Researching in cross cultural contexts: a socially just process.

In this paper, we explore culture and its relationship to cross cultural research. The context for this research is Vanuatu, a small South Pacific Island nation. The action research process used was a collaboration between two New Zealand academics, two Ni Vanuatu women researchers and 13 participants over a two year period. The focus of the action research was the design and delivery of a culturally appropriate educational leadership development programme for women. The collaborative research process raised a number of ethical and methodological considerations, for example, the importance of mutually respectful relationships, working in partnership, collaboration, capacity building, transparent communication and consideration of the local context. Using stories from the Vanuatu context, we illustrate how we navigated culture to be able to research in socially just ways. Being involved in socially just, cross cultural research calls for a thoughtful, well-designed and culturally informed approach throughout all stages of the research process, from initial planning through to follow up and capacity building and finally, the sharing of research findings

The autonomy and function of eukaryotic signal sequences : segregation of variants of preprochymosin and prelysozyme in "Xenopus oocytes" and "in vitro"

Cloned complementary DNAs encoding the secretory proteins chick prelysozyme and calf preprochymosin were inserted downstream from various viral promoters in modified recombinant “shuttle" vectors. The microinjection of these constructs into the nuclei of Xenopus laevis oocytes resulted in the efficient expression of lysozyme and prochymosin proteins which were segregated into membranes and secreted by the oocyte. The signal sequences of the proteins were correctly processed as judged from molecular weight estimations. Injection of DNA encoding prochymosin without its signal sequence resulted in the synthesis of a prochymosin protein which was localised in the oocyte cytoplasm; whereas when DNA encoding mature chymosin was injected no proteins were detected by immunoprécipitation with prochymosin antisera. The same cDNAs were subsequently cloned into SP6 vectors and synthetic, capped RNA was prepared. Following cytoplasmic injection of SP6 RNA into oocytes the same compartmentation of the proteins was observed but again no chymosin protein was detected following injection of RNA encoding mature chymosin, although translation of this RNA in vitro produced a protein with the expected molecular weight of chymosin which was precipitated by prochymosin antisera. The expression of preprochymosin messenger RNA, following cytoplasmic injection into oocytes and also using in vitro translation systems, showed the mRNA encoded two preprochymosin proteins specifically precipitated by prochymosin antisera. In the oocyte both forms were processed, segregated and secreted; whilst in vitro the precursors were cleaved on translocation within dog pancreatic microsomes where they became resistant to digestion by exogenous proteases. The translation of preprochymosin mRNA in vitro has previously been reported to produce only one major polypeptide on gel electrophoresis of products precipitated by antiprochymosin sera. The origin and nature of the two electrophoretically distinct species is not certain; but it was noted that the protein product of the cloned preprochymosin cDNA showed the same mobility on SDS-polyacrylamide gels as the faster migrating species encoded by the mRNA. Two hybrid genes were constructed encoding proteins in which the signal sequence of prelysozyme was replaced with different N-terminal regions of preprochymosin. C₆L contained a fragment from the preprochymosin cDHA which encoded the signal sequence and the first six amino acids of prochymosin; this was fused to codons 8 to 129 of mature lysozyme. The second construct C₆₂L carried a larger portion of preprochymosin, up to codon 62 of prochymosin, with the same C-terminal region of lysozyme. These fusions showed poor and variable expression following nuclear injection of the hybrid genes contained in the shuttle vector. However cytoplasmic injection of the corresponding SP6 RNAs demonstrated that both fusion proteins were synthesized in the oocyte and segregated into membranes, but did not get secreted from the oocyte. The distribution of C₆₂L protein within the oocyte corresponded with that observed for the majority of other secretory proteins including preprochymosin, with most protein fractionating with vesicles. In contrast C₆L displayed the anomalous fractionation previously observed for lysozyme, with approximately equal amounts of the processed protein fractionating with the cytoplasm and the membranes. Relative to the precursor polypeptides produced by in vitro translation of the SP6 RNAs for C₆L and C₆₂L, the respective proteins expressed in oocytes each showed an increased mobility on electrophoresis consistent with the cleavage of the signal peptide. The same processing of the preC₆L and preC₆₂L proteins was observed when in vitro translation was carried out In the presence of pancreatic mlcro6omes. The observed compartmentation and processing of these hybrid proteins Indicates that a eukaryotic signal sequence functions autonomously in Initiating the translocation of secretory proteins, but that other properties of the protein conformation are necessary to achieve subsequent secretion

Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes

Aims/hypothesis: We investigated whether biochemical cardiovascular risk factors and/or markers of subclinical cardiovascular disease were associated with the development of reduced renal function in people with type 2 diabetes. Methods: A cohort of 1066 Scottish men and women aged 60–74 years with type 2 diabetes from the Edinburgh Type 2 Diabetes Study were followed up for a median of 6.7 years. New-onset reduced renal function was defined as two eGFRs <60 ml−1 min−1 (1.73 m)−2 at least 3 months apart with a > 25% decline from baseline eGFR. Ankle brachial pressure index (ABI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) were measured at baseline. Pulse wave velocity (PWV) and carotid intima media thickness were measured 1 year into follow-up. Data were analysed using Cox proportional hazards models. Results: A total of 119 participants developed reduced renal function during follow-up. ABI, PWV, NT-proBNP and hsTnT were all associated with onset of decline in renal function following adjustment for age and sex. These associations were attenuated after adjustment for additional diabetes renal disease risk factors (systolic BP, baseline eGFR, albumin:creatinine ratio and smoking pack-years), with the exception of hsTnT which remained independently associated (HR 1.51 [95% CI 1.22, 1.87]). Inclusion of hsTnT in a predictive model improved the continuous net reclassification index by 0.165 (0.008, 0.286). Conclusions/interpretation: Our findings demonstrate an association between hsTnT, a marker of subclinical cardiac ischaemia, and subsequent renal function decline. Further research is required to establish the predictive value of hsTnT and response to intervention

Higher baseline inflammatory marker levels predict greater cognitive decline in older people with type 2 diabetes:year 10 follow-up of the Edinburgh Type 2 Diabetes Study

AIMS/HYPOTHESIS: We aimed to determine the longitudinal association of circulating markers of systemic inflammation with subsequent long-term cognitive change in older people with type 2 diabetes. METHODS: The Edinburgh Type 2 Diabetes Study is a prospective cohort study of 1066 adults aged 60 to 75 years with type 2 diabetes. Baseline data included C-reactive protein, IL-6, TNF-α fibrinogen and neuropsychological testing on major cognitive domains. Cognitive testing was repeated after 10 years in 581 participants. A general cognitive ability score was derived from the battery of seven individual cognitive tests using principal component analysis. Linear regression was used to determine longitudinal associations between baseline inflammatory markers and cognitive outcomes at follow-up, with baseline cognitive test results included as covariables to model cognitive change over time. RESULTS: Following adjustment for age, sex and baseline general cognitive ability, higher baseline fibrinogen and IL-6 were associated with greater decline in general cognitive ability (standardised βs = −0.059, p=0.032 and −0.064, p=0.018, respectively). These associations lost statistical significance after adjustment for baseline vascular and diabetes-related covariables. When assessing associations with individual cognitive tests, higher IL-6 was associated with greater decline in tests of executive function and abstract reasoning (standardised βs = 0.095, p=0.006 and −0.127, p=0.001, respectively). Similarly, raised fibrinogen and C-reactive protein levels were associated with greater decline in processing speed (standardised βs = −0.115, p=0.001 and −0.111, p=0.001, respectively). These associations remained statistically significant after adjustment for the diabetes- and vascular-related risk factors. CONCLUSIONS/INTERPRETATION: Higher baseline levels of inflammatory markers, including plasma IL-6, fibrinogen and C-reactive protein, were associated with subsequent cognitive decline in older people with type 2 diabetes. At least some of this association appeared to be specific to certain cognitive domains and to be independent of vascular and diabetes-related risk factors. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05634-w

‘Surgery is my only hope’:A qualitative study exploring perceptions of living with obesity and the prospect of having bariatric surgery

Summary: The health benefits of bariatric surgery are well documented; however, the occurrence of weight‐regain after surgery, along with the development of mental health difficulties poses a question of how contemporary psychology could assist to prepare people living with obesity prior to undergoing bariatric surgery. This research explored individuals' (in the immediate pre‐operative and post‐operative population) attitudes, beliefs and experiences towards obesity and their journey to bariatric surgery. Seventeen adult participants (males n = 4; age range: 26–64 years) were recruited and participated in a semi‐structured interview. Twelve individuals participated prior to undergoing bariatric surgery. Five individuals participated in the early post‐operative period

The protective effect of SARS-CoV-2 antibodies in Scottish healthcare workers

BACKGROUND: Healthcare workers (HCW) are believed to be at increased risk of SARS-CoV-2 infection. It is not known to what extent the natural production of antibodies to SARS-CoV-2 is protective against re-infection. METHODS: A prospective observational study of HCW's in Scotland (UK) from May to September 2020. The Siemens SARS-CoV-2 total antibody assay was used to establish seroprevalence in this cohort. Controls, matched for age and sex to the general local population, were studied for comparison. New infections (up to 2/12/2020) post antibody testing were recorded to determine if the presence of SARS-CoV-2 antibodies protect against re-infection. RESULTS: A total of 2063 health and social care workers were recruited for this study. At enrolment 300 HCW had a positive antibody test (14.5%). 11/231 control sera tested positive (4.8%). HCW therefore had an increased likelihood of a positive test (Odds ratio 3.4 95% CI 1.85–6.16, p<0.0001). Dentists were most likely to test positive. 97.3% of patients who had previously tested positive for SARS-CoV-2 by RT-PCR had positive antibodies. 18.7% had an asymptomatic infection. There were 38 new infections with SARS-CoV-2 in HCW who were previously antibody negative and one symptomatic RT-PCR positive re-infection. The presence of antibodies was therefore associated with an 85% reduced risk of re-infection with SARS-CoV-2 (HR 0.15, 95% CI 0.06 to 0.35, p=0.026). CONCLUSION: HCW were three times more likely to test positive for SARS-CoV-2 than the general population. Almost all infected individuals developed an antibody response which was 85% effective in protecting against re-infection with SARS-CoV-2

Using non-invasive biomarkers to identify hepatic fibrosis in people with type 2 diabetes mellitus: the Edinburgh type 2 diabetes study

BACKGROUND & AIMS: It is difficult to determine the different stages of non-alcoholic fatty liver disease without the use of invasive liver biopsy. In this study we investigated five non-invasive biomarkers used previously to detect hepatic fibrosis and determined the level of agreement between them in order to inform future research. METHODS: In the Edinburgh Type 2 Diabetes Study, a population-based cohort aged 60-74 years with type 2 diabetes, 831 participants underwent ultrasound assessment for fatty liver and had serum aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), aspartate to platelet ratio index (APRI), European Liver Fibrosis panel (ELF), Fibrosis-4 Score (FIB4) and liver stiffness measurement (LSM) measured. RESULTS: Literature based cut-offs yielded marked differences in the proportions of the cohort with probable liver fibrosis in the full cohort. Agreement between the top 5% of the distribution for each biomarker pair was poor. APRI and FIB4 had the best positive agreement at 76.4%, but agreement for all of the other serum biomarker pairs was between 18% and 34%. Agreement with LSM was poor (9-16%). CONCLUSIONS: We found poor correlation between the five biomarkers of liver fibrosis studied. Using the top 5% of each biomarker resulted in good agreement on the absence of advanced liver disease but poor agreement on the presence of advanced disease. Further work is required to validate these markers against liver biopsy and to determine their predictive value for clinical liver-related endpoints, in a range of different low and high risk population groups

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis