The Adaptive Cycle As a Lens for Service Learning – Community Engagement Partnerships

This paper deploys the adaptive cycle as a construct to understand the dynamics of community engagement and partnership building during an international service-learning project. A multi-disciplinary team of USA-based university students collaborated with a local community in Zambia to build two ventilated improved pit (VIP) latrines. Post-field project reflection challenged the ‘product-first’ view commonly held in service learning projects.  Time was a central point of post-field reflection. Through critical scrutiny, the team came to recognize that contextually sensitive relationship building had been essential in enabling community ownership of the project.  The construct of the adaptive cycle provided a crucial analytical tool for tracing the process through which partners from very different backgrounds achieved a sense of common purpose and opened the way for an understanding of community engagement as weaving a thread through the complex dynamics of partnership. The adaptive cycle may be useful in the preparation and implementation framework for other service learning projects emanating from institutions of higher education

Osteoprotegerin reduces the development of pain behaviour and joint pathology in a model of osteoarthritis

Acknowledgements: OPG-Fc was a kind gift from Amgen Ltd. Funding: This work was supported by Arthritis Research UK, grant number 18769Peer reviewedPublisher PD

Sociodemographic Variations in the Uptake of Faecal Immunochemical Tests in Primary Care

Background: Faecal Immunochemical Testing (FIT) usage for symptomatic patients is increasing, but variations in use by sociodemographics are unknown. We introduced FIT for symptomatic patients in November 2017. Aim: Identify whether demographics, ethnicity or social deprivation affect FIT return in symptomatic patients. Design and Setting: FIT was introduced as a triage tool in Primary Care and was mandated for all colorectal referrals (except rectal bleeding/mass) to secondary care. FIT was used, alongside full blood count and ferritin, to stratify colorectal cancer risk. Method: All referrals November 2017-December 2021 were retrospectively reviewed. Sociodemographic factors affecting FIT return were analysed by multivariate logistic regression. Results: 35,289 patients returned their index FIT (90.7%), 3631 (9.3%) did not. On multivariate analysis, males were less likely to return FIT (OR 1.11, 95%CI 1.03-1.19). Patients over 65 were more likely to return FIT (OR 0.78 for non-return, 95%CI 0.72-0.83). Unreturned FIT was more than doubled in the most compared to the least deprived (OR 2.20, 95%CI 1.99-2.43). Patients from Asian (OR 1.82, 95%CI 1.58-2.10), Black (OR 1.21, 95%CI 0.98-1.49) and Mixed/Other ethnic groups (OR 1.29, 95%CI 1.05-1.59) were more likely to not return FIT compared to White ethnicity. 599 colorectal cancers were detected (1.5%), 561 in those who returned a first FIT request, 38 in those who did not. Conclusion: FIT return in those suspected of having colorectal cancer varies by gender, age, ethnicity, and socioeconomic deprivation. Strategies to mitigate effects on FIT return and colorectal cancer detection should be considered as FIT usage expands

Faecal immunochemical testing and blood tests for prioritization of urgent colorectal cancer referrals in symptomatic patients: a 2-year evaluation

BackgroundA novel pathway incorporating faecal immunochemical testing (FIT) for rapid colorectal cancer diagnosis (RCCD) was introduced in 2017. This paper reports on the service evaluation after 2 years of pathway implementation.MethodsThe RCCD protocol was based on FIT, blood results and symptoms to stratify adult patients in primary care. Two-week-wait (2WW) investigation was indicated for patients with rectal bleeding, rectal mass and faecal haemoglobin (fHb) level of 10 µg Hb/g faeces or above or 4 µg Hb/g faeces or more in the presence of anaemia, low ferritin or thrombocytosis, in all other symptom groups. Patients with 100 µg Hb/g faeces or above had expedited investigation . A retrospective audit of colorectal cancer detected between 2017 and 2019 was conducted, fHb thresholds were reviewed and critically assessed for cancer diagnoses.ResultsIn 2 years, 14788 FIT tests were dispatched with 13361 (90.4 per cent) completed returns. Overall, fHb was less than 4 µg Hb/g faeces in 9208 results (68.9 per cent), 4–9.9 µg Hb/g in 1583 (11.8 per cent), 10–99.9 µg Hb/g in 1850 (13.8 per cent) and 100 µg Hb/g faeces or above in 720 (5.4 per cent). During follow-up (median 10.4 months), 227 colorectal cancers were diagnosed. The cancer detection rate was 0.1 per cent in patients with fHb below 4 µg Hb/g faeces, 0.6 per cent in those with fHb 4–9.9 µg Hb/g faeces, 3.3 per cent for fHb 10–99.9 µg Hb/g faeces and 20.7 per cent for fHb 100 µg Hb/g faeces or above. The detection rate in the cohort with 10–19.9 µg Hb/g faeces was 1.4 per cent, below the National Institute for Health and Care Excellence threshold for urgent referral. The colorectal cancer rate in patients with fHb below 20 µg Hb/g faeces was less than 0.3 per cent.ConclusionUse of FIT to "rule out" urgent referral from primary care misses a small number of cases. The threshold for referral may be adjusted with blood results to improve stratification

Choice of faecal immunochemical test matters: Comparison of OC-Sensor and HM-JACKarc, in the assessment of patients at high risk of colorectal cancer

Objectives: Currently NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 μg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed.Methods: Two specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 µg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons.Results: 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 µg Hb/g faeces for OC-S and 318.1 and 1.0 µg Hb/g faeces for HM-J respectively.Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p[less than]0.001. Using a f-Hb of 4μg Hb/g faeces for both tests found an agreement of 88.1%, at 10μg Hb/g faeces 91.7% and at 150μg Hb/g faeces 96.3%.114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p[less than]0.001.Conclusion: We found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb

The SHARP study: a quantitative and qualitative evaluation of the short-term outcomes of housing and neighbourhood renewal

<p><b>Background:</b> The SHARP study was set up to evaluate the short (1 year) and longer-term (2 year) effects on health and wellbeing of providing new social housing to tenants. This paper presents the study background, the design and methods, and the findings at one year.</p> <p><b>Methods:</b> Data were collected from social tenants who were rehoused into a new, general-purpose socially-rented home developed and let by a Scottish Registered Social Landlord (the "Intervention" group). These data were collected at three points in time: before moving (Wave 1), one year after moving (Wave 2) and two years after moving (Wave 3). Data were collected from a Comparison group using the same methods at Baseline (Wave 1) and after two years of follow-up (Wave 3). Qualitative data were also collected by means of individual interviews. This paper presents the quantitative and qualitative findings at 1 year (after Wave 2).</p> <p><b>Results:</b> 339 Intervention group interviews and 392 Comparison group interviews were completed. One year after moving to a new home there was a significant reduction in the proportion of Intervention group respondents reporting problems with the home, such as damp and noise. There was also a significant increase in neighbourhood satisfaction compared with Baseline (χ2 = 35.51, p < 0.0001). Many aspects of the neighbourhood improved significantly, including antisocial behaviour. In terms of environmental aspects and services the greatest improvements were in the general appearance of the area, the reputation of the area, litter and rubbish, and speeding traffic. However, lack of facilities for children/young people and lack of safe children's play areas remained a concern for tenants.</p> <p><b>Conclusion:</b> This study found that self-reported health changed little in the first year after moving. Nonetheless, the quantitative and qualitative data point to improvements in the quality of housing and of the local environment, as well as in tenant satisfaction and other related outcomes. Further analyses will explore whether these effects are sustained, and whether differences in health outcomes emerge at 2 years compared with the Comparison group.</p&gt

Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults

Background & aims: Mortality resulting from influenza (flu) virus infections occurs primarily in the elderly through declining immunity. Studies in mice have suggested beneficial effects of selenium (Se) supplementation on immunity to flu but similar evidence is lacking in humans. A dietary intervention study was therefore designed to test the effects of Se-supplementation on a variety of parameters of anti-flu immunity in healthy subjects aged 50–64 years. Methods: A 12-week randomized, double-blinded, placebo-controlled clinical trial (ClinicalTrials.gov NCT00279812) was undertaken in six groups of individuals with plasma Se levels <110 ng/mL. Four groups were given daily capsules of yeast enriched with 0 μg Se/day (SeY-0/d; n = 20), 50 μg Se/d (SeY-50/d; n = 18), 100 μg Se/d (SeY-100/d; n = 21) or 200 μg Se/d (SeY-200/d; n = 23). Two groups were given onion-containing meals with either <1 μg Se/d (SeO-0/d; n = 17) or 50 μg Se/d (SeO-50/d; n = 18). Flu vaccine was administrated at week 10 and immune parameters were assessed until week 12. Results: Primary study endpoints were changes in cellular and humoral immune responses. Supplementation with SeY and SeO affected different aspects of cellular immunity. SeY increased Tctx-ADCC cell counts in blood (214%, SeY-100/d) before flu vaccination and a dose-dependent increase in T cell proliferation (500%, SeY-50/100/200/d), IL-8 (169%, SeY-100/d) and IL-10 (317%, SeY-200/d) secretion after in vivo flu challenge. Positive effects were contrasted by lower granzyme B content of CD8 cells (55%, SeY-200/d). SeO (Se 50 μg/d) also enhanced T cell proliferation after vaccination (650%), IFN-γ (289%), and IL-8 secretion (139%), granzyme (209%) and perforin (190%) content of CD8 cells but inhibited TNF-α synthesis (42%). Onion on its own reduced the number of NKT cells in blood (38%). These effects were determined by comparison to group-specific baseline yeast or onion control groups. Mucosal flu-specific antibody responses were unaffected by Se-supplementation. Conclusion: Se-supplementation in healthy human adults with marginal Se status resulted in both beneficial and detrimental effects on cellular immunity to flu that was affected by the form of Se, supplemental dose and delivery matrix. These observations call for a thorough evaluation of the risks and benefits associated with Se-supplementation

Convergent evidence that ZNF804A is a regulator of pre-messenger RNA processing and gene expression

Genome-wide association studies have linked common variation in ZNF804A with an increased risk of schizophrenia. However, little is known about the biology of ZNF804A and its role in schizophrenia. Here, we investigate the function of ZNF804A using a variety of complementary molecular techniques. We show that ZNF804A is a nuclear protein that interacts with neuronal RNA splicing factors and RNA-binding proteins including RBFOX1, which is also associated with schizophrenia, CELF3/4, components of the ubiquitin-proteasome system and the ZNF804A paralog, GPATCH8. GPATCH8 also interacts with splicing factors and is localized to nuclear speckles indicative of a role in pre-messenger RNA (mRNA) processing. Sequence analysis showed that GPATCH8 contains ultraconserved, alternatively spliced poison exons that are also regulated by RBFOX proteins. ZNF804A knockdown in SH-SY5Y cells resulted in robust changes in gene expression and pre-mRNA splicing converging on pathways associated with nervous system development, synaptic contact, and cell adhesion. We observed enrichment (P = 1.66 × 10–9) for differentially spliced genes in ZNF804A-depleted cells among genes that contain RBFOX-dependent alternatively spliced exons. Differentially spliced genes in ZNF804A-depleted cells were also enriched for genes harboring de novo loss of function mutations in autism spectrum disorder (P = 6.25 × 10–7, enrichment 2.16) and common variant alleles associated with schizophrenia (P = .014), bipolar disorder and schizophrenia (P = .003), and autism spectrum disorder (P = .005). These data suggest that ZNF804A and its paralogs may interact with neuronal-splicing factors and RNA-binding proteins to regulate the expression of a subset of synaptic and neurodevelopmental genes

Serum autoantibody measurement for the detection of hepatocellular carcinoma

Background: Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC) which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs) in the serum of patients with HCC.Methods: Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA.Results: Varying autoantibody specificities (97–100%) and sensitivities (0–10%) were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel.Conclusions: This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography) and to similar tests in other cancers (EarlyCDT-Lung)

Determinants of Non-Vaccination against Pandemic 2009 H1N1 Influenza in Pregnant Women: A Prospective Cohort Study

International audienceBACKGROUND: In October 2009, the French government organized a national-wide, free of charge vaccination campaign against pandemic H1N1 influenza virus, especially targeting pregnant women, a high risk group for severe illness. The study objective was to evaluate pandemic flu vaccine uptake and factors associated with non-vaccination in a population of pregnant women. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective cohort conducted in 3 maternity hospitals in Paris, 882 pregnant women were randomly included between October 12, 2009 and February 3, 2010, with the aim to study characteristics of pandemic influenza during pregnancy. At inclusion, socio-demographic, medical, obstetrical factors and those associated with a higher risk of flu exposition and disease-spreading were systematically collected. Pandemic flu vaccine uptake was checked until delivery. 555 (62.9%) women did not get vaccinated. Determinants associated with non-vaccination in a multivariate logistic regression were: geographic origin (Sub-Saharan African origin, adjusted Odd Ratio aOR = 5.4[2.3-12.7], North African origin, aOR = 2.5[1.3-4.7] and Asian origin, aOR = 2.1[1.7-2.6] compared to French and European origin) and socio-professional categories (farmers, craftsmen and tradesmen, aOR = 2.3[2.0-2.6], intermediate professionals, aOR = 1.3[1.0-1.6], employees and manual workers, aOR = 2.5[1.4-4.4] compared to managers and intellectual professionals). The probability of not receiving pandemic flu vaccine was lower among women vaccinated against seasonal flu in the previous 5 years (aOR = 0.6[0.4-0.8]) and among those who stopped smoking before or early during pregnancy (aOR = 0.6[0.4-0.8]). Number of children less than 18 years old living at home, work in contact with children or in healthcare area, or professional contact with the public, were not associated with a higher vaccine uptake. CONCLUSIONS/SIGNIFICANCE: In this cohort of pregnant women, vaccine coverage against pandemic 2009 A/H1N1 flu was low, particularly in immigrant women and those having a low socio-economic status. To improve its effectiveness, future vaccination campaign for pregnant women should be more specifically tailored for these populations