Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

Article approval pendingPaediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children

Quantifying the UK's carbon dioxide flux: An atmospheric inverse modelling approach using a regional measurement network

We present a method to derive atmosphericobservation-based estimates of carbon dioxide (CO 2 ) fluxes at the national scale, demonstrated using data from a network of surface tall-tower sites across the UK and Ireland over the period 2013-2014. The inversion is carried out using simulations from a Lagrangian chemical transport model and an innovative hierarchical Bayesian Markov chain Monte Carlo (MCMC) framework, which addresses some of the traditional problems faced by inverse modelling studies, such as subjectivity in the specification of model and prior uncertainties. Biospheric fluxes related to gross primary productivity and terrestrial ecosystem respiration are solved separately in the inversion and then combined a posteriori to determine net ecosystem exchange of CO 2 . Two different models, Data Assimilation Linked Ecosystem Carbon (DALEC) and Joint UK Land Environment Simulator (JULES), provide prior estimates for these fluxes. We carry out separate inversions to assess the impact of these different priors on the posterior flux estimates and evaluate the differences between the prior and posterior estimates in terms of missing model components. The Numerical Atmospheric dispersion Modelling Environment (NAME) is used to relate fluxes to the measurements taken across the regional network. Posterior CO2 estimates from the two inversions agree within estimated uncertainties, despite large differences in the prior fluxes from the different models. With our method, averaging results from 2013 and 2014, we find a total annual net biospheric flux for the UK of 8±79 TgCO 2 yr -1 (DALEC prior) and 64±85 TgCO 2 yr -1 (JULES prior), where negative values represent an uptake of CO 2 . These biospheric CO 2 estimates show that annual UK biospheric sources and sinks are roughly in balance. These annual mean estimates consistently indicate a greater net release of CO 2 than the prior estimates, which show much more pronounced uptake in summer months

COVID-19 Risk Factors for Cancer Patients: A First Report with Comparator Data from COVID-19 Negative Cancer Patients

none32siSimple SummaryThe COVID-19 pandemic has had a detrimental impact on cancer patients globally. Whilst there are several studies looking at the potential risk factors for COVID-19 disease and related death, most of these include non-cancerous patients as the COVID-19 negative comparator group, meaning it is difficult to draw hard conclusions as to the implications for cancer patients. In our study, we utilized data from over 2000 cancer patients from a large tertiary Cancer Centre in London. In summary, our study found that patients who are male, of Black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19. The use of cancer patients as the COVID-19 negative comparator group is a major advantage to the study as it means we can better understand the true impact of COVID-19 on cancer patients and identify which factors pose the biggest risk to their likelihood of infection with SARS-CoV2.Very few studies investigating COVID-19 in cancer patients have included cancer patients as controls. We aimed to identify factors associated with the risk of testing positive for SARS CoV2 infection in a cohort of cancer patients. We analyzed data from all cancer patients swabbed for COVID-19 between 1(st) March and 31(st) July 2020 at Guy's Cancer Centre. We conducted logistic regression analyses to identify which factors were associated with a positive COVID-19 test. Results: Of the 2152 patients tested for COVID-19, 190 (9%) tested positive. Male sex, black ethnicity, and hematological cancer type were positively associated with risk of COVID-19 (OR = 1.85, 95%CI:1.37-2.51; OR = 1.93, 95%CI:1.31-2.84; OR = 2.29, 95%CI:1.45-3.62, respectively) as compared to females, white ethnicity, or solid cancer type, respectively. Male, Asian ethnicity, and hematological cancer type were associated with an increased risk of severe COVID-19 (OR = 3.12, 95%CI:1.58-6.14; OR = 2.97, 95%CI:1.00-8.93; OR = 2.43, 95%CI:1.00-5.90, respectively). This study is one of the first to compare the risk of COVID-19 incidence and severity in cancer patients when including cancer patients as controls. Results from this study have echoed those of previous reports, that patients who are male, of black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19.openRussell, Beth; Moss, Charlotte L; Palmer, Kieran; Sylva, Rushan; D'Souza, Andrea; Wylie, Harriet; Haire, Anna; Cahill, Fidelma; Steel, Renee; Hoyes, Angela; Wilson, Isabelle; Macneil, Alyson; Shifa, Belul; Monroy-Iglesias, Maria J; Papa, Sophie; Irshad, Sheeba; Ross, Paul; Spicer, James; Kordasti, Shahram; Crawley, Danielle; Zaki, Kamarul; Sita-Lumsden, Ailsa; Josephs, Debra; Enting, Deborah; Swampillai, Angela; Sawyer, Elinor; Fields, Paul; Wrench, David; Rigg, Anne; Sullivan, Richard; Van Hemelrijck, Mieke; Dolly, SaoirseRussell, Beth; Moss, Charlotte L; Palmer, Kieran; Sylva, Rushan; D'Souza, Andrea; Wylie, Harriet; Haire, Anna; Cahill, Fidelma; Steel, Renee; Hoyes, Angela; Wilson, Isabelle; Macneil, Alyson; Shifa, Belul; Monroy-Iglesias, Maria J; Papa, Sophie; Irshad, Sheeba; Ross, Paul; Spicer, James; Kordasti, Shahram; Crawley, Danielle; Zaki, Kamarul; Sita-Lumsden, Ailsa; Josephs, Debra; Enting, Deborah; Swampillai, Angela; Sawyer, Elinor; Fields, Paul; Wrench, David; Rigg, Anne; Sullivan, Richard; Van Hemelrijck, Mieke; Dolly, Saoirs

A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart

Elevated levels of cardiac mitochondrial uncoupling protein 3 (UCP3) and decreased cardiac efficiency (hydraulic power/oxygen consumption) with abnormal cardiac function occur in obese, diabetic mice. To determine whether cardiac mitochondrial uncoupling occurs in non-genetic obesity, we fed rats a high fat diet (55% kcal from fat) or standard laboratory chow (7% kcal from fat) for 3 weeks, after which we measured cardiac function in vivo using cine MRI, efficiency in isolated working hearts and respiration rates and ADP/O ratios in isolated interfibrillar mitochondria; also, measured were medium chain acyl-CoA dehydrogenase (MCAD) and citrate synthase activities plus uncoupling protein 3 (UCP3), mitochondrial thioesterase 1 (MTE-1), adenine nucleotide translocase (ANT) and ATP synthase protein levels. We found that in vivo cardiac function was the same for all rats, yet oxygen consumption was 19% higher in high fat-fed rat hearts, therefore, efficiency was 21% lower than in controls. We found that mitochondrial fatty acid oxidation rates were 25% higher, and MCAD activity was 23% higher, in hearts from rats fed the high fat diet when compared with controls. Mitochondria from high fat-fed rat hearts had lower ADP/O ratios than controls, indicating increased respiratory uncoupling, which was ameliorated by GDP, a UCP3 inhibitor. Mitochondrial UCP3 and MTE-1 levels were both increased by 20% in high fat-fed rat hearts when compared with controls, with no significant change in ATP synthase or ANT levels, or citrate synthase activity. We conclude that increased cardiac oxygen utilisation, and thereby decreased cardiac efficiency, occurs in non-genetic obesity, which is associated with increased mitochondrial uncoupling due to elevated UCP3 and MTE-1 levels

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Mesenteric Variceal Haemorrhage and Ectopic Cushing's Syndrome as Presenting Features of a Pancreatic Neuroendocrine Tumour Recurrence

Pancreatic neuroendocrine tumours can have varied and complex presentations. Whilst hormone hypersecretion often induces characteristic clinical syndromes, non-specific symptoms may arise due to localized tumour effects. Malignant invasion of local vasculature is an increasingly recognized complication of these neoplasms and can be associated with significant morbidity. Herein, we present the case of a 47-year-old male with a recurrence of a pancreatic neuroendocrine tumour who presented with unusual upper gastrointestinal bleeding. The tumour had recurred within the superior mesenteric vein, replacing the vessel and invading its branches. This resulted in porto-mesenteric hypertension and the formation of bleeding mesenteric varices. The patient subsequently developed progressive metabolic disturbances and was diagnosed with ectopic Cushing's syndrome, despite his primary tumour having been non-functional. This case demonstrates not only a rare pattern of tumour recurrence but also the potential for pancreatic neuroendocrine tumours to de-differentiate and change from non-functional to hormone secreting, a phenomenon which may complicate diagnosis and management