Nonlinear and delayed impacts of climate on dengue risk in Barbados: A modelling study

Background: Over the last 5 years (2013–2017), the Caribbean region has faced an unprecedented crisis of co-occurring epidemics of febrile illness due to arboviruses transmitted by the Aedes sp. mosquito (dengue, chikungunya, and Zika). Since 2013, the Caribbean island of Barbados has experienced 3 dengue outbreaks, 1 chikungunya outbreak, and 1 Zika fever outbreak. Prior studies have demonstrated that climate variability influences arbovirus transmission and vector population dynamics in the region, indicating the potential to develop public health interventions using climate information. The aim of this study is to quantify the nonlinear and delayed effects of climate indicators, such as drought and extreme rainfall, on dengue risk in Barbados from 1999 to 2016. Methods and findings: Distributed lag nonlinear models (DLNMs) coupled with a hierarchal mixed-model framework were used to understand the exposure–lag–response association between dengue relative risk and key climate indicators, including the standardised precipitation index (SPI) and minimum temperature (Tmin). The model parameters were estimated in a Bayesian framework to produce probabilistic predictions of exceeding an island-specific outbreak threshold. The ability of the model to successfully detect outbreaks was assessed and compared to a baseline model, representative of standard dengue surveillance practice. Drought conditions were found to positively influence dengue relative risk at long lead times of up to 5 months, while excess rainfall increased the risk at shorter lead times between 1 and 2 months. The SPI averaged over a 6-month period (SPI-6), designed to monitor drought and extreme rainfall, better explained variations in dengue risk than monthly precipitation data measured in millimetres. Tmin was found to be a better predictor than mean and maximum temperature. Furthermore, including bidimensional exposure–lag–response functions of these indicators—rather than linear effects for individual lags—more appropriately described the climate–disease associations than traditional modelling approaches. In prediction mode, the model was successfully able to distinguish outbreaks from nonoutbreaks for most years, with an overall proportion of correct predictions (hits and correct rejections) of 86% (81%:91%) compared with 64% (58%:71%) for the baseline model. The ability of the model to predict dengue outbreaks in recent years was complicated by the lack of data on the emergence of new arboviruses, including chikungunya and Zika. Conclusion: We present a modelling approach to infer the risk of dengue outbreaks given the cumulative effect of climate variations in the months leading up to an outbreak. By combining the dengue prediction model with climate indicators, which are routinely monitored and forecasted by the Regional Climate Centre (RCC) at the Caribbean Institute for Meteorology and Hydrology (CIMH), probabilistic dengue outlooks could be included in the Caribbean Health-Climatic Bulletin, issued on a quarterly basis to provide climate-smart decision-making guidance for Caribbean health practitioners. This flexible modelling approach could be extended to model the risk of dengue and other arboviruses in the Caribbean region

Measurement of the 3He(e,e'p)pn reaction at high missing energies and momenta

Results of the Jefferson Lab Hall A quasielastic 3He(e,e'p)pn measurements are presented. These measurements were performed at fixed transferred momentum and energy, q = 1502 MeV/c and omega = 840 MeV, respectively, for missing momenta p_m up to 1 GeV/c and missing energies in the continuum region, up to pion threshold; this kinematic coverage is much more extensive than that of any previous experiment. The cross section data are presented along with the effective momentum density distribution and compared to theoretical models.Comment: 5 pages, 3 figures, updated to reflect published paper: minor text changes from previous version along with updated and added reference

The Quasielastic 3He(e,e'p)d Reaction at Q^2 = 1.5 GeV^2 for Recoil Momenta up to 1 GeV/c

We have studied the quasielastic 3He(e,e'p)d reaction in perpendicular coplanar kinematics, with the energy and momentum transferred by the electron fixed at 840 MeV and 1502 MeV/c, respectively. The 3He(e,e'p)d cross section was measured for missing momenta up to 1000 MeV/c, while the A_TL asymmetry was extracted for missing momenta up to 660 MeV/c. For missing momenta up to 150 MeV/c, the measured cross section is described well by calculations that use a variational ground-state wave function of the 3He nucleus derived from a potential that includes three-body forces. For missing momenta from 150 to 750 MeV/c, strong final-state interaction effects are observed. Near 1000 MeV/c, the experimental cross section is more than an order of magnitude larger than predicted by available theories. The A_TL asymmetry displays characteristic features of broken factorization, and is described reasonably well by available models.Comment: 5 pages, 3 figures, submitted to Physical Review Letters, v3: changed conten

Fracture of jammed colloidal suspensions

Concentrated colloidal suspensions display dramatic rises in viscosity, leading to jamming and granulation, with increasing shear rate. It has been proposed that these effects result from inter particle friction, as lubrication forces are overcome. This suggests the jamming of concentrated colloidal suspensions should exhibit some shared phenomenology with macroscopic granular systems where friction leads to two different types of jammed state. Here we show that transient rheological measurements can be used to probe the processes of granulation in concentrated colloidal suspensions. Our results support the idea that frictional contacts are created between jammed particles. The jamming behaviour displays two qualitatively different regimes separated by a critical strain rate with qualitatively different types of fracture/break up behaviour. In the lower strain rate regime, it is found that vibrations can be used to control jamming and granulation, resulting in a flowable fluid

Probing the high momentum component of the deuteron at high Q^2

The d(e,e'p) cross section at a momentum transfer of 3.5 (GeV/c)^2 was measured over a kinematical range that made it possible to study this reaction for a set of fixed missing momenta as a function of the neutron recoil angle theta_nq and to extract missing momentum distributions for fixed values of theta_nq up to 0.55 GeV/c. In the region of 35 (deg) <= theta_nq <= 45 (deg) recent calculations, which predict that final state interactions are small, agree reasonably well with the experimental data. Therefore these experimental reduced cross sections provide direct access to the high momentum component of the deuteron momentum distribution in exclusive deuteron electro-disintegration.Comment: 5 pages, 2 figure

Recoil Polarization Measurements for Neutral Pion Electroproduction at Q^2=1 (GeV/c)^2 Near the Delta Resonance

We measured angular distributions of differential cross section, beam analyzing power, and recoil polarization for neutral pion electroproduction at Q^2 = 1.0 (GeV/c)^2 in 10 bins of W across the Delta resonance. A total of 16 independent response functions were extracted, of which 12 were observed for the first time. Comparisons with recent model calculations show that response functions governed by real parts of interference products are determined relatively well near 1.232 GeV, but variations among models is large for response functions governed by imaginary parts and for both increases rapidly with W. We performed a nearly model-independent multipole analysis that adjusts complex multipoles with high partial waves constrained by baseline models. Parabolic fits to the W dependence of the multipole analysis around the Delta mass gives values for SMR = (-6.61 +/- 0.18)% and EMR = (-2.87 +/- 0.19)% that are distinctly larger than those from Legendre analysis of the same data. Similarly, the multipole analysis gives Re(S0+/M1+) = (+7.1 +/- 0.8)% at W=1.232 GeV, consistent with recent models, while the traditional Legendre analysis gives the opposite sign because its truncation errors are quite severe. Finally, using a unitary isobar model (UIM), we find that excitation of the Roper resonance is dominantly longitudinal with S1/2 = (0.05 +/- 0.01) GeV^(-1/2) at Q^2=1. The ReS0+ and ReE0+ multipoles favor pseudovector coupling over pseudoscalar coupling or a recently proposed mixed-coupling scheme, but the UIM does not reproduce the imaginary parts of 0+ multipoles well.Comment: 60 pages, 54 figure

Precision Measurement of the Neutron Spin Asymmetries and Spin-dependent Structure Functions in the Valence Quark Region

We report on measurements of the neutron spin asymmetries $A_{1,2}^n$ and polarized structure functions $g_{1,2}^n$ at three kinematics in the deep inelastic region, with $x=0.33$, 0.47 and 0.60 and $Q^2=2.7$, 3.5 and 4.8 (GeV/c)$^2$, respectively. These measurements were performed using a 5.7 GeV longitudinally-polarized electron beam and a polarized $^3$He target. The results for $A_1^n$ and $g_1^n$ at $x=0.33$ are consistent with previous world data and, at the two higher $x$ points, have improved the precision of the world data by about an order of magnitude. The new $A_1^n$ data show a zero crossing around $x=0.47$ and the value at $x=0.60$ is significantly positive. These results agree with a next-to-leading order QCD analysis of previous world data. The trend of data at high $x$ agrees with constituent quark model predictions but disagrees with that from leading-order perturbative QCD (pQCD) assuming hadron helicity conservation. Results for $A_2^n$ and $g_2^n$ have a precision comparable to the best world data in this kinematic region. Combined with previous world data, the moment $d_2^n$ was evaluated and the new result has improved the precision of this quantity by about a factor of two. When combined with the world proton data, polarized quark distribution functions were extracted from the new $g_1^n/F_1^n$ values based on the quark parton model. While results for $\Delta u/u$ agree well with predictions from various models, results for $\Delta d/d$ disagree with the leading-order pQCD prediction when hadron helicity conservation is imposed.Comment: A typing error in A_\parallel(3He) at x=0.47 in Table VII of Phys. Rev. C has been noticed and correcte

Clinical pharmacodynamic factors in docetaxel toxicity

Neutropenia is the main dose-limiting toxicity occurring in docetaxel treatment. The objective of this study was to identify pharmacodynamic (PD) factors responsible for the neutropaenia caused by docetaxel. Data were obtained from 92 patients treated with docetaxel as a monochemotherapy in two different treatment centres. A semiphysiological population pharmacokinetic–pharmacodynamic (PK/PD) model was applied to describe the time course of neutrophils and the neutropaenic effect of docetaxel. The plasma docetaxel concentration was assumed to inhibit the proliferation of neutrophil precursors through a linear model: Drug effect=Slope × Conc. Slope corresponds to the patients' sensitivity to the neutropaenic effect of docetaxel. Covariate analysis was performed by testing the relationship between the patients' characteristics and Slope using the program NONMEM. The neutropaenic effect of docetaxel showed a high interindividual variability. Three significant PD covariates were identified: serum α1-acid glycoprotein levels (AAG), level of chemotherapy pretreatment, and treatment centre. Extensive pretreatment was associated with an increase in Slope values meaning a higher haematotoxicity. An increase in AAG was associated with a decrease of both Slope and docetaxel plasma clearance. Patients treated in one centre had both higher Slope and docetaxel clearance. The centre effect (most likely due to a bias in the PK part of the study between the two centres) reveals the robustness of the PK/PD model. Individual dosing of docetaxel should be based on previous chemotherapy but not on the AAG level since it has a similar influence on PD and PK docetaxel parameters. This methodology should be applied to further investigate elderly patients and to identify more precisely the characteristics of previous chemotherapy that contribute to the cumulative myelotoxicity

Nanoparticle–membrane interactions

Engineered nanomaterials have a wide range of applications and as a result, are increasingly present in the environment. While they offer new technological opportunities, there is also the potential for adverse impact, in particular through possible toxicity. In this review, we discuss the current state of the art in the experimental characterisation of nanoparticle-membrane interactions relevant to the prediction of toxicity arising from disruption of biological systems. One key point of discussion is the urgent need for more quantitative studies of nano-bio interactions in experimental models of lipid system that mimic in vivo membranes

Building resilience to mosquito-borne diseases in the Caribbean.

Small island developing states in the Caribbean are among the most vulnerable countries on the planet to climate variability and climate change. In the last 3 decades, the Caribbean region has undergone frequent and intense heat waves, storms, floods, and droughts. This has had a detrimental impact on population health and well-being, including an increase in infectious disease outbreaks. Recent advances in climate science have enhanced our ability to anticipate hydrometeorological hazards and associated public health challenges. Here, we discuss progress towards bridging the gap between climate science and public health decision-making in the Caribbean to build health system resilience to extreme climatic events. We focus on the development of climate services to help manage mosquito-transmitted disease epidemics. There are numerous areas of ongoing biological research aimed at better understanding the direct and indirect impacts of climate change on the transmission of mosquito-borne diseases. Here, we emphasise additional factors that affect our ability to operationalise this biological understanding. We highlight a lack of financial resources, technical expertise, data sharing, and formalised partnerships between climate and health communities as major limiting factors to developing sustainable climate services for health. Recommendations include investing in integrated climate, health and mosquito surveillance systems, building regional and local human resource capacities, and designing national and regional cross-sectoral policies and national action plans. This will contribute towards achieving the Sustainable Development Goals (SDGs) and maximising regional development partnerships and co-benefits for improved health and well-being in the Caribbean