Neural Dynamics Underlying Impaired Autonomic and Conditioned Responses Following Amygdala and Orbitofrontal Lesions

A neural model is presented that explains how outcome-specific learning modulates affect, decision-making and Pavlovian conditioned approach responses. The model addresses how brain regions responsible for affective learning and habit learning interact, and answers a central question: What are the relative contributions of the amygdala and orbitofrontal cortex to emotion and behavior? In the model, the amygdala calculates outcome value while the orbitofrontal cortex influences attention and conditioned responding by assigning value information to stimuli. Model simulations replicate autonomic, electrophysiological, and behavioral data associated with three tasks commonly used to assay these phenomena: Food consumption, Pavlovian conditioning, and visual discrimination. Interactions of the basal ganglia and amygdala with sensory and orbitofrontal cortices enable the model to replicate the complex pattern of spared and impaired behavioral and emotional capacities seen following lesions of the amygdala and orbitofrontal cortex.

Examining the post-adoptive infusion of mobile technology in a healthcare domain: determinants and outcomes

The healthcare industry is beginning to appreciate the benefits which can be obtained from using Mobile Health Systems (MHS) at the point-of-care. As a result, healthcare organisations are investing heavily in mobile health initiatives with the expectation that users will employ the system to enhance performance. Despite widespread endorsement and support for the implementation of MHS, empirical evidence surrounding the benefits of MHS remains to be fully established. For MHS to be truly valuable, it is argued that the technological tool be infused within healthcare practitioners work practices and used to its full potential in post-adoptive scenarios. Yet, there is a paucity of research focusing on the infusion of MHS by healthcare practitioners. In order to address this gap in the literature, the objective of this study is to explore the determinants and outcomes of MHS infusion by healthcare practitioners. This research study adopts a post-positivist theory building approach to MHS infusion. Existing literature is utilised to develop a conceptual model by which the research objective is explored. Employing a mixed-method approach, this conceptual model is first advanced through a case study in the UK whereby propositions established from the literature are refined into testable hypotheses. The final phase of this research study involves the collection of empirical data from a Canadian hospital which supports the refined model and its associated hypotheses. The results from both phases of data collection are employed to develop a model of MHS infusion. The study contributes to IS theory and practice by: (1) developing a model with six determinants (Availability, MHS Self-Efficacy, Time-Criticality, Habit, Technology Trust, and Task Behaviour) and individual performance-related outcomes of MHS infusion (Effectiveness, Efficiency, and Learning), (2) examining undocumented determinants and relationships, (3) identifying prerequisite conditions that both healthcare practitioners and organisations can employ to assist with MHS infusion, (4) developing a taxonomy that provides conceptual refinement of IT infusion, and (5) informing healthcare organisations and vendors as to the performance of MHS in post-adoptive scenarios.

Burning a hole in the budget: tobacco spending and its crowd-out of other goods.

Smoking is an expensive habit. Smoking households spend, on average, more than $US1000 annually on cigarettes. When a family member quits, in addition to the former smoker's improved long-term health, families benefit because savings from reduced cigarette expenditures can be allocated to other goods. For households in which some members continue to smoke, smoking expenditures crowd-out other purchases, which may affect other household members, as well as the smoker. We empirically analyse how expenditures on tobacco crowd-out consumption of other goods, estimating the patterns of substitution and complementarity between tobacco products and other categories of household expenditure. We use the Consumer Expenditure Survey data for the years 1995-2001, which we complement with regional price data and state cigarette prices. We estimate a consumer demand system that includes several main expenditure categories (cigarettes, food, alcohol, housing, apparel, transportation, medical care) and controls for socioeconomic variables and other sources of observable heterogeneity. Descriptive data indicate that, comparing smokers to nonsmokers, smokers spend less on housing. Results from the demand system indicate that as the price of cigarettes rises, households increase the quantity of food purchased, and, in some samples, reduce the quantity of apparel and housing purchased.

Acute eosinophilic pneumonia secondary to daptomycin: a report of three cases.

We describe 3 cases of daptomycin-induced pulmonary toxic effects that are consistent with drug-induced acute eosinophilic pneumonia. Patients presented similarly with dyspnea, cough, hypoxia, and diffuse ground-glass opacities at chest computed tomography. Clinical suspicion for this adverse drug event and cessation of daptomycin until definitive diagnosis can be made is crucial.

Bioenergetic and ecological consequences of diet variability in Atlantic croaker Micropogonias undulatus

Atlantic croaker Micropogonias undulatus is a commercially and ecologically important bottom-associated fish that occurs in marine and estuarine systems from Cape Cod, MA to Mexico. I documented the temporal and spatial variability in the diet of Atlantic croaker in Chesapeake Bay and found that in the summer fish, particularly bay anchovies Anchoa mitchilli, make up at least 20% of the diet of croaker by weight. The use of a pelagic food source seems unusual for a bottom-associated fish such as croaker, but appears to be a crepuscular feeding habit that has not been previously detected. Thus, I investigated the bioenergetic consequences of secondary piscivory to the distribution of croaker, to the condition of individuals within the population and to the ecosystem. Generalized additive models revealed that the biomass of anchovy explained some of the variability in croaker occurrence and abundance in Chesapeake Bay. However, physical factors, specifically temperature, salinity, and seasonal dynamics were stronger determinants of croaker distribution than potential prey availability. To better understand the bioenergetic consequences of diet variability at the individual level, I tested the hypothesis that croaker feeding on anchovies would be in better condition than those feeding on polychaetes using a variety of condition measures that operate on multiple time scales, including RNA:DNA, Fulton's condition factor (K), relative weight (Wr), energy density, hepatosomatic index (HSI), and gonadosomatic index (GSI). Of these condition measures, several morphometric measures were significantly positively correlated with each other and with the percentage (by weight) of anchovy in croaker diets, suggesting that the type of prey eaten is important in improving the overall condition of individual croaker. To estimate the bioenergetic consequences of diet variability on growth and consumption in croaker, I developed and validated a bioenergetic model for Atlantic croaker in the laboratory. The application of this model suggested that croaker could be an important competitor with weakfish and striped bass for food resources during the spring and summer when population abundances of these three fishes are high in Chesapeake Bay. Even though anchovies made up a relatively small portion of croaker diet and only at certain times of the year, croaker consumed more anchovy at the population level than striped bass in all simulated years and nearly as much anchovy as weakfish. This indicates that weak trophic interactions between species are important in understanding ecosystem processes and should be considered in ecosystem-based management.

Correlates of poor health among orphans and abandoned children in less wealthy countries: the importance of caregiver health.

BACKGROUND: More than 153 million children worldwide have been orphaned by the loss of one or both parents, and millions more have been abandoned. We investigated relationships between the health of orphaned and abandoned children (OAC) and child, caregiver, and household characteristics among randomly selected OAC in five countries. METHODOLOGY: Using a two-stage random sampling strategy in 6 study areas in Cambodia, Ethiopia, India, Kenya, and Tanzania, the Positive Outcomes for Orphans (POFO) study identified 1,480 community-living OAC ages 6 to 12. Detailed interviews were conducted with 1,305 primary caregivers at baseline and after 6 and 12 months. Multivariable logistic regression models describe associations between the characteristics of children, caregivers, and households and child health outcomes: fair or poor child health; fever, cough, or diarrhea within the past two weeks; illness in the past 6 months; and fair or poor health on at least two assessments. PRINCIPAL FINDINGS: Across the six study areas, 23% of OAC were reported to be in fair or poor health; 19%, 18%, and 2% had fever, cough, or diarrhea, respectively, within the past two weeks; 55% had illnesses within the past 6 months; and 23% were in fair or poor health on at least two assessments. Female gender, suspected HIV infection, experiences of potentially traumatic events, including the loss of both parents, urban residence, eating fewer than 3 meals per day, and low caregiver involvement were associated with poorer child health outcomes. Particularly strong associations were observed between child health measures and the health of their primary caregivers. CONCLUSIONS: Poor caregiver health is a strong signal for poor health of OAC. Strategies to support OAC should target the caregiver-child dyad. Steps to ensure food security, foster gender equality, and prevent and treat traumatic events are needed.

Impact of a Point-of-Care Rapid Influenza Test on Antibiotic Prescribing Patterns in Southern Sri Lanka

Background: Acute febrile respiratory illnesses, including influenza, account for a large proportion of ambulatory care visits worldwide. In the developed world, these encounters commonly result in unwarranted antibiotic prescriptions; data from more resource-limited settings are lacking. The purpose of this study was to describe the epidemiology of influenza among outpatients in southern Sri Lanka and to determine if access to rapid influenza test results was associated with decreased antibiotic prescriptions.

Methods: In this pretest- posttest study, consecutive patients presenting from March 2013- April 2014 to the Outpatient Department of the largest tertiary care hospital in southern Sri Lanka were surveyed for influenza-like illness (ILI). Patients meeting World Health Organization criteria for ILI-- acute onset of fever ≥38.0°C and cough in the prior 7 days--were enrolled. Consenting patients were administered a structured questionnaire, physical examination, and nasal/nasopharyngeal sampling. Rapid influenza A/B testing (Veritor System, Becton Dickinson) was performed on all patients, but test results were only released to patients and clinicians during the second phase of the study (December 2013- April 2014).

Results: We enrolled 397 patients with ILI, with 217 (54.7%) adults ≥12 years and 188 (47.4%) females. A total of 179 (45.8%) tested positive for influenza by rapid testing, with April- July 2013 and September- November 2013 being the periods with the highest proportion of ILI due to influenza. A total of 310 (78.1%) patients with ILI received a prescription for an antibiotic from their outpatient provider. The proportion of patients prescribed antibiotics decreased from 81.4% in the first phase to 66.3% in the second phase (p=.005); among rapid influenza-positive patients, antibiotic prescriptions decreased from 83.7% in the first phase to 56.3% in the second phase (p=.001). On multivariable analysis, having a positive rapid influenza test available to clinicians was associated with decreased antibiotic use (OR 0.20, 95% CI 0.05- 0.82).

Conclusions: Influenza virus accounted for almost 50% of acute febrile respiratory illness in this study, but most patients were prescribed antibiotics. Providing rapid influenza test results to clinicians was associated with fewer antibiotic prescriptions, but overall prescription of antibiotics remained high. In this developing country setting, a multi-faceted approach that includes improved access to rapid diagnostic tests may help decrease antibiotic use and combat antimicrobial resistance.

Between two fern genomes.

Ferns are the only major lineage of vascular plants not represented by a sequenced nuclear genome. This lack of genome sequence information significantly impedes our ability to understand and reconstruct genome evolution not only in ferns, but across all land plants. Azolla and Ceratopteris are ideal and complementary candidates to be the first ferns to have their nuclear genomes sequenced. They differ dramatically in genome size, life history, and habit, and thus represent the immense diversity of extant ferns. Together, this pair of genomes will facilitate myriad large-scale comparative analyses across ferns and all land plants. Here we review the unique biological characteristics of ferns and describe a number of outstanding questions in plant biology that will benefit from the addition of ferns to the set of taxa with sequenced nuclear genomes. We explain why the fern clade is pivotal for understanding genome evolution across land plants, and we provide a rationale for how knowledge of fern genomes will enable progress in research beyond the ferns themselves.

Cumulative early life adversity predicts longevity in wild baboons.

In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations.

Identification of pertussis-specific effector memory T cells in preschool children

Whooping cough remains a problem despite vaccination, and worldwide resurgence of pertussis is evident. Since cellular immunity plays a role in long-term protection against pertussis, we studied pertussis-specific T-cell responses. Around the time of the preschool acellular pertussis (aP) booster dose at 4 years of age, T-cell memory responses were compared in children who were primed during infancy with either a whole-cell pertussis (wP) or an aP vaccine. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with pertussis vaccine antigens for 5 days. T cells were characterized by flow-based analysis of carboxyfluorescein succinimidyl ester (CFSE) dilution and CD4, CD3, CD45RA, CCR7, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) expression. Before the aP preschool booster vaccination, both the proliferated pertussis toxin (PT)-specific CD4⁺ and CD8⁺ T-cell fractions (CFSE^dim) were higher in aP-than in wP-primed children. Post-booster vaccination, more pertussis-specific CD4⁺ effector memory cells (CD45RA^- CCR7^-) were induced in aP-primed children than in those primed with wP. The booster vaccination did not appear to significantly affect the T-cell memory subsets and functionality in aP-primed or wP-primed children. Although the percentages of Th1 cytokine-producing cells were alike in aP- and wP-primed children pre-booster vaccination, aP-primed children produced more Th1 cytokines due to higher numbers of proliferated pertussis-specific effector memory cells. At present, infant vaccinations with four aP vaccines in the first year of life result in pertussis-specific CD4⁺ and CD8⁺ effector memory T-cell responses that persist in children until 4 years of age and are higher than those in wP-primed children. The booster at 4 years of age is therefore questionable; this may be postponed to 6 years of age.

Bordetella pertussis infection in 2-month-old infants promotes type 1 T cell responses.

Neonatal immaturity of the immune system is currently believed to generally limit the induction of immune responses to vaccine Ags and to skew them toward type 2 responses. We demonstrated here that Bordetella pertussis infection in very young infants (median, 2 mo old) as well as the first administration of whole-cell pertussis vaccine induces B. pertussis Ag-specific IFN-gamma secretion by the PBMC of these infants. IFN-gamma was secreted by both CD4(+) and CD8(+) T lymphocytes, and the levels of Ag-induced IFN-gamma secretion did not correlate with the age of the infants. Appearance of the specific Th-1 cell-mediated immunity was accompanied by a general shift of the cytokine secretion profile of these infants toward a stronger Th1 profile, as evidenced by the response to a polyclonal stimulation. We conclude that the immune system of 2-mo-old infants is developmentally mature enough to develop Th1 responses in vivo upon infection by B. pertussis or vaccination with whole-cell pertussis vaccines.

Monocyte-derived interleukin-10 depresses the Bordetella pertussis- specific gamma interferon response in vaccinated infants.

Antigen-specific gamma interferon (IFN-gamma) has been demonstrated to participate in protection against Bordetella pertussis infection. Circulating mononuclear cells from B. pertussis-infected and from pertussis-vaccinated infants secrete high amounts of IFN-gamma after in vitro stimulation by B. pertussis antigens, but with a large variation in the secreted IFN-gamma levels between individuals. We show here that the inhibition of the specific IFN-gamma response can be at least partially attributed to IL-10 secretion by monocytes. This IL-10 secretion was not associated with polymorphisms at positions -1082, -819, and -592 of the IL-10 gene promoter, suggesting that other genetic or environmental factors affect IL-10 expression and secretion.

Different T cell memory in preadolescents after whole-cell or acellular pertussis vaccination.

To better understand vaccine-induced protection and its potential failure in light of recent whooping cough resurgence, we evaluated quantity as well as quality of memory T cell responses in B. pertussis-vaccinated preadolescent children. Using a technique based on flow cytometry to detect proliferation, cytokine production and phenotype of antigen-specific cells, we evaluated residual T cell memory in a cohort of preadolescents who received a whole-cell pertussis (wP; n=11) or an acellular pertussis vaccine (aP; n=13) during infancy, and with a median of 4 years elapsed from the last pertussis booster vaccine, which was aP for all children. We demonstrated that B. pertussis-specific memory T cells are detectable in the majority of preadolescent children several years after vaccination. CD4(+) and CD8(+) T cell proliferation in response to pertussis toxin and/or filamentous hemagglutinin was detected in 79% and 60% of the children respectively, and interferon-γ or tumor necrosis factor-α producing CD4(+) T cells were detected in 65% and 53% of the children respectively. Phenotyping of the responding cells showed that the majority of antigen-specific cells, whether defined by proliferation or cytokine production, were CD45RA(-)CCR7(-) effector memory T cells. Although the time since the last booster vaccine was significantly longer for wP-compared to aP-vaccinated children, their proliferation capacity in response to antigenic stimulation was comparable, and more children had a detectable cytokine response after wP- compared to aP-vaccination. This study supports at the immunological level recent epidemiological studies indicating that infant vaccination with wP induces longer lasting immunity than vaccination with aP-vaccines.

Cytokine and antibody profiles in 1-year-old children vaccinated with either acellular or whole-cell pertussis vaccine during infancy.

Two different types of pertussis vaccines are currently available to protect children against whooping cough, the first-generation whole-cell (Pw) vaccines and the more recent acellular (Pa) vaccines. Both types provide good protection, yet induce different types of immune responses in 6-month-old infants, with a strong Th1 response induced by Pw vaccines compared to a mixed Th1/Th2 response and a delay in non-specific IFN-gamma secretions after the administration of Pa vaccines. We show here that at 13 months of age, most Pw- or Pa-vaccinated children display Bordetella pertussis-specific T-cell responses, in addition to significant antibody levels, although a higher Th2/Th1 cytokine ratio remained in Pa recipients compared to Pw recipients. In contrast, the proportion of children with tetanus toxin-specific T-cell responses was lower in Pa than in Pw vaccine recipients, although most children had protective anti-tetanus toxin IgG levels. In addition, the global Th2 bias observed in 6-month-old infants vaccinated with a Pa vaccine was normalized at 13 months.

Bordetella pertussis from functional genomics to intranasal vaccination.

Whooping cough still represents a major health problem, despite the use of effective vaccines for several decades. Being classically a typical childhood disease, whooping cough in young adults is now more common than it used to be, suggesting that protection after vaccination wanes during adolescence. As an alternative to the current vaccines, we wish to develop live attenuated vaccines to be delivered by the nasal route, such as to mimic the natural route of infection and to induce long lasting immunity. Bordetella pertussis, the etiological agent of whooping cough, produces a number of virulence factors, including toxins. Its recently determined genome sequence makes it now possible to apply functional genomics, such as transcriptomics and systematic knock-out mutagenesis. The expression of most known B. pertussis virulence genes is controlled by the two-component system BvgA/S. DNA microarray analyses have led to the identification of novel genes in the BvgA/S regulon, some of which are activated by BvgA/S and others are repressed by BvgA/S. In addition, some genes appear to be differentially modulated by nicotinic acid and MgSO4, both known to modulate the expression of BvgA/S-regulated genes. Among others, the functional genomics approach has uncovered two strongly BvgA/S-activated genes, named hotA and hotB (for 'homolog of toxin'), the products of which show high sequence similarities to pertussis toxin subunits. The identification of the full array of virulence factors, as well as an integrated understanding of the bacterial physiology should allow us to design attenuated B. pertussis strains useful for intranasal vaccination. A first generation of attenuated strains has already shown full protection in mice after a single intranasal administration. Such strains may also serve as vaccine carriers for heterologous antigens, in order to vaccinate against several different pathogens simultaneously.