Ebola virus disease epidemic in West Africa: Lessons learned and issues arising from West African countries

© Royal College of Physicians 2015. All rights reserved.The current Ebola virus disease (EVD) outbreak ravaging three nations in West Africa has affected more than 14,000 persons and killed over 5,000. It is the longest and most widely spread Ebola epidemic ever seen. At the time of this overview (written November 2014), having affected eight different nations, Nigeria and Senegal were able to control and eliminate the virus within a record time. Ghana has successfully, to date, kept the virus away from the country, despite economic and social relationships with affected nations. What lessons can we learn from Nigeria, Senegal and Ghana in the current epidemic? How can the world improve the health systems in low- and middle-income countries to effectively manage future outbreaks? Recently, the Royal College of Physicians launched a new partnership with the West African College of Physicians to curtail the effects of HIV/AIDS, malaria and tuberculosis in the region. We believe that strengthened health systems, skilled human resources for health and national ownership of problems are key to effective management of outbreaks such as EVD

Sustainable Health Development Goals (SHDG): breaking down the walls.

The worlds governments failed to achieve the Health for All 2000 goals from the Alma Ata Declaration of 1978. Although a lot of milestones have been covered since 2000, the worlds governing authorities are unlikely to achieve the current Millennium Development Goals (MDGs) which expire by the end of this year. The inability to achieve these goals may be linked to the multiplicity of health-related directives and fragmentation of health systems in many countries. However, with the proposed 17 sustainability development goals, health has only one universal aim: to ensure healthy lives and promote wellbeing for all at all ages. Accomplishing this will require a focus on health systems (system-thinking), commonization of services and full integration of services with total dismantling of vertical programs across the world

Beyond crystallography: diffractive imaging using coherent x-ray light sources

X-ray crystallography has been central to the development of many fields of science over the past century. It has now matured to a point that as long as good-quality crystals are available, their atomic structure can be routinely determined in three dimensions. However, many samples in physics, chemistry, materials science, nanoscience, geology, and biology are noncrystalline, and thus their three-dimensional structures are not accessible by traditional x-ray crystallography. Overcoming this hurdle has required the development of new coherent imaging methods to harness new coherent x-ray light sources. Here we review the revolutionary advances that are transforming x-ray sources and imaging in the 21st century

Hepatocellular carcinoma: Review of disease and tumor biomarkers.

© The Author(s) 2016.Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburgs phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest

Challenges of liver cancer: Future emerging tools in imaging and urinary biomarkers.

© The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.Chronic liver disease has become a global health problem as a result of the increasing incidence of viral hepatitis, obesity and alcohol misuse. Over the past three decades, in the United Kingdom alone, deaths from chronic liver disease have increased both in men and in women. Currently, 2.5% of deaths worldwide are attributed to liver disease and projected figures suggest a doubling in hospitalisation and associated mortality by 2020. Chronic liver diseases vary for clinical manifestations and natural history, with some individuals having relatively indolent disease and others with a rapidly progressive course. About 30% of patients affected by hepatitis C has a progressive disease and develop cirrhosis over a 20 years period from the infection, usually 5-10 years after initial medical presentation. The aim of the current therapeutic strategies is preventing the progression from hepatitis to fibrosis and subsequently, cirrhosis. Hepatic steatosis is a risk factor for chronic liver disease and is affecting about the half of patients who abuse alcohol. Moreover non-alcoholic fatty liver disease is part of the metabolic syndrome, associated with obesity, hypertension, type ? diabetes mellitus and dyslipidaemia, and a subgroup of patients develops non-alcoholic steatohepatitis and fibrosis with subsequent cirrhosis. The strengths and pitfalls of liver biopsy are discussed and a variety of new techniques to assess liver damage from transient elastography to experimental techniques, such as in vitro urinary nuclear magnetic resonance spectroscopy. Some of the techniques and tests described are already suitable for more widespread clinical application, as is the case with ultrasound-based liver diagnostics, but others, such as urinary metabonomics, requires a period of critical evaluation or development to take them from the research arena to clinical practice

Impact of CTLA-4 checkpoint antibodies on ligand binding and Transendocytosis

Anti-CTLA-4 antibodies have pioneered the field of tumour immunotherapy. However, despite impressive clinical response data, the mechanism by which anti-CTLA-4 antibodies work is still controversial. Two major checkpoint antibodies (ipilimumab and tremelimumab) have been trialled clinically. Both have high affinity binding to CTLA-4 and occupy the ligand binding site, however recently it has been suggested that in some settings such antibodies may not block ligand-CTLA-4 interactions. Here we evaluated blocking capabilities of these antibodies in a variety of settings using both soluble and cell bound target proteins. We found that when ligands (CD80 or CD86) were expressed on cells, soluble CTLA-4-Ig bound in line with affinity expectations and that this interaction was effectively disrupted by both ipilimumab and tremelimumab antibodies. Similarly, cellular CTLA-4 binding to soluble ligands was comparably prevented. We further tested the ability of these antibodies to block transendocytosis, whereby CTLA-4 captures ligands from target cells during a cognate cell-cell interaction. Once again ipilimumab and tremelimumab were similar in preventing removal of ligand by transendocytosis. Furthermore, even once transendocytosis was ongoing and cell contact was fully established, the addition of these antibodies could prevent further ligand transfer. Together these data indicate that the above checkpoint inhibitors performed in-line with predictions based on affinity and binding site data and are capable of blocking CTLA-4-ligand interactions in a wide range of settings tested

Social creatures: model animal systems for studying the neuroendocrine mechanisms of social behaviour

Work was supported by grants awarded to ML (BBSRC BB/S000224/1), OJB (BO 1958/8-2, GRK 2174), KEB (Wellcome Trust 109614/Z/15/Z, MRC MR/N004574/1), AJ (BBSRC BB/S000801) and GL (Israel Science Foundation #1511/16; United States-Israel Binational Science Foundation #2017325; Nella and Leon Benoziyo Center for Neurological Diseases, Richard F. Goodman Yale/Weizmann Exchange Program and Estate of Emile Mimran).The interaction of animals with conspecifics, termed social behaviour, has a major impact on the survival of many vertebrate species. Neuropeptide hormones modulate the underlying physiology that governs social interactions, and many findings concerning the neuroendocrine mechanisms of social behaviours have been extrapolated from animal models to humans. Neurones expressing neuropeptides show similar distribution patterns within the hypothalamic nucleus, even when evolutionarily distant species are compared. During evolution, hypothalamic neuropeptides and releasing hormones have retained not only their structures, but also their biological functions, including their effects on behaviour. Here, we review the current understanding of the mechanisms of social behaviours in several classes of animals, such as worms, insects and fish, as well as laboratory, wild and domesticated mammals.Publisher PDFPeer reviewe

Bias-free photoelectrochemical water splitting with photosystem II on a dye-sensitized photoanode wired to hydrogenase

Natural photosynthesis stores sunlight in chemical energy carriers, but it has not evolved for the efficient synthesis of fuels, such as H2. Semi-artificial photosynthesis combines the strengths of natural photosynthesis with synthetic chemistry and materials science to develop model systems that overcome Nature’s limitations, such as low-yielding metabolic pathways and non-complementary light absorption by Photosystem (PS) I and II. Here, we report a bias-free semi-artificial tandem platform that wires PSII to hydrogenase for overall water splitting. This photoelectrochemical cell integrated the red and blue light-absorber PSII with a green light-absorbing diketopyrrolopyrrole dye-sensitised TiO2 photoanode enabling complementary panchromatic solar light absorption. Effective electronic communication at the enzyme-material interface was engineered using an Os complex-modified redox polymer on a hierarchically-structured TiO2. This system provides a design protocol for bias-free semi-artificial Z-schemes in vitro and provides an extended toolbox of biotic and abiotic components to re-engineer photosynthetic pathways.ERC Consolidator Grant, EPSRC (nanoDTC, DTA studentship), Christian Doppler Research Association, OMV Group, Royal Society Newton International Fellowship, Cluster of Excellence RESOLV (DFG) and European Unions' Horizon 202

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

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