| 1. |
- Myers, L., et al.
(författare)
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Variable neurodevelopmental and morphological phenotypes of carriers with 12q12 duplications
- 2020
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Ingår i: Molecular Genetics & Genomic Medicine. - : Wiley. - 2324-9269. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Variable size deletions affecting 12q12 have been found in individuals with neurodevelopmental disorders (NDDs) and distinct facial and physical features. For many genetic loci affected by deletions in individuals with NDDs, reciprocal duplications have been described. However, for the 12q12 region, there are no detailed descriptions of duplication cases in the literature. Methods We report a phenotypic description of a family with monozygotic twins diagnosed with NDDs, carrying a 9 Mb duplication at 12q12, and five other individuals with overlapping duplications ranging from 4.54 Mb up to 15.16 Mb. Results The duplication carriers had language delays, cognitive delays, and were diagnosed with autism spectrum disorder. Additionally, distinct facial features (e.g., high foreheads, deeply set eyes, short palpebral fissures, small ears, high nasal bridges, abnormalities of the nose tip, thin lips), large feet, and abnormalities in the digits were noted. We also describe incomplete penetrance of the NDD phenotypes among the individuals with 12q12 duplication. Conclusion This case series expands our knowledge on this rare genetic aberration and suggests that large 12q12 duplications may increase the risk for developing NDDs.
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| 2. |
- Nicholas, M. K., et al.
(författare)
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Implementation of Early Intervention Protocol in Australia for 'High Risk' Injured Workers is Associated with Fewer Lost Work Days Over 2 Years Than Usual (Stepped) Care
- 2020
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Ingår i: Journal of occupational rehabilitation. - : Springer. - 1053-0487 .- 1573-3688. ; 30:1, s. 93-104
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate whether a protocol for early intervention addressing the psychosocial risk factors for delayed return to work in workers with soft tissue injuries would achieve better long-term outcomes than usual (stepped) care.Methods: The study used a controlled, non-randomised prospective design to compare two case management approaches. For the intervention condition, workers screened within 1-3 weeks of injury as being at high risk of delayed returned to work by the Örebro Musculoskeletal Pain Screening Questionnaire-short version (ÖMPSQ-SF) were offered psychological assessment and a comprehensive protocol to address the identified obstacles for return to work. Similarly identified injured workers in the control condition were managed under usual (stepped) care arrangements.Results: At 2-year follow-up, the mean lost work days for the Intervention group was less than half that of the usual care group, their claim costs were 30% lower, as was the growth trajectory of their costs after 11 months.Conclusions: The findings supported the hypothesis that brief psychological risk factor screening, combined with a protocol for active collaboration between key stakeholders to address identified psychological and workplace factors for delayed return to work, can achieve better return on investment than usual (stepped) care.
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| 4. |
- Briggs, Andrew M., et al.
(författare)
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Health systems strengthening to arrest the global disability burden : Empirical development of prioritised components for a global strategy for improving musculoskeletal health
- 2021
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Ingår i: BMJ Global Health. - : BMJ. - 2059-7908. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Despite the profound burden of disease, a strategic global response to optimise musculoskeletal (MSK) health and guide national-level health systems strengthening priorities remains absent. Auspiced by the Global Alliance for Musculoskeletal Health (G-MUSC), we aimed to empirically derive requisite priorities and components of a strategic response to guide global and national-level action on MSK health. Methods Design: mixed-methods, three-phase design. Phase 1: qualitative study with international key informants (KIs), including patient representatives and people with lived experience. KIs characterised the contemporary landscape for MSK health and priorities for a global strategic response. Phase 2: scoping review of national health policies to identify contemporary MSK policy trends and foci. Phase 3: informed by phases 1-2, was a global eDelphi where multisectoral panellists rated and iterated a framework of priorities and detailed components/actions. Results Phase 1: 31 KIs representing 25 organisations were sampled from 20 countries (40% low and middle income (LMIC)). Inductively derived themes were used to construct a logic model to underpin latter phases, consisting of five guiding principles, eight strategic priority areas and seven accelerators for action. Phase 2: of the 165 documents identified, 41 (24.8%) from 22 countries (88% high-income countries) and 2 regions met the inclusion criteria. Eight overarching policy themes, supported by 47 subthemes, were derived, aligning closely with the logic model. Phase 3: 674 panellists from 72 countries (46% LMICs) participated in round 1 and 439 (65%) in round 2 of the eDelphi. Fifty-nine components were retained with 10 (17%) identified as essential for health systems. 97.6% and 94.8% agreed or strongly agreed the framework was valuable and credible, respectively, for health systems strengthening. Conclusion An empirically derived framework, co-designed and strongly supported by multisectoral stakeholders, can now be used as a blueprint for global and country-level responses to improve MSK health and prioritise system strengthening initiatives.
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| 5. |
- Suzuki, Toshiyasu, et al.
(författare)
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b-Catenin Drives Butyrophilin-like Molecule Loss and gd T-cell Exclusion in Colon Cancer
- 2023
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Ingår i: CANCER IMMUNOLOGY RESEARCH. - : AMER ASSOC CANCER RESEARCH. - 2326-6066. ; 11:8, s. 1137-1155
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Tidskriftsartikel (refereegranskat)abstract
- Intraepithelial lymphocytes (IEL) expressing y8 T-cell receptors (y8TCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immu-nosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic y8IELs. In contrast with healthy intestinal or colonic tissue, we found that y8IELs were largely absent from the micro-environment of both mouse and human tumors, and that butyr-ophilin-like (BTNL) molecules, which can critically regulate y8IEL through direct y8TCR interactions, were also downregulated in tumors. We then demonstrated that 13-catenin activation through loss of Apc rapidly suppressed expression of the mRNA encoding the HNF4A and HNF4G transcription factors, preventing their binding to promoter regions of Btnl genes. Reexpression of BTNL1 and BTNL6 in cancer cells increased y8IEL survival and activation in coculture assays but failed to augment their cancer-killing ability in vitro or their recruitment to orthotopic tumors. However, inhibition of 13-catenin signaling via genetic deletion of Bcl9/Bcl9L in either Apc-deficient or mutant 13-catenin mouse models restored Hnf4a, Hnf4g, and Btnl gene expression and y8 T-cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts y8IEL immunosurveillance and furthers cancer progression.
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| 6. |
- Cannone, Carla, et al.
(författare)
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Addressing Challenges in Long-Term Strategic Energy Planning in LMICs : Learning Pathways in an Energy Planning Ecosystem
- 2023
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Ingår i: Energies. - : MDPI AG. - 1996-1073. ; 16:21
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an innovative approach to addressing critical global challenges in long-term energy planning for low- and middle-income countries (LMICs). The paper proposes and tests an international enabling environment, a delivery ecosystem, and a community of practice. These components are integrated into workflows that yield four self-sustaining capacity-development outcomes. Planning long-term energy strategies in LMICs is particularly challenging due to limited national agency and poor international coordination. While outsourcing energy planning to foreign experts may appear to be a viable solution, it can lead to a reduction in government agency (the ability of a government to make its own informed analysis and decisions). Additionally, studies commissioned by external experts may have conflicting terms of reference, and a lack of familiarity with local conditions can result in misrepresentations of on-the-ground realities. It is argued here that enhancing national agency and analytical capacity can improve coordination and lead to more robust planning across line ministries and technical assistance (TA) providers. Moreover, the prevailing consulting model hampers the release and accessibility of underlying analytics, making it difficult to retrieve, reuse, and reconstruct consultant outputs. The absence of interoperability among outputs from various consultants hinders the ability to combine and audit the insights they provide. To overcome these challenges, five strategic principles for energy planning in LMICs have been introduced and developed in collaboration with 21 international and research organizations, including the AfDB, IEA, IRENA, IAEA, UNDP, UNECA, the World Bank, and WRI. These principles prioritize national ownership, coherence and inclusivity, capacity, robustness, transparency and accessibility. In this enabling environment, a unique delivery ecosystem consisting of knowledge products and activities is established. The paper focuses on two key knowledge products as examples of this ecosystem: the open-source energy modeling system (OSeMOSYS) and the power system flexibility tool (IRENA FlexTool). These ecosystem elements are designed to meet user-friendliness, retrievability, reusability, reconstructability, repeatability, interoperability, and audibility (U4RIA) goals. To ensure the sustainability of this ecosystem, OpTIMUS is introduced—a community of practice dedicated to maintaining, supporting, expanding, and nurturing the elements within the ecosystem. Among other ecosystem elements, training and research initiatives are introduced, namely the Energy Modelling Platform for Africa, Latin America and the Caribbean, and Asia-Pacific as well as the ICTP Joint Summer School on Modelling Tools for Sustainable Development. Once deployed via workflows, the preliminary outcomes of these capacity-development learning pathways show promise. Further investigation is necessary to evaluate their long-term impacts, scalability, replication, and deployment costs.
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