (DP), Cdyn and oxygenation were recorded. Iterated CT scans were taken at every change of ventilation for measurement of aeration during the first two studies and during the follow-up-ventilation in three studies. The effect of a RM and PEEP titration for a prolonged (3 h) follow-up-ventilation was compared with a group with elevated PEEP (PEEP10-group) but without a foregoing RM. Ventilation after a RM was also compared with a control group ventilated with standard ventilation without a prior RM. In a final study continuous cardiac output (CO) was measured during the RM and PEEP titration for detailed information of central hemodynamics in eight piglets. Results: During the different follow-up-ventilation periods; 5, 15, 60 and 180 min, ventilation performed with the titrated PEEP resulted in improved aeration as assessed by repetitive CT scans, higher Cdyn, lower DP and better oxygenation compared with ventilation before the RM. VTCO2 peaked or levelled off during the recruitment and corresponding CT scans showed a recruited lung. In addition minimally improved aeration was found when airway pressure was increased above the VTCO2 peak/plateau. The first decline of Cdyn during PEEP titration corresponded to an increasing amount of lung collapse according to CT scans. CO and blood pressure decreased at the highest airway pressure during the RM. CO remained at a lower level but blood pressure recovered entirely. PEEP elevation in the PEEP10-group resulted in improved aeration, higher Cdyn and oxygenation and lower DP but not as much as in the RM-group. The control group did not improve in aeration, Cdyn or oxygenation but was stable. Conclusion: Ventilation after a RM and PEEP titration results in improved aeration, improved lung mechanics and lower airway pressures compared with baseline and compared with control groups ventilated without a foregoing lung recruitment. VTCO2 peak/plateau indicates a recruited lung and Cdyn is a good indicator of increasing derecruitment during the PEEP titration. CO was persistingly and blood pressure temporarily decreased during the RM.
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| 9. |
- Hanson, Angela, et al.
(författare)
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VTCO2 and dynamic compliance-guided lung recruitment in surfactant-depleted piglets: a computed tomography study.
- 2009
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Ingår i: Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. - 1529-7535 .- 1947-3893. ; 10:6, s. 687-92
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Using computed tomography (CT) as reference, our primary objectives were to test if maximal tidal elimination of carbon dioxide (VTCO2) could be used as a marker of "optimal recruitment," indicating maximal available lung tissue for gas exchange and if a decrease in dynamic compliance (Cdyn) indicated the beginning of lung collapse during a downward positive end-expiratory pressure (PEEP) titration. DESIGN: Prospective laboratory animal investigation. SETTING: Clinical physiology research laboratory. SUBJECTS: Six piglets undergoing lung lavage. INTERVENTIONS: Saline-lavaged piglets were initially ventilated without PEEP at a tidal volume (VT) of 10 mL/kg followed by baseline ventilation at end-inspiratory pressure (EIP) 25 cm H2O and PEEP 6 cm H2O. PEEP was increased to 12 or 15 cm H2O. Then EIP was increased in steps of 5 cm H2O and the EIP where VTCO2 peaked or leveled off was assumed to define optimally recruited lungs. A downward PEEP titration followed from 12 or 15 to 4 cm H2O in steps of 1 cm H2O. First decline of Cdyn was assumed to define onset of lung collapse. VTCO2 and Cdyn were continuously recorded and CT scans iterated for each change of ventilation. "Open-lung PEEP" was set 2 cm H2O above PEEP at the first Cdyn decline and was used for a final period of "open-lung ventilation." MEASUREMENTS AND MAIN RESULTS: CT images showed recruited lungs at peak VTCO2 and that a minimal amount of normally aerated lung was added by further increase in EIP. Cdyn declined just before CT scans indicated lung collapse. Compared with baseline, the target VT of 10 mL/kg was achieved at lower EIP and pressure amplitude (EIP-PEEP) during the final open-lung ventilation with more normally aerated and fewer collapsed lungs. Cdyn was doubled after recruitment. CONCLUSIONS: The lung recruitment maneuver was effective and lungs optimally recruited at maximal VTCO2. A fall in Cdyn indicated lung collapse during downward PEEP titration as confirmed by CT.
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| 10. |
- Ly, Han, et al.
(författare)
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The association of circulating amylin with β-amyloid in familial Alzheimer's disease.
- 2021
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Ingår i: Alzheimer's & dementia. - : Wiley. - 2352-8737. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- This study assessed the hypothesis that circulating human amylin (amyloid-forming) cross-seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).Evidence of amylin-AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non-APP/PS1 rats.Amylin-Aβ cross-seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected APP/PS1 rats against AD-associated effects. In contrast, hypersecretion or intravenous injection of human amylin in APP/PS1 rats exacerbated AD-like pathology through disruption of CSF-brain Aβ exchange and amylin-Aβ cross-seeding.These findings strengthened the hypothesis of circulating amylin-AD interaction and suggest that modulation of blood amylin levels may alter Aβ-related pathology/symptoms.
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