Terpyridyl Complexes as Antimalarial Agents

Anumber of transition metals and their terpyridyl complexes have been evaluated for antimalarial activity on the strain 3D7. The metals, ligands and complexes were each in turn investigated for their efficacy. All activities were in the sub-micromolar range (0.1–1 μM). Their modes of action were compared with that of chloroquine to discover whether or not they were capable of inhibiting haemozoin formation. The data indicate that efficacy could be a result of several mechanisms and that speciation of the metal complex and the manner in which the agents are added to the parasitic broth have a profound effect on the activity of the agents. We believe that our study offers a template by which other researchers should approach their experiments using transition metal complex agents.KEYWORDS Antimalarial agents, terpyridyl and transition metals

Predicting Incremental and Future Visual Change in Neovascular Age-Related Macular Degeneration Using Deep Learning

PURPOSE: To evaluate the predictive utility of quantitative imaging biomarkers, acquired automatically from optical coherence tomography (OCT) scans, of cross-sectional and future visual outcomes of patients with neovascular age-related macular degeneration (AMD) starting anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naïve, first-treated eyes of patients with neovascular AMD between 2007 and 2017 at Moorfields Eye Hospital (a large, UK single-centre) undergoing anti-VEGF therapy METHODS: Automatic segmentation was carried out by applying a deep learning segmentation algorithm to 137,379 OCT scans from 6467 eyes of 3261 patients with neovascular AMD. After applying selection criteria 926 eyes of 926 patients were taken forward for analysis. MAIN OUTCOME MEASURES: Correlation coefficients (R2) and mean absolute error (MAE) between quantitative OCT (qOCT) parameters and cross-sectional visual-function. The predictive value of these parameters for short-term visual change i.e. incremental visual acuity [VA] resulting from an individual injection, as well as, VA at distant timepoints (up to 12 months post-baseline). RESULTS: VA at distant timepoints could be predicted: R2 0.80 (MAE 5.0 ETDRS letters) and R2 0.7 (MAE 7.2) post-injection 3 and at 12 months post-baseline (both p < 0.001), respectively. Best performing models included both baseline qOCT parameters and treatment-response. Furthermore, we present proof-of-principle evidence that the incremental change in VA from an injection can be predicted: R2 0.14 (MAE 5.6) for injection 2 and R2 0.11 (MAE 5.0) for injection 3 (both p < 0.001). CONCLUSIONS: Automatic segmentation enables rapid acquisition of quantitative and reproducible OCT biomarkers with potential to inform treatment decisions in the care of neovascular AMD. This furthers development of point-of-care decision-aid systems for personalized medicine

Stepped Care for Maternal Mental Health: A Case Study of the Perinatal Mental Health Project in South Africa

As one article in a series on Global Mental Health Practice, Simone Honikman and colleagues from South Africa provide a case study of the Perinatal Mental Health Project, which delivered mental health care to pregnant women in a collaborative, step-wise manner, making use of existing resources in primary care

Quantitative analysis of optical coherence tomography for neovascular age-related macular degeneration using deep learning

PURPOSE: To apply a deep learning algorithm for automated, objective, and comprehensive quantification of optical coherence tomography (OCT) scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD), and make the raw segmentation output data openly available for further research. DESIGN: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. PARTICIPANTS: 2473 first-treated eyes and another 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017. METHODS: A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first and second eyes, by visual acuity (VA) and by race/ethnicity, and correlations between volumes. MAIN OUTCOME MEASURES: Volumes of segmented features (mm3), central subfield thickness (CST) (μm). RESULTS: In first-treated eyes, the majority had both IRF and SRF (54.7%). First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED and SRF. Eyes from black individuals had higher SRF, RPE and serous PED volumes, compared with other ethnic groups. Greater volumes of the vast majority of features were associated with worse VA. CONCLUSION: We report the results of large scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care, and the detection of novel structure-function correlations. These data will be made publicly available for replication and future investigation by the AMD research community

Moorfields AMD database report 2: fellow eye involvement with neovascular age-related macular degeneration.

BACKGROUND/AIMS: Neovascular age-related macular degeneration (nAMD) is frequently bilateral, and previous reports on 'fellow eyes' have assumed sequential treatment after a period of treatment of the first eye only. The aim of our study was to analyse baseline characteristics and visual acuity (VA) outcomes of fellow eye involvement with nAMD, specifically differentiating between sequential and non-sequential (due to macular scarring in the first eye) antivascular endothelial growth factor treatment and timelines for fellow eye involvement. METHODS: Retrospective, electronic medical record database study of the Moorfields AMD database of 6265 patients/120 286 single entries with data extracted between 21 October 2008 and 9 August 2018. The data set for analysis consisted of 1180 sequential, 807 non-sequential and 3410 unilateral eyes. RESULTS: Mean VA (ETDRS letters±SD) of sequentially treated fellow eyes at baseline was significantly higher (63±13), VA gain over 2 years lower (0.37±14) and proportion of eyes with good VA (≥70 letters) higher (46%) than the respective first eyes (baseline VA 54±16, VA gain at 2 years 5.6±15, percentage of eyes with good VA 39%). Non-sequential fellow eyes showed baseline characteristics and VA outcomes similar to first eyes. Fellow eye involvement rate was 32% at 2 years, and median time interval to fellow eye involvement was 71 (IQR: 27-147) weeks. CONCLUSION: This report shows that sequentially treated nAMD fellow eyes have better baseline and final VA than non-sequentially treated eyes after 2 years of treatment. Sequentially treated eyes also had a greater proportion with good VA after 2 years

Gallbladder agenesis diagnosed intra-operatively: a case report

<p>Abstract</p> <p>Introduction</p> <p>Agenesis of the gallbladder is a rare congenital anomaly occurring in 13 to 65 people of a population of 100,000. The rarity of the condition, combined with clinical and radiologic features that are indistinguishable from those of more common biliary conditions, means that it is rarely diagnosed preoperatively, and patients undergo unnecessary operative intervention.</p> <p>Case presentation</p> <p>This case report describes the case of a 79-year-old symptomatic Caucasian man who underwent laparoscopic cholecystectomy for suspected choledocholithiasis despite imaging studies raising suspicion of gallbladder agenesis. Intra-operatively, the diagnosis of gallbladder agenesis and associated common bile duct stones was made.</p> <p>Conclusion</p> <p>The preoperative diagnosis of this rare condition is difficult to make. However, with advances in biliary tract imaging and with heightened awareness of this anomaly, fewer patients will need to undergo unnecessary operative intervention. The authors review the different imaging modalities available to help diagnose this condition and highlight the importance of being aware of this rare anomaly to avoid an operation that carries a high risk of iatrogenic injury.</p

An effectiveness study of an integrated, community-based package for maternal, newborn, child and HIV care in South Africa: study protocol for a randomized controlled trial

BACKGROUND: Progress towards MDG4 in South Africa will depend largely on scaling up effective prevention against mother to child transmission (PMTCT) of HIV and also addressing neonatal mortality. This imperative drives increasing focus on the neonatal period and particularly on the development and testing of appropriate models of sustainable, community-based care in South Africa in order to reach the poor. A number of key implementation gaps affecting progress have been identified. Implementation gaps for HIV prevention in neonates; implementation gaps for neonatal care especially home postnatal care; and implementation gaps for maternal mental health support. We have developed and are evaluating and costing an integrated and scaleable home visit package delivered by community health workers targeting pregnant and postnatal women and their newborns to provide essential maternal/newborn care as well as interventions for Prevention of Mother to Child Transmission (PMTCT) of HIV. METHODS: The trial is a cluster randomized controlled trial that is being implemented in Umlazi which is a peri-urban settlement with a total population of 1 million close to Durban in KwaZulu Natal, South Africa. The trial consists of 30 randomized clusters (15 in each arm). A baseline survey established the homogeneity of clusters and neither stratification nor matching was performed. Sample size was based on increasing HIV-free survival from 74% to 84%, and calculated to be 120 pregnant women per cluster. Primary outcomes are higher levels of HIV free survival and levels of exclusive and appropriate infant feeding at 12 weeks postnatally. The intervention is home based with community health workers delivering two antenatal visits, a postnatal visit within 48 hours of birth, and a further four visits during the first two months of the infants life. We are undertaking programmatic and cost effectiveness analysis to cost the intervention. DISCUSSION: The question is not merely to develop an efficacious package but also to identify and test delivery strategies that enable scaling up, which requires effectiveness studies in a health systems context, adapting and testing Asian community-based studies in various African contexts

Influence of packing density and stress on the dynamic response of granular materials

Laboratory geophysics tests including bender elements and acoustic emission measure the speed of propagation of stress or sound waves in granular materials to derive elastic stiffness parameters. This contribution builds on earlier studies to assess whether the received signal characteristics can provide additional information about either the material’s behaviour or the nature of the material itself. Specifically it considers the maximum frequency that the material can transmit; it also assesses whether there is a simple link between the spectrum of the received signal and the natural frequencies of the sample. Discrete element method (DEM) simulations of planar compression wave propagation were performed to generate the data for the study. Restricting consideration to uniform (monodisperse) spheres, the material fabric was varied by considering face-centred cubic lattice packings as well as random configurations with different packing densities. Supplemental analyses, in addition to the DEM simulations, were used to develop a more comprehensive understanding of the system dynamics. The assembly stiffness and mass matrices were extracted from the DEM model and these data were used in an eigenmode analysis that provided significant insight into the observed overall dynamic response. The close agreement of the wave velocities estimated using eigenmode analysis with the DEM results confirms that DEM wave propagation simulations can reliably be used to extract material stiffness data. The data show that increasing either stress or density allows higher frequencies to propagate through the media, but the low-pass wavelength is a function of packing density rather than stress level. Prior research which had hypothesised that there is a simple link between the spectrum of the received signal and the natural sample frequencies was not substantiated