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1.  Child Care Enrollment Decisions Among Dual Language Learner Families: The Role of Spanish Language Instruction in the Child Care Setting 
Data from the Head Start Impact Study (N = 1,141) and the Head Start Family and Child Experiences Survey, 2009 Cohort (N = 825) were used to describe child care enrollment decisions among Spanish-speaking Dual Language Learner (DLL) families. In particular, logistic regression models tested which child, family, and institutional characteristics predicted enrollment in early care and education (ECE) settings that used Spanish for instruction versus enrollment in settings that did not use Spanish. Results showed that whether the child’s first language was exclusively Spanish and whether other DLL families previously attended the ECE arrangement strongly predicted whether that child enrolled. Policy implications for Head Start-eligible Spanish-speaking DLLs are discussed.
PMCID: PMC4754984  PMID: 26900255
DLLs; Head Start; child care decisions; enrollment
2.  Lactobacilli Dominance and Vaginal pH: Why Is the Human Vaginal Microbiome Unique? 
The human vaginal microbiome is dominated by bacteria from the genus Lactobacillus, which create an acidic environment thought to protect women against sexually transmitted pathogens and opportunistic infections. Strikingly, lactobacilli dominance appears to be unique to humans; while the relative abundance of lactobacilli in the human vagina is typically >70%, in other mammals lactobacilli rarely comprise more than 1% of vaginal microbiota. Several hypotheses have been proposed to explain humans' unique vaginal microbiota, including humans' distinct reproductive physiology, high risk of STDs, and high risk of microbial complications linked to pregnancy and birth. Here, we test these hypotheses using comparative data on vaginal pH and the relative abundance of lactobacilli in 26 mammalian species and 50 studies (N = 21 mammals for pH and 14 mammals for lactobacilli relative abundance). We found that non-human mammals, like humans, exhibit the lowest vaginal pH during the period of highest estrogen. However, the vaginal pH of non-human mammals is never as low as is typical for humans (median vaginal pH in humans = 4.5; range of pH across all 21 non-human mammals = 5.4–7.8). Contrary to disease and obstetric risk hypotheses, we found no significant relationship between vaginal pH or lactobacilli relative abundance and multiple metrics of STD or birth injury risk (P-values ranged from 0.13 to 0.99). Given the lack of evidence for these hypotheses, we discuss two alternative explanations: the common function hypothesis and a novel hypothesis related to the diet of agricultural humans. Specifically, with regard to diet we propose that high levels of starch in human diets have led to increased levels of glycogen in the vaginal tract, which, in turn, promotes the proliferation of lactobacilli. If true, human diet may have paved the way for a novel, protective microbiome in human vaginal tracts. Overall, our results highlight the need for continuing research on non-human vaginal microbial communities and the importance of investigating both the physiological mechanisms and the broad evolutionary processes underlying human lactobacilli dominance.
PMCID: PMC5143676  PMID: 28008325
vaginal microbiome; lactobacilli; pH; estrogen; mammals; evolution
3.  Sec24 phosphorylation regulates autophagosome abundance during nutrient deprivation 
eLife  null;5:e21167.
Endoplasmic Reticulum (ER)-derived COPII coated vesicles constitutively transport secretory cargo to the Golgi. However, during starvation-induced stress, COPII vesicles have been implicated as a membrane source for autophagosomes, distinct organelles that engulf cellular components for degradation by macroautophagy (hereafter called autophagy). How cells regulate core trafficking machinery to fulfill dramatically different cellular roles in response to environmental cues is unknown. Here we show that phosphorylation of conserved amino acids on the membrane-distal surface of the Saccharomyces cerevisiae COPII cargo adaptor, Sec24, reprograms COPII vesicles for autophagy. We also show casein kinase 1 (Hrr25) is a key kinase that phosphorylates this regulatory surface. During autophagy, Sec24 phosphorylation regulates autophagosome number and its interaction with the C-terminus of Atg9, a component of the autophagy machinery required for autophagosome initiation. We propose that the acute need to produce autophagosomes during starvation drives the interaction of Sec24 with Atg9 to increase autophagosome abundance.
eLife digest
When cells experience stressful conditions, such as a shortage of nutrients, they can digest their own material via a ‘self-eating’ process called autophagy and then recycle the products for further use. When autophagy is triggered, a new membrane structure called the autophagosome forms within the cell as it engulfs the material that is to be digested. The autophagosome delivers these materials to a compartment where they are broken down into smaller parts and the resulting raw materials are reused as needed.
The membranes that make up the autophagosome are derived from other membranes within the cell. These include small membrane-bound compartments called vesicles, which carry proteins from one part of the cell to another, or to the outside of the cell. COPII vesicles, for example, carry out the first transport step in the pathway that leads out of the cell – the so-called secretory pathway. Recently it was found that, when cells are starving, COPII vesicles can be diverted to the autophagy pathway and provide a source of membrane to build the autophagosome. However, it was not understood how the membrane of a COPII vesicle is reprogrammed so that it can interact with the cellular machinery that builds autophagosomes.
Using genetic and biochemical methods, Davis et al. have now teased apart the distinct roles of COPII vesicles in autophagy and the secretory pathway in budding yeast. The results show that a protein called Sec24, a component of the coat on the vesicles, interacts with another protein called Atg9, which is needed for the first steps of autophagosome formation. Davis et al. observed that Sec24 could be modified by the attachment of phosphate groups at a distinct site on the surface of Sec24. This modification promotes Sec24 to interact with Atg9 and increases the number of autophagosomes that form when cells are starving. Davis et al. also found that the enzyme casein kinase 1 is one of the enzymes responsible for attaching phosphate groups to Sec24.
Following on from this work, it will be important to test whether modification of vesicle coat proteins is a widespread mechanism for reprogramming membranes for different uses in other situations as well.
PMCID: PMC5148606  PMID: 27855785
Autophagy; COPII vesicles; Secretory pathway; Hrr25; S. cerevisiae
4.  Sustained Effectiveness of the Maternal Pertussis Immunization Program in England 3 Years Following Introduction 
The effectiveness of maternal immunization in preventing infant pertussis was first demonstrated in England, 1 year after the program using diphtheria–tetanus–5-component acellular pertussis–inactivated polio vaccine (dT5aP-IPV) was introduced in 2012. Vaccine effectiveness against laboratory-confirmed pertussis has been sustained >90% in the 3 years following its introduction, despite changing to another acellular vaccine with different antigen composition. Consistent with this, disease incidence in infants <3 months of age has remained low despite high activity persisting in those aged 1 year and older. Vaccine effectiveness against infant deaths was estimated at 95% (95% confidence interval, 79%–100%). Additional protection from maternal immunization is retained in infants who received their first dose of the primary series. There is no longer evidence of additional protection from maternal vaccination after the third infant dose. Although numbers are small and ongoing assessment is required, there is no evidence of increased risk of disease after primary immunization in infants whose mothers received maternal vaccination.
PMCID: PMC5106626  PMID: 27838678
maternal pertussis vaccination; vaccine effectiveness
9.  Sailing in Uncharted Waters: Carefully Navigating the Polio Endgame 
PLoS Medicine  2016;13(10):e1002141.
In a Perspective linked to the research article by Isobel Blake and colleagues, Elizabeth Miller and T. Jacob John discuss the path towards global polio eradication and the challenges, strategies, and necessary precautions around oral polio vaccine cessation.
PMCID: PMC5049750  PMID: 27701414
10.  Parents’ role in adolescent depression care: primary care provider perspectives 
The Journal of pediatrics  2015;167(4):911-918.
To understand how primary care providers (PCPs) perceive barriers to adolescent depression care to inform strategies to increase treatment engagement.
Study design
We conducted semi-structured interviews with 15 PCPs recruited from community pediatric offices with access to integrated behavioral health services (i.e., low system-level barriers to care) who participated in a larger study on treating adolescent depression. Interviews addressed PCP perceptions of barriers to adolescents’ uptake of care for depression. Interviews were audio-recorded, transcribed, and coded for key themes.
Although PCPs mentioned several adolescent barriers to care, they thought parents played a critical role in assisting adolescents in accessing mental health services. Important aspects of the parental role in accessing treatment included transportation, financial support, and social support. PCP’s perceived that parental unwillingness to accept the depression diagnosis, family dysfunction and trauma were common barriers. PCPs contrasted this with examples of good family support they believed would enable adolescents to attend follow-up appointments and have a “life coach” at home to help monitor for side effects and watch for increased suicidality when starting antidepressants.
In this PCP population, which had enhanced access to mental health specialists, PCPs primarily reported attitudinal barriers to adolescent depression treatment, focusing mainly on perceived parent barriers. The results of these qualitative interviews provide a framework for understanding PCP perceptions of parental barriers to care, identifying that addressing complex parental barriers to care may be important for future interventions.
PMCID: PMC4586359  PMID: 26143382
primary health care; depressive disorder; adolescent; parents
11.  Psychiatric Disorders Prior to Dating Initiation and Physical Dating Violence Before Age 21: Findings from the National Comorbidity Survey Replication (NCS-R) 
Poor mental health is associated with teen dating violence (TDV), but whether there are specific types of psychiatric disorders that could be targeted with intervention to reduce TDV remains unknown.
Multivariable logistic regression models were used to assess the associations of psychiatric disorders that emerged prior to dating initiation with subsequent physical dating violence in a nationally representative sample from the National Comorbidity Survey Replication, adjusting statistically for adverse childhood experiences.
In adjusted models, internalizing disorders (AOR 1.14, 95% CI 1.04, 1.25; no sex differences noted) and externalizing disorders (males: AOR 1.28, 95% CI 1.10, 1.49; females: AOR 1.85, 95% CI 1.55, 2.21) were associated with subsequent involvement in any physical dating violence victimization or perpetration before the age of 21. Those at greatest risk included girls with ADHD and substance use, in particular.
The range of psychiatric disorders associated with of TDV is broader than has generally been recognized for both boys and girls. Clinical and public health prevention programs should incorporate strategies for addressing multiple pathways through which poor mental health may put adolescents at risk for TDV.
PMCID: PMC4569529  PMID: 25773524
Dating violence; adolescents; mental health; adverse childhood experiences
12.  Investigating the pertussis resurgence in England and Wales, and options for future control 
BMC Medicine  2016;14(1):121.
In 2012 England and Wales experienced a resurgence of pertussis and an increase in infant deaths. This occurred 8 years after acellular pertussis (aP) vaccine replaced whole cell (wP) primary vaccine despite continued high coverage for the primary series and pre-school aP booster. We developed a mathematical model to describe pertussis transmission dynamics in England and Wales since the 1950s and used it to investigate the cause of the resurgence and the potential impact of additional vaccination strategies.
An age-structured, compartmental, deterministic model of the pertussis transmission dynamics was fitted to 60 continuous years of age-stratified pertussis notification data in England and Wales. The model incorporated vaccine-induced and natural immunity and differentiated between vaccine-induced protection against clinical disease and infection.
The degree of protection of wP vaccine against infection was estimated to be higher than that of aP vaccine. Furthermore, the duration of protection for natural and wP-induced immunity was likely to be at least 15 years, but for aP vaccine it could be as low as 5 years. Model results indicated that the likely cause of the resurgence was the replacement of wP by less efficacious aP vaccine and that an elevated level of pertussis would continue. The collapse in wP vaccine coverage in the 1970s and resultant outbreaks in the late 1970s and early 1980s could not explain the resurgence. Addition of an adolescent or toddler booster was predicted to have little impact on the disease in infants.
Our findings support the recent recommendation by the World Health Organisation that countries currently using wP vaccine for primary immunisation should not change to aP vaccine unless additional strategies to control infant disease such as maternal immunisation can be assured. Improved pertussis vaccines that provide better protection against infection are needed.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-016-0665-8) contains supplementary material, which is available to authorized users.
PMCID: PMC5007864  PMID: 27580649
Pertussis; Vaccine; Resurgence; Mathematical model; Transmission; Intervention
13.  Naturally Occurring Major and Minor Capsid Protein Variants of Human Papillomavirus 45 (HPV45): Differential Recognition by Cross-Neutralizing Antibodies Generated by HPV Vaccines 
Journal of Virology  2016;90(6):3247-3252.
We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of human papillomavirus genotype 45 (HPV45). Pseudoviruses (PsVs) representing HPV45 sublineages A1, A2, A3, B1, and B2 exhibited comparable particle-to-infectivity ratios and morphologies but demonstrated both increased (A2, A3, and B1) and decreased (B2) sensitivities to cross-neutralization by HPV vaccine antibodies compared to that of the A1 sublineage. Mutant PsVs identified HI loop residue 357 as being critical for conferring this differential sensitivity.
PMCID: PMC4810639  PMID: 26719255
15.  Virus Infection of Plants Alters Pollinator Preference: A Payback for Susceptible Hosts? 
PLoS Pathogens  2016;12(8):e1005790.
Plant volatiles play important roles in attraction of certain pollinators and in host location by herbivorous insects. Virus infection induces changes in plant volatile emission profiles, and this can make plants more attractive to insect herbivores, such as aphids, that act as viral vectors. However, it is unknown if virus-induced alterations in volatile production affect plant-pollinator interactions. We found that volatiles emitted by cucumber mosaic virus (CMV)-infected tomato (Solanum lycopersicum) and Arabidopsis thaliana plants altered the foraging behaviour of bumblebees (Bombus terrestris). Virus-induced quantitative and qualitative changes in blends of volatile organic compounds emitted by tomato plants were identified by gas chromatography-coupled mass spectrometry. Experiments with a CMV mutant unable to express the 2b RNA silencing suppressor protein and with Arabidopsis silencing mutants implicate microRNAs in regulating emission of pollinator-perceivable volatiles. In tomato, CMV infection made plants emit volatiles attractive to bumblebees. Bumblebees pollinate tomato by ‘buzzing’ (sonicating) the flowers, which releases pollen and enhances self-fertilization and seed production as well as pollen export. Without buzz-pollination, CMV infection decreased seed yield, but when flowers of mock-inoculated and CMV-infected plants were buzz-pollinated, the increased seed yield for CMV-infected plants was similar to that for mock-inoculated plants. Increased pollinator preference can potentially increase plant reproductive success in two ways: i) as female parents, by increasing the probability that ovules are fertilized; ii) as male parents, by increasing pollen export. Mathematical modeling suggested that over a wide range of conditions in the wild, these increases to the number of offspring of infected susceptible plants resulting from increased pollinator preference could outweigh underlying strong selection pressures favoring pathogen resistance, allowing genes for disease susceptibility to persist in plant populations. We speculate that enhanced pollinator service for infected individuals in wild plant populations might provide mutual benefits to the virus and its susceptible hosts.
Author Summary
Cucumber mosaic virus, an important pathogen of tomato, causes plants to emit volatile chemicals that attract bumblebees. Bumblebees are important tomato pollinators, but do not transmit this virus. We propose that under natural conditions, helping host reproduction by encouraging bee visitation might represent a ‘payback’ by the virus to susceptible hosts. Although tomato flowers can give rise to seed through self-fertilization, bumblebee-mediated ‘buzz-pollination’ enhances this, increasing the number of seeds produced per fruit. Buzz-pollination further favors reproductive success of a plant by facilitating pollen export. Mathematical modeling suggests that if self-fertilization by infected plants, as well as pollen transfer from these plants (cross-fertilization) to surrounding plants is increased, this might favor reproduction of susceptible over that of resistant plants. This raises the possibility that under natural conditions some viruses might enhance competitiveness of susceptible plants and inhibit the emergence of resistant plant strains. We speculate that it may be in a virus’ interest to pay back a susceptible host by enhancing its attractiveness to pollinators, which will likely increase fertilization rates and the dissemination of susceptible plant pollen and may compensate for a decreased yield of seeds on the virus-infected plants.
PMCID: PMC4981420  PMID: 27513727
16.  Sexual and Reproductive Health Indicators and Intimate Partner Violence Victimization Among Female Family Planning Clinic Patients Who Have Sex with Women and Men 
Journal of Women's Health  2015;24(8):621-628.
Background: Sexual minority women are more likely than heterosexual women to have ever experienced intimate partner violence (IPV). Although IPV is associated with sexual risk and poor reproductive health outcomes among US women overall, little is known about whether IPV is related to sexual and reproductive health indicators among sexual minority women in particular.
Methods: Baseline data from a prospective intervention trial were collected from women ages 16–29 years at 24 family planning clinics in western PA (n=3,455). Multivariable logistic regression for clustered survey data was used to compare women who have sex with men only (WSM) and women who have sex with women and men (WSWM) on (1) IPV prevalence and (2) sexual and reproductive health behaviors, outcomes, and services use, controlling for IPV. Finally, we tested the interaction of sexual minority status and IPV.
Results: WSWM were significantly more likely than WSM to report a lifetime history of IPV (adjusted odds ratio (AOR): 3.00; 95% confidence interval (CI): 2.30, 3.09). Controlling for IPV, WSWM reported higher levels of sexual risk behaviors (e.g., unprotected vaginal and anal sex), male-perpetrated reproductive coercion, unwanted pregnancy, and sexually transmitted infection (STI) and pregnancy testing but less contraceptive care seeking. The association between IPV and lifetime STI diagnosis was greater among WSWM than among WSM.
Conclusions: IPV was pervasive and associated with sexual risk and reproductive health indicators among WSWM in this clinic-based setting. Healthcare providers' sexual risk assessment and provision of sexual and reproductive health services should be informed by an understanding of women's sexual histories, including sex of sexual partners and IPV history, in order to help ensure that all women receive the clinical care they need.
PMCID: PMC4545318  PMID: 25961855
17.  Optimizing Telehealth Strategies for Subspecialty Care: Recommendations from Rural Pediatricians 
Telemedicine Journal and e-Health  2015;21(8):622-629.
Background: Telehealth offers strategies to improve access to subspecialty care for children in rural communities. Rural pediatrician experiences and preferences regarding the use of these telehealth strategies for children's subspecialty care needs are not known. We elicited rural pediatrician experiences and preferences regarding different pediatric subspecialty telehealth strategies. Materials and Methods: Seventeen semistructured telephone interviews were conducted with rural pediatricians from 17 states within the United States. Interviewees were recruited by e-mails to a pediatric rural health listserv and to rural pediatricians identified through snowball sampling. Themes were identified through thematic analysis of interview transcripts. Institutional Review Board approval was obtained. Results: Rural pediatricians identified several telehealth strategies to improve access to subspecialty care, including physician access hotlines, remote electronic medical record access, electronic messaging systems, live video telemedicine, and telehealth triage systems. Rural pediatricians provided recommendations for optimizing the utility of each of these strategies based on their experiences with different systems. Rural pediatricians preferred specific telehealth strategies for specific clinical contexts, resulting in a proposed framework describing the complementary role of different telehealth strategies for pediatric subspecialty care. Finally, rural pediatricians identified additional benefits associated with the use of telehealth strategies and described a desire for telehealth systems that enhanced (rather than replaced) personal relationships between rural pediatricians and subspecialists. Conclusions: Rural pediatricians described complementary roles for different subspecialty care telehealth strategies. Additionally, rural pediatricians provided recommendations for optimizing individual telehealth strategies. Input from rural pediatricians will be crucial for optimizing specific telehealth strategies and designing effective telehealth systems.
PMCID: PMC4855729  PMID: 25919585
communication; coordination; electronic medical record; pediatrician; physician access hotline; rural; subspecialty; telehealth; telemedicine
18.  Soluble CD40 ligand contributes to dendritic cell mediated T-cell dysfunction in HIV-1 infection 
AIDS (London, England)  2015;29(11):1287-1296.
Plasma soluble CD40L (sCD40L) is increased during human immunodeficiency virus-1 (HIV) infection, but it is unknown whether it circulates in monomeric or multimeric forms, and whether the circulating forms have differential effects on myeloid dendritic cell (DC) function and adaptive regulation.
sCD40L forms were measured in plasma samples from HIV-infected donors. The effects of sCD40L forms on DC function were measured in vitro.
To delineate which forms of sCD40L are present in plasma from HIV-infected donors, immunoblots were performed following enrichment of plasma for medium and low abundance proteins. DCs from seronegative donors were exposed to multiple forms of sCD40L prior to Toll-like receptor (TLR) stimulation and DC function and adaptive regulation was assessed in vitro.
Monomeric and multimeric forms of sCD40L were identified in plasma from ART-treated HIV-infected donors. Though monomeric and multimeric forms of sCD40L had differential effects on DC activation when given alone, both strongly suppressed secretion of the Th1 skewing cytokine, IL-12, upon subsequent TLR stimulation. Furthermore, DCs exposed to both monomeric and multimeric sCD40L induced regulatory T cell formation and T cell anergy.
Elevated sCD40L during HIV infection impairs DC function, contributing to innate and adaptive immune dysfunction. Antiretroviral adjunctive therapies that decrease sCD40L may provide immune modulatory benefits.
PMCID: PMC4478195  PMID: 26091297
19.  Heritability of Biomarkers of Oxidized Lipoproteins: A Twin Pair Study 
To determine if biomarkers of oxidized lipoproteins are genetically determined. Lipoprotein(a) [Lp(a)] is a heritable risk factor and carrier of oxidized phospholipids (OxPL).
Approach and Results
We measured OxPL-apoB, Lp(a), IgG and IgM autoantibodies to malondialdehyde-modified low density lipoprotein (MDA-LDL), copper oxidized LDL (CuOxLDL) and apoB-immune complexes (ApoB-IC) in 386 monozygotic and dizygotic twins to estimate trait heritability (h2) and determine specific genetic effects among traits. A genome wide linkage study followed by genetic association was performed. The h2 (scale:0-1) for Lp(a) was 0.91±0.01 and for OxPL-apoB 0.87±0.02, which were higher than physiologic, inflammatory, or lipid traits. h2 of IgM MDA-LDL, CuOxLDL and ApoB-IC were 0.69±0.04, 0.67±0.05, and 0.80±0.03, respectively, and for IgG MDA-LDL, CuOxLDL and apoB-IC 0.62±0.05, 0.52±0.06, and 0.53±0.06, respectively. There was an inverse correlation between the major apo(a) isoform and OxPL-apoB (R=-0.49, p<0.001), and Lp(a) (R=-0.48, p<0.001) and OxPL-apoB was modestly correlated with Lp(a) (ρ=0.57, p<0.0001). The correlation in major apo(a) isoform size was concordant (R=1.0, p<0.001) among monozygotic twins but not dizygotic twins (R=0.40, p=0.055). Lp(a) and OxPL-apoB shared genetic co-determination (genetic covariance: ρG = 0.774±0.032, p=1.09×10-38), though not environmental determination (environmental covariance: ρE= 0.081±0.15, p=0.15). In contrast, Lp(a) shared environmental but not genetic co-determination with autoantibodies to MDA-LDL and CuOxLDL and ApoB-IC. Sib-pair genetic linkage of the Lp(a) trait revealed that SNP rs10455872 was significantly associated with OxPL-apoB after adjusting for Lp(a).
OxPL-apoB and other biomarkers of oxidized lipoproteins are highly heritable cardiovascular risk factors that suggest novel genetic origins of atherothrombosis.
PMCID: PMC4483152  PMID: 25953646
heritability; lipoproteins; oxidation; atherosclerosis; thrombosis
20.  Modeling the spread of polio in an IPV-vaccinated population: lessons learned from the 2013 silent outbreak in southern Israel 
BMC Medicine  2016;14:95.
Polio eradication is an extraordinary globally coordinated health program in terms of its magnitude and reach, leading to the elimination of wild poliovirus (WPV) in most parts of the world. In 2013, a silent outbreak of WPV was detected in Israel, a country using an inactivated polio vaccine (IPV) exclusively since 2005. The outbreak was detected using environmental surveillance (ES) of sewage reservoirs. Stool surveys indicated the outbreak to be restricted mainly to children under the age of 10 in the Bedouin population of southern Israel. In order to curtail the outbreak, a nationwide vaccination campaign using oral polio vaccine (OPV) was conducted, targeting all children under 10.
A transmission model, fitted to the results of the stool surveys, with additional conditions set by the ES measurements, was used to evaluate the prevalence of WPV in Bedouin children and the effectiveness of the vaccination campaign. Employing the parameter estimates of the model fitting, the model was used to investigate the effect of alternative timings, coverages and dosages of the OPV campaign on the outcome of the outbreak.
The mean estimate for the mean reproductive number was 1.77 (95 % credible interval, 1.46–2.30). With seasonal variation, the reproductive number maximum range was between zero and six. The mean estimate for the mean infectious periods was 16.8 (8.6–24.9) days. The modeling indicates the OPV campaign was effective in curtailing the outbreak. The mean estimate for the attack rate in Bedouin children under 10 at the end of 2014 was 42 % (22–65 %), whereas without the campaign the mean projected attack rate was 57 % (35–74 %). The campaign also likely shortened the duration of the outbreak by a mean estimate of 309 (2–846) days. A faster initiation of the OPV campaign could have reduced the incidence of WPV even if a lower coverage was reached, at the risk of prolonging the outbreak.
OPV campaigns are essential for interrupting WPV transmission, even in a developed country setting with a high coverage of IPV. In this setting, establishing ES of WPV circulation is particularly crucial for early detection and containment of an outbreak.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-016-0637-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4918056  PMID: 27334457
Polio; Inactivated polio vaccine; Oral polio vaccine; Transmission model; Model fitting; Vaccination strategies
21.  Traffic of p24 proteins and COPII coat composition mutually influence membrane scaffolding 
Current biology : CB  2015;25(10):1296-1305.
Eukaryotic protein secretion requires efficient and accurate delivery of diverse secretory and membrane proteins. This process initiates in the endoplasmic reticulum, where vesicles are sculpted by the essential COPII coat. The Sec13p subunit of the COPII coat contributes to membrane scaffolding, which enforces curvature on the nascent vesicle. A requirement for Sec13p can be bypassed when traffic of lumenally oriented membrane proteins is abrogated. Here, we sought to further explore the impact of cargo proteins on vesicle formation. We show that efficient ER export of the p24 family of proteins is a major driver of the requirement for Sec13p. The scaffolding burden presented by the p24 complex is met in part by the cargo adaptor, Lst1p, which binds to a subset of cargo, including the p24 proteins. We propose that the scaffolding function of Lst1p is required to generate vesicles that can accommodate difficult cargo proteins that include large oligomeric assemblies and asymmetrically distributed membrane proteins. Vesicles that contain such cargoes are also more dependent on scaffolding by Sec13p and may serve as a model for large carrier formation in other systems.
PMCID: PMC4439346  PMID: 25936552
22.  Childhood adversities and adult use of potentially injurious physical discipline in Japan 
Journal of family violence  2015;30(4):515-527.
Using data derived from the World Mental Health Japan Survey (n = 1,186), this study examined the intergenerational continuity of potentially injurious physical discipline of children in a community sample from Japan with a special focus on the confounding effects of 11 other types of childhood adversities (CAs) and the intervening effects of mental disorders and socioeconomic status. Bivariate analyses revealed that having experienced physical discipline as children and five other CAs was significantly associated with the use of physical discipline as parents in the Japanese community examined. However, childhood physical discipline was the only CA that remained significant after adjusting for the other CAs. The association of childhood physical discipline with adult perpetration was independent of the respondents’ mental disorders and household income. No significant gender differences were found in the associations between childhood physical discipline and adult perpetration. The current study on Japan provided empirical support consistent with results found in other countries regarding the intergenerational transmission of child physical abuse.
PMCID: PMC4607286  PMID: 26478655
Intergenerational transmission; child physical abuse; childhood adversity; Japan; physical discipline; World Mental Health Survey
23.  Race and reproductive coercion: A qualitative assessment 
Unintended pregnancy is common and disproportionately occurs among low-income and African American (AA) women. Male partners may influence women’s risk of unintended pregnancy through reproductive coercion, although studies have not assessed whether racial differences in reproductive coercion impact AA women’s disparate risk for unintended pregnancy. We sought to describe women’s experiences with pregnancy-promoting behaviors by male partners and explore differences in such experiences by race.
Semi-structured interviews were conducted with low-income, AA and white women aged 18–45 recruited from reproductive health clinics in Western Pennsylvania to explore contextual factors that shape women’s contraceptive behaviors. Narratives were analyzed using content analysis and the constant comparison method.
Among the 66 participants (36 AA and 30 white), 25 (38%) described experiences with male partner reproductive coercion. Narratives provided accounts of contraceptive sabotage, verbal pressure to promote pregnancy and specific pregnancy outcomes, and potential motives behind these behaviors. AA women in the sample reported experiences of reproductive coercion more often than white women (53% and 20%, respectively). AA women were also more likely than white women to attribute a current or prior pregnancy to reproductive coercion. AA women identified relationship transiency and impending incarceration as potential motivations for men to secure a connection with a female partner via pregnancy.
Our findings suggest that reproductive coercion may be a factor contributing to disparities in unintended pregnancy. More research, including population-level studies, is needed to determine the impact of reproductive coercion on unintended pregnancy and to understand the social and structural factors associated with pregnancy-promoting behaviors.
PMCID: PMC4430345  PMID: 25748823
Reproductive coercion; race; pregnancy; contraception
24.  Racial and Ethnic Differences in Young Men’s Sex and Contraceptive Education 
Racial/ethnic disparities exist in young men’s contraceptive knowledge. This study examines whether the likelihood of receiving sexual health education varies by race/ethnicity.
Study Design
We examined racial/ethnic differences in sex and contraceptive education both in school and from parents with multivariable logistic regression models among 4,104 men aged 15–24 years using data from the 2006–2010 National Survey of Family Growth.
Nearly all respondents (96.6%) reported formal sex education. Fewer reported formal birth control education (66.6%), parental sex discussions (66.8%), and parental discussions specifically about birth control (49.2%). In multivariable analysis, black men were less likely than white men to report receiving formal contraceptive education (aOR:0.70;95%CI:0.51–0.96). Black and US-born Hispanic men reported more parental sex discussions than white men (aOR:1.44;95%CI:1.07–1.94, aOR:1.47;95%CI:1.09–1.99, respectively).
Nearly all respondents reported having received formal sexual health education. Fewer reported receiving education about birth control either at school or at home. Black men were less likely to report receiving formal contraceptive education.
PMCID: PMC4371132  PMID: 25797633
Race; disparities; men; sex education; contraceptive education
25.  Cost-Effectiveness of Vaccinating Immunocompetent ≥65 Year Olds with the 13-Valent Pneumococcal Conjugate Vaccine in England 
PLoS ONE  2016;11(2):e0149540.
Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ≥65 years.
A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results.
The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust.
Vaccinating immunocompetent individuals aged ≥65 years with PCV13 is efficacious. However the absolute incidence of vaccine-type disease will likely become very low due to wider benefits of the childhood PCV13 vaccination programme, such that a specific PCV13 vaccination programme targeting the immunocompetent elderly would not be cost-effective.
PMCID: PMC4767406  PMID: 26914907

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