Making room for faith in English dispute resolution proceedings

The case of Baby MB (An NHS Trust v MB (A child represented by the CAFCASS as Guardian ad Litem) [2006] EWHC 507 (Fam) [2006] 2FLR 319 reveals some of the difficulties faced by persons of faith when they are involved in legal proceedings in the English law courts. It raises the question of whether faith is relevant when decisions are taken in court, and if so how it is relevant. What high profile healthcare cases like this also illustrate is that there are legal cases that involve not just legal issues, but also ethical and faith issues. However, when these cases come to court they are framed as though they are primarily legal disputes that require a purely legal solution. While judges address the legal issues, they are reluctant to address the ethical and faith issues, and if they do address the ethical and faith issues, they address them in strictly legal terms. These difficulties are not restricted to one faith but encompass all faiths, and they are not restricted to litigants but also include representatives of Christian churches who make submissions to court. Although the difficulties are often revealed in healthcare cases they are not restricted to these cases but include other types of legal case and extend to employment tribunals. These cases raise important questions about how courts and tribunals deal with persons of faith, how we understand conflict and resolve disputes, the nature and aim of law, the relationship between law, ethics and religion, the role of judges, and how we perceive and deal procedurally with cases that involve issues of faith. This thesis will explore these issues, and discuss whether room can be made for faith in English Dispute Resolution proceedings, and if so, how this might be accomplished.A.H.R.C

A Nutritious bread

The data reported in this paper were taken from theses presented by Elizabeth R. Harding and Elizabeth Hamilton Bay to the Faculty of the Graduate school of the University of Missouri in partial fulfillment of the requirements for the degree of Master of Arts and from a special problem by Dorothy Tyrrell, a graduate student--P. [3].Digitized 2007 AES.Includes bibliographical references (pages 23-24)

'A beginning and not the end’: Work after a diagnosis of dementia

YesWhile there is a growing literature on the experiences of disabled workers, this article presents an account of a work experience not frequently documented: being employed while living with dementia. It does this through the account of Elizabeth Draper, an NHS Hospital Trust manager, who received a diagnosis of dementia while employed. The article offers new ways of conceptualizing the struggles of disabled workers to continue with their project of self-becoming through work. It shows how work practices can enact violence through ‘non-recognition’ and how workers can subvert this violence to create opportunities for future development

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

Biobehavioral effects of Tai Chi Qigong in men with prostate cancer: Study design of a three-arm randomized clinical trial.

Fatigue is often one of the most commonly reported symptoms in prostate cancer survivors, but it is also one of the least understood cancer-related symptoms. Fatigue is associated with psychological distress, disruptions in sleep quality, and impairments in health-related quality of life. Moreover, inflammatory processes and changes related to the hypothalamic-pituitary-adrenal (HPA) axis and/or autonomic nervous system may also play a role in cancer-related fatigue. Thus, effective treatments for fatigue in prostate cancer survivors represent a current unmet need. Prior research has shown that Tai Chi Qigong, a mind-body exercise intervention, can improve physical and emotional health. Herein, we describe the protocol of the ongoing 3-arm randomized controlled Health Empowerment & Recovery Outcomes (HERO) clincal trial. One hundred sixty-six prostate cancer survivors with fatigue are randomized to a modified Tai Chi Qigong intervention (TCQ), intensity-matched body training intervention (BT), or usual care (UC) condition. Guided by biopsychosocial and psychoneuroimmunology models, we propose that TCQ, as compared to BT or UC will: i) reduce fatigue (primary outcome) in prostate cancer survivors; ii) reduce inflammation; and iii) regulate the expression of genes from two major functional clusters: a) inflammation, vasodilation and metabolite sensing and b) energy and adrenergic activation. Assessments are conducted at baseline, the 6-week midpoint of the intervention, and 1 week, 3 months, and 12 months post-intervention. If our findings show that TCQ promotes recovery from prostate cancer and its treatment, this type of intervention can be integrated into survivorship care plans as the standard of care. The study's findings will also provide novel information about underlying biobehavioral mechanisms of cancer-related fatigue. Trial registration number:NCT03326713; clinicaltrials.gov

Supermassive black holes at high redshifts

MeV blazars are the most luminous persistent sources in the Universe and emit most of their energy in the MeV band. These objects display very large jet powers and accretion luminosities and are known to host black holes with a mass often exceeding $10^9 M_{\odot}$. An MeV survey, performed by a new generation MeV telescope which will bridge the entire energy and sensitivity gap between the current generation of hard X-ray and gamma-ray instruments, will detect $>$1000 MeV blazars up to a redshift of $z=5-6$. Here we show that this would allow us: 1) to probe the formation and growth mechanisms of supermassive black holes at high redshifts, 2) to pinpoint the location of the emission region in powerful blazars, 3) to determine how accretion and black hole spin interplay to power the jet.Comment: 7 pages, 4 figure. Submitted to the Astro2020 call for Science White Paper

A spatial judgement task to determine background emotional state in laboratory rats (Rattus norvegicus)

Humans experiencing different background emotional states display contrasting cognitive (e.g. judgement) biases when responding to ambiguous stimuli. We have proposed that such biases may be used as indicators of animal emotional state. Here, we use a spatial judgement task, in which animals are trained to expect food in one location and not another, to determine whether rats in relatively positive or negative emotional states respond differently to ambiguous stimuli of intermediate spatial location. We housed 24 rats with environmental enrichment for seven weeks. Enrichment was removed for half the animals prior to the start of training (‘U’: unenriched) to induce a relatively negative emotional state, whilst being left in place for the remaining rats (‘E’: enriched). After six training days, the rats successfully discriminated between the rewarded and unrewarded locations in terms of an increased latency to arrive at the unrewarded location, with no housing treatment difference. The subjects then received three days of testing in which three ambiguous ‘probe’ locations, intermediate between the rewarded and unrewarded locations, were introduced. There was no difference between the treatments in the rats’ judgement of two out of the three probe locations, the exception being when the ambiguous probe was positioned closest to the unrewarded location. This result suggests that rats housed without enrichment, and in an assumed relatively negative emotional state, respond differently to an ambiguous stimulus compared to rats housed with enrichment, providing evidence that cognitive biases may be used to assess animal emotional state in a spatial judgement task

Isogenic Pairs of hiPSC-CMs with Hypertrophic Cardiomyopathy/LVNC-Associated ACTC1 E99K Mutation Unveil Differential Functional Deficits

Hypertrophic cardiomyopathy (HCM) is a primary disorder of contractility in heart muscle. To gain mechanistic insight and guide pharmacological rescue, this study models HCM using isogenic pairs of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the E99K-ACTC1 cardiac actin mutation. In both 3D engineered heart tissues and 2D monolayers, arrhythmogenesis was evident in all E99K-ACTC1 hiPSC-CMs. Aberrant phenotypes were most common in hiPSC-CMs produced from the heterozygote father. Unexpectedly, pathological phenotypes were less evident in E99K-expressing hiPSC-CMs from the two sons. Mechanistic insight from Ca2+ handling expression studies prompted pharmacological rescue experiments, wherein dual dantroline/ranolazine treatment was most effective. Our data are consistent with E99K mutant protein being a central cause of HCM but the three-way interaction between the primary genetic lesion, background (epi)genetics, and donor patient age may influence the pathogenic phenotype. This illustrates the value of isogenic hiPSC-CMs in genotype-phenotype correlations

Muscle Atrophy Marker Expression Differs between Rotary Cell Culture System and Animal Studies

Muscular atrophy, defined as the loss of muscle tissue, is a serious issue for immobilized patients on Earth and for humans during spaceflight, where microgravity prevents normal muscle loading. In vitro modeling is an important step in understanding atrophy mechanisms and testing countermeasures before animal trials. The most ideal environment for modeling must be empirically determined to best mimic known responses in vivo. To simulate microgravity conditions, murine C2C12 myoblasts were cultured in a rotary cell culture system (RCCS). Alginate encapsulation was compared against polystyrene microcarrier beads as a substrate for culturing these adherent muscle cells. Changes after culture under simulated microgravity were characterized by assessing mRNA expression of MuRF1, MAFbx, Caspase 3, Akt2, mTOR, Ankrd1, and Foxo3. Protein concentration of myosin heavy chain 4 (Myh4) was used as a differentiation marker. Cell morphology and substrate structure were evaluated with brightfield and fluorescent imaging. Differentiated C2C12 cells encapsulated in alginate had a significant increase in MuRF1 only following simulated microgravity culture and were morphologically dissimilar to normal cultured muscle tissue. On the other hand, C2C12 cells cultured on polystyrene microcarriers had significantly increased expression of MuRF1, Caspase 3, and Foxo3 and easily identifiable multinucleated myotubes. The extent of differentiation was higher in simulated microgravity and protein synthesis more active with increased Myh4, Akt2, and mTOR. The in vitro microcarrier model described herein significantly increases expression of several of the same atrophy markers as in vivo models. However, unlike animal models, MAFbx and Ankrd1 were not significantly increased and the fold change in MuRF1 and Foxo3 was lower than expected. Using a standard commercially available RCCS, the substrates and culture methods described only partially model changes in mRNAs associated with atrophy in vivo