Feasibility and design of a trial regarding the optimal mode of delivery for preterm birth:the CASSAVA multiple methods study

Background: Around 60,000 babies are born preterm (prior to 37 weeks’ gestation) each year in the UK. There is little evidence on the optimal birth mode (vaginal or caesarean section). Objective: The overall aim of the CASSAVA project was to determine if a trial to define the optimal mode of preterm birth could be carried out and, if so, determine what sort of trial could be conducted and how it could best be performed. We aimed to determine the specific groups of preterm women and babies for whom there are uncertainties about the best planned mode of birth, and if there would be willingness to recruit to, and participate in, a randomised trial to address some, but not all, of these uncertainties. This project was conducted in response to a Heath Technology Assessment programme commissioning call (17/22 ‘Mode of delivery for preterm infants’). Methods: We conducted clinician and patient surveys (n = 224 and n = 379, respectively) to identify current practice and opinion, and a consensus survey and Delphi workshop (n = 76 and n = 22 participants, respectively) to inform the design of a hypothetical clinical trial. The protocol for this clinical trial/vignette was used in telephone interviews with clinicians (n = 24) and in focus groups with potential participants (n = 13). Results: Planned sample size and data saturation was achieved for all groups except for focus groups with participants, as this had to be curtailed because of the COVID-19 pandemic and data saturation was not achieved. There was broad agreement from parents and health-care professionals that a trial is needed. The clinician survey demonstrated a variety of practice and opinion. The parent survey suggested that women and their families generally preferred vaginal birth at later gestations and caesarean section for preterm infants. The interactive workshop and Delphi consensus process confirmed the need for more evidence (hence the case for a trial) and provided rich information on what a future trial should entail. It was agreed that any trial should address the areas with most uncertainty, including the management of women at 26–32 weeks’ gestation, with either spontaneous preterm labour (cephalic presentation) or where preterm birth was medically indicated. Clear themes around the challenges inherent in conducting any trial emerged, including the concept of equipoise itself. Specific issues were as follows: different clinicians and participants would be in equipoise for each clinical scenario, effective conduct of the trial would require appropriate resources and expertise within the hospital conducting the trial, potential participants would welcome information on the trial well before the onset of labour and minority ethnic groups would require tailored approaches. Conclusion: Given the lack of evidence and the variation of practice and opinion in this area, and having listened to clinicians and potential participants, we conclude that a trial should be conducted and the outlined challenges resolved. Future work: The CASSAVA project could be used to inform the design of a randomised trial and indicates how such a trial could be carried out. Any future trial would benefit from a pilot with qualitative input and a study within a trial to inform optimal recruitment. Limitations: Certainty that a trial could be conducted can be determined only when it is attempted. Trial registration: Current Controlled Trials ISRCTN12295730. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 61. See the NIHR Journals Library website for further project information

On the cubic interactions of massive and partially-massless higher spins in (A)dS

Cubic interactions of massive and partially-massless totally-symmetric higher-spin fields in any constant-curvature background of dimension greater than three are investigated. Making use of the ambient-space formalism, the consistency condition for the traceless and transverse parts of the parity-invariant interactions is recast into a system of partial differential equations. The latter can be explicitly solved for given s_1-s_2-s_3 couplings and the 2-2-2 and 3-3-2 examples are provided in detail for general choices of the masses. On the other hand, the general solutions for the interactions involving massive and massless fields are expressed in a compact form as generating functions of all the consistent couplings. The St\"uckelberg formulation of the cubic interactions as well as their massless limits are also analyzed.Comment: 42 pages, 2 tables, LaTex. Comments on two-derivative couplings involving partially-massless spin-2 fields added, typos corrected, references added. v2: final version to appear in JHEP. v3: formulae (3.4) and (3.9) correcte

Maxwell-like Lagrangians for higher spins

We show how implementing invariance under divergence-free gauge transformations leads to a remarkably simple Lagrangian description of massless bosons of any spin. Our construction covers both flat and (A)dS backgrounds and extends to tensors of arbitrary mixed-symmetry type. Irreducible and traceless fields produce single-particle actions, while whenever trace constraints can be dispensed with the resulting Lagrangians display the same reducible, multi-particle spectra as those emerging from the tensionless limit of free open-string field theory. For all explored options the corresponding kinetic operators take essentially the same form as in the spin-one, Maxwell case.Comment: 77 pages, revised version. Erroneous interpretation and proof of the gauge-fixing procedure for mixed-symmetry fields corrected. As a consequence, the mixed-symmetry, one-particle Lagrangians are to be complemented with conditions on the divergences of the fields; all other conclusions unchanged. Additional minor changes including references added. To appear in JHE

Returning genome sequences to research participants:Policy and practice

Despite advances in genomic science stimulating an explosion of literature around returning health-related findings, the possibility of returning entire genome sequences to individual research participants has not been widely considered. Through direct involvement in large-scale translational genomics studies, we have identified a number of logistical challenges that would need to be overcome prior to returning individual genome sequence data, including verifying that the data belong to the requestor and providing appropriate informatics support. In addition, we identify a number of ethico-legal issues that require careful consideration, including returning data to family members, mitigating against unintended consequences, and ensuring appropriate governance. Finally, recognising that there is an opportunity cost to addressing these issues, we make some specific pragmatic suggestions for studies that are considering whether to share individual genomic datasets with individual study participants. If data are shared, research should be undertaken into the personal, familial and societal impact of receiving individual genome sequence data

Informed decision making about predictive DNA tests: arguments for more public visibility of personal deliberations about the good life

Since its advent, predictive DNA testing has been perceived as a technology that may have considerable impact on the quality of people’s life. The decision whether or not to use this technology is up to the individual client. However, to enable well considered decision making both the negative as well as the positive freedom of the individual should be supported. In this paper, we argue that current professional and public discourse on predictive DNA-testing is lacking when it comes to supporting positive freedom, because it is usually framed in terms of risk and risk management. We show how this ‘risk discourse’ steers thinking on the good life in a particular way. We go on to argue that empirical research into the actual deliberation and decision making processes of individuals and families may be used to enrich the environment of personal deliberation in three ways: (1) it points at a richer set of values that deliberators can take into account, (2) it acknowledges the shared nature of genes, and (3) it shows how one might frame decisions in a non-binary way. We argue that the public sharing and discussing of stories about personal deliberations offers valuable input for others who face similar choices: it fosters their positive freedom to shape their view of the good life in relation to DNA-diagnostics. We conclude by offering some suggestions as to how to realize such public sharing of personal stories

Half-integer Higher Spin Fields in (A)dS from Spinning Particle Models

We make use of O(2r+1) spinning particle models to construct linearized higher-spin curvatures in (A)dS spaces for fields of arbitrary half-integer spin propagating in a space of arbitrary (even) dimension: the field potentials, whose curvatures are computed with the present models, are spinor-tensors of mixed symmetry corresponding to Young tableaux with D/2 - 1 rows and r columns, thus reducing to totally symmetric spinor-tensors in four dimensions. The paper generalizes similar results obtained in the context of integer spins in (A)dS.Comment: 1+18 pages; minor changes in the notation, references updated. Published versio

Beta-gamma systems and the deformations of the BRST operator

We describe the relation between simple logarithmic CFTs associated with closed and open strings, and their "infinite metric" limits, corresponding to the beta-gamma systems. This relation is studied on the level of the BRST complex: we show that the consideration of metric as a perturbation leads to a certain deformation of the algebraic operations of the Lian-Zuckerman type on the vertex algebra, associated with the beta-gamma systems. The Maurer-Cartan equations corresponding to this deformed structure in the quasiclassical approximation lead to the nonlinear field equations. As an explicit example, we demonstrate, that using this construction, Yang-Mills equations can be derived. This gives rise to a nontrivial relation between the Courant-Dorfman algebroid and homotopy algebras emerging from the gauge theory. We also discuss possible algebraic approach to the study of beta-functions in sigma-models.Comment: LaTeX2e, 15 pages; minor revision, typos corrected, Journal of Physics A, in pres

Shortened time interval between colorectal cancer diagnosis and risk testing for hereditary colorectal cancer is not related to higher psychological distress

Current diagnostic practices have shortened the interval between colorectal cancer (CRC) diagnosis and genetic analysis for Lynch syndrome by MSI-testing. We studied the relation of time between MSI-testing since CRC diagnosis (MSI–CRC interval) and psychological distress. We performed a cross-sectional study in 89 patients who had previously been treated for CRC. Data were collected during MSI-testing after genetic counseling. Psychological distress was measured with the IES, the SCL-90 and the POMS; social issues with the ISS, ISB and the ODHCF. The median time of MSI–CRC interval was 24 months (range 0–332), with 23% of the patients diagnosed less than 12 months and 42% more than 36 months prior to MSI-testing. In 34% of the patients cancer specific distress was high (IES scores >26). Mean psychopathology (SCL-90) scores were low, mean mood states (POMS) scores were moderate. Interval MSI–CRC was not related to psychological distress. High cancer specific distress was reported by 24% of patients diagnosed with CRC less than 12 months ago versus 39 and 35% by those diagnosed between 12 and 36 months and more than 36 months ago respectively. Distress was positively related to female gender (P = 0.04), religiousness (P = 0.01), low social support (P = 0.02) and difficulties with family communication (P < 0.001). Shortened time interval between CRC diagnosis and MSI-testing is not associated with higher psychological distress. Females, religious persons, those having low social support and those reporting difficulties communicating hereditary colorectal cancer with relatives are at higher risk for psychological distress

Impact of Covid-19 on Health and Safety in the Construction Sector

Construction has been significantly affected by COVID-19 yet is critical to the post-COVID economic recovery. Specifically, construction needs to be constantly aware of safety and risk balanced with timely project delivery. Guidance for COVID–19 must therefore be implemented in a way that reflects working practice and pressures. There is, however, a potential knowledge gap regarding the practical feasibility and impact of applying COVID-19 measures within construction, made more difficult by factors such as the temporary nature of projects and complex working arrangements. This paper presents a commentary on safe construction during, and beyond, COVID-19, covering the human factors challenges and practicalities of implementing COVID-19 measures. We observe that while guidance is strong on risk management, understanding of how best to implement this guidance is not yet stable. Also, care must be taken that implementing guidance does not detract from general safety, which is also challenged by increased pressures on delivery arising from COVID-19. There may, however, be opportunities for safer working practice arising from new awareness of health, hygiene and safety risk. The role of safety leadership is overlooked in guidance yet is vital to ensure safe application of COVID-19 working practices. The key message is that COVID-19 needs to be integrated and promoted within a general risk management approach, in part because this takes account of differing priorities regarding safety risks, rather than overly focussing on COVID-19, and also because the effectiveness of COVID-19 mitigations can be amplified by integration with pre-existing safety processes

Is genetic counseling a stressful event?

Purpose. The aim of this paper was to investigate whether cancer genetic counseling could be considered as a stressful event and associated with more anxiety and/or depression compared to other cancer-related events for instance attending mammography screening or receiving a cancer diagnosis. Methods. A total of 4911 individuals from three Scandinavian countries were included in the study. Data was collected from individuals who had attended either cancer genetic counseling (self-referred and physician-referred) or routine mammography screening, were recalled for a second mammograpy due to a suspicious mammogram, had received a cancer diagnosis or had received medical follow-up after a breast cancer-surgery. Data from the genetic counseling group was also compared to normative data. Participants filled in the Hospital Anxiety and Depression Scale twice: prior to a potentially stressful event and 14 days after the event. Results. Pre-counseling cancer genetic counselees reported significant lower level of anxiety compared to the cancer-related group, but higher levels of anxiety compared to the general population. Furthermore, the level of depression observed within the genetic counseling group was lower compared to other participants. Post-event there was no significant difference in anxiety levels between the cancer genetic counselees and all other groups; however, the level of depression reported in the self-referred group was significantly lower than observed in all other groups. Notably, the level of anxiety and depression had decreased significantly from pre-to post-events within the genetic counseling group. In the cancer-related group only the level of anxiety had decreased significantly post-event. Conclusion. Individuals who attend cancer genetic counseling do not suffer more anxiety or depression compared to all other cancer-related groups. However, some counselees might need additional sessions and extended support. Thus, identifying extremely worried individuals who need more support, and allocating further resources to their care, seems to be more sufficient