The COVID-19 Pandemic and Its Implications for Rural Economies

This paper presents a rapid assessment of current and likely future impacts of the COVID-19 outbreak on rural economies given their socio-economic characteristics. Drawing principally on current evidence for the UK, as well as lessons from the 2001 Foot and Mouth Disease outbreak and the 2007/8 financial crises, it outlines the likely key demand and supply effects, paying attention to the situation for agriculture as well as discussing the implications for rural communities. A distinction is made between the effects on businesses offering goods and services for out-of-home as opposed to in-home consumption. Gendered dimensions are also noted as likely business and household strategies for coping and adaptation. The paper concludes with a brief mapping of a research agenda for studying the longer-term effects of COVID-19 on rural economies

Evidence that Fetal Death is Associated with Placental Aging

Background: The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. Objective: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. Study Design: We collected placentas from women at 37-39 weeks’ gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. Results: Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the aldehyde oxidase 1 inhibitor raloxifene. Conclusion: Our data are consistent with a role for aldehyde oxidase 1 and G-protein-coupled estrogen receptor 1 in mediating aging of the placenta that may contribute to stillbirth. The placenta is a tractable model of aging in human tissue

The pathogenic diversity and host range of Colletotrichum spp. causing pepper spot and anthracnose of lychee (Litchi chinensis) in Australia

Lychee pepper spot, a field disease affecting lychee fruit skin, pedicels and petioles, is caused by Colletotrichum siamense, a fungal pathogen within the gloeosporioides species complex. Members of Colletotrichum from the gloeosporioides species complex and occasionally those from the acutatum species complex also cause postharvest anthracnose of lychee. Pepper spot was first described in Australia many years after anthracnose on lychee was first described, giving rise to the hypothesis that a novel species or strain within the gloeosporioides species complex causes pepper spot. In the present study, 19 isolates of Colletotrichum spp., collected from pepper spot and anthracnose symptoms on lychee fruit, representing 13 different genotypes across five species, were inoculated onto lychee fruit in the field or on detached fruit in the laboratory, to understand more about their pathogenic diversity. We found that symptoms were specific to genotype of the pathogen, as three genetically similar isolates of C. siamense consistently caused pepper spot and anthracnose, whilst other isolates caused anthracnose only. Cross-inoculation studies on detached fruit of lychee, banana, avocado and mango also provided some evidence of host specialization in isolates of C. siamense infecting lychee in Australia. Our experiments provided further evidence that detached fruit assays cannot be used as a reliable proxy for field inoculation studies. This research confirms that C. siamense is a causal agent of both lychee pepper spot and lychee anthracnose in Australia, and Colletotrichum alienum and Colletotrichum queenslandicum are reported as causal agents of anthracnose of lychee for the first time

Green and brown bridges between weeds and crops reveal novel Diaporthe species in Australia

Diaporthe (syn. Phomopsis) species are well-known saprobes, endophytes or pathogens on a range of plants. Several species have wide host ranges and multiple species may sometimes colonise the same host species. This study describes eight novel Diaporthe species isolated from live and/or dead tissue from the broad acre crops lupin, maize, mungbean, soybean and sunflower, and associated weed species in Queensland and New South Wales, as well as the environmental weed bitou bush (Chrysanthemoides monilifera subsp. rotundata) in eastern Australia. The new taxa are differentiated on the basis of morphology and DNA sequence analyses based on the nuclear ribosomal internal transcribed spacer region, and part of the translation elongation factor-1α and ß-tubulin genes. The possible agricultural significance of live weeds and crop residues ('green bridges') as well as dead weeds and crop residues ('brown bridges') in aiding survival of the newly described Diaporthe species is discussed

Improving arteriovenous fistula patency : transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation

Creation of an autologous arteriovenous fistula (AVF) for vascular access in haemodialysis is the modality of choice. However neointimal hyperplasia and loss of the luminal compartment result in AVF patency rates of ~60% at 12months. The exact cause of neointimal hyperplasia in the AVF is poorly understood. Vascular trauma has long been associated with hyperplasia. With this in mind in our rabbit model of AVF we simulated cannulation autologous to that undertaken in vascular access procedures and observed significant neointimal hyperplasia as a direct consequence of cannulation. The neointimal hyperplasia was completely inhibited by topical transdermal delivery of the non-steroidal anti-inflammatory (NSAID) diclofenac. In addition to the well documented anti-inflammatory properties we have identified novel anti-proliferative mechanisms demonstrating diclofenac increases AMPK-dependent signalling and reduced expression of the cell cycle protein cyclin D1. In summary prophylactic transdermal delivery of diclofenac to the sight of AVF cannulation prevents adverse neointimal hyperplasic remodelling and potentially offers a novel treatment option that may help prolong AVF patency and flow rates

Improving arteriovenous fistula patency : transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation

Creation of an autologous arteriovenous fistula (AVF) for vascular access in haemodialysis is the modality of choice. However neointimal hyperplasia and loss of the luminal compartment result in AVF patency rates of ~60% at 12months. The exact cause of neointimal hyperplasia in the AVF is poorly understood. Vascular trauma has long been associated with hyperplasia. With this in mind in our rabbit model of AVF we simulated cannulation autologous to that undertaken in vascular access procedures and observed significant neointimal hyperplasia as a direct consequence of cannulation. The neointimal hyperplasia was completely inhibited by topical transdermal delivery of the non-steroidal anti-inflammatory (NSAID) diclofenac. In addition to the well documented anti-inflammatory properties we have identified novel anti-proliferative mechanisms demonstrating diclofenac increases AMPK-dependent signalling and reduced expression of the cell cycle protein cyclin D1. In summary prophylactic transdermal delivery of diclofenac to the sight of AVF cannulation prevents adverse neointimal hyperplasic remodelling and potentially offers a novel treatment option that may help prolong AVF patency and flow rates

The Wellbeing of Working-Age Adults with and without Disability in the UK : Associations with Age, Gender, Ethnicity, Partnership Status, Educational Attainment and Employment Status

Background Few population-based studies have examined the association between disability and personal wellbeing (PWB) among working-age adults. Objective/Hypothesis: To determine: (1) the magnitude of differences in wellbeing between working-age adults with and without disability in contemporary samples representative of the UK population; and (2) whether the size of any observed differences between people with and without disability is moderated by age, gender, ethnicity, partnership status, educational attainment or employment status. Methods Secondary analysis of data from three national cross-sectional surveys. Results In each survey, people with disability scored lower than people without disability on all four indicators of PWB. Adjusting for the main effects of potentially moderating variables reduced the effect size of disability on PWB by an average of 24%. Subsequently adjusting for the two-way interaction terms between disability and potentially moderating variables reduced the effect size of disability (main effect) on PWB by an additional average of 73%. PWB among people with disability was significantly lower for: (1) men; (2) younger people; (3) those who belong to the majority ethnic group (white British); (4) those without a partner; and (5) people with lower socio-economic position. Conclusions Our findings indicate that demographic characteristics and exposure to specific social determinants of poor health play a major role in the negative association between disability and personal wellbeing. A more sophisticated understanding of how social determinants interact to produce inequities associated with identities such as disability, gender, race, sexuality, and class (intersectionality) can inform effective policy interventions

Ocular late effects in childhood and adolescent cancer survivors: A report from the childhood cancer survivor study

Introduction—Approximately 80% of children currently survive 5 years following diagnosis of their cancer. Studies based on limited data have implicated certain cancer therapies in the development of ocular sequelae in these survivors. Procedure—The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study investigating health outcomes of 5+ year survivors diagnosed and treated between 1970 and 1986 compared to a sibling cohort. The baseline questionnaire included questions about the first occurrence of 6 ocular conditions. Relative risks (RR) and 95% confidence intervals (CI) were calculated from responses of 14,362 survivors and 3,901 siblings. Results—Five or more years from the diagnosis, survivors were at increased risk of cataracts (RR:10.8; 95% CI: 6.2–18.9), glaucoma (RR: 2.5; 95% CI: 1.1–5.7), legal blindness (RR: 2.6; 95% CI: 1.7–4.0), double vision (RR:4.1; 95% CI: 2.7–6.1), and dry eyes (RR: 1.9; 95% CI: 1.6–2.4), when compared to siblings. Dose of radiation to the eye was significantly associated with risk of cataracts, legal blindness, double vision, and dry eyes, in a dose-dependent fashion. Risk of cataracts were also associated with radiation 3000+ cGy to the posterior fossa (RR: 8.4; 95% CI: 5.0–14.3), temporal lobe (RR: 9.4; 95% CI: 5.6–15.6), and exposure to prednisone (RR:2.3; 95% CI:.1.6–3.4) Conclusions—Childhood cancer survivors are at risk of developing late occurring ocular complications, with exposure to glucocorticoids and cranial radiation being important determinants of increased risk. Long-term follow-up is needed to evaluate potential progression of ocular deficits and impact on quality of life

Health and healthcare for people with disabilities in the UK during the COVID-19 pandemic

BACKGROUND: While emerging evidence shows increased mortality from COVID-19 among people with disability, evidence regarding whether there are disability-related inequalities in health during the pandemic is lacking. OBJECTIVE: This study compares access to COVID-19 and non-COVID-19 related health care and mental health of people with and without disability. METHODS: Longitudinal analysis of 12,703 adults (16-64 years) who participated in W9 (2017-2019) and the April and/or May COVID-19 special surveys of the UK Understanding Society study. Descriptive analyses and Poisson regression (adjusted for age, gender, ethnicity and financial stress) were conducted to estimate associations between disability (measured at Wave 9) and a number of different COVID-19-related health and health care outcomes (COVID-19 symptoms, testing and hospitalisation), mental health and loneliness, and non-COVID-19 related health care (e.g. outpatient and inpatient hospital care, prescription medications). RESULTS: Results from the fully-adjusted regression models found that people with disability were more likely: to be hospitalised if symptomatic (adjusted PRR 3.0 95% 1.07-8.43); to experience current symptoms of psychological distress (PRR 1.15, 95% CI 1.05-1.26) and to report being lonely (PRR 1.75, 95% CI 1.46-2.09) compared to non-disabled people. People with disability reported much higher levels of comorbidities than people without disability. However, inability to access health care and treatment were similar. CONCLUSIONS: As the UK opens up, it is important that health care services and social policy address the poor mental health and social isolation of people with disability so that the inequalities occurring early in the pandemic do not become further entrenched

Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing

Objectives It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. Methods This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. Results Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. Conclusions Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based AR