Design of financial incentive interventions to improve lifestyle behaviors and health outcomes: A systematic review [version 1; peer review: awaiting peer review]

Background: Financial incentives may improve the initiation and engagement of behaviour change that reduce the negative outcomes associated with non-communicable diseases. There is still a paucity in guidelines or recommendations that help define key aspects of incentive-oriented interventions, including the type of incentive (e.g. cash rewards, vouchers), the frequency and magnitude of the incentive, and its mode of delivery. We aimed to systematically review the literature on financial incentives that promote healthy lifestyle behaviours or improve health profiles, and focused on the methodological approach to define the incentive intervention and its delivery. The protocol was registered at PROSPERO on 26 July 2018 (CRD42018102556). Methods: We sought studies in which a financial incentive was delivered to improve a health-related lifestyle behaviour (e.g., physical activity) or a health profile (e.g., HbA1c in people with diabetes). The search (which took place on March 3rd 2018) was conducted using OVID (MEDLINE and Embase), CINAHL and Scopus. Results: The search yielded 7,575 results and 37 were included for synthesis. Of the total, 83.8% (31/37) of the studies were conducted in the US, and 40.5% (15/37) were randomised controlled trials. Only one study reported the background and rationale followed to develop the incentive and conducted a focus group to understand what sort of incentives would be acceptable for their study population. There was a degree of consistency across the studies in terms of the direction, form, certainty, and recipient of the financial incentives used, but the magnitude and immediacy of the incentives were heterogeneous. Conclusions: The available literature on financial incentives to improve health-related lifestyles rarely reports on the rationale or background that defines the incentive approach, the magnitude of the incentive and other relevant details of the intervention, and the reporting of this information is essential to foster its use as potential effective interventions

Characterization of the Extraterrestrial Magnesium Source in the Atmosphere Using a Meteoric Ablation Simulator

Ablation of Mg from meteoroids entering the Earth's atmosphere was studied experimentally using a Meteoric Ablation Simulator: micron‐sized particles of representative meteoritic material were flash heated to simulate atmospheric entry and the ablation rate of Mg with respect to Na measured by fast time‐resolved laser‐induced fluorescence. Over the range of particle diameters and entry velocities studied, Mg ablates 4.3 ± 2.1 times less efficiently than Na and 2.4 ± 0.8 times less efficiently than Fe. The resulting evaporation profiles indicate that Mg mostly ablates around 84 km in the atmosphere, compared with Fe at 88 km and Na at 95 km. The chemical ablation model Chemical Ablation Model predicts satisfactorily the measured peak ablation altitudes and relative ablated fractions of Mg, Na, Fe, and Ca but does not capture the breadth of the ablation profiles, probably due to the inhomogeneity of the minerals present in meteoroids combined with experimental limitations

Expression of a barley cystatin gene in maize enhances resistance against phytophagous mites by altering their cysteine-proteases

Phytocystatins are inhibitors of cysteine-proteases from plants putatively involved in plant defence based on their capability of inhibit heterologous enzymes. We have previously characterised the whole cystatin gene family members from barley (HvCPI-1 to HvCPI-13). The aim of this study was to assess the effects of barley cystatins on two phytophagous spider mites, Tetranychus urticae and Brevipalpus chilensis. The determination of proteolytic activity profile in both mite species showed the presence of the cysteine-proteases, putative targets of cystatins, among other enzymatic activities. All barley cystatins, except HvCPI-1 and HvCPI-7, inhibited in vitro mite cathepsin L- and/or cathepsin B-like activities, HvCPI-6 being the strongest inhibitor for both mite species. Transgenic maize plants expressing HvCPI-6 protein were generated and the functional integrity of the cystatin transgene was confirmed by in vitro inhibitory effect observed against T. urticae and B. chilensis protein extracts. Feeding experiments impaired on transgenic lines performed with T. urticae impaired mite development and reproductive performance. Besides, a significant reduction of cathepsin L-like and/or cathepsin B-like activities was observed when the spider mite fed on maize plants expressing HvCPI-6 cystatin. These findings reveal the potential of barley cystatins as acaricide proteins to protect plants against two important mite pests

Phylodynamics of HIV-1 Circulating Recombinant Forms 12_BF and 38_BF in Argentina and Uruguay

<p>Abstract</p> <p>Background</p> <p>Although HIV-1 CRF12_BF and CRF38_BF are two epidemiologically important recombinant lineages circulating in Argentina and Uruguay, little is known about their population dynamics.</p> <p>Methods</p> <p>A total of 120 "CRF12_BF-like" and 20 "CRF38_BF-like" <it>pol </it>recombinant sequences collected in Argentina and Uruguay from 1997 to 2009 were subjected to phylogenetic and Bayesian coalescent-based analyses to estimate evolutionary and demographic parameters.</p> <p>Results</p> <p>Phylogenetic analyses revealed that CRF12_BF viruses from Argentina and Uruguay constitute a single epidemic with multiple genetic exchanges among countries; whereas circulation of the CRF38_BF seems to be confined to Uruguay. The mean estimated substitution rate of CRF12_BF at <it>pol </it>gene (2.5 × 10-3 substitutions/site/year) was similar to that previously described for subtype B. According to our estimates, CRF12_BF and CRF38_BF originated at 1983 (1978-1988) and 1986 (1981-1990), respectively. After their emergence, the CRF12_BF and CRF38_BF epidemics seem to have experienced a period of rapid expansion with initial growth rates of around 1.2 year^-1and 0.9 year^-1, respectively. Later, the rate of spread of these CRFs_BF seems to have slowed down since the mid-1990s.</p> <p>Conclusions</p> <p>Our results suggest that CRF12_BF and CRF38_BF viruses were generated during the 1980s, shortly after the estimated introduction of subtype F1 in South America (~1975-1980). After an initial phase of fast exponential expansion, the rate of spread of both CRFs_BF epidemics seems to have slowed down, thereby following a demographic pattern that resembles those previously reported for the HIV-1 epidemics in Brazil, USA, and Western Europe.</p

MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4

Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically

Reconstructing the three-dimensional GABAergic microcircuit of the striatum

A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study

In Situ Compatibilization of Biopolymer Ternary Blends by Reactive Extrusion with Low-Functionality Epoxy-Based Styrene Acrylic Oligomer

[EN] The present study reports on the use of low-functionality epoxy-based styrene¿acrylic oligomer (ESAO) to compatibilize immiscible ternary blends made of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), polylactide (PLA), and poly(butylene adipate-co-terephthalate) (PBAT). The addition during melt processing of low-functionality ESAO at two parts per hundred resin (phr) of biopolymer successfully changed the soften inclusion phase in the blend system to a thinner morphology, yielding biopolymer ternary blends with higher mechanical ductility and also improved oxygen barrier performance. The compatibilization achieved was ascribed to the in situ formation of a newly block terpolymer, i.e. PHBVb- PLA-b-PBAT, which was produced at the blend interface by the reaction of the multiple epoxy groups present in ESAO with the functional terminal groups of the biopolymers. This chemical reaction was mainly linear due to the inherently low functionality of ESAO and the more favorable reactivity of the epoxy groups with the carboxyl groups of the biopolymers, which avoided the formation of highly branched and/or cross-linked structures and thus facilitated the films processability. Therefore, the reactive blending of biopolymers at different mixing ratios with low-functionality ESAO represents a straightforward methodology to prepare sustainable plastics at industrial scale with different physical properties that can be of interest in, for instance, food packaging applications.This research was funded by the EU H2020 project YPACK (Reference number 773872) and by the Spanish Ministry of Science, Innovation, and Universities (MICIU) with project numbers MAT2017-84909-C2-2-R and AGL2015-63855-C2-1-R. L. Quiles-Carrillo wants to thank the Spanish Ministry of Education, Culture, and Sports (MECD) for financial support through his FPU Grant Number FPU15/03812. Torres-Giner also acknowledges the MICIU for his Juan de la Cierva contract (IJCI-2016-29675).Quiles-Carrillo, L.; Montanes, N.; Lagaron, J.; Balart, R.; Torres-Giner, S. (2019). In Situ Compatibilization of Biopolymer Ternary Blends by Reactive Extrusion with Low-Functionality Epoxy-Based Styrene Acrylic Oligomer. 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Biologically inspired herding of animal groups by robots

A single sheepdog can bring together and manoeuvre hundreds of sheep from one location to another. Engineers and ecologists are fascinated by this sheepdog herding because of the potential it provides for ‘bio-herding’: a biologically inspired herding of animal groups by robots. Although many herding algorithms have been proposed, most are studied via simulation. There are a variety of ecological problems where management of wild animal groups is currently impossible, dangerous and/or costly for humans to manage directly, and which may benefit from bio-herding solutions. Unmanned aerial vehicles (UAVs) now deliver significant benefits to the economy and society. Here, we suggest the use of UAVs for bio-herding. Given their mobility and speed, UAVs can be used in a wide range of environments and interact with animal groups at sea, over the land and in the air. We present a potential roadmap for achieving bio-herding using a pair of UAVs. In our framework, one UAV performs ‘surveillance’ of animal groups, informing the movement of a second UAV that herds them. We highlight the promise and flexibility of a paired UAV approach while emphasising its practical and ethical challenges. We start by describing the types of experiments and data required to understand individual and collective responses to UAVs. Next, we describe how to develop appropriate herding algorithms. Finally, we describe the integration of bio-herding algorithms into software and hardware architecture

Design of a Protective Single-Dose Intranasal Nanoparticle-Based Vaccine Platform for Respiratory Infectious Diseases

Despite the successes provided by vaccination, many challenges still exist with respect to controlling new and re-emerging infectious diseases. Innovative vaccine platforms composed of adaptable adjuvants able to appropriately modulate immune responses, induce long-lived immunity in a single dose, and deliver immunogens in a safe and stable manner via multiple routes of administration are needed. This work describes the development of a novel biodegradable polyanhydride nanoparticle-based vaccine platform administered as a single intranasal dose that induced long-lived protective immunity against respiratory disease caused by Yesinia pestis, the causative agent of pneumonic plague. Relative to the responses induced by the recombinant protein F1-V alone and MPLA-adjuvanted F1-V, the nanoparticle-based vaccination regimen induced an immune response that was characterized by high titer and high avidity IgG1 anti-F1-V antibody that persisted for at least 23 weeks post-vaccination. After challenge, no Y. pestis were recovered from the lungs, livers, or spleens of mice vaccinated with the nanoparticle-based formulation and histopathological appearance of lung, liver, and splenic tissues from these mice post-vaccination was remarkably similar to uninfected control mice

Tamoxifen-associated vasculitis in a breast cancer patient

BACKGROUND: Estrogen plays a critical role in breast cancer. Thereafter, endocrine therapy is a standard of care in patients with breast carcinoma, expressing ER or PR. CASE PRESENTATION: Herein we report the case of a 53-year old patient, who developed cholestasis and vasculitis during the treatment with tamoxifen. This toxicity was reversable after the removal of the drug. Thereafter she continued adjuvant treatment for breast carcinoma with anastrazole. Since tamoxifen has been widely indicated for patients with breast carcinoma, we did a literature review, looking for other cases with this type of toxicity. CONCLUSION: This case is the third with vasculitis informed in the literature, but the first one that additionally developed cholestasis and arthritis. Although it is rare, we discuss the indication of this drug in the actual era, where aromatase inhibitors offer a better security profile