| 1. |
- Ba, Alexandre, et al.
(författare)
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Inter-laboratory comparison of channelized hotelling observer computation
- 2018
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Ingår i: Medical Physics. - : Wiley. - 0094-2405 .- 2473-4209. ; 45:7, s. 3019-3030
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The task-based assessment of image quality using model observers is increasingly used for the assessment of different imaging modalities. However, the performance computation of model observers needs standardization as well as a well-established trust in its implementation methodology and uncertainty estimation. The purpose of this work was to determine the degree of equivalence of the channelized Hotelling observer performance and uncertainty estimation using an intercomparison exercise. Materials and Methods: Image samples to estimate model observer performance for detection tasks were generated from two-dimensional CT image slices of a uniform water phantom. A common set of images was sent to participating laboratories to perform and document the following tasks: (a) estimate the detectability index of a well-defined CHO and its uncertainty in three conditions involving different sized targets all at the same dose, and (b) apply this CHO to an image set where ground truth was unknown to participants (lower image dose). In addition, and on an optional basis, we asked the participating laboratories to (c) estimate the performance of real human observers from a psychophysical experiment of their choice. Each of the 13 participating laboratories was confidentially assigned a participant number and image sets could be downloaded through a secure server. Results were distributed with each participant recognizable by its number and then each laboratory was able to modify their results with justification as model observer calculation are not yet a routine and potentially error prone. Results: Detectability index increased with signal size for all participants and was very consistent for 6 mm sized target while showing higher variability for 8 and 10 mm sized target. There was one order of magnitude between the lowest and the largest uncertainty estimation. Conclusions: This intercomparison helped define the state of the art of model observer performance computation and with thirteen participants, reflects openness and trust within the medical imaging community. The performance of a CHO with explicitly defined channels and a relatively large number of test images was consistently estimated by all participants. In contrast, the paper demonstrates that there is no agreement on estimating the variance of detectability in the training and testing setting.
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| 2. |
- Dumitrescu, L., et al.
(författare)
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Sex differences in the genetic predictors of Alzheimer's pathology
- 2019
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 142, s. 2581-2589
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Tidskriftsartikel (refereegranskat)abstract
- Autopsy measures of Alzheimer's disease neuropathology have been leveraged as endophenotypes in previous genome-wide association studies (GWAS). However, despite evidence of sex differences in Alzheimer's disease risk, sex-stratified models have not been incorporated into previous GWAS analyses. We looked for sex-specific genetic associations with Alzheimer's disease endophenotypes from six brain bank data repositories. The pooled dataset included 2701 males and 3275 females, the majority of whom were diagnosed with Alzheimer's disease at autopsy (70%). Sex-stratified GWAS were performed within each dataset and then meta-analysed. Loci that reached genome-wide significance (P < 5 x 10(-8)) in stratified models were further assessed for sex interactions. Additional analyses were performed in independent datasets leveraging cognitive, neuroimaging and CSF endophenotypes, along with age-at-onset data. Outside of the APOE region, one locus on chromosome 7 (rs34331204) showed a sex-specific association with neurofibrillary tangles among males (P = 2.5 x 10(-8)) but not females (P = 0.85, sex-interaction P = 2.9 x 10(-4)). In follow-up analyses, rs34331204 was also associated with hippocampal volume, executive function, and age-at-onset only among males. These results implicate a novel locus that confers male-specific protection from tau pathology and highlight the value of assessing genetic associations in a sex-specific manner.
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| 3. |
- Gifford W., W., et al.
(författare)
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Theoretical foundations of dissemination and implementation leadership : a conceptual model for leadership development
- 2014
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Konferensbidrag (refereegranskat)abstract
- Introduction: The leadership of healthcare managers is considered critical to implementing evidence based practice for strengthened healthcare delivery and improved patient, provider and system outcomes. However, lack of clarity exists regarding what leaders actually do and the basis for their actions, or how to develop leadership capacity for successful dissemination and implementation.Objectives: To describe a conceptual model that explicates key components of a leadership intervention and the subsequent leadership knowledge, skills and behaviours required by senior and front line managers for implementation.Method: Using principals from the UK Medical Research Council’s Complex Interventions Framework, evidenceand theories on leadership and implementation science were synthesized with the tacit knowledge of researchers and healthcare managers from Canada, United States and Sweden in a 3 day planning meeting in Ottawa, Canada. An intervention was developed and the key components were graphically depicted in a conceptual model with the hypothesized leadership processes and outcomes.Findings: The conceptual model depicts the knowledge, skills and behaviours that health care managers require to create a strong leadership process for implementing high quality evidence-based care. The leadership process involves relations, change and task-oriented knowledge and behaviours to: prioritize improvements; set goals for change; assess and manage multi-level barriers; secure resources; and engage clinical and management staff. Together the leadership behaviours influence individuals, the practice environment and the organizational infrastructure for successful dissemination and implementation.Conclusion: Leadership of healthcare managers is key to building effective healthcare systems; however what they do to influence dissemination and implementation of evidence based practice is not clear. The conceptual model provides conceptual clarity on what healthcare managers do to lead the implementation of evidence based practice, thereby advancing the field of D & I. PrimaryFunding Source: Canadian Institute of Health Research
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| 4. |
- Tistad, Malin, et al.
(författare)
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Developing Leadership in Managers to Facilitate the Implementation of National Guideline Recommendations: A Process Evaluation of Feasibility and Usefulness
- 2016
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Ingår i: International Journal of Health Policy and Management-Ijhpm. - : Maad Rayan Publishing Company. - 2322-5939. ; 5:8, s. 477-486
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous research supports the claim that managers are vital players in the implementation of clinical practice guidelines (CPGs), yet little is known about interventions aiming to develop managers' leadership in facilitating implementation. In this pilot study, process evaluation was employed to study the feasibility and usefulness of a leadership intervention by exploring the intervention's potential to support managers in the implementation of national guideline recommendations for stroke care in outpatient rehabilitation. Methods: Eleven senior and frontline managers from five outpatient stroke rehabilitation centers participated in a four-month leadership intervention that included workshops, seminars, and teleconferences. The focus was on developing knowledge and skills to enhance the implementation of CPG recommendations, with a particular focus on leadership behaviors. Each dyad of managers was assigned to develop a leadership plan with specific goals and leadership behaviors for implementing three rehabilitation recommendations. Feasibility and usefulness were explored through observations and interviews with the managers and staff members prior to the intervention, and then one month and one year after the intervention. Results: Managers considered the intervention beneficial, particularly the participation of both senior and frontline managers and the focus on leadership knowledge and skills for implementing CPG recommendations. All the managers developed a leadership plan, but only two units identified goals specific to implementing the three stroke rehabilitation recommendations. Of these, only one identified leadership behaviors that support implementation. Conclusion: Managers found that the intervention was delivered in a feasible way and appreciated the focus on leadership to facilitate implementation. However, the intervention appeared to have limited impact on managers' behaviors or clinical practice at the units. Future interventions directed towards managers should have a stronger focus on developing leadership skills and behaviors to tailor implementation plans and support implementation of CPG recommendations.
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| 5. |
- Bisteau, Xavier, et al.
(författare)
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The Greatwall kinase safeguards the genome integrity by affecting the kinome activity in mitosis
- 2020
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594.
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Tidskriftsartikel (refereegranskat)abstract
- Progression through mitosis is balanced by the timely regulation of phosphorylation and dephosphorylation events ensuring the correct segregation of chromosomes before cytokinesis. This balance is regulated by the opposing actions of CDK1 and PP2A, as well as the Greatwall kinase/MASTL. MASTL is commonly overexpressed in cancer, which makes it a potential therapeutic anticancer target. Loss of Mastl induces multiple chromosomal errors that lead to the accumulation of micronuclei and multilobulated cells in mitosis. Our analyses revealed that loss of Mastl leads to chromosome breaks and abnormalities impairing correct segregation. Phospho-proteomic data for Mastl knockout cells revealed alterations in proteins implicated in multiple processes during mitosis including double-strand DNA damage repair. In silico prediction of the kinases with affected activity unveiled NEK2 to be regulated in the absence of Mastl. We uncovered that, RAD51AP1, involved in regulation of homologous recombination, is phosphorylated by NEK2 and CDK1 but also efficiently dephosphorylated by PP2A/B55. Our results suggest that MastlKO disturbs the equilibrium of the mitotic phosphoproteome that leads to the disruption of DNA damage repair and triggers an accumulation of chromosome breaks even in noncancerous cells.
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| 6. |
- Daneshjou, Roxana, et al.
(författare)
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Working toward precision medicine : Predicting phenotypes from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges
- 2017
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 38:9, s. 1182-1192
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Tidskriftsartikel (refereegranskat)abstract
- Precision medicine aims to predict a patient's disease risk and best therapeutic options by using that individual's genetic sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. For CAGI 4, three challenges involved using exome-sequencing data: Crohn's disease, bipolar disorder, and warfarin dosing. Previous CAGI challenges included prior versions of the Crohn's disease challenge. Here, we discuss the range of techniques used for phenotype prediction as well as the methods used for assessing predictive models. Additionally, we outline some of the difficulties associated with making predictions and evaluating them. The lessons learned from the exome challenges can be applied to both research and clinical efforts to improve phenotype prediction from genotype. In addition, these challenges serve as a vehicle for sharing clinical and research exome data in a secure manner with scientists who have a broad range of expertise, contributing to a collaborative effort to advance our understanding of genotype-phenotype relationships.
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| 7. |
- Deming, Yuetiva, et al.
(författare)
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Sex-specific genetic predictors of Alzheimer’s disease biomarkers
- 2018
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 136:6, s. 857-872
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer’s disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aβ42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (β = − 0.03, p = 4.25 × 10−8; β = 0.03, p = 3.97 × 10−8) than males (β = − 0.02, p = 0.009; β = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (β = 0.05, p = 4.57 × 10−10) compared to males (β = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale = 0.047; pmale = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD’s genetic architecture.
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| 8. |
- Eldh, Ann Catrine, et al.
(författare)
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Clinical interventions, implementation interventions, and the potential greyness in between -a discussion paper
- 2017
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 17:16
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is increasing awareness that regardless of the proven value of clinical interventions, the use of effective strategies to implement such interventions into clinical practice is necessary to ensure that patients receive the benefits. However, there is often confusion between what is the clinical intervention and what is the implementation intervention. This may be caused by a lack of conceptual clarity between 'intervention' and 'implementation', yet at other times by ambiguity in application. We suggest that both the scientific and the clinical communities would benefit from greater clarity; therefore, in this paper, we address the concepts of intervention and implementation, primarily as in clinical interventions and implementation interventions, and explore the grey area in between. Discussion: To begin, we consider the similarities, differences and potential greyness between clinical interventions and implementation interventions through an overview of concepts. This is illustrated with reference to two examples of clinical interventions and implementation intervention studies, including the potential ambiguity in between. We then discuss strategies to explore the hybridity of clinical-implementation intervention studies, including the role of theories, frameworks, models, and reporting guidelines that can be applied to help clarify the clinical and implementation intervention, respectively. Conclusion: Semantics provide opportunities for improved precision in depicting what is 'intervention' and what is 'implementation' in health care research. Further, attention to study design, the use of theory, and adoption of reporting guidelines can assist in distinguishing between the clinical intervention and the implementation intervention. However, certain aspects may remain unclear in analyses of hybrid studies of clinical and implementation interventions. Recognizing this potential greyness can inform further discourse.
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| 9. |
- Gifford, W. A., et al.
(författare)
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Managerial leadership for research use in nursing and allied health care professions: a systematic review
- 2018
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Ingår i: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Leadership by point-of-care and senior managers is increasingly recognized as critical to the acceptance and use of research evidence in practice. The purpose of this systematic review was to identify the leadership behaviours of managers that are associated with research use by clinical staff in nursing and allied health professionals. Methods: A mixed methods systematic review was performed. Eight electronic bibliographic databases were searched. Studies examining the association between leadership behaviours and nurses and allied health professionals' use of research were eligible for inclusion. Studies were excluded if leadership could not be clearly attributed to someone in a management position. Two reviewers independently screened abstracts, reviewed full-text articles, extracted data and performed quality assessments. Narrative synthesis was conducted. Results: The search yielded 7019 unique titles and abstracts after duplicates were removed. Three hundred five full-text articles were reviewed, and 31 studies reported in 34 articles were included. Methods used were qualitative (n = 19), cross-sectional survey (n = 9), and mixed methods (n = 3). All studies included nurses, and six also included allied health professionals. Twelve leadership behaviours were extracted from the data for point-of-care managers and ten for senior managers. Findings indicated that managers performed a diverse range of leadership behaviours that encompassed change-oriented, relation-oriented and task-oriented behaviours. The most commonly described behavior was support for the change, which involved demonstrating conceptual and operational commitment to research-based practices. Conclusions: This systematic review adds to the growing body of evidence that indicates that manager-staff dyads are influential in translating research evidence into action. Findings also reveal that leadership for research use involves change and task-oriented behaviours that influence the environmental milieu and the organisational infrastructure that supports clinical care. While findings explain how managers enact leadership for research use, we now require robust methodological studies to determine which behaviours are effective in enabling research use with nurses and allied health professionals for high-quality evidence-based care.
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| 10. |
- Gifford, W., et al.
(författare)
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Feasibility and usefulness of a leadership intervention to implement evidence-based falls prevention practices in residential care in Canada
- 2019
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Ingår i: Pilot and Feasibility Studies. - : Springer Science and Business Media LLC. - 2055-5784. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Leadership is critical to supporting and facilitating the implementation of evidence-based practices in health care. Yet, little is known about how to develop leadership capacity for this purpose. The aims of this study were to explore the (1) feasibility of delivering a leadership intervention to promote implementation, (2) usefulness of the leadership intervention, and (3) participants' engagement in leadership to implement evidence-based fall prevention practices in Canadian residential care. Methods: We conducted a mixed-method before-and-after feasibility study on two units in a Canadian residential care facility. The leadership intervention was based on the Ottawa model of implementation leadership (O-MILe) and consisted of two workshops and two individualized coaching sessions over 3 months to develop leadership capacity for implementing evidence-based fall prevention practices. Participants (n = 10) included both formal (e.g., managers) and informal (e.g., nurses and care AIDS leaders). Outcome measures were parameters of feasibility (e.g., number of eligible candidates who attended the workshops and coaching sessions) and usefulness of the leadership intervention (e.g., ratings, suggested modifications). We conducted semi-structured interviews guided by the Implementation Leadership Scale (ILS), a validated measure of 12-item in four subcategories (proactive, supportive, knowledgeable, and perseverant), to explore the leadership behaviors that participants used to implement fall prevention practices. We repeated the ILS in a focus group meeting to understand the collective leadership behaviors used by the intervention team. Barriers and facilitators to leading implementation were also explored. Results: Delivery of the leadership intervention was feasible. All participants (n = 10) attended the workshops and eight participated in at least one coaching session. Workshops and coaching were rated useful (≥ 3 on a 0-4 Likert scale where 4 = highly useful) by 71% and 86% of participants, respectively. Participants rated the O-MILe subcategories of supportive and perseverant leadership highest for individual leadership, whereas supportive and knowledgeable leadership were rated highest for team leadership. Conclusions: The leadership intervention was feasible to deliver, deemed useful by participants, and fostered engagement in implementation leadership activities. Study findings highlight the complexity of developing implementation leadership and modifications required to optimize impact. Future trials are now required to test the effectiveness of the leadership intervention on developing leadership for implementing evidence-based practices. © The Author(s). 2019.
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