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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Begley, Cecily, 1954, et al.
(författare)
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A qualitative exploration of techniques used by expert midwives to preserve the perineum intact
- 2019
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Ingår i: Women and Birth. - : Elsevier BV. - 1871-5192. ; 32:1, s. 87-97
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Tidskriftsartikel (refereegranskat)abstract
- Background: The perineum stretches during birth to allow passage of the baby, but 85% of women sustain some degree of perineal trauma during childbirth, which is painful post-partum. Episiotomy rates vary significantly, with some countries having rates of >60%. Recent Irish and New Zealand studies showed lower severe perineal trauma and episiotomy rates than other countries. Aim: To explore expert Irish and New Zealand midwives' views of the skills that they employ in preserving the perineum intact during spontaneous vaginal birth. Methods: Following ethical approval a qualitative, descriptive study was undertaken. Semi-structured, recorded, interviews were transcribed and analysed using the constant comparative method. Expert midwives employed in New Zealand and one setting in Ireland, were invited to join the study. "Expert" was defined as achieving, in the preceding 3.5 years, an episiotomy rate for nulliparous women of <11.8%, a `no suture' rate of 40% or greater, and a severe perineal tear rate of < 3.2%. Twenty-one midwives consented to join the study. Results: Fourcore themes emerged: 'Calm, controlled birth', 'Position and techniques in early second stage', 'Hands on or off?' and 'Slow, blow and breathe the baby out.' Using the techniques described enabled these midwives to achieve rates, in nulliparous women, of 3.91% for episiotomy, 59.24% for 'no sutures', and 1.08% for serious lacerations. Conclusions: This study provides further understanding of the techniques used by expert midwives at birth. These findings, combined with existing quantitative research, increases the evidence on how to preserve the perineum intact during spontaneous birth. (c) 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.
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| 5. |
- Begley, V, et al.
(författare)
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The mRNA degradation factor Xrn1 regulates transcription elongation in parallel to Ccr4
- 2019
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 47:18, s. 9524-9541
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Tidskriftsartikel (refereegranskat)abstract
- Co-transcriptional imprinting of mRNA by Rpb4 and Rpb7 subunits of RNA polymerase II (RNAPII) and by the Ccr4–Not complex conditions its post-transcriptional fate. In turn, mRNA degradation factors like Xrn1 are able to influence RNAPII-dependent transcription, making a feedback loop that contributes to mRNA homeostasis. In this work, we have used repressible yeast GAL genes to perform accurate measurements of transcription and mRNA degradation in a set of mutants. This genetic analysis uncovered a link from mRNA decay to transcription elongation. We combined this experimental approach with computational multi-agent modelling and tested different possibilities of Xrn1 and Ccr4 action in gene transcription. This double strategy brought us to conclude that both Xrn1–decaysome and Ccr4–Not regulate RNAPII elongation, and that they do it in parallel. We validated this conclusion measuring TFIIS genome-wide recruitment to elongating RNAPII. We found that xrn1Δ and ccr4Δ exhibited very different patterns of TFIIS versus RNAPII occupancy, which confirmed their distinct role in controlling transcription elongation. We also found that the relative influence of Xrn1 and Ccr4 is different in the genes encoding ribosomal proteins as compared to the rest of the genome.
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| 6. |
- Dencker, Anna, 1956, et al.
(författare)
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Midwife-led maternity care in Ireland - a retrospective cohort study
- 2017
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 17:101
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Tidskriftsartikel (refereegranskat)abstract
- Background: Midwife-led maternity care is shown to be safe for women with low-risk during pregnancy. In Ireland, two midwife-led units (MLUs) were introduced in 2004 when a randomised controlled trial (the MidU study) was performed to compare MLU care with consultant-led care (CLU). Following study completion the two MLUs have remained as a maternity care option in Ireland. The aim of this study was to evaluate maternal and neonatal outcomes and transfer rates during six years in the larger of the MLU sites. Methods: MLU data for the six years 2008-2013 were retrospectively analysed, following ethical approval. Rates of transfer, reasons for transfer, mode of birth, and maternal and fetal outcomes were assessed. Linear-by-Linear Association trend analysis was used for categorical data to evaluate trends over the years and one-way ANOVA was used when comparing continuous variables. Results: During the study period, 3,884 women were registered at the MLU. The antenatal transfer rate was 37.4% and 2,410 women came to labour in the MLU. Throughout labour and birth, 567 women (14.6%) transferred to the CLU, of which 23 were transferred after birth due to need for suturing or postpartum hemorrhage. The most common reasons for intrapartum transfer were meconium stained liquor/abnormal fetal heart rate (30.3%), delayed labour progress in first or second stage (24.9%) and woman's wish for epidural analgesia (15.1%). Of the 1,903 babies born in the MLU, 1,878 (98.7%) were spontaneous vaginal births and 25 (1.3%) were instrumental (ventouse/forceps). Only 25 babies (1.3%) were admitted to neonatal intensive care unit. All spontaneous vaginal births from the MLU registered population, occurring in the study period in both the MLU and CLU settings (n = 2,785), were compared. In the MLU more often 1-2 midwives (90.9% vs 69.7%) cared for the women during birth, more women had three vaginal examinations or fewer (93.6% vs 79.9%) and gave birth in an upright position (standing, squatting or kneeling) (52.0% vs 9.4%), fewer women had an amniotomy (5.9% vs 25.9%) or episiotomy (3.4% vs 9.7%) and more women had a physiological management of third stage of labour (50.9% vs 4.6%). Conclusions: Midwife-led care is a safe option that could be offered to a large proportion of healthy pregnant women. With strict transfer criteria there are very few complications during labour and birth. Maternity units without the option of MLU care should consider its introduction.
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| 7. |
- Healy, P., et al.
(författare)
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Process evaluation for OptiBIRTH, a randomised controlled trial of a complex intervention designed to increase rates of vaginal birth after caesarean section
- 2018
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Complex interventions encompassing several interconnecting and interacting components can be challenging to evaluate. Examining the underlying trial processes while an intervention is being tested can assist in explaining why an intervention was effective (or not). This paper describes a process evaluation of a pan-European cluster randomised controlled trial, OptiBIRTH (undertaken in Ireland, Italy and Germany), that successfully used both quantitative and qualitative methods to enhance understanding of the underlying trial mechanisms and their effect on the trial outcome. Methods: We carried out a mixed methods process evaluation. Quantitative and qualitative data were collected from observation of the implementation of the intervention in practice to determine whether it was delivered according to the original protocol. Data were examined to assess the delivery of the various components of the intervention and the receipt of the intervention by key stakeholders (pregnant women, midwives, obstetricians). Using ethnography, an exploration of perceived experiences from a range of recipients was conducted to understand the perspective of both those delivering and those receiving the intervention. Results: Engagement by stakeholders with the different components of the intervention varied from minimal intensity of women's engagement with antenatal classes, to moderate intensity of engagement with online resources, to high intensity of clinicians' exposure to the education sessions provided. The ethnography determined that, although the overall culture in the intervention site did not change, smaller, more individual cultural changes were observed. The fidelity of the delivery of the intervention scored average quality marks of 80% and above on repeat assessments. Conclusion: Nesting a process evaluation within the trial enabled the observation of the mode of action of the intervention in its practice context and ensured that the intervention was delivered with a good level of consistency. Implementation problems were identified as they arose and were addressed accordingly. When dealing with a complex intervention, collecting and analysing both quantitative and qualitative data, as we did, can greatly enhance the process evaluation.
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| 8. |
- Nilsson, Christina, 1959, et al.
(författare)
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Women-centred interventions to increase vaginal birth after caesarean section (VBAC): A systematic review
- 2015
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Ingår i: Midwifery. - : Elsevier BV. - 0266-6138 .- 1532-3099. ; 31:7, s. 657-663
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Tidskriftsartikel (refereegranskat)abstract
- Objective: to evaluate the effectiveness of women centred interventions during pregnancy and birth to increase rates of vaginal birth after caesarean. Design: we searched bibliographic databases for randomised trials or cluster randomised trials on women centred interventions during pregnancy and birth designed to increase VBAC rates in women with at least one previous caesarean section. Comparator groups included standard or usual care or an alternative treatment aimed at increasing VBAC rates. The methodological quality of included studies was assessed independently by two authors using the Effective Public Health Practice Project quality assessment tool. Outcome data were extracted independently from each included study by two review authors. Findings: in total, 821 citations were identified and screened by title and abstract; 806 were excluded and full text of 15 assessed. Of these, 12 were excluded leaving three papers included in the review. Two studies evaluated the effectiveness of decision aids for mode of birth and one evaluated the effectiveness of an antenatal education programme. The findings demonstrate that neither the use of decision aids nor information/education of women have a significant effect on VBAC rates. Nevertheless, decision-aids significantly decrease women's decisional conflict about mode of birth, and information programmes significantly increase their knowledge about the risks and benefits of possible modes of birth. Key conclusions: few studies evaluated women-centred interventions designed to improve VBAC rates, and all interventions were applied in pregnancy only, none during the birth. There is an urgent need to develop and evaluate the effectiveness of all types of women-centred interventions during pregnancy and birth, designed to improve VBAC rates. Implications for practice: decision-aids and information programmes during pregnancy should be provided for women as, even though they do not affect the rate of VBAC, they decrease women's decisional conflict and increase their knowledge about possible modes of birth. (C) 2015 Elsevier Ltd. All rights reserved.
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| 9. |
- O'Malley, D., et al.
(författare)
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Prevalence of and risk factors associated with sexual health issues in primiparous women at 6 and 12 months postpartum; a longitudinal prospective cohort study (the MAMMI study)
- 2018
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 18:196
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many women are not prepared for changes to their sexual health after childbirth. The aim of this paper is to report on the prevalence of and the potential risk factors (pre-pregnancy dyspareunia, mode of birth, perineal trauma and breastfeeding) for sexual health issues (dyspareunia, lack of vaginal lubrication and a loss of interest in sexual activity) at 6 and 12 months postpartum. Methods: A longitudinal cohort study of 832 first-time mothers who were recruited in early pregnancy and returned postnatal surveys at 3, 6, 9 and 12 months postpartum were assessed for sexual health issues and associated risk factors. Results: Nearly half of the women (46.3%) reported a lack of interest in sexual activity, 43% experienced a lack of vaginal lubrication and 37.5% of included women had dyspareunia 6 months after birth. On univariate analysis, vacuum-assisted birth, 2nd degree perineal tears, 3rd degree perineal tears and episiotomy were all associated with dyspareunia 6 months postpartum, but, of these only 3rd degree tears, in association with breastfeeding and pre-existing dyspareunia, remained significant on multivariable analysis. Breastfeeding, in combination, with other significant factors, was associated with dyspareunia, a lack of vaginal lubrication and a loss of interest in sexual activity 6 months postpartum, and, dissatisfaction with body image emerged as a significant factor associated with lack of interest in sexual activity at 12 months postpartum. Pre-pregnancy dyspareunia and breastfeeding emerged as common factors associated with all three outcomes of dyspareunia, a lack of vaginal lubrication and a loss of interest in sexual activity at 6 months postpartum. Conclusion: Breastfeeding and pre-existing dyspareunia are associated with sexual health issues at 6 months postpartum. Pre-existing dyspareunia is associated with a lack of vaginal lubrication at 12 months postpartum and breastfeeding is associated with dissatisfaction with body image. Preparing women and their partners during the antenatal period and advising on simple measures, such as use of lubrication to avoid or minimise sexual health issues, could potentially remove stress, anxiety and fears regarding intimacy after birth. Introducing the topic of pre-existing sexual health issues antenatally may facilitate appropriate support, treatment or counselling for women.
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| 10. |
- Sjöberg, Karin, et al.
(författare)
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Multi-decadal surface ozone trends at globally distributed remote locations.
- 2020
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Ingår i: Elementa. - : University of California Press. - 2325-1026. ; 8:23
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Tidskriftsartikel (refereegranskat)abstract
- Extracting globally representative trend information from lower tropospheric ozone observations is extremely difficult due to the highly variable distribution and interannual variability of ozone, and the ongoing shift of ozone precursor emissions from high latitudes to low latitudes. Here we report surface ozone trends at 27 globally distributed remote locations (20 in the Northern Hemisphere, 7 in the Southern Hemisphere), focusing on continuous time series that extend from the present back to at least 1995. While these sites are only representative of less than 25% of the global surface area, this analysis provides a range of regional long-term ozone trends for the evaluation of global chemistry-climate models. Trends are based on monthly mean ozone anomalies, and all sites have at least 20 years of data, which improves the likelihood that a robust trend value is due to changes in ozone precursor emissions and/or forced climate change rather than naturally occurring climate variability. Since 1995, the Northern Hemisphere sites are nearly evenly split between positive and negative ozone trends, while 5 of 7 Southern Hemisphere sites have positive trends. Positive trends are in the range of 0.5–2 ppbv decade–1, with ozone increasing at Mauna Loa by roughly 50% since the late 1950s. Two high elevation Alpine sites, discussed by previous assessments, exhibit decreasing ozone trends in contrast to the positive trend observed by IAGOS commercial aircraft in the European lower free-troposphere. The Alpine sites frequently sample polluted European boundary layer air, especially in summer, and can only be representative of lower free tropospheric ozone if the data are carefully filtered to avoid boundary layer air. The highly variable ozone trends at these 27 surface sites are not necessarily indicative of free tropospheric trends, which have been overwhelmingly positive since the mid-1990s, as shown by recent studies of ozonesonde and aircraft observations.
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| 11. |
- Smith, V., et al.
(författare)
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Irish and New Zealand Midwives' expertise at preserving the perineum intact (the MEPPI study): Perspectives on preparations for birth
- 2017
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Ingår i: Midwifery. - : Elsevier BV. - 0266-6138. ; 55, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: perineal trauma during birth can result in short or long term morbidity for women. Internationally, rates of episiotomy and severe perineal tears vary considerably. In New Zealand, in 2011, and in a trial of midwife-led care in Ireland, episiotomy rates were found to be considerably lower than those in many other countries. A qualitative exploratory study was undertaken to ascertain how midwives achieve these low rates, in these countries and settings. Design and participants: a qualitative exploratory study was conducted. Midwives expert in preserving the perineum intact (PPI) from two maternity units in the Republic of Ireland and from varied birth settings in New Zealand, were eligible to participate. Twenty-one consenting midwives took part, seven from Ireland and 14 from New Zealand. Methods: university ethical approval was granted. Face-to-face, semi-structured interviews were used to collect the data. Interviews were recorded and transcribed verbatim. The data were analysed using Ethnograph software and were organised into prominent themes. Findings: four themes were identified; 'Sources of knowledge for PPI', 'Associated factors', 'Decision-making on episiotomy', and 'Preparations for PPI'. Participants drew heavily on multiple sources of knowledge in building their own expertise for PPI. Physical characteristics of the perineum featured prominently as factors leading to PPI. Episiotomy was, in the main, only performed when there were signs of fetal distress. Antenatal perineal massage was supported. Conclusion: this study provides valuable insight into the views and skills of midwives, with expertise in PPI at birth, adding to the body of evidence on this topic.
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| 12. |
- Voskuil, Jan L. A., et al.
(författare)
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The Antibody Society's antibody validation webinar series
- 2020
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Ingår i: mAbs. - : Informa UK Limited. - 1942-0862 .- 1942-0870. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- In the wake of the reproducibility crisis and numerous discussions on how commercially available antibodies as research tool contribute to it, The Antibody Society developed a series of 10 webinars to address the issues involved. The webinars were delivered by speakers with both academic and commercial backgrounds. This report highlights the problems, and offers solutions to help the scientific community appropriately identify the right antibodies and to validate them for their research and development projects. Despite the various solutions proposed here, they must be applied on a case-by-case basis. Each antibody must be verified based on the content of the product sheet, and subsequently through experimentation to confirm integrity, specificity and selectivity. Verification needs to focus on the precise application and tissue/cell type for which the antibody will be used, and all verification data must be reported openly. The various approaches discussed here all have caveats, so a combination of solutions must be considered.
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