Morphological and Habitat Quality of Salmonid Streams and their Relationship with Fish-Based Indices in Aotearoa New Zealand and Ontario (Canada).

Habitat degradation is one of the major reasons for freshwater species decline. Hydrogeomorphological processes (such as sediment transport, bank erosion, and flooding) operate at the catchment scale and determine habitat features in river reaches. However, habitat quality indices and restoration for freshwater fish species are often implemented at small spatial scales of a few hundred metres. The Morphological Quality Index (MQI) considers fluvial processes at larger scales as well as channel forms, human impacts, and historical changes, but few studies have assessed its relevance for ecosystem health. We investigated relationships between the MQI, habitat quality (using the Qualitative Habitat Evaluation Index, QHEI), land cover, and fish metrics (number of fish species, index of biotic integrity (IBI), and trout biomass) in 26 salmonid streams in Aotearoa New Zealand and Southern Ontario, Canada. We found a significant correlation between the MQI and QHEI, and both metrics were correlated with urban and native forest proportion in the catchment. However, we found no relation between the MQI and the proportion of agricultural land in the catchment, while the QHEI was correlated with agricultural land in the riparian zone, highlighting the importance of vegetated riparian buffers in providing fish habitat. Establishing a strong correlation with fish metrics remains challenging. Nevertheless, a modified MQI targeting ecological health could be used as an effective management tool for aquatic conservation.

Intracerebroventricular dosing of N-sulfoglucosamine sulfohydrolase in mucopolysaccharidosis IIIA mice reduces markers of brain lysosomal dysfunction.

Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused by N-sulfoglucosamine sulfohydrolase (SGSH) deficiency. SGSH removes the sulfate from N-sulfoglucosamine residues on the nonreducing end of heparan sulfate (HS-NRE) within lysosomes. Enzyme deficiency results in accumulation of partially degraded HS within lysosomes throughout the body, leading to a progressive severe neurological disease. Enzyme replacement therapy has been proposed, but further evaluation of the treatment strategy is needed. Here, we used Chinese hamster ovary cells to produce a highly soluble and fully active recombinant human sulfamidase (rhSGSH). We discovered that rhSGSH utilizes both the CI-MPR and LRP1 receptors for uptake into patient fibroblasts. A single intracerebroventricular (ICV) injection of rhSGSH in MPS IIIA mice resulted in a tissue half-life of 9 days and widespread distribution throughout the brain. Following a single ICV dose, both total HS and the MPS IIIA disease-specific HS-NRE were dramatically reduced, reaching a nadir 2 weeks post dose. The durability of effect for reduction of both substrate and protein markers of lysosomal dysfunction and a neuroimmune response lasted through the 56 days tested. Furthermore, seven weekly 148 µg doses ICV reduced those markers to near normal and produced a 99.5% reduction in HS-NRE levels. A pilot study utilizing every other week dosing in two animals supports further evaluation of less frequent dosing. Finally, our dose-response study also suggests lower doses may be efficacious. Our findings show that rhSGSH can normalize lysosomal HS storage and markers of a neuroimmune response when delivered ICV.

HIV and HCV testing at clinical encounters among people who inject drugs, 2013-2018-Opportunities for increased testing and prevention.

People who inject drugs (PWID) with unsafe injection practices have substantial risk for HIV and hepatitis C virus (HCV) infections. We describe frequency of, and factors associated with, HIV and HCV testing during clinical encounters with PWID. Inpatient and Emergency Department clinical encounters at an Atlanta hospital were abstracted from medical records spanning January 2013-December 2018. We estimated frequency of HIV and HCV testing during injection drug use (IDU)-related encounters among PWID without previous diagnoses. We assessed associations between patient factors and testing using generalized estimating equations models. HIV testing occurred in 39.3% and HCV testing occurred in 17.1% of eligible IDU-related encounters. Testing was more likely in IDU-related encounters during 2017-2018 than in encounters during 2013-2014; (HIV, AOR = 2.14, 95% CI, 1.32-3.49, p < .01). Testing was less likely among Black/African American patients compared to White patients (adjusted odds ratio [AOR]: HIV, AOR = 0.48, 95% confidence interval [CI], 0.33-0.72, p < .01); HCV, AOR = 0.41, 95% CI, 0.24-0.70, p < .01). This difference may be attributable to recent testing among Black patients in non-IDU related encounters. HIV and HCV testing improved over time; however, missed opportunities for testing still existed. Strategies should aim to improve equitable HIV and HCV testing among PWID.

Barriers Driving Racial Disparities in Colorectal Cancer Screening in African Americans.

PURPOSE OF REVIEW: Colorectal cancer screening has been shown to decrease mortality from colorectal cancer. Screening disparities continue to exist among ethnic minorities, particularly for African Americans. We herein review the barriers of colorectal cancer screening in this population. RECENT FINDINGS: At its foundation are patient barriers, which are further compounded by physician-related barriers and the idiosyncrasies of the healthcare system. Interventions to address the barriers include patient outreach, provider education, and healthcare legislation addressing financial barriers. Recent research has focused on factors predicting intentions to undergo colorectal cancer screening. Underlying all of the barriers is the systemic racism that affects and influences the healthcare system as much as all other institutions and contributes to inequities in the delivery of effective cancer prevention efforts. Perpetual disparities in CRC screening within the African American community are due to multifactorial barriers from the individual patient to provider and healthcare system and societal influences. An awareness of the behavioral and systemic factors that affect African Americans must underpin efforts to reach full equity in delivering CRC screening to this often medically underserved segment of our society.

Determinants of diagnostic discordance for non-diabetic hyperglycaemia and Type 2 diabetes using paired glycated haemoglobin measurements in a large English primary care population: cross-sectional study.

AIM: To investigate factors influencing diagnostic discordance for non-diabetic hyperglycaemia and Type 2 diabetes. METHODS: Some 10 000 adults at increased risk of diabetes were screened with HbA1c and fasting plasma glucose (FPG). The 2208 participants with initial HbA1c ≥ 42 mmol/mol (≥ 6.0%) or FPG ≥ 6.1 mmol/l were retested after a median 40 days. We compared the first and second HbA1c results, and consequent diagnoses of non-diabetic hyperglycaemia and Type 2 diabetes, and investigated predictors of discordant diagnoses. RESULTS: Of 1463 participants with non-diabetic hyperglycaemia and 394 with Type 2 diabetes on first testing, 28.4% and 21.1% respectively had discordant diagnoses on repeated testing. Initial diagnosis of non-diabetic hyperglycaemia and/or impaired fasting glucose according to both HbA1c and FPG criteria, or to FPG only, made reclassification as Type 2 diabetes more likely than initial classification according to HbA1c alone. Initial diagnosis of Type 2 diabetes according to both HbA1c and FPG criteria made reclassification much less likely than initial classification according to HbA1c alone. Age, and anthropometric and biological measurements independently but inconsistently predicted discordant diagnoses and changes in HbA1c . CONCLUSIONS: Diagnosis of non-diabetic hyperglycaemia or Type 2 diabetes with a single measurement of HbA1c in a screening programme for entry to diabetes prevention trials is unreliable. Diagnosis of non-diabetic hyperglycaemia and Type 2 diabetes should be confirmed by repeat testing. FPG results could help prioritise retesting. These findings do not apply to people classified as normal on a single test, who were not retested.

Delivery of an enzyme-IGFII fusion protein to the mouse brain is therapeutic for mucopolysaccharidosis type IIIB.

Mucopolysaccharidosis type IIIB (MPS IIIB, Sanfilippo syndrome type B) is a lysosomal storage disease characterized by profound intellectual disability, dementia, and a lifespan of about two decades. The cause is mutation in the gene encoding α-N-acetylglucosaminidase (NAGLU), deficiency of NAGLU, and accumulation of heparan sulfate. Impediments to enzyme replacement therapy are the absence of mannose 6-phosphate on recombinant human NAGLU and the blood-brain barrier. To overcome the first impediment, a fusion protein of recombinant NAGLU and a fragment of insulin-like growth factor II (IGFII) was prepared for endocytosis by the mannose 6-phosphate/IGFII receptor. To bypass the blood-brain barrier, the fusion protein ("enzyme") in artificial cerebrospinal fluid ("vehicle") was administered intracerebroventricularly to the brain of adult MPS IIIB mice, four times over 2 wk. The brains were analyzed 1-28 d later and compared with brains of MPS IIIB mice that received vehicle alone or control (heterozygous) mice that received vehicle. There was marked uptake of the administered enzyme in many parts of the brain, where it persisted with a half-life of approximately 10 d. Heparan sulfate, and especially disease-specific heparan sulfate, was reduced to control level. A number of secondary accumulations in neurons [ß-hexosaminidase, LAMP1(lysosome-associated membrane protein 1), SCMAS (subunit c of mitochondrial ATP synthase), glypican 5, ß-amyloid, P-tau] were reduced almost to control level. CD68, a microglial protein, was reduced halfway. A large amount of enzyme also appeared in liver cells, where it reduced heparan sulfate and ß-hexosaminidase accumulation to control levels. These results suggest the feasibility of enzyme replacement therapy for MPS IIIB.

Ryan White HIV/AIDS Program Assistance and HIV Treatment Outcomes.

BACKGROUND: The Ryan White HIV/AIDS Program (RWHAP) provides persons infected with human immunodeficiency virus (HIV) with services not covered by other healthcare payer types. Limited data exist to inform policy decisions about the most appropriate role for RWHAP under the Patient Protection and Affordable Care Act (ACA). METHODS: We assessed associations between RWHAP assistance and antiretroviral therapy (ART) prescription and viral suppression. We used data from the Medical Monitoring Project, a surveillance system assessing characteristics of HIV-infected adults receiving medical care in the United States. Interview and medical record data were collected in 2009-2013 from 18 095 patients. RESULTS: Nearly 41% of patients had RWHAP assistance; 15% relied solely on RWHAP assistance for HIV care. Overall, 91% were prescribed ART, and 75% were virally suppressed. Uninsured patients receiving RWHAP assistance were significantly more likely to be prescribed ART (52% vs 94%; P < .01) and virally suppressed (39% vs 77%; P < .01) than uninsured patients without RWHAP assistance. Patients with private insurance and Medicaid were 6% and 7% less likely, respectively, to be prescribed ART than those with RWHAP only (P < .01). Those with private insurance and Medicaid were 5% and 12% less likely, respectively, to be virally suppressed (P ≤ .02) than those with RWHAP only. Patients whose private or Medicaid coverage was supplemented by RWHAP were more likely to be prescribed ART and virally suppressed than those without RWHAP supplementation (P ≤ .01). CONCLUSIONS: Uninsured and underinsured HIV-infected persons receiving RWHAP assistance were more likely to be prescribed ART and virally suppressed than those with other types of healthcare coverage.

An anomalous positron abundance in cosmic rays with energies 1.5-100 GeV.

Antiparticles account for a small fraction of cosmic rays and are known to be produced in interactions between cosmic-ray nuclei and atoms in the interstellar medium, which is referred to as a 'secondary source'. Positrons might also originate in objects such as pulsars and microquasars or through dark matter annihilation, which would be 'primary sources'. Previous statistically limited measurements of the ratio of positron and electron fluxes have been interpreted as evidence for a primary source for the positrons, as has an increase in the total electron+positron flux at energies between 300 and 600 GeV (ref. 8). Here we report a measurement of the positron fraction in the energy range 1.5-100 GeV. We find that the positron fraction increases sharply over much of that range, in a way that appears to be completely inconsistent with secondary sources. We therefore conclude that a primary source, be it an astrophysical object or dark matter annihilation, is necessary.

Immunization information systems to increase vaccination rates: a community guide systematic review.

CONTEXT: Immunizations are the most effective way to reduce incidence of vaccine-preventable diseases. Immunization information systems (IISs) are confidential, population-based, computerized databases that record all vaccination doses administered by participating providers to people residing within a given geopolitical area. They facilitate consolidation of vaccination histories for use by health care providers in determining appropriate client vaccinations. Immunization information systems also provide aggregate data on immunizations for use in monitoring coverage and program operations and to guide public health action. EVIDENCE ACQUISITION: Methods for conducting systematic reviews for the Guide to Community Preventive Services were used to assess the effectiveness of IISs. Reviewed evidence examined changes in vaccination rates in client populations or described expanded IIS capabilities related to improving vaccinations. The literature search identified 108 published articles and 132 conference abstracts describing or evaluating the use of IISs in different assessment categories. EVIDENCE SYNTHESIS: Studies described or evaluated IIS capabilities to (1) create or support effective interventions to increase vaccination rates, such as client reminder and recall, provider assessment and feedback, and provider reminders; (2) determine client vaccination status to inform decisions by clinicians, health care systems, and schools; (3) guide public health responses to outbreaks of vaccine-preventable disease; (4) inform assessments of vaccination coverage, missed vaccination opportunities, invalid dose administration, and disparities; and (5) facilitate vaccine management and accountability. CONCLUSIONS: Findings from 240 articles and abstracts demonstrate IIS capabilities and actions in increasing vaccination rates with the goal of reducing vaccine-preventable disease.

Growth-promoting action and growth factor release by different platelet derivatives.

Abstract Platelet derivatives are commonly used in wound healing and tissue regeneration. Different procedures of platelet preparation may differentially affect growth factor release and cell growth. Preparation of platelet-rich fibrin (PRF) is accompanied by release of growth factors, including platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor ß1 (TGFß1), and several cytokines. When compared with the standard procedure for platelet-rich plasma (PRP), PRF released 2-fold less PDGF, but >15-fold and >2-fold VEGF and TGFß1, respectively. Also, the release of several cytokines (IL-4, IL-6, IL-8, IL-10, IFNγ, MIP-1α, MIP-1ß and TNFα) was significantly increased in PRF-conditioned medium (CM), compared to PRP-CM. Incubation of both human skin fibroblasts and human umbilical vein endothelial cells (HUVECs) with PRF-derived membrane (mPRF) or with PRF-CM enhanced cell proliferation by >2-fold (p<0.05). Interestingly, PRP elicited fibroblast growth at a higher extent compared to PRF. At variance, PRF effect on HUVEC growth was significantly greater than that of PRP, consistent with a higher concentration of VEGF in the PRF-CM. Thus, the procedure of PRP preparation leads to a larger release of PDGF, as a possible result of platelet degranulation, while PRF enhances the release of proangiogenic factors.

Effects of impoverished environmental conditions on working memory performance.

This cross-cultural study investigates the impact of background experience on four verbal and visuo-spatial working memory (WM) tasks. A total of 84 children from low-income families were recruited from the following groups: (1) Portuguese immigrant children from Luxembourg impoverished in terms of language experience; (2) Brazilian children deprived in terms of scholastic background; (3) Portuguese children from Portugal with no disadvantage in either scholastic or language background. Children were matched on age, gender, fluid intelligence, and socioeconomic status and completed four simple and complex span tasks of WM and a vocabulary measure. Results indicate that, despite large differences in their backgrounds and language abilities, the groups exhibited comparable performance on the visuo-spatial tasks dot matrix and odd-one-out and on the verbal simple span task digit recall. Group differences emerged on the verbal complex span task counting recall with children from Luxembourg and Portugal outperforming children from disadvantaged schools in Brazil. The study suggests that whereas contributions of prior knowledge to digit span, dot matrix, and odd-one-out are likely to be minimal, background experience can affect performance on counting recall. Implications for testing WM capacity in children growing up in poverty are discussed.

Clinical outcomes and molecular genotyping of Staphylococcus aureus isolated from milk samples of dairy primiparous Mediterranean buffaloes (Bubalus bubalis).

Staphylococcus aureus is one of the most important pathogens causing mastitis in dairy cows and in Mediterranean buffaloes. Genotype B (GTB) is contagious in dairy cows and may occur in up to 87% of cows of a dairy herd. It was the aim of this study to evaluate genotypes present, clinical outcomes, and prevalence of Staph. aureus in milk samples of primiparous Mediterranean dairy buffaloes. Two hundred composite milk samples originating from 40 primiparous buffaloes were collected from May to June 2012, at d 10, 30, 60, 90, and 150 d in milk (DIM) to perform somatic cell counts and bacteriological cultures. Daily milk yields were recorded. Before parturition until 40 to 50 DIM, all primiparous animals were housed separated from the pluriparous animals. Milking was performed in the same milking parlor, but the primiparous animals were milked first. After 50 DIM, the primiparous were mixed with the pluriparous animals, including the milking procedure. Individual quarter samples were collected from each animal, and aliquots of 1 mL were mixed and used for molecular identification and genotyping of Staph. aureus. The identification of Staph. aureus was performed verifying the presence of nuc gene by nuc gene PCR. All the nuc-positive isolates were subjected to genotype analysis by means of PCR amplification of the 16S-23S rRNA intergenic spacer region and analyzed by a miniaturized electrophoresis system. Of all 200 composite samples, 41 (20.5%) were positive for Staph. aureus, and no genotype other than GTB was identified. The prevalence of samples positive for Staph. aureus was 0% at 10 DIM and increased to a maximum of 22/40 (55%) at 90 DIM. During the period of interest, 14 buffaloes tested positive for Staph. aureus once, 6 were positive twice, and 5 were positive 3 times, whereas 15 animals were negative at every sampling. At 90 and 150 DIM, 7 (17.5%) and 3 buffaloes (7.5%), respectively, showed clinical mastitis (CM), and only 1 (2.5%) showed CM at both samplings. At 60, 90, and 150 DIM, 1 buffalo was found with subclinical mastitis at each sampling. At 30, 60, 90, and 150 DIM, 2.5 (1/40), 22.5 (9/40), 35 (14/40), and 10% (4/40) were considered affected by intramammary infection, respectively. Buffaloes with CM caused by Staph. aureus had statistically significantly higher mean somatic cell count values (6.06 ± 0.29, Log10 cells/mL ± standard deviation) and statistically significantly lower mean daily milk yields (7.15 ± 1.49, liters/animal per day) than healthy animals (4.69 ± 0.23 and 13.87 ± 2.64, respectively), buffaloes with IMI (4.82 ± 0.23 and 11.16 ± 1.80, respectively), or with subclinical mastitis (5.47 ± 0.10 and 10.33 ± 0.68, respectively). Based on our knowledge, this is the first time that Staph. aureus GTB has been identified in milk samples of dairy Mediterranean buffaloes.

Short communication: effects of systemic treatment with penethamate hydriodide on udder health and milk yields in dry primiparous Mediterranean buffaloes (Bubalus bubalis).

The effects of penethamate hydriodide (Mamyzin, Boehringer Ingelheim, Ingelheim, Germany) on udder health and milk yields were evaluated in primiparous Mediterranean buffaloes (Bubalus bubalis). An intramuscular administration of 10 million international units was performed in 20 buffaloes at 7 d precalving (treatment group; TG), and 20 animals were enrolled as the control group (CG). Evening milk samplings were performed at 10, 30, and 60 d in milk (DIM). Somatic cell count (SCC) values were evaluated on composite milk samples, whereas bacteriological culture and California Mastitis Test were performed on quarter milk. Daily milk yields were recorded after all milkings. After 60 DIM, composite milk samples from each animal were collected for monthly SCC and bacteriological culture until drying off. Statistically significant differences were found between the prevalence of mastitic quarters in the 2 groups at 10 and 30 DIM, and between the incidence of mastitic animals during the examined period (TG: 4/20, 20% vs. CG: 10/20, 50%). Even though lower and higher values of SCC and milk yields were found in TG during each sampling, statistically significant differences were only found at 30 (SCC) and 60 DIM (milk yields). In our study, the antibiotic administration precalving showed good bactericidal activity against the most common udder-specific pathogens that cause mastitis in primiparous Mediterranean buffaloes, and greater efficacy was observed at 10 and 30 DIM compared with 60 DIM. Given the significant decrease in SCC and increase in yields achieved, use of this antibiotic could be economically beneficial in buffalo breeding.

Specific language impairment in language-minority children from low-income families.

BACKGROUND: Recent evidence suggests that specific language impairment (SLI) might be secondary to general cognitive processing limitations in the domain of executive functioning. Previous research has focused almost exclusively on monolingual children with SLI and offers little evidence-based guidance on executive functioning in bilingual children with SLI. Studying bilinguals with SLI is important, especially in the light of increasing evidence that bilingualism can bring advantages in certain domains of executive functioning. AIMS: To determine whether executive functioning represents an area of difficulty for bilingual language-minority children with SLI and, if so, which specific executive processes are affected. METHODS & PROCEDURES: This cross-cultural research was conducted with bilingual children from Luxembourg and monolingual children from Portugal who all had Portuguese as their first language. The data from 81 eight-year-olds from the following three groups were analysed: (1) 15 Portuguese-Luxembourgish bilinguals from Luxembourg with an SLI diagnosis; (2) 33 typically developing Portuguese-Luxembourgish bilinguals from Luxembourg; and (3) 33 typically developing Portuguese-speaking monolinguals from Portugal. Groups were matched on first language, ethnicity, chronological age and socioeconomic status, and they did not differ in nonverbal intelligence. Children completed a battery of tests tapping: expressive and receptive vocabulary, syntactic comprehension, verbal and visuospatial working memory, selective attention and interference suppression. OUTCOMES & RESULTS: The bilingual SLI group performed equally well compared with their typically developing peers on measures of visuospatial working memory, but had lower scores than both control groups on tasks of verbal working memory. On measures of selective attention and interference suppression, typically developing children who were bilingual outperformed their monolingual counterparts. For selective attention, performance of the bilingual SLI group did not differ significantly from the controls. For interference suppression the bilingual SLI group performed significantly less well than typically developing bilinguals but not monolinguals. CONCLUSIONS & IMPLICATIONS: This research provides further support to the position that SLI is not a language-specific disorder. The study indicates that although bilingual children with SLI do not demonstrate the same advantages in selective attention and interference suppression as typically developing bilinguals, they do not lag behind typically developing monolinguals in these domains of executive functioning. This finding raises the possibility that bilingualism might represent a protective factor against some of the cognitive limitations that are associated with SLI in monolinguals.

Freedom space for rivers: a sustainable management approach to enhance river resilience.

River systems are increasingly under stress and pressure from agriculture and urbanization in riparian zones, resulting in frequent engineering interventions such as bank stabilization or flood protection. This study provides guidelines for a more sustainable approach to river management based on hydrogeomorphology concepts applied to three contrasted rivers in Quebec (Canada). Mobility and flooding spaces are determined for the three rivers, and three levels of "freedom space" are subsequently defined based on the combination of the two spaces. The first level of freedom space includes very frequently flooded and highly mobile zones over the next 50 years, as well as riparian wetlands. It provides the minimum space for both fluvial and ecological functionality of the river system. On average for the three studied sites, this minimum space was approximately 1.7 times the channel width, but this minimum space corresponds to a highly variable width which must be determined from a thorough hydrogeomorphic assessment and cannot be predicted using a representative average. The second level includes space for floods of larger magnitude and provides for meanders to migrate freely over a longer time period. The last level of freedom space represents exceptional flood zones. We propose the freedom space concept to be implemented in current river management legislation because it promotes a sustainable way to manage river systems, and it increases their resilience to climate and land use changes in comparison with traditional river management approaches which are based on frequent and spatially restricted interventions.

Differences in adult influenza vaccine-seeking behavior: the roles of race and attitudes.

BACKGROUND: Racial/ethnic disparities in influenza vaccination among adults are longstanding, and research suggests they result from multiple factors. Influenza vaccine-seeking behavior may be an important aspect to consider when evaluating disparities in vaccination coverage. OBJECTIVE: To determine whether there are differences between blacks and whites in influenza vaccine-seeking behavior among adults 65 years and older. METHODS: Data were analyzed from a national sample of 3138 adults 65 years and older collected through the adult module of the 2007 National Immunization Survey, a random digit dialing telephone survey, which included an oversample of non-Hispanic blacks. Analysis included influenza vaccination rate, location of vaccination, and whether vaccinated individuals specifically went to the location to receive the vaccine (vaccine seekers) by race. The relationship between attitudes about influenza vaccination and vaccine-seeking behavior by race was also examined. RESULTS: White adults 65 years and older were significantly more likely to receive influenza vaccine than blacks, during the 2006-2007 influenza season (68% ± 4% vs 54% ± 3%, respectively), and a significantly higher proportion of vaccinated whites reported seeking out the vaccine than vaccinated blacks (66% ± 4% vs 47% ± 4%, respectively). Blacks were less likely to be vaccine seekers, regardless of education or poverty levels. Among persons vaccinated in a doctor's office, 52% of whites specifically went there to get vaccinated, compared with 37% of blacks. Among persons who believe the vaccine is very effective, 66% ± 5% of whites versus 50% ± 6% of blacks were vaccine seekers. CONCLUSIONS: This study points to the importance of improving our understanding of what factors, in addition to beliefs about vaccination, lead to vaccine seeking and reinforces the need for systematically offering vaccine.