text:
Model parameterization
Vaccination against 2009 pandemic H1N1 in a population dynamical model of Vancouver, Canada: timing is everything
Jessica M Conway1, 2,
Ashleigh R Tuite3,
David N Fisman3,
Nathaniel Hupert4, 5,
Rafael Meza1,
Bahman Davoudi1,
Krista English1,
P van den Driessche6,
Fred Brauer2,
Junling Ma6,
Lauren Ancel Meyers7,
Marek Smieja8,
Amy Greer3, 9,
Danuta M Skowronski10,
David L Buckeridge11, 12,
Jeffrey C Kwong3, 13,
Jianhong Wu14,
Seyed M Moghadas14,
Daniel Coombs2,
Robert C Brunham1 and
Babak Pourbohloul1, 15Email author
© Conway et al.; licensee BioMed Central Ltd. 2011
Much remains unknown about the effect of timing and prioritization of vaccination against pandemic (pH1N1) 2009 virus on health outcomes. We adapted a city-level contact network model to study different campaigns on influenza morbidity and mortality.
We modeled different distribution strategies initiated between July and November 2009 using a compartmental epidemic model that includes age structure and transmission network dynamics. The model represents the Greater Vancouver Regional District, a major North American city and surrounding suburbs with a population of 2 million, and is parameterized using data from the British Columbia Ministry of Health, published studies, and expert opinion. Outcomes are expressed as the number of infections and deaths averted due to vaccination.
The model output was consistent with provincial surveillance data. Assuming a basic reproduction number = 1.4, an 8-week vaccination campaign initiated 2 weeks before the epidemic onset reduced morbidity and mortality by 79-91% and 80-87%, respectively, compared to no vaccination. Prioritizing children and parents for vaccination may have reduced transmission compared to actual practice, but the mortality benefit of this strategy appears highly sensitive to campaign timing. Modeling the actual late October start date resulted in modest reductions in morbidity and mortality (13-25% and 16-20%, respectively) with little variation by prioritization scheme.
Delays in vaccine production due to technological or logistical barriers may reduce potential benefits of vaccination for pandemic influenza, and these temporal effects can outweigh any additional theoretical benefits from population targeting. Careful modeling may provide decision makers with estimates of these effects before the epidemic peak to guide production goals and inform policy. Integration of real-time surveillance data with mathematical models holds the promise of enabling public health planners to optimize the community benefits from proposed interventions before the pandemic peak.
Attack Rate
Basic Reproduction Number
Vaccination Campaign
The emergence of a novel swine-origin influenza A/H1N1 virus in the spring of 2009 led the WHO to declare the first influenza pandemic of the 21st century [1]. In the Canadian province of British Columbia, Canada it first appeared as a spring-summer wave of very low intensity, but resurged as a more substantial and widespread second wave in the fall, as in the rest of Canada and many other countries worldwide [2, 3]. The commencement of this second wave varied by jurisdiction, likely depending in part upon prior first wave experience, demographic and environmental factors. In British Columbia, second wave pandemic H1N1 (pH1N1) activity began slowly in early September 2009, coinciding with the reconvening of schools and universities; increased more abruptly in mid-October; peaked during the last week of October; and fully resolved by the end of the calendar year [4]. This stands in marked contrast with Canada's usual influenza season, which typically spans November to April [5].
Characterization of the epidemiology of pH1N1 began early in the outbreak. One of the striking features of this novel influenza strain is its association with higher attack rates in younger individuals, compared to what is usually observed for seasonal influenza [6–12]. Proposed explanations for an apparently reduced susceptibility in older adults include pre-existing immunity due to prior exposure to related H1N1 strains circulating prior to 1957 [13], accumulated cross-protection derived from seasonal human H1N1 infection across the lifespan [14], and/or differences in the contact networks of younger individuals, who are more highly connected (and hence more likely to be exposed to pH1N1 early in an epidemic) than older individuals [15]. Regardless of the reasons underlying differential vulnerability to infection by age, this observation has important implications for the design and implementation of mitigation strategies for pH1N1 and future pandemic influenza viruses.
Vaccination is an important influenza control measure and was a key component of many countries' pandemic preparedness plans. Production of pH1N1 vaccine began soon after the pandemic potential of pH1N1 was recognized. However, the early arrival of the second wave of pH1N1 in many regions of the northern hemisphere, combined with production delays, resulted in the implementation of vaccination programs in populations already experiencing moderate to high incidence of pH1N1, a sequence of events expected to reduce the ultimate population impact of immunization. Quantifying this reduction and determining how it might have been mitigated through alternative dispensing schemes motivated the modeling effort reported here.
Seasonal influenza vaccination campaigns have historically targeted those at greatest risk of the severe outcomes of influenza--notably the very young, the elderly and individuals of all ages with underlying medical conditions, as well as their close contacts, including health care workers [5]. It has been suggested that vaccination of schoolchildren might be a more effective strategy [16], since younger age groups are responsible for a disproportionate amount of influenza transmission, and targeting these groups would indirectly protect at-risk groups [17, 18]. Some regions--notably the province of Ontario--have adopted a universal influenza immunization program (UIIP) whereby influenza vaccine is provided free to all citizens over the age of 6 months [19]. In the case of pH1N1, the misalignment between vaccine availability and the onset and peak of the second pandemic wave in the fall 2009 required prioritization of vaccine. Greater infection risk and poor outcomes in younger individuals argued for targeted vaccination of younger age groups [18]. Conversely, older individuals were at decreased risk of infection with pH1N1, but experienced higher rates of severe outcomes, including mortality [20–22]. This is illustrated in outcome surveillance data from British Columbia for both waves, showing that pH1N1 detection was higher in children, but both the per-laboratory confirmed case hospitalization and fatality rates were greatest in older adults, with substantial increase beginning at age 50. The pH1N1 vaccine prioritization schemes adopted by many countries required a balance of these competing considerations and ultimately differed from seasonal influenza recommendations as a result of vaccine delay and unique pandemic patterns of age-related risk [12, 23–26].
Mathematical models of the spread of the pH1N1 virus across the population played a prominent role in the assessment of the pH1N1 pandemic risk and in the evaluation and design of intervention and control strategies. During the early stages of the pH1N1 pandemic, mathematical analyses of the initial data from Mexico and other countries allowed researchers to estimate the transmissibility of the pH1N1 virus, as measured by the basic reproduction number [8, 11, 27, 28]. As the pandemic progressed, many modeling studies investigated the impact of different kinds of containment strategies like social distancing [29], vaccination [18, 28–30], and the use of antivirals [29, 31]. These studies among many others provided important information to policy makers and demonstrated the value of mathematical modeling as a risk assessment tool during the emergence of new infectious disease agents.
We developed a mathematical model of the transmission dynamics of the pH1N1 virus in the Greater Vancouver Regional District (GVRD) to quantify the impact of vaccination campaign timing in relation to the pandemic peak on the projected outcomes of these strategies. Models incorporating age structure and/or heterogeneity in disease vulnerability have long been used to investigate issues surrounding immunization, either with instantaneous vaccinations (e.g. [18, 32–34]) or with vaccinations concurrent with the epidemic (e.g. [35]). In particular such models have been used to investigate vaccination strategies in combination with campaign timing, as in [36–38]. Our aim was to develop a population dynamical model that represents the transmission of pH1N1 influenza in a realistic urban setting. We therefore incorporated into this model detailed demographic and behavioural factors that provide the basis for pandemic transmission dynamics. In particular, in addition to modeling the age structure of the population, we also considered the heterogeneity in the contact rates between individuals by age to better represent the overall contact structure of the population and better approximate the time course of the epidemic. To parameterize our model we used data from the Greater Vancouver Regional District (GVRD), British Columbia (BC), Canada. This model was used to assist policymakers in evaluating different intervention strategies throughout the Fall (2009) including the impact of vaccination of schoolchildren in addition to the specified target groups, social distancing, as well as assessing the likelihood of observing a third wave in the winter of 2010. However, as we discuss below, one should observe similar outcomes in most urban settings.
We developed a susceptible-infected-recovered (SIR)-type compartmental model, extended to capture heterogeneity in age and behaviour, both of which affect contact patterns between individuals. A complete description of the model is provided in the Appendix, Additional file 1. The population was divided into six compartments representing different disease states: susceptible (S), vaccinated against pH1N1 (SW), exposed (E), pre-symptomatically infectious (before clinical infection onset) (A), infectious (either symptomatic, after clinical infection onset; or asymptomatic) (I), and immune (M). In an attempt to capture the social network-type dynamics in a more computationally tractable manner, the population was stratified by age and activity level. Activity level groupings correspond to the average number of contacts that individuals have per week. Mixing of the different age/activity groups was obtained from models of the GVRD contact network [39, 40]. Each compartment is comprised of many sub-compartments for each age and activity level grouping. We ran the model to investigate the time period from September 1, 2009 until May 31, 2010.
Epidemiological parameters for pH1N1 were derived from the published literature and empirical data, with some assumptions reflecting the nature of influenza infection (Table 1). For simulations, the baseline transmission parameter values were: basic reproduction number R 0 of 1.4, latent period of 3 days, and infectious period of 7 days (1 day before clinical infection onset and 6 days either symptomatic, after clinical infection onset, or asymptomatic) [21, 41]. Demographic and behavioural data used to derive age-specific average number of contacts per week was obtained for the GVRD [39, 42].
Model parameter values
Value (range)
Population size
2006 Census [42]
Latent period (days)
3 (2-4)
Tuite et al. 2010 [22]
Initial asymptomatic infectious period (in all infected individuals) (days)
Liao et al. 2010 [43]
Total duration of infectiousness (days)
Tuite et al. 2010 [22]; De Serres [44]
Basic Reproduction number (R 0)
1.4 (1.2-1.8)
Pourbohloul et al. 2009 [27]
Proportion of population with pre-existing immunity
Centers for Disease Control and Prevention 2009 [13]; Fisman et al. 2009 [6]
0.9 (0.5-1)
Product Monograph Arepanrix(tm) H1N1 [45]; Waddington et al., 2010 [46]
Proportion of infected individuals who self-isolate
Mortality (per 100,000 infections)
Donaldson et al. 2009 [47]
Initial condition
We set the start time of the epidemic to September 6th, which corresponds to the start of school in Vancouver. As of August 31st there had been only a total of 812 laboratory-confirmed cases of pH1N1 influenza since April of 2009 in British Columbia [48]. We assumed that the number of actual (currently infected) cases on September 6th was 100. We then distributed them through the age and behaviour compartments randomly with probably weighted by population fraction and contact rate in each compartment. Each result we show in the following represents the mean of 10000 simulations starting with different random initial conditions. We further assume that the rest of the population is completely susceptible. Although there was pH1N1 activity in the GVRD in Spring 2009 which would result in some background immunity, it was quite low, as evidenced by numbers of laboratory-confirmed cases and reported hospitalizations [48]. We therefore assumed the effect of background immunity was negligible.
Vaccination implementation
The time to administer vaccine across the population was assumed to be 8 weeks. Vaccine distribution spanned this roll-out period and resulted in final coverage levels in different age groups (described below). For results shown below, we assumed the daily number of vaccinations gradually decreased throughout the campaign. However using different vaccination rates gave quantitatively and qualitatively similar results; see Appendix, Additional file 1 for details and additional information. We assumed that there was no intra-group age prioritization for vaccine distribution among those who were eligible to receive the vaccine. We assumed a 2-week delay between vaccine receipt and development of a protective immune response [49].
All individuals receiving vaccine were assumed to have a reduction in pH1N1 acquisition risk equal to 90% (modeled as a "leaky vaccine"). Although this number may seem high at first, studies of both the efficacy and the effectiveness of the pH1N1 vaccine used in Canada have shown remarkably high levels of protection [45, 46, 50]. In particular, initial studies of seroconversion and seroprotection rates by the adjuvanted pH1N1 vaccine used in Canada showed high levels (>90%) of both consistently across all age groups [45, 46]. Further, a recent study with over 500 participants in Canada showed that this vaccine was highly effective at preventing laboratory-confirmed pH1N1 influenza [50]. The reported high vaccine protection (effectiveness), generally over 90%, was maintained across most sensitivity analyses [50]. These results are supported by a similar study investigating the effectiveness of a the same vaccine in children <10 years of age, which reported statistically significant 100% vaccine effectiveness for a single dose assuming a 2-week development of protective immune response [51]. We therefore assumed a baseline vaccine efficacy/effectiveness of 0.9 across all age groups. Although as mentioned here there is strong evidence that the protection offered by the pH1N1 vaccine predominantly distributed in Canada was extremely high, we nevertheless also performed extensive sensitivity analyses of our results and conclusions assuming much lower values of vaccine protection (see Figures S5 and S6, Additional file 1).
Vaccination scenarios
We considered four different vaccination strategies. In the first two and fourth scenarios, the final population vaccination coverage was approximately 47%, matching age-standardized estimates of overall pH1N1 vaccine coverage in the GVRD. However, each of these scenarios simulated different patterns of vaccine distribution across age groups. The Actual Coverage (AC) strategy assumed a vaccine uptake in the different age groups corresponding to the observed uptake of pH1N1 vaccine in the GVRD during the Fall vaccination campaign of 2009, which covered an aggregate of 47% of the population (BC Centre for Disease Control, personal communication; see Table 2 for age-specific vaccination coverage). For the Uniform Coverage (UC) strategy, final vaccine uptake was set at 47% within each age group.
Age-specific coverage levels for the different vaccination scenarios
Vaccination strategy
Vaccination coverage (%)
Actual pH1N1 vaccination in the Greater Vancouver Regional District (AC)
≥65, community-dwelling
≥65, long-term care
Uniform coverage (UC)
Parents and children (PC)
All other ages
Parents and children/actual sequence (PC+)
Because of heightened interest in prioritization of demographic groups potentially capable of accelerating early transmission of influenza [18], we also modeled a Parents and Children (PC) strategy in which 100% of children aged 5-17 and their parents (represented by 100% of adults aged 30-39) received the vaccine. No other members of the population were vaccinated under this strategy, which had a final population coverage of only 36% in contrast to the 47% of the first two scenarios, a difference that corresponds to over 230,000 fewer doses distributed throughout the GVRD.
Finally since the PC strategy has a lower population coverage than the first two, we formulated a fourth strategy that combines it with a more general vaccine distribution to attain a final 47% coverage. In the AC and UC coverage scenarios described above, 36% population coverage is achieved in approximately 38 days. For this fourth scenario, the parents-and-children/actual sequence strategy (PC+), we assume that after that point (38 days) the vaccine is then made available to the general public for the remaining time of the campaign. We model this using AC coverages scaled down proportionally to make up for the 11% deficit in coverage of the PC strategy.
To reflect actual pH1N1 response activities in GVRD, we initiated each of the modeled vaccination programs on October 26, 2009. For the baseline 8-week campaign length, vaccination was completed by the end of the week of December 14, 2009.
Sensitivity analyses
We tested the robustness of projections to model assumptions by performing sensitivity analyses over plausible ranges of parameter values. A range of values for R 0, latent period, infectious period, vaccine efficacy, and vaccination campaign lengths (see Table 1) were tested in the absence of vaccination (where appropriate) and in the presence of each of the three vaccination strategies. For each vaccination strategy, we also tested the effect of varying the start date of vaccination campaigns under baseline transmission parameter values. Model outputs were assessed for vaccination campaigns initiated at the beginning of each week from July 5, 2009, to November 22, 2009. Finally, we also assessed the impact of using different pH1N1 age-specific mortality profiles on our results.
Baseline case without and with vaccination
Although true pH1N1 infection incidence is difficult to determine, the recorded spread of pH1N1 through different age groups in the GVRD starting in the early autumn of 2009 was closely reproduced by the model using the baseline parameter values for pH1N1 (Figure 1). In particular, the model predicted that the highest number of infections in the 18-54 age group, followed by the 5-17, 0-4, and ≥55 age groups (Figure 1d), which is similar to what was observed within laboratory-confirmed reported cases. Further, the model predicted a peak of pH1N1 activity in Vancouver in early November and highest age-specific attack rates in the 5-17 age group, followed by the 18-54, 0-4, and ≥55 age groups (Figure 2, dashed lines).
Age distribution of reported cases and comparison to model predictions. Population denominators for the given age groups were derived from 2006 census data for the GVRD [41]. a New infections in September 2009 only, b new infections in October 2009 only, c new infections in November 2009 only, and d cumulative number of infections, September 1-December 1, 2009. Vaccination began the week of October 26, 2009 and continued for 8 weeks, to obtain the actual coverage levels outlined in Table 2. The resulting epidemic curves assume R 0 of 1.4, latent period of 3 days, and infectious period of 7 days.
Age-specific daily incidence of pH1N1 cases. The number of new cases per day per 100,000 individuals is presented in the absence (solid lines) and presence (dotted lines) of pH1N1 vaccination. Vaccination began the week of October 26, 2009 and continued for 8 weeks, to obtain the actual coverage levels outlined in Table 2. The resulting epidemic curves assume R 0 of 1.4, latent period of 3 days, and infectious period of 7 days.
Figure 2 shows the impact of simulating the actual GVRD pH1N1 vaccination campaign to the baseline model (Actual Coverage strategy initiated October 26, 2009, dashed lines). This intervention reduced the simulated cumulative attack rate from 48.3% to 42.0%, representing over 120,000 pH1N1 infections prevented in the Vancouver population. The number of cases prevented is greatest in the 5-17 year old age group (7625 per 100,000 population), followed by the 18-54 (6011 per 100,000), 0-4 (5824 per 100,000), and ≥55 (4152 per 100,000) age groups. The fraction of cases prevented is not equivalent across age groups with this strategy: individuals aged 0-4 and ≥55 years experience the largest relative reduction in final attack rate (18% decrease), while those in the 5-17 age group have the smallest (10% decrease).
Impact of timing of vaccination campaign on final attack rates
As expected, earlier implementation of the Actual Coverage strategy resulted in smaller final attack rates (Figure 3). Initiation of vaccination campaigns in the presence of moderate levels of circulating pH1N1, but prior to the epidemic peak, had a modest but detectable impact on final attack rates. For example, under baseline assumptions, an 8-week campaign initiated 2 weeks before epidemic onset (August 24) reduced the attack rate by approximately 83%; an 8-week campaign initiated 1 month into the epidemic (October 5) reduced the attack rate by approximately 47%. Additionally, distribution of vaccine in a shorter period of time resulted in a greater reduction in attack rates for a given vaccination campaign start date.
Effect of vaccination campaign start date on overall attack rate. For a given vaccination campaign start date, the percent reduction in final attack rate relative to that observed in the absence of vaccination is presented for campaign lengths of between 4 and 12 weeks. Vaccination campaigns were implemented weekly, starting July 5, 2009, with the last campaign started November 22, 2009. The start of the Vancouver influenza season on September 6, 2009 is indicated by a vertical line. All simulations assumed R 0 of 1.4, latent period of 3 days, and infectious period of 7 days.
Transmission and mortality impact of different vaccination strategies
Under baseline assumptions (i.e., vaccination initiated on October 26, 2009 with an 8-week campaign), vaccination of not only parents and children/general population in sequence (PC+), but also of parents and children (PC) alone were more effective than the actual coverage (AC) or a uniform coverage (UC) strategy in reducing the influenza attack rate but each achieved equivalent mortality reduction (see Tables 3 and 4, Figure 4a and 4b, and Figures S1 and S2, Additional file 1 for additional values of R 0). Comparing the AC, UC PC, and PC+ strategies for different campaign initiation end times yielded more complex results. Prior to the start of the fall wave (August 24, 2009 or earlier), the PC strategy resulted in lower attack rates and mortality in the protected age groups (5-17 and 18-54) but higher attack rates and mortality in the other age groups (0-4 and ≥55) than either the AC or the UC strategies. The PC+ strategy yielded lower still attack rates but also the lowest overall mortality reduction. For campaigns initiated during the fall wave but prior to the epidemic peak (September 28 and October 26, respectively), the PC and PC+ strategies were superior in both attack rate and mortality reductions. During this same time frame the AC strategy was more successful at reducing attack rates than the UC strategy, with a minor exception in the 18-54 age group for which the UC strategy was favorable. This general trend likely resulted from higher AC coverage in the age groups with both the highest age-specific attack rates (5-17 year olds) and the most vulnerable age groups (0-4 year olds and ≥65). This explanation is supported by the overall success, in both attack rate reduction and mortality reduction, of the PC+ strategy: as with the PC strategy, the age group with highest age-specific attack rates is completely protected, but there is also limited protection for the most vulnerable age groups. There were no substantive differences in the outcomes of all vaccination strategies (AC, UC, PC, or PC+) when the campaigns were initiated well after the epidemic peak (on November 23).
Overall and age-specific final attack rates for pH1N1 for different vaccination scenarios for R 0 1.4 and an 8-week vaccine campaign length.
Vaccination start date
Attack rate,% (% reduction vs. None)
24-Aug
PC+
23-Nov
Attack rate is defined here as the total number of infections. 'AC' indicates the actual vaccination coverage for pH1N1 in the GVRD, 'UC' the uniform coverage vaccination strategy, 'PC' the parents and children vaccination strategy, and 'PC+' the PC/actual sequence strategy
Overall and age-specific pH1N1-attributable mortality for different vaccination scenarios for R 0 1.4 and an 8-week vaccine campaign length.
Mortality per 100,000 population (% reduction vs. None)
Attack rate is defined here as the total number of infections. 'AC' indicates the actual vaccination coverage for pH1N1 in the GVRD, 'UC' the uniform coverage vaccination strategy, 'UC' the uniform coverage vaccination strategy, 'PC' the parents and children vaccination strategy, and 'PC+' the PC/actual sequence strategy
Impact of timing on the effectiveness of different vaccination strategies. Vaccination campaigns were implemented weekly, starting July 5, 2009, with the last campaign started November 22, 2009. For a given campaign start date, the reduction in a final attack rates and b mortality relative to no vaccination was assessed using actual (blue, solid line), uniform (green, dashed line), parents and children only (red, dash-dotted line), or parents and children only/actual sequence (cyan, dotted line) vaccination strategies. All simulations assumed R 0 of 1.4, latent period of 3 days, infectious period of 7 days and an 8-week vaccine roll-out period.
These results are especially notable because of the difference in the overall coverage between the strategies: 47% for the AC, UC, and PC+ strategies vs 36% for the PC strategy. Similar results were observed for pandemic viruses exhibiting less transmissibility than pH1N1 (e.g., R 0 = 1.2) (see Figures S1 and S2, Additional file 1 and Tables S1-S6, Additional file 1 for additional values of R 0), assuming different reported age-specific mortality profiles (see Figure S3, Additional file 1), and considering only the PC strategy assuming lower coverage levels in the parents and children groups (see Figure S4, Additional file 1).
We evaluated the interplay between pH1N1 vaccine efficacy and the timing of the vaccination campaign for the Actual Coverage strategy (Figure 5, see Figure S5, Additional file 1 for sensitivity of cumulative attack rate to vaccine efficacy). If the simulated campaign begins well before the onset of the epidemic, vaccine efficacy was observed to have an important impact on depleting the size of the susceptible population and consequently reducing the outbreak size. For a vaccine with 85% or 95% efficacy, for example, the percent reduction in final attack rate relative to that observed in the absence of vaccination was 85% or 92%, respectively. However, for vaccination campaigns initiated after the onset of the epidemic, reductions in final attack rates were not highly sensitive to vaccine efficacy. For example, when vaccinations were implemented late in the epidemic stage (October or November) the percent reduction in final attack rate varied only slightly when vaccine efficacy increased from 50% to 100% (almost vertical lines representing the 5% and 15% contours in Figure 5). We observed similar patterns for other coverage scenarios (see Figure S6, Additional file 1).
Effect of vaccination campaign start date and vaccine efficacy on overall attack rates. For a given vaccination campaign start date, the percent reduction in final attack rate relative to that observed in the absence of vaccination is presented for vaccine efficacy of between 50% and 100%. The ranges of the percent reduction in attack rates are indicated by solid lines and labeled. Vaccination campaigns were implemented weekly, starting July 5, 2009, with the last campaign started November 22, 2009. The start of the Vancouver influenza season on September 6, 2009 is indicated by a vertical line. All simulations assumed R 0 of 1.4, latent period of 3 days, and infectious period of 7 days.
Sensitivity of results to transmission parameters for pH1N1
Varying epidemiological parameters changed the cumulative attack rate in the presence of the Actual Coverage strategy in predictable ways. This is clear from Figure 6 (see Figure S7, Additional file 1 for results in the absence of vaccination), where we show a sensitivity analysis on the cumulative attack rate for a given R 0. To generate the shaded areas, we ran simulations for parameter combinations from the ranges given in Table 1 with each combination given equal wait. We observed in particular that the lengths of shortening the infectious and latent periods resulted in more rapid epidemic growth and larger final outbreak sizes for a given value of R 0, due to the shorter window of opportunity for vaccination to have an effect. Lengthening these parameters had the opposite effect. The sensitivity of final attack rates to the latent and infectious periods diminished as transmissibility (represented by R 0) increased.
Sensitivity of cumulative attack rates to epidemiological parameters. Cumulative attack rates were determined for a range of values of R 0 (1.2-1.8), latent period (2-4 days), and infectious period (5-7 days) in the presence of pH1N1 vaccination. The range of results observed for varying latent and infectious period lengths are presented for each value of R 0. Vaccination began the week of October 26, 2009 and continued for 8 weeks, to obtain the actual coverage levels outlined in Table 2. For a given value of R 0, the most steep curves (and highest attack rates in the presence of vaccination) were observed with a latent period of 2 days and infectious period of 5 days, and the least steep curves (lowest attack rates with vaccination) were observed with a latent period of 4 days and infectious period of 7 days.
Using detailed demographic information for the GVRD, we have developed a compartmental mathematical model to estimate the transmission of pH1N1 in this population and to examine the impact of timing and age-specific coverage of different vaccination strategies for reducing the disease burden of pH1N1. Our simulations and sensitivity analyses uncovered findings with significant public health implications. First, we quantified the effect of delay in vaccine distribution relative to levels of pandemic influenza virus circulation in the population. Although vaccination is a well-established influenza preventive measure, we showed that its effectiveness during a pandemic depends greatly on the capacity to produce, distribute, and dispense vaccine in a timely manner. We demonstrated as well the importance of considering the interplay between vaccine campaign timing, demographics (especially age-specific contact rates), and the epidemiologic characteristics of the disease when developing vaccination strategies. Our sensitivity analyses verified the robustness of the results reported herein, despite the necessary inclusion of parameters in our model for which accurate estimates are currently non-existent.
We included population activity levels in our mathematical model based on a realistic representation of the contact network in the GVRD. We believe that this substantially improves the realism of the model, and gives us greater confidence in our results. For example, certain small subpopulations (e.g. health care workers or children) can have a large number of potentially disease-transmitting contacts per week, and are therefore more likely to acquire and transmit infection. Our model captures this important effect, while simplified models with homogenized activity levels would not. Age groupings addressed age-related variations in pH1N1 vulnerability to infection versus severe outcomes (mortality) each of which may constitute competing goals of the influenza immunization program. For example, vaccinating children, who tend to have higher contact rates than others, could result in a lower overall attack rate. However, as our results for the early initiation of the PC scenario showed, this strategy could leave the elderly (who experience higher mortality) relatively unprotected, thus increasing overall mortality.
In this study we included both symptomatic and asymptomatic infections in estimates of the overall attack rate. There are various estimates of the ratio of asymptomatic to symptomatic influenza cases in the literature [52, 53]. More research should be directed towards conducting large-scale seroprevalence studies around the globe to reach a consensus on a plausible range corresponding to this ratio for pH1N1. When symptomatically infected, individuals may change their behaviour, deciding to stay home or cancel appointments, resulting in a reduction in their social contacts. Meanwhile, asymptomatically infected individuals may not observe such stringent self-isolation procedures but may also be less contagious owing to fewer projectile symptoms (i.e. coughing or sneezing). This effect was taken into account in the model and the related parameters were varied during sensitivity analyses. Similarly, other parameters that lack definitive parameterization in the public health literature (e.g., latent period, infectious periods) were included in the sensitivity analyses, to ensure the robustness of the reported results.
We assumed that during the herald wave in spring and early summer 2009, a relatively small fraction of the population was infected by pH1N1 symptomatically or asymptomatically. This assumption was supported by the marked difference in influenza activity in the province of BC between the two periods of April to August and September to December, based on both laboratory-confirmed cases and physicians' visit counts (see Figure S8, Additional file 1). This pattern is in contrast with the attack rate reported in other geographic areas, such as England [43, 44, 47], where sizable pH1N1 activity was observed in June and July. In the latter case, before comparing various immunization strategies, adjustments should be made to the assumption on the number of remaining susceptible individuals at the beginning of the second wave.
We demonstrated that while vaccine efficacy is an important factor in the outcome of vaccination before or during the early stages of an epidemic, its impact on the overall attack rate diminishes significantly when the start of the campaign approaches or passes the epidemic peak-time. Simulation results suggest that when vaccination begins near the peak of the epidemic, a 50% efficacious vaccine may reduce the overall attack rate by only 5% less than a 100% efficacious vaccine. This result, along with our findings about the importance of vaccination timing, confirm the nostrum that no matter how effective a vaccine may be in theory, it must be administered in a timely fashion to have an effect on individual or herd immune protection.
True pH1N1 infection incidence is difficult to determine, as many cases go unreported, and an unknown fraction of pH1N1 cases are asymptomatic. To support our claim that our model predictions are consistent with the epidemic, we compared the age-distribution of reported, laboratory-confirmed pH1N1 cases in the GVRD (data from the BCCDC Laboratory and BC Ministry of Health) with the age distribution of infections predicted by our model (Figure 1). We found reasonable agreement between model predictions and reported cases in age-related trends.
Our results support, to a degree, the growing modeling literature claiming that the choice of vaccination strategy can have a substantial impact on the overall attack rate of pandemic influenza. This literature largely relies on careful, detailed modeling of age structure and/or disease vulnerability levels (e.g. [32], and more recently [33, 38]). The novelty we bring into this growing body of research is the incorporation of contact structure, in addition to age structure, as derived from the underlying GVRD contact network model. However, as in [37], these results also highlight the relatively greater importance of vaccination campaign timing and speed than prioritization scheme before or during the initial phase of an epidemic. Importantly, our model predicts a general equivalence of different prioritization schemes when vaccination begins at or beyond the epidemic peak.
Our results suggest that there can be two "best" targeting strategies: best given the specific vaccination campaign start time relative to the epidemic peak, and best overall given ignorance of the occurrence time of the epidemic peak (cf. Figure 4). Optimizing targeting strategies according to timing, age and disease vulnerability were carefully discussed in [18, 34–36]. We leave the corresponding difficult optimization calculation using our model--which again, in contrast to previous work incorporates contact structure in addition to age structure--for future work. However we should comment that the PC strategy was chosen for comparison with the optimal strategy proposed in [18]; in there the PC strategy, when applied before the initiation of the epidemic, is the best choice in terms of both attack rate and mortality reduction. That our predictions differ may be in part due to the difference in assumptions on vaccine efficacy: while we assume equal efficacy across all age groups, Medlock et al. [18] assume that vaccines offer lesser protection in the elderly population, the population with the highest case mortality rates.
It should be noted that we assumed 100% coverage in our parents and children and parents and children/actual sequence scenarios, which may be unrealistically high. We acknowledge that this exaggerates the apparent superiority of this approach, relative to the other strategies. However this strategy has a lower overall coverage (36%) than the actual coverage or uniform coverage strategies (47%). Given the success of the PC strategy in spite of its lower overall coverage, our results therefore suggest that, for campaigns initiated before the epidemic peak, it would be worthwhile for policy-makers to consider age-based vaccine targeting strategies assuming that high coverage rates are achievable in the targeted groups. The improvements in attack rate and mortality reduction offered by the PC+ strategy, at equal coverage to AC and UC, strengthen this suggestion.
In addition, it should be noted that our results apply to the pandemic scenario where a shift in the age distribution toward greater morbidity and mortality in younger age groups is a recognized hallmark compared to seasonal influenza [14]. Our results of superior reduction in mortality with the PC strategy administered during the early rise in a pandemic wave may not apply during seasonal campaigns when attack rates are much lower and thus population mortality due to influenza is much lower for children and adults but higher for the elderly, who remain at intrinsically higher risk of severe influenza outcomes if infected.
In circumstances in which vaccine production is delayed due to technological or logistical barriers, as seen with the pH1N1 vaccine, it is critical to have a good estimate of the timing of the epidemic peak before making policy decisions on vaccination strategies. Careful modeling may provide decision makers with estimates of these effects before the epidemic peak to motivate production efficiencies and inform policy decisions. Integration of real-time surveillance data with mathematical models is paramount to detect early upswings in illness activity heralding an epidemic peak and to enable public health to optimize the community benefits from proposed interventions before that occurs.
The authors would like to acknowledge the support of the Canadian Institute of Health Research (CIHR) through the grant no. PTL-97126 to the Canadian Consortium for Pandemic Preparedness Modeling (CanPan). This research has been enabled by the use of computing resources provided by WestGrid and Compute/Calcul Canada. We would like to thank Robert Smith from the Population Health, Surveillance and Epidemiology Division, the British Columbia Ministry of Health for providing the physicians' billing data and summary of the BC Centre for Disease Control Virology Laboratory pH1N1 laboratory confirmation. Authors recognize local health care providers and public health practitioners for their invaluable contribution to pandemic H1N1 surveillance in British Columbia and Travis Hottes and Naveed Janjua of the BC Centre for Disease Control Influenza Team for their analysis and summary of that.
12889_2011_3766_MOESM1_ESM.PDF Additional file 1: (PDF 901 KB)
12889_2011_3766_MOESM2_ESM.eps Authors' original file for figure 1
Conception and design of the study: CJM, TA, FD, HN, PB; Execution of mathematical simulations: CJM, TA, MR; Draft of the manuscript and supplementary material: CJM, TA, FD, HN, PB; Analysis of BC Health data: CJM, MR, DB, EK, SD, BRC, PB; Building Vancouver Contact Network: DB, EK, PB; Verification and validation of the mathematical modeling framework: CJM, MR, PvdD, BF, MJ, ML, GA, WJ, MS, CD, PB; Providing clinical and public health insight into analyzing the results: FD, HN, SM, SD, BD, KJ, BR; Providing critical input on various drafts of the manuscript: All Authors.
Division of Mathematical Modeling, University of British Columbia Centre for Disease Control, 655 West 12th Avenue, V5Z 4R4 Vancouver, British Columbia, Canada
Department of Mathematics, University of British Columbia, Vancouver, British Columbia, Canada
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Departments of Public Health and Medicine, Weill Medical College of Cornell University, New York, NY, USA
New York-Presbyterian Hospital, New York, NY, USA
Department of Mathematics and Statistics, University of Victoria, Victoria, British Columbia, Canada
Section of Integrative Biology, The University of Texas at Austin, Austin, TX, USA
Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Toronto, Ontario, Canada
Epidemiology Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
Surveillance Lab, Department of Epidemiology and Biostatistics, McGill University, Montreal, Québec, Canada
Bureau de surveillance épidémiologique, Direction de santé publique de Montréal, Montréal, Québec, Canada
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
Centre for Disease Modelling, York University, Toronto, Ontario, Canada
School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, Canada
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Biostatistics and methods


The Stirling bed frame features a distinctive sculptured headboard design, which follows an inspired and accute line adjacent to the side rail. This feature creates a unique look, playing to the modern Scandi cool theme.
As shown here in Marinello Olive.
Available to purchase online in a Grade B fabric as shown in Marinello Oilve. Other fabric and wood finish options can be purchased in store.


text:
Phil Selman
Corporate Roaster
Author Archives: Phil
Phil Selman is the comedian that comedians come to see on their night off! Phil has played the national and international comedy club circuit. He's been seen in four major motion pictures, including the soon-to-be released horror-comedy film Blood Night
Here's some of Phil's promo videos.
YouTube Rants
Check out some of Phil's rants. He's mad as hell and he's not going to take it anymore. Or maybe he's just really annoyed but you can't stop watching.
Phil Selman on the radio. Nuff said.
Phil Selman DVD
So it's time to honor your boss, your coworker, that office retiree… and you want to do something really special. No plaque, no flowers, no fancy pen with the company logo engraved on it. You want something fresh and unique
Phil has a lot of fans and some of them hold down real jobs and own a corporation or two. Here's a recommendation letter from one of many companies he's worked for. The Soaring Society of America, Inc. P.
Operators are standing by. Phil Selman philselman@gmail.com

redpajama_set_name: RedPajamaCommonCrawl


not so much. This, thankfully, is the former. Oh my goodness, there is a reason everyone is obsessed with the Laura Mercier - Translucent Loose Setting Powder! Priced at $38. it is beyond worth the it.
This is the finest loose powder I've ever used. It practically melts into the skin leaving a velvety finish that doesn't look cakey. Though it is powder it is still luminous and skin like. This is the first powder that has given me the look I really want for setting the under eye while also preventing creasing. It doesn't leave the skin dry or flat looking. A++ in my book! Though translucent the powder isn't white so there is no flashback and because of the natural yellow toned shade it really can work on almost all skin tones.
The packaging is a simple and luxurious. Laura Mercier is a high end brand and the packaging says it all. The holes in the sifter are just right so that too much product isn't coming out and the jar holds 1.oz or 29g.
This is a home run! From formula to finish this powder feels and looks amazing. My makeup has been lasting longer. The price, though not cheap, when considered with the compared gram pricing it's actually an amazing deal and a powder you won't be repurchasing as often due to the volume you get. Love! I suggest this product in the highest regard.
the comments! I hope you enjoyed this post and that it has been helpful in your journey to the perfect makeup bag!Thanks for reading and if I am slow to my replies it is just because I'm moving and may not have Wifi at the moment as I'm on the road.


Palace On Wheels Tour Package – 7 Nights / 8 Days Trip | Luxury Train Tour Package | Rajasthan Tour on Wheels: – Tourism is one of the biggest industries in India and is a major contributor to the economic development of the country. After the developments in the tourism sector, the government started exploring the luxurious side of the sector in order to appeal to a lot of tourists internationally, as well as domestically, who want to explore the tourist destinations around the country in a lavish and royal way.
The Palace on Wheels was the first luxury train ever started in India. It was a joint venture of the Rajasthan Tourism and the Indian Railways in the early 1980s. As soon as it was introduced, it quickly gained popularity. This luxury train tour package has redefined the meaning of luxury travel in the country and has taken tourism to a more advanced level. The train is inspired by the design and architecture of the exterior and interiors of the personal train coaches that were once used by the Maharajas of the country. The lavish interiors of the luxury train tour package make it one of the best places in which you can explore the beauty of India for Rajasthan tour on wheels.
The Rajasthan tour on wheels takes you on a magical journey through the beautiful tourist destinations like Jaipur, Sawai Madhopur, Chittorgarh, and Udaipur in Rajasthan for 7 nights / 8 days trip. Exploring all these cities and their tourist destinations offers you a peek into the cultural heritage of the state in the comfort and luxury of the Palace on Wheels.
The journey starts at the Safdarjung Railway Station and the tourists have to reach the station on the mentioned reporting time for check in. After the formalities, they leave for Jaipur and a royal dinner is served aboard the Palace on Wheels.
The tourists arrive in Jaipur early next morning and they receive a refreshing breakfast onboard. They are given a traditional welcome according to the rituals at the Jaipur Railway Station after which they debark the train to explore the city of Jaipur. The tourists visit various tourist spots and have a tantalizing lunch right at the Amber Fort, which is followed by a tour of the fort. The tourists can then look around in the local markets. They board the train for tea and snacks after which a grand dinner is served at the Jai Mahal Palace. The tourists then continue with their journey towards Sawai Madhopur.
The day starts with an early morning forest safari to the popular Ranthambore National Park where breakfast is served in a forest lodge. The tourists return to Palace on Wheels and move further on towards Chittorgarh. They have lunch onboard before arriving in Chittorgarh. The arrival is followed by a sightseeing tour of the massive Chittorgarh Fort accompanied by refreshments at the fort and a wonderful light and sound show.
The arrival is marked by a refreshing breakfast at a deluxe hotel in Udaipur followed by an excursion tour of the popular city attractions. The tourists enjoy an adventurous boat ride after having lunch at a heritage hotel. They return to the railway station for evening refreshments onboard the Palace on Wheels. The journey continues towards Jaisalmer as the tourists have a lavish dinner.
The day starts with a sightseeing tour of the city of the Jaisalmer. The tourists will either have a deluxe lunch on board the Palace of Wheelstantalizing or at the Hotel Moomal. They receive the evening refreshments in the sand dunes of Jaisalmer, which is followed by a venturous camel ride. The dinner is also served in the sand dunes that extend until the eyes can reach which is accompanied by a colourful and fun cultural program. They reach the train again and continue their journey towards Jodhpur.
The tourists have an onboard breakfast lavishly in the Palace of Wheels. The breakfast is followed by a local sightseeing tour of the popular tourist destinations around the city. The tourists explore the scenic beauty of the golden skyline with miles and miles of desert that are a feast to the eyes. They have lunch in a deluxe resort after which they return to the train for a relaxing ride to Bharatpur accompanied by dinner.
The last day starts with an early morning bird viewing in the Keoladeo Ghana National Park followed by a breakfast in a forest lodge. The tourists return to the train and continue their journey towards their last destination, Agra. After arrival in Agra, the tourists embark on a sightseeing tour of the popular heritage sites in the city. They explore the mesmerizing beauty of the Taj Mahal and they have an option to look around in the city market. The day ends with a fun light and sound show.
The tourists arrive at the Safdarjung Railway station early next morning. They receive an onboard breakfast, which is followed by farewell formalities and memories to remember forever of your Palace On Wheels Tour Package – 7 Nights / 8 Days Trip.
we were very satisfied with the service levels and would highly recommend them to others !…… the hotel choices were very good and within the budget we had decided for the vacations .
We were with Trippy Holidays on a tour. Everything was very good. The boss is also great and he tries to help in every situation. Indie is incredible country and with Trippy Holidays you can enjoy it.
We had GeTS organize a two week driving tour of Kerela India on-line from Canada and it was excellent. The hotels, attractions and beach resorts included were great and the driver provided was very knowledgeable and professional.
We have had a great time with Trippy Holidays programme. First we made our plan defining which cities to visit, then Trippy holidays planned the tour. When we arrived everything happened as planned and scheduled, with no delays and with some flexibility.


According to a police report, Smollett claims the men not only shouted at him, but that they hit him in the face, and poured an "unknown substance" on him. They then proceeded to wrap a rope around his neck.
The Associated Press reports police spokesman Anthony Guglielmi indicated Smollett still had the rope around his neck when police first came into contact with him. Guglielmi also indicated that the alleged attackers were wearing masks.
After Smollett was interviewed by police inside an apartment he took himself to Northwestern Memorial Hospital and he was reportedly in good condition.
Police responded to the initial call from a man who was with Smollett inside an apartment. He would eventually self-transport to Northwestern Hospital.
Guglielmi has been updating the public on the proceedings of the case via Twitter.
He noted the Chicago Police are investigating the alleged attack as a hate crime.
Elgas indicates that the Chicago Police are currently being assisted by the FBI. The investigation has turned up video of Smollett at a local Subway near the location of the crime as well as other video of him at the scene of the crime. However, they do not have any video of the assailants.
Black Panther stars Michael B. Jordan and Chadwick Boseman took to Instagram to indicate their support for the Empire actor.
The Chicago Police are still conducting their investigation and this is an on-going story.
Chicago Officials Furious Over Prosecution's Decision to Drop Charges Against Jussie Smollett as Empire Writers Taunt Public!


I had puttied the GM and was sanding it but decided that before I started priming I really needed to work on the gun and shield, which I had put off until later. I started with the shield. I needed to adapt it to fit the different shield mount that fits on the NT-1's arms, but I also wanted to give the shield a range of motion. So, I cut the square peg off the inside of the shield and replaced it with the ball from this large hand (I think it was from my old Gelgoog kit). I pinned it with part of a thick paperclip.
I then cut off the bottom of the mechanical frame of the arm of the Ground Gundam I had already butchered, and voila!
Not liking how the shield stuck out in space on a stick, I drilled a hole in a Koto thruster bell and glued it upside down so it looks like the ball sticks out of something meatier.
Next I turned to the rifle. I'm giving it an upgrade with the same feel as I gave the same kind of rifle that I put in the off hand of my Hazel Hummingbird.
I lengthened the thick part of the barrel and shortened the thin part of the barrel. I added a brass tube below the barrel as well. I've smoothed out the basic gun, now I need to add the details, which will include a bayonet. I would have done a beam saber bayonet like I did on the Hazel, but the GM will already have a "hidden" beam saber so I skipped the one on the gun.
I also went to Valley Con, the IPMS show in Pasadena. Since I was going to take my Mustang vs. Citroen diorama, I decided to take another look at it since I know that I was more done with it than it was complete. I knew it wasn't going to win any contests with all the problems I had with the Mustang, but I didn't want to embarrass myself by bringing it as-is.
The thing that's been taking up much of my free time for the last month and a half is my front yard. I can't really call it my lawn since it started out as a bunch of dirt and dead grass. After a few months of watering, it became about 1/3 good grass, 1/3 weeds, and 1/3 tangled dead grass and roots that nothing would grow in.
I've spent a lot of weekend and afternoon hours with a pickaxe breaking the bad 2/3 up one square foot at a time, removing the weeds and roots. This is why I say, "I don't hire a Mexican. I am a Mexican." lol! I've planted grass seeds in the main part of the lawn and I'm about to plant seeds in the part between the sidewalk and curb. The new grass is just starting to grow.


Module 2: Figure cell signalling pathways - Summary of the major signalling pathways used by cells to regulate cellular processes.
The 'classical' nuclear factor κB (NF-κB) signalling pathway activated by the tumour necrosis factor receptor (TNFR).
The p50 and p65 isoforms of the nuclear factor κB (NF-κB)/Rel family form the NF-κB dimer that is activated in the tumour necrosis factor α (TNFα) signalling pathway. The activated TNF receptor (TNFR) recruits a signalling complex to the membrane (Step 2), which contains the inhibitor of NF-κB (IκB) kinase (IKK) α/IKKβ dimer that is responsible for phosphorylating the IκBα subunit that retains p50/p65 in the cytoplasm (Step 3). When the IκBα is phosphorylated, it is ubiquitinated and degraded by the proteasome (Step 4). The p50/p65 homoclimer is imported into the nucleus (Step 5), where it activates a large number of genes (Step 6). One of these genes codes for IκBα, which sets up a negative-feedback loop by exporting p50/p65 from the nucleus (Step 7). Adapted from Trends Biochem. Sci., Vol. 30, Viatour, P., Merville, M.-P., Bours, V. and Chariot, A., Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation, pp. 43–52. Copyright (2004), with permission from Elsevier; see Viatour et al. 2005.


What a fun weekend. I am so not ready to have had to come home.
We ended up going all the way to Grand Marais because Z behaved so well in the car.
So I got a this years pic of her at the lighthouse on the pier.
This was taken in August of last year she seems so much bigger.
We tried to figure out what some of the names on the rocks were. This one says 1902.
D jumped the rocks with Z.
She did not want to go back to the car but fell asleep as soon as we hit the road.
We spent the first part of Sunday throwing rocks into the water in Duluth.
We also did some more hiking until someone fell asleep so we headed home to plan our next adventure.


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Aston Martin Boss Teases Project 003 Hybrid Hypercar's Behind Via Twitter
It's expected to release in 2021 and it will be limited to just 500 units.
By Chris TsuiFebruary 21, 2019
After confirming its existence back in September 2018, Aston Martin is teasing its upcoming Project '003' once again. To recap, the mid-engined hybrid hypercar will drop in late 2021, after the Valkyrie and Valkyrie AMR Pro (hence the 003 designations). It'll feature technology trickled down directly from the Valkyrie and be limited to just 500 units worldwide.
Based on the single shot released of its backside, the 003 will feature a pair of taillights laid out horizontally, a sumptuous-looking hypercar body, and seemingly not much of a rear window. Here's the sketch released in September to give you a vague idea of what to expect from the rest of the car, appearance-wise.
The 003, whatever it ultimately ends up being called, will be built on a super lightweight structure and use a turbocharged gasoline-powered engine coupled to electric motors. Active aerodynamics and active suspension contribute to what Aston claims will be "class-leading dynamics on both road and track."
Unlike its Valkyrie predecessors, the 003 will apparently be quite practical—as practical as a hypercar can be, anyway. Aston says it's designing the car to accommodate "practical concessions to road use, including space for luggage." One suitcase-sized compartment between the seats it is, then. The 003 will also be available in both left and right-hand drive. Whether or not its well-traveled buyers can reserve one in each configuration though is unclear.
Aston Martin boss Andy Palmer said back in September, "It was always the intention for the Aston Martin Valkyrie to be a once-in-a-lifetime project, however, it was also vital to us that Valkyrie would create a legacy: a direct descendant that would also set new standards within its own area of the hypercar market, creating a bloodline of highly specialized, limited production machines that can exist in parallel with Aston Martin's series production models."
Until the next tease, folks.
Aston Martin Confirms 'Once-in-a-Lifetime' Project 003 Hybrid Hypercar
Project 003 will be the successor to the $3.2-million Valkyrie AMR Pro.
You Can Spec Your $3.3M Aston Martin Valkyrie With 24K Gold Paint
Owning a one-of-150 hypercar isn't enough for some people, so Aston will let them spec extra carbon fiber, titanium, and other exotic materials.
The Aston Martin Valkyrie's 11,100-RPM V-12 Will Produce 1,000 HP
The specs are in on the $3.3 million hybrid hypercar's naturally aspirated powerplant, and it's 153.8 hp per liter of banshee-like goodness.
New Photos of Aston Martin Valkyrie's F1-Inspired Cabin Will Make You Drool
The $3.3-million car was developed with Red Bull Racing F1 team and will feature a 'feet up,' F1-style driving position.
First Look: Aston Martin Lagonda Teases Uber Luxurious, All-Electric SUV Concept
The automaker has released a teaser of the All-Terrain Concept coming to Geneva in March, and fortunately, it's scheduled for production thereafter.


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Q: Calculate Euclidean Distance within points in numpy array I have 3D array as
 A = [[x1 y1 z1]
      [x2 y2 z2]
      [x3 y3 z3]]

I have to find euclidean distance between each points so that I'll get output with only 3 distance between (row0,row1),(row1,row2) and (row0,row2).
I have some code
dist = scipy.spatial.distance.cdist(A,A, 'euclidean')

but it will give distance in matrix form as
dist= [[0  a   b]
       [a  0   c]
       [b  c   0]]

I want results as [a  b  c].

A: Consider using scipy.spatial.distance.pdist.
You can do like this.
>>> A = np.array([[1, 2, 3], [4, 5, 6], [10, 20, 30]])
>>> scipy.spatial.distance.pdist(A)
array([  5.19615242,  33.67491648,  28.93095228])

But be careful the order of the output distance is (row0,row1),(row0,row2) and (row1,row2).

A: You can do something like this:
>>> import numpy as np
>>> from itertools import combinations
>>> A = np.array([[1, 2, 3], [4, 5, 6], [10, 20, 30]])
>>> [np.linalg.norm(a-b) for a, b in combinations(A, 2)]
[5.196152422706632, 33.674916480965472, 28.930952282978865]

redpajama_set_name: RedPajamaStackExchange


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Unless otherwise indicated, individuals may post material from the Gospel Media portion of this site to another website or on a computer network for their own personal, noncommercial use. This right can be revoked at any time and for any reason. Organizations and legal entities desiring to use material from Gospel Media may request permission from our Permissions page. For more information about using and sharing Church media, check out our FAQ page. Biblical Verses Image
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When Samuel was seeking who would be the king of Israel, He had all of Jesse's sons pass before him and time after time, Samuel thought that surely one of these young men would be the next king. Some were tall and muscular but that was not God's standard. Jesse didn't call David who was what we might call the "runt of the litter" but God said that He looks not on the outward appearance but what is inside. He doesn't have regard for what a person's looks are like but He looks at the heart because the most important attributes of a person are never what we see but the things we don't see and what we cannot see, God can. That's all that really matters. Christian Images
Unless otherwise indicated, all content is licensed under a Creative Commons Attribution License. All Scripture quotations, unless otherwise indicated, are taken from The Holy Bible, English Standard Version. Copyright ©2001 by Crossway Bibles, a publishing ministry of Good News Publishers. Contact me: openbibleinfo (at) gmail.com. Cite this page: Editor: Stephen Smith. Publication date: Aug 1, 2019. Publisher: OpenBible.info. Scripture Images
Jack Wellman is a father and grandfather and a Christian author, freelance writer, and Prison Minister. Graduate work at Moody Bible Institute. His books are inexpensive paperbacks that are theological in nature: "Teaching Children The Gospel/How to Raise Godly Children," "Do Babies Go To Heaven?/Why Does God Allow Suffering?," "The Great Omission; Reaching the Lost for Christ," and "Blind Chance or Intelligent Design?, Empirical Methodologies & the Bible." Scripture Images
Each Tuesday and Wednesday volunteers meet in the Church kitchen to prepare these delicious offerings that stock our freezer. If you enjoy prepping, cooking, and packaging in the kitchen, consider volunteering with us once a month for two hours, or as often as you like. It's a wonderful opportunity for fellowship! Contact Jane Coulter at jwcoulter@gmail.com to learn more. Christian Images
Then God said, "Let us make man in our image, after our likeness. And let them have dominion over the fish of the sea and over the birds of the heavens and over the livestock and over all the earth and over every creeping thing that creeps on the earth." So God created man in his own image, in the image of God he created him; male and female he created them. And God blessed them. And God said to them, "Be fruitful and multiply and fill the earth and subdue it and have dominion over the fish of the sea and over the birds of the heavens and over every living thing that moves on the earth."
Being Cleansed From SinSittingLikenessExpiationGod Made Visible In ChristGod's Glory RevealedPerfection, DivineGospel, Historical Foundation OfAdoration, Of ChristGod Is TranscendentLight, SpiritualExaltation Of ChristChrist's NatureAccuracyRevelation, In NtHoliness, Believers' Growth InGlory, Revelation OfGlory Of GodDivinity Of ChristEarth, God SustainingSelf ImageImage Of God Christian Wall Art
This is a list of Christian worship music artists or bands. This list includes notable artists or bands that have recorded or been known to perform contemporary worship music at some point in their careers. This includes worship leaders, Christian songwriters, and contemporary Christian music artists. It is not a list of contemporary Christian music artists alone. Biblical Verses Image
As a private, nonprofit organization, the Shop donates all of its sales proceeds in the form of grants to worthy nonprofit initiatives, especially focused on the needs of women and children in the local community and abroad. In its 40-year history, GoodNews has funded grants totaling well over $1,000,000. The Shop is also a ministry that builds community and supplies books and other resources for Christ Church programs. Scripture Images
Sadly, many people will look at us and judge us by appearances and as we've already read, they can miss-read us because they don't see what's on the inside which is what is of ultimate importance. Jesus said "You judge by human standards; I pass judgment on no one" (John 8:15). Every time that someone looks at us and they judge us by appearances, they are judging us by human standards and very likely miss-judging us. What they can't see is what is most important anyway. The religious leaders of Jesus' day were only concerned with what people saw them doing but God knew their hearts and saw that they were inwardly full of sin. Christian Wall Art
Gospel music is one of the oldest forms of music. With its origins being traced back as far as the 17th century, Gospel singers have preached the words of the good book for centuries and are making some of the best gospel and Christian songs of 2018. Gospel singers for a long time had to sing without musical accompaniment outside of clapping and stomping - black gospel music has a strong tradition of using the human hands and feet as instruments. More recently, these hymns and songs feature the same strong harmonies, but also organs to tambourines to electric guitars. Beginning in the 1920s and 1930s, gospel artists became some of the most popular singers in the world. The best gospel singers are wildly popular in the Christian community are closely associated with other Christian singers. Today, within the Christian community, gospel singers are as, if not more popular than Christian rock bands, which is saying a lot. Christian Wall Art
Country music is a wildly popular genre, but there are other sub-genres that could exist beneath it, such as Christian country music (CCM). CCM, sometimes called country gospel or inspirational country, blends the style of country with biblical lyrics. Like country music itself, it is an expansive genre, and no two CCM artists will sound exactly alike.
Genesis 1:26-27 "Then God said, "Let us make man in our image, after our likeness. And let them have dominion over the fish of the sea and over the birds of the heavens and over the livestock and over all the earth and over every creeping thing that creeps on the earth." So God created man in his own image, in the image of God he created him; male and female he created them."
As a private, nonprofit organization, the Shop donates all of its sales proceeds in the form of grants to worthy nonprofit initiatives, especially focused on the needs of women and children in the local community and abroad. In its 40-year history, GoodNews has funded grants totaling well over $1,000,000. The Shop is also a ministry that builds community and supplies books and other resources for Christ Church programs. Christian Wall Art
Sadly, many people will look at us and judge us by appearances and as we've already read, they can miss-read us because they don't see what's on the inside which is what is of ultimate importance. Jesus said "You judge by human standards; I pass judgment on no one" (John 8:15). Every time that someone looks at us and they judge us by appearances, they are judging us by human standards and very likely miss-judging us. What they can't see is what is most important anyway. The religious leaders of Jesus' day were only concerned with what people saw them doing but God knew their hearts and saw that they were inwardly full of sin. Christian Images
GoodNews, the Shop@Christ Church is a mission of the Episcopal Church Women (ECW) at Christ Church. We proudly feature books, cards, candles, lotions, jewelry, handbags, decorative pillows, baby and children gifts, tabletop accessories, men's accessories, crosses, paper products, linens, food items, and kitchen accessories. We offer free gift wrapping too! Please think of us first when you shop for gifts for all occasions. Christian Images
Country music is a wildly popular genre, but there are other sub-genres that could exist beneath it, such as Christian country music (CCM). CCM, sometimes called country gospel or inspirational country, blends the style of country with biblical lyrics. Like country music itself, it is an expansive genre, and no two CCM artists will sound exactly alike. Biblical Verses Image
This comprehensive Christian Image Directory includes every category of PowerPoint sets, background images, photographs, religious borders, Christian clipart and word art with Scriptures and phrases within the ShareFaith collection. With hundreds of categories in this index, you can quickly search for specific subjects and find several types of images together. For example, when searching on Easter, you can click on 7 different category types to make sure you don't miss out on any of the art related to that special holiday. The same is true for Christmas and other seasons, holidays and subjects. Christian Wall Art
Country music is a wildly popular genre, but there are other sub-genres that could exist beneath it, such as Christian country music (CCM). CCM, sometimes called country gospel or inspirational country, blends the style of country with biblical lyrics. Like country music itself, it is an expansive genre, and no two CCM artists will sound exactly alike. Christian Wall Art
Our mission is simple: Art and Christianity no longer resonate as an inherent, magnificent pairing. Actually it is a feeling that goes both ways: most Christians no longer see Art as being important or even as a relevant way of promoting the faith; and non believers don't value Christianity as having been at the forefront of the arts throughout the centuries, responsible for creating some of the most magnificent artworks out there. Our offering is simple: one newsletter a day where we simply send you the Gospel reading of the day, alongside a work of art that we believe is poignant, reflective and appropriate to that reading. We offer a short reflection on the artwork and the reading. We simply give you the tools for you to meditate on the daily Gospel alongside a work of art. We are an apostolate within the Roman Catholic Church, based in London. Christian Wall Art
This is a list of Christian worship music artists or bands. This list includes notable artists or bands that have recorded or been known to perform contemporary worship music at some point in their careers. This includes worship leaders, Christian songwriters, and contemporary Christian music artists. It is not a list of contemporary Christian music artists alone. Christian Wall Art
And you were dead in the trespasses and sins in which you once walked, following the course of this world, following the prince of the power of the air, the spirit that is now at work in the sons of disobedience— among whom we all once lived in the passions of our flesh, carrying out the desires of the body and the mind, and were by nature children of wrath, like the rest of mankind. Christian Images
With a five-octave vocal range, Earnest Pugh is a powerhouse singer. He's appeared on networks like the Trinity Broadcasting Network (TBN) and Black Entertainment Television (BET) as well as on stage, acting in major plays such as "Love the One You're With," "Secret Lover" (Michael Matthews), "Crazy Love" (D'Atra Hicks) and "Real Men Pray" (Angela Barrow and Lizzie Berry). Biblical Verses Image
So, who are the best gospel singers? Any list of gospel artists has to include male gospel singers like Kirk Franklin, Marvin Sapp, BeBe Winans, and Fred Hammond, as well as female Christian singers like CeCe Winans, Yalonda Adams and Shirley Caesar. These gospel singers are considered some of the best in the genre and it's with good reason that they're at or near the top of this poll. The best gospel artists are well represented on this list and with good reason. When you think of Christian singers and gospel artists, you should be able to use this list as a great point of reference. Scripture Images
Being Cleansed From SinSittingLikenessExpiationGod Made Visible In ChristGod's Glory RevealedPerfection, DivineGospel, Historical Foundation OfAdoration, Of ChristGod Is TranscendentLight, SpiritualExaltation Of ChristChrist's NatureAccuracyRevelation, In NtHoliness, Believers' Growth InGlory, Revelation OfGlory Of GodDivinity Of ChristEarth, God SustainingSelf ImageImage Of God
Our mission is simple: Art and Christianity no longer resonate as an inherent, magnificent pairing. Actually it is a feeling that goes both ways: most Christians no longer see Art as being important or even as a relevant way of promoting the faith; and non believers don't value Christianity as having been at the forefront of the arts throughout the centuries, responsible for creating some of the most magnificent artworks out there. Our offering is simple: one newsletter a day where we simply send you the Gospel reading of the day, alongside a work of art that we believe is poignant, reflective and appropriate to that reading. We offer a short reflection on the artwork and the reading. We simply give you the tools for you to meditate on the daily Gospel alongside a work of art. We are an apostolate within the Roman Catholic Church, based in London. Christian Images
And it will come about in that day, that every place where there used to be a thousand vines, valued at a thousand shekels of silver, will become briars and thorns. People will come there with bows and arrows because all the land will be briars and thorns. As for all the hills which used to be cultivated with the hoe, you will not go there for fear of briars and thorns; but they will become a place for pasturing oxen and for sheep to trample.
Then God said, "Let us make man in our image, after our likeness. And let them have dominion over the fish of the sea and over the birds of the heavens and over the livestock and over all the earth and over every creeping thing that creeps on the earth." So God created man in his own image, in the image of God he created him; male and female he created them. Christian Images
In the beginning, God created the heavens and the earth. The earth was without form and void, and darkness was over the face of the deep. And the Spirit of God was hovering over the face of the waters. And God said, "Let there be light," and there was light. And God saw that the light was good. And God separated the light from the darkness. God called the light Day, and the darkness he called Night. And there was evening and there was morning, the first day. ... Christian Wall Art
How true this is. You can put lipstick and earrings on a pig but inwardly they're still a pig so Peter writes that "the hidden person of the heart" is precious to God and the "imperishable beauty of a gentle and quite spirit" to God is "very precious" and that's all that matters eternally. We'll all get new bodies someday anyway and so why should we be so preoccupied with what we look like when God only cares about what we are like on the inside? Biblical Verses Image
But that is not the way you learned Christ!— assuming that you have heard about him and were taught in him, as the truth is in Jesus, to put off your old self, which belongs to your former manner of life and is corrupt through deceitful desires, and to be renewed in the spirit of your minds, and to put on the new self, created after the likeness of God in true righteousness and holiness. Christian Images
Then God said, "Let us make man in our image, after our likeness. And let them have dominion over the fish of the sea and over the birds of the heavens and over the livestock and over all the earth and over every creeping thing that creeps on the earth." So God created man in his own image, in the image of God he created him; male and female he created them.
That said, it's up to you to determine who are the best gospel singers. If you notice that a gospel singer is missing, feel free to add them. This list answers the questions "who are the best gospel music bands of all time?" and "who is the greatest gospel musician ever?" If you know enough about the genre, please vote based on the quality of the band's music instead of just voting for the most popular gospel music bands that you might've heard of. Scripture Images


Local 677 represents approximately 2400 men and women at more than 67 Employers throughout the Northwest Region of Connecticut. Members of Local 677 cover almost every profession imaginable, from warehouse workers to truck drivers, from UPS drivers to waste water treatment professionals, from office clerical to skilled maintenance employees, from mechanics to bus drivers, from sales men and women to public works employees, from school lunch personnel to school bus drivers, from construction workers to custodians. If you can think of an occupation, there is probably a Local 677 member performing that job somewhere in our Region.
Local 677 was first organized in 1935. We were chartered by the International Brotherhood of Teamsters in 1940 and since our inception have evolved into a diverse and dynamic Local, changing and adapting as conditions demand. The strength of our Local has always been our membership. The active participation of the men and women of our Local Union provides the strength and solidarity necessary to achieve industry-leading contracts, which insure that our members' wages, hours, and working conditions are protected. Our health and pension benefits consistently rank in the top percentile of Taft-Hartley plans in the Country.
Thank you for visiting our website. We hope it proves to be a valuable resource for all of our membership. Please check back often as we will be continually updating and adding information.


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Thursday 21st August - Live Mix & Interview Guest NDL DJ
DNBWorldwide 0 Views: 4780 21st Aug 2014
This week's live call in guest is NDLDJ, one of the main players and part of the MORPHED Collective based in Linz, Austria. Ever since the collective's beginnings at Lederfabrik they've organised Club Sessions with locals and international artists at various locations and - on a regular basis - at Stadtwerkstatt.
NEW RELEASE - 'The Razors Edge 2014' 20th Anniversary Edition
Drum & Bass 0 Views: 8745 2nd Jul 2014
This year sees the 20th anniversary of 'The Razors Edge', a well known Drum & Bass track that was Originally released in 1994 on the Skeleton Recordings label (SKEL012), this track used to be a regular in the record box of LTJ Bukem and still to this day is quite a sought after piece of vinyl.
Funktion-One has new competition from Bowers & Wilkins!
Technology 0 Views: 11189 12th May 2014
For almost a decade now, any loud, crystal clear, non-custom sound system worth its salt has been comprised of the UK made Funktion-One cabinets. Whether at a club or festival, Funktion-One have been the go to company for clarity and loudness in any environment. This may all be about to change though, as Bowers & Wilkins prepare to unveil their new Sound System specifically designed for the large scale festival and possibly large club settings.
Old Skool Archives - Remarc
Old Skool 0 Views: 4754 9th May 2014
This weeks old skool archives goes back to 1994, with the first tune the Jungle legend Remarc ever produced, although some of his later tunes got releases before this came out! The tune in question is Sound Murderer, Released on White House Records, a label started by Paul Oakenfold in 1992.
Jungle Fever Documentary on Channel 4
TV 0 Views: 12508 3rd May 2014
On Wednesday 30th April 2014, Channel 4 aired part five of their Music Nation series, this time covering the Jungle scene with a documentary by Ollie Evans called Jungle Fever.
An exploration of the movement that redefined British urban music: jungle. The programme charts the rise and fall of this iconic scene and features Fabio & Grooverider, DJ Hype, Kenny Ken, Brockie and more.


MASSIMILIANO ALLEGRI has begun to learn English as he prepares for approaches from Chelsea and Manchester United, according to reports.
The Juventus boss, who has just 18 months left on his contract in Turin, has been heavily linked with a move to the Premier League.
And the Daily Mirror claim the Italian has set his sights on the top job at either Stamford Bridge or Old Trafford.
Allegri won Serie A with AC Milan in 2010-2011, his debut season with Milan, and has been hugely successful since taking over at Juventus.
He led them to a treble and the Champions League final in his first campaign in charge last year, earning him a nomination for FIFA's World Coach of the Year award.
And he could be ready for a new challenge next summer, with Chelsea already known to be looking for a new manager.
Blues owner Roman Abramovich has put the 48-year-old on his short-list of potential candidates to take over from interim boss Guus Hiddink next summer.
Abramovich fears Pep Guardiola has already made up his mind to move to Manchester City in the summer after announcing he will leave Bayern Munich.
And although Atletico Madrid boss Diego Simeone is also on Chelsea's wanted list, Allegri looks set to be sounded out for the role.