A Right to a Child of One’s Own? The Legal Justification in Limiting Access to Assisted Reproductive Treatment

The revolution in IVF treatment in recent years has resulted in the conception of over 4 million babies worldwide prompting stricter legal regulation and control of medical practice. This article explores the demand and availability for IVF, and how international and domestic legislation operates and applies in relation to the notion of ‘a right to a child.’ It considers whether there is, or should be, an established right to such treatment and the extent to which interferences by the state to prohibit or limit assisted reproductive treatments are legitimately justified

Reproductive Isolation, in Individuals and During Evolution, as Result of Gross Genomic Rearrangement in Pigs, Birds and Dinosaurs

Chromosomal (karyotypic) analysis in animals is performed for three primary reasons: to diagnose genetic disease; to map genes to their place in the genome and to retrace evolutionary events by cross species comparison. Technology for analysis has progressed from chromosome banding (cytogenetics), to fluorescence in-situ hybridisation (FISH - molecular cytogenetics) through to microarrays and ultimately whole genome sequence analysis (cytogenomics or chromonomics). Indeed, the past 10-15 years has seen a revolution in whole genome sequencing, first with the human genome project, followed by those of key model and agricultural species and, more recently, ~60 de novo avian genome assemblies. Whole genome analysis provides detailed insight into the biology of chromosome rearrangements that occur both in individuals (for diagnostic purposes) and at an evolutionary level. It permits the study of gene mapping, trait linkage, phylogenomics, and gross genomic organisation and change. An essential pre-requisite however is an unbroken length of contiguous DNA sequence along the length of each chromosome. Most recent de novo genome assemblies fall short of this level of resolution producing lengths of contiguous sequence that are sub-chromosomal in size (scaffolds). Chromosome rearrangements can affect reproductive capability at an individual level (causing reduced fertility) and at a population level leading to reproductive isolation and subsequent speciation. The purpose of this thesis was to implement a step change in the combination of FISH technology with genome sequence data to provide greater insight into the nature of chromosomal rearrangement at an individual and evolutionary level. It therefore had four specific aims: The first was to isolate sub-telomeric sequences from the pig, cattle and chicken genome assemblies to develop a tool for the rapid screening of chromosome rearrangements. Now routinely used for porcine translocation screening (and in the future bovine screening), development work revealed serious integrity errors in the pig genome. The second aim was to isolate evolutionary conserved sequences from avian chromosomes to create a means of screening for macro-and microchromosomal rearrangements in birds. Results confirmed the hypothesis that microchromosomal rearrangements were rare in birds, except for previously known whole chromosomal fusions. The third was to use the above tools to complete scaffold based genome assemblies in two key avian species - the peregrine falcon and the pigeon. Finally, bioinformatic tools were used to infer the overall genome structure of hypothetical saurian and avian ancestors. Retracing of the evolutionary changes that occurred up until the emergence of birds allowed an assessment of chromosome evolution along the saurischia-maniraptora- avialae lineage. Analysis of evolutionary breakpoint regions (EBRs) allowed testing of the hypothesis that the ontology of genes within EBRs corresponded to measurable phenotypic change in the lineage under investigation. An enrichment of genes associated with body height corresponded to rapid size change in the dinosaur linage that led to modern birds. Taken together, these results paint a picture of a genome that, from about 260 million years ago formed a 'signature' highly successful avian-dinosaur karyotype that remained largely unchanged interchromosomally to the present day. These results represent significant insight into amniote genomic organization with the added benefit of developing tools that are widely applicable and transferrable for commercial animal breeding, for constructing de novo genome assemblies and for reconstructing, by inference, the overall genomic structure and evolution of extinct animals

Where's the logic in commissioning?: exploring the influence of institutional logics on inter-organisational working in the English National Health

This thesis explores inter-organisational relationships and behaviours when complex healthcare pathways are planned, designed, procured and implemented in the English National Health Service (NHS) in a process known as commissioning. Commissioning and healthcare provision in the NHS is organised separately and operates as a quasi-market system. Clinical Commissioning Groups (CCGs) commission the majority of local healthcare for their populations and purchase services accordingly from many different types of healthcare provider organisations. Poor integration between different provider organisations has been suggested a contributing factor to the unsustainable demands the NHS is currently facing. New models of provision have been recommended in policy as a commissioning strategy to improve integration and these require collaboration and effective inter-organisational working between organisations. Healthcare is a highly complex institutional field and the institutional logics perspective offers a theoretical framework to explore how institutions embedded within a field guide behaviour. Bureaucratic, market, corporate and professional logics are known to exist in healthcare and can be used to break down institutional complexity into abstract constructs to understand the demands organisations face but enquiry has tended to focus on sole organisations rather than inter-organisational behaviour. However the institutional logics perspective offers the opportunity to explore the influence of institutional demands on inter-organisational relationships in complex institutional fields. This study sought to explain how logics influence inter-organisational behaviours as organisations work together to develop integrated care pathways. Using stroke service commissioning as a contextual example, the study explored three comparative case studies of the commissioning processes used to reorganise and develop stroke services into integrated care pathways across acute and community providers. Using methods associated with the ethnographic tradition, fifty-four semi-structured interviews with commissioners, providers, patient representatives and advisory bodies were completed, ten commissioning meetings were observed and strategic documentation for each organisation were collected. Thematic analysis was used to identify key themes which were then viewed through the institutional logics framework lens to explore how logics were present and influencing the commissioning processes as they progressed. The empirical findings suggest that an organisation’s interpretation of the institutional environment influences how an organisation and their individuals behave. In turn those behaviours influence how the organisations they are attempting to work with respond. Establishing a shared goal between the organisations was crucial but an organisations response to institutional demands may make this difficult to achieve. Collaboration was considered key to successful integration but this was only successful when commissioners were able to negotiate complex logics to facilitate shared goals and means of achieving them. This was most successful when organisations co-opted an alternative logic to compliment the organisations they were attempting to work with for different phases of the commissioning process. When complimentary logics were op-opted, organisations were better equipped to work collaboratively but if contradictory logics were in play, there was increased risk of inter-organisational relationships breaking down. Some commissioners used this strategy effectively to develop inter-organisational relationships while hiding the logic which informed their underlying goal which allowed them to maintain control of the commissioning process. This suggested that an organisations interpretation of the institutional environment and skills at using logics to manipulate the means of achieving goals was important. In conclusion, when logics are used by organisations to compliment the beliefs and behaviours of other organisations when they attempt to work together, they are able to establish effective inter-organisational relationships that allow collaborative work towards shared goals. This may be an important characteristic of commissioning organisations as they attempt to commission new models of integrated care

Pain and Sickness Behavior Associated with Corneal Lesions in Dairy Calves

Infectious bovine keratoconjunctivitis (IBK) is a common corneal disease of calves that adversely affects animal welfare by causing pain and weight loss. Identifying behavioral indicators of pain and sickness in calves with IBK is necessary for designing studies that aim to identify effective means of pain mitigation. Consistent with principles of the 3Rs for animal use in research, data from a randomized blinded challenge study was used to identify and describe variation of behaviors that could serve as reliable indicators of pain and sickness in calves with corneal injuries. Behavioral observations were collected from 29 Holstein calves 8 to 12 weeks of age randomly allocated to one of three treatments: (1) corneal scarification only, (2) corneal scarification with inoculation with Moraxella bovoculi and (3) corneal scarification with inoculation with Moraxella bovis. Behavior was continuously observed between time 1230 - 1730 h on day -1 (baseline time period) and day 0 (scarification time period). Corneal scarification and inoculation occurred between 0800 - 1000 h on day 0. Frequency of head-directed behaviors (head shaking, head rubbing, head scratching) and durations of head rubbing, feeding, standing with head lifted, lying with head lifted and sleeping were compared between study days and groups. Following scarification, the frequency of head-directed behavior significantly increased (p = 0.0001), as did duration of head rubbing (p=0.02). There was no significant effect of trial, trial day, treatment or treatment-day interaction on other behaviors studied. Our study demonstrated that head-directed behavior, such as head shaking, rubbing and scratching, was associated with scarification of eyes using an IBK challenge model, but sickness behavior was not observed

A transdiagnostic comparison of enhanced cognitive behaviour therapy (CBT-E) and interpersonal psychotherapy in the treatment of eating disorders.

Eating disorders may be viewed from a transdiagnostic perspective and there is evidence supporting a transdiagnostic form of cognitive behaviour therapy (CBT-E). The aim of the present study was to compare CBT-E with interpersonal psychotherapy (IPT), a leading alternative treatment for adults with an eating disorder. One hundred and thirty patients with any form of eating disorder (body mass index >17.5 to <40.0) were randomized to either CBT-E or IPT. Both treatments involved 20 sessions over 20 weeks followed by a 60-week closed follow-up period. Outcome was measured by independent blinded assessors. Twenty-nine participants (22.3%) did not complete treatment or were withdrawn. At post-treatment 65.5% of the CBT-E participants met criteria for remission compared with 33.3% of the IPT participants (p < 0.001). Over follow-up the proportion of participants meeting criteria for remission increased, particularly in the IPT condition, but the CBT-E remission rate remained higher (CBT-E 69.4%, IPT 49.0%; p = 0.028). The response to CBT-E was very similar to that observed in an earlier study. The findings indicate that CBT-E is potent treatment for the majority of outpatients with an eating disorder. IPT remains an alternative to CBT-E, but the response is less pronounced and slower to be expressed. CURRENT CONTROLLED TRIALS: ISRCTN 15562271

Patterns of microchromosome organization remain highly conserved throughout avian evolution

The structure and organization of a species genome at a karyotypic level, and in interphase nuclei, have broad functional significance. Although regular sized chromosomes are studied extensively in this regard, microchromosomes, which are present in many terrestrial vertebrates, remain poorly explored. Birds have more cytologically indistinguishable microchromosomes (~ 30 pairs) than other vertebrates; however, the degree to which genome organization patterns at a karyotypic and interphase level differ between species is unknown. In species where microchromosomes have fused to other chromosomes, they retain genomic features such as gene density and GC content; however, the extent to which they retain a central nuclear position has not been investigated. In studying 22 avian species from 10 orders, we established that, other than in species where microchromosomal fusion is obvious (Falconiformes and Psittaciformes), there was no evidence of microchromosomal rearrangement, suggesting an evolutionarily stable avian genome (karyotypic) organization. Moreover, in species where microchromosomal fusion has occurred, they retain a central nuclear location, suggesting that the nuclear position of microchromosomes is a function of their genomic features rather than their physical size

Prioritising models of healthcare service delivery for a more sustainable health system: a Delphi study of Australian health policy, clinical practice and management, academic and consumer stakeholders

Published online: 18 March 2021Objectives. Healthcare expenditure is growing at an unsustainable rate in developed countries. A recent scoping review identified several alternative healthcare delivery models with the potential to improve health system sustainability. Our objective was to obtain input and consensus from an expert Delphi panel about which alternative models they considered most promising for increasing value in healthcare delivery in Australia and to contribute to shaping a research agenda in the field. Methods. The panel first reviewed a list of 84 models obtained through the preceding scoping review and contributed additional ideas in an open round. In a subsequent scoring round, the panel rated the priority of each model in terms of its potential to improve health care sustainability in Australia. Consensus was assumed when 50% of the panel rated a model as (very) high priority (consensus on high priority) or as not a priority or low priority (consensus on low priority). Results. Eighty-two of 149 invited participants (55%) representing all Australian states/territories and wide expertise completed round one; 71 completed round two. Consensus on high priority was achieved for 59 alternative models; 14 were rated as (very) high priority by 70% of the panel. Top priorities included improving medical service provision in aged care facilities, providing single-point-access multidisciplinary care for people with chronic conditions and providing tailored early discharge and hospital at home instead of in-patient care. No consensus was reached on 47 models, but no model was deemed low priority. Conclusions. Input froman expert stakeholder panel identified healthcare deliverymodels not previously synthesised in systematic reviews that are a priority to investigate. Strong consensus exists among stakeholders regarding which models require the most urgent attention in terms of (cost-)effectiveness research. These findings contribute to shaping a research agenda on healthcare delivery models and where stakeholder engagement in Australia is likely to be high. What is known about the topic? Healthcare expenditure is growing at an unsustainable rate in high-income countries worldwide. A recent scoping review of systematic reviews identified a substantial body of evidence about the effects of a wide range of models of healthcare service delivery that can inform health system improvements. Given the large number of systematic reviews available on numerous models of care, a method for gaining consensus on the models of highest priority for implementation (where evidence demonstrates this will lead to beneficial effects and resource savings) or for further research (where evidence about effects is uncertain) in the Australian context is warranted. What does this paper add? This paper describes a method for reaching consensus on high-priority alternative models of service delivery in Australia. Stakeholders with leadership roles in health policy and government organisations, hospital and primary care networks, academic institutions and consumer advocacy organisations were asked to identify and rate alternative models based on their knowledge of the healthcare system. We reached consensus among 70% of stakeholders that improving medical care in residential aged care facilities, providing single-point-access multidisciplinary care for patients with a range of chronic conditions and providing early discharge and hospital at home instead of in-patient stay for people with a range of conditions are of highest priority for further investigation. What are the implications for practitioners? Decision makers seeking to optimise the efficiency and sustainability of healthcare service delivery in Australia could consider the alternative models rated as high priority by the expert stakeholder panel in this Delphi study. These models reflect the most promising alternatives for increasing value in the delivery of health care in Australia based on stakeholders’ knowledge of the health system. Although they indicate areas where stakeholder engagement is likely to be high, further research is needed to demonstrate the effectiveness and costeffectiveness of some of these models.Polina Putrik, Rebecca Jessup, Rachelle Buchbinder, Paul Glasziou, Jonathan Karnon and Denise A. O’Conno

Case Report: An MRI Traumatic Brain Injury Longitudinal Case Study at 7 Tesla: Pre- and Post-injury Structural Network and Volumetric Reorganization and Recovery.

Importance: A significant limitation of many neuroimaging studies examining mild traumatic brain injury (mTBI) is the unavailability of pre-injury data. Objective: We therefore aimed to utilize pre-injury ultra-high field brain MRI and compare a collection of neuroimaging metrics pre- and post-injury to determine mTBI related changes and evaluate the enhanced sensitivity of high-resolution MRI. Design: In the present case study, we leveraged multi-modal 7 Tesla MRI data acquired at two timepoints prior to mTBI (23 and 12 months prior to injury), and at two timepoints post-injury (2 weeks and 8 months after injury) to examine how a right parietal bone impact affects gross brain structure, subcortical volumetrics, microstructural order, and connectivity. Setting: This research was carried out as a case investigation at a single primary care site. Participants: The case participant was a 38-year-old female selected for inclusion based on a mTBI where a right parietal impact was sustained. Main outcomes: The main outcome measurements of this investigation were high spatial resolution structural brain metrics including volumetric assessment and connection density of the white matter connectome. Results: At the first scan timepoint post-injury, the cortical gray matter and cerebral white matter in both hemispheres appeared to be volumetrically reduced compared to the pre-injury and subsequent post-injury scans. Connectomes produced from whole-brain diffusion-weighted probabilistic tractography showed a widespread decrease in connectivity after trauma when comparing mean post-injury and mean pre-injury connection densities. Findings of reduced fractional anisotropy in the cerebral white matter of both hemispheres at post-injury time point 1 supports reduced connection density at a microstructural level. Trauma-related alterations to whole-brain connection density were markedly reduced at the final scan timepoint, consistent with symptom resolution. Conclusions and Relevance: This case study investigates the structural effects of traumatic brain injury for the first time using pre-injury and post-injury 7 Tesla MRI longitudinal data. We report findings of initial volumetric changes, decreased structural connectivity and reduced microstructural order that appear to return to baseline 8 months post-injury, demonstrating in-depth metrics of physiological recovery. Default mode, salience, occipital, and executive function network alterations reflect patient-reported hypersomnolence, reduced cognitive processing speed and dizziness

The concordance of directly and indirectly measured built environment attributes and physical activity adoption

<p/> <p>Background</p> <p>Physical activity (PA) adoption is essential for obesity prevention and control, yet ethnic minority women report lower levels of PA and are at higher risk for obesity and its comorbidities compared to Caucasians. Epidemiological studies and ecologic models of health behavior suggest that built environmental factors are associated with health behaviors like PA, but few studies have examined the association between built environment attribute concordance and PA, and no known studies have examined attribute concordance and PA adoption.</p> <p>Purpose</p> <p>The purpose of this study was to associate the degree of concordance between directly and indirectly measured built environment attributes with changes in PA over time among African American and Hispanic Latina women participating in a PA intervention.</p> <p>Method</p> <p>Women (<it>N </it>= 410) completed measures of PA at Time 1 (T1) and Time 2 (T2); environmental data collected at T1 were used to compute concordance between directly and indirectly measured built environment attributes. The association between changes in PA and the degree of concordance between each directly and indirectly measured environmental attribute was assessed using repeated measures analyses.</p> <p>Results</p> <p>There were no significant associations between built environment attribute concordance values and change in self-reported or objectively measured PA. Self-reported PA significantly increased over time (<it>F</it>(1,184) = 7.82, <it>p </it>= .006), but this increase did not vary by ethnicity or any built environment attribute concordance variable.</p> <p>Conclusions</p> <p>Built environment attribute concordance may not be associated with PA changes over time among minority women. In an effort to promote PA, investigators should clarify specific built environment attributes that are important for PA adoption and whether accurate perceptions of these attributes are necessary, particularly among the vulnerable population of minority women.</p