Investment in vaccine product development should be guided by up-to-date and transparent global burden of disease estimates, which are also fundamental to policy recommendation and vaccine ...introduction decisions. For low- and middle-income countries (LMICs), vaccine prioritization is primarily driven by the number of deaths caused by different pathogens. Enteric diseases are known to be a major cause of death in LMICs. The two main modelling groups providing mortality estimates for enteric diseases are the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle and the Maternal Child Epidemiology Estimation (MCEE) group, led by Johns Hopkins Bloomberg School of Public Health. Whilst previous global diarrhoea mortality estimates for under five-year-olds from these two groups were closely aligned, more recent estimates for 2016 have diverged, particularly with respect to numbers of deaths attributable to different enteric pathogens. This has impacted prioritization and investment decisions for vaccines in the development pipeline.
The mission of the Product Development for Vaccines Advisory Committee (PDVAC) at the World Health Organisation (WHO) is to accelerate product development of vaccines and technologies that are urgently needed and ensure they are appropriately targeted for use in LMICs. At their 2018 meeting, PDVAC recommended the formation of an independent working group of subject matter experts to explore the reasons for the difference between the IHME and MCEE estimates, and to assess the respective strengths and limitations of the estimation approaches adopted, including a review of the data on which the estimates are based.
Here, we report on the proceedings and recommendations from a consultation with the working group of experts, the IHME and MCEE modelling groups, and other key stakeholders. We briefly review the methodological approaches of both groups and provide a series of proposals for investigating the drivers for the differences in enteric disease burden estimates.
Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation that is well‐characterized in allergic disease states. However, FeNO is also involved in nonallergic inflammatory and ...pulmonary vascular mechanisms or responses to environmental stimuli. We sought to determine the extent to which obesity or sedentary lifestyle is associated with FeNO in adolescents not selected on the basis of allergic disease. In Project Viva, a prebirth cohort study, we measured body mass index (BMI), skinfold thicknesses, waist circumference, body fat, hours watching television, hours of physical activity, and heart rate after exercise among 929 adolescents (median age, 12.9). We measured FeNO twice and averaged these as a continuous, log‐transformed outcome. We performed linear regression models, adjusted for child age, sex, height, and race/ethnicity, maternal education and smoking during pregnancy, household income and smoking, and neighbourhood characteristics. In secondary analysis, we additionally adjusted for asthma. More than 2 hours spent watching TV was associated with 10% lower FeNO (95% confidence interval CI: −20, 0%). Higher body fat percentage was also associated with lower FeNO. After additional adjustment for asthma, teens who are underweight (BMI <5th %tile, 3%) had 22% lower FeNO (95%CI: −40, 2%) and teens who are overweight (BMI ≥85th %ile, 28%) had 13% lower FeNO (95%CI: −23, −2%). Each of these associations of lifestyle and body weight with lower FeNO were greater in magnitude after adjusting for asthma. In summary, sedentary lifestyle, high and low BMI were all associated with lower FeNO in this adolescent cohort.
Background. Diarrhea causes enormous morbidity and mortality in developing countries, yet the relative importance of multiple potential enteropathogens has been difficult to ascertain. Methods. We ...performed a longitudinal cohort study from birth to 1 year of age in 147 infants in Dhaka, Bangladesh. Using multiplex polymerase chain reaction, we analyzed 420 episodes of diarrhea and 1385 monthly surveillance stool specimens for 32 enteropathogen gene targets. For each infant we examined enteropathogen quantities over time to ascribe each positive target as a probable or less-likely contributor to diarrhea. Results. Multiple enteropathogens were detected by the first month of life. Diarrhea was associated with a state of overall pathogen excess (mean number of enteropathogen gene targets (±SE), 5.6 ± 0.1 vs 4.3 ± 0.1 in surveillance stool specimens; P < .05). After a longitudinal, quantitative approach was applied to filter out less-likely contributors, each diarrheal episode still had an average of 3.3 probable or dominant targets. Enteroaggregative Escherichia coli, Campylobacter, enteropathogenic E. coli, rotavirus, and Entamoeba histolytica were the most frequent probable contributors to diarrhea. Rotavirus was enriched in moderate to severe diarrheal episodes. Conclusions. In this community-based study diarrhea seemed to be a multipathogen event and a state of enteropathogen excess above a high carriage baseline.
Conventional approaches to the diagnosis of infectious diarrhea must include several modalities to detect an array of potential viruses, bacteria, and parasites. We will provide a general overview of ...the wide range of diagnostic modalities available for enteropathogens, briefly discuss some of the limitations of conventional methods, and then focus on new molecular methods, including real-time PCR and next-generation sequencing. In particular, we will discuss quantitation of pathogen load with these techniques. We will then describe examples whereby novel diagnostics may help illuminate the etiology of infectious diarrhea, where they may not, and how they may benefit studies of immunity to enteric infections.
This paper investigates the success and failure of performance measurement system design interventions in ten companies. In each case, the senior management team was facilitated through a management ...process to redesign their performance measurement systems. Analysis of the initial pilot case studies suggested three important differences between companies that proceeded to implement the measures agreed during the process and those that did not. Post intervention semi-structured interviews with the directors and managers directly involved revealed two main perceived drivers of implementation and four perceived factors that block implementation. The results are of specific interest for performance measurement system implementation but have wider implications for our view of management commitment in change management.
This paper addresses issues met when designing, implementing, using and continuously updating performance measurement systems in manufacturing companies. The paper develops, from theory, a framework ...for analysing the implementation of a performance measurement system and uses this framework to interpret three longitudinal case studies. The paper concludes that specific processes are required to continuously align the performance measurement system with strategy. When these processes are combined with a well defined model of strategic success, the measurement system can enhance the strategic management process by challenging the assumptions and the strategy itself.
Testing manufacturing strategy formulation processes Platts, K.W.; Mills, J.F.; Bourne, M.C. ...
International journal of production economics,
09/1998, Volume:
56, Issue:
1
Journal Article, Conference Proceeding
Peer reviewed
The process of formulating and implementing manufacturing strategy is one of the key tasks for operations managers; however, it is extremely complex and not well understood. Over the years there have ...been many attempts to both prescribe and describe strategy formulation processes but the literature on the rigorous
testing of prescribed processes is sparse. This paper discusses the testing of one such process for formulating manufacturing strategy, and reports findings. Two aspects are addressed: the initial testing of the process to assess feasibility, usability and utility; and more detailed testing to investigate factors which affect the implementation of the process. This detailed testing is being carried out as a preliminary step to investigating the tailoring of the process to different contextual factors.
The paper begins by briefly outlining the strategy formulation process which is under test. This process has been developed in stages since 1987 and has been widely applied in various forms over this period. Having described the process, the paper then discusses testing problems and presents the rationale behind the testing approach chosen.
Although endotoxin is known to increase symptoms in allergic individuals, early exposure might decrease sensitization. Similarly, the presence of an animal in the home has been associated with ...decreased sensitization to animal allergens. It has been suggested that the effect of animals could be explained by increased endotoxin exposure.
We sought to investigate the effects of domestic animals on airborne endotoxin.
By using a silent particle collector, air was sampled over 24 hours in homes with or without animals. The total volume sampled was approximately 1000 m
3, which provides quantities of allergen and endotoxin that can easily be measured with standard assays.
The quantity of endotoxin ranged from less than 0.5 to more than 500 pg/m
3, whereas cat and dog allergen ranged from less than 0.002 to more than 5 ng/m
3. Overall, the quantity of airborne endotoxin was not higher in homes with at least one animal. However, airborne endotoxin levels were significantly lower in homes with a cat compared with homes with a dog (
P < .001). In keeping with this, there was a significant correlation between airborne Can f 1 and airborne endotoxin (
r
=
0.50,
P < .01) but not between endotoxin and Fel d 1 (
r
=
0.17,
P
=
.27).
The results demonstrate that endotoxin is present in the air of almost all homes. Although higher levels were seen in homes with a dog, similar levels might be present in homes with no animals. The results argue that the effects of cat ownership cannot be explained by increased exposure to endotoxin.
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