| 1. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
- Ferreira, Mjv, et al.
(författare)
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Poster Session 3 : Tuesday 5 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Aderne, Rian E., et al.
(författare)
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On the energy gap determination of organic optoelectronic materials : the case of porphyrin derivatives
- 2022
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Ingår i: Materials Advances. - : Royal Society of Chemistry. - 2633-5409. ; :3, s. 1791-1803
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Tidskriftsartikel (refereegranskat)abstract
- The correct determination of the ionization potential (IP) and electron affinity (EA) as well as the energy gap is essential to properly characterize a series of key phenomena related to the applications of organic semiconductors. For example, energy offsets play an essential role in charge separation in organic photovoltaics. Yet there has been a lot of confusion involving the real physical meaning behind those quantities. Experimentally the energy gap can be measured by direct techniques such as UV-Vis absorption, or indirect techniques such as cyclic voltammetry (CV). Another spectroscopic method is the Reflection Electron Energy Loss Spectroscopy (REELS). Regarding data correlation, there is little consensus on how the REELS' energy gap can be interpreted in light of the energies obtained from other methodologies such as CV, UV-Vis, or photoemission. In addition, even data acquired using those traditional techniques has been misinterpreted or applied to derive conclusions beyond the limits imposed by the physics of the measurement. A similar situation also happens when different theoretical approaches are used to assess the energy gap or employed to explain outcomes from experiments. By using a set of porphyrin derivatives as model molecules, we discuss some key aspects of those important issues. The peculiar properties of these porphyrins demonstrate that even straightforward measurements or calculations performed in a group of very similar molecules need a careful interpretation of the outcomes. Differences up to 660 meV (similar to 190 meV) are found comparing REELS (electrochemical) measurements with UV-Vis energy gaps, for instance. From the theoretical point of view, a reasonable agreement with electrochemical measurements of the IP, EA, and the gap of the porphyrins is only obtained when the calculations involve the full thermodynamics of the redox processes. The purpose of this work is to shed light on the differences and similarities of those aforementioned characterization methods and provide some insight that might help one to develop a critical analysis of the different experimental and theoretical methodologies.
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| 14. |
- Thomas, R. D., et al.
(författare)
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Hot Water from Cold. The Dissociative Recombination of Water Cluster Ions
- 2010
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 114:14, s. 4843-4846
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Tidskriftsartikel (refereegranskat)abstract
- Dissociative recombination of the Zundel cation D(5)O(2)(+) almost exclusively produces D + 2 D(2)O with a maximum kinetic energy release of 5.1 eV. An imaging technique is used to investigate the distribution of the available reaction energy among these products. Analysis shows that as much as 4 eV can be stored internally by the molecular fragments, with a preference for producing highly excited molecular fragments, and that the deuteron shows a nonrandom distribution of kinetic energies. A possible mechanism and the implications for these observations are addressed.
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| 15. |
- Al-Khalili, A, et al.
(författare)
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Dissociative recombination cross section and branching ratios of protonated dimethyl disulfide and N-methylacetamide
- 2004
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 121:12, s. 5700-5708
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Tidskriftsartikel (refereegranskat)abstract
- Dimethyl disulfide (DMDS) and N-methylacetamide are two first choice model systems that represent the disulfide bridge bonding and the peptide bonding in proteins. These molecules are therefore suitable for investigation of the mechanisms involved when proteins fragment under electron capture dissociation (ECD). The dissociative recombination cross sections for both protonated DMDS and protonated N-methylacetamide were determined at electron energies ranging from 0.001 to 0.3 eV. Also, the branching ratios at 0 eV center-of-mass collision energy were determined. The present results give support for the indirect mechanism of ECD, where free hydrogen atoms produced in the initial fragmentation step induce further decomposition. We suggest that both indirect and direct dissociations play a role in ECD.
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| 16. |
- Andersson, Patrik U, 1970, et al.
(författare)
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Formation of Highly Rovibrationally Excited Ammonia from Dissociative Recombination of NH4
- 2010
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Ingår i: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 1:17, s. 2519-2523
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Tidskriftsartikel (refereegranskat)abstract
- The internal energy distribution of ammonia formed in the dissociative recombination (DR) of NH4+ with electrons has been studied by an imaging technique at the ion storage ring CRYRING. The DR process resulted in the formation of NH3 + H (0.90 ± 0.01), with minor contributions from channels producing NH2 + H2 (0.05 ± 0.01) and NH2 + 2H (0.04 ± 0.02). The formed NH3 molecules were highly internally excited, with a mean rovibrational energy of 3.3 ± 0.4 eV, which corresponds to 70% of the energy released in the neutralization process. The internal energy distribution was semiquantitatively reproduced by ab initio direct dynamics simulations, and the calculations suggested that the NH3 molecules are highly vibrationally excited while rotational excitation is limited. The high internal excitation and the translational energy of NH3 and H will influence their subsequent reactivity, an aspect that should be taken into account when developing detailed models of the interstellar medium and ammonia-containing plasmas.
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| 19. |
- Bohm, Christian, et al.
(författare)
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A MHz-repetition-rate hard X-ray free-electron laser driven by a superconducting linear accelerator
- 2020
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Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 14:6, s. 391-397
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Tidskriftsartikel (refereegranskat)abstract
- The European XFEL is a hard X-ray free-electron laser (FEL) based on a high-electron-energy superconducting linear accelerator. The superconducting technology allows for the acceleration of many electron bunches within one radio-frequency pulse of the accelerating voltage and, in turn, for the generation of a large number of hard X-ray pulses. We report on the performance of the European XFEL accelerator with up to 5,000 electron bunches per second and demonstrating a full energy of 17.5 GeV. Feedback mechanisms enable stabilization of the electron beam delivery at the FEL undulator in space and time. The measured FEL gain curve at 9.3 keV is in good agreement with predictions for saturated FEL radiation. Hard X-ray lasing was achieved between 7 keV and 14 keV with pulse energies of up to 2.0 mJ. Using the high repetition rate, an FEL beam with 6 W average power was created. The first operation of the European X-ray free-electron laser facility accelerator based on superconducting technology is reported. The maximum electron energy is 17.5 GeV. A laser average power of 6 W is achieved at a photon energy of 9.3 keV.
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| 22. |
- Clausen, Frederik Banch, et al.
(författare)
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Recommendation for validation and quality assurance of non-invasive prenatal testing for foetal blood groups and implications for IVD risk classification according to EU regulations
- 2022
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 117:2, s. 157-165
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Forskningsöversikt (refereegranskat)abstract
- Background and Objectives: Non-invasive assays for predicting foetal blood group status in pregnancy serve as valuable clinical tools in the management of pregnancies at risk of detrimental consequences due to blood group antigen incompatibility. To secure clinical applicability, assays for non-invasive prenatal testing of foetal blood groups need to follow strict rules for validation and quality assurance. Here, we present a multi-national position paper with specific recommendations for validation and quality assurance for such assays and discuss their risk classification according to EU regulations. Materials and Methods: We reviewed the literature covering validation for in-vitro diagnostic (IVD) assays in general and for non-invasive foetal RHD genotyping in particular. Recommendations were based on the result of discussions between co-authors. Results: In relation to Annex VIII of the In-Vitro-Diagnostic Medical Device Regulation 2017/746 of the European Parliament and the Council, assays for non-invasive prenatal testing of foetal blood groups are risk class D devices. In our opinion, screening for targeted anti-D prophylaxis for non-immunized RhD negative women should be placed under risk class C. To ensure high quality of non-invasive foetal blood group assays within and beyond the European Union, we present specific recommendations for validation and quality assurance in terms of analytical detection limit, range and linearity, precision, robustness, pre-analytics and use of controls in routine testing. With respect to immunized women, different requirements for validation and IVD risk classification are discussed. Conclusion: These recommendations should be followed to ensure appropriate assay performance and applicability for clinical use of both commercial and in-house assays.
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| 23. |
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| 24. |
- Ehlerding, A., et al.
(författare)
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The dissociative recombination of fluorocarbon ions III : CF2+ and CF3
- 2006
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Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 39:4, s. 805-812
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Tidskriftsartikel (refereegranskat)abstract
- Cross sections and branching ratios are presented for the dissociative recombination of the CF2+ and C-3(+) ions with electrons. It is found that the channel producing CF + F is dominant for the reaction with CF2+ and the production of CF2 + F is dominant for the reaction with CF3+. The cross sections for these two ions are very similar.
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| 25. |
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| 26. |
- Enochsson, L, et al.
(författare)
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Laparoscopic vs open appendectomy in overweight patients
- 2001
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 15:4, s. 387-392
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Tidskriftsartikel (refereegranskat)abstract
- Background: Laparoscopic appendectomy (LA) has been associated with a faster recovery and less postoperative pain than the open technique. However, few data are available on the clinical outcome of LA in overweight patients. Methods: A group of 106 patients with a body mass index (BMI) > 26.4, representing the upper quintile of 500 prospectively randomized patients, were included in the study. They were randomized to undergo either laparoscopic or open appendectomy (OA). Operating and anesthesia times, postoperative pain, complications, hospital stay, functional index (1 week postoperatively), sick leave, and time to full recovery were documented. Results: In OA, the operating time for overweight patients was significantly longer than that for patients in the normal weight range (40 vs 35 min, p < 0.05). In LA, there was no difference in operating time between the normal and overweight patients. Overweight patients who underwent LA had longer operating and anesthesia times than their OA counterparts (55 vs 40 min, p < 0.001, and 125 vs 100 min, p < 0.001, respectively). Postoperative pain was significantly greater in overweight patients who underwent OA than in those treated with the laparoscopic technique. Postoperative pain was also significantly greater in overweight patients subjected to OA than in patients of normal weight after 4 weeks, the clinical significance may, however, be of less importance since the values are low (0.26 vs 0.09, p < 0.05). There were no significant differences between the two operating techniques in terms of complications. Hospital stay was longer for overweight patients than for normal-weight patients undergoing OA (3.0 vs 2.0, p < 0.01). The functional index did not differ between any group of patients. Sick leave was longer for overweight patients who underwent OA than for normal-weight patients treated with the same technique (17 vs 13 days, p < 0.01). In the laparoscopic group, however, there were no differences between the overweight and normal-weight patients. Time to full recovery was greater in overweight patients subjected to OA than in the overweight patients in the LA group (22 vs 15 days, p < 0.001). Conclusion: In this study, overweight patients who were submitted to LA had less postoperative pain and a faster postoperative recovery than overweight patients who had OA. LA also abolished some of the negative effects that overweight had on operating time, hospital stay, and sick leave with the open technique. However, anesthesia and operating times were significantly longer in LA for both overweight patients and those with a normal BMI.
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| 27. |
- Enochsson, L, et al.
(författare)
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The Fenyo-Lindberg scoring system for appendicitis increases positive predictive value in fertile women - A prospective study in 455 patients randomized to either laparoscopic or open appendectomy
- 2004
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 18:10, s. 1509-1513
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Tidskriftsartikel (refereegranskat)abstract
- Background: Suspected appendicitis is one of the most common indications for acute laparotomy or laparoscopy. The negative laparotomy and laparoscopy rates are high, often in the range of 15-30%, and especially high in some groups of patients such as women of child-bearing age and young patients. Different scoring systems have been introduced in order to improve diagnostic accuracy. The aim of the present study was to analyse the outcome of the Fenyo-Lindberg scoring system in a prospectively randomized multicenter trial and to analyze how well the score performed in stratified subgroups. Methods: The variables of the Fenyo-Lindberg scoring system were collected in a prospective study comparing laparoscopic and open surgery in suspected appendicitis and with four participating centers. None of the hospitals had used the scoring system previously. Since surgeons were unfamiliar with the score, they could not use it as a diagnostic aid. When comparing the score with the clinical outcome, retrospectively, the investigators interpreting the score were blinded regarding the surgical outcome. Results: Positive predictive value (PPV) of the Fenyo-Lindberg score was higher than that of the surgeon's clinical diagnosis in the patient cohort [0.90 vs 0.79 (p < 0.001)]. The score demonstrated an improvement of PPV in women [0.83 vs 0.70 (p < 0.01)]. PPV was increased in women between 15 and 50 years of age. In women aged 15-30 years and 31-50 years PPV increased from 0.69 to 0.82 and 0.68 to 0.86, respectively (p < 0.01). Both the sensitivity (0.77) and the specificity (0.69) of the score were, however, low. Conclusion: The Fenyo-Lindberg score is an inexpensive clinical tool that may improve the diagnostic accuracy for acute appendicitis in women of childbearing age, which is a group of patients where the diagnostic accuracy usually is low and where the arsenal of diagnostic tools such Lis Computed tomography is limited because of radiation. The low specificity of the score in women of childbearing age must, however, be kept in mind.
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| 28. |
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| 30. |
- Gillberg, Christopher, 1950, et al.
(författare)
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Childhood psychosis and monoamine metabolites in spinal fluid.
- 1983
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Ingår i: Journal of Autism and Developmental Disorders. - 0162-3257. ; 13:4, s. 383-396
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Tidskriftsartikel (refereegranskat)abstract
- Determination of monoamine metabolites was accomplished in the spinal fluid of 22 psychotic children and in 22 sex- and almost-age-matched "normal" controls. Also, specimens from groups of mentally retarded children and children with progressive encephalopathy or meningitis were used for comparison. The psychotic children showed raised levels of homovanillic acid. Thirteen children diagnosed as autistic by Rutter's criteria showed isolated increase of this metabolite. In the group of 9 children with other psychoses, both the level of homovanillic acid and that of 5-hydroxy-indoleacetic acid was raised. The comparison with the group of "simply" mentally retarded children and results within the psychotic group revealed that the increased concentration of monoamines was not attributable to mental retardation per se.
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| 31. |
- Gustafson, Daniel, et al.
(författare)
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Större vattensalamander i tio Natura 2000-områden i Örebro län: test och utvärdering av övervakningsmetodik 2002.
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sommaren 2002 inventerades tio Natura 2000-områden i Örebro län efter större vattensalamander (Triturus cristatus). Syftet med inventeringen var dels att kartlägga förekomst av större vattensalamander i länets Natura 2000-områden och dels att testa och utvärdera metoder för övervakning av arten. Under maj och juni inventerades vuxna individer och i augusti inventerades larver. Större vattensalamander hittades i 9 av de inventerade områdena och i 27 av 48 inventerade småvatten. I sex områden och nio vatten hittades larver av större vattensalamander. Detta visar att trots noggrant urval av inventerade områden och vatten är den större vattensalamandern relativt sällsynt, och metapopulationer svårfunna. Inventeringsmetoderna som testades var visuell observation med lampa och flaskfälleinventering. Av dessa visade sig den visuella metoden ge störst utbyte både vad gäller konstaterande av närvaro/frånvaro och antal funna individer. Flaskfällemetoden är mest användbar vid dåliga siktförhållanden i vattnet. Vid inventering efter larver användes håvningsmetodik.
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| 34. |
- Hellberg, C., et al.
(författare)
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Evidence and evidence gaps in assessments and interventions in areas related to social work research and practice - an overview of four evidence maps
- 2023
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Ingår i: European Journal of Social Work. - : Informa UK Limited. - 1369-1457 .- 1468-2664. ; 26:5
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Tidskriftsartikel (refereegranskat)abstract
- This overview of four evidence maps is based on systematic reviews of assessment and interventions in social work practice. The aim was to investigate the evidence and evidence gaps within four important areas for social work research and practice. Descriptive data on search strategies and domains were collected from four evidence maps, on Social Assistance, Substance Dependence, Care for older adults respectively for persons with disabilities. The scientific quality and scientific evidence were assessed. Key findings were summarised by analyzing and discussing common and specific elements in the evidence maps. The overview was undertaken in close collaboration between researchers with expertise in the field and a government agency. The overview identified both evidence and evidence gaps with respect to effects and experiences of interventions and assessment methods in four evidence maps. Evidence maps provide a comprehensive picture of the state of social services research and can thereby be of use to both researchers and practitioners, and in the production of evidence based social work.
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| 35. |
- Hellberg, C, et al.
(författare)
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Important research outcomes for treatment studies of perinatal depression: systematic overview and development of a core outcome set
- 2021
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Ingår i: British Journal of Obstetrics and Gynecology. - : John Wiley & Sons. - 1470-0328 .- 1471-0528. ; 128:13, s. 2141-2149
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Tidskriftsartikel (refereegranskat)abstract
- Objective To develop a Core Outcome Set (COS) for treatment of perinatal depression.Design Systematic overview of outcomes reported in the literature and consensus development study.SettingInternational.Population Two hundred and twenty-two participants, mainly patients, healthcare professionals and researchers, representing 13 countries.Methods A systematic overview of outcomes reported in recently published research, a two-round Delphi survey and a consensus meeting at which the final COS was decided using modified nominal group technique.Main results In the literature search, 1772 abstracts were identified and evaluated, and 165 studies were finally included in the review. In all, 106 outcomes were identified and included in the Delphi survey. In all, 222 participants registered for the first round of the Delphi survey and 151 (68%) responded. In the second round, 123 (55%) participants responded. Thirteen participants attended the consensus meeting, where the following nine outcomes were agreed upon for inclusion in the final COS: self-assessed symptoms of depression, diagnosis of depression by a clinician, parent to infant bonding, self-assessed symptoms of anxiety, quality of life, satisfaction with intervention, suicidal thoughts, attempted or committed suicide, thoughts of harming the baby, and adverse events.Conclusions The relevant stakeholders prioritised outcomes and reached consensus on a COS comprising nine outcomes. We expect that this COS will contribute to the consistency and uniformity of outcome selection and reporting in future clinical trials involving treatment of perinatal depression.
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| 36. |
- Hellberg, Eva, et al.
(författare)
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Större vattensalamander i Örebro län: inventering 2003 : sammanställning av kända lokaler 1989-2003.
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I denna rapport presenteras resultaten från den inventering av större vattensalamander (Triturus cristatus) som genomfördes i Örebro län sommaren 2003. Syftet med inventeringen var att få ökad kännedom om den hotade större vattensalamanderns utbredning och status i Örebro län. Inventeringen pågick från början av april till slutet av juni. Områdena i inventeringen valdes ut efter specifika kriterier. Målet var att ett område per kartblad av fastighetskartan i länet skulle inventeras. Minst tre och max sex vatten inventerades i varje område. Metoderna som användes var visuell observation med lampa nattetid, alternativt flaskfällor. Totalt inventerades 135 områden och 530 vatten. Fynd av större vattensalamander gjordes i 52 av områdena och 86 av vattnen. I endast 16 av vattnen (ca 19 % av fyndvattnen) observerades fler än 10 individer under inventeringen. I 24 av de 52 fyndområdena hittade vi större vattensalamander i fler än ett av de inventerade vattnen. Resultaten tyder således på att det finns relativt få stora och livskraftiga populationer/metapopulationer av större vattensalamander i länet. Dessa bör skyddas inom en snar framtid och ges skötselåtgärder som garanterar deras fortlevnad. I rapporten sammanfattas också de kunskaper om större vattensalamander som vi har idag i länet, i kartor och tabeller. Korta rekommendationer för bevarandeåtgärder och övervakning av större vattensalamander ges. Tillsammans med tidigare kunskaper ger resultatet från inventeringen 2003 en bra grund för framtida miljöövervakning av och bevarandearbete för större vattensalamander i Örebro län. Vi har också lärt oss mer om vilka områden som har hög sannolikhet att härbärgera större vattensalamander. Vi har kännedom om ett flertal områden där potentiella metapopulationsstrukturer finns. Dessa områden är väl värda att satsa på i framtida bevarandearbete.
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| 37. |
- Hellberg, F, et al.
(författare)
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Investigating the breakup dynamics of dihydrogen sulfide ions recombining with electrons
- 2005
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 122:22, s. 224314-
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents results concerning measurements of the dissociative recombination (DR) of dihydrogen sulfide ions. In combination with the ion storage ring CRYRING an imaging technique was used to investigate the breakup dynamics of the three-body channel in the DR of (SD2+)-S-32. The two energetically available product channels S(P-3)+2D(S-2) and S(D-1)+2D(S-2) were both populated, with a branching fraction of the ground-state channel of 0.6(0.1). Information about the angle between the two deuterium atoms upon dissociation was obtained together with information about how the available kinetic energy was distributed between the two light fragments. The recombination cross sections as functions of energy in the interval of 1 meV to 0.3 eV in the center-of-mass frame are presented for (SH2+)-S-34. The thermal rate coefficient for the DR of (SH2+)-S-34 was determined to be (4.8 +/- 1.0)x10(-7)(T/300)(-0.72 +/- 0.1) cm(3) s(-1) over this interval.
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| 50. |
- McGowan, Eunike C., et al.
(författare)
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A Bioinformatically Initiated Approach to Evaluate GATA1 Regulatory Regions in Samples with Weak D, Del, or D- Phenotypes Despite Normal RHD Exons
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Ingår i: Transfusion Medicine and Hemotherapy. - 1660-3796.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: With over 360 blood group antigens in systems recognized, there are antigens, such as RhD, which demonstrate a quantitative reduction in antigen expression due to nucleotide variants in the non-coding region of the gene that result in aberrant splicing or a regulatory mechanism. This study aimed to evaluate bioinformatically predicted GATA1-binding regulatory motifs in the RHD gene for samples presenting with weak or apparently negative RhD antigen expression but showing normal RHD exons. Methods: Publicly available open chromatin region data were overlayed with GATA1 motif candidates in RHD. Genomic DNA from weak D, Del or D- samples with normal RHD exons (n = 13) was used to confirm RHD zygosity by quantitative PCR. Then, RHD promoter, intron 1, and intron 2 regions were amplified for Sanger sequencing to detect potential disruptions in the GATA1 motif candidates. Electrophoretic mobility shift assay (EMSA) was performed to assess GATA1-binding. Luciferase assays were used to assess transcriptional activity. Results: Bioinformatic analysis identified five of six GATA1 motif candidates in the promoter, intron 1 and intron 2 for investigation in the samples. Luciferase assays showed an enhancement in transcription for GATA1 motifs in intron 1 and for intron 2 only when the R2 haplotype variant (rs675072G>A) was present. GATA1 motifs were intact in 12 of 13 samples. For one sample with a Del phenotype, a novel RHD c.1-110A>C variant disrupted the GATA1 motif in the promoter which was supported by a lack of a GATA1 supershift in the EMSA and 73% transcriptional activity in the luciferase assay. Two samples were D+/ D- chimeras. Conclusion: The bioinformatic predictions enabled the identification of a novel DEL allele, RHD c.1-110A>C, which disrupted the GATA1 motif in the proximal promoter. Although the majority of the samples investigated here remain unexplained, we provide GATA1 targets which may benefit future RHD regulatory investigations.
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