Crowdfunding our health: economic risks and benefits

Crowdfunding is an expanding form of alternative financing that is gaining traction in the health sector. This article presents a typology for crowdfunded health projects and a review of the main economic benefits and risks of crowdfunding in the health market. We use evidence from a literature review, complimented by expert interviews, to extend the fundamental principles and established theories of crowdfunding to a health market context. Crowdfunded health projects can be classified into four types according to the venture's purpose and funding method. These are projects covering health expenses, fundraising health initiatives, supporting health research, or financing commercial health innovation. Crowdfunding could economically benefit the health sector by expanding market participation, drawing money and awareness to neglected health issues, improving access to funding, and fostering project accountability and social engagement. However, the economic risks of health-related crowdfunding include inefficient priority setting, heightened financial risk, inconsistent regulatory policies, intellectual property rights concerns, and fraud. Theorized crowdfunding behaviours such as signalling and herding can be observed in the market for health-related crowdfunding. Broader threats of market failure stemming from adverse selection and moral hazard also apply. Many of the discussed economic benefits and risks of crowdfunding health campaigns are shared more broadly with those of crowdfunding projects in other sectors. Where crowdfunding health care appears to diverge from theory is the negative externality inefficient priority setting may have towards achieving broader public health goals. Therefore, the market for crowdfunding health care must be economically stable, as well as designed to optimally and equitably improve public health

Structural equation model for estimating risk factors in type 2 diabetes mellitus in a Middle Eastern setting: evidence from the STEPS Qatar.

AIMS: Understanding type 2 diabetes mellitus is critical for designing effective diabetes prevention policies in Qatar and the Middle East. METHODS: Using the Qatar 2012 WHO STEPwise approach to surveillance survey, a subsample of 1224 Qatari participants aged 18-64 years was selected. Subjects had their fasting blood glucose levels tested, had not been diagnosed with or treated for diabetes, had a fasting time >12 hours and were not pregnant. We applied a hypothesized structural equation model (SEM) to assess sociodemographic, behavioral, anthropometric and metabolic variables affecting persons with type 2 diabetes mellitus. RESULTS: There is a direct effect of triglyceride levels (0.336) and body mass index (BMI) (0.164) on diabetes status. We also found that physical activity levels negatively affect BMI (-0.148) and positively affect high-density lipoprotein (HDL) (0.106); sociodemographic background negatively affects diet (-0.522) and BMI (-0.352); HDL positively affects total cholesterol (0.230) and has a negative effect on BMI (-0.108), triglycerides (-0.128) and waist circumference (-0.104). Diet has a positive effect on triglycerides (0.281) while family history of diabetes negatively affects total cholesterol (-0.104). BMI has a positive effect on waist circumference (0.788) and mediates the effects of physical activity over diabetes status (-0.028). BMI also mediates the effects that sociodemographic factors (-0.058) and physical activity (-0.024) have on diabetes status. BMI and HDL (-0.002) together mediate the effect of physical activity on diabetes status and similarly HDL and tryglycerides (-0.005) also mediate the effect of physical activity on diabetes status. Finally diet and tryglycerides mediate the effects that sociodemographic factors have on diabetes status (-0.049). CONCLUSIONS: This study's main finding is that triglyceride levels and BMI are the main variables directly affecting diabetes status in the Qatari population

Incentivising innovation in antibiotic drug discovery and development: progress, challenges and next steps

Political momentum and funding for combatting antimicrobial resistance (AMR) continues to build. Numerous major international and national initiatives aimed at financially incentivising the research and development (R&D) of antibiotics have been implemented. However, it remains unclear how to effectively strengthen the current set of incentive programmes to further accelerate antibiotic innovation. Based on a literature review and expert input, this study first identifies and assesses the major international, European Union, US and UK antibiotic R&D funding programmes. These programmes are then evaluated across market and public health criteria necessary for comprehensively improving the antibiotic market. The current set of incentive programmes are an important initial step to improving the economic feasibility of antibiotic development. However, there appears to be a lack of global coordination across all initiatives, which risks duplicating efforts, leaving funding gaps in the value chain and overlooking important AMR goals. This study finds that incentive programmes are overly committed to early-stage push funding of basic science and preclinical research, while there is limited late-stage push funding of clinical development. Moreover, there are almost no pull incentives to facilitate transition of antibiotic products from early clinical phases to commercialisation, focus developer concentration on the highest priority antibiotics and attract large pharmaceutical companies to invest in the market. Finally, it seems that antibiotic sustainability and patient access requirements are poorly integrated into the array of incentive mechanism

South Pacific Convergence Zone dynamics, variability and impacts in a changing climate

The South Pacific Convergence Zone (SPCZ) is a diagonal band of intense rainfall and deep atmospheric convection extending from the equator to the subtropical South Pacific. Displacement of the SPCZ causes variability in rainfall, tropical-cyclone activity and sea level that affects South Pacific island populations and surrounding ecosystems. In this Review, we synthesize recent advances in understanding the physical mechanisms responsible for the SPCZ location and orientation, its interactions with the principal drivers of tropical climate variability, regional and global effects of the SPCZ and its response to anthropogenic climate change. Emerging insight is beginning to provide a coherent description of the character and variability of the SPCZ over synoptic, intraseasonal, interannual and longer timescales. For example, the diagonal orientation of the SPCZ and its natural variability are both the result of a subtle chain of interactions between the tropical and extratropical atmosphere, forced and modulated by the underlying sea surface temperature gradients. However, persistent biases in, and deficiencies of, existing models limit confidence in future projections. Improved climate models and new methods for regional modelling might better constrain future SPCZ projections, aiding climate change adaptation and planning among vulnerable South Pacific communities

Pedagogy and deliberative democracy: Insights from recent experiments in the United Kingdom

A growing body of research suggests the existence of a disconnection between citizens, politicians and representative politics in advanced industrial democracies. This has led to a literature on the emergence of post-democratic or post-representative politics that connects to a parallel seam of scholarship on the capacity of deliberative democratic innovations to ‘close the gap’. This latter body of work has delivered major insights in terms of democratic design in ways that traverse ‘politics as theory’ and ‘politics as practice’. And yet the main argument of this article is that this seam of scholarship has generally failed to explore the existence of numerous pedagogical relationships that exist within the very fibre of deliberative processes. As such, the core contribution of this article focuses around the explication of a ‘pedagogical pyramid’ that applies a micro-political lens to deliberative processes. This theoretical contribution is empirically assessed with reference to a recent project that sought to test different citizen assembly pilots around plans for English regional devolution. The proposition being tested is that a better understanding of relational pedagogy within innovations is vital, not just to increase levels of knowledge, but also to build the capacity, confidence and contribution of democratically active citizens

Intramolecular Epistasis and the Evolution of a New Enzymatic Function

Atrazine chlorohydrolase (AtzA) and its close relative melamine deaminase (TriA) differ by just nine amino acid substitutions but have distinct catalytic activities. Together, they offer an informative model system to study the molecular processes that underpin the emergence of new enzymatic function. Here we have constructed the potential evolutionary trajectories between AtzA and TriA, and characterized the catalytic activities and biophysical properties of the intermediates along those trajectories. The order in which the nine amino acid substitutions that separate the enzymes could be introduced to either enzyme, while maintaining significant catalytic activity, was dictated by epistatic interactions, principally between three amino acids within the active site: namely, S331C, N328D and F84L. The mechanistic basis for the epistatic relationships is consistent with a model for the catalytic mechanisms in which protonation is required for hydrolysis of melamine, but not atrazine

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The Sodium Sialic Acid Symporter From Staphylococcus aureus Has Altered Substrate Specificity

Mammalian cell surfaces are decorated with complex glycoconjugates that terminate with negatively charged sialic acids. Commensal and pathogenic bacteria can use host-derived sialic acids for a competitive advantage, but require a functional sialic acid transporter to import the sugar into the cell. This work investigates the sodium sialic acid symporter (SiaT) from Staphylococcus aureus (SaSiaT). We demonstrate that SaSiaT rescues an Escherichia coli strain lacking its endogenous sialic acid transporter when grown on the sialic acids N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc). We then develop an expression, purification and detergent solubilization system for SaSiaT and demonstrate that the protein is largely monodisperse in solution with a stable monomeric oligomeric state. Binding studies reveal that SaSiaT has a higher affinity for Neu5Gc over Neu5Ac, which was unexpected and is not seen in another SiaT homolog. We develop a homology model and use comparative sequence analyses to identify substitutions in the substrate-binding site of SaSiaT that may explain the altered specificity. SaSiaT is shown to be electrogenic, and transport is dependent upon more than one Na+ ion for every sialic acid molecule. A functional sialic acid transporter is essential for the uptake and utilization of sialic acid in a range of pathogenic bacteria, and developing new inhibitors that target these transporters is a valid mechanism for inhibiting bacterial growth. By demonstrating a route to functional recombinant SaSiaT, and developing the in vivo and in vitro assay systems, our work underpins the design of inhibitors to this transporter

Crowdfunding our health: economic risks and benefits

Crowdfunding is an expanding form of alternative financing that is gaining traction in the health sector. This article presents a typology for crowdfunded health projects and a review of the main economic benefits and risks of crowdfunding in the health market. We use evidence from a literature review, complimented by expert interviews, to extend the fundamental principles and established theories of crowdfunding to a health market context. Crowdfunded health projects can be classified into four types according to the venture's purpose and funding method. These are projects covering health expenses, fundraising health initiatives, supporting health research, or financing commercial health innovation. Crowdfunding could economically benefit the health sector by expanding market participation, drawing money and awareness to neglected health issues, improving access to funding, and fostering project accountability and social engagement. However, the economic risks of health-related crowdfunding include inefficient priority setting, heightened financial risk, inconsistent regulatory policies, intellectual property rights concerns, and fraud. Theorized crowdfunding behaviours such as signalling and herding can be observed in the market for health-related crowdfunding. Broader threats of market failure stemming from adverse selection and moral hazard also apply. Many of the discussed economic benefits and risks of crowdfunding health campaigns are shared more broadly with those of crowdfunding projects in other sectors. Where crowdfunding health care appears to diverge from theory is the negative externality inefficient priority setting may have towards achieving broader public health goals. Therefore, the market for crowdfunding health care must be economically stable, as well as designed to optimally and equitably improve public health

Crystal, Solution and In silico Structural Studies of Dihydrodipicolinate Synthase from the Common Grapevine

Dihydrodipicolinate synthase (DHDPS) catalyzes the rate limiting step in lysine biosynthesis in bacteria and plants. The structure of DHDPS has been determined from several bacterial species and shown in most cases to form a homotetramer or dimer of dimers. However, only one plant DHDPS structure has been determined to date from the wild tobacco species, Nicotiana sylvestris (Blickling et al. (1997) J. Mol. Biol. 274, 608–621). Whilst N. sylvestris DHDPS also forms a homotetramer, the plant enzyme adopts a ‘back-to-back’ dimer of dimers compared to the ‘head-to-head’ architecture observed for bacterial DHDPS tetramers. This raises the question of whether the alternative quaternary architecture observed for N. sylvestris DHDPS is common to all plant DHDPS enzymes. Here, we describe the structure of DHDPS from the grapevine plant, Vitis vinifera, and show using analytical ultracentrifugation, small-angle X-ray scattering and X-ray crystallography that V. vinifera DHDPS forms a ‘back-to-back’ homotetramer, consistent with N. sylvestris DHDPS. This study is the first to demonstrate using both crystal and solution state measurements that DHDPS from the grapevine plant adopts an alternative tetrameric architecture to the bacterial form, which is important for optimizing protein dynamics as suggested by molecular dynamics simulations reported in this study