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Evaluating Hospital-Based Surveillance for Outbreak Detection in Bangladesh: Analysis of Healthcare Utilization Data
Birgit Nikolay,
Affiliations Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris, France, Centre National de la Recherche Scientifique, URA3012, Paris, France, Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, France
Henrik Salje ,
* E-mail: henrik.salje@pasteur.fr
Affiliations Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris, France, Centre National de la Recherche Scientifique, URA3012, Paris, France, Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, France, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
Katharine Sturm-Ramirez,
Affiliations Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
Eduardo Azziz-Baumgartner,
Affiliation Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
Nusrat Homaira,
Affiliations Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh, Discipline of Paediatrics, School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
Makhdum Ahmed,
Affiliations School of Public Health, University of Texas Health Science Center, Houston, Texas, United States of America, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
A. Danielle Iuliano,
Repon C. Paul,
Affiliations Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh, School of Public Health and Community Medicine, University of New South Wales Australia, Sydney, New South Wales, Australia
Mahmudur Rahman,
Affiliation Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
M. Jahangir Hossain,
Affiliation Medical Research Council Unit The Gambia, Banjul, The Gambia
Stephen P. Luby,
Affiliation Infectious Diseases Division, Stanford University, Stanford, California, United States of America
Simon Cauchemez ,
¶These authors are joint senior authors on this work.
Emily S. Gurley
Affiliation Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
Henrik Salje,
M. Jahangir Hossain
Birgit Nikolay Henrik Salje ... Emily S. Gurley
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The International Health Regulations outline core requirements to ensure the detection of public health threats of international concern. Assessing the capacity of surveillance systems to detect these threats is crucial for evaluating a country's ability to meet these requirements.
We propose a framework to evaluate the sensitivity and representativeness of hospital-based surveillance and apply it to severe neurological infectious diseases and fatal respiratory infectious diseases in Bangladesh. We identified cases in selected communities within surveillance hospital catchment areas using key informant and house-to-house surveys and ascertained where cases had sought care. We estimated the probability of surveillance detecting different sized outbreaks by distance from the surveillance hospital and compared characteristics of cases identified in the community and cases attending surveillance hospitals.
We estimated that surveillance detected 26% (95% CI 18%–33%) of severe neurological disease cases and 18% (95% CI 16%–21%) of fatal respiratory disease cases residing at 10 km distance from a surveillance hospital. Detection probabilities decreased markedly with distance. The probability of detecting small outbreaks (three cases) dropped below 50% at distances greater than 26 km for severe neurological disease and at distances greater than 7 km for fatal respiratory disease. Characteristics of cases attending surveillance hospitals were largely representative of all cases; however, neurological disease cases aged <5 y or from the lowest socioeconomic group and fatal respiratory disease cases aged ≥60 y were underrepresented.
Our estimates of outbreak detection rely on suspected cases that attend a surveillance hospital receiving laboratory confirmation of disease and being reported to the surveillance system. The extent to which this occurs will depend on disease characteristics (e.g., severity and symptom specificity) and surveillance resources.
We present a new approach to evaluating the sensitivity and representativeness of hospital-based surveillance, making it possible to predict its ability to detect emerging threats.
Author Summary
Why Was This Study Done?
Many countries rely on hospital-based surveillance for the detection of infectious diseases of national and global public health relevance.
It is often difficult to access suitable external reference data to assess the capacity of a surveillance system to detect cases and outbreaks or to characterize cases.
What Did the Researchers Do and Find?
We demonstrate a novel approach using healthcare utilization data to evaluate the sensitivity and representativeness of severe infectious disease surveillance in Bangladesh.
The capacity to detect cases and outbreaks decreased with distance from surveillance hospitals.
Cases captured by surveillance differed from cases in communities by age and socioeconomic status.
Geographic coverage of surveillance could be improved by including other hospitals in the surveillance system.
What Do These Findings Mean?
The presented approach is applicable for a wide range of infectious diseases in different settings, taking some practical considerations into account.
Hospital-based surveillance may have low sensitivity in rural areas at greater distances from surveillance hospitals, suggesting a risk of unrecognized transmission of emerging infectious diseases.
Alternative surveillance strategies, such as including additional hospitals in the surveillance system or considering alternative data streams, may help to increase surveillance performance in such remote regions.
Citation: Nikolay B, Salje H, Sturm-Ramirez K, Azziz-Baumgartner E, Homaira N, Ahmed M, et al. (2017) Evaluating Hospital-Based Surveillance for Outbreak Detection in Bangladesh: Analysis of Healthcare Utilization Data. PLoS Med 14(1): e1002218. https://doi.org/10.1371/journal.pmed.1002218
Academic Editor: Marc Lipsitch, Harvard School of Public Health, UNITED STATES
Received: July 22, 2016; Accepted: December 9, 2016; Published: January 17, 2017
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Data Availability: The data are available to download as Supporting Information files (S1 Dataset and S2 Dataset).
Funding: The study was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement number 278433- PREDEMICS (http://predemics.biomedtrain.eu/cms/), The Laboratory of Excellence – Integrative Biology of Emerging Infectious Diseases (https://research.pasteur.fr/fr/program_project/integrative-biology-of-emerging-infectious-diseases/), AXA Research Fund (https://www.axa-research.org), National Institute for General Medical Sciences–The Models of Infectious Disease Agent Study (https://www.nigms.nih.gov/Research/SpecificAreas/MIDAS/Pages/default.aspx), and US Centers for Disease Control and Prevention (http://www.cdc.gov/). Co-authors who work for CDC were involved in survey design and report writing. Other sponsors had no involvement in study design; collection, analysis, and interpretation of data; writing of the report; or the decision to publish.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: AIC, Akaike information criterion; ARI, acute respiratory infection; WHO, World Health Organization
A well-functioning disease surveillance system is crucial for the identification and control of outbreaks, and hence the prevention of national and global health emergencies [1]. The World Health Organization (WHO) highlighted the value of national surveillance systems in the International Health Regulations (2005), an agreement among all member states to develop and maintain sufficient capacity for the detection, reporting, and control of public health threats of international concern [2]. Infectious disease surveillance should enable (i) the timely detection of outbreaks, (ii) the quantification of health problems, (iii) the identification of subpopulations at risk, and (iv) the assessment of temporal trends including the impact of control strategies [3,4].
National surveillance systems typically collect data from patients seeking care at sentinel hospitals or other healthcare facilities and can provide useful information for public health purposes. However, hospital-based surveillance generally underestimates disease burden since only a proportion of cases visit a hospital for care [5]. Low case detection may also undermine the value of hospital-based surveillance for outbreak detection. Moreover, if patients captured by the surveillance system are not representative of all cases in the community, surveillance statistics could lead to erroneous interpretations of disease patterns and misallocation of prevention resources. In particular, sex, socioeconomic status, or distance can affect healthcare seeking at hospitals, especially where access to care is limited [6–9]. Surveillance evaluation guidelines, such as those established by the US Centers of Disease Control and Prevention, list sensitivity and representativeness among the attributes that a public health surveillance system should possess and that require assessment [10,11]. In order to follow these guidelines, we need external reference data that are often unavailable in resource-poor settings [12].
Here, we present a new approach to evaluating the capacity of a surveillance system to detect and characterize disease cases, with emphasis on outbreaks of emerging infections that often occur as small case clusters in remote areas. We apply our methodology to assess hospital-based surveillance of severe neurological infectious disease and fatal respiratory infectious disease in Bangladesh.
The field teams obtained written informed consent from participants or their guardians (if <18 y of age) during community surveys. Healthcare utilization survey protocols were reviewed and approved by the Ethical Review Committee of the International Centre for Diarrhoeal Disease Research, Bangladesh.
Protocol for Evaluating Sensitivity and Representativeness of Surveillance Systems
Evaluating the sensitivity and representativeness of surveillance systems may be hampered by difficulties in identifying and characterizing the underlying case population. Here we describe how epidemiological studies can be used to identify cases with severe symptoms in communities and capture their personal and healthcare utilization characteristics (data collection stage) (Fig 1). In addition to detailing how we collected the data in this study, we provide information about how the approach could be varied in other settings. We subsequently demonstrate how such data can be used to evaluate the sensitivity and representativeness of surveillance systems (evaluation stage). We then apply our approach to the detection of severe neurological infectious diseases and fatal respiratory infectious diseases in Bangladesh as a case study.
PowerPoint slide
Fig 1. Key steps of the collection of healthcare utilization data to evaluate the sensitivity and representativeness of surveillance systems.
In the Bangladesh example, the catchment areas of surveillance hospitals were first defined based on hospital records (e.g., areas where >50% or >75% of cases reside) [13,14]. Subsequently, small administrative units were chosen at random from within the catchment area, and all communities in the selected areas were surveyed. Cases in the community were identified based on lists of deaths in addition to community networking strategies (rural settings) or house-to-house surveys (urban settings). Information on symptoms (to establish case definitions), healthcare seeking behavior, and characteristics of cases was collected. In other settings, the exact survey procedures may vary according to the context.
https://doi.org/10.1371/journal.pmed.1002218.g001
Selecting study locations.
The first step was to randomly select communities at differing distances from the surveillance hospitals. We specified catchment areas of selected hospitals based on hospital records and subsequently randomly selected small administrative units from which all communities were surveyed. Selection of communities could also be done through census data or using detailed population maps of the area.
Identifying people with diseases in the selected community.
Study teams visited the selected communities and identified cases that had had the disease of interest. The retrospective identification of severe disease cases in the community was based on syndromic criteria, used as a proxy for clinical case definitions that would be applied in healthcare facilities. The identification of such cases in the community is often the most problematic step, and the optimum strategy will depend on the local context, the severity of the disease, and the specificity of disease symptoms.
Collecting information on healthcare seeking and personal case characteristics.
To estimate case detection probabilities, identify biases in case statistics, and characterize the healthcare utilization behavior in the population, we needed information about the healthcare seeking and personal characteristics of cases. In particular, we needed to identify whether the cases attended a surveillance hospital. Such information was obtained during household visits of identified cases. To understand the impact of distance from the hospital, we approximated the locations of households by the central positions of the small administrative units. Alternatively, household locations could be recorded precisely using GPS devices.
Evaluation of the Surveillance System
Quantifying the probability of detecting a case.
We estimated the case detection probability as the proportion of cases who reportedly attended a surveillance hospital among all cases identified in the community. We further assessed how this probability changed with distance from the surveillance hospital.
Quantifying the probability of detecting outbreaks.
We subsequently used the estimated case detection probabilities to quantify the capacity of the surveillance system to identify disease outbreaks. We estimated outbreak detection probabilities for varying outbreak sizes and for outbreaks occurring at different distances from surveillance hospitals.
Assessing the representativeness of detected cases.
We evaluated the representativeness of detected cases by estimating the difference between case statistics (proportions of specific case characteristics) based on all cases in the community and based on identified cases who attended the surveillance hospital. The investigated characteristics included sex, age, and socioeconomic status.
Assessing alternative surveillance strategies.
To investigate how sensitivity and representativeness of the surveillance system could be improved by integrating other healthcare providers, we applied the evaluation procedures as described above to other healthcare provider types.
Example Using Severe Neurological Infectious Diseases and Fatal Respiratory Infectious Diseases in Bangladesh
We demonstrate the application of the proposed evaluation strategy by using it to assess the capacity of hospital-based surveillance for severe infectious diseases in Bangladesh, which is based on tertiary care hospitals located throughout the country. We used data from two surveys carried out in catchment areas of some of these hospitals that investigated the healthcare utilization behavior of individuals with severe neurological infectious disease or fatal respiratory infectious disease (Fig 2A) [14,15]. These disease types are of great public health relevance in Bangladesh (e.g., Japanese encephalitis and influenza) but also represent symptoms typical of other emerging infectious diseases (e.g., Nipah and severe acute respiratory syndrome). A first survey collected data between 10 June 2008 and 30 March 2009 about cases with symptoms of severe neurological infection that occurred within the previous 12 mo in 60 small administrative units (mean population size of 28,000 people) in the catchment areas of three surveillance hospitals [14]. A second survey collected data between 3 April 2012 and 22 February 2013 about acute respiratory infection (ARI)–related deaths that occurred within the previous 24 mo in 22 administrative units in the catchment areas of 11 surveillance hospitals [15]. We considered ARI-related deaths as a proxy for respiratory disease of sufficient severity to require medical attention. The surveillance hospital in Dhaka City was excluded from the original studies because of the difficulty of defining the catchment area (a step necessary for the original study purpose), as people nationwide seek medical care in Dhaka. The surveys followed procedures as previously described and summarized below [13,14]. Characteristics of the study population are described in Fig. A in S1 Text.
Fig 2. Location of administrative units and case detection probabilities by distance.
(A) Location of surveillance hospitals and administrative units. The hospital in Dhaka City was excluded from the original studies. (B) Population density map of Bangladesh [16]. Sixty-eight percent of the population in Bangladesh lives >30 km from a surveillance hospital (including the Dhaka surveillance hospital), a distance at which case and outbreak detection probabilities are low. (C) Probability of surveillance case detection by distance. The observed probability was calculated as a moving average over a 25 km distance window. Case detection probabilities were estimated using log-binomial regression models including distance as an explanatory variable.
Community Healthcare Utilization Surveys
The catchment areas of selected hospitals were first specified based on hospital records (S1 Text). Small administrative units (mean population of 28,000 people) were subsequently selected randomly within the catchment areas, and all communities in the selected areas surveyed. The identification of cases in selected communities was based on social structures, i.e., cases were identified by visiting public meeting points, such as mosques, markets, or tea-stalls, where health problems in the community are often publicly discussed. Cases were subsequently confirmed by household visits. In urban areas, house-to-house surveys were conducted to compensate for less pronounced community structures. Additional fatal respiratory infectious disease cases were identified through lists of deaths provided by administrative officers. For both disease types, the identification of cases was based on syndromic criteria. We defined severe neurological infectious disease as fever with altered mental status for >6 h or with unconsciousness for ≥1 h, or fever with altered mental status, unconsciousness, or a new onset seizure that resulted in death. Fatal respiratory infectious disease (ARI-related death) was defined as having any two of the following symptoms in the 30 d prior to death: sudden onset of fever, cough, breathing difficulty, feeding difficulty, or runny nose. Deaths in children aged <5 y were also classified as ARI-related deaths if there was a sudden onset of breathing difficulty in the 30 d prior to death.
During surveys, information was collected on healthcare utilization behavior and personal characteristics of identified severe neurological and fatal respiratory disease cases. Cases or their household members were asked whether the case visited the surveillance hospital or any other healthcare provider, including other nonlocal hospitals, during his/her illness. Further, information on sex, age, socioeconomic status, and geographic location of households of cases was collected.
Classification of Case Characteristics
We defined "community cases" as all severe neurological or fatal respiratory disease cases identified during community surveys (whether they attended a surveillance hospital or not) and "surveillance cases" as the subset of community cases who reportedly attended a surveillance hospital. For each case identified in community surveys, we identified whether they attended their nearest surveillance hospital. We then estimated the distance to that surveillance hospital as the distance between the residence administrative unit centroid and that specific surveillance hospital using QGIS [17]. Age was categorized as <5, 5–14, 15–59, and ≥60 y. A socioeconomic status index was generated by principal component analysis based on household assets (electricity, working television, bicycle, motorcycle, sewing machine, mobile phone) and categorized into tertiles (lowest, middle, and highest) [18]. In sensitivity analyses, we explored the use of continuous age and socioeconomic status classified into quintiles (S1 Text). Socioeconomic status was missing for 45 of 1,633 fatal respiratory disease cases, who were excluded from the analysis where this information was required. Three fatal respiratory disease cases were excluded from all analyses due to missing healthcare seeking information.
Quantifying the Probability of Detecting Cases
We estimated the disease-specific case detection probability as the proportion of cases who reportedly sought care at a surveillance hospital among all cases identified during community surveys (number of surveillance cases/number of community cases) and computed 95% confidence intervals (95% CIs) based on the Clopper-Pearson exact method [19]. We quantified case detection probabilities by distance from a surveillance hospital using log-binomial regression analysis separately for severe neurological and fatal respiratory disease cases. We further investigated more complex functional forms of distance in log-binomial regression models. We fitted models with polynomial terms up to the fifth degree and models with basic splines with knots at various positions (between 20 and 50 km distance). Model fit was compared based on the Akaike information criterion (AIC), and the models with lowest AIC were selected. The fit of selected models was compared to the observed proportion of cases who attended surveillance hospitals at different distances (moving average over a distance window of 25 km). We estimated the proportion of the population living >30 km and >50 km from a surveillance hospital using gridded population density estimates of 100 × 100 m resolution [16].
Quantifying the Probability of Detecting Outbreaks
To quantify the capacity of the surveillance system to detect outbreaks of varying sizes, we calculated the probability that at least one case was detected: Proutbreak1 is the outbreak detection probability based on a one-case threshold, Pr is the case detection probability, and s is the outbreak size. This calculation assumes that the probability of detecting a sentinel case is independent of other cases. We used distance-specific case detection probabilities estimated by log-binomial regression and obtained confidence intervals of outbreak detection probabilities based on the 95% CI limits of case detection probabilities. We further estimated the size of the smallest outbreak that would be detected with ≥90% probability by distance from the surveillance hospital. For emerging infectious diseases of global health importance, such as Nipah, severe acute respiratory syndrome, or avian influenza, a single detected case may be considered an outbreak. For other disease systems (e.g., endemic diseases or diseases for which differential diagnosis is difficult), an outbreak may be declared only after more than a single case is detected over a specified period of time and within specified geographic boundaries [20]. We can extend the framework to estimate the probability of identifying an outbreak with different outbreak thresholds applied, and we provide examples for outbreaks defined as detection of at least two cases or at least five cases. We calculated the probability of detecting at least two cases (Proutbreak2) as one minus the probability of detecting no cases (Pr0) and exactly one case (Pr1):
Likewise, we estimated the probability of detecting at least five cases (Proutbreak5) as one minus the probability of detecting no cases (Pr0) and exactly one (Pr1), two (Pr2), three (Pr3), and four cases (Pr4):
Assessing the Representativeness of Surveillance Cases
We investigated the representativeness of surveillance cases (sex, age, and socioeconomic group) by comparing the proportion of cases with a specific characteristic (and exact binomial confidence intervals) among community cases to the proportion of cases with that characteristic among surveillance cases. We quantified the absolute difference in proportions (proportion of cases with characteristic among surveillance cases minus proportion among community cases) with 95% CIs and p-values using bootstrapping (2,000 bootstrap iterations) [21].
Evaluating Alternative Surveillance Strategies
Based on the collected healthcare utilization data, we evaluated how the sensitivity and representativeness of a surveillance system may be improved by integrating other healthcare providers. We classified healthcare providers as (i) surveillance hospitals, (ii) other hospitals (government and private clinics), (iii) qualified private practitioners, and (iv) the informal sector (unqualified practitioners such as traditional healers, village doctors, homeopaths, and pharmacies). We estimated the proportion of cases attending each healthcare provider class, with exact binomial confidence intervals, and estimated outbreak detection probabilities based on proportions attending the surveillance hospital plus (i) other hospitals, (ii) qualified private practitioners, or (iii) informal healthcare providers. Furthermore, we compared the proportion of cases with each characteristic (sex, age, and socioeconomic group) among community cases to the proportion among those attending each healthcare provider class and quantified absolute differences in proportions with 95% CIs and p-values using bootstrapping (2,000 bootstrap iterations).
All statistical analyses and graphics were implemented in the R computing environment; maps were created using QGIS software [17,22].
The studied communities were located within 95 km (severe neurological infectious disease) and 62 km (fatal respiratory infectious disease) of a surveillance hospital. In these communities, 76 of 426 severe neurological disease cases (18%, 95% CI 14%–22%) and 234 of 1,630 fatal respiratory disease cases (14%, 95% CI 13%–16%) attended a surveillance hospital. Adjusting for distance, the case detection probability was nearly twice as high among severe neurological disease cases than among fatal respiratory disease cases (risk ratio 1.8, 95% CI 1.4–2.3; p < 0.001). At 10 km distance, an estimated 26% (95% CI 18%–33%) of severe neurological disease cases and 18% (95% CI 16%–21%) of fatal respiratory disease cases were detected by the hospital-based surveillance. The detection probability decreased with distance from the surveillance hospital, and the decline was faster for fatal respiratory disease than for severe neurological disease. A 10 km distance increase resulted in a 12% (95% CI 4%–19%; p = 0.003) relative reduction in case detection probability for severe neurological disease but a 36% (95% CI 29%–43%; p < 0.001) relative reduction for fatal respiratory disease (Fig 2C). Including more complex functional forms of distance in the log-binomial regression models did not improve model fit based on AIC (Table A and Figs. B and C in S1 Text).
The probability of detecting an outbreak of exactly three cases (if a single detected case was considered an outbreak) dropped below 50% at distances greater than 26 km for severe neurological disease and at distances greater than 7 km for fatal respiratory disease (Fig 3A). Fig 3B and 3C show the minimum number of cases required for surveillance to detect outbreaks with a probability of ≥90% if different outbreak thresholds are applied. For outbreaks defined as detection of at least one case, we found that an outbreak of fatal respiratory disease required 12 cases (95% CI 11–13) to be detected with 90% probability at 10 km from a surveillance hospital, but 30 cases (95% CI 24–39) to be detected at 30 km. In contrast, the impact of distance on the outbreak size requirement was much more limited for severe neurological disease: eight cases (95% CI 6–12) at 10 km and 11 cases (95% CI 9–14) at 30 km. For outbreaks defined as detection of at least two cases, 14 severe neurological disease cases (95% CI 11–20) and 20 fatal respiratory disease cases (95% CI 18–23) would be necessary for an outbreak to be detected at 10 km distance, and 19 severe neurological disease cases (95% CI 15–24) and 51 fatal respiratory disease cases (95% CI 41–66) at 30 km. The necessary outbreak sizes increased further when a five-case threshold was applied, so that 28 severe neurological disease cases (95% CI 21–39) and 39 fatal respiratory disease cases (95% CI 35–44) would need to occur for an outbreak to be detected at 10 km distance, and 36 (95% CI 30–46) and 97 (95% CI 79–128), respectively, cases at 30 km.
Fig 3. Outbreak detection capacity.
(A) Probability of detecting outbreaks with exactly three cases of severe neurological or fatal respiratory disease by distance from surveillance hospital if a single detected case is considered an outbreak. (B) Smallest size of severe neurological disease outbreak that would be detected with ≥90% probability by distance from surveillance hospital for outbreak thresholds of at least one, two, or five detected cases. (C) Smallest size of fatal respiratory disease outbreak that would be detected with ≥90% probability by distance from surveillance hospital for outbreak thresholds of at least one, two, or five detected cases.
Surveillance hospital attendance among community cases varied by case characteristics, leading sometimes to biased disease statistics among surveillance cases (Table B in S1 Text). For severe neurological disease, individuals aged <5 y represented 48% of community cases but only 29% of surveillance cases (p < 0.001). Additionally, the proportion of cases in the lowest socioeconomic group was lower among surveillance cases than among community cases (43% versus 57%; p = 0.012), while the proportion of individuals aged 15–59 y was higher (43% versus 29%; p = 0.005) (Fig 4A). For fatal respiratory disease, the proportion of individuals aged ≥60 y (47% versus 62%; p < 0.001) was lower among surveillance cases than among community cases, while the proportion of individuals aged <5 y (24% versus 18%; p = 0.020), individuals aged 15–59 y (27% versus 18%; p < 0.001), and cases in the highest socioeconomic group (43% versus 37%; p = 0.022) was higher (Fig 4B). We observed a slight difference in the proportion of females for fatal respiratory disease (34% among surveillance cases versus 38% among community cases; p = 0.108), but not for severe neurological disease (39% versus 40%; p = 0.861). Results were consistent in sensitivity analyses with age as a continuous variable and socioeconomic status classified into quintiles (Figs. D and E in S1 Text).
Fig 4. Representativeness of surveillance cases.
Comparison of case statistics (proportion of cases with a characteristic) estimated for community cases to those estimated for surveillance cases for (A) severe neurological infectious disease and (B) fatal respiratory infectious disease. Significant differences (bootstrap p ≤ 0.05) are indicated with an asterisk. SES, socioeconomic status.
A substantial proportion of cases (severe neurological disease 42% [95% CI 38%–47%]; fatal respiratory disease 26% [95% CI 24%–28%]) visited multiple healthcare providers during their illness. Forty-eight percent (95% CI 44%–53%) of severe neurological disease cases and 31% (95% CI 29%–34%) of fatal respiratory disease cases attended any hospital, including surveillance hospitals (Fig 5). Including other hospitals that were attended by cases in the surveillance system could have increased the overall case detection probability by 31% (absolute increase) for severe neurological disease cases and 17% for fatal respiratory disease cases. The capacity to detect outbreaks would have increased, so that outbreaks containing four severe neurological or eight fatal respiratory disease cases would have been detected with ≥90% probability for any distance in the range 0–40 km from the original surveillance hospital, compared to 13 and 47 cases, respectively, with the current system (Fig. F in S1 Text). However, since individuals who attended any hospital had similar characteristics in terms of sex, age, and socioeconomic status as those attending surveillance hospitals (Fig. G in S1 Text), this expansion would not have increased disease detection in key groups such as the lowest socioeconomic group. Only with the informal sector incorporated in the surveillance system would cases in such groups be detected.
Fig 5. Attendance at surveillance hospitals and alternative healthcare providers.
Proportion of (A) severe neurological and (B) fatal respiratory disease cases attending surveillance hospitals and other healthcare providers. Cases may attend several different healthcare providers during their sickness. Cases who attended a surveillance hospital at any time are indicated with diagonal hatching.
We described an analytic approach for evaluating the sensitivity and representativeness of hospital-based surveillance systems and applied it to surveillance for severe neurological diseases and fatal respiratory infectious diseases in Bangladesh. We quantified the proportion of cases detected and the probability that the surveillance system would detect different sized outbreaks by distance from the surveillance hospital. Finally, we characterized biases in surveillance statistics and identified potential improvements to the surveillance platform.
We estimated that approximately one-quarter of severe neurological disease cases and one-fifth of fatal respiratory disease cases occurring 10 km from a surveillance hospital would be detected with current surveillance. The proportion of cases attending a surveillance hospital declined significantly with increasing distance between individuals' residence and the surveillance hospital, substantially faster for fatal respiratory disease than for severe neurological disease. These low detection probabilities mean that hospital-based surveillance in Bangladesh (like in most other resource-poor countries presumably) would likely miss a high proportion of single-case public health events. Of greater relevance is that surveillance system capacity to detect outbreaks and detection probabilities increased substantially with the number of cases. The required number of cases to detect outbreaks with high probability varied with disease type and distance from the surveillance hospital. It could be as low as about ten cases if the outbreak occurred <10 km from the surveillance hospital but increased quickly with distance for fatal respiratory disease. For outbreaks defined as a single detected case, we found that more than half of outbreaks with ten cases of fatal respiratory disease would be missed if the outbreak occurred >32 km from the hospital. Such detailed quantification of outbreak detection probability is essential to ascertain the likelihood that an emerging threat can be detected early enough to be contained [23].
In some circumstances, authorities may have to wait until more than a single case is detected to recognize that an outbreak is occurring. In particular, difficult differential diagnoses and lack of appropriate diagnostic tests mean that only when a number of cases are detected from the same area and over a short time frame will an outbreak be identified and further investigations conducted. In addition, where a low background level of transmission is expected (such as with endemic diseases), public health authorities may wait until a particular threshold is exceeded before declaring an outbreak. In both of these scenarios, where multiple cases need to be detected by the hospital before an outbreak is recognized, the optimal number of detected cases and their spatial and temporal separation will depend on the disease system. We can incorporate this information into our flexible framework and provide examples where we calculate the size an outbreak needs to be for scenarios where at least two or five cases need to be detected (Fig 3B and 3C). In particular, this demonstrates that if an outbreak is identified only once five cases are detected at the surveillance hospital, the size of the outbreak would have to be substantially larger (e.g., nearly 100 total cases of a fatal respiratory disease at 30 km from a surveillance hospital) for there to be a 90% chance of an outbreak being identified. This highlights the possibility that, by the time an outbreak reaches sufficient size to be detected by the system, outbreak control measures may be much less effective at controlling spread. Thresholds for case counts that trigger an outbreak response should be crafted taking this possibility into account.
Low detection probabilities for outbreaks that occur far from surveillance hospitals are an important concern because pathogens with high case fatality such as Japanese encephalitis and Nipah virus are nearly exclusively found in rural communities in Bangladesh [24,25], and these communities are usually located far from surveillance hospitals. Rural environments are also considered to be at highest risk for the emergence of novel pathogens [26,27]. Population distribution maps suggest that 68% of the population in Bangladesh live in communities >30 km from a surveillance hospital (representing 108 million individuals) and 40% live >50 km from a surveillance hospital (representing 63 million people) (Fig 2B). Strengthening healthcare-based surveillance in these areas should be a priority, and cost-effective approaches to achieving surveillance targets need to be identified. There is increasing recognition of the value of novel data sources to improve the sensitivity of infectious disease surveillance, some of which can provide crucial information in remote areas [20]. Novel approaches include surveillance for media reports of disease clusters, as used for various infectious diseases in Bangladesh [12,28], and training of local drug sellers to recognize and report disease symptoms, as rolled out nationally to enhance tuberculosis surveillance in Ghana [29]. Other surveillance data streams, such as monitoring over-the-counter medication sales, telephone triage, and web-based queries, have been successfully integrated in surveillance systems in resource-rich settings [30].
We found that cases attending surveillance hospitals were not necessarily representative of all cases in the community. In particular, the youngest severe neurological disease cases and the oldest fatal respiratory disease cases were less likely to attend surveillance hospitals, and attendance was also lower among cases in the lowest socioeconomic group. Similar variation in hospital attendance has been reported in other resource-poor settings [6,8,9], indicating that hospital-based surveillance in these countries may have comparable limitations. Disease statistics obtained through hospital-based surveillance have to be interpreted in the light of detected biases, and correction factors may need to be applied. For example, underestimating severe neurological disease among young children may mislead any future Japanese encephalitis vaccination strategy [31,32]. Differential surveillance hospital attendance may also influence the capacity to detect emerging infections, such as the avian influenza A (H7N9) virus that emerged in 2013 in China with observed cases mainly among elderly men [33].
Overall, access to appropriate care was poor—over 30% of community cases with severe disease or who died in our study never saw a qualified provider. Such low access is a common problem in low-income settings and means that a large proportion of the population, and particularly subgroups that are potentially at highest need, do not receive the required medical attention [6–9]. For example, difficulties accessing qualified healthcare providers for elderly people, who are often at greatest risk of respiratory disease, can have severe consequences for the outcome of disease. Previous studies have demonstrated that accessibility to healthcare is a significant predictor of morbidity and mortality among elderly individuals with respiratory disease [34].
The study showed that healthcare utilization behavior varied by disease type, which may be due to different characteristics of cases such as their age, socioeconomic status, and geographic location (Fig. A in S1 Text). The majority of fatal respiratory disease cases were ≥60 y old and may have faced limitations in mobility; moreover, rapid progression of disease to death may have prevented cases in this age group from seeking appropriate care. Cases and their family members in general may have also perceived neurological symptoms as more severe, resulting in higher motivation to attend a qualified healthcare provider [7].
We evaluated potential improvements of surveillance by analyzing healthcare seeking behavior among cases identified in communities. While the majority of individuals did seek care, much of this was in the informal sector, which cannot easily be incorporated into surveillance activity. Nevertheless, including other hospitals attended by cases in the surveillance system (the exact location and number of these hospitals was unfortunately not identified during surveys) would double case detection probabilities and allow detection of medium-sized outbreaks (<10 cases) in a wider geographic area. However, in the case of Bangladesh, such extension is likely to be prohibitively expensive. Mapping other hospitals in Bangladesh that may serve as surveillance sites would allow testing of various surveillance scenarios to identify the optimal location of surveillance sites while keeping the same total number or to quantify the number of sites needed to achieve a target surveillance coverage [35]. Many emerging infectious diseases originate as spillover infections of zoonotic diseases into the human population [36]. Therefore, mapping the occurrence of relevant zoonotic diseases (e.g., avian influenza) and combining such maps with the estimated outbreak detection probabilities would allow highlighting of surveillance gaps for particular types of emerging infectious diseases.
The capacity of surveillance systems to detect outbreaks will depend not only on the probability that a case attends a surveillance hospital, but also on whether the case undergoes confirmatory laboratory testing and is subsequently reported through the surveillance system by the hospital. Here we assumed a "best-case scenario" with a fully functional surveillance system at the hospital level, where each case who attends the surveillance hospital is ultimately recognized and confirmed as a case. Case detection at the hospital may however be incomplete, since case definitions at hospitals may differ from syndromic definitions, a surveillance sampling frame may be applied, or resources and trained personnel for the diagnosis and reporting of cases may be limited [37]. The calculation of case and outbreak detection probabilities may be adjusted for misdiagnosis and underreporting at hospitals if such information is available. We further assumed complete detection of cases in communities during surveys. Although a few cases may have been missed, this assumption is justified as we investigated severe disease conditions that are easily remembered by family and community members. Moreover, survey procedures combining interviews of key informants and house-to-house visits were specifically designed to capture near-complete case information. Further, any missed cases are unlikely to impact our estimates, as such impacts would occur only if there was differential healthcare seeking between those detected and those missed. We investigated spatial differences in hospital attendance based on the straight-line distance of communities from the surveillance hospital. If available, other distance measures such as travel distance or travel time may provide a more accurate indicator of distance from the surveillance hospital. In some cases, these measures may strongly vary with the season, and it would be interesting to explore how that may impact the probability of detecting an outbreak. We assumed that cases did not visit other surveillance hospitals than the catchment hospital. Given the poor road infrastructure in the country, it would be very unusual to travel to a tertiary care hospital that was not the closest one. It is possible that some individuals traveled to Dhaka; however, these are likely to be wealthier individuals who would visit small private healthcare facilities that are not part of the surveillance network. The surveillance hospital in Dhaka was not included in our study. This is unlikely to have biased our assessment of the performance of the surveillance system outside the capital. Indeed, this would introduce a bias only under the unlikely scenario that many cases in our study who did not attend the nearest surveillance hospital (and were therefore not captured there) instead attended the surveillance hospital in Dhaka (and were captured there). Surveillance system performance in the capital city may however differ from elsewhere, and a comprehensive assessment of the national surveillance system would therefore have to include Dhaka. Moreover, hospital-based surveillance is only one surveillance type in Bangladesh, and other data sources need to be considered to assess the country's overall capacity to detect public health events.
The described methodology is applicable to assessing surveillance for other severe diseases in resource-poor settings, keeping in mind practical constraints. Conducting community surveys may be labor intensive, time consuming, and expensive depending on the setting and may be particularly challenging in densely populated areas such as Dhaka. Nonetheless, such surveys are valuable tools for obtaining external reference data and simultaneously assess heterogeneities in healthcare access. The effectiveness of community networking may depend on the social structures in the study area; where social links are weaker (e.g., in urban areas), house-to-house surveys, even though more labor intensive, may be more suitable for the identification of cases in the community. The proposed strategy is valid for diseases of sufficient severity to require medical attention and to be remembered by cases and family members. The approach is syndromic (i.e., disease types are classified based on a set of symptoms), and the classification specificity may vary by disease.
In conclusion, this study allowed us to quantify the sensitivity and representativeness of hospital-based surveillance and to identify weaknesses, particularly in detecting small- to medium-sized outbreaks in remote areas. These findings highlight difficulties that low-middle-income countries may have in meeting International Health Regulations requirements, despite considerable investment in hospital-based surveillance platforms.
S1 Dataset. Healthcare utilization by distance from surveillance hospital.
https://doi.org/10.1371/journal.pmed.1002218.s001
(XLSX)
S2 Dataset. Healthcare utilization by case characteristics.
S1 Text. Additional results and figures.
The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) acknowledges with gratitude the commitment of the US Centers for Disease Control and Prevention to its research efforts. icddr,b is also grateful to the governments of Bangladesh, Canada, Sweden, and the UK for providing core/unrestricted support.
Conceptualization: BN HS SC ESG.
Formal analysis: BN.
Investigation: KSR EAB NH MA ADI RCP MR MJH SPL.
Methodology: BN HS SC ESG.
Writing – original draft: BN HS SC ESG.
Writing – review & editing: BN HS KSR EAB NH MA ADI RCP MR MJH SPL SC ESG.
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Infectious disease surveillance
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Socioeconomic aspects of health
Is the Subject Area "Socioeconomic aspects of health" applicable to this article?
Is the Subject Area "Infectious diseases" applicable to this article?


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⇐ Hey, I'd be just as happy with it for 50% off. Who doesn't love a good deal?
AKA I didn't do the Valentine's Day Romance Books push this year. I'm not sure I've ever bothered, actually. Probably, I have. After all, I've been at this a while.
Anyway, I write romance, kind of. Not what many would call romance since it's not genre fitting. It's lit fic meshed romantic artsy love stories with up endings. Women's fiction, more or less but not precisely.
It is relationship based, but even action adventures feature romance in some way.
Since I buck the trend in my writing, I figure I can do the same with the whole Love For Sale thing.
Prices include media mail shipping within U.S. and matching bookmarks.
They will be personally signed!
This is Finishing Touches (2003) combined with its sequel Final Strokes (2013) in one edition.
These two novels are related but can be read separately. OTM was written first, but M&T is set 9 years earlier.
I only have a handful of these left, as well, and it's not much of a discount because the original price is already very low.
Not a romance, a picture book that has a lot of adult fans.
To order, I accept and prefer Paypal. Please email Loraine [at] LKHunsaker.com (no spaces, no caps needed) for Paypal address.
If you're outside the U.S. shipping costs make it unviable to mail books at prices lower than you can get them through your own bookstores. If you order any of my books and would like a signed bookplate, email your mailing address.
I haven't forgotten my other books! Stay tuned for Rehearsal news and sales.
Questions? Ask here or email.


The Globe theatre along river Thames is one of the most famous Shakespearean stages were mere mortal actors walk in and out playing their respective parts thereby recreating the bard's Aura.
The theatre itself is a near perfect replica of the original Rose theatre which stood closeby and was destroyed in a fire in the 17th Century. Shakespeare used to perform in the old Rose theatre and was a shareholder. Use of traditional material like Oak wood, Reed Thatch and a circular design lends an air of authenticity to the new Globe transporting viewers to an Elizabethan era.
The plays usually run for more that 2 hours with an interval. Latecomers are not entertained. When there are no performances the visitors can take part in Globe Theatre tours which gives an opportunity to learn more about the building and the bard himself.
Theatre is located in Bankside close to Tate Modern . It is best accessed by foot along the Thames pathway either from the Southwark or Waterloo bridge. The pedestrian Millenium Bridge is very close connecting with St.Paul's Cathedral. London Bridge , Cannon Street and Blackfriars stations are at a walkable distance.


This is such a sweet and special session because Tiffany was one of my very first photographer friends when we moved to Richmond. It was definitely meant to be because we both attended a photographers meet-up (such a rare thing for both of us to do!) and sat eating our fries with the rest of the group while everyone awkwardly connected over a love for our careers and a desperate need for faces that engaged a bit more than the ones in our Lightroom catalogs. Fast forward almost two years and many Urban Farmhouse lunch dates later, we've become great friends who chat endlessly over our businesses, marriages, puppy children and our pregnancies. Ahead of my by a trimester, it has been such a joy to watch Tiffany enter motherhood (and leave pregnancy behind!) and reap from her wealth of knowledge about all things!
Erik and Tiffany you guys are already amazing parents and little Willow is the cutest little ginger baby I've had the privilege to know! I hope our kids grow to be good friends and don't mind that we will have cameras in their faces...well, forever. :) It is so amazing that she is finally here, all those fingers and toes and that cute button nose...Oh little Willow welcome to the world! Congratulations you guys!


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Jason van Rassel reviews Analog Brewing, Bowser Brewing, Evan Bowser, Great Falls, hefeweizen, jalapeno, Little Guy Liquor Store, Montana, Sherwood Park, Whtiefish
When we lived in Calgary, my wife Lea and I enjoyed a few getaways to Montana. It was mainly for skiing and other outdoor pursuits in and around Whitefish, but I was always eager for an opportunity to dive into Montana's rich craft beer culture — particularly in the pre-2013 era before Alberta's scene took off.
I enjoyed visiting several breweries during our trips to Montana, but I regret never making it to Bowser Brewing in Great Falls before it closed in 2017. A few friends recommended the place, and there was one beer that immediately caught my eye when I visited their website several years ago: a hefeweizen made with jalapeno peppers. With the right execution, I thought it could be an interesting and highly drinkable beer.
Bowser Brewing's demise prevented me from finding out — until now, that is. I recently discovered Edmonton's Analog Brewing made a jalapeno hefeweizen called Na'cho Hefe, and I just knew that I had to try it.
From what I can tell, it's a small-batch release available on tap at the brewery and other select locations. I tracked it down at Little Guy Liquor Store in Sherwood Park, where it was available at the growler bar. After trying the beer over the long weekend, I can say it was worth the drive from downtown Edmonton.
When I first heard about Bowser's jalapeno hefeweizen, an idea formed in my mind about what the beer should taste like. While I never got to try theirs, Analog's Na'cho Hefe lived up to my lofty expectations.
You notice jalapeno in Na'cho Hefe right away: it's in the aroma when you smell it. But so are the elements you expect in a well-made hefeweizen, banana esters and some spicy, earthy cloves. The flavour mainly follows the aroma, but the esters shift a bit from banana on the nose to some bubblegum on the palate as well. The mouthfeel is medium-bodied and just right for the style. The jalapeno is there, but it's an undertone and provides just a slight spicy tingle. (I took a bit of licence with "Hot and hefe" in the headline, because of its pun value and for the sake of making a Seinfeld reference on that basis. This beer isn't "hot" at all, so don't let that deter you.)
Flavouring beer with added ingredients is always a balancing act: First, you have to choose something that will marry well with the base beer. Then, you have to add it in a manner and in a quantity that hits a sweet spot between ensuring people know it's there, but not so much that it detracts from the drinkability of the beer.
Analog has successfully walked that metaphorical tightrope and made a beer that has a distinct jalapeno flavour, but remains unmistakably a hefeweizen. Most importantly of all, it's not a one-and-done novelty: I reached for a second glass and enjoyed it as much as the first.
Having said all that, I should acknowledge that I'm more open to experimentation than a lot of beer drinkers. At its worst, beer nerd subculture is insular and isn't concerned with what a wider audience may want. Fanbois and fangirls often venerate brewers for outlandish things they can do, as opposed to considering whether they should have done it. A beer made with kids' breakfast cereal may rate as a technical achievement and become a cool conversation piece, but does it have any lasting appeal?
I found Na'cho Hefe plenty drinkable on its own, and I think it has added appeal as a pairing with the right kind of food. I enjoyed it with some barbecue chicken I made for supper, and I bet it would be awesome with (yes) nachos and/or chicken wings, too. I'd love to see Analog make more of this beer, but that's easy for me to say as someone who isn't a brewery owner with bills to pay. I'd be happy to see it again, but I also understand if it's a long time before I do.
Coalbanks Porter: black gold from Lethbridge
Jason van Rassel reviews Canadian Brewing Awards, Coulee Brew Co., Lethbridge, porter
If there's an upside to the unseasonably cold weather that has descended upon Alberta, it's been an opportunity for me to dive back into some darker beer styles I typically put aside for a couple of months.
It's also been a chance for me to discover Coalbanks Porter from Coulee Brew Co. in Lethbridge. Coulee's opening, and a few others in southern Alberta, coincided with the time I started working in Edmonton, so I have to admit breweries from that part of the province haven't caught my attention maybe as much as they should.
That appears to be my loss, at least as far as Coalbanks Porter is concerned. It won gold in its category at the 2018 Canadian Brewing Awards — and as much as competition results aren't the be-all and end-all (which would make an interesting blog piece in its own right), earning some hardware at a reputable competition overseen by knowledgeable judges is a reasonable indicator of quality.
Coalbanks pours a nearly opaque dark brown, with a thin head and a cocoa-like aroma with a coffee undertone. The flavour follows the same general combination, but there's a bit more complexity on the palate than on the nose. Coalbanks is sweet at first, but not cloyingly so. It's more like semi-sweet chocolate. The dark malts bring some roastiness with them, too — but it's moderate, like a lightly-sugared coffee with some milk. The carbonation is low and Coalbanks is smooth going down.
Although there's a building dryness as you go, this porter definitely falls on the milder side for the style. It could be a tad fuller-bodied, but it's a nice comforting sipper for the colder days ahead.
Django: unchained and enjoyable
Jason van Rassel reviews Ale Architect, Avenue Edmonton, coriander, ginger, Mason Pimm, Norsemen Brewing, peppercorns, Ryan Stang, sushi, Two Sergeants Brewing, witbier
From the moment I heard about it, I liked the idea behind Ale Architect, one of the latest entries to Edmonton's craft beer scene.
I've always thought of brewing as a combination of creativity and precision, which is why the name appealed to me. While the two principals behind Ale Architect, Mason Pimm and Ryan Stang, are both beer industry veterans, their backgrounds outside the biz reflect that yin and yang of zymurgy: Mason, a partner at Two Sergeants Brewing, is a mechanical engineer while Ryan, who was head brewer at Norsemen Brewing in Camrose, has worked in the design field. (He used his creative chops to give Ale Architect its cool look.)
Mason and Ryan have launched Ale Architect as a contract operation, a move that they believe will allow them to take some risks and make adventurous beers without the significant costs involved in owning a bricks-and-mortar brewery. (At least not initially.)
After a couple of collaborations with other breweries, Ale Architect has come out with the first beer of its own: Django, a Belgian-style witbier (wheat ale) spiced with ginger and Szechuan pepper.
The exotic additions certainly fit the concept that initially piqued my interest in Ale Architect. After trying Django, I'm happy to say I'm a fan of their execution too. For as much as Django is a break from a conventional witbier, it's as approachable and easy-drinking as a traditional example of the style.
Django pours cloudy and straw-coloured like you'd expect from a witbier, but the aroma quickly hints that you're in for something different: instead of orange and citrus, there's a distinct — but not overpowering — whiff of ginger. Ginger is also the first thing to hit the palate, but again, it's pleasant. The carbonation is light and spritzy and Django finishes dry, with a slight tingle of ginger on the tongue — not unlike how pickled ginger is used to cleanse the palate when eating sushi. The peppercorns are there, too, but I'd say they're subtle. Witbiers traditionally have mild spiciness and earthiness from additions like coriander; in Django, it's from peppercorns. When it comes to putting peppercorns in beer, I'd argue less is more: I once had a porter spiced with peppercorns from Hong Kong and they overpowered the beer, basically rendering it an interesting but not entirely pleasant experiment rather than something I'd want to drink even a second time.
Django, on the other hand, is a refreshing and thirst-quenching beer worthy of repeat enjoyment. If I'm disappointed about anything, it's that it's coming out near the end of summer. Here's hoping there are a few more hot and sunny days to let it shine.
I have more about Ale Architect and some other new breweries on the local scene in the September issue of Avenue Edmonton. Read the article here or pick up the magazine at various locations around the city.
Bench Creek Brewing's new pilsner is tops
Jason van Rassel reviews Andrew Kulynych, Apex Predator, Bench Creek Brewing, Bohemian pilsner, noble hops, pilsner, Steamworks
There have been some big changes at Bench Creek Brewing lately — most notably, the introduction of two new beers to its year-round line-up: a Bohemian (Czech-style) pilsner and a Czech amber lager.
The changes are part of a larger rebranding that saw Bench Creek expand the Apex Predator name — used up until now for its popular seasonal double IPA — to a line of year-round releases that includes the two new beers, as well as the existing porter (no longer called Black Spruce), session ale (the former Flint and Steel) and red ale (RIP, Northern Grace). Bench Creek also killed off the Naked Woodsman name for its pale ale and rechristened it Dead Woodsman. White Raven IPA is still White Raven. Got all that?
I've heard some grumbling about the name changes being confusing and/or arbitrary, but my own reaction is: "So what?" It's not that branding isn't important: woe betide any company that tries to get away with tasteless marketing in this day and age — and rightly so. Nor would it be smart to use names or imagery that make your product seem unappealing, particularly if you're selling something you want people to eat or drink. "Tailings Pond Stout" is probably not a good name for a beer, no matter how good it is. Considering Bench Creek's rebranding doesn't cross either of those lines, what we're left with is a subjective debate about personal preference. Tomayto, tomahto. The guy who owns Bench Creek, Andrew Kulynych, decided it was time for a change — and that's, quite literally, his business.
Thanks to that little rant, I've gone and buried the lead, which is Apex Predator Bohemian Pilsner is a first-class beer. My many years as a reporter, a job where offering opinions was usually verboten, have left me averse to using absolutes or superlatives so I don't mean it lightly when I say I think it's among the best Czech-style pilsners made in Canada, right up there with Steamworks Pilsner from Vancouver.
The problem with a lot of mediocre and subpar pilsners is that many are just golden lagers in disguise, lacking the spicy noble hop punch that sets pilsners apart. Apex Predator is all pilsner, from the minute you open it: it's an appealing straw colour and pours with a smooth white head. The noble hops are there on the nose, with a spicy and slightly herbal aroma that mingles nicely with some bready malt. The flavour combines the same elements, but it accomplishes that neat trick of being complex and drinkable at the same time. Start with bready malt and a bit of grain husk, followed by some spicy, slightly bitter hops and a touch of honey sweetness. Back to bready malt and moderate bitterness. All in one sip.
Apex Predator finishes crisp and clean like a well-made lager should. It's tasty, balanced and refreshing — and I mean that as high praise. In an age when barrel-aged, high-alcohol and out-there beers get the lion's share of attention from fanboys and fangirls it's easy to take a straightforward quality like drinkability for granted. It's ironic, if not a little unfair, because beer nerds, of all people, should know how difficult it is to achieve the kind of subtlety and balance that make a great pilsner. Apex Predator has it.
#ABbeer and baseball: a collaboration with Alberta Dugout Stories
Jason van Rassel places, reviews #ABbeer, Alan Ashby, Alberta Dugout Stories, Barry Bonds, Doug Ault, Edmonton Prospects, George Bell, Jesse Barfield, Joe Carter, Lloyd Moseby, Montreal Expos, Okotoks Dawgs, Otto Velez, Re/Max Field, Seaman Stadium, Toronto Blue Jays, Western Major Baseball League, WMBL, World Series
I loved baseball, once.
I grew up in Toronto, where I witnessed the birth of the Blue Jays and their progression from a collection of likeable journeymen (Doug Ault, Alan Ashby, Otto Velez) into contenders (1985 AL East champs with George Bell, Lloyd Moseby and Jesse Barfield in the outfield) and finally, World Series champs in 1992 and 1993. I watched Joe Carter's series-winning walk-off homer in 1993 by myself, at my then-girlfriend's place on Concord Ave., while she was at work. I couldn't wait for her to come in the door as the celebrations erupted outside, so I ran onto Bloor Street and high-fived stranger after stranger as I went to meet her at Ossington subway station. I was there for it all, often freezing in the metal bleachers of Exhibition Stadium (the Mistake by the Lake) and then joining the throngs that flocked to see the SkyDome and its retractable roof when the building opened in 1989.
Then came the strike of 1994, when my equally beloved Expos seemed destined for a date with the New York Yankees in the World Series, until a players' strike scuttled the season. (This was before regular season interleague play, so it was easy to cheer for a National League team without risking divided loyalties.) By the time the strike was over, the Expos had lost many of their stars to free agency and ownership was no longer interested in fielding a contender. The team's slide in the standings sparked a decline in fan interest that eventually led to the team packing up for Washington, D.C. in 2005.
Between watching the slow death of the Expos and ascendance of surly and thoroughly unlikable giant-headed steroid freaks, I'd had enough. I stopped paying attention to baseball. And that's why this blog has no baseball equivalent of my Hops and Hockey Cards feature. Baseball simply doesn't hold the same place in my heart as hockey.
Nevertheless, during my 20 years in Alberta, I've felt flickers of the old fondness come back. I've enjoyed hot summer afternoons at Seaman Stadium, home of the Okotoks Dawgs of the Western Major Baseball League. It's a charming ballpark where just a few bucks gets you a seat where you can hear the crack of the bat up close and smell the fresh-cut grass on the field.
So, when Alberta Dugout Stories approached me about reviewing the beer available at WMBL parks in Alberta, it was an easy sell. WMBL clubs, like craft breweries, are local ventures that enrich our communities — and many teams serve local beer at home games. There are a few that don't, but I think it's important to point out here that these are grassroots organizations doing their best with what they can. It's not fair to beat up on minor league ball clubs made up of college kids for getting the best possible deal on beer, regardless of who made it.
Q. What's wrong with this photo?
A. Nothing.
The Edmonton Prospects are one of the WMBL teams that don't offer craft beer at the ballpark. Although I would have preferred to have one during my recent outing at Re/Max Field, I can tell you that the absence of craft beer had absolutely no negative effect on my enjoyment of the game: it was a mild, sunny evening with a spectacular view of the river valley beyond the left field fence and I had a primo seat on the first base line for the princely sum of $18. It was also the night Okotoks Dawgs head coach Mitch Schmidt lost his mind over an ump's call and threw a bunch of chairs onto the field after getting tossed out of the game. That, alone, was worth the price of admission.
Head to Alberta Dugout Stories for my rundown of Alberta's ballpark beer. Better yet: head out to the ballpark before the season is over and watch some pretty entertaining baseball.
A beer named Pierre
Jason van Rassel reviews Blindman Brewing, brettanomyces, foeder, saison
Blindman Brewing recently released its first beer aged in one of two oaken foeders it bought from a cognac maker in France — and it did not approach the new venture timidly.
The brewery threw a metaphorical kitchen sink of ingredients into the recipe for Pierre, named in honour of a French barrel maker named Jean-Pierre who repurposed the foeders for making beer. No less than a dozen yeast and bacteria strains went into the beer, along with barley, wheat, rye, oats, coriander, Grains of Paradise and whatever flavours and microbiota have been left behind from years of aging cognac inside the foeders.
The resulting beer is complex — and enjoyable. The two don't always go hand in hand if all the elements don't work well together, but here they do.
Pierre poured a cloudy gold, with a hint of coriander in the aroma. The initial flavour and sensations on my palate were bright and lemony. This is one of the tamer (and more pleasing, IMO) manifestations of the wild brettanomyces yeast strain and I feel it's usually a good complement to the traditional saison yeasts that give the style its characteristic tartness and dryness. There's a mild peppery quality, either from the yeast, the coriander, the Grains of Paradise — or a combination of all of them. The fact it's impossible to tell where one starts and another ends shows the brewery had a deft hand with all of them. The oats are there for mouthfeel, giving the beer a bit more softness than typical saisons, which are usually highly carbonated and effervescent. If you put nerdy style considerations aside and just consider whether it's enjoyable or not, I would argue it is.
Just as "complex" doesn't always mean "good," complexity in a beer doesn't mean it's unapproachable. There's a building tartness and some moderate acidity as you keep drinking, but Pierre never tips over into full-on, puckering sourness. I struggled for a good 20 minutes trying to put my finger on how to describe it before the answer emerged from one of the recesses of my addled brain: it's kind of like the SweeTarts candy I remember having as a kid. (And yes, I mean that as a compliment.) For all Pierre's stylistic flourishes, it finishes like a solid traditional saison should: dry and dusty.

redpajama_set_name: RedPajamaCommonCrawl


setmaillist reads a mailing list from its standard input.
setmaillist writes the mailing list in a binary format to tmp; it then moves tmp to bin. tmp and bin must be on the same filesystem.
If there is a problem creating tmp, setmaillist complains and leaves bin alone.
The binary mailing list format is portable across machines.
setmaillist always creates bin world-readable.
The mailing list read by setmaillist is a series of lines. NUL bytes are not allowed.
If a line begins with a dot or slash, setmaillist takes the entire line as an include file name.
If a line begins with an ampersand, setmaillist takes the rest of the line as a recipient address. If a line begins with a letter or number, setmaillist takes the entire line as a recipient address. Each recipient address must include a fully qualified domain name. Recipient addresses longer than 800 bytes are not allowed.
setmaillist ignores blank lines and lines beginning with #. It also ignores spaces and tabs at the ends of lines.
is a mailing list with two addresses.


26 Jun 2017 Washington, D.C.
Three CNN employees have resigned amid the network's very fake news scandal in which it was forced to retract a hit piece on President Donald Trump and his associates.
Stelter quoted an anonymous CNN spokesperson—the network refused to comment to him on Sunday night over the scandal—as saying the network accepted their resignations. As Stelter acknowledged — not in this piece, but in his Sunday evening "Reliable Sources" newsletter — it was a Breitbart News investigation that forced CNN's retraction and now the resignations of three top network officials.
An internal investigation by CNN management found that some standard editorial processes were not followed when the article was published, people briefed on the results of the investigation said. The story, which reported that Congress was investigating a 'Russian investment fund with ties to Trump officials,' cited a single anonymous source. These types of stories are typically reviewed by several departments within CNN — including fact-checkers, journalism standards experts and lawyers — before publication. This breakdown in editorial workflow disturbed the CNN executives who learned about it. In a staff meeting Monday afternoon, investigative unit members were told that the retraction did not mean the facts of the story were necessarily wrong. Rather, it meant that 'the story wasn't solid enough to publish as-is,' one of the people briefed on the investigation said. The reporting about the Russian investment fund and Trump officials was not relayed on CNN's television channels, but it was published on the web and shared on social media. On Friday, one of the people named in the story, Trump ally Anthony Scaramucci, disputed Frank's reporting and said, 'I did nothing wrong.' Friday night, once it was determined that editorial processes were not followed, CNN deleted the story from CNN.com. Soon thereafter, the story was officially retracted and replaced with an editor's note.
CNN is still not commenting via official on-record statements from its public relations department and continues refusing to provide network President Jeff Zucker for interviews. There are many questions the network is still not answering about what is now the most serious scandal in its history.
Haris, the head of the CNN investigative unit who has resigned, is the only CNN official who resigned who gave a statement for the story. Stelter wrote that he "was named the executive editor of CNN Investigates in January" and was previously the executive editor of CNNMoney.
Frank worked for USA Today and Newsday for three decades, pursuing investigations and covering the Iraq war as an embedded reporter, before coming to work at CNN. He was part of an ambitious new investigative unit that was created last winter, bringing together existing teams from within the company and new hires like Lichtblau. A veteran of The New York Times who won a Pulitzer Prize for national reporting in 2006, Lichtblau joined CNN just three months ago.
This is a developing story. More information is forthcoming.


The Chop House opened its doors in December 2009, offering a new food concept within a Dublin 4 pub! Our focus to produce high quality dishes using the best of Irish produce. As the name suggests our main ingredient is Irish Meat, the winner of which is our beef.


1Franchising is a popular option for businesses looking to expand and for entrepreneurs looking to run their own business within a supportive structure. Over the last 5 years franchising has gained in popularity, but it's important that both franchisors and franchisees understand the legal issues involved in the franchising process.
2The Franchising Code of Conduct governs franchising in Australia. It's vital that any prospective franchisor ensures every element of their franchise is compliant with the Code.
3The most important document governing a franchise relationship is the franchise agreement. A franchise agreement sets out the legal relationship between the franchisor and franchisee, includes the franchise history, and details how the franchise will work. This includes upfront and ongoing payments by the franchisee, and what the franchisee receives for those payments.
4A franchise disclosure document must be provided to each prospective franchisee. A disclosure document is designed to give a franchisee an overview of the franchise agreement terms he or she is agreeing to. Every franchisee should have the franchise agreement and the disclosure document reviewed.
5Franchises generally involve considerable up-front and ongoing payments, and have a minimum term of several years. Setting up a franchise, or entering into a franchise as a franchisee, is a considerable commitment. It is important that both sides of the franchise are well-advised by lawyers and accountants who have expertise with franchises. Specialist advisers know what to look for and can advise you on what is standard and acceptable.
LegalVision's Franchise Team has assisted hundreds of franchisors and franchisees with their franchise needs.
We can assist with drafting key documents, leasing, negotiations, intellectual property and buying and selling a franchise.
Watch the video and learn more about our franchise lawyers and tips on running a successful franchise.


I don't want to live where the deer and the antelope play, but even still...what an amazing palette of landscape colors this would be to see from day to day.
What are these colors? Buff, chartreuse, slate? Pantones #1345, #100, #425? The color of dry?
I took this photo out the car window in Wyoming.
Note to those who suffer with colorblindness, check this out.
I saw blue, but Mr Kubrick saw an azure sky of deepest summer !
I am glad not to show you a California lake picture (that astonishing pink one?), Photofan!
yeck, maybe that's where Winsor Newton produces it's Scarlet Lake. However, it's the dry-as-dirt California lakes more fit for antelope than fish so in the news of late that've been scarin' me.


text:
Q: How to use Taglet or Tag in Eclipse with Java I'm trying to use the Taglet or Tag for my project because I need to create new kind of tags in my javadoc. But I'm not finding any example useful to start.
  What do I need to know is if exist any good example of the usage. I'm not finding videos teaching about it. Just the documentation at Oracle API - http://docs.oracle.com/javase/7/docs/technotes/tools/windows/javadoc.html#tag.
  Any tip will be helpful.

A: The Taglet documentation contains a small but explaining example to get started with. A step-by-step guide with some more examples can be found here.

redpajama_set_name: RedPajamaStackExchange


Interior designer, creator of objects, scenographer… at 41 years old, Brussels native Benoît Deneufbourg brings multiple crafts into coexistence within the studio he founded exactly 15 years ago. This pluralistic approach fits his vision of design, and has earned him his first solo show at the CID in Hornu.
TLmag: How was this innate desire to multitask conceived?
Benoît Deneufbourg: Through a combination of circumstances. I have a degree in interior design, but my true passion is designing objects. That's where I started my career. I created my studio in 2004 after spending two years alongside Xavier Lust. Interior design came into my life much later, about two years ago. The scenography is then directly linked to La Fabrika, the furniture store of my companion Kelly Claessens. It was while organising an exhibition on knives for the stores that I created my first project as a scenographer.
TLmag: So we could say that all your projects overlap?
B.D.: It is indeed often the case. That exhibition convinced the Finnish cultural centre to choose us to curate an exhibit. And so on…It's the same for all my projects. If, as has happened when designing an interior for a private home, I can't find the kitchen cabinet handles I want, I create them myself. So it comes back to object design.
TLmag: When you start off your career with Xavier Lust, does it then take time, when you launch your own studio, to find your own brands?
B.D.: I interned at his studio when I was still a student. In the end, I stayed there two years. Xavier Lust and I followed the same path. Like me, he is an interior designer. His success in designing objects opened new perspectives for me. By working with him, I had the opportunity to meet editors and understand how that market works.
TLmag: Learning is the common thread of your work, wouldn't you say?
B.D.: I get bored quickly. I need to be continuously learning. When I start a new project, I systematically visit the production sites to understand how the workers and crafters work. To create the rigid frame for my Donald chair, a piece made of interconnected stainless-steel tubes, I carried out many tests at a metalworker's. It isn't so much the material itself that interests me, but instead the manufacturing processes involved in using that material. When I spend time at La Fabrika, I observe how the furniture arrives, if it is mounted or unmounted, as well as the packaging. It's very instructive. For the CID exhibition at Grand-Hornu, I created an accessory collection at the Keramis centre (an art and design space on the site of the former Royal Boch pottery in La Louvière). This project allowed me to visit the workshops to see how the production was progressing. My constant questioning guides my work. I tend to have a lot of doubts.
TLmag: The solo exhibition at CID doesn't quiet those doubts?
TLmag: This is the doubt of an artist, isn't it?
B.D.: I do not consider myself as such. My only similarity to an artist is my sensibility, which guides my projects. In my work, the aesthetic never takes precedence over material and function.
TLmag: You are about to create the scenography for the joint stand of the designers supported by the WBDM at Milan. What similarities will there be to your CID exhibition?
B.D.: In my scenography work, I take into account the ephemeral aspect of the installations. These days, you cannot design a stand without thinking about economising on materials and on recycling. I try to avoid the disposable. When possible, I retain the exposed structured. Whatever doesn't need to be invisible remains visible. This approach enables me to create a new language of my own. It's more than a search for economy. It's a philosophy.
TLmag: You live in Brussels. Is it important to you to keep these roots?
B.D.: When I was starting out, I thought it was integral to my identity. Today, even though I love the creative effervescence of Brussels, I realise that influences circulate, and ideas are everywhere. But I do find that Belgium invests more than other countries in new talents, offering tools and design support. This is less so in France, for example. Myself, I need to collaborate with workshops in other regions of the country and in France. By not confining myself to a single place or a single type of project, I have space to breathe and to free my spirit. In my job, you can never say never. Why insist you will never work in plastic if an object made in this material (as long as it can be dismantled and easily recycled) has its own reason for being?


Institute of Cancer Research Repository - Comparative expressed sequence hybridization studies of high-hyperdiploid childhood acute lymphoblastic leukemia.
Comparative expressed sequence hybridization studies of high-hyperdiploid childhood acute lymphoblastic leukemia.
"Comparative expressed sequence hybridization studies of high-hyperdiploid childhood acute lymphoblastic leukemia The functional consequences of a high-hyperdiploid karyotype found in up to one-third of cases of acute lymphoblastic leukemia (ALL) are unknown. Using the technique of comparative expressed sequence hybridization (CESH) we sought to address the question of whether increased chromosome copies in hyperdiploid ALL lead to increased gene expression. Relative expression of hyperdiploid ALL blasts versus peripheral blood mononuclear cells was analyzed in 18 patients. Common regions of overexpression corresponding to the presence of tri-/tetrasomies included: Xp22.1-22.2 4q28 6q14-15 6q24 10p13 14q23-24 17q21 18q12 and 21q21 identified in 28-89% of cases. However increased expression without underlying trisomy occurred at 3p21.3 7q11.2 8p21 and 8q24.1 in 39-90% of cases. High expression at 7q11.2 the most consistent change detected was confirmed by quantitative PCR. Poor correlation between the presence of tri-/tetrasomy and overexpression was observed for chromosomes 14 and 17. Two cases were reanalyzed versus (i) B cells (ii) transformed B cells and (iii) CD34+19+ cells (the putative counterpart of the leukemic cell). A reduction in the number of relatively overexpressed regions was observed with CD34+19+ cells. In particular the peak at 7q11.2 disappeared suggesting up-regulation of genes from this region in the early ontology of normal B-cell development. In conclusion we have shown that tri-/tetrasomies in hyperdiploid ALL lead to an increase in the expression of associated sequences. The choice of a biologically relevant reference is crucial for data interpretation.	"
Gruszka-Westwood, A. M., Horsley, S. W., Martinez-Ramirez, A., Harrison, C. J., Kempski, H., Moorman, A. V., Ross, F. M., Griffiths, M., Greaves, M. F., Kearney, L.


Moxon, E. R., P. B. Rainey, and R. E. Lenski. 1998. Mutability and variability in disease (Letter). Perspectives in Biology and Medicine 42:154-155.
Lenski, R. E., and J. E. Mittler. 1993. Whither directed mutation? (Letter). Science 262:318-319.
Lenski, R. E., and J. E. Mittler. 1993. Unusual mutational mechanisms and evolution (Technical Comment). Science 260:1959-1960.
Lenski, R. E., and J. E. Mittler. 1993. Directed mutation (Letter). Science 260:1222-1224.
Mittler, J. E., and R. E. Lenski. 1990. Causes of mutation and Mu excision (Scientific Correspondence). Nature 345:213.


text:
List of lakes of Washington may refer to:

 List of lakes of Washington (state)
 List of lakes of the Washington, D.C., area

redpajama_set_name: RedPajamaWikipedia