Socially sensitive lactation: Exploring the social context of breastfeeding

Many women report difficulties with breastfeeding and do not maintain the practice for as long as intended. Although psychologists and other researchers have explored some of the difficulties they experience, fuller exploration of the relational contexts in which breastfeeding takes place is warranted to enable more in-depth analysis of the challenges these pose for breastfeeding women. The present paper is based on qualitative data collected from 22 first-time breastfeeding mothers through two phases of interviews and audio-diaries which explored how the participants experienced their relationships with significant others and the wider social context of breastfeeding in the first five weeks postpartum. Using a thematic analysis informed by symbolic interactionism, we develop the overarching theme of ‘Practising socially sensitive lactation’ which captures how participants felt the need to manage tensions between breastfeeding and their perceptions of the needs, expectations and comfort of others. We argue that breastfeeding remains a problematic social act, despite its agreed importance for child health. Whilst acknowledging the limitations of our sample and analytic approach, we suggest ways in which perinatal and public health interventions can take more effective account of the social challenges of breastfeeding in order to facilitate the health and psychological well-being of mothers and their infants

Development of an efficient cis-trans-cis ribozyme cassette to inactivate plant genes

Summary Inactivation of a targeted gene is one of the main strategies used to understand their precise cellular role. In plants, apart from chemical or physical mutagenesis and random insertions of DNA elements followed by screening for a desired phenotype, the most common strategy to inhibit the expression of a given gene involves RNA silencing. This can be achieved either through antisense suppression, sense over-expression leading to co-suppression, or expression of double-stranded DNA constructs (dsRNA). The use of ribozymes to inhibit gene product accumulation has only been occasionally attempted, mainly because of the more complex genetic engineering procedure involved, although the specificity of ribozymes can be an important factor when targeting close members of a gene family. We report here the development of a new cis -acting ribozyme cassette for the production of RNAs with desired termini. Attention to many details has been brought in order to provide a powerful procedure for plant application. For example, ultrastable GNRA tetraloops were substituted for both loops II and III of cis -acting hammerhead sequences, thereby favouring folding into the catalytically active structure that results in the self-cleavage of all transcripts. We demonstrate the usefulness of this cassette by producing a ribozyme that cleaves in trans , originally embedded in the cis -acting self-cleaving cassette. The activity of the cistrans-cis construct, was demonstrated both in vitro and in vivo , in transgenic plants with the specific cleavage of an mRNA encoding a 2-oxo-glutarate-dependant dioxygenase predominantly expressed in pistils tissues and in leaves, from the wild potato Solanum chacoense

An objective metric of individual health and aging for population surveys

Background We have previously developed and validated a biomarker-based metric of overall health status using Mahalanobis distance (DM) to measure how far from the norm of a reference population (RP) an individual’s biomarker profile is. DM is not particularly sensitive to the choice of biomarkers; however, this makes comparison across studies difficult. Here we aimed to identify and validate a standard, optimized version of DM that would be highly stable across populations, while using fewer and more commonly measured biomarkers. Methods Using three datasets (the Baltimore Longitudinal Study of Aging, Invecchiare in Chianti and the National Health and Nutrition Examination Survey), we selected the most stable sets of biomarkers in all three populations, notably when interchanging RPs across populations. We performed regression models, using a fourth dataset (the Women’s Health and Aging Study), to compare the new DM sets to other well-known metrics [allostatic load (AL) and self-assessed health (SAH)] in their association with diverse health outcomes: mortality, frailty, cardiovascular disease (CVD), diabetes, and comorbidity number. Results A nine- (DM9) and a seventeen-biomarker set (DM17) were identified as highly stable regardless of the chosen RP (e.g.: mean correlation among versions generated by interchanging RPs across dataset of r = 0.94 for both DM9 and DM17). In general, DM17 and DM9 were both competitive compared with AL and SAH in predicting aging correlates, with some exceptions for DM9. For example, DM9, DM17, AL, and SAH all predicted mortality to a similar extent (ranges of hazard ratios of 1.15–1.30, 1.21–1.36, 1.17–1.38, and 1.17–1.49, respectively). On the other hand, DM9 predicted CVD less well than DM17 (ranges of odds ratios of 0.97–1.08, 1.07–1.85, respectively). Conclusions The metrics we propose here are easy to measure with data that are already available in a wide array of panel, cohort, and clinical studies. The standardized versions here lose a small amount of predictive power compared to more complete versions, but are nonetheless competitive with existing metrics of overall health. DM17 performs slightly better than DM9 and should be preferred in most cases, but DM9 may still be used when a more limited number of biomarkers is available

Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial

Abstract Introduction Benzodiazepines and α2 adrenoceptor agonists exert opposing effects on innate immunity and mortality in animal models of infection. We hypothesized that sedation with dexmedetomidine (an α2 adrenoceptor agonist), as compared with lorazepam (a benzodiazepine), would provide greater improvements in clinical outcomes among septic patients than among non-septic patients. Methods In this a priori-determined subgroup analysis of septic vs non-septic patients from the MENDS double-blind randomized controlled trial, adult medical/surgical mechanically ventilated patients were randomized to receive dexmedetomidine-based or lorazepam-based sedation for up to 5 days. Delirium and other clinical outcomes were analyzed comparing sedation groups, adjusting for clinically relevant covariates as well as assessing interactions between sedation group and sepsis. Results Of the 103 patients randomized, 63 (31 dexmedetomidine; 32 lorazepam) were admitted with sepsis and 40 (21 dexmedetomidine; 19 lorazepam) without sepsis. Baseline characteristics were similar between treatment groups for both septic and non-septic patients. Compared with septic patients who received lorazepam, the dexmedetomidine septic patients had 3.2 more delirium/coma-free days (DCFD) on average (95% CI for difference, 1.1 to 4.9), 1.5 (-0.1, 2.8) more delirium-free days (DFD) and 6 (0.3, 11.1) more ventilator-free days (VFD). The beneficial effects of dexmedetomidine were more pronounced in septic patients than in non-septic patients for both DCFDs and VFDs (P-value for interaction = 0.09 and 0.02 respectively). Additionally, sedation with dexmedetomidine, compared with lorazepam, reduced the daily risk of delirium [OR, CI 0.3 (0.1, 0.7)] in both septic and non-septic patients (P-value for interaction = 0.94). Risk of dying at 28 days was reduced by 70% [hazard ratio 0.3 (0.1, 0.9)] in dexmedetomidine patients with sepsis as compared to the lorazepam patients; this reduction in death was not seen in non-septic patients (P-value for interaction = 0.11). Conclusions In this subgroup analysis, septic patients receiving dexmedetomidine had more days free of brain dysfunction and mechanical ventilation and were less likely to die than those that received a lorazepam-based sedation regimen. These results were more pronounced in septic patients than in non-septic patients. Prospective clinical studies and further preclinical mechanistic studies are needed to confirm these results. Trial Registration NCT00095251

PACIFIC-R: First real-world study of patients with unresectable, stage III NSCLC treated with durvalumab after chemoradiotherapy

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JWST/MIRI coronagraphic performances as measured on-sky

Characterization of directly imaged exoplanets is one of the most eagerly anticipated science functions of the James Webb Space Telescope. MIRI, the mid-IR instrument has the capability to provide unique spatially resolved photometric data points in a spectral range never achieved so far for such objects. We aim to present the very first on-sky contrast measurements of the MIRI's coronagraphs. In addition to a classical Lyot coronagraph at the longest wavelength, this observing mode implements the concept of the four quadrant phase mask for the very first time in a space telescope. We observed single stars together with a series of reference stars to measure raw contrasts as they are delivered on the detector, as well as reference subtracted contrasts. MIRI's coronagraphs achieve raw contrasts greater than $10^3$ at the smallest angular separations (within $1''$) and about $10^5$ further out (beyond $5\sim6''$). Subtracting the residual diffracted light left unattenuated by the coronagraph has the potential to bring the final contrast down to the background and detector limited noise floor at most angular separations (a few times $10^4$ at less than $1''$). MIRI coronagraphs behave as expected from simulations. In particular the raw contrasts for all four coronagraphs are fully consistent with the diffractive model. Contrasts obtained with subtracting reference stars also meet expectations and are fully demonstrated for two four quadrant phase masks (F1065C and F1140C). The worst contrast, measured at F1550C, is very likely due to a variation of the phase aberrations at the primary mirror during the observations, and not an issue of the coronagraph itself. We did not perform reference star subtraction with the Lyot mask at F2300C, but we anticipate that it would bring the contrast down to the noise floor.Comment: submitted to A&

The Continuing Slow Decline of AG Pegasi

We analyze optical and ultraviolet observations of the symbiotic binary AG Pegasi acquired during 1992-97. The bolometric luminosity of the hot component declined by a factor of 2-3 from 1980-1985 to 1997. Since 1992, the effective temperature of the hot component may have declined by 10%-20%, but this decline is comparable to the measurement errors. Optical observations of H-beta and He I emission show a clear illumination effect, where high energy photons from the hot component ionize the outer atmosphere of the red giant. Simple illumination models generally account for the magnitude of the optical and ultraviolet emission line fluxes. High ionization emission lines - [Ne V], [Mg V], and [Fe VII] - suggest mechanical heating in the outer portions of the photoionized red giant wind. This emission probably originates in a low density region $\sim$ 30-300 AU from the central binary.Comment: 17 pages, 7 pages, 5 tables; to be published in the Astronomical Journal, July 200