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Several dietary supplements are currently marketed for management of hypertension, but the evidence for effectiveness is conflicting. Our objective was to critically appraise and evaluate the evidence for the effectiveness of chlorogenic acids (CGAs) on blood pressure, using data from published randomized clinical trials (RCTs). Electronic searches were conducted in Medline, Embase, Amed, Cinahl and The Cochrane Library. We also hand-searched the bibliographies of all retrieved articles. Two reviewers independently determined the eligibility of studies and extracted the data. The reporting quality of all included studies was assessed by the use of a quality assessment checklist adapted from the Consolidated Standard of Reporting Trials Statement. Disagreements were resolved through discussion. Seven eligible studies were identified, and five including 364 participants were included. There were variations in the reporting quality of the included RCTs. Meta-analysis revealed a statistically significant reduction in systolic blood pressure in favour of CGA (mean difference (MD): −4.31 mm Hg; 95% confidence interval (CI): −5.60 to −3.01; I 2 =65%; P <0.00001). Meta-analysis also showed a significant reduction in diastolic blood pressure favouring CGA (MD: −3.68 mm Hg; 95% CI: −3.91 to −3.45; I 2 =97%; P <0.00001). All studies reported no adverse events. In conclusion, the evidence from published RCTs suggests that CGA intake causes statistically significant reductions in systolic and diastolic blood pressures. The size of the effect is moderate. Few clinical trials have been conducted; they vary in design and methodology and are confined to Asian populations and funded by CGA manufacturers. Large independent trials evaluating the effects of CGA on blood pressure are warranted.

African American women have increasingly begun to see their plays performed from regional stages to Broadway. Yet many of these artists still struggle to gain attention. In this volume, Sandra Adell draws from the vital wellspring of works created by African American women in the twenty-first century to present ten plays by both prominent and up-and-coming writers. Taken together, the selections portray how these women engage with history as they delve into--and shake up--issues of gender and class to craft compelling stories of African American life. Gliding from gritty urbanism to rural landscapes, these works expand boundaries and boldly disrupt modes of theatrical representation.

Adaptation is commonly a multidimensional problem, with changes in multiple traits required to match a complex environment. This is epitomized by balanced polymorphisms in which multiple phenotypes co-exist and are maintained in a population by a balance of selective forces. Consideration of such polymorphisms led to the concept of the supergene, where alternative phenotypes in a balanced polymorphism segregate as if controlled by a single genetic locus, resulting from tight genetic linkage between multiple functional loci. Recently, the molecular basis for several supergenes has been resolved. Thus, major chromosomal inversions have been shown to be associated with polymorphisms in butterflies, ants and birds, offering a mechanism for localised reduction in recombination. In several examples of plant self-incompatibility, the functional role of multiple elements within the supergene architecture has been demonstrated, conclusively showing that balanced polymorphism can be maintained at multiple coadapted and tightly linked elements. Despite recent criticism, we argue that the supergene concept remains relevant and is more testable than ever with modern molecular methods.

Many respiratory viruses cause morbidity in young children, but a licensed vaccine and effective oral therapy are available only for influenzavirus. To determine the incidence of laboratory-confirmed influenza illness, we prospectively followed up 1665 healthy children aged <5 years who were enrolled in the Vanderbilt Vaccine Clinic at some point from 1974 through 1999. Viral cultures were obtained when the children presented with clinical illness. The isolation of influenzavirus was associated with an estimated 95 health care visits for children with symptoms of influenza, 46 episodes of acute otitis media, and 8 episodes of lower respiratory tract disease per 1000 children yearly. Rates of acute otitis media and lower respiratory tract disease were highest among children aged <2 years. Hospitalizations associated with culture-positive influenza occurred at an annual rate of 3–4 per 1000 children aged <2 years. Influenza is associated with substantial morbidity in otherwise healthy children aged <5 years

Background: Cigarette smokers with asthma are insensitive to short term inhaled corticosteroid therapy, but efficacy when given for a longer duration at different doses is unknown. Methods: Ninety five individuals with mild asthma were recruited to a multicentre, randomised, double blind, parallel group study comparing inhaled beclomethasone in doses of 400 μg or 2000 μg daily for 12 weeks in smokers and non-smokers. The primary end point was the change in morning peak expiratory flow (PEF). Secondary end points included evening PEF, use of reliever inhaler, number of asthma exacerbations, spirometric parameters, and asthma control score. Results: After 12 weeks of inhaled beclomethasone there was a considerable difference between the morning PEF measurements of smokers and non-smokers with asthma (−18 (95% CI −35 to −1), adjusted p = 0.035). Among those receiving 400 μg daily there was a difference between the mean (95% CI) morning PEF (l/min) in smokers and non-smokers (−25 (95% CI −45 to −4), adjusted p = 0.019) and in the number of asthma exacerbations (6 v 1 in smokers and non-smokers, respectively, p = 0.007). These differences were reduced between smokers and non-smokers receiving 2000 μg inhaled beclomethasone daily. Conclusions: Compared with non-smokers, smokers with mild persistent asthma are insensitive to the therapeutic effect of low dose inhaled corticosteroid treatment administered for a 12 week period. The disparity of the response between smokers and non-smokers appears to be reduced with high dose inhaled corticosteroid. These findings have important implications for the management of individuals with mild asthma who smoke.

We describe the development and validation of a Sudden Unexpected Death in Infancy (SUDI) risk assessment clinical tool. An initial SUDI risk assessment algorithm was developed from an individual participant data meta-analysis of five international SIDS/SUDI case–control studies. The algorithm was translated into a clinical web tool called the Safe Sleep Calculator, which was tested at the routine infant 6-week check-up in primary care clinics in New Zealand. Evidence was gathered through mixed-methods research to inform the revision of the algorithm and the clinical tool. The revised algorithm performance was validated on a new contemporary New Zealand SUDI case–control study dataset and the pilot population data set. The area under the Receiver Operator Characteristic (ROC) curve is 0.89, with a sensitivity of 83.0% and a specificity of 80.9% in the NZ infant population when 0.3 per 1000 live births or more risk is used to define ‘at higher risk’. The Safe Sleep Calculator SUDI risk assessment tool provides individualized evidence-based specific SUDI prevention advice for every infant and enables the concentration of additional SUDI prevention efforts and resource for infants at higher risk.

RationaleAntibiotics are commonly prescribed for infants. In addition to increasing concern about antibiotic resistance, there is a concern about the potential negative impact of antibiotics on the gut microbiota and health and development outcomes.ObjectiveThe aim of this study was to investigate the association between early life antibiotic exposure and later neurocognitive outcomes.MethodsParticipants were infants born to mothers enrolled in the probiotics study. The initial study was designed to evaluate the effect of two different probiotics on allergy outcomes in childhood. Antibiotic exposure was based on parent report and categorised according to the following timing of the first exposure: 0–6 months, 6–12 months, 12–24 months or not at all. At 11 years of age, children’s neurocognitive outcomes were assessed using psychologist-administered, parent-report and self-report measures. The relationship between the timing of antibiotic exposure and neurocognitive outcomes was examined using regression models.ResultsOf the 474 participants initially enrolled, 342 (72%) children had a neurocognitive assessment at 11 years of age. After adjustment for mode of delivery, probiotic treatment group assignment, income and breastfeeding, children who had received antibiotics in the first 6 months of life had significantly lower overall cognitive and verbal comprehension abilities, increased risk of problems with metacognition, executive function, impulsivity, hyperactivity, attention-deficit hyperactivity disorder, anxiety and emotional problems.ConclusionsThese results provide further evidence that early exposure to antibiotics may be associated with detrimental neurodevelopmental outcomes.

Reovirus is a naturally occurring oncolytic virus currently in early clinical trials. However, the rapid induction of neutralizing antibodies represents a major obstacle to successful systemic delivery. This study addresses, for the first time, the ability of cellular carriers in the form of T cells and dendritic cells (DC) to protect reovirus from systemic neutralization. In addition, the ability of these cellular carriers to manipulate the subsequent balance of anti-viral versus anti-tumour immune response is explored. Reovirus, either neat or loaded onto DC or T cells, was delivered intravenously into reovirus-naive or reovirus-immune C57Bl/6 mice bearing lymph node B16tk melanoma metastases. Three and 10 days after treatment, reovirus delivery, carrier cell trafficking, metastatic clearance and priming of anti-tumour/anti-viral immunity were assessed. In naive mice, reovirus delivered either neat or through cell carriage was detectable in the tumour-draining lymph nodes 3 days after treatment, though complete clearance of metastases was only obtained when the virus was delivered on T cells or mature DC (mDC); neat reovirus or loaded immature DC (iDC) gave only partial early tumour clearance. Furthermore, only T cells carrying reovirus generated anti-tumour immune responses and long-term tumour clearance; reovirus-loaded DC, in contrast, generated only an anti-viral immune response. In reovirus-immune mice, however, the results were different. Neat reovirus was completely ineffective as a therapy, whereas mDC—though not iDC—as well as T cells, effectively delivered reovirus to melanoma in vivo for therapy and anti-tumour immune priming. Moreover, mDC were more effective than T cells over a range of viral loads. These data show that systemically administered neat reovirus is not optimal for therapy, and that DC may be an appropriate vehicle for carriage of significant levels of reovirus to tumours. The pre-existing immune status against the virus is critical in determining the balance between anti-viral and anti-tumour immunity elicited when reovirus is delivered by cell carriage, and the viral dose and mode of delivery, as well as the immune status of patients, may profoundly affect the success of any clinical anti-tumour viral therapy. These findings are therefore of direct translational relevance for the future design of clinical trials.

Bands of slower and faster rotation, the so-called torsional oscillations, are observed at the Sun's surface to migrate in latitude over the 11-year solar cycle. Here, we report on the temporal variations of the Sun's internal rotation from solar p-mode frequencies obtained over nearly 6 years by the Michelson Doppler Imager (MDI) instrument on board the Solar and Heliospheric Observatory (SOHO) satellite. The entire solar convective envelope appears to be involved in the torsional oscillations, with phase propagating poleward and equatorward from midlatitudes at all depths throughout the convective envelope.