Challenges in Real-Time Prediction of Infectious Disease: A Case Study of Dengue in Thailand.

Epidemics of communicable diseases place a huge burden on public health infrastructures across the world. Producing accurate and actionable forecasts of infectious disease incidence at short and long time scales will improve public health response to outbreaks. However, scientists and public health officials face many obstacles in trying to create such real-time forecasts of infectious disease incidence. Dengue is a mosquito-borne virus that annually infects over 400 million people worldwide. We developed a real-time forecasting model for dengue hemorrhagic fever in the 77 provinces of Thailand. We created a practical computational infrastructure that generated multi-step predictions of dengue incidence in Thai provinces every two weeks throughout 2014. These predictions show mixed performance across provinces, out-performing seasonal baseline models in over half of provinces at a 1.5 month horizon. Additionally, to assess the degree to which delays in case reporting make long-range prediction a challenging task, we compared the performance of our real-time predictions with predictions made with fully reported data. This paper provides valuable lessons for the implementation of real-time predictions in the context of public health decision making

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (<i>Xiphophorus helleri</i>) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

GABA(A) receptors containing (alpha)5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: an extended ethanol reward circuitry

GABA receptors within the mesolimbic circuitry have been proposed to play a role in regulating alcohol-seeking behaviors in the alcohol-preferring (P) rat. However, the precise GABA(A) receptor subunit(s) mediating the reinforcing properties of EtOH remains unknown. We examined the capacity of intrahippocampal infusions of an alpha5 subunit-selective ( approximately 75-fold) benzodiazepine (BDZ) inverse agonist [i.e., RY 023 (RY) (tert-butyl 8-(trimethylsilyl) acetylene-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate)] to alter lever pressing maintained by concurrent presentation of EtOH (10% v/v) and a saccharin solution (0.05% w/v). Bilateral (1.5-20 microgram) and unilateral (0.01-40 microgram) RY dose-dependently reduced EtOH-maintained responding, with saccharin-maintained responding being reduced only with the highest doses (e.g., 20 and 40 microgram). The competitive BDZ antagonist ZK 93426 (ZK) (7 microgram) reversed the RY-induced suppression on EtOH-maintained responding, confirming that the effect was mediated via the BDZ site on the GABA(A) receptor complex. Intrahippocampal modulation of the EtOH-maintained responding was site-specific; no antagonism by RY after intra-accumbens [nucleus accumbens (NACC)] and intraventral tegmental [ventral tegmental area (VTA)] infusions was observed. Because the VTA and NACC contain very high densities of alpha1 and alpha2 subunits, respectively, we determined whether RY exhibited a "negative" or "neutral" pharmacological profile at recombinant alpha1beta3gamma2, alpha2beta3gamma2, and alpha5beta3gamma2 receptors expressed in Xenopus oocytes. RY produced "classic" inverse agonism at all alpha receptor subtypes; thus, a neutral efficacy was not sufficient to explain the failure of RY to alter EtOH responding in the NACC or VTA. The results provide the first demonstration that the alpha5-containing GABA(A) receptors in the hippocampus play an important role in regulating EtOH-seeking behaviors

Fall prevention intervention technologies: A conceptual framework and survey of the state of the art

In recent years, an ever increasing range of technology-based applications have been developed with the goal of assisting in the delivery of more effective and efficient fall prevention interventions. Whilst there have been a number of studies that have surveyed technologies for a particular sub-domain of fall prevention, there is no existing research which surveys the full spectrum of falls prevention interventions and characterises the range of technologies that have augmented this landscape. This study presents a conceptual framework and survey of the state of the art of technology-based fall prevention systems which is derived from a systematic template analysis of studies presented in contemporary research literature. The framework proposes four broad categories of fall prevention intervention system: Pre-fall prevention; Post-fall prevention; Fall injury prevention; Cross-fall prevention. Other categories include, Application type, Technology deployment platform, Information sources, Deployment environment, User interface type, and Collaborative function. After presenting the conceptual framework, a detailed survey of the state of the art is presented as a function of the proposed framework. A number of research challenges emerge as a result of surveying the research literature, which include a need for: new systems that focus on overcoming extrinsic falls risk factors; systems that support the environmental risk assessment process; systems that enable patients and practitioners to develop more collaborative relationships and engage in shared decision making during falls risk assessment and prevention activities. In response to these challenges, recommendations and future research directions are proposed to overcome each respective challenge.The Royal Society, grant Ref: RG13082

The Influence of Molecular Adsorption on Elongating Gold Nanowires

Using molecular dynamics simulations, we study the impact of physisorbing adsorbates on the structural and mechanical evolution of gold nanowires (AuNWs) undergoing elongation. We used various adsorbate models in our simulations, with each model giving rise to a different surface coverage and mobility of the adsorbed phase. We find that the local structure and mobility of the adsorbed phase remains relatively uniform across all segments of an elongating AuNW, except for the thinning region of the wire where the high mobility of Au atoms disrupts the monolayer structure, giving rise to higher solvent mobility. We analyzed the AuNW trajectories by measuring the ductile elongation of the wires and detecting the presence of characteristic structural motifs that appeared during elongation. Our findings indicate that adsorbates facilitate the formation of high-energy structural motifs and lead to significantly higher ductile elongations. In particular, our simulations result in a large number of monatomic chains and helical structures possessing mechanical stability in excess of what we observe in vacuum. Conversely, we find that a molecular species that interacts weakly (i.e., does not adsorb) with AuNWs worsens the mechanical stability of monatomic chains.Comment: To appear in Journal of Physical Chemistry

Determination of the D0 -> K+pi- Relative Strong Phase Using Quantum-Correlated Measurements in e+e- -> D0 D0bar at CLEO

We exploit the quantum coherence between pair-produced D0 and D0bar in psi(3770) decays to study charm mixing, which is characterized by the parameters x and y, and to make a first determination of the relative strong phase \delta between doubly Cabibbo-suppressed D0 -> K+pi- and Cabibbo-favored D0bar -> K+pi-. We analyze a sample of 1.0 million D0D0bar pairs from 281 pb^-1 of e+e- collision data collected with the CLEO-c detector at E_cm = 3.77 GeV. By combining CLEO-c measurements with branching fraction input and time-integrated measurements of R_M = (x^2+y^2)/2 and R_{WS} = Gamma(D0 -> K+pi-)/Gamma(D0bar -> K+pi-) from other experiments, we find \cos\delta = 1.03 +0.31-0.17 +- 0.06, where the uncertainties are statistical and systematic, respectively. In addition, by further including external measurements of charm mixing parameters, we obtain an alternate measurement of \cos\delta = 1.10 +- 0.35 +- 0.07, as well as x\sin\delta = (4.4 +2.7-1.8 +- 2.9) x 10^-3 and \delta = 22 +11-12 +9-11 degrees.Comment: 37 pages, also available through http://www.lns.cornell.edu/public/CLNS/2007/. Incorporated referee's comment

Structure of hadron resonances with a nearby zero of the amplitude

We discuss the relation between the analytic structure of the scattering amplitude and the origin of an eigenstate represented by a pole of the amplitude.If the eigenstate is not dynamically generated by the interaction in the channel of interest, the residue of the pole vanishes in the zero coupling limit. Based on the topological nature of the phase of the scattering amplitude, we show that the pole must encounter with the Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the dynamical component of the eigenstate is small if a CDD zero exists near the eigenstate pole. We show that the line shape of the resonance is distorted from the Breit-Wigner form as an observable consequence of the nearby CDD zero. Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio

Improved Constraints on Sterile Neutrino Mixing from Disappearance Searches in the MINOS, MINOS+, Daya Bay, and Bugey-3 Experiments.

Searches for electron antineutrino, muon neutrino, and muon antineutrino disappearance driven by sterile neutrino mixing have been carried out by the Daya Bay and MINOS+ collaborations. This Letter presents the combined results of these searches, along with exclusion results from the Bugey-3 reactor experiment, framed in a minimally extended four-neutrino scenario. Significantly improved constraints on the θ_{μe} mixing angle are derived that constitute the most constraining limits to date over five orders of magnitude in the mass-squared splitting Δm_{41}^{2}, excluding the 90% C.L. sterile-neutrino parameter space allowed by the LSND and MiniBooNE observations at 90% CL_{s} for Δm_{41}^{2}<13  eV^{2}. Furthermore, the LSND and MiniBooNE 99% C.L. allowed regions are excluded at 99% CL_{s} for Δm_{41}^{2}<1.6 eV^{2}

Selecting the touched vertebra as the lowest instrumented vertebra in patients with Lenke type-1 and 2 curves: Radiographic results after a minimum 5-year follow-up

BACKGROUND: The selection of the lowest instrumented vertebra (LIV) in patients with adolescent idiopathic scoliosis (AIS) is still controversial. Although multiple radiographic methods have been proposed, there is no universally accepted guideline for appropriate selection of the LIV. We developed a simple and reproducible method for selection of the LIV in patients with Lenke type-1 (main thoracic) and 2 (double thoracic) curves and investigated its effectiveness in producing optimal positioning of the LIV at 5 years of follow-up. METHODS: The radiographs for 299 patients with Lenke type-1 or 2 AIS curves that were included in a multicenter database were evaluated after a minimum duration of follow-up of 5 years. The touched vertebra (TV) was selected on preoperative radiographs by 2 independent examiners. The LIV on postoperative radiographs was compared with the preoperative TV. The final LIV position in relation to the center sacral vertical line (CSVL) was assessed. The CSVL-LIV distance and coronal balance in patients who had fusion to the TV were compared with those in patients who had fusion cephalad and caudad to the TV. The sagittal plane was also reviewed. RESULTS: In 86.6% of patients, the LIV was selected at or immediately adjacent to the TV. Among patients with an A lumbar modifier, those who had fusion cephalad to the TV had a significantly greater CSVL-LIV distance than those who had fusion to the TV (p = 0.006) or caudad to the TV (p = 0.002). In the groups with B (p = 0.424) and C (p = 0.326) lumbar modifiers, there were no differences among the TV groups. CONCLUSIONS: We recommend the TV rule as a third modifier in the Lenke AIS classification system. Selecting the TV as the LIV in patients with Lenke type-1 and 2 curves provides acceptable positioning of the LIV at long-term follow-up. The position of the LIV was not different when fusion was performed caudad to the TV but came at the expense of fewer motion segments. Patients with lumbar modifier A who had fusion cephalad to the TV had greater translation of the LIV, putting these patients at risk for poor long-term outcomes. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence