Holocene record of Tuggerah Lake estuary development on the Australian east coast: sedimentary responses to sea-level fluctuations and climate variability

We investigated the Holocene palaeo-environmental record of the Tuggerah Lake barrier estuary on the south-east coast of Australia to determine the influence of local, regional and global environmental changes on estuary development. Using multi-proxy approaches, we identified significant down-core variation in sediment cores relating to sea-level rise and regional climate change. Following erosion of the antecedent land surface during the post-glacial marine transgression, sediment began to accumulate at the more seaward location at ~8500. years before present, some 1500. years prior to barrier emplacement and ~4000. years earlier than at the landward site. The delay in sediment accumulation at the landward site was a consequence of exposure to wave action prior to barrier emplacement, and due to high river flows of the mid-Holocene post-barrier emplacement. As a consequence of the mid-Holocene reduction in river flows, coupled with a moderate decline in sea-level, the lake experienced major changes in conditions at ~4000. years before present. The entrance channel connecting the lake with the ocean became periodically constricted, producing cyclic alternation between intervals of fluvial- and marine-dominated conditions. Overall, this study provides a detailed, multi-proxy investigation of the physical evolution of Tuggerah Lake with causative environmental processes that have influenced development of the estuary

Do ENSO and coastal development enhance coastal burial of terrestrial carbon?

Carbon cycling on the east coast of Australia has the potential to be strongly affected by El Niño-Southern Oscillation (ENSO) intensification and coastal development (industrialization and urbanization). We performed paleoreconstructions of estuarine sediments from a seagrass-dominated estuary on the east coast of Australia (Tuggerah Lake, New South Wales) to test the hypothesis that millennial-scale ENSO intensification and European settlement in Australia have increased the transfer of organic carbon from land into coastal waters. Our data show that carbon accumulation rates within coastal sediments increased significantly during periods of maximum millennial-scale ENSO intensity ("super-ENSO") and coastal development. We suggest that ENSO and coastal development destabilize and liberate terrestrial soil carbon, which, during rainfall events (e.g., La Niña), washes into estuaries and becomes trapped and buried by coastal vegetation (seagrass in this case). Indeed, periods of high carbon burial were generally characterized as having rapid sedimentation rates, higher content of fine-grained sediments, and increased content of wood and charcoal fragments. These results, though preliminary, suggest that coastal development and ENSO intensificationboth of which are predicted to increase over the coming centurycan enhance capture and burial of terrestrial carbon by coastal ecosystems. These findings have important relevance for current efforts to build an understanding of terrestrial- marine carbon connectivity into global carbon budgets

Is it feasible to conduct a randomised controlled trial of pretransplant exercise (prehabilitation) for patients with multiple myeloma awaiting autologous haematopoietic stem cell transplantation? Protocol for the PREeMPT study

Introduction While myeloma is an incurable malignancy, developments in disease management have led to increased life expectancy in recent years. Treatment typically involves stem-cell transplantation. Increased survival rates equate to more patients living with the burden of both the disease and its treatment for increasing number of years, rendering myeloma a long-term condition. Evidence exists to demonstrate the benefits of exercise for patients recovering from stem-cell transplantation, and prehabilitation—exercise before treatment—has been shown to be effective in other disease areas. To date there has been no research into prehabilitation in patients with myeloma awaiting transplantation treatment. Our objective is to determine whether it is feasible to conduct a randomised controlled trial into pretransplant exercise for patients with multiple myeloma who are awaiting autologous stem-cell transplantation. Methods and analysis This mixed methods study identifies patients with diagnosis of multiple myeloma who have been assigned to the autologous transplantation list and invites them to participate in six weekly sessions of individualised, supervised exercise while awaiting transplantation. Quantitative data to determine feasibility targets include rates of recruitment, adherence and adverse events, and outcome measures including 6 min walking distance test and quality of life. Qualitative interviews are undertaken with a purposive sample of patients to capture their experiences of the study and the intervention

Risk factors for executive function difficulties in preschool and early school-age preterm children

Aim:To investigate the relationship between executive functioning and social and perinatal risk factors in four- to five-year-old preterm children.Methods:141 children born preterm (Results:The preterm group performed significantly more poorly than the comparison group on all intelligence and executive function tests. The parental reports of the preterm and term comparison children's executive function did not differ significantly, but the teachers reported elevated executive function difficulties for the preterm group. Higher social risk, in particular lower educational level of the main caregiver, was the strongest predictor for the preterm children's intelligence and executive function results.Conclusion:Social risk factors are strongly associated with impaired early executive function outcomes in preterm children

Feasibility and benefits of a structured prehabilitation programme prior to autologous stem cell transplantation (ASCT) in patients with myeloma; a prospective feasibility study

Evidence supports the benefits of exercise-based rehabilitation in promoting recovery in myeloma patients following autologous stem-cell transplantation (ASCT). However, ‘prehabilitation’ has never been evaluated prior to ASCT, despite evidence of effectiveness in other cancers. Utilising a mixed method approach the authors investigated the feasibility of a mixed strength and cardiovascular exercise intervention pre-ASCT. Quantitative data were collected to determine feasibility targets; rates of recruitment, adherence and adverse events, including 6 minute walking distance (6MWD) test and patient reported outcome measures (PROMs). Qualitative interviews were undertaken with a purposive sample of patients to capture their experiences of the study and the intervention. The authors recruited 23 patients who attended a mean percentage of 75% scheduled exercise sessions. However, retention rates were limited, with only 14/23 (62%) completing the programme. In these patients, the 6MWD increased from a mean of 346 to 451 m (i.e. by 105 m, 95% CI 62 to 148 m) with no serious adverse events. Whist participants found the exercise programme acceptable and reported improvement in their physical fitness and overall mental health and wellbeing prior to ASCT, the study identified challenges in hospital attendance for the prehabilitation schedule whilst receiving induction or re-induction chemotherapy. Evaluation of digitally-enhanced directed but remote prehabilitation models for this patient group is warranted. Trial registration number NCT0313592

Copy number, linkage disequilibrium and disease association in the FCGR locus.

The response of a leukocyte to immune complexes (ICs) is modulated by receptors for the Fc region of IgG (FcgammaRs), and alterations in their affinity or function have been associated with risk of autoimmune diseases, including systemic lupus erythematosus (SLE). The low-affinity FcgammaR genomic locus is complex, containing regions of copy number variation (CNV) which can alter receptor expression and leukocyte responses to IgG. Combined paralogue ratio tests (PRTs) were used to distinguish three intervals within the FCGR locus which undergo CNV, and to determine FCGR gene copy number (CN). There were significant differences in FCGR3B and FCGR3A CNV profiles between Caucasian, East Asian and Kenyan populations. A previously noted association of low FCGR3B CN with SLE in Caucasians was supported [OR = 1.57 (1.08-2.27), P = 0.018], and replicated in Chinese [OR = 1.65 (1.25-2.18), P = 4 x 10(-4)]. There was no association of FCGR3B CNV with vasculitis, nor with malarial or bacterial infection. Linkage disequilibrium (LD) between multi-allelic FCGR3B CNV and SLE-associated SNPs in the FCGR locus was defined for the first time. Despite LD between FCGR3B CNV and a variant in FcgammaRIIB (I232T) which abolishes inhibitory function, both reduced CN of FCGR3B and homozygosity of the FcgammaRIIB-232T allele were individually strongly associated with SLE risk. Thus CN of FCGR3B, which controls IC responses and uptake by neutrophils, and variations in FCGR2B, which controls factors such as antibody production and macrophage activation, are important in SLE pathogenesis. Further interpretations of contributions to pathogenesis by FcgammaRs must be made in the context of LD involving CNV regions

A method to determine spatial access to specialized palliative care services using GIS

Background: Providing palliative care is a growing priority for health service administratorsworldwide as the populations of many nations continue to age rapidly. In many countries, palliativecare services are presently inadequate and this problem will be exacerbated in the coming years.The provision of palliative care, moreover, has been piecemeal in many jurisdictions and there islittle distinction made at present between levels of service provision. There is a pressing need todetermine which populations do not enjoy access to specialized palliative care services in particular.Methods: Catchments around existing specialized palliative care services in the Canadian provinceof British Columbia were calculated based on real road travel time. Census block face populationcounts were linked to postal codes associated with road segments in order to determine thepercentage of the total population more than one hour road travel time from specialized palliativecare.Results: Whilst 81% of the province\u27s population resides within one hour from at least onespecialized palliative care service, spatial access varies greatly by regional health authority. Based onthe definition of specialized palliative care adopted for the study, the Northern Health Authorityhas, for instance, just two such service locations, and well over half of its population do not havereasonable spatial access to such care.Conclusion: Strategic location analysis methods must be developed and used to accurately locatefuture palliative services in order to provide spatial access to the greatest number of people, andto ensure that limited health resources are allocated wisely. Improved spatial access has thepotential to reduce travel-times for patients, for palliative care workers making home visits, and fortravelling practitioners. These methods are particularly useful for health service planners – andprovide a means to rationalize their decision-making. Moreover, they are extendable to a numberof health service allocation problems

Whatever happened to curriculum theory? Critical realism and curriculum change

In the face of what has been characterised as a ‘crisis’ in curriculum – an apparent decline of some aspects of curriculum studies combined with the emergence of new types of national curriculum which downgrade knowledge – some writers have been arguing for the use of realist theory to address these issues. This paper offers a contribution to this debate, drawing upon critical realism, and especially upon the social theory of Margaret Archer. The paper first outlines the supposed crisis in curriculum, before providing an overview of some of the key tenets of critical realism. The paper concludes by speculating on how critical realism may offer new ways of thinking to inform policy and practice in a key curricular problematic. This is the issue of curriculum change

Study design and methods of the BoTULS trial: a randomised controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A

Background Following a stroke, 55–75% of patients experience upper limb problems in the longer term. Upper limb spasticity may cause pain, deformity and reduced function, affecting mood and independence. Botulinum toxin is used increasingly to treat focal spasticity, but its impact on upper limb function after stroke is unclear. The aim of this study is to evaluate the clinical and cost effectiveness of botulinum toxin type A plus an upper limb therapy programme in the treatment of post stroke upper limb spasticity. Methods Trial design : A multi-centre open label parallel group randomised controlled trial and economic evaluation. Participants : Adults with upper limb spasticity at the shoulder, elbow, wrist or hand and reduced upper limb function due to stroke more than 1 month previously. Interventions : Botulinum toxin type A plus upper limb therapy (intervention group) or upper limb therapy alone (control group). Outcomes : Outcome assessments are undertaken at 1, 3 and 12 months. The primary outcome is upper limb function one month after study entry measured by the Action Research Arm Test (ARAT). Secondary outcomes include: spasticity (Modified Ashworth Scale); grip strength; dexterity (Nine Hole Peg Test); disability (Barthel Activities of Daily Living Index); quality of life (Stroke Impact Scale, Euroqol EQ-5D) and attainment of patient-selected goals (Canadian Occupational Performance Measure). Health and social services resource use, adverse events, use of other antispasticity treatments and patient views on the treatment will be compared. Participants are clinically reassessed at 3, 6 and 9 months to determine the need for repeat botulinum toxin type A and/or therapy. Randomisation : A web based central independent randomisation service. Blinding : Outcome assessments are undertaken by an assessor who is blinded to the randomisation group. Sample size : 332 participants provide 80% power to detect a 15% difference in treatment successes between intervention and control groups. Treatment success is defined as improvement of 3 points for those with a baseline ARAT of 0–3 and 6 points for those with ARAT of 4–56