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1.  Comparison of media literacy and usual education to prevent tobacco use: a cluster randomized trial 
The Journal of school health  2014;84(2):106-115.
Media literacy programs have shown potential for reduction of adolescent tobacco use. We aimed to determine if an anti-smoking media literacy curriculum improves students’ media literacy and affects factors related to adolescent smoking.
We recruited 1170 9th grade students from 64 classrooms in 3 public urban high schools. Students were randomized by classroom to a media literacy curriculum versus a standard educational program. In an intent-to-treat analysis, we used multi-level modeling to determine if changes in study outcomes were associated with the curricular intervention, controlling for baseline student covariates and the clustering of students within classrooms.
Among participants, mean age was 14.5 years and 51% were male, with no significant differences in baseline characteristics between groups. Smoking media literacy changed more among intervention participants compared with control participants (0.24 vs. 0.08, p < .001). Compared with controls, intervention students exhibited a greater reduction in the perceived prevalence of smoking (−14.0% vs. −4.6%, p < .001). Among those initially susceptible to smoking, intervention participants more commonly reverted to being non-susceptible post-intervention (24% vs. 16%, p = .08).
A school-based media literacy curriculum is more effective than a standard educational program in teaching media literacy and improving perceptions of the true prevalence of smoking among adolescents.
PMCID: PMC4126196  PMID: 25099425
media literacy; media education; smoking; tobacco; school-based; social influences; attitudes; normative beliefs; youth; adolescents
2.  Recent partner violence and sexual and drug-related STI/HIV risk among adolescent and young adult women attending family planning clinics 
Sexually transmitted infections  2013;90(2):145-149.
Adolescent and young adult women are at high risk for both STI/HIV and intimate partner violence (IPV). We evaluate the prevalence of IPV in the past three months and its associations with STI/HIV risk, STI, and related care-seeking over the same time period.
Female family planning clinic patients ages 16–29 (n=3,504) participated in a cross-sectional survey in 2011–2012 as a baseline assessment for an intervention study. We examined associations of recent IPV with sexual and drug-related STI/HIV risk behavior, self-reported STI, and STI-related clinical care seeking via logistic regression.
Recent physical or sexual IPV (prevalence 11%) was associated with recent sexual and drug-related STI/HIV risk, specifically unprotected vaginal sex (AOR 1.93, 95% CI 1.52, 2.44), unprotected anal sex (AOR 2.22, 95% CI 1.51, 3.27) and injection drug use, both their own (AOR 3.39, 95% CI 1.47, 7.79) and their partner’s (AOR 3.85, 1.91, 7.75). IPV was also linked with coercive sexual risk: involuntary condom non-use (AOR 1.87, 95% CI 1.51, 2.33), and fears of requesting condoms (AOR 4.15, 95% CI 2.73, 6.30) and refusing sex (AOR 11.84, 95% CI 7.59, 18.45). STI-related care-seeking was also more common among those abused (AOR 2.49, 95% CI 1.87, 3.31).
Recent IPV is concurrent with sexual and drug-related STI/HIV risk, including coercive sexual risk, thus compromising women’s agency in STI/HIV risk reduction. Clinical risk assessments should broaden to include unprotected heterosexual anal sex, coercive sexual risk, and IPV, and should promote safety and harm reduction.
PMCID: PMC4305329  PMID: 24234072
intimate partner violence; sexual risk; injection drug use; STI/HIV risk; adolescent
3.  The Role of Access to Head Start and Quality Ratings for Spanish-Speaking Dual Language Learners’ (DLLs) Participation in Early Childhood Education 
Data from the Head Start Impact Study (N = 4,442) were used to test for differences between Spanish-speaking Dual Language Learners (DLLs) and monolingual English-speaking children in: (1) Head Start attendance rates when randomly assigned admission; and (2) quality ratings of other early childhood education (ECE) programs attended when not randomly assigned admission to Head Start. Logistic regressions showed that Spanish-speaking DLL children randomly assigned a spot in Head Start were more likely than monolingual-English learners to attend. Further, Spanish-speaking DLLs not randomly assigned a spot in Head Start were more likely to attend higher-quality ECE centers than non-DLL children. Policy implications are discussed, suggesting that, if given access, Spanish-speaking DLL families will take advantage of quality ECE programs.
PMCID: PMC4088314  PMID: 25018585
Dual Language Learners; English language learners; Hispanic children; early childhood education; participation in Head Start; quality ratings
4.  Primary Care Providers’ Initial Treatment Decisions and Antidepressant Prescribing for Adolescent Depression 
Adolescent depression is a serious and undertreated public health problem. Nonetheless, pediatric primary care providers (PCPs) may have low rates of antidepressant prescribing due to structural and training barriers. We examined the impact of symptom severity and provider characteristics on initial depression treatment decisions in a setting with fewer structural barriers, an integrated behavioral health network.
We administered a cross sectional survey to 58 PCPs within a large pediatric practice network. We compared PCP reports of initial treatment decisions in response to two vignettes describing depressed adolescents with either moderate or severe symptoms. We measured PCP depression knowledge, attitudes toward addressing psychosocial concerns, demographics, and practice characteristics.
Few PCPs (25% for moderate, 32% for severe) recommended an antidepressant. Compared with treatment recommendations for moderate depression, severe depression was associated with a greater likelihood of child psychiatry referral (OR 5.50[95% CI 2.47-12.2] p<.001). Depression severity did not affect the likelihood of antidepressant recommendation (OR 1.58[95% CI 0.80-3.11] p=.19). Antidepressants were more likely to be recommended by PCPs with greater depression knowledge (OR 1.72[95% CI 1.14-2.59] p=.009) and access to an on-site mental health provider (OR 5.13[95% CI 1.24-21.2] p=.02) and less likely to be recommended by PCPs who reported higher provider burden when addressing psychosocial concerns (OR 0.85[95% CI 0.75-0.98] p=.02).
PCPs infrequently recommended antidepressants for adolescents, regardless of depression severity. Continued PCP support through experiential training, accounting for provider burden when addressing psychosocial concerns, and co-management with mental health providers may increase PCPs’ antidepressant prescribing.
PMCID: PMC4105359  PMID: 24336091
primary health care; depressive disorder; adolescent; antidepressant agents; physician's practice patterns
5.  Racial disparities in human papillomavirus vaccination: Does access matter? 
To examine the association between race/ethnicity and HPV vaccine initiation and to determine how access to healthcare influences this relationship.
We used nationally representative data from the National Survey of Family Growth to assess HPV vaccine initiation in 2,168 females aged 15–24. A series of regression analyses were performed to determine the independent effect of race/ethnicity on HPV vaccine initiation after controlling for socio-demographic variables and healthcare access measures. Age-stratified regression analyses were also performed to assess whether the relationship between race/ethnicity and HPV vaccine initiation differed between females aged 15–18 and 19–24.
There were significant racial/ethnic disparities in HPV vaccination with US-born Hispanics, foreign-born Hispanics, and African-Americans less likely to have initiated vaccination than whites (p<0.001). Adjusting for socio-demographic characteristics attenuated the disparity for both US-born and foreign-born Hispanics (adjusted odds ratio (AOR): 0.76; 95% confidence interval (CI): 0.50–1.16 and AOR: 0.67; 95% CI: 0.37–1.19) but not for African-Americans (AOR: 0.47; 95% CI: 0.33–0.66). Adding healthcare access measures further attenuated the disparity for US-born and foreign-born Hispanics (AOR: 0.85; 95% CI: 0.54–1.34 and AOR: 0.84; 95% CI: 0.45–1.55). African-Americans, however, remained less likely than whites to have initiated vaccination (AOR: 0.49; 95% CI: 0.36–0.68). These racial/ethnic trends were similar for females aged 15–18 and 19–24.
Lower rates of HPV vaccination among African-American females do not appear to be explained by differential access to healthcare. More research is necessary to elucidate factors contributing to HPV vaccination in this population.
PMCID: PMC4058822  PMID: 23992645
race/ethnicity; HPV; NSFG; disparities; vaccination
6.  The Burden of Disease and Health Care Use among Pertussis Cases in School Aged Children and Adults in England and Wales; A Patient Survey 
PLoS ONE  2014;9(11):e111807.
In 2011–2012 a large pertussis outbreak occurred in England. This provided an opportunity to estimate the disease burden in those aged 5 years and over. As pertussis is likely to be under reported both laboratory-confirmed and non-confirmed cases were included.
Laboratory-confirmed cases of pertussis, as well as their coughing but non-confirmed household members, were sent a questionnaire that collected information on clinical features and quality of life for the most severe day of disease and the day the patient filled in the questionnaire. The EuroQol-5 dimension questionnaire (EQ-5D) was used to evaluate quality of life. The duration of symptoms was obtained by contacting the patient every two weeks until symptoms stopped.
Data for 535 (out of 1262) laboratory confirmed pertussis patients and 44 (out of 140) coughing household contacts was available for analysis. On the most severe day, 56% of laboratory-confirmed cases reported they had 20+ more paroxysms, 58% reported they had a severe cough and 46% reported disruption of sleep for more than 4 hours. For non-confirmed coughing household contacts there were a similar number of coughing spells per day at the height, though the cough was reported to be less severe and to cause less sleep disruption. The main clinical symptoms on the worst day for both were shortness of breath, tiredness, sore ribs and vomiting. The duration of symptoms for both patient groups was around 160 days (162 and 168 days). Under base case assumptions the overall loss of quality of life was 0.097 QALY (0.089–0.106) for confirmed pertussis cases and 0.0365 QALY (0.023–0.054) for coughing household contacts.
Pertussis is a serious disease in those aged 5 years and over, causing disruption of sleep and daily activities over long period of time. The burden of illness due to undiagnosed pertussis is also considerable.
PMCID: PMC4244040  PMID: 25423321
7.  Iron Status and Reproduction in US Women: National Health and Nutrition Examination Survey, 1999-2006 
PLoS ONE  2014;9(11):e112216.
Women experience significant changes in iron status throughout their reproductive lifespans. While this is evident in regions with high rates of malnutrition and infectious disease, the extent of reproductive-related changes is less well known in countries with low rates of iron deficiency anemia, such as the United States. The goal of this study is determine the relationship between women's reproductive variables (pregnancy, parity, currently breastfeeding, regular menstruation, hormonal contraceptive use, and age at menarche) and iron status (hemoglobin, ferritin, transferrin receptor, and % transferrin saturation) using an anthropological framework for interpreting the results. Data from women aged 18–49 were taken from the 1999–2006 US NHANES, a nationally representative cross-sectional sample of US women. Using multiple imputation and complex survey statistics, women's reproductive variables were regressed against indicators of iron status. Pregnant women had significantly poorer iron status, by most indicators, than non-pregnant women. All biomarkers demonstrated significantly lower iron levels with increasing parity. Women who were having regular periods had iron indicators that suggested decreased iron levels, while women who used hormonal contraceptives had iron indicators that suggested increased iron levels. Despite relatively good iron status and widespread availability of iron-rich foods in the US, women still exhibit patterns of iron depletion across several reproductive variables of interest. These results contribute to an ecological approach to iron status that seeks to understand variation in iron status, with the hopes that appropriate, population-specific recommendations can be developed to improve women's health.
PMCID: PMC4223055  PMID: 25375360
8.  Vesicle-mediated export from the ER: COPII coat function and regulation 
Biochimica et biophysica acta  2013;1833(11):2464-2472.
Vesicle trafficking from the endoplasmic reticulum (ER) is a vital cellular process in all eukaryotes responsible for moving secretory cargoes from the ER to the Golgi apparatus. To accomplish this feat, the cell employs a set of conserved cytoplasmic coat proteins – the coat protein II (COPII) complex – that recruits cargo into nascent buds and deforms the ER membrane to drive vesicle formation. While our understanding of COPII coat mechanics has developed substantially since its discovery, we have only recently begun to appreciate the factors that regulate this complex and, in turn, ER-to-Golgi trafficking. Here, we describe these factors and their influences on COPII vesicle formation. Properties intrinsic to the GTP cycle of the coat, as well as coat structure, have critical implications for COPII vesicle trafficking. Extrinsic factors in the cytosol can modulate COPII activity through direct interaction with the coat or with scaffolding components, or by changing composition of the ER membrane. Further, lumenal and membrane-bound cargoes and cargo receptors can influence COPII-mediated trafficking in equally profound ways. Together, these factors work in concert to ensure proper cargo movement in this first step of the secretory pathway.
PMCID: PMC3676692  PMID: 23419775
COPII; Vesicle; Endoplasmic reticulum; Cargo export; Cargo receptor
9.  Characteristics of Natural Mentoring Relationships from the Perspectives of Homeless Youth 
Homeless youth experience high risks for poor mental health outcomes. The purpose of this qualitative study was to explore the characteristics of natural mentoring relationships among homeless youth and to identify possible mechanisms that can enhance social support for this population.
Semi-structured interviews were conducted with 23 homeless youth aged 14 to 21 who had natural mentors. The interviews focused on how youth met their natural mentors, the function of these relationships, and how natural mentoring relationships differed from other relationships in the youth’s social networks.
Main themes that emerged from the interviews included parental absence, natural mentors as surrogate parents, and social support from mentors.
Findings suggest that social supports provided by mentors enhance youth’s adaptive functioning and may promote resilience, thus the use of natural mentors may be an important untapped asset in designing interventions to improve outcomes for homeless youth.
PMCID: PMC3818248  PMID: 24180604
homeless youth; natural mentor; social support
10.  Transformational Leadership Moderates the Relationship between Emotional Exhaustion and Turnover Intention among Community Mental Health Providers 
Community mental health journal  2011;49(4):373-379.
Public sector mental health care providers are at high risk for burnout and emotional exhaustion which negatively affect job performance and client satisfaction with services. Few studies have examined ways to reduce these associations, but transformational leadership may have a positive effect. We examine the relationships between transformational leadership, emotional exhaustion, and turnover intention in a sample of 388 community mental health providers. Emotional exhaustion was positively related to turnover intention, and transformational leadership was negatively related to both emotional exhaustion and turnover intention. Transformational leadership moderated the relationship between emotional exhaustion and turnover intention, indicating that having a transformational leader may buffer the effects of providers’ emotional exhaustion on turnover intention. Investing in transformational leadership development for supervisors could reduce emotional exhaustion and turnover among public sector mental health providers.
PMCID: PMC4209723  PMID: 22052429
emotional exhaustion; burnout; turnover; leadership; mental health services
11.  Development of the preterm infant gut microbiome: a research priority 
Microbiome  2014;2:38.
The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role of the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. The paper concludes with speculation about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.
PMCID: PMC4203464  PMID: 25332768
Preterm infants; VLBW; Gut microbiota; Health
12.  A Bloody Mess: Dendritic Cells use hemophagocytosis to regulate viral inflammation 
Immunity  2013;39(3):10.1016/j.immuni.2013.08.024.
Previous studies have highlighted the immune-dampening effects of apoptotic cell uptake by phagocytes.Ohyagi et al. expose a unique mechanism of immune regulation during viral infection, which is mediated throughphagocytosis of apoptotic red cells by dendritic cells.
PMCID: PMC3882075  PMID: 24054326
13.  Current treatment of early breast cancer: adjuvant and neoadjuvant therapy 
F1000Research  2014;3:198.
Breast cancer is the most commonly diagnosed cancer in women. The latest world cancer statistics calculated by the International Agency for Research on Cancer (IARC) revealed that 1,677,000 women were diagnosed with breast cancer in 2012 and 577,000 died. The TNM classification of malignant tumor (TNM) is the most commonly used staging system for breast cancer. Breast cancer is a group of very heterogeneous diseases. The molecular subtype of breast cancer carries important predictive and prognostic values, and thus has been incorporated in the basic initial process of breast cancer assessment/diagnosis. Molecular subtypes of breast cancers are divided into human epidermal growth factor receptor 2 positive (HER2 +), hormone receptor positive (estrogen or progesterone +), both positive, and triple negative breast cancer. By virtue of early detection via mammogram, the majority of breast cancers in developed parts of world are diagnosed in the early stage of the disease. Early stage breast cancers can be completely resected by surgery. Over time however, the disease may come back even after complete resection, which has prompted the development of an adjuvant therapy. Surgery followed by adjuvant treatment has been the gold standard for breast cancer treatment for a long time. More recently, neoadjuvant treatment has been recognized as an important strategy in biomarker and target evaluation. It is clinically indicated for patients with large tumor size, high nodal involvement, an inflammatory component, or for those wish to preserve remnant breast tissue. Here we review the most up to date conventional and developing treatments for different subtypes of early stage breast cancer.
PMCID: PMC4224200  PMID: 25400908
14.  Foundations for Literacy: An Early Literacy Intervention for Deaf and Hard-of-Hearing Children 
The present study evaluated the efficacy of a new preschool early literacy intervention created specifically for deaf and hard-of-hearing (DHH) children with functional hearing. Teachers implemented Foundations for Literacy with 25 DHH children in 2 schools (intervention group). One school used only spoken language, and the other used sign with and without spoken language. A “business as usual” comparison group included 33 DHH children who were matched on key characteristics with the intervention children but attended schools that did not implement Foundations for Literacy. Children’s hearing losses ranged from moderate to profound. Approximately half of the children had cochlear implants. All children had sufficient speech perception skills to identify referents of spoken words from closed sets of items. Teachers taught small groups of intervention children an hour a day, 4 days a week for the school year. From fall to spring, intervention children made significantly greater gains on tests of phonological awareness, letter–sound knowledge, and expressive vocabulary than did comparison children. In addition, intervention children showed significant increases in standard scores (based on hearing norms) on phonological awareness and vocabulary tests. This quasi-experimental study suggests that the intervention shows promise for improving early literacy skills of DHH children with functional hearing.
PMCID: PMC4146385  PMID: 25125456
15.  Evaluation of the safety and immunogenicity in United Kingdom laboratory workers of a combined Haemophilus influenzae type b and meningococcal capsular group C conjugate vaccine 
Although a combined Haemophilus influenzae type b (Hib)/meningococcal capsular group C (MenC) conjugate vaccine with a tetanus toxoid carrier protein (Hib/MenC-TT) is not licensed for use in those above 2 years of age due to lack of data on safety and efficacy, certain patient groups at high risk of MenC and/or Hib disease are recommended to receive it. Laboratory workers working with Hib and/or MenC cultures may be at a potentially increased risk of acquiring infectious diseases and vaccination is therefore an important safety consideration. We undertook a clinical trial to investigate the safety and immunogenicity of Hib/MenC-TT vaccine in this cohort.
A total of 33 subjects were recruited to the trial, all of whom were vaccinated. Serology was completed on samples taken at baseline and four weeks following vaccination to determine MenC specific IgG, MenC serum bactericidal antibody (SBA), anti-Hib polyribosylribitol phosphate (PRP) IgG and anti-tetanus toxoid IgG responses.
At baseline, high proportions of subjects had protective antibody concentrations against MenC, Hib and tetanus due to previous vaccination and/or natural exposure. Vaccination induced > 3, 10 and 220 fold increases in geometric mean concentrations for MenC SBA, anti-tetanus toxoid IgG and anti-Hib PRP IgG, respectively. Following vaccination, 97% of subjects had putative protective SBA titres ≥ 8, 100% had short term protective anti-Hib PRP IgG concentrations ≥ 0.15 μg/mL and 97% had protective anti-tetanus toxoid concentrations ≥ 0.1 IU/mL. No safety concerns were reported with minor local reactions being reported by 21% of subjects.
Immunological responses determined in this trial are likely a combination of primary and secondary responses due to previous vaccination and natural exposure. Subjects were a representative cross-section of laboratory workers, enabling us to conclude that a single dose of Hib/MenC-TT was safe and immunogenic in healthy adults providing the evidence that this vaccine may be used for providing protection in an occupational setting.
PMCID: PMC4112987  PMID: 25071861
Meningococcal; Haemophilus influenzae type b; Tetanus; Vaccine; Laboratory workers; Occupational immunisation
16.  Early menarche and childhood adversities in a nationally representative sample 
Epidemiological evidence suggests that early menarche, defined as onset of menses at age 11 or earlier, has increased in prevalence in recent birth cohorts and is associated with multiple poor medical and mental health outcomes in adulthood. There is evidence that childhood adversities occurring prior to menarche contribute to early menarche.
Data collected in face-to-face interviews with a nationally representative sample of women age 18 and over (N = 3288), as part of the National Comorbidity Survey-Replication, were analyzed. Associations between pre-menarchal childhood adversities and menarche at age 11 or earlier were estimated in discrete time survival models with statistical adjustment for age at interview, ethnicity, and body mass index. Adversities investigated included physical abuse, sexual abuse, neglect, biological father absence from the home, other parent loss, parent mental illness, parent substance abuse, parent criminality, inter-parental violence, serious physical illness in childhood, and family economic adversity.
Mean age at menarche varied across decadal birth cohorts (χ2₍₄₎ = 21.41, p < .001) ranging from a high of 12.9 years in the oldest cohort (age 59 or older at the time of interview) to a low of 12.4 in the second youngest cohort (age 28-37). Childhood adversities were also more common in younger than older cohorts. Of the 11 childhood adversities, 5 were associated with menarche at age 11 or earlier, with OR of 1.3 or greater. Each of these five adversities is associated with a 26% increase in the odds of early menarche (OR = 1.26, 95% CI 1.14-1.39). The relationship between childhood sexual abuse and early menarche was sustained after adjustment for co-occurring adversities. (OR = 1.77, 95% CI 1.21-2.6).
Evidence from this study is consistent with hypothesized physiological effects of early childhood family environment on endocrine development. Childhood sexual abuse is the adversity most strongly associated with early menarche. However, because of the complex way that childhood adversities cluster within families, the more generalized influence of highly dysfunctional family environments cannot be ruled out.
PMCID: PMC4118267  PMID: 25089128
17.  Oral Fluid Testing for Pertussis, England and Wales, June 2007–August 2009  
Emerging Infectious Diseases  2014;20(6):968-975.
Existing pertussis surveillance systems tend to underidentify less severe cases among older children and adults. For routine follow-up of notified, nonconfirmed, clinically diagnosed pertussis cases, use of an oral fluid test was pilot tested in England and Wales during June 2007–August 2009. During that period, 1,852 cases of pertussis were confirmed by established laboratory methods and another 591 by oral fluid testing only. Although introduction of serologic testing in 2002 led to the greatest increase in ascertainment of pertussis, oral fluid testing increased laboratory ascertainment by 32% overall; maximal increase (124%) occurred among children 5–9 years of age. Patients whose pertussis was confirmed by oral fluid testing were least likely to be hospitalized, suggesting that milder community cases were being confirmed by this method. Oral fluid testing is an easily administered, noninvasive surveillance tool that could further our understanding of pertussis epidemiology and thereby contribute to decisions on vaccination strategies.
PMCID: PMC4036755  PMID: 24856627
18.  Case conferences between general practitioners and specialist teams to plan end of life care of people with end stage heart failure and lung disease: an exploratory pilot study 
BMC Palliative Care  2014;13:24.
Most people die of non-malignant disease, but most patients of specialist palliative care services have cancer. Adequate end of life care for people with non-malignant disease requires acknowledgement of their limited prognosis and appropriate care planning. Case conferences between specialist palliative care services and GPs improve outcomes in cancer-based populations. We report a pilot study of case conferences between the patient’s GP and specialist staff to facilitate care planning for people with end stage heart failure or non-malignant lung disease in a regional health service in Queensland Australia.
Single face to face case conferences about patients with a primary diagnosis of advanced heart failure or respiratory failure from non-malignant disease were conducted between a palliative care consultant, a case management nurse and the patient’s GP. Annualised rates of service utilisation (emergency department [ED] presentations, ED discharges back to home, hospital admissions, and admission length of stay) before and after case conference were calculated. Content and counts of case conference recommendations, and the rate of adherence to recommendations were also assessed. A process evaluation of case conferences was undertaken.
Twenty-three case conferences involving 21 GPs were conducted between November 2011 and November 2012. One GP refused to participate. Ten patients died, three at home. Of 82 management recommendations made, 55 (67%) were enacted. ED admissions fell from 13.9 per annum (pa) to 2.1 (difference 11.8, 95% CI 2.2-21.3, p = 0.001); ED admissions leading to discharge home from 3.9 to 0.4 pa (difference 3.5, 95% CI -0.4-7.5, p = 0.05); hospital admissions from 11.4 to 3.5 pa (difference 7.9, 95% CI 2.2-13.7, p = 0.002); and length of stay from 7.0 to 3.7 days (difference 3.4, 95% CI 0.9-5.8, p = 0.007). Participating health professionals were enthusiastic about the process.
This pilot is the initial step in the development and testing of a complex intervention based on a model of integrated care. A single case conference involving the patient’s heart or lung failure team is associated with significant reductions in service utilization, apparently by improving case coordination, enhancing symptom management and assessing and managing carer needs. A randomized controlled trial is being developed.
Trial registration
Australian and New Zealand Controlled Trials Register ACTRN12613001377729: Registered 16/12/2013.
PMCID: PMC4020309  PMID: 24829539
19.  Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration 
Nature genetics  2013;45(11):1366-1370.
To define the role of rare variants in advanced age-related macular degeneration (AMD) risk, we sequenced the exons of 681 genes within AMD-associated loci and pathways in 2,493 cases and controls. We first tested each gene for increased or decreased burden of rare variants in cases compared to controls. We found that 7.8% of AMD cases compared to 2.3% of controls are carriers of rare missense CFI variants (OR=3.6, p=2×10−8). There was a predominance of dysfunctional variants in cases compared to controls. We then tested individual variants for association to disease. We observed significant association with rare missense alleles outside CFI. Genotyping in 5,115 independent samples confirmed associations to AMD with a K155Q allele in C3 (replication p=3.5×10−5, OR=2.8; joint p=5.2×10−9, OR=3.8) and a P167S allele in C9 (replication p=2.4×10−5, OR=2.2; joint p=6.5×10−7, OR=2.2). Finally, we show that the 155Q allele in C3 results in resistance to proteolytic inactivation by CFH and CFI. These results implicate loss of C3 protein regulation and excessive alternative complement activation in AMD pathogenesis, thus informing both the direction of effect and mechanistic underpinnings of this disorder.
PMCID: PMC3902040  PMID: 24036952
20.  A cost-benefit analysis of the physical mechanisms of membrane curvature 
Nature cell biology  2013;15(9):10.1038/ncb2832.
Many cellular membrane-bound structures exhibit distinct curvature that is driven by the physical properties of their lipid and protein constituents. Here we review how cells manipulate and control this curvature in the context of dynamic events such as vesicle-mediated membrane traffic. Lipids and cargo proteins each contribute energetic barriers that must be overcome during vesicle formation. In contrast, protein coats and their associated accessory proteins drive membrane bending using a variety of interdependent physical mechanisms. We survey the energetic costs and drivers involved in membrane curvature, drawing a contrast between the stochastic contributions of molecular crowding and the deterministic assembly of protein coats. These basic principles also apply to other cellular examples of membrane bending events, including important disease-related problems like viral egress.
PMCID: PMC3813008  PMID: 23999615
21.  Validity of a reported history of chickenpox in targeting varicella vaccination at susceptible adolescents in England☆ 
Vaccine  2014;32(10):1213-1217.
•Chickenpox history may enable cost-effective vaccination of susceptible individuals.•We tested the validity of reported chickenpox history in adolescents.•Vaccine would be wasted in most adolescents with a negative or uncertain history.•6–9% of those with a positive chickenpox history would remain susceptible.•These data are needed to inform cost-effectiveness of proposed vaccine programmes.
In the UK, primary varicella is usually a mild infection in children, but can cause serious illness in susceptible pregnant women and adults. The UK Joint Committee on Vaccination and Immunisation is considering an adolescent varicella vaccination programme. Cost-effectiveness depends upon identifying susceptibles and minimising vaccine wastage, and chickenpox history is one method to screen for eligibility. To inform this approach, we estimated the proportion of adolescents with varicella antibodies by reported chickenpox history.
Recruitment occurred through secondary schools in England from February to September 2012. Parents were asked about their child's history of chickenpox, explicitly setting the context in terms of the implications for vaccination. 247 adolescents, whose parents reported positive (120), negative (77) or uncertain (50) chickenpox history provided oral fluid for varicella zoster virus-specific immunoglobulin-G (VZV-IgG) testing.
109 (90.8% [85.6–96.0%]) adolescents with a positive chickenpox history, 52 (67.5% [57.0–78.1%]) with a negative history and 42 (84.0% [73.7–94.3%]) with an uncertain history had VZV-IgG suggesting prior infection. Combining negative and uncertain histories, 74% had VZV-IgG (best-case). When discounting low total-IgG samples and counting equivocals as positive (worst-case), 84% had VZV-IgG. We also modelled outcomes by varying the negative predictive value (NPV) for the antibody assay, and found 74–87% under the best-case and 84–92% under the worst-case scenario would receive vaccine unnecessarily as NPV falls to 50%.
Reported chickenpox history discriminates between varicella immunity and susceptibility in adolescents, but significant vaccine wastage would occur if this approach alone were used to determine vaccine eligibility. A small but important proportion of those with positive chickenpox history would remain susceptible. These data are needed to determine whether reported history, with or without oral fluid testing in those with negative and uncertain history, is sufficiently discriminatory to underpin a cost-effective adolescent varicella vaccination programme.
PMCID: PMC3969712  PMID: 23871823
Varicella; Chickenpox; Reported history; Validity; Adolescent; Vaccination programme
22.  Visual Voices: A Participatory Method for Engaging Adolescents in Research and Knowledge Transfer 
Integrating the expertise and perspectives of adolescents in the process of generating and translating research knowledge into practice is often missed, yet is essential for designing and implementing programs to promote adolescent health. This paper describes the use of the arts-based participatory Visual Voices method in translational research. Visual Voices involves systematic creative writing, drawing and painting activities to yield culturally relevant information which is generated by and examined with adolescents. Qualitative data products include the created art products and transcripts from group discussions of the content developed and presented. Data are analyzed and compared across traditional (e.g., transcripts) and non-traditional (e.g., drawings and paintings) media. Findings are reviewed and interpreted with participants and shared publicly to stimulate community discussions and local policy and practice changes. Visual Voices is a novel method for involving adolescents in translational research though Integrated Knowledge Transfer (IKT), a process for bringing researchers and stakeholders together from the stage of idea generation to implementing evidence-based initiatives.
PMCID: PMC3575688  PMID: 23399093
23.  COPII – a flexible vesicle formation system 
Current opinion in cell biology  2013;25(4):420-427.
Long known as a coat system that generates small transport vesicles from the endoplasmic reticulum (ER), the COPII coat also drives ER export of cargo proteins that are too large to be contained within these canonical carriers. With crystal and cryo-EM structures giving an atomic level view of coat structure, current advances in the field have focused on understanding how the coat adapts to the different geometries of the underlying cargo. Combined with a growing appreciation for the specific roles of individual COPII paralogs in diverse aspects of mammalian physiology, the field is poised to understand how coat assembly and post-translational modification permits structural rigidity but geometric flexibility to handle the diverse cargoes that exit the ER.
PMCID: PMC3736695  PMID: 23702145
24.  A sustained passion for intracellular trafficking 
Molecular Biology of the Cell  2013;24(21):3270-3272.
I am honored to be the first recipient of the Women in Cell Biology Sustained Excellence in Research Award. Since my graduate school days, I have enjoyed being part of a stimulating scientific community the American Society for Cell Biology embodies. Having found myself largely by accident in a career that I find deeply enjoyable and fulfilling, I hope here to convey a sense that one need not have a “grand plan” to have a successful life in science. Simply following one's interests and passions can sustain a career, even though it may involve some migration.
PMCID: PMC3814137  PMID: 24174458
25.  Plasma Factors during Chronic HIV-1 Infection Impair IL-12 Secretion by Myeloid Dendritic Cells via a Virus-Independent Pathway 
Myeloid dendritic cell (mDC) dysfunction during HIV infection may hinder the formation of both innate and adaptive immune responses and contribute to pathogenesis. Our objective was to determine whether circulating factors during chronic HIV infection impair mDC function with respect to secretion of IL-12, a pro-Th1 cytokine, and T cell stimulatory capacity. Particular focus was placed on the effect of combination anti-retroviral therapy (cART) and the role of HIV itself on mDC function.
Monocyte-derived DC (moDC) from uninfected donors were exposed to plasma from HIV-infected individuals prior to Toll-like receptor (TLR) stimulation. Cytokine secretion was measured via cytokine bead arrays, and T cell proliferation and IFNγ secretion was evaluated following co-culture with naive CD4+ T cells. Expression of genes central to TLR-mediated signal transduction was analyzed via qRT-PCR arrays and western blot.
Exposure of moDC to plasma from untreated HIV-infected donors suppressed secretion of IL-12, and impaired Th1-skewing of CD4+ T cells. The suppressive effect was less by plasma donors receiving cART. Removal of virus from plasma did not relieve suppression, nor was IL-12 secretion decreased upon addition of HIV to control plasma. On a transcriptional level, decreased expression of IKKβ, a key regulator in the TLR/NF-kappaB signaling pathway, corresponded to suppressed cytokine secretion.
Plasma factors during chronic HIV infection impair mDC function in a manner that likely impacts the formation of immune responses to HIV, opportunistic pathogens, and vaccines. Despite partial alleviation by cART, this suppression was not directly mediated by HIV.
PMCID: PMC3508089  PMID: 22902724
HIV-1; Myeloid Dendritic Cell; Innate Immunity; Toll-like receptor; IL-12; I-kappa B kinase

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