Safe Expectations: Current State and Future Directions for Medication Safety in Pregnancy Research

Medication use in pregnancy is common, but information about the safety of most medications in pregnant women or their infants is limited. In the absence of data from randomized clinical trials to guide decisions made by regulators, clinicians, and patients, we often have to rely on well-designed observational studies to generate valid evidence about the benefits and risks of medications in pregnancy. Spontaneous reporting, primary case–control and cohort studies, pregnancy exposure registries, and electronic health data have been used extensively for studying medication safety in pregnancy. This article discusses these data sources, their strengths and limitations, and possible strategies and approaches to mitigating limitations when planning studies or interpreting findings from the literature. Strategies discussed include combining data sources across institutional or national borders, developing and using more sophisticated study designs, and taking advantage of existing analytic methods for more complex data structures, such as time-varying exposure or unmeasured confounding. Finally, we make recommendations for study designs that aid in better risk-related communication

An assessment of a three-beam Doppler lidar wind profiling method for use in urban areas

Currently there are few observations of the urban wind field at heights other than rooftop level. Remote sensing instruments such as Doppler lidars provide wind speed data at many heights, which would be useful in determining wind loadings of tall buildings, and predicting local air quality. Studies comparing remote sensing with traditional anemometers carried out in flat, homogeneous terrain often use scan patterns which take several minutes. In an urban context the flow changes quickly in space and time, so faster scans are required to ensure little change in the flow over the scan period. We compare 3993 h of wind speed data collected using a three-beam Doppler lidar wind profiling method with data from a sonic anemometer (190 m). Both instruments are located in central London, UK; a highly built-up area. Based on wind profile measurements every 2 min, the uncertainty in the hourly mean wind speed due to the sampling frequency is 0.05–0.11 m s−1. The lidar tended to overestimate the wind speed by ≈0.5 m s−1 for wind speeds below 20 m s−1. Accuracy may be improved by increasing the scanning frequency of the lidar. This method is considered suitable for use in urban areas

Spaces for smoking in a psychiatric hospital: social capital, resistance to control, and significance for 'therapeutic landscapes'

This paper reports on research framed by theories of therapeutic landscapes and the ways that the social, physical and symbolic dimensions of landscapes relate to wellbeing and healing. We focus especially on the question of how attributes of therapeutic landscapes are constructed in different ways according to the variable perspectives of individuals and groups. Through an ethnographic case study in a psychiatric hospital in the North of England we explore the perceived significance for wellbeing of ‘smoking spaces’ (where tobacco smoking is practiced in ways that may, or may not be officially sanctioned). We interpret our findings in light of literature on how smoking spaces are linked to the socio-geographical power relations that determine how smoking is organised within the hospital and how this is understood by different groups using the hospital building. We draw on qualitative research findings from discussion groups, observations, and interviews with patients, carers and staff. These focused on their views about the building design and setting of the new psychiatric hospital in relation to their wellbeing, and issues relating to smoking spaces emerged as important for many participants. Creating and managing smoking spaces as a public health measure in psychiatric hospitals is shown to be a controversial issue involving conflicting aims for health and wellbeing of patients and staff. Our findings indicate that although from a physical health perspective, smoking is detrimental, the spaces in which patients and staff smoke have social and psychological significance, providing a forum for the creation of social capital and resistance to institutional control. While the findings relate to one case study setting, the paper illustrates issues of wider relevance and contributes to an international literature concerning the tensions between perceived psychological and psychosocial benefits of smoking vs. physical harm that smoking is likely to cause. We consider the implications for hospital design and the model of care

Compassionate containment? Balancing technical safety and therapy in the design of psychiatric wards

This paper contributes to the international literature examining design of inpatient settings for mental health care. Theoretically, it elaborates the connections between conceptual frameworks from different strands of literature relating to therapeutic landscapes, social control and the social construction of risk. It does so through a discussion of the substantive example of research to evaluate the design of a purpose built inpatient psychiatric health care facility, opened in 2010 as part of the National Health Service (NHS) in England. Findings are reported from interviews or discussion groups with staff, patients and their family and friends. This paper demonstrates a strong, and often critical awareness among members of staff and other participants about how responsibilities for risk governance of ‘persons’ are exercised through ‘technical safety’ measures and the implications for therapeutic settings. Our participants often emphasised how responsibility for technical safety was being invested in the physical infrastructure of certain ‘places’ within the hospital where risks are seen to be ‘located’. This illuminates how the spatial dimensions of social constructions of risk are incorporated into understandings about therapeutic landscapes. There were also more subtle implications, partly relating to ‘Panopticist’ theories about how the institution uses technical safety to supervise its own mechanisms, through the observation of staff behaviour as well as patients and visitors. Furthermore, staff seemed to feel that in relying on technical safety measures they were, to a degree, divesting themselves of human responsibility for risks they are required to manage. However, their critical assessment showed their concerns about how this might conflict with a more therapeutic approach and they contemplated ways that they might be able to engage more effectively with patients without the imposition of technical safety measures. These findings advance our thinking about the construction of therapeutic landscapes in theory and in practice

'Therapeutic landscapes' and the importance of nostalgia, solastalgia, salvage and abandonment for psychiatric hospital design

We examine emotional reactions to changes to medical spaces of care, linked with past experiences. In this paper we draw on findings from a qualitative study of the transfer of psychiatric inpatient care from an old to a newly built facility. We show how the meanings attributed to ‘therapeutic landscapes’ from one׳s past can evoke emotions and memories, manifesting in ideas about nostalgia, solastalgia, salvage and abandonment, which can impinge on one׳s present therapeutic experience. We reflect on how consideration of these ideas might contribute to better future design of psychiatric inpatient facilities and the wellbeing of those using them

Properties of pattern formation and selection processes in nonequilibrium systems with external fluctuations

We extend the phase field crystal method for nonequilibrium patterning to stochastic systems with external source where transient dynamics is essential. It was shown that at short time scales the system manifests pattern selection processes. These processes are studied by means of the structure function dynamics analysis. Nonequilibrium pattern-forming transitions are analyzed by means of numerical simulations.Comment: 15 poages, 8 figure

Comparative proteomics of thylakoids from Arabidopsis grown in laboratory and field conditions

Compared to controlled laboratory conditions, plant growth in the field is rarely optimal since it is frequently challenged by large fluctuations in light and temperature which lower the efficiency of photosynthesis and lead to photo-oxidative stress. Plants grown under natural conditions therefore place an increased onus on the regulatory mechanisms that protect and repair the delicate photosynthetic machinery. Yet, the exact changes in thylakoid proteome composition which allow plants to acclimate to the natural environment remain largely unexplored. Here, we use quantitative label-free proteomics to demonstrate that field-grown Arabidopsis plants incorporate aspects of both the low and high light acclimation strategies previously observed in laboratory-grown plants. Field plants showed increases in the relative abundance of ATP synthase, cytochrome b6f, ferredoxin-NADP+ reductases (FNR1 and FNR2) and their membrane tethers TIC62 and TROL, thylakoid architecture proteins CURT1A, CURT1B, RIQ1, and RIQ2, the minor monomeric antenna complex CP29.3, rapidly-relaxing non-photochemical quenching (qE)-related proteins PSBS and VDE, the photosystem II (PSII) repair machinery and the cyclic electron transfer complexes NDH, PGRL1B, and PGR5, in addition to decreases in the amounts of LHCII trimers composed of LHCB1.1, LHCB1.2, LHCB1.4, and LHCB2 proteins and CP29.2, all features typical of a laboratory high light acclimation response. Conversely, field plants also showed increases in the abundance of light harvesting proteins LHCB1.3 and CP29.1, zeaxanthin epoxidase (ZEP) and the slowly-relaxing non-photochemical quenching (qI)-related protein LCNP, changes previously associated with a laboratory low light acclimation response. Field plants also showed distinct changes to the proteome including the appearance of stress-related proteins ELIP1 and ELIP2 and changes to proteins that are largely invariant under laboratory conditions such as state transition related proteins STN7 and TAP38. We discuss the significance of these alterations in the thylakoid proteome considering the unique set of challenges faced by plants growing under natural conditions

Perinatal risks in female cancer survivors: a population-based analysis

<div><p>Background/objectives</p><p>Advances in cancer management have resulted in improved survival rates, particularly in children and young adults. However, treatment may adversely affect reproductive outcomes among female cancer survivors. The objective of this study was to investigate their risk of adverse perinatal outcomes compared to the general population.</p><p>Design/methods</p><p>We performed a population-based analysis, including all female cancer survivors diagnosed before the age of 40 years between 1981 and 2012. Pregnancy and perinatal complications were identified through linkage of the Scottish Cancer Registry with hospital discharge records based on the Community Health Index (CHI) database. We compared 1,629 female cancer survivors with a first ever singleton pregnancy after diagnosis, with controls matched on age, deprivation quintile, and year of cancer diagnosis selected from the general population (n = 8,899). Relative risks and 95%-confidence intervals of perinatal risks were calculated using log-binomial regression.</p><p>Results</p><p>Survivors were more likely to give birth before 37 weeks of gestation (relative risk (RR]) 1.32, 95%-CI 1.10–1.59), but did not show an increased risk of low birth weight (<2.5kg: RR 1.15, 95%-CI 0.94–1.39), and were less likely to give birth to offspring small for gestational age (RR 0.81, 95%-CI 0.68–0.98). Operative delivery and postpartum haemorrhage were more common but approached rates in controls with more recent diagnosis. The risk of congenital abnormalities was not increased (RR 1.01, 95%-CI 0.85–1.20).</p><p>Conclusion</p><p>Cancer survivors have an increased risk of premature delivery and postpartum haemorrhage, but their offspring are not at increased risk for low birth weight or congenital abnormalities. In recent decades there has been a normalisation of delivery method in cancer survivors, nevertheless careful management remains appropriate particularly for those diagnosed in childhood.</p></div

Inhibition of somatosensory mechanotransduction by annexin A6

Mechanically activated, slowly adapting currents in sensory neurons have been linked to noxious mechanosensation. The conotoxin NMB-1 (noxious mechanosensation blocker-1) blocks such currents and inhibits mechanical pain. Using a biotinylated form of NMB-1 in mass spectrometry analysis, we identified 67 binding proteins in sensory neurons and a sensory neuron-derived cell line, of which the top candidate was annexin A6, a membrane-associated calcium-binding protein. Annexin A6-deficient mice showed increased sensitivity to mechanical stimuli. Sensory neurons from these mice showed increased activity of the cation channel Piezo2, which mediates a rapidly adapting mechano-gated current linked to proprioception and touch, and a decrease in mechanically activated, slowly adapting currents. Conversely, overexpression of annexin A6 in sensory neurons inhibited rapidly adapting currents that were partially mediated by Piezo2. Furthermore, overexpression of annexin A6 in sensory neurons attenuated mechanical pain in a mouse model of osteoarthritis, a disease in which mechanically evoked pain is particularly problematic. These data suggest that annexin A6 can be exploited to inhibit chronic mechanical pain