Deep learning in ophthalmology: The technical and clinical considerations

The advent of computer graphic processing units, improvement in mathematical models and availability of big data has allowed artificial intelligence (AI) using machine learning (ML) and deep learning (DL) techniques to achieve robust performance for broad applications in social-media, the internet of things, the automotive industry and healthcare. DL systems in particular provide improved capability in image, speech and motion recognition as well as in natural language processing. In medicine, significant progress of AI and DL systems has been demonstrated in image-centric specialties such as radiology, dermatology, pathology and ophthalmology. New studies, including pre-registered prospective clinical trials, have shown DL systems are accurate and effective in detecting diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), retinopathy of prematurity, refractive error and in identifying cardiovascular risk factors and diseases, from digital fundus photographs. There is also increasing attention on the use of AI and DL systems in identifying disease features, progression and treatment response for retinal diseases such as neovascular AMD and diabetic macular edema using optical coherence tomography (OCT). Additionally, the application of ML to visual fields may be useful in detecting glaucoma progression. There are limited studies that incorporate clinical data including electronic health records, in AL and DL algorithms, and no prospective studies to demonstrate that AI and DL algorithms can predict the development of clinical eye disease. This article describes global eye disease burden, unmet needs and common conditions of public health importance for which AI and DL systems may be applicable. Technical and clinical aspects to build a DL system to address those needs, and the potential challenges for clinical adoption are discussed. AI, ML and DL will likely play a crucial role in clinical ophthalmology practice, with implications for screening, diagnosis and follow up of the major causes of vision impairment in the setting of ageing populations globally

Thermal and Sedimentation Stress Are Unlikely Causes of Brown Spot Syndrome in the Coral Reef Sponge, Ianthella basta

Background: Marine diseases are being increasingly linked to anthropogenic factors including global and local stressors. On the Great Barrier Reef, up to 66% of the Ianthella basta population was recently found to be afflicted by a syndrome characterized by brown spot lesions and necrotic tissue.\ud \ud Methodology/Principal Findings: Manipulative experiments were undertaken to ascertain the role of environmental stressors in this syndrome. Specifically, the effects of elevated temperature and sedimentation on sponge health and symbiont stability in I. basta were examined. Neither elevated temperature nor increased sedimentation were responsible for the brown spot lesions, but sponges exposed to 32°C developed substantial discoloration and deterioration of their tissues, resulting in death after eight days and a higher microbial diversity in those samples. No shifts in the microbial community of I. basta were observed across a latitudinal gradient or with increased sedimentation, with three previously described symbionts dominating the community of all sponges (Alphaproteobacteria, Gammaproteobacteria and Thaumarchaea).\ud \ud Conclusions/Significance: Results from this study highlight the stable microbial community of I. basta and indicate that thermal and sedimentation stress are not responsible for the brown spot lesions currently affecting this abundant and ecologically important sponge species

Early and efficient detection of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures.

Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein-Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (p = 0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7-13), versus 21 days (IQR 14-28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US $4.56 per sample, versus US$11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings

Microbial contributions to the persistence of coral reefs

On contemplating the adaptive capacity of reef organisms to a rapidly changing environment, the microbiome offers significant and greatly unrecognised potential. Microbial symbionts contribute to the physiology, development, immunity and behaviour of their hosts, and can respond very rapidly to changing environmental conditions, providing a powerful mechanism for acclimatisation and also possibly rapid evolution of coral reef holobionts. Environmentally acquired fluctuations in the microbiome can have significant functional consequences for the holobiont phenotype upon which selection can act. Environmentally induced changes in microbial abundance may be analogous to host gene duplication, symbiont switching / shuffling as a result of environmental change can either remove or introduce raw genetic material into the holobiont; and horizontal gene transfer can facilitate rapid evolution within microbial strains. Vertical transmission of symbionts is a key feature of many reef holobionts and this would enable environmentally acquired microbial traits to be faithfully passed to future generations, ultimately facilitating microbiome-mediated transgenerational acclimatisation (MMTA) and potentially even adaptation of reef species in a rapidly changing climate. In this commentary, we highlight the capacity and mechanisms for MMTA in reef species, propose a modified Price equation as a framework for assessing MMTA and recommend future areas of research to better understand how microorganisms contribute to the transgenerational acclimatisation of reef organisms, which is essential if we are to reliably predict the consequences of global change for reef ecosystems

The impact of health system governance and policy processes on health services in Iraqi Kurdistan

BACKGROUND: Relative to the amount of global attention and media coverage since the first and second Gulf Wars, very little has been published in the health services research literature regarding the state of health services in Iraq, and particularly on the semi-autonomous region of Kurdistan. Building on findings from a field visit, this paper describes the state of health services in Kurdistan, analyzes their underlying governance structures and policy processes, and their overall impact on the quality, accessibility and cost of the health system, while stressing the importance of reinvesting in public health and community-based primary care. DISCUSSION: Very little validated, research-based data exists relating to the state of population health and health services in Kurdistan. What little evidence exists, points to a region experiencing an epidemiological polarization, with different segments of the population experiencing rapidly-diverging rates of morbidity and mortality related to different etiological patterns of communicable, non-communicable, acute and chronic illness and disease. Simply put, the rural poor suffer from malnutrition and cholera, while the urban middle and upper classes deal with issues of obesity and Type 2 diabetes. The inequity is exacerbated by a poorly governed, fragmented, unregulated, specialized and heavily privatized system, that not only leads to poor quality of care and catastrophic health expenditures, but also threatens the economic and political stability of the region. There is an urgent need to revisit and clearly define the core values and goals of a future health system, and to develop an inclusive governance and policy framework for change, towards a more equitable and effective primary care-based health system, with attention to broader social determinants of health and salutogenesis. SUMMARY: This paper not only frames the situation in Kurdistan in terms of a human rights or special political issue of a minority population, but provides important generalizable lessons for other constituencies, highlighting the need for political action before effective public health policies can be implemented - as embodied by Rudolf Virchow, the father of European public health and pathology, in his famous quote "politics is nothing but medicine at a larger scale"

A model to control the epidemic of H5N1 influenza at the source

<p>Abstract</p> <p>Background</p> <p>No country is fully prepared for a 1918-like pandemic influenza. Averting a pandemic of H5N1 influenza virus depends on the successful control of its endemicity, outbreaks in poultry and occasional spillage into human which carries a case-fatality rate of over 50%. The use of perimetric depopulation and vaccination has failed to halt the spread of the epidemic. Blanket vaccination for all poultry over a large geographical area is difficult. A combination of moratorium, segregation of water fowls from chickens and vaccination have been proved to be effective in the Hong Kong Special Administrative Region (HKSAR) since 2002 despite endemicity and outbreaks in neighbouring regions. Systematic surveillance in southern China showed that ducks and geese are the primary reservoirs which transmit the virus to chickens, minor poultry and even migratory birds.</p> <p>Presentation of the hypothesis</p> <p>We hypothesize that this combination of moratorium, poultry segregation and targeted vaccination if successfully adapted to an affected district or province in any geographical region with high endemicity would set an example for the control in other regions.</p> <p>Testing the hypothesis</p> <p>A planned one-off moratorium of 3 weeks at the hottest month of the year should decrease the environmental burden as a source of re-infection. Backyard farms will then be re-populated by hatchlings from virus-free chickens and minor poultry only. Targeted immunization of the ducks and geese present only in the industrial farms and also the chickens would be strictly implemented as blanket immunization of all backyard poultry is almost impossible. Freely grazing ducks and geese would not be allowed until neutralizing antibodies of H5 subtype virus is achieved. As a proof of concept, a simple mathematical model with susceptible-infected-recovered (SIR) structure of coupled epidemics between aquatic birds (mainly ducks and geese) and chickens was used to estimate transmissibility within and between these two poultry populations. In the field the hypothesis is tested by prospective surveillance of poultry and immunocompetent patients hospitalized for severe pneumonia for the virus before and after the institution of these measures.</p> <p>Implications of the Hypothesis</p> <p>A combination of targeted immunization with the correct vaccine, segregation of poultry species and moratorium of poultry in addition to the present surveillance, biosecurity and hygienic measures at the farm, market and personal levels could be important in the successful control of the H5N1 virus in poultry and human for an extensive geographical region with continuing outbreaks. Alternatively a lesser scale of intervention at the district level can be considered if there is virus detection without evidence of excess poultry deaths since asymptomatic shedding is common in waterfowls.</p

The Neurotropic Parasite Toxoplasma Gondii Increases Dopamine Metabolism

The highly prevalent parasite Toxoplasma gondii manipulates its host's behavior. In infected rodents, the behavioral changes increase the likelihood that the parasite will be transmitted back to its definitive cat host, an essential step in completion of the parasite's life cycle. The mechanism(s) responsible for behavioral changes in the host is unknown but two lines of published evidence suggest that the parasite alters neurotransmitter signal transduction: the disruption of the parasite-induced behavioral changes with medications used to treat psychiatric disease (specifically dopamine antagonists) and identification of a tyrosine hydroxylase encoded in the parasite genome. In this study, infection of mammalian dopaminergic cells with T. gondii enhanced the levels of K+-induced release of dopamine several-fold, with a direct correlation between the number of infected cells and the quantity of dopamine released. Immunostaining brain sections of infected mice with dopamine antibody showed intense staining of encysted parasites. Based on these analyses, T. gondii orchestrates a significant increase in dopamine metabolism in neural cells. Tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, was also found in intracellular tissue cysts in brain tissue with antibodies specific for the parasite-encoded tyrosine hydroxylase. These observations provide a mechanism for parasite-induced behavioral changes. The observed effects on dopamine metabolism could also be relevant in interpreting reports of psychobehavioral changes in toxoplasmosis-infected humans

Modeling influenza epidemics and pandemics: insights into the future of swine flu (H1N1)

Here we present a review of the literature of influenza modeling studies, and discuss how these models can provide insights into the future of the currently circulating novel strain of influenza A (H1N1), formerly known as swine flu. We discuss how the feasibility of controlling an epidemic critically depends on the value of the Basic Reproduction Number (R0). The R0 for novel influenza A (H1N1) has recently been estimated to be between 1.4 and 1.6. This value is below values of R0 estimated for the 1918–1919 pandemic strain (mean R0~2: range 1.4 to 2.8) and is comparable to R0 values estimated for seasonal strains of influenza (mean R0 1.3: range 0.9 to 2.1). By reviewing results from previous modeling studies we conclude it is theoretically possible that a pandemic of H1N1 could be contained. However it may not be feasible, even in resource-rich countries, to achieve the necessary levels of vaccination and treatment for control. As a recent modeling study has shown, a global cooperative strategy will be essential in order to control a pandemic. This strategy will require resource-rich countries to share their vaccines and antivirals with resource-constrained and resource-poor countries. We conclude our review by discussing the necessity of developing new biologically complex models. We suggest that these models should simultaneously track the transmission dynamics of multiple strains of influenza in bird, pig and human populations. Such models could be critical for identifying effective new interventions, and informing pandemic preparedness planning. Finally, we show that by modeling cross-species transmission it may be possible to predict the emergence of pandemic strains of influenza

Biological Characterisation of Haliclona (?gellius) sp.: Sponge and Associated Microorganisms

We have characterised the northern Pacific undescribed sponge Haliclona (?gellius) sp. based on rDNA of the sponge and its associated microorganisms. The sponge is closely related to Amphimedon queenslandica from the Great Barrier Reef as the near-complete 18S rDNA sequences of both sponges were identical. The microbial fingerprint of three specimens harvested at different times and of a transplanted specimen was compared to identify stably associated microorganisms. Most bacterial phyla were detected in each sample, but only a few bacterial species were determined to be stably associated with the sponge. A sponge-specific β- and γ-Proteobacterium were abundant clones and both of them were present in three of the four specimens analysed. In addition, a Planctomycete and a Crenarchaea were detected in all sponge individuals. Both were closely related to operational taxonomic units that have been found in other sponges, but not exclusively in sponges. Interestingly, also a number of clones that are closely related to intracellular symbionts from insects and amoeba were detected