A 680,000-person megastudy of nudges to encourage vaccination in pharmacies

Encouraging vaccination is a pressing policy problem. To assess whether text-based reminders can encourage pharmacy vaccination and what kinds of messages work best, we conducted a megastudy. We randomly assigned 689,693 Walmart pharmacy patients to receive one of 22 different text reminders using a variety of different behavioral science principles to nudge flu vaccination or to a business-as-usual control condition that received no messages. We found that the reminder texts that we tested increased pharmacy vaccination rates by an average of 2.0 percentage points, or 6.8%, over a 3-mo follow-up period. The most-effective messages reminded patients that a flu shot was waiting for them and delivered reminders on multiple days. The top-performing intervention included two texts delivered 3 d apart and communicated to patients that a vaccine was “waiting for you.” Neither experts nor lay people anticipated that this would be the best-performing treatment, underscoring the value of simultaneously testing many different nudges in a highly powered megastudy

Infant and child mortality in South Africa in the context of a high HIV prevalence : an investigation into changing mortality patterns at a fine age resolution

Includes bibliographical references (leaves 98-111).South Africa has very high levels of HIV prevalence, with some provinces having among the highest levels in the world. Within this context it is imperative to have a clear understanding of how the epidemic is affecting infants and children in the population and to what extent interventions are affecting mortality. However, establishing accurate estimates of infant and child mortality levels is very difficult in South Africa because the data available is nearly a decade out of date. Demographic modelling techniques and extrapolations from out of date data provide the closest estimates but are less than ideal in the middle of an HIV epidemic. What is needed is a surveillance method that can provide rapid, up to date information on infant and child mortality, within an environment of high HIV prevalence that can inform health policy for South Africa's youngest citizens. This study utilized routinely collected national vital events data to describe trends in infant and child mortality from 1990 to 2006. Mortality was examined by age of death in months, a finer age resolution than has been previously published. Data used in this study consisted of unpublished mortality statistics collected by Statistics South Africa from 1990 to 2002, and data extracted from the Population Register database maintained by the Department of Home Affairs for the years 1998 to 2006. The Population Register database was investigated for use as a potential mortality surveillance tool to measure current trends in infant and child mortality and to measure any effects by HIV/IAIDS interventions at a population level. Several new and unique findings were revealed in this study. First, a new and increasing all-cause peak in mortality was discovered centring at 3 months of age - a new, previously unpublished, demographic phenomenon. Second, a coding error was found in causes of death of infants under 1 year of age in the data recorded by Statistics South Africa (Stats SA) resulting in the incorrect coding of the majority of deaths in this age group. Despite the problems with coding of cause of death, the peak in mortality at 3 months was shown to be due to HIV/AIDS mortality and was the third finding in this study. The fourth finding was that the Population Register data could further be used with the 3 month peak in mortality as a rapid surveillance tool to measure trends in infant mortality. By utilizing the up to date data from the Population Register database and monitoring the peak in mortality at 3 months, this study was able to show that HIV/AIDS interventions such as the ARV rollout and PMTCT programs are beginning to have a positive effect at a population level. This method of surveillance was able to examine changes in mortality at 3 -months at both a national and provincial level

Replication Initiation Patterns in the β-Globin Loci of Totipotent and Differentiated Murine Cells: Evidence for Multiple Initiation Regions

The replication initiation pattern of the murine β-globin locus was analyzed in totipotent embryonic stem cells and in differentiated cell lines. Initiation events in the murine β-globin locus were detected in a region extending from the embryonic Ey gene to the adult βminor gene, unlike the restricted initiation observed in the human locus. Totipotent and differentiated cells exhibited similar initiation patterns. Deletion of the region between the adult globin genes did not prevent initiation in the remainder of the locus, suggesting that the potential to initiate DNA replication was not contained exclusively within the primary sequence of the deleted region. In addition, a deletion encompassing the six identified 5′ hypersensitive sites in the mouse locus control region had no effect on initiation from within the locus. As this deletion also did not affect the chromatin structure of the locus, we propose that the sequences determining both chromatin structure and replication initiation lie outside the hypersensitive sites removed by the deletion

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.

BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. FINDINGS: A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity. INTERPRETATION: This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. FUNDING: UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR