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| 2. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 4. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 7. |
- Zavala, J. A., et al.
(författare)
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The Evolution of the IR Luminosity Function and Dust-obscured Star Formation over the Past 13 Billion Years
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 909:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first results from the Mapping Obscuration to Reionization with ALMA (MORA) survey, the largest Atacama Large Millimeter/submillimeter Array (ALMA) blank-field contiguous survey to date (184 arcmin(2)) and the only at 2 mm to search for dusty star-forming galaxies (DSFGs). We use the 13 sources detected above 5 sigma to estimate the first ALMA galaxy number counts at this wavelength. These number counts are then combined with the state-of-the-art galaxy number counts at 1.2 and 3 mm and with a backward evolution model to place constraints on the evolution of the IR luminosity function and dust-obscured star formation in the past 13 billion years. Our results suggest a steep redshift evolution on the space density of DSFGs and confirm the flattening of the IR luminosity function at faint luminosities, with a slope of alpha(LF) = -0.42(-0.04)(+0.02). We conclude that the dust-obscured component, which peaks at z approximate to 2-2.5, has dominated the cosmic history of star formation for the past similar to 12 billion years, back to z similar to 4. At z = 5, the dust-obscured star formation is estimated to be similar to 35% of the total star formation rate density and decreases to 25%-20% at z = 6-7, implying a minor contribution of dusten-shrouded star formation in the first billion years of the universe. With the dust-obscured star formation history constrained up to the end of the epoch of reionization, our results provide a benchmark to test galaxy formation models, to study the galaxy mass assembly history, and to understand the dust and metal enrichment of the universe at early times.
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| 15. |
- Bonefeld-Jorgensen, Eva C, et al.
(författare)
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Xenoestrogenic activity in blood of European and Inuit populations
- 2006
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Ingår i: Environmental Health. - 1476-069X. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human exposure to persistent organic pollutants (POPs) is ubiquitous and found in all individuals. Studies have documented endocrine disrupting effects and impact on reproduction. The aim of the present study was to compare the level of xenoestrogenic activity in serum of groups with varying POP exposure, and to evaluate correlations to the POP biomarkers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 358 men: Greenlandic Inuit's, Swedish fishermen, and Warsaw (Poland) and Kharkiv (Ukraine) inhabitants. Xenoestrogenicity of serum extracts alone (XER) and XER competitive (XERcomp) effect on 17beta-estradiol induced estrogen receptor (ER) transactivity were assessed in the hormone free, lipophilic serum fraction containing the POPs using the MVLN human breast cancer cell line. RESULTS: No agonistic XER activity was exhibited for Inuit serum samples, while 12 - 24% of the European samples had detectable agonistic XER activity. On the contrary, 71% of Inuit serum samples antagonized XERcomp compared to 7 - 30 % in the other regions. XER and XERcomp were not or weakly correlated to the two POP markers. XER activity of Inuit samples was negatively associated to levels of CB-153 and p,p'-DDE. For the Warsaw group a positive and negative correlation between XER and p,p'-DDE and estradiol equivalence level and CB-153 levels was found. CONCLUSION: No strong consistent association between xenoestrogenic net activity and the two POP markers was found. The results showed that the selected POP markers alone can not predict the integrated xenoestrogenic serum activity. Correlations to the POP markers were found at the extreme edge; the Inuit's and Warsaw study groups eliciting high frequency of samples with ER antagonistic and agonistic activity, respectively. We suggest that the variation in xenoestrogenic serum activity reflects differences in POP exposure mixture, genetic factors and/or life style factors.
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| 16. |
- Heintz, K. E., et al.
(författare)
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The Gas and Stellar Content of a Metal-poor Galaxy at z = 8.496 as Revealed by JWST and ALMA
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 944:2
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Tidskriftsartikel (refereegranskat)abstract
- We present a joint analysis of the galaxy S04590 at z = 8.496 based on NIRSpec, NIRCam, and NIRISS observations obtained as part of the Early Release Observations program of the James Webb Space Telescope (JWST) and the far-infrared [C ii] 158 μm emission line detected by dedicated Atacama Large Millimeter/submillimeter Array (ALMA) observations. We determine the physical properties of S04590 from modeling of the spectral energy distribution (SED) and through the redshifted optical nebular emission lines detected with JWST/NIRSpec. The best-fit SED model reveals a low-mass (M ⋆ = 107.2-108 M ⊙) galaxy with a low oxygen abundance of 12 + log ( O / H ) = 7.16 − 0.12 + 0.10 derived from the strong nebular and auroral emission lines. Assuming that [C ii] effectively traces the interstellar medium, we estimate the total gas mass of the galaxy to be M gas = (8.0 ± 4.0) × 108 M ⊙ based on the luminosity and spatial extent of [C ii]. This yields an exceptionally high gas fraction, f gas = M gas/(M gas + M ⋆) ≳ 90%, though one still consistent with the range expected for low metallicity. We further derive the metal mass of the galaxy based on the gas mass and gas-phase metallicity, which we find to be consistent with the expected metal production from Type II supernovae. Finally, we make the first constraints on the dust-to-gas (DTG) and dust-to-metal (DTM) ratios of galaxies in the epoch of reionization at z ≳ 6, showing overall low mass ratios of logDTG < −3.8 and logDTM < −0.5, though they are consistent with established scaling relations and in particular with those of the local metal-poor galaxy I Zwicky 18. Our analysis highlights the synergy between ALMA and JWST in characterizing the gas, metal, and stellar content of the first generation of galaxies.
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| 19. |
- Knaapila, Matti, et al.
(författare)
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A new small-angle X-ray scattering set-up on the crystallography beamline I711 at MAX-lab.
- 2009
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Ingår i: Journal of Synchrotron Radiation. - 1600-5775. ; 16:Pt 4, s. 498-504
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Tidskriftsartikel (refereegranskat)abstract
- A small-angle X-ray scattering (SAXS) set-up has recently been developed at beamline I711 at the MAX II storage ring in Lund (Sweden). An overview of the required modifications is presented here together with a number of application examples. The accessible q range in a SAXS experiment is 0.009-0.3 A(-1) for the standard set-up but depends on the sample-to-detector distance, detector offset, beamstop size and wavelength. The SAXS camera has been designed to have a low background and has three collinear slit sets for collimating the incident beam. The standard beam size is about 0.37 mm x 0.37 mm (full width at half-maximum) at the sample position, with a flux of 4 x 10(10) photons s(-1) and lambda = 1.1 A. The vacuum is of the order of 0.05 mbar in the unbroken beam path from the first slits until the exit window in front of the detector. A large sample chamber with a number of lead-throughs allows different sample environments to be mounted. This station is used for measurements on weakly scattering proteins in solutions and also for colloids, polymers and other nanoscale structures. A special application supported by the beamline is the effort to establish a micro-fluidic sample environment for structural analysis of samples that are only available in limited quantities. Overall, this work demonstrates how a cost-effective SAXS station can be constructed on a multipurpose beamline.
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| 22. |
- Modvig, S, et al.
(författare)
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Value of Flow Cytometry for MRD-Based Relapse Prediction in B-Cell Precursor Acute Lymphoblastic Leukemia in a Multi-Center Setting
- 2019
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Ingår i: Blood. - 0006-4971 .- 1528-0020.
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Konferensbidrag (refereegranskat)abstract
- Background: PCR of rearranged antigen receptor genes is the method of choice for MRD quantification in ALL. Although FCM-MRD is faster and biologically more informative than PCR, the analysis requires a high level of training. The only larger published studies using FCM-MRD based stratification (Borowitz, Blood, 2008 and 2015) showed a clear association with clinical outcome in BCP-ALL. However, MRD analyses were centralized and these studies included only one MRD-based stratification (MRD levels at the end of induction). Patients and methods: We examined FCM-MRD as stratification tool in BCP-ALL at various timepoints in a large-scale multicenter (18 MRD centers) study. A total of 1487 patients with BCP-ALL (1298 children (younger than 18 years) and 189 adults (18-45 years) are included in the study and were treated according to the NOPHO ALL2008 protocol between July 2008 and February 2016. The median follow-up time for patients in first remission was 51 months (IQR 32-75). MRD was measured by FCM and/or real time quantitative PCR on days 15, 29 (end of induction) and 79 (for standard (SR) and intermediate risk (IR) patients) and prior to and after high risk blocks. A 6-colour FCM analysis including 3 standardized antibody combinations was used and performed in 18 laboratories. Patients were stratified by FCM-MRD, or by PCR-MRD if no FCM-MRD marker was available. End-of-induction MRD (cut-off 10-3) was used to stratify patients to standard risk (SR) vs intermediate risk (IR) or IR vs high risk consolidation therapy (in case of WBC > 100 x 109/L at diagnosis). Patients with MRD >=2.5x10-1 on day 15 were stratified to high risk block therapy. Patients with MRD >=5x10-2 on day 29 or day 79/post high risk-2 block MRD >=10-3 were stratified to HSCT. Primary outcomes were 5year event-free survival (5y EFS) and 5year cumulative incidence of relapse (5y CIR). Results: Only two patients (0.14% of total) had neither an informative FCM nor a PCR marker, and an informative FCM marker combination for MRD monitoring was identified in 96.2% of patients. There was a significant correlation between FCM- and PCR-MRD levels on day 15 (r=0.77, p<0.0001, n=153) and 29 (r=0.81, p<0.0001, n=140). Based on FCM-MRD only, the median MRD level on day 15, 29 and 79/post high risk-2 block was 5x10-3, 1.1x10-4, and below detection limit, respectively. Adults had significantly higher MRD levels at all time-points (p<0.0001 for day 15 and 29, p=0.0019 for day 79, Mann-Whitney). The 5y EFS was 86.1% (95% CI 84.1-88.1) with a 5y CIR of 9.5% (95% CI 7.8-11.3, n=1487). The day 29 FCM-MRD level was closely associated with clinical outcome and a higher hazard of relapse was seen independently for a FCM-MRD >=10-3 (hazard ratio (HR) 2.4, CI 1.6-3.7, p<0.0001), age>18 year (HR 3.0, CI 1.7-5.3, p<0.0001), WBC>=100 (HR 2.7, CI 1.6-4.6, p=0.0001), and B-other (HR 2.1, CI 1.2-3.5, p=0.0052) or high risk B-ALL cytogenetic aberration (rearranged KMT2A/iAMPchr21/hypodiploid) (HR 3.2, CI 1.6-6.1, p=0.0006) (multivariate cause-specific Cox regression, n=1328). Patients with a day 79 FCM-MRD >=10-4 and <10-3 had a significantly higher CIR (22.1%, CI 10.8-33.5%, n=68) compared to FCM-MRD <10-4 (7.5%, CI 2.1-12.8%, n=110) or undetectable (6.3%, CI 4.5-8.2%, n=999, p=0.0087 for FCM-MRD >=10-4 and <10-3vs <10-4 or undetectable). After adjusting for WBC, age, and the day 29 FCM-MRD level, a day 79 FCM-MRD >=10-4 and <10-3 was still significantly associated with a worse 5y CIR for non-transplanted patients (HR 2.3, CI 1.19-4.36, p=0.012 compared to undetectable FCM-MRD, n=1171). Patients with day 15 FCM-MRD <10-3 had a significantly better 5y EFS (92.0%, CI 89.2-95.0%) and CIR (3.9%, CI 1.7-6.1%, n=432) than patients with FCM-MRD >=10-3 and <2.5x10-1, who had a 5y EFS of 85.5% (CI 82.7-88.3%, p=0.0016, n=837) and a 3-fold higher 5y CIR (11.0%, CI 8.4-13.5%, p<0.0001, n=432). Among patients with day 15 FCM-MRD<10-3, the relapse incidence was comparable for patients with FCM-MRD 10-4 - <10-3 and below 10-4 (CIR 3.6, CI 0.5-6.7 vs. CIR 4.1, CI 1.0-7.2, p=0.83, n=432). Conclusion: FCM-MRD performed in a multi-center setting is a clinically useful method for disease monitoring and MRD-based treatment stratification in BCP-ALL. Moreover, FCM-MRD is a reliable indicator of outcome in BCP-ALL independently of other key risk factors. Residual disease >=10-4 and <10-3 at day 79 in SR/IR patients not allocated to HSCT further identifies patients with a high risk of relapse.
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| 23. |
- Modvig, S, et al.
(författare)
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Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting.
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35, s. 1894-1906
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Tidskriftsartikel (refereegranskat)abstract
- PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p<0.0001), 29 (HzR 2.7, p<0.0001), and 79 (HzR 3.5, p<0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4×10-2 versus 5.2×10-3, p<0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y=3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD>10-4 associated with a CIR5y=22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.
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| 25. |
- Schjørring, O. L., et al.
(författare)
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Intensive care doctors’ preferences for arterial oxygen tension levels in mechanically ventilated patients
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 62:10, s. 1443-1451
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oxygen is liberally administered in intensive care units (ICUs). Nevertheless, ICU doctors’ preferences for supplementing oxygen are inadequately described. The aim was to identify ICU doctors’ preferences for arterial oxygenation levels in mechanically ventilated adult ICU patients. Methods: In April to August 2016, an online multiple-choice 17-part-questionnaire was distributed to 1080 ICU doctors in seven Northern European countries. Repeated reminder e-mails were sent. The study ended in October 2016. Results: The response rate was 63%. When evaluating oxygenation 52% of respondents rated arterial oxygen tension (PaO2) the most important parameter; 24% a combination of PaO2 and arterial oxygen saturation (SaO2); and 23% preferred SaO2. Increasing, decreasing or not changing a default fraction of inspired oxygen of 0.50 showed preferences for a PaO2 around 8 kPa in patients with chronic obstructive pulmonary disease, a PaO2 around 10 kPa in patients with healthy lungs, acute respiratory distress syndrome or sepsis, and a PaO2 around 12 kPa in patients with cardiac or cerebral ischaemia. Eighty per cent would accept a PaO2 of 8 kPa or lower and 77% would accept a PaO2 of 12 kPa or higher in a clinical trial of oxygenation targets. Conclusion: Intensive care unit doctors preferred PaO2 to SaO2 in monitoring oxygen treatment when peripheral oxygen saturation was not included in the question. The identification of PaO2 as the preferred target and the thorough clarification of preferences are important when ascertaining optimal oxygenation targets. In particular when designing future clinical trials of higher vs lower oxygenation targets in ICU patients.
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| 26. |
- Tulstrup, M., et al.
(författare)
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NT5C2 germline variants alter thiopurine metabolism and are associated with acquired NT5C2 relapse mutations in childhood acute lymphoblastic leukaemia
- 2018
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 32:12, s. 2527-2535
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Tidskriftsartikel (refereegranskat)abstract
- The antileukaemic drug 6-mercaptopurine is converted into thioguanine nucleotides (TGN) and incorporated into DNA (DNA-TG), the active end metabolite. In a series of genome-wide association studies, we analysed time-weighted means ((wm)) of erythrocyte concentrations of TGN (Ery-TGN) and DNA-TG in 1009 patients undergoing maintenance therapy for acute lymphoblastic leukaemia (ALL). In discovery analyses (454 patients), the propensity for DNA-TG incorporation ((wm)DNA-TG/(wm)Ery-TGN ratio) was significantly associated with three intronic SNPs in NT5C2 (top hit: rs72846714; P - 2.09 x 10(-10), minor allele frequency 15%). In validation analyses (555 patients), this association remained significant during both early and late maintenance therapy (P - 8.4 x 10(-6) and 1.3 x 10(-3), respectively). The association was mostly driven by differences in (wm)Ery-TGN, but in regression analyses adjusted for wmEry-TGN (P < 0.0001), rs72846714-A genotype was also associated with a higher (wm)DNA-TG (P - 0.029). Targeted sequencing of NT5C2 did not identify any missense variants associated with rs72846714 or (wm)Ery-TGN/(wm)DNA-TG. rs72846714 was not associated with relapse risk, but in a separate cohort of 180 children with relapsed ALL, rs72846714-A genotype was associated with increased occurrence of relapse-specific NT5C2 gain-of-function mutations that reduce cytosol TGN levels (P = 0.03). These observations highlight the impact of both germline and acquired mutations in drug metabolism and disease trajectory.
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| 28. |
- Boulakh, L., et al.
(författare)
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Nationwide Incidence of Thyroid Eye Disease and Cumulative Incidence of Strabismus and Surgical Interventions in Denmark
- 2022
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Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 140:7, s. 667-673
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Thyroid eye disease (TED) is a serious condition that can cause proptosis and strabismus and, in rare cases, lead to blindness. Incidence data for TED and strabismus and surgical interventions after TED are sparce. OBJECTIVE To investigate the nationwide incidence of TED, strabismus, and surgical interventions associated with TED. DESIGN, SETTING, AND PARTICIPANTS A Danish nationwide registry-based cohort study between 2000, which marks the beginning of uniform coding for the decompression surgery nationwide, and 2018. The cohort consisted of a mean 4.3 million people aged 18 to 100 years with no prior TED diagnosis each year. Total observation time was 8.22 x 10(7) person-years (women, 4.18 x 10(7) person-years; men, 4.04 x 10(7) person-years). MAIN OUTCOME MEASURES The annual numeric and age-standardized incidence of hospital-treated TED and cumulative incidence of strabismus, strabismus surgery, and orbital decompression surgery in patients with TED. The incidence was stratified by sex, thyroid diagnosis, and age. RESULTS A total of 4106 incident diagnoses of TED were identified during 19 years among 3344 women (81.4%) and 762 men (18.6%). The mean numeric annual nationwide incidence rate of TED was 5,0 per 100 000 person-years overall, 8.0 per 100 000 person-years in women, and 1.9 per 100 000 person-years in men, resulting in a 4:1 ratio of women to men with TED. The age-standardized incidence was similar. The mean (SD) age at onset was 51.3 (14.5) years. At the time of TED diagnosis, 611 patients (14.9%) were euthyroid, 477 (11.6%) were hypothyroid, and 3018 (73.5%) were hyperthyroid. In patients with TED who were euthyroid, the 4-year cumulative incidence was 41% for antithyroid medication and 13% for L-thyroxine. In patients with TED, the 4-year cumulative incidence for strabismus was 10%. The 4-year cumulative incidence of surgical interventions after TED was 8% for strabismus surgery and 5% for orbital decompression. At 4 years, strabismus surgery was more common in men (13.3%; 95% CI, 10.75-15.86) than in women (7.2%; 95% CI, 6.24-8.08), and the absolute difference was 6.1% (95% CI, 3.42-8.14; P < .001). CONCLUSIONS AND RELEVANCE This study in Denmark provides nationwide empirical incidence of TED and strabismus and surgical interventions after TED that required inpatient or outpatient hospital treatment, and might be used for patient information and health care planning.
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| 29. |
- Boulakh, L., et al.
(författare)
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Topical anaesthesia in strabismus surgery for Graves' orbitopathy: a comparative study of 111 patients
- 2022
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 100:4, s. 447-453
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To evaluate the tolerability and usability of topical anaesthesia in single rectus muscle recession for strabismus caused by Graves' orbitopathy (GO). To compare the perioperative pain score and surgical outcome between GO patients and non-GO patients. Methods A retrospective comparative study of consecutive single rectus muscle recession performed under topical anaesthesia was carried out. All patients scheduled for one-stage single rectus muscle recession under topical anaesthesia were included. Numerical visual analogue pain score scale (NVAS) points, rates of motor success (horizontal deviation < 8 prism diopters (PD) and vertical deviation <= 6 PD) and sensory success (no diplopia without prisms), complications and postoperative adjustment frequencies were compared between GO and non-GO patients. Results A total of 111 patients were included. The mean perioperative pain scores were 2.3 (SD +/- 1.3) in GO and 1.6 (SD +/- 1.1) in non-GO patients (p = 0.06 adjusted for gender). The postoperative mean alignments in GO and non-GO patients were 2 versus 3 PD horizontally and 1 versus 1 PD vertically respectively. Both motor and sensory success rates were 98% in GO patients and 94% versus 93% in non-GO patients. Adjustments as a second procedure the day after surgery was performed in 10% of the GO patients and 15% of the non-GO patients. The oculocardiac reflex was not triggered in any of the GO patients. Conclusion Topical anaesthesia in single muscle recession for GO is safe, well-tolerated and gives comparable surgical outcomes to those achieved in non-GO patients.
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| 30. |
- Ding, Ming, et al.
(författare)
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Dairy consumption, systolic blood pressure, and risk of hypertension : Mendelian randomization study
- 2017
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 356
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.
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| 31. |
- Hagstrom-Toft, E, et al.
(författare)
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Evidence for a major role of skeletal muscle lipolysis in the regulation of lipid oxidation during caloric restriction in vivo
- 2001
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 50:7, s. 1604-1611
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Tidskriftsartikel (refereegranskat)abstract
- A lipolytic process in skeletal muscle has recently been demonstrated. However, the physiological importance of this process is unknown. We investigated the role of skeletal muscle lipolysis for lipid utilization during caloric restriction in eight obese women before and after 11 days of very low–calorie diet (VLCD) (2.2 MJ per day). Subjects were studied with indirect calorimetry and microdialysis of skeletal muscle and adipose tissue in order to analyze substrate utilization and glycerol (lipolysis index) in connection with a two-step euglycemic-hyperinsulinemic (12 and 80 mU/m2 · min) clamp. Local blood flow rates in the two tissues were determined with 133Xe-clearance. Circulating free fatty acids and glycerol decreased to a similar extent during insulin infusion before and during VLCD, and there was a less marked insulin-induced reduction in lipid oxidation during VLCD. Adipose tissue glycerol release was hampered by insulin infusion to the same extent (∼40%) before and during VLCD. Skeletal muscle glycerol release was not influenced by insulin before VLCD. However, during VLCD insulin caused a marked (fivefold) (P < 0.01) increase in skeletal muscle glycerol release. The effect was accompanied by a fourfold stimulation of skeletal muscle blood flow (P < 0.01). We propose that, during short-term caloric restriction, the reduced ability of insulin to inhibit lipids, despite a preserved antilipolytic effect of the hormone in adipose tissue, is caused by an augmented mobilization of fat from skeletal muscle, and that a physiological role of muscle lipolysis provides a local source of fatty acids.
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| 32. |
- Huang, Tao, et al.
(författare)
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Dairy Consumption and Body Mass Index Among Adults : Mendelian Randomization Analysis of 184802 Individuals from 25 Studies
- 2018
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 64:1, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined.METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies.RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00–0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P = 3.15 × 10−12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P = 2.11 × 10−5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27–0.92; P = 3.0 × 10−4).CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.
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| 33. |
- Landegren, Nils, et al.
(författare)
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Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis
- 2016
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Ingår i: Journal of the American Society of Nephrology: JASN. - 1533-3450 .- 1046-6673. ; 27:10, s. 3220-3228
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Tidskriftsartikel (refereegranskat)abstract
- Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.
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| 34. |
- Long, Manhai, et al.
(författare)
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Dioxin-like activities in serum across European and Inuit populations
- 2006
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Ingår i: Environmental Health. - 1476-069X. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals and humans, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study was to compare the integrated serum level of AhR mediated activity among European and Inuit populations, and evaluate whether the activity was associated to the selected POP markers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). The AhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction containing the POPs using the AhR mediated luciferase reporter Hepa1.12cR cell assay. RESULTS: The European groups showed higher median level of AhR-TEQ (TCDD toxic equivalents) compared to the Inuit's, whereas higher incidence of Inuits sample further induced AhRcomp activity. Neither AhRag nor AhR-TEQ were correlated to CB-153 or p,p'-DDE for any of the study groups. Multiple regressions showed a significant heterogeneity of association between the CB-153 and the AhRcomp across the study groups, and accordingly a negative association between AhRcomp and CB-153 was found for the Kharkiv group. CONCLUSION: No consistent correlation between AhR activities and two POP markers was found. Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors.
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| 35. |
- Mikkelsen, L. H., et al.
(författare)
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Genomic and immunohistochemical characterisation of a lacrimal gland oncocytoma and review of literature
- 2017
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 14:4, s. 4176-4182
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to report the genetic and immunohistochemical profile of a rare case of lacrimal gland oncocytoma. A 20-year-old male underwent magnetic resonance imaging (MRI) due to viral encephalitis. Notably, the MRI revealed a multicystic tumor in the left lacrimal gland. A lateral orbitotomy was performed and the tumor was completely excised. Four months following surgery, the patient was free of symptoms. Histopathologically, the tumor was composed of large, eosinophilic and polyhedral cells with small round nuclei. The tumor cells stained strongly for antimitochondrial antibody MU213-UC, cytokeratin (CK) 5/6, CK 7, CK 17, CK 8/18 and CK 19. The final diagnosis was an oncocytoma of the lacrimal gland without any signs of malignancy. Array-based comparative genomic hybridisation demonstrated a gain of one copy of chromosome 8 and loss of one copy of chromosome 22 as the sole genomic imbalances. These chromosomal alterations have not previously been identified in oncocytoma and may be specific to lacrimal gland oncocytoma. Sequencing of the mitochondrial genome demonstrated multiple alterations of the NADH-ubiquinone oxidoreductase chain 5 (ND5) gene involved in mitochondrial oxidative phosphorylation. This may support the notion of a common genetic background of oncocytic lesions in the lacrimal gland and other anatomical sites. © 2017, Spandidos Publications. All rights reserved.
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| 36. |
- Modvig, S, et al.
(författare)
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Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia
- 2019
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Ingår i: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 33:6, s. 1324-1336
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Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.
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| 37. |
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| 38. |
- Qi, Qibin, et al.
(författare)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
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Tidskriftsartikel (refereegranskat)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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| 39. |
- Quist-Paulsen, P., et al.
(författare)
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T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol
- 2020
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:2, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD >= 5% on day 29 or >= 0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.
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| 40. |
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| 41. |
- Rongve, Arvid, et al.
(författare)
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GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample. We performed a genome wide association study in Norwegian and European cohorts of 720 DLB cases and 6490 controls and included 19 top-associated single-nucleotide polymorphisms in an additional cohort of 108 DLB cases and 75545 controls from Iceland. Overall the study included 828 DLB cases and 82035 controls. Variants in the ASH1L/GBA (Chr1q22) and APOE ε4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 × 10 −8 ). One additional genetic locus previously linked to psychosis in Alzheimer’s disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value < 1 × 10 −6 . We report two susceptibility loci for DLB at genome-wide significance, providing insight into etiological factors. These findings highlight the complex relationship between the genetic architecture of DLB and other neurodegenerative disorders.
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| 42. |
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| 43. |
- Toft, A., et al.
(författare)
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Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused by CHMP2B mutation
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionIncreasing evidence implicates proteostatic dysfunction as an early event in the development of frontotemporal dementia (FTD). This study aimed to explore potential cerebrospinal fluid (CSF) biomarkers associated with the proteolytic systems in genetic FTD caused by CHMP2B mutation. MethodsCombining solid-phase extraction and parallel reaction monitoring mass spectrometry, a panel of 47 peptides derived from 20 proteins was analyzed in CSF from 31 members of the Danish CHMP2B-FTD family. ResultsCompared with family controls, mutation carriers had significantly higher levels of complement C9, lysozyme and transcobalamin II, and lower levels of ubiquitin, cathepsin B, and amyloid precursor protein. DiscussionLower CSF ubiquitin concentrations in CHMP2B mutation carriers indicate that ubiquitin levels relate to the specific disease pathology, rather than all-cause neurodegeneration. Increased lysozyme and complement proteins may indicate innate immune activation. Altered levels of amyloid precursor protein and cathepsins have previously been associated with impaired lysosomal proteolysis in FTD. HighlightsCSF markers of proteostasis were explored in CHMP2B-mediated frontotemporal dementia (FTD).31 members of the Danish CHMP2B-FTD family were included.We used solid-phase extraction and parallel reaction monitoring mass spectrometry.Six protein levels were significantly altered in CHMP2B-FTD compared with controls.Lower CSF ubiquitin levels in patients suggest association with disease mechanisms.
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| 44. |
- Toft, Gunnar, et al.
(författare)
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Semen quality in relation to xenohormone and dioxin-like serum activity among inuits and three european populations
- 2007
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 115:SUPPL1, s. 15-20
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Semen quality in humans may be influenced by exposure to endocrine-disrupting compounds. OBJECTIVES: We analyzed associations between semen characteristics and serum xenoestrogen receptor (XER), xenoandrogen receptor (XAR), and aryl hydrocarbon receptor (AhR) transactivity. XER and XAR activity were measured in serum samples cleared for endogenous steroid hormones and AhR activity in raw lipophilic serum extracts free of proteins. RESULTS: All together, 319 men from Warsaw (Poland), Greenland, Kharkiv (Ukraine), and Sweden provided semen and blood samples. No strong and consistent associations between xenobiotic activity and semen quality measures were observed in the four populations. However, when the data were combined across populations sperm concentration increased 40% per unit increase in XER activity [95% confidence interval (CI), 1-79%] in the subgroup with XER activity below the reference level. Among subjects with XER activity above the reference level an increase of 14% (95% CI, 2-28%) was found. Furthermore, an increase of 10% motile sperm per unit increase in XER activity below reference level (95% CI, 0.2-20) was found. We are unable to exclude that the associations are chance findings. CONCLUSION: Alteration of XER, XAR, or AhR transactivity within the range found in serum from the general European and Inuit population seems not to markedly deteriorate sperm cell concentration, motility, or morphology in adult men.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Anand-Ivell, Ravinder, et al.
(författare)
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Amniotic fluid INSL3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias, and phthalate load : A large case-control study
- 2018
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:APR
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Tidskriftsartikel (refereegranskat)abstract
- The period of the first to second trimester transition in human pregnancy represents a sensitive window for fetal organogenesis, particularly in regard to the development of the male reproductive system. This is a time of relative analytical inaccessibility. We have used a large national biobank of amniotic fluid samples collected at routine amniocentesis to determine the impacts of exogenous endocrine disruptor load on specific fetal biomarkers at this critical time. While adrenal and testicular steroids are highly correlated, they are also mostly positively influenced by increasing phthalate load, represented by the metabolites 7cx-MMeHP and 5cx-MEPP, by perfluorooctane sulfonate (PFOS) exposure, and by smoking, suggesting an adrenal stress response. In contrast, the testis specific biomarkers insulin-like peptide 3 (INSL3) and androstenedione are negatively impacted by the phthalate endocrine disruptors. Using a case-control design, we show that cryptorchidism and hypospadias are both significantly associated with increased amniotic concentration of INSL3 during gestational weeks 13-16, and some, though not all steroid biomarkers. Cases are also linked to a specifically increased variance in the Leydig cell biomarker INSL3 compared to controls, an effect exacerbated by maternal smoking. No influence of phthalate metabolites or PFOS was evident on the distribution of cases and controls. Considering that several animal and human studies have shown a negative impact of phthalate load on fetal and cord blood INSL3, respectively, the present results suggest that such endocrine disruptors may rather be altering the relative dynamics of testicular development and consequent hormone production, leading to a desynchronization of tissue organization during fetal development. Being born small for gestational age appears not to impact on the testicular biomarker INSL3 in second trimester amniotic fluid.
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| 49. |
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| 50. |
- Babkevich, P., et al.
(författare)
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Dimensional Reduction in Quantum Dipolar Antiferromagnets
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 116:19
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Tidskriftsartikel (refereegranskat)abstract
- We report ac susceptibility, specific heat, and neutron scattering measurements on a dipolar-coupled antiferromagnet LiYbF4. For the thermal transition, the order-parameter critical exponent is found to be 0.20(1) and the specific-heat critical exponent -0.25(1). The exponents agree with the 2D XY/h(4) universality class despite the lack of apparent two-dimensionality in the structure. The order-parameter exponent for the quantum phase transitions is found to be 0.35(1) corresponding to (2 + 1)D. These results are in line with those found for LiErF4 which has the same crystal structure, but largely different T-N, crystal field environment and hyperfine interactions. Our results therefore experimentally establish that the dimensional reduction is universal to quantum dipolar antiferromagnets on a distorted diamond lattice.
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