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- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Reeves, Jessica M., et al.
(författare)
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Palaeoenvironmental change in tropical Australasia over the last 30,000 years - a synthesis by the OZ-INTIMATE group
- 2013
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 74, s. 97-114
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Tidskriftsartikel (refereegranskat)abstract
- The tropics are the major source of heat and moisture for the Australasian region. Determining the tropics' response over time to changes in climate forcing mechanisms, such as summer insolation, and the effects of relative sea level on exposed continental shelves during the Last Glacial period, is an ongoing process of re-evaluation. We present a synthesis of climate proxy data from tropical Australasia spanning the last 30,000 years that incorporates deep sea core, coral, speleothem, pollen, charcoal and terrestrial sedimentary records. Today, seasonal variability is governed largely by the annual migration of the inter-tropical convergence zone (ITCZ), influencing this region most strongly during the austral summer. However, the position of the ITCZ has varied through time. Towards the end of Marine Isotope Stage (MIS) 3, conditions were far wetter throughout the region, becoming drier first in the south. Universally cooler land and sea-surface temperature (SST) were characteristic of the Last Glacial Maximum, with drier conditions than previously, although episodic wet periods are noted in the fluvial records of northern Australia. The deglacial period saw warming first in the Coral Sea and then the Indonesian seas, with a pause in this trend around the time of the Antarctic Cold Reversal (c. 14.5 ka), coincident with the flooding of the Sunda Shelf. Wetter conditions occurred first in Indonesia around 17 ka and northern Australia after 14 ka. The early Holocene saw a peak in marine SST to the northwest and northeast of Australia. Modern vegetation was first established on Indonesia, then progressively south and eastward to NE Australia. Flores and the Atherton Tablelands show a dry period around 11.6 ka, steadily becoming wetter through the early Holocene. The mid-late Holocene was punctuated by millennial-scale variability, associated with the El Nino-Southern Oscillation; this is evident in the marine, coral, speleothem and pollen records of the region.
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| 3. |
- Sloot, Frea, et al.
(författare)
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Inventory of current EU paediatric vision and hearing screening programmes
- 2015
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Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 22:2, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the diversity in paediatric vision and hearing screening programmes in Europe. Methods: Themes for comparison of screening programmes derived from literature were used to compile three questionnaires on vision, hearing, and public health screening. Tests used, professions involved, age, and frequency of testing seem to influence sensitivity, specificity, and costs most. Questionnaires were sent to ophthalmologists, orthoptists, otolaryngologists, and audiologists involved in paediatric screening in all EU full-member, candidate, and associate states. Answers were cross-checked. Results: Thirty-nine countries participated; 35 have a vision screening programme, 33 a nation-wide neonatal hearing screening programme. Visual acuity (VA) is measured in 35 countries, in 71% of these more than once. First measurement of VA varies from three to seven years of age, but is usually before age five. At age three and four, picture charts, including Lea Hyvarinen, are used most; in children over four, Tumbling-E and Snellen. As first hearing screening test, otoacoustic emission is used most in healthy neonates, and auditory brainstem response in premature newborns. The majority of hearing testing programmes are staged; children are referred after 1–4 abnormal tests. Vision screening is performed mostly by paediatricians, ophthalmologists, or nurses. Funding is mostly by health insurance or state. Coverage was reported as >95% in half of countries, but reporting was often not first-hand. Conclusion: Largest differences were found in VA charts used (12), professions involved in vision screening (10), number of hearing screening tests before referral (1–4), and funding sources (8).
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| 4. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 8. |
- Bassford, Chris, et al.
(författare)
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Developing an intervention around referral and admissions to intensive care : a mixed-methods study
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Background: Intensive care treatment can be life-saving, but it is invasive and distressing for patients receiving it and it is not always successful. Deciding whether or not a patient will benefit from intensive care is a difficult clinical and ethical challenge.Objectives: To explore the decision-making process for referral and admission to the intensive care unit and to develop and test an intervention to improve it.Methods: A mixed-methods study comprising (1) two systematic reviews investigating the factors associated with decisions to admit patients to the intensive care unit and the experiences of clinicians, patients and families; (2) observation of decisions and interviews with intensive care unit doctors, referring doctors, and patients and families in six NHS trusts in the Midlands, UK; (3) a choice experiment survey distributed to UKintensive care unit consultants and critical care outreach nurses, eliciting their preferences for factors used in decision-making for intensive care unit admission; (4) development of a decision-support intervention informed by the previous work streams, including an ethical framework for decision-making and supporting referral and decision-support forms and patient and family information leaflets. Implementation feasibility was tested in three NHS trusts; (5) development and testing of a tool to evaluate the ethical quality of decision-making related to intensive care unit admission, based on the assessment of patient records The tool was tested for inter-rater and intersite reliability in 120 patient records.Results: Influences on decision-making identified in the systematic review and ethnographic study included age, presence of chronic illness, functional status, presence of a do not attempt cardiopulmonary resuscitation order, referring specialty, referrer seniority and intensive care unit bed availability. Intensive care unit doctors used a gestalt assessment of the patient when making decisions. The choice experiment showed that age was the most important factor in consultants’ and critical care outreach nurses’ preferences for admission. The ethnographic study illuminated the complexity of the decision-making process, and the importanceof interprofessional relationships and good communication between teams and with patients and families. Doctors found it difficult to articulate and balance the benefits and burdens of intensive care unit treatment for a patient. There was low uptake of the decision-support intervention, although doctors who used it noted that it improved articulation of reasons for decisions and communication with patients.Limitations: Limitations existed in each of the component studies; for example, we had difficulty recruiting patients and families in our qualitative work. However, the project benefited from a mixed-method approachthat mitigated the potential limitations of the component studies. Conclusions: Decision-making surrounding referral and admission to the intensive care unit is complex. This study has provided evidence and resources to help clinicians and organisations aiming to improve thedecision-making for and, ultimately, the care of critically ill patients.Future work: Further research is needed into decision-making practices, particularly in how best to engage with patients and families during the decision process. The development and evaluation of trainingfor clinicians involved in these decisions should be a priority for future work.
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| 9. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 10. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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