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| 3. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 5. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 6. |
- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 7. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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| 9. |
- Harner, Tom, et al.
(author)
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Air synthesis review : polycyclic aromatic compounds in the oil sands region
- 2018
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In: Environmental Reviews. - : Canadian Science Publishing. - 1181-8700 .- 1208-6053. ; 26:4, s. 430-468
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Research review (peer-reviewed)abstract
- This air synthesis review presents the current state of knowledge on the sources, fates, and effects for polycyclic aromatic compounds (PACs) and related chemicals released to air in the oil sands region (OSR) in Alberta, Canada. Through the implementation of the Joint Canada-Alberta Oil Sands Monitoring Program in 2012 a vast amount of new information on PACs has been acquired through directed monitoring and research projects and reported to the scientific community and public. This new knowledge addresses questions related to cumulative effects and informs the sustainable management of the oil sands resource while helping to identify gaps in understanding and priorities for future work. As a result of this air synthesis review on PACs, the following topics have been identified as new science priorities: (i) improving emissions reporting to better account for fugitive mining emissions of PACs that includes a broader range of PACs beyond the conventional polycyclic aromatic hydrocarbons (PAHs) including, inter alia, alkylated-PAHs (alk-PAHs), dibenzothiophene (DBT), alk-DBTs, nitro-PAHs, oxy-PAHs including quinones and thia-and aza-arenes; (ii) improving information on the ambient concentrations, long-range transport, and atmospheric deposition of these broader classes of PACs and their release (with co-contaminants) from different types of mining activities; (iii) further optimizing electricity-free and cost-effective approaches for assessing PAC deposition (e.g., snow sampling, lichens, passive ambient sampling) spatially across the OSR and downwind regions; (iv) designing projects that integrate monitoring efforts with source attribution models and ecosystem health studies to improve understanding of sources, receptors, and effects; (v) further optimizing natural deposition archives (e.g., sediment, peat, tree rings) and advanced forensic techniques (e.g., isotope analysis, marker compounds) to provide better understanding of sources of PACs in the OSR over space and time; (vi) conducting process research to improve model capabilities for simulating atmospheric chemistry of PACs and assessing exposure to wildlife and humans; and (vii) developing tools and integrated strategies for assessing cumulative risk to wildlife and humans by accounting for the toxicity of the mixture of chemicals in air rather than on a single compound basis.
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| 10. |
- Massaro, Giulia, et al.
(author)
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Fetal gene therapy for neurodegenerative disease of infants
- 2018
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 24:9, s. 1317-1323
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Journal article (peer-reviewed)abstract
- For inherited genetic diseases, fetal gene therapy offers the potential of prophylaxis against early, irreversible and lethal pathological change. To explore this, we studied neuronopathic Gaucher disease (nGD), caused by mutations in GBA. In adult patients, the milder form presents with hepatomegaly, splenomegaly and occasional lung and bone disease; this is managed, symptomatically, by enzyme replacement therapy. The acute childhood lethal form of nGD is untreatable since enzyme cannot cross the blood–brain barrier. Patients with nGD exhibit signs consistent with hindbrain neurodegeneration, including neck hyperextension, strabismus and, often, fatal apnea1. We selected a mouse model of nGD carrying a loxP-flanked neomycin disruption of Gba plus Cre recombinase regulated by the keratinocyte-specific K14 promoter. Exclusive skin expression of Gba prevents fatal neonatal dehydration. Instead, mice develop fatal neurodegeneration within 15 days2. Using this model, fetal intracranial injection of adeno-associated virus (AAV) vector reconstituted neuronal glucocerebrosidase expression. Mice lived for up to at least 18 weeks, were fertile and fully mobile. Neurodegeneration was abolished and neuroinflammation ameliorated. Neonatal intervention also rescued mice but less effectively. As the next step to clinical translation, we also demonstrated the feasibility of ultrasound-guided global AAV gene transfer to fetal macaque brains.
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| 11. |
- Osman-Gani, A. Ahad M., et al.
(author)
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Repatriation readjustment of international managers : an empirical study of HRD interventions
- 2008
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In: Career Development International. - UK : Emerald. - 1362-0436 .- 1758-6003. ; 13:5, s. 456-475
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Journal article (peer-reviewed)abstract
- Purpose - With increasing interest in overseas business expansion, particularly in the Asia-Pacific region, expatriate management, including repatriation readjustmenst, has become a critical international human resource development (HRD) issue for multinational enterprises (MNEs). This empirical study therefore aims to investigate the use of HRD interventions relating to training and development for effective readjustment of international managers on repatriation. Design/methodology/approach - The data were collected through a field survey conducted on repatriation experience of international managers from more than five countries, who are working in Singapore. Findings - The study provides valuable insights about repatriation training programmes, training contents, programme duration, delivery modes, and providers of effective training programmes. Research limitations/implications - HRD professionals and senior executives of MNEs will benefit from the findings of this study in making decisions on effective design and implementation of training and career development programmes. Practical implications - The findings have significant implications for career development of managers involved in international business operations. Originality/value - This paper discusses readjustment problems of the repatriating managers and suggests how realistic HRD programmes, mainly based on training, can be developed and implemented for retaining international managers. These findings from the dynamic region of Asia will also help in developing appropriate career development programmes.
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| 12. |
- Tordo, Julie, et al.
(author)
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A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency
- 2018
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 141:7, s. 2014-2031
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Journal article (peer-reviewed)abstract
- Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology.
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