| 1. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 2. |
- Patterson, Elaine, et al.
(författare)
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Streptozotocin-induced type-1-diabetes disease onset in Sprague-Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity
- 2015
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Ingår i: Microbiology. - London, UK : The Microbiology Society. - 1350-0872 .- 1465-2080. ; 161:Pt 1, s. 182-93
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Tidskriftsartikel (refereegranskat)abstract
- There is a growing appreciation that microbiota composition can significantly affect host health and play a role in disease onset and progression. This study assessed the impact of streptozotocin (STZ)-induced type-1-diabetes (T1D) on intestinal microbiota composition and diversity in Sprague-Dawley rats, compared with healthy controls over time. T1D was induced by injection of a single dose (60 mg STZ kg(-1)) of STZ, administered via the intraperitoneal cavity. Total DNA was isolated from faecal pellets at weeks 0 (pre-STZ injection), 1, 2 and 4 and from caecal content at week 5 from both healthy and T1D groups. High-throughput 16S rRNA sequencing was employed to investigate intestinal microbiota composition. The data revealed that although intestinal microbiota composition between the groups was similar at week 0, a dramatic impact of T1D development on the microbiota was apparent post-STZ injection and for up to 5 weeks. Most notably, T1D onset was associated with a shift in the Bacteroidetes : Firmicutes ratio (P<0.05), while at the genus level, increased proportions of lactic acid producing bacteria such as Lactobacillus and Bifidobacterium were associated with the later stages of T1D progression (P<0.05). Coincidently, T1D increased caecal lactate levels (P<0.05). Microbial diversity was also reduced following T1D (P<0.05). Principle co-ordinate analyses demonstrated temporal clustering in T1D and control groups with distinct separation between groups. The results provide a comprehensive account of how T1D is associated with an altered intestinal microbiota composition and reduced microbial diversity over time.
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| 3. |
- 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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| 4. |
- Archambault, Alexi N., et al.
(författare)
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Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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| 5. |
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| 6. |
- Evans, Alistair R., et al.
(författare)
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The maximum rate of mammal evolution
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:11, s. 4187-4190
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Tidskriftsartikel (refereegranskat)abstract
- How fast can a mammal evolve from the size of a mouse to the size of an elephant? Achieving such a large transformation calls for major biological reorganization. Thus, the speed at which this occurs has important implications for extensive faunal changes, including adaptive radiations and recovery from mass extinctions. To quantify the pace of large-scale evolution we developed a metric, clade maximum rate, which represents the maximum evolutionary rate of a trait within a clade. We applied this metric to body mass evolution in mammals over the last 70 million years, during which multiple large evolutionary transitions occurred in oceans and on continents and islands. Our computations suggest that it took a minimum of 1.6, 5.1, and 10 million generations for terrestrial mammal mass to increase 100-, and 1,000-, and 5,000-fold, respectively. Values for whales were down to half the length (i.e., 1.1, 3, and 5 million generations), perhaps due to the reduced mechanical constraints of living in an aquatic environment. When differences in generation time are considered, we find an exponential increase in maximum mammal body mass during the 35 million years following the Cretaceous-Paleogene (K-Pg) extinction event. Our results also indicate a basic asymmetry in macroevolution: very large decreases (such as extreme insular dwarfism) can happen at more than 10 times the rate of increases. Our findings allow more rigorous comparisons of microevolutionary and macroevolutionary patterns and processes.
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| 7. |
- Falkmer, Marita, et al.
(författare)
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Local visual perception bias in children with high-functioning autism spectrum disorders: do we have the whole picture?
- 2016
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Ingår i: Developmental Neurorehabilitation. - : Informa UK Limited. - 1751-8423 .- 1751-8431. ; 19:2, s. 117-122
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Tidskriftsartikel (refereegranskat)abstract
- Objective: While local bias in visual processing in children with autism spectrum disorders (ASD) has been reported to result in difficulties in recognizing faces and facially expressed emotions, but superior ability in disembedding figures, associations between these abilities within a group of children with and without ASD have not been explored.Methods: Possible associations in performance on the Visual Perception Skills Figure–Ground test, a face recognition test and an emotion recognition test were investigated within 25 8–12-years-old children with high-functioning autism/Asperger syndrome, and in comparison to 33 typically developing children.Results: Analyses indicated a weak positive correlation between accuracy in Figure–Ground recognition and emotion recognition. No other correlation estimates were significant.Conclusion: These findings challenge both the enhanced perceptual function hypothesis and the weak central coherence hypothesis, and accentuate the importance of further scrutinizing the existance and nature of local visual bias in ASD.
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| 8. |
- Henry, Carole, et al.
(författare)
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Monoclonal Antibody Responses after Recombinant Hemagglutinin Vaccine versus Subunit Inactivated Influenza Virus Vaccine : a Comparative Study
- 2019
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Ingår i: Journal of Virology. - : AMER SOC MICROBIOLOGY. - 0022-538X .- 1098-5514. ; 93:21
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Tidskriftsartikel (refereegranskat)abstract
- Vaccination is the best measure of protection against influenza virus infection. Vaccine-induced antibody responses target mainly the hemagglutinin (HA) surface glycoprotein, composed of the head and the stalk domains. Recently two novel vaccine platforms have been developed for seasonal influenza vaccination: a recombinant HA vaccine produced in insect cells (Flublok) and Flucelvax, prepared from virions produced in mammalian cells. In order to compare the fine specificity of the antibodies induced by these two novel vaccine platforms, we characterized 42 Flublok-induced monoclonal antibodies (MAbs) and 38 Flucelvax-induced MAbs for avidity, cross-reactivity, and any selectivity toward the head versus the stalk domain. These studies revealed that Flublok induced a greater proportion of MAbs targeting epitopes near the receptor-binding domain on HA head (hemagglutinin inhibition-positive MAbs) than Flucelvax, while the two vaccines induced similar low frequencies of stalk-reactive MAbs. Finally, mice immunized with Flublok and Flucelvax also induced similar frequencies of stalk-reactive antibody-secreting cells, showing that HA head immunodominance is independent of immune memory bias. Collectively, our results suggest that these vaccine formulations are similarly immunogenic but differ in the preferences of the elicited antibodies toward the receptor-binding domain on the HA head.IMPORTANCE: There are ongoing efforts to increase the efficacy of influenza vaccines and to promote production strategies that can rapidly respond to newly emerging viruses. It is important to understand if current alternative seasonal vaccines, such as Flublok and Flucelvax, that use alternate production strategies can induce protective influenza-specific antibodies and to evaluate what type of epitopes are targeted by distinct vaccine formulations.
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| 9. |
- Hoey, Hilary, et al.
(författare)
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Parent and health professional perspectives in the management of adolescents with diabetes : development of assessment instruments for international studies
- 2006
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 15:6, s. 1033-1042
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Assessment of quality of life (QOL) in adolescents with diabetes requires patient, parent and health professional input. Psychometrically robust instruments to assess parent and professional perspectives are required. RESEARCH DESIGN AND METHODS: Questionnaires concerning adolescent QOL were developed for completion by parents and health professionals. In an international study assessing QOL in 2,101 adolescents with diabetes (median age 14 years, range 10-18; from 17 countries including Europe, Japan and North America), parents and health professionals completed their respective questionnaires between March and August 1998. RESULTS: Feasibility and acceptability of the new questionnaires were indicated by high questionnaire completion rates (adolescents 92%; parents 89%; health professionals 94%). Internal consistency was confirmed (Cronbach's alpha coefficients 0.80 parent; 0.86 health professional). Correlations of Diabetes Quality of Life Questionnaire for Youths (DQOLY) scores with parent and health professional global QOL ratings were generally low (r ranging from 0.12 to 0.36). Parent-rated burden decreased incrementally across adolescence, particularly for girls. Professional-rated burden followed a similar profile but only after age 15 years. Until then, burden was rated as uniformly high. Clinically relevant discrepancies in parent and professional burden scores were noted for one-parent families and families where adolescents had been referred for psychological help. In both cases, health professionals but not one-parent families perceived these as high burden situations. The clinical significance of this relates to the significantly poorer metabolic control recorded for adolescents in both situations. CONCLUSIONS: Parent and health professional questionnaires were found to have adequate internal consistency, and convergent and discriminant validity in relation to key clinical and QOL outcomes. The questionnaires are brief, easy to administer and score. They may also enable comparisons across countries and languages to facilitate development of international health outcome parameters. The inclusion of the parent and health professional perspectives completes a comprehensive assessment of adolescent QOL relevant to diabetes.
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| 10. |
- Horlin, Chiara, et al.
(författare)
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The influence of static versus naturalistic stimuli on face processing in children with and without Asperger syndrome or high-functioning autism
- 2013
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Ingår i: Research in Autism Spectrum Disorders. - : Elsevier. - 1750-9467 .- 1878-0237. ; 7:12, s. 1617-1624
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Tidskriftsartikel (refereegranskat)abstract
- Questions regarding the use of static or dynamic facial stimuli in experimental studies investigating facial processing of individuals with AS/HFA raises issues of both ecological validity and the applicability of experimental findings to clinical or everyday practice. Children with and without AS/HFA (n = 38) were fitted with a head-mounted eye-tracker and exposed to either static or interactive dynamic facial stimuli. Average fixation duration, the proportion of fixations in areas of interest and a comparative index that was independent of differences in presentation length between stimuli types were calculated. Visual scanning patterns of individuals with AS/HFA were not affected by stimuli type. However, control participants exhibited different scanning patterns between dynamic and static stimuli for certain regions of the face. Visual scanning patterns in children with AS/HFA are consistent regardless of the stimuli being a static photo or dynamic in the form of a real face. Hence, information from experimental studies with static photos of faces provide information that is valid and can be generalised to "real world" interactions.
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