Gene Context Analysis in the Integrated Microbial Genomes (IMG) Data Management System

Computational methods for determining the function of genes in newly sequenced genomes have been traditionally based on sequence similarity to genes whose function has been identified experimentally. Function prediction methods can be extended using gene context analysis approaches such as examining the conservation of chromosomal gene clusters, gene fusion events and co-occurrence profiles across genomes. Context analysis is based on the observation that functionally related genes are often having similar gene context and relies on the identification of such events across phylogenetically diverse collection of genomes. We have used the data management system of the Integrated Microbial Genomes (IMG) as the framework to implement and explore the power of gene context analysis methods because it provides one of the largest available genome integrations. Visualization and search tools to facilitate gene context analysis have been developed and applied across all publicly available archaeal and bacterial genomes in IMG. These computations are now maintained as part of IMG''s regular genome content update cycle. IMG is available at: http://img.jgi.doe.gov.     

Cytokine Expression Profile of Dengue Patients at Different Phases of Illness

Background

Dengue is an important medical problem, with symptoms ranging from mild dengue fever to severe forms of the disease, where vascular leakage leads to hypovolemic shock. Cytokines have been implicated to play a role in the progression of severe dengue disease; however, their profile in dengue patients and the synergy that leads to continued plasma leakage is not clearly understood. Herein, we investigated the cytokine kinetics and profiles of dengue patients at different phases of illness to further understand the role of cytokines in dengue disease.

Methods and Findings

Circulating levels of 29 different types of cytokines were assessed by bead-based ELISA method in dengue patients at the 3 different phases of illness. The association between significant changes in the levels of cytokines and clinical parameters were analyzed. At the febrile phase, IP-10 was significant in dengue patients with and without warning signs. However, MIP-1β was found to be significant in only patients with warning signs at this phase. IP-10 was also significant in both with and without warning signs patients during defervescence. At this phase, MIP-1β and G-CSF were significant in patients without warning signs, whereas MCP-1 was noted to be elevated significantly in patients with warning signs. Significant correlations between the levels of VEGF, RANTES, IL-7, IL-12, PDGF and IL-5 with platelets; VEGF with lymphocytes and neutrophils; G-CSF and IP-10 with atypical lymphocytes and various other cytokines with the liver enzymes were observed in this study.

Conclusions

The cytokine profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression to dengue with warning signs.     

The Cultural Context of Health, Illness, and Medicine

The Cultural Context of Health, Illness, and Medicine. Martha O. Loustaunau and Elisa J. Sobo. Westport, CT: Begin & Garvey, 1997. 222 pp.     

Unsuspected Dengue as a Cause of Acute Febrile Illness in Children and Adults in Western Nicaragua

BackgroundDengue is an emerging infectious disease of global significance. Suspected dengue, especially in children in Nicaragua’s heavily-urbanized capital of Managua, has been well documented, but unsuspected dengue among children and adults with undifferentitated fever has not.Conclusions/SignificanceDengue is an important and largely unrecognized cause of fever in rural western Nicaragua. Since Zika virus is transmitted by the same vector and has been associated with severe congenital infections, the population we studied is at particular risk for being devastated by the Zika epidemic that has now reached Central America.     

Day-to-Day Population Movement and the Management of Dengue Epidemics

Dengue is a growing public health problem in tropical and subtropical cities. It is transmitted by mosquitoes, and the main strategy for epidemic prevention and control is insecticide fumigation. Effective management is, however, proving elusive. People’s day-to-day movement about the city is believed to be an important factor in the epidemiological dynamics. We use a simple model to examine the fundamental roles of broad demographic and spatial structures in epidemic initiation, growth and control. We show that the key factors are local dilution, characterised by the vector–host ratio, and spatial connectivity, characterised by the extent of habitually variable movement patterns. Epidemic risk in the population is driven by the demographic groups that frequent the areas with the highest vector–host ratio, even if they only spend some of their time there. Synchronisation of epidemic trajectories in different demographic groups is governed by the vector–host ratios to which they are exposed and the strength of connectivity. Strategies for epidemic prevention and management may be made more effective if they take into account the fluctuating landscape of transmission intensity associated with spatial heterogeneity in the vector–host ratio and people’s day-to-day movement patterns.     

Influenza Illness among Case-Patients Hospitalized for Suspected Dengue,El Salvador, 2012

We estimate the proportion of patients hospitalized for suspected dengue that tested positive for influenza virus in El Salvador during the 2012 influenza season. We tested specimens from 321 hospitalized patients: 198 patients with SARI and 123 patients with suspected dengue. Among 121 hospitalized suspected dengue (two co-infected excluded) patients, 28% tested positive for dengue and 19% positive for influenza; among 35 with suspected dengue and respiratory symptoms, 14% were positive for dengue and 39% positive for influenza. One percent presented co-infection between influenza and dengue. Clinicians should consider the diagnosis of influenza among patients with suspected dengue during the influenza season.     

Cost Effectiveness of Implementing Integrated Management of Neonatal and Childhood Illnesses Program in District Faridabad,India

Introduction

Despite the evidence for preventing childhood morbidity and mortality, financial resources are cited as a constraint for Governments to scale up the key health interventions in some countries. We evaluate the cost effectiveness of implementing IMNCI program in India from a health system and societal perspective.

Methods

We parameterized a decision analytic model to assess incremental cost effectiveness of IMNCI program as against routine child health services for infant population at district level in India. Using a 15-years time horizon from 2007 to 2022, we populated the model using data on costs and effects as found from a cluster-randomized trial to assess effectiveness of IMNCI program in Haryana state. Effectiveness was estimated as reduction in infant illness episodes, deaths and disability adjusted life years (DALY). Incremental cost per DALY averted was used to estimate cost effectiveness of IMNCI. Future costs and effects were discounted at a rate of 3%. Probabilistic sensitivity analysis was undertaken to estimate the probability of IMNCI to be cost effective at varying willingness to pay thresholds.

Results

Implementation of IMNCI results in a cumulative reduction of 57384 illness episodes, 2369 deaths and 76158 DALYs among infants at district level from 2007 to 2022. Overall, from a health system perspective, IMNCI program incurs an incremental cost of USD 34.5 (INR 1554) per DALY averted, USD 34.5 (INR 1554) per life year gained, USD 1110 (INR 49963) per infant death averted. There is 90% probability for ICER to be cost effective at INR 2300 willingness to pay, which is 5.5% of India’s GDP per capita. From a societal perspective, IMNCI program incurs an additional cost of USD 24.1 (INR 1082) per DALY averted, USD 773 (INR 34799) per infant death averted and USD 26.3 (INR 1183) per illness averted in during infancy.

Conclusion

IMNCI program in Indian context is very cost effective and should be scaled-up as a major child survival strategy.     

整合医学在急诊科危重病救治中的应用

整合医学是医学发展的必然方向和必由之路,强调将医学各领域最先进的理论知识和临床各专科最有效的实践经验进行有机整合,是更加符合人体健康和疾病治疗的新医学体系。急诊科危重病员往往同时存在多脏器功能障碍,救治中应运用整体观、整合观和医学观的原则,切实解决临床实践中遇到的问题。当前,有必要在组织管理层面上借力整合医学推动急诊医学的建设与发展。     

Community Involvement in Dengue Outbreak Control: An Integrated Rigorous Intervention Strategy

BackgroundAn explosive outbreak of dengue fever occurred in Guangdong Province, China in 2014. A community-based integrated intervention was applied to control this outbreak in the capital city Guangzhou, where dengue epidemic was mainly caused by imported cases.ConclusionsThis study suggests that an integrated dengue intervention program has significant effects to control a dengue outbreak in areas where dengue epidemic was mainly caused by imported dengue cases.     

Ambulatory Management of Childhood Obesity

Objective: Childhood obesity is one of the most challenging issues facing healthcare providers today. The aims of this study were to describe the ambulatory management of childhood obesity by pediatricians (PDs) and family physicians (FPs) and to evaluate knowledge of and adherence to published recommendations. Research Methods and Procedures: A 42‐item, self‐administered questionnaire was mailed to 1207 randomly selected primary care physicians (PDs = 700, FPs = 507) between September 2001 and January 2002. Results: Of 339 (28%) responses, 287 were eligible (PDs = 213, FPs = 74). Most respondents were in group or solo practice (87%) in a suburban or urban, non‐inner city location (67%). The average age was 48 years (range = 31 to 85 years), and the mean years in practice was 17 (range = 1 to 55 years). Nineteen percent of physicians were aware of national recommendations. Three percent of physicians reported adherence to all recommendations. Knowledge of recommendations was not associated with a greater likelihood of adherence. However, physicians who were aware of recommendations were more likely to have positive attitudes about personal counseling ability (odds ratio = 2.4, confidence interval = 1.3 to 4.4) and the overall efficacy of obesity counseling (odds ratio = 4.3, confidence interval = 1.7 to 10.8). Poor patient motivation, patient noncompliance, and treatment futility were perceived as the most frequently encountered barriers to obesity treatment. Discussion: Most physicians are not aware of or adherent to national recommendations regarding childhood obesity. Awareness of recommendations was associated with more positive attitudes about personal counseling ability and the effectiveness of obesity counseling in general.     

Management of Ingested Foreign Bodies in Childhood

A total of 660 patients with ingested foreign bodies admitted to the general surgical services in two children''s hospitals in Liverpool are reviewed. Endoscopic removal (205 cases) is recommended for all foreign objects impacted in the oesophagus, with the exception of rounded or blunt objects in the lower third, which should be observed for a maximum of 12 hours. The indications for laparotomy for removal of a foreign body (43 cases, 6·5%) are the danger of perforation and failure of progression. The ingestion of a long slender object—for example a hair-grip—in a child under 2 years of age, is an absolute indication for prophylactic operative removal owing to the high incidence of impaction and perforation of the duodenum.     

Associations of Different Phenotypes of Wheezing Illness in Early Childhood with Environmental Variables Implicated in the Aetiology of Asthma

Rationale

Asthma is a complex heterogeneous disease that has increased in prevalence in many industrialised countries. However, the causes of asthma inception remain elusive. Consideration of sub-phenotypes of wheezing may reveal important clues to aetiological risk factors.

Methods

Longitudinal phenotypes capturing population heterogeneity in wheezing reports from birth to 7 years were derived using latent class analysis in the Avon Longitudinal Study of Parents and Children (ALSPAC). Probability of class membership was used to examine the association between five wheezing phenotypes (transient early, prolonged early, intermediate-onset, late-onset, persistent) and early life risk factors for asthma.

Results

Phenotypes had similar patterns and strengths of associations with early environmental factors. Comparing transient early with prolonged early wheezing showed a similar pattern of association with most exposure variables considered in terms of the direction of the effect estimates but with prolonged early wheezing tending to have stronger associations than transient early wheezing except for parity and day care attendance.

Conclusions

Associations with early life risk factors suggested that prolonged early wheeze might be a severe form of transient early wheezing. Although differences were found in the associations of early life risk factors with individual phenotypes, these did not point to novel aetiological pathways. Persistent wheezing phenotype has features suggesting overlap of early and late-onset phenotypes.     

Monitoring in the Context of Structured Decision-Making and Adaptive Management

Abstract: In a natural resource management setting, monitoring is a crucial component of an informed process for making decisions, and monitoring design should be driven by the decision context and associated uncertainties. Monitoring itself can play ≥3 roles. First, it is important for state-dependent decision-making, as when managers need to know the system state before deciding on the appropriate course of action during the ensuing management cycle. Second, monitoring is critical for evaluating the effectiveness of management actions relative to objectives. Third, in an adaptive management setting, monitoring provides the feedback loop for learning about the system; learning is sought not for its own sake but primarily to better achieve management objectives. In this case, monitoring should be designed to reduce the critical uncertainties in models of the managed system. The United States Geological Survey and United States Fish and Wildlife Service are conducting a large-scale management experiment on 23 National Wildlife Refuges across the Northeast and Midwest Regions. The primary management objective is to provide habitat for migratory waterbirds, particularly during migration, using water-level manipulations in managed wetlands. Key uncertainties are related to the potential trade-offs created by management for a specific waterbird guild (e.g., migratory shorebirds) and the response of waterbirds, plant communities, and invertebrates to specific experimental hydroperiods. We reviewed the monitoring program associated with this study, and the ways that specific observations fill ≥1 of the roles identified above. We used observations from our monitoring to improve state-dependent decisions to control undesired plants, to evaluate management performance relative to shallow-water habitat objectives, and to evaluate potential trade-offs between waterfowl and shorebird habitat management. With limited staff and budgets, management agencies need efficient monitoring programs that are used for decision-making, not comprehensive studies that elucidate all manner of ecological relationships.     

Ecosystem Management in the Context of Large, Infrequent Disturbances

Large, infrequent disturbances (LIDs) can have significant impacts yet seldom are included in management plans. Although this neglect may stem from relative unfamiliarity with a kind of event that rarely occurs in the experience or jurisdiction of individual managers, it may also reflect the assumption that LIDs are so large and powerful as to be beyond the ability of managers to affect. However, some LIDs can be affected by management, and for many of those that cannot be affected, the resilience or recovery of the system disrupted by the disturbance can be influenced to meet management goals. Such results can be achieved through advanced planning that allows for LIDs, whether caused by natural events, human activities, or a combination of the two. Management plans for LIDs may adopt a variety of goals, depending on the nature of the system and the nature of the anticipated disturbance regime. Managers can choose to influence (a) the system prior to the disturbance, (b) the disturbance itself, (c) the system after the disturbance, or (d) the recovery process. Prior to the disturbance, the system can be managed in ways that alter its vulnerability or change how it will respond to a disturbance. The disturbance can be managed through no action, preventive measures, or manipulations that can affect the intensity or frequency of the disturbance. Recovery efforts can focus on either managing the state of the system immediately after the disturbance or managing the ongoing process of recovery. This review of the management implications of LIDs suggests that management actions should be tailored to particular disturbance characteristics and management goals. Management actions should foster survival of residuals and spatial heterogeneity that promote the desired recovery pattern and process. Most importantly, however, management plans need to recognize LIDs and include the potential for such disturbances to occur. Received 14 July 1998; accepted 16 September 1998     

Nation-Wide,Web-Based,Geographic Information System for the Integrated Surveillance and Control of Dengue Fever in Mexico

Dengue fever incidence and its geographical distribution are increasing throughout the world. Quality and timely information is essential for its prevention and control. A web based, geographically enabled, dengue integral surveillance system (Dengue-GIS) was developed for the nation-wide collection, integration, analysis and reporting of geo-referenced epidemiologic, entomologic, and control interventions data. Consensus in the design and practical operation of the system was a key factor for its acceptance. Working with information systems already implemented as a starting point facilitated its acceptance by officials and operative personnel. Dengue-GIS provides the geographical detail needed to plan, asses and evaluate the impact of control activities. The system is beginning to be adopted as a knowledge base by vector control programs. It is used to generate evidence on impact and cost-effectiveness of control activities, promoting the use of information for decision making at all levels of the vector control program. Dengue-GIS has also been used as a hypothesis generator for the academic community. This GIS-based model system for dengue surveillance and the experience gathered during its development and implementation could be useful in other dengue endemic countries and extended to other infectious or chronic diseases.