High Accuracy of Common HIV-Related Oral Disease Diagnoses by Non-Oral Health Specialists in the AIDS Clinical Trial Group

Objective: Many studies include oral HIV-related endpoints that may be diagnosed by non-oral-health specialists (non-OHS) like nurses or physicians. Our objective was to assess the accuracy of clinical diagnoses of HIV-related oral lesions made by non-OHS compared to diagnoses made by OHS. Methods: A5254, a cross-sectional study conducted by the Oral HIV/AIDS Research Alliance within the AIDS Clinical Trial Group, enrolled HIV-1-infected adults participants from six clinical trial units (CTU) in the US (San Francisco, New York, Chapel Hill, Cleveland, Atlanta) and Haiti. CTU examiners (non-OHS) received standardized training on how to perform an oral examination and make clinical diagnoses of specific oral disease endpoints. Diagnoses by calibrated non-OHS were compared to those made by calibrated OHS, and sensitivity and specificity computed. Results: Among 324 participants, the majority were black (73%), men (66%), and the median CD4+ cell count 138 cells/mm3. The overall frequency of oral mucosal disease diagnosed by OHS was 43% in US sites, and 90% in Haiti. Oral candidiasis (OC) was detected in 153 (47%) by OHS, with erythematous candidiasis (EC) the most common type (39%) followed by pseudomembranous candidiasis (PC; 26%). The highest prevalence of OC (79%) was among participants in Haiti, and among those with CD4+ cell count ≤ 200 cells/mm3 and HIV-1 RNA > 1000 copies/mL (71%). The sensitivity and specificity of OC diagnoses by non-OHS were 90% and 92% (for EC: 81% and 94%; PC: 82% and 95%). Sensitivity and specificity were also high for KS (87% and 94%, respectively), but sensitivity was < 60% for HL and oral warts in all sites combined. The Candida culture confirmation of OC clinical diagnoses (as defined by ≥ 1 colony forming unit per mL of oral/throat rinse) was ≥ 93% for both PC and EC. Conclusion: Trained non-OHS showed high accuracy of clinical diagnoses of OC in comparison with OHS, suggesting their usefulness in studies in resource-poor settings, but detection of less common lesions may require OHS

Pangolins in global camera trap data: Implications for ecological monitoring

Despite being heavily exploited, pangolins (Pholidota: Manidae) have been subject to limited research, resulting in a lack of reliable population estimates and standardised survey methods for the eight extant species. Camera trapping represents a unique opportunity for broad-scale collaborative species monitoring due to its largely non-discriminatory nature, which creates considerable volumes of data on a relatively wide range of species. This has the potential to shed light on the ecology of rare, cryptic and understudied taxa, with implications for conservation decision-making. We undertook a global analysis of available pangolin data from camera trapping studies across their range in Africa and Asia. Our aims were (1) to assess the utility of existing camera trapping efforts as a method for monitoring pangolin populations, and (2) to gain insights into the distribution and ecology of pangolins. We analysed data collated from 103 camera trap surveys undertaken across 22 countries that fell within the range of seven of the eight pangolin species, which yielded more than half a million trap nights and 888 pangolin encounters. We ran occupancy analyses on three species (Sunda pangolin Manis javanica, white-bellied pangolin Phataginus tricuspis and giant pangolin Smutsia gigantea). Detection probabilities varied with forest cover and levels of human influence for P. tricuspis, but were low (<0.05) for all species. Occupancy was associated with distance from rivers for M. javanica and S. gigantea, elevation for P. tricuspis and S. gigantea, forest cover for P. tricuspis and protected area status for M. javanica and P. tricuspis. We conclude that camera traps are suitable for the detection of pangolins and large-scale assessment of their distributions. However, the trapping effort required to monitor populations at any given study site using existing methods appears prohibitively high. This may change in the future should anticipated technological and methodological advances in camera trapping facilitate greater sampling efforts and/or higher probabilities of detection. In particular, targeted camera placement for pangolins is likely to make pangolin monitoring more feasible with moderate sampling efforts

Pangolins in Global Camera Trap Data: Implications for Ecological Monitoring

Despite being heavily exploited, pangolins (Pholidota: Manidae) have been subject to limited research, resulting in a lack of reliable population estimates and standardised survey methods for the eight extant species. Camera trapping represents a unique opportunity for broad-scale collaborative species monitoring due to its largely non-discriminatory nature, which creates considerable volumes of data on a relatively wide range of species. This has the potential to shed light on the ecology of rare, cryptic and understudied taxa, with implications for conservation decision-making. We undertook a global analysis of available pangolin data from camera trapping studies across their range in Africa and Asia. Our aims were (1) to assess the utility of existing camera trapping efforts as a method for monitoring pangolin populations, and (2) to gain insights into the distribution and ecology of pangolins. We analysed data collated from 103 camera trap surveys undertaken across 22 countries that fell within the range of seven of the eight pangolin species, which yielded more than half a million trap nights and 888 pangolin encounters. We ran occupancy analyses on three species (Sunda pangolin Manis javanica, white-bellied pangolin Phataginus tricuspis and giant pangolin Smutsia gigantea). Detection probabilities varied with forest cover and levels of human influence for P. tricuspis, but were low (M. javanica and S. gigantea, elevation for P. tricuspis and S. gigantea, forest cover for P. tricuspis and protected area status for M. javanica and P. tricuspis. We conclude that camera traps are suitable for the detection of pangolins and large-scale assessment of their distributions. However, the trapping effort required to monitor populations at any given study site using existing methods appears prohibitively high. This may change in the future should anticipated technological and methodological advances in camera trapping facilitate greater sampling efforts and/or higher probabilities of detection. In particular, targeted camera placement for pangolins is likely to make pangolin monitoring more feasible with moderate sampling efforts

The influence of speed and size on avian terrestrial locomotor biomechanics: predicting locomotion in extinct theropod dinosaurs

How extinct, non-avian theropod dinosaurs moved is a subject of considerable interest and controversy. A better understanding of non-avian theropod locomotion can be achieved by better understanding terrestrial locomotor biomechanics in their modern descendants, birds. Despite much research on the subject, avian terrestrial locomotion remains little explored in regards to how kinematic and kinetic factors vary together with speed and body size. Here, terrestrial locomotion was investigated in twelve species of ground-dwelling bird, spanning a 1,780-fold range in body mass, across almost their entire speed range. Particular attention was devoted to the ground reaction force (GRF), the force that the feet exert upon the ground. Comparable data for the only other extant obligate, striding biped, humans, were also collected and studied. In birds, all kinematic and kinetic parameters examined changed continuously with increasing speed, while in humans all but one of those same parameters changed abruptly at the walk-run transition. This result supports previous studies that show birds to have a highly continuous locomotor repertoire compared to humans, where discrete ‘walking’ and ‘running’ gaits are not easily distinguished based on kinematic patterns alone. The influences of speed and body size on kinematic and kinetic factors in birds are developed into a set of predictive relationships that may be applied to extinct, non-avian theropods. The resulting predictive model is able to explain 79–93% of the observed variation in kinematics and 69–83% of the observed variation in GRFs, and also performs well in extrapolation tests. However, this study also found that the location of the whole-body centre of mass may exert an important influence on the nature of the GRF, and hence some caution is warranted, in lieu of further investigation

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

Novel markers in chronic liver disease and hepatocellular carcinoma

© 2013 Anthony Philip RodeChronic liver disease is associated with a number of metabolic changes and nutritional deficiencies, and these may have important consequences on the natural history of liver disease. Chronic liver disease is a continuum of progressive liver fibrosis with replacement of injured tissue by a collagenous scar. Fibrosis is a multi-step process and progresses at variable rates depending on the cause of the liver disease, environmental factors, and host factors. Cirrhosis is an advanced stage of liver fibrosis, and is a common cause of morbidity and mortality worldwide, including a predisposition to hepatocellular carcinoma of 2–7% per year. Hepatocellular carcinoma is one of the most common malignant tumours in the world accounting for 500,000 deaths per year, making it the 3rd most common cause of cancer death worldwide. In this thesis, I have reviewed the epidemiology, natural history and current investigations used in chronic liver disease and hepatocellular carcinoma. The progression of liver disease to cirrhosis, and hepatocellular carcinoma, are multi-step pathways. The poor outcomes highlight the need for novel factors to be explored to determine if they can predict and/or alter the natural history. In this thesis, I review the previous literature on CD163, CD147 and 25(OH)D as novel markers in liver disease assessment, to determine their relationship to liver disease severity and outcome. CD163 is a marker of activated macrophages and sCD163 is found in normal plasma. Upregulation of sCD163 occurs during inflammation and increased levels are seen in acute and chronic liver disease. Routine biochemistry and imaging are often insensitive for complications of chronic liver disease, and in this thesis we demonstrate that sCD163 levels predict chronic liver disease progression and portal hypertension. sCD163 is a good marker of chronic liver disease patients who have developed cirrhosis, stratifying patients based on the degree of liver impairment. High sCD163 levels may be used for screening purposes and in the early identification of the need for interventions, such as starting anti-viral treatment in patients with chronic viral hepatitis, or in screening for oesophageal varices. CD147 is a cell surface transmembrane protein that regulates tumour-stromal interactions, and induces the secretion of MMP in the tumor local environment, thus promoting tumor invasion and metastasis. CD147 is highly expressed on hepatocellular carcinoma cells and is associated with a poor prognosis. Soluble CD147 is released by shedding, and in this thesis, we demonstrate that increased sCD147 levels predict patients with more advanced hepatocellular carcinoma and a high likelihood of death within 90 days. This may assist in the identification of HCC patients with a poor prognosis and help clinician’s define patients unsuitable for ongoing active treatment. 1,25-dihydroxyvitamin D3 has been shown to exert potent immunoregulatory effects that are mediated through binding to an intracellular receptor protein, the vitamin D receptor. In this thesis, we demonstrate that vitamin D deficiency is more common in chronic liver disease and hepatocellular carcinoma compared to the Australian population. Higher serum 25(OH)D concentrations were demonstrated to be associated with a reduced risk of disease progression and death due to liver disease in both the chronic liver disease and hepatocellular carcinoma cohorts. Vitamin D deficiency is a common problem in the Australian population

Multivalent ligands control stem cell behaviour in vitro and in vivo.

There is broad interest in designing nanostructured materials that can interact with cells and regulate key downstream functions. In particular, materials with nanoscale features may enable control over multivalent interactions, which involve the simultaneous binding of multiple ligands on one entity to multiple receptors on another and are ubiquitous throughout biology. Cellular signal transduction of growth factor and morphogen cues (which have critical roles in regulating cell function and fate) often begins with such multivalent binding of ligands, either secreted or cell-surface-tethered to target cell receptors, leading to receptor clustering. Cellular mechanisms that orchestrate ligand-receptor oligomerization are complex, however, so the capacity to control multivalent interactions and thereby modulate key signalling events within living systems is currently very limited. Here, we demonstrate the design of potent multivalent conjugates that can organize stem cell receptors into nanoscale clusters and control stem cell behaviour in vitro and in vivo. The ectodomain of ephrin-B2, normally an integral membrane protein ligand, was conjugated to a soluble biopolymer to yield multivalent nanoscale conjugates that potently induce signalling in neural stem cells and promote their neuronal differentiation both in culture and within the brain. Super-resolution microscopy analysis yielded insights into the organization of the receptor-ligand clusters at the nanoscale. We also found that synthetic multivalent conjugates of ephrin-B1 strongly enhance human embryonic and induced pluripotent stem cell differentiation into functional dopaminergic neurons. Multivalent bioconjugates are therefore powerful tools and potential nanoscale therapeutics for controlling the behaviour of target stem cells in vitro and in vivo