Finding Fault? Divorce Law and Practice in England and Wales

This is the final version of the report. Available from Nuffield Foundation via the link in this record.1. Key messages The law of divorce in England and Wales has been subject to criticism for decades, most recently following the rare defended case of Owens v Owens. This major research study aimed to explore how the law is working in practice. The current law and use of fault The sole ground for divorce in England and Wales is the irretrievable breakdown of the marriage. But a divorce may be granted only if one of five ‘Facts’ is proved. Whilst many people might assume this is required, it is not necessary to prove that that ‘Fact’ was a cause of the breakdown. Three Facts are fault-based: adultery, behaviour, and desertion. Two Facts are based on separation: two years if the other spouse consents to divorce, five years if they do not. In 2015, 60% of English and Welsh divorces were granted on adultery or behaviour. In Scotland, where different procedural and related legal rules create different incentive structures, it was just 6%. Elsewhere, fault has been abolished or is just one option, and often a practically insignificant one, among several divorce grounds. The continuing problems of fault Academic research and Law Commission reviews from the 1970s onwards reported serious problems with the divorce law, including the lack of honesty of the system with the parties exaggerating behaviour allegations to get a quick divorce, while the court could do little more than ‘pretend’ to inquire into allegations. This study found that those problems continue and have worsened in some respects. Fault, especially behaviour, continues to be relied on to secure a faster divorce. The consequence is that parties often feel under pressure to exaggerate allegations or retro-fit the reasons for their separation into one of the legal Facts, even though the court’s expectations of what is required to make out each Fact is now actually very low, particularly for behaviour. The court has a duty to inquire into allegations but in practice in undefended cases only has the capacity to take the petitioner’s allegations at face value. That is procedurally unfair for the great majority of respondents who cannot defend themselves against the allegations. Parties embarking on the process might reasonably assume that the law is underpinned by a fault-based logic: that petitions should reflect who and what was to blame for the relationship breakdown. Yet whilst the law invites parties to rely on fault-based Facts, it does not require the court to adjudicate on responsibility in that way – not least because it will very often be impossible to allocate blame accurately in this context. Yet respondents on the receiving end of fault-based petitions inevitably feel cast as the ‘guilty’ party. The study found no evidence that fault prevents or slows down the decision to divorce and some evidence that it may shorten the time from break up to filing. We also found, as previously, that producing evidence of fault can create or exacerbate unnecessary conflict with damaging consequences for children and contrary to the thrust of family law policy. 10 The current divorce law is now nearly 50 years old. Its apparent rationale and operation are at odds with a modern, transparent, problem-solving family justice system that seeks to minimise the consequences of relationship breakdown for both adults and children. The need for law reform to finally remove fault The study shows that we already have something tantamount to immediate unilateral divorce ‘on demand’, but masked by an often painful, and sometimes destructive, legal ritual with no obvious benefits for the parties or the state. A clearer and more honest approach, that would also be fairer, more child-centred and cost-effective, would be to reform the law to remove fault entirely. We propose a notification system where divorce would be available if one or both parties register that the marriage has broken down irretrievably and that intention is confirmed by one or both parties after a minimum period of six months.Nuffield Foundatio

The Response Phase - The First Six Hours After Acute Airway Injury by SO2 Inhalation: An in vivo and in vitro Study

We have identified an airway epithelial response following acute injury that cannot be termed \u27repair\u27 or regeneration. It precedes these well characterized events and it is termed the \u27response phase\u27. We tested the hypothesis that for the first 6 h following acute injury to the tracheal mucosa, the initial cellular events of the response phase will continue as in vivo even if the tissue is maintained in vitro in an Ussing chamber. The tracheal mucosa of anesthetized, intubated mongrel dogs was injured by the inhalation of SO2 500 ppm for 1 h (7 dogs); controls (3 dogs) breathed filtered, compressed air for 1 h. 4 dogs were killed, in pairs, at 1 and 6 h after 500ppm of SO2; their tracheas were removed and fixed for microscopic examination. 3 dogs were killed immediately after the SO2 exposure, their tracheas were removed and epithelium isolated from the posterior-membranous sheath was mounted in Ussing chambers in oxygenated, Krebs-Henseleit buffer (8 per dog with aperature area of 1.5 cm2). These tissues (and those from control dogs prepared identically) were fixed after 1 and 6 h incubation for microscopic examination. Epithelial damage was not observed in any controls but was in all tissues exposed to SO2. A wide spectrum of mucosal cell injury during the response phase was observed. The patterns of exfoliation noted were: individual cells, rows (several cells wide) of mucosal cells and entire regions (several hundred μm2). At 1 h after exposure, in some lesions, the injury is difficult to assess because the tracheal surface was either blanketed in exfoliated cells or appeared in total disarray. By 6 h, the lesions were well defined and large flattened cells (130 μm2 in surface area) covered the basement membrane in areas where mucosal cells had exfoliated. Some ciliated cells still remained attached at their base in these areas. These were the findings whether the tissues were taken fresh from the animal or have been maintained in Ussing chambers for up to 6 h. These results show that cellular repair of the tracheal epithelium can be studied in vitro during the first 6 h after injury, even if the injury has occurred in situ

Design and Administration of Patient-Centred Outcome Measures: The Perspectives of Children and Young People with Life-Limiting or Life-Threatening Conditions and Their Family Members

BACKGROUND: Self-reported health data from children with life-limiting conditions is rarely collected. To improve acceptability and feasibility of child and family-centred outcome measures for children, they need to be designed in a way that reflects preferences, priorities and abilities. OBJECTIVES: The aim was to identify preferences for patient-reported outcome measure design (recall period, response format, length, administration mode) to improve the feasibility, acceptability, comprehensibility and relevance of a child and family-centred outcome measure, among children with life-limiting conditions and their family members. METHOD: A semi-structured qualitative interview study seeking the perspectives of children with life-limiting conditions, their siblings and parents on measure design was conducted. Participants were purposively sampled and recruited from nine UK sites. Verbatim transcripts were analysed using framework analysis. RESULTS: A total of 79 participants were recruited: 39 children aged 5–17 years (26 living with a life-limiting condition; 13 healthy siblings) and 40 parents (of children aged 0–17 years). Children found a short recall period and a visually appealing measure with ten questions or fewer most acceptable. Children with life-limiting conditions were more familiar with using rating scales such as numeric and Likert than their healthy siblings. Children emphasised the importance of completing the measure alongside interactions with a healthcare professional to enable them to talk about their responses. While parents assumed that electronic completion methods would be most feasible and acceptable, a small number of children preferred paper. CONCLUSIONS: This study demonstrates that children with life-limiting conditions can engage in communicating preferences regarding the design of a patient-centred outcome measure. Where possible, children should be given the opportunity to participate in the measure development process to enhance acceptability and uptake in clinical practice. Results of this study should be considered in future research on outcome measure development in children

Examining the effect of evaluation sample size on the sensitivity and specificity of COVID-19 diagnostic tests in practice: a simulation study

Background In response to the global COVID-19 pandemic, many in vitro diagnostic (IVD) tests for SARS-CoV-2 have been developed. Given the urgent clinical demand, researchers must balance the desire for precise estimates of sensitivity and specificity against the need for rapid implementation. To complement estimates of precision used for sample size calculations, we aimed to estimate the probability that an IVD will fail to perform to expected standards after implementation, following clinical studies with varying sample sizes. Methods We assumed that clinical validation study estimates met the ‘desirable’ performance (sensitivity 97%, specificity 99%) in the target product profile (TPP) published by the Medicines and Healthcare products Regulatory Agency (MHRA). To estimate the real-world impact of imprecision imposed by sample size we used Bayesian posterior calculations along with Monte Carlo simulations with 10,000 independent iterations of 5,000 participants. We varied the prevalence between 1 and 15% and the sample size between 30 and 2,000. For each sample size, we estimated the probability that diagnostic accuracy would fail to meet the TPP criteria after implementation. Results For a validation study that demonstrates ‘desirable’ sensitivity within a sample of 30 participants who test positive for COVID-19 using the reference standard, the probability that real-world performance will fail to meet the ‘desirable’ criteria is 10.7–13.5%, depending on prevalence. Theoretically, demonstrating the 'desirable' performance in 90 positive participants would reduce that probability to below 5%. A marked reduction in the probability of failure to hit ‘desirable’ specificity occurred between samples of 100 (19.1–21.5%) and 160 (4.3–4.8%) negative participants. There was little further improvement above sample sizes of 160 negative participants. Conclusion Based on imprecision alone, small evaluation studies can lead to the acceptance of diagnostic tests which are likely to fail to meet performance targets when deployed. There is diminished return on uncertainty surrounding an accuracy estimate above a total sample size of 250 (90 positive and 160 negative)

X-Linked Genes and Risk of Orofacial Clefts: Evidence from Two Population-Based Studies in Scandinavia

Background: Orofacial clefts are common birth defects of complex etiology, with an excess of males among babies with cleft lip and palate, and an excess of females among those with cleft palate only. Although genes on the X chromosome have been implicated in clefting, there has been no association analysis of X-linked markers. Methodology/Principal Findings: We added new functionalities in the HAPLIN statistical software to enable association analysis of X-linked markers and an exploration of various causal scenarios relevant to orofacial clefts. Genotypes for 48 SNPs in 18 candidate genes on the X chromosome were analyzed in two population-based samples from Scandinavia (562 Norwegian and 235 Danish case-parent triads). For haplotype analysis, we used a sliding-window approach and assessed isolated cleft lip with or without cleft palate (iCL/P) separately from isolated cleft palate only (iCPO). We tested three statistical models in HAPLIN, allowing for: i) the same relative risk in males and females, ii) sex-specific relative risks, and iii) X-inactivation in females. We found weak but consistent associations with the oral-facial-digital syndrome 1 (OFD1) gene (formerly known as CXORF5) in the Danish iCL/P samples across all models, but not in the Norwegian iCL/P samples. In sex-specific analyses, the association with OFD1 was in male cases only. No analyses showed associations with iCPO in either the Norwegian or the Danish sample. Conclusions: The association of OFD1 with iCL/P is plausible given the biological relevance of this gene. However, the lack of replication in the Norwegian samples highlights the need to verify these preliminary findings in other large datasets. More generally, the novel analytic methods presented here are widely applicable to investigations of the role of X-linked genes in complex traits

Missense mutations that cause Van der Woude syndrome and popliteal pterygium syndrome affect the DNA-binding and transcriptional activation functions of IRF6

Cleft lip and cleft palate (CLP) are common disorders that occur either as part of a syndrome, where structures other than the lip and palate are affected, or in the absence of other anomalies. Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) are autosomal dominant disorders characterized by combinations of cleft lip, CLP, lip pits, skin-folds, syndactyly and oral adhesions which arise as the result of mutations in interferon regulatory factor 6 (IRF6). IRF6 belongs to a family of transcription factors that share a highly conserved N-terminal, DNA-binding domain and a less well-conserved protein-binding domain. To date, mutation analyses have suggested a broad genotype–phenotype correlation in which missense and nonsense mutations occurring throughout IRF6 may cause VWS; in contrast, PPS-causing mutations are highly associated with the DNA-binding domain, and appear to preferentially affect residues that are predicted to interact directly with the DNA. Nevertheless, this genotype–phenotype correlation is based on the analysis of structural models rather than on the investigation of the DNA-binding properties of IRF6. Moreover, the effects of mutations in the protein interaction domain have not been analysed. In the current investigation, we have determined the sequence to which IRF6 binds and used this sequence to analyse the effect of VWS- and PPS-associated mutations in the DNA-binding domain of IRF6. In addition, we have demonstrated that IRF6 functions as a co-operative transcriptional activator and that mutations in the protein interaction domain of IRF6 disrupt this activity

A Feedback Quenched Oscillator Produces Turing Patterning with One Diffuser

Efforts to engineer synthetic gene networks that spontaneously produce patterning in multicellular ensembles have focused on Turing's original model and the “activator-inhibitor” models of Meinhardt and Gierer. Systems based on this model are notoriously difficult to engineer. We present the first demonstration that Turing pattern formation can arise in a new family of oscillator-driven gene network topologies, specifically when a second feedback loop is introduced which quenches oscillations and incorporates a diffusible molecule. We provide an analysis of the system that predicts the range of kinetic parameters over which patterning should emerge and demonstrate the system's viability using stochastic simulations of a field of cells using realistic parameters. The primary goal of this paper is to provide a circuit architecture which can be implemented with relative ease by practitioners and which could serve as a model system for pattern generation in synthetic multicellular systems. Given the wide range of oscillatory circuits in natural systems, our system supports the tantalizing possibility that Turing pattern formation in natural multicellular systems can arise from oscillator-driven mechanisms

Microdeletion del(22)(q12.2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Pierre-Robin sequence (PRS) is defined by micro- and/or retrognathia, glossoptosis and cleft soft palate, either caused by deformational defect or part of a malformation syndrome. Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by mutations in the <it>NF2 </it>gene on chromosome 22q12.2. NF2 is characterized by bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas and ependymomas, and juvenile cataracts. To date, NF2 and PRS have not been described together in the same patient.</p> <p>Case presentation</p> <p>We report a female with PRS (micrognathia, cleft palate), microcephaly, ocular hypertelorism, mental retardation and bilateral hearing loss, who at age 15 was also diagnosed with severe NF2 (bilateral cerebellopontine schwannomas and multiple extramedullary/intradural spine tumors). This is the first published report of an individual with both diagnosed PRS and NF2. High resolution karyotype revealed 46, XX, del(22)(q12.1q12.3), FISH confirmed a deletion encompassing <it>NF2</it>, and chromosomal microarray identified a 3,693 kb deletion encompassing multiple genes including <it>NF2 </it>and <it>MN1 </it>(meningioma 1).</p> <p>Five additional patients with craniofacial dysmorphism and deletion in chromosome 22-adjacent-to or containing <it>NF2 </it>were identified in PubMed and the DECIPHER clinical chromosomal database. Their shared chromosomal deletion encompassed <it>MN1</it>, <it>PITPNB </it>and <it>TTC28</it>. <it>MN1</it>, initially cloned from a patient with meningioma, is an oncogene in murine hematopoiesis and participates as a fusion gene (<it>TEL</it>/<it>MN1</it>) in human myeloid leukemias. Interestingly, <it>Mn1</it>-haploinsufficient mice have abnormal skull development and secondary cleft palate. Additionally, <it>Mn1 </it>regulates maturation and function of calvarial osteoblasts and is an upstream regulator of <it>Tbx22</it>, a gene associated with murine and human cleft palate. This suggests that deletion of <it>MN1 </it>in the six patients we describe may be causally linked to their cleft palates and/or craniofacial abnormalities.</p> <p>Conclusions</p> <p>Thus, our report describes a <it>NF2</it>-adjacent chromosome 22q12.2 deletion syndrome and is the first to report association of <it>MN1 </it>deletion with abnormal craniofacial development and/or cleft palate in humans.</p

Morphological Plant Modeling: Unleashing Geometric and Topological Potential within the Plant Sciences

The geometries and topologies of leaves, flowers, roots, shoots, and their arrangements have fascinated plant biologists and mathematicians alike. As such, plant morphology is inherently mathematical in that it describes plant form and architecture with geometrical and topological techniques. Gaining an understanding of how to modify plant morphology, through molecular biology and breeding, aided by a mathematical perspective, is critical to improving agriculture, and the monitoring of ecosystems is vital to modeling a future with fewer natural resources. In this white paper, we begin with an overview in quantifying the form of plants and mathematical models of patterning in plants. We then explore the fundamental challenges that remain unanswered concerning plant morphology, from the barriers preventing the prediction of phenotype from genotype to modeling the movement of leaves in air streams. We end with a discussion concerning the education of plant morphology synthesizing biological and mathematical approaches and ways to facilitate research advances through outreach, cross-disciplinary training, and open science. Unleashing the potential of geometric and topological approaches in the plant sciences promises to transform our understanding of both plants and mathematics