The Waiting Time for Inter-Country Spread of Pandemic Influenza

BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza

Refolding by High Pressure of a Toxin Containing Seven Disulfide Bonds: Bothropstoxin-1 from Bothrops jararacussu

Aggregation is a serious obstacle for recovery of biologically active heterologous proteins from inclusion bodies (IBs) produced by recombinant bacteria. E. coli transformed with a vector containing the cDNA for Bothropstoxin-1 (BthTx-1) expressed the recombinant product as IBs. In order to obtain the native toxin, insoluble and aggregated protein was refolded using high hydrostatic pressure (HHP). IBs were dissolved and refolded (2 kbar, 16 h), and the effects of protein concentration, as well as changes in ratio and concentration of oxido-shuffling reagents, guanidine hydrochloride (GdnHCl), and pH in the refolding buffer, were assayed. A 32% yield (7.6 mg per liter of bacterial culture) in refolding of the native BthTx-1 was obtained using optimal conditions of the refolding buffer (Tris–HCl buffer, pH 7.5, containing 3 mM of a 2:3 ratio of GSH/GSSG, and 1 M GdnHCl). Scanning electron microscopy (SEM) showed that that disaggregation of part of IBs particles occurred upon compression and that the morphology of the remaining IBs, spherical particles, was not substantially altered. Dose-dependent cytotoxic activity of high-pressure refolded BthTx-1 was shown in C2C12 muscle cells

Global response to pandemic flu: more research needed on a critical front

If and when sustained human-to-human transmission of H5N1 becomes a reality, the world will no longer be dealing with sporadic avian flu borne along migratory flight paths of birds, but aviation flu – winged at subsonic speed along commercial air conduits to every corner of planet Earth. Given that air transportation is the one feature that most differentiates present day transmission scenarios from those in 1918, our present inability to prevent spread of influenza by international air travel, as reckoned by the World Health Organization, constitutes a major weakness in the current global preparedness plan against pandemic flu. Despite the lessons of SARS, it is surprising that aviation-related health policy options have not been more rigorously evaluated, or scientific research aimed at strengthening public health measures on the air transportation front, more energetically pursued

Structure-based programming of lymph-node targeting in molecular vaccines

In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these compounds to LNs, where they are efficiently filtered by resident phagocytes1, 2. Here we translate this ‘albumin hitchhiking’ approach to molecular vaccines, through the synthesis of amphiphiles (amph-vaccines) comprising an antigen or adjuvant cargo linked to a lipophilic albumin-binding tail by a solubility-promoting polar polymer chain. Administration of structurally optimized CpG-DNA/peptide amph-vaccines in mice resulted in marked increases in LN accumulation and decreased systemic dissemination relative to their parent compounds, leading to 30-fold increases in T-cell priming and enhanced anti-tumour efficacy while greatly reducing systemic toxicity. Amph-vaccines provide a simple, broadly applicable strategy to simultaneously increase the potency and safety of subunit vaccines.David H. Koch Institute for Integrative Cancer Research at MIT (Koch Institute Support (core) Grant P30-CA14051)National Cancer Institute (U.S.)National Institutes of Health (U.S.) (grant AI091693)National Institutes of Health (U.S.) (grant AI104715)National Institutes of Health (U.S.) (AI095109)United States. Dept. of Defense (contract W911NF-13-D-0001)United States. Dept. of Defense (contract W911NF-07-D-0004)Ragon Institute of MGH, MIT, and Harvar

Sequential biventricular pacing improves regional contractility, longitudinal function and dyssynchrony in patients with heart failure and prolonged QRS

<p>Abstract</p> <p>Aims</p> <p>Biventricular pacing (BiP) is an effective treatment in systolic heart failure (HF) patients with prolonged QRS. However, approximately 35% of the patients receiving BiP are classified as non-responders. The aim of this study is to evaluate the acute effects of VV-optimization on systolic heart function.</p> <p>Methods</p> <p>Twenty-one HF patients aged 72 (46-88) years, QRS 154 (120-190) ms, were studied with echocardiography, Tissue Doppler Imaging (TDI) and 3D-echo the first day after receiving a BiP device. TDI was performed; during simultaneous pacing (LV-lead pacing 4 ms before the RV-lead) and during sequential pacing (LV 20 and 40 ms before RV and RV 20 and 40 ms before LV-lead pacing). Systolic heart function was studied by tissue tracking (TT) for longitudinal function and systolic maximal velocity (SMV) for regional contractility and signs of dyssynchrony assessed by time-delays standard deviation of aortic valve opening to SMV, AVO-SMV/SD and tissue synchronization imaging (TSI).</p> <p>Results</p> <p>The TT mean value preoperatively was 4,2 ± 1,5 and increased at simultaneous pacing to 5,0 ± 1,2 mm (p < 0,05), and at best VV-interval to 5,4 ± 1,2 (p < 0,001). Simultaneous pacing achieved better TT distance compared with preoperative in 16 patients (76%). However, it was still higher after VV-optimization in 12 patients 57%. Corresponding figures for SMV were 3,0 ± 0,7, 3,5 ± 0,8 (p < 0,01), and 3,6 ± 0,8 (p < 0,001). Also dyssynchrony improved.</p> <p>Conclusions</p> <p>VV-optimization in the acute phase improves systolic heart function more than simultaneous BiP pacing. Long-term effects should be evaluated in prospective randomized trials.</p

Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study

Background: Infrared thermal image scanners (ITIS) appear an attractive option for the mass screening of travellers for influenza, but there are no published data on their performance in airports. Methods: ITIS was used to measure cutaneous temperature in 1275 airline travellers who had agreed to tympanic temperature measurement and respiratory sampling. The prediction by ITIS of tympanic temperature (37.8uC and 37.5uC) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). Findings: Using front of face ITIS for prediction of tympanic temperature $37.8uC, the area under the ROC curve was 0.86 (95$37.8uC at screening (95%CI 0 % to 12%); three had no influenza symptoms. Conclusion: ITIS performed moderately well in detecting fever but in this study, during a seasonal epidemic of predominantly influenza type B, the proportion of influenza-infected travellers who were febrile was low and ITIS were no

Comparative study of the stability of bimatoprost 0.03% and latanoprost 0.005%: A patient-use study

<p>Abstract</p> <p>Background</p> <p>The stability of ophthalmic preparations in multidose containers is influenced by the preservative as well as the stability of the active ingredient. Unstable drugs may require refrigeration to preserve their active ingredient level and they are more likely to degrade over time, therefore becoming more susceptible to degradation based on patient mishandling. The purpose of this study was to determine the degree of molecular degradation that occurs in bimatoprost and latanoprost in a patient-use setting.</p> <p>Methods</p> <p>This was an open-label, laboratory evaluation of the relative stability of bimatoprost and latanoprost. Patients presently using bimatoprost (n = 31) or latanoprost (n = 34) were identified at 2 clinical sites in Brazil. Patients were instructed to use and store their drops as usual and return all used medication bottles between day 28 and day 34 after opening.</p> <p>Results</p> <p>Bimatoprost demonstrated no degradation, but latanoprost degraded at various levels. The mean age of bimatoprost was 43.0 ± 3.4 days and the mean age of latanoprost was 43.9 ± 2.8 days (P = .072). The mean percentage of labeled concentration was 103.7% in the bimatoprost bottles and 88.1% in the latanoprost bottles (P < 001).</p> <p>Conclusion</p> <p>This study showed that bimatoprost maintained ≥100% concentration throughout the study period while latanoprost did not.</p

Re-Shuffling of Species with Climate Disruption: A No-Analog Future for California Birds?

By facilitating independent shifts in species' distributions, climate disruption may result in the rapid development of novel species assemblages that challenge the capacity of species to co-exist and adapt. We used a multivariate approach borrowed from paleoecology to quantify the potential change in California terrestrial breeding bird communities based on current and future species-distribution models for 60 focal species. Projections of future no-analog communities based on two climate models and two species-distribution-model algorithms indicate that by 2070 over half of California could be occupied by novel assemblages of bird species, implying the potential for dramatic community reshuffling and altered patterns of species interactions. The expected percentage of no-analog bird communities was dependent on the community scale examined, but consistent geographic patterns indicated several locations that are particularly likely to host novel bird communities in the future. These no-analog areas did not always coincide with areas of greatest projected species turnover. Efforts to conserve and manage biodiversity could be substantially improved by considering not just future changes in the distribution of individual species, but including the potential for unprecedented changes in community composition and unanticipated consequences of novel species assemblages

HIV-associated neurocognitive disorders in sub-Saharan Africa: a pilot study in Cameroon

<p>Abstract</p> <p>Background</p> <p>The disease burden of human immunodeficiency virus (HIV) - acquired immunodeficiency syndrome (AIDS) is highest in sub-Saharan Africa but there are few studies on the associated neurocognitive disorders in this region. The objectives of this study were to determine whether Western neuropsychological (NP) methods are appropriate for use in Cameroon, and to evaluate cognitive function in a sample of HIV-infected adults.</p> <p>Methods</p> <p>We used a battery of 19 NP measures in a cross-sectional study with 44 HIV+ adults and 44 demographically matched HIV- controls, to explore the validity of these NP measures in Cameroon, and evaluate the effect of viral infection on seven cognitive ability domains.</p> <p>Results</p> <p>In this pilot study, the global mean z-score on the NP battery showed worse overall cognition in the HIV+ individuals. Significantly lower performance was seen in the HIV+ sample on tests of executive function, speed of information processing, working memory, and psychomotor speed. HIV+ participants with AIDS performed worse than those with less advanced HIV disease.</p> <p>Conclusions</p> <p>Similar to findings in Western cohorts, our results in Cameroon suggest that HIV infection, particularly in advanced stages, is associated with worse performance on standardized, Western neurocognitive tests. The tests used here appear to be promising for studying NeuroAIDS in sub-Saharan Africa.</p