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- Rosenhahn, Erik, et al.
(författare)
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Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy, and periventricular calcifications
- 2022
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 109:8, s. 1421-1435
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Tidskriftsartikel (refereegranskat)abstract
- PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy, and progressive microcephaly. Further common clinical findings included muscular hyper- and hypotonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, ventriculomegaly, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM domain region that is essential for protein-protein interaction. For further insight into the effects of PPFIBP1 loss of function, we performed automated behavioral phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model, which revealed defects in spontaneous and light-induced behavior and confirmed resistance to the acetylcholinesterase inhibitor aldicarb, suggesting a defect in the neuronal presynaptic zone. In conclusion, we establish bi-allelic loss-of-function variants in PPFIBP1 as a cause of an autosomal recessive severe neurodevelopmental disorder with early-onset epilepsy, microcephaly, and periventricular calcifications.
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- Gleeson, Tom, et al.
(författare)
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Illuminating water cycle modifications and Earth system resilience in the Anthropocene
- 2020
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Ingår i: Water resources research. - 0043-1397 .- 1944-7973. ; 56:4
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Tidskriftsartikel (refereegranskat)abstract
- Fresh water—the bloodstream of the biosphere—is at the center of the planetary drama of the Anthropocene. Water fluxes and stores regulate the Earth's climate and are essential for thriving aquatic and terrestrial ecosystems, as well as water, food, and energy security. But the water cycle is also being modified by humans at an unprecedented scale and rate. A holistic understanding of freshwater's role for Earth system resilience and the detection and monitoring of anthropogenic water cycle modifications across scales is urgent, yet existing methods and frameworks are not well suited for this. In this paper we highlight four core Earth system functions of water (hydroclimatic regulation, hydroecological regulation, storage, and transport) and key related processes. Building on systems and resilience theory, we review the evidence of regional‐scale regime shifts and disruptions of the Earth system functions of water. We then propose a framework for detecting, monitoring, and establishing safe limits to water cycle modifications and identify four possible spatially explicit methods for their quantification. In sum, this paper presents an ambitious scientific and policy grand challenge that could substantially improve our understanding of the role of water in the Earth system and cross‐scale management of water cycle modifications that would be a complementary approach to existing water management tools.
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- Latenstein, Anouk E.J., et al.
(författare)
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The use and clinical outcome of total pancreatectomy in the United States, Germany, the Netherlands, and Sweden
- 2021
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Ingår i: Surgery (United States). - : Elsevier BV. - 0039-6060. ; 170:2, s. 563-570
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Tidskriftsartikel (refereegranskat)abstract
- Background: Total pancreatectomy has high morbidity and mortality and differences among countries are currently unknown. This study compared the use and postoperative outcomes of total pancreatectomy among 4 Western countries. Methods: Patients who underwent one-stage total pancreatectomy were included from registries in the United States, Germany, the Netherlands, and Sweden (2014–2018). Use of total pancreatectomy was assessed by calculating the ratio total pancreatectomy to pancreatoduodenectomy. Primary outcomes were major morbidity (Clavien Dindo ≥3) and in-hospital mortality. Predictors for the primary outcomes were assessed in multivariable logistic regression analyses. Sensitivity analysis assessed the impact of volume (low-volume <40 or high-volume ≥40 pancreatoduodenectomies annually; data available for the Netherlands and Germany). Results: In total, 1,579 patients underwent one-stage total pancreatectomy. The relative use of total pancreatectomy to pancreatoduodenectomy varied up to fivefold (United States 0.03, Germany 0.15, the Netherlands 0.03, and Sweden 0.15; P <.001). Both the indication and several baseline characteristics differed significantly among countries. Major morbidity occurred in 423 patients (26.8%) and differed (22.3%, 34.9%, 38.3%, and 15.9%, respectively; P <.001). In-hospital mortality occurred in 85 patients (5.4%) and also differed (1.8%, 10.2%, 10.8%, 1.9%, respectively; P <.001). Country, age ≥75, and vascular resection were predictors for in-hospital mortality. In-hospital mortality was lower in high-volume centers in the Netherlands (4.9% vs 23.1%; P =.002), but not in Germany (9.8% vs 10.6%; P =.733). Conclusion: Considerable differences in the use of total pancreatectomy, patient characteristics, and postoperative outcome were noted among 4 Western countries with better outcomes in the United States and Sweden. These large, yet unexplained, differences require further research to ultimately improve patient outcome.
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- 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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- Richardson, Katherine, et al.
(författare)
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Earth beyond six of nine planetary boundaries
- 2023
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Ingår i: Science Advances. - 2375-2548. ; 9:37
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Tidskriftsartikel (refereegranskat)abstract
- This planetary boundaries framework update finds that six of the nine boundaries are transgressed, suggesting that Earth is now well outside of the safe operating space for humanity. Ocean acidification is close to being breached, while aerosol loading regionally exceeds the boundary. Stratospheric ozone levels have slightly recovered. The transgression level has increased for all boundaries earlier identified as overstepped. As primary production drives Earth system biosphere functions, human appropriation of net primary production is proposed as a control variable for functional biosphere integrity. This boundary is also transgressed. Earth system modeling of different levels of the transgression of the climate and land system change boundaries illustrates that these anthropogenic impacts on Earth system must be considered in a systemic context.
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- Wang-Erlandsson, Lan, et al.
(författare)
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A planetary boundary for green water
- 2022
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Ingår i: Nature Reviews Earth & Environment. - : Springer Science and Business Media LLC. - 2662-138X. ; 3:6, s. 380-392
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Tidskriftsartikel (refereegranskat)abstract
- Green water — terrestrial precipitation, evaporation and soil moisture — is fundamental to Earth system dynamics and is now extensively perturbed by human pressures at continental to planetary scales. However, green water lacks explicit consideration in the existing planetary boundaries framework that demarcates a global safe operating space for humanity. In this Perspective, we propose a green water planetary boundary and estimate its current status. The green water planetary boundary can be represented by the percentage of ice-free land area on which root-zone soil moisture deviates from Holocene variability for any month of the year. Provisional estimates of departures from Holocene-like conditions, alongside evidence of widespread deterioration in Earth system functioning, indicate that the green water planetary boundary is already transgressed. Moving forward, research needs to address and account for the role of root-zone soil moisture for Earth system resilience in view of ecohydrological, hydroclimatic and sociohydrological interactions.
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