The effect of intravenous iron on postoperative transfusion requirements in hip fracture patients: study protocol for a randomized controlled trial

Background Anaemia following hip fracture is common. Approximately 30 to 45% of patients have haemoglobin concentrations below population norms on admission, and around 10% are severely anaemic. Anaemia on admission, and in the postoperative period, is associated with poor outcomes with regard to mobility, postoperative mortality and readmission. There is currently no clear consensus on the optimal method of managing perioperative anaemia in this group of frail patients with frequent comorbidity. Liberal red cell transfusion in the postoperative period does not appear to improve outcome, whereas tranexamic acid appears to reduce transfusion rate at the expense of increased cardiovascular morbidity. There are encouraging results from one centre with the use of agents to stimulate red cell production, including intravenous iron and erythropoietin. UK practice differs significantly from these patients and these studies, and it is not clear whether these promising results will translate to the UK population. Methods/Design This is a single-centre randomized controlled parallel group trial, in a British university hospital.Randomization is achieved using a website and computer-generated concealed tables. Participants are 80 patients 70 years or over with acute hip fracture undergoing operative repair. The intervention group receive three daily infusions of 200 mg iron sucrose, starting within 24 hours of admission. The control group receive standard hospital care at the discretion of the clinical team. Red cell transfusions for each group are given in accordance with standard clinical triggers. The primary outcome is an increase in mean reticulocyte count in the intervention group at day 7. Secondary outcome measures include haemoglobin concentrations, early and late transfusion rates, infectious and cardiovascular complications, mobility and 30-day mortality. Discussion This is a pilot study to demonstrate haematopoietic efficacy of intravenous iron in this setting. Hence, we have chosen to measure change in reticulocyte count rather than the more clinically relevant differences in haemoglobin concentration or transfusion rate. If our results are positive, the study will provide the necessary information for development of a full-scale trial of intravenous iron. Trial registration Current Controlled Trials ISRCTN76424792; UK Medicines and Healthcare products Regulatory Authority (EuDRACT: 2011-003233-34)

A comparison of analytical approaches to investigate associations for accelerometry-derived physical activity spectra with health and developmental outcomes in children

Under embargo until: 2021-09-20The use of high-resolution physical activity intensity spectra obtained from accelerometry can improve knowledge of associations with health and development beyond the use of traditional summary measures of intensity. The aim of the present study was to compare three different approaches for determining associations for spectrum descriptors of physical activity (the intensity gradient, principal component analysis, and multivariate pattern analysis) with relevant outcomes in children. We used two datasets including physical activity spectrum data (ActiGraph GT3X+) and 1) a cardiometabolic health outcome in 841 schoolchildren and 2) a motor skill outcome in 1081 preschool children. We compared variance explained (R2) and associations with the outcomes for the intensity gradient (slope) across the physical activity spectra, a two-component principal component model describing the physical activity variables, and multivariate pattern analysis using the intensity spectra as the explanatory data matrices. Results were broadly similar for all analytical approaches. Multivariate pattern analysis explained the most variance in both datasets, likely resulting from use of more of the information available from the intensity spectra. Yet, volume and intensity dimensions of physical activity are not easily disentangled and their relative importance may be interpreted differently using different methodology.acceptedVersio

Sex-dependent influence of endogenous estrogen in pulmonary hypertension

Rationale: The incidence of pulmonary arterial hypertension (PAH) is greater in women suggesting estrogens may play a role in the disease pathogenesis. Experimentally, in males exogenously administered estrogen can protect against PH; however in models that display female susceptibility estrogens may play a causative role. Objectives: To clarify the influence of endogenous estrogen and gender in PH and assess the therapeutic potential of a clinically available aromatase inhibitor. Methods: We interrogated the effect of reduced endogenous estrogen in males and females using the aromatase inhibitor, anastrozole, in two models of PH; the hypoxic mouse and Sugen 5416/hypoxic rat. We also determined the effects of gender on pulmonary expression of aromatase in these models and in lungs from PAH patients. Results: Anastrozole attenuated PH in both models studied, but only in females. To verify this effect was due to reduced estrogenic activity we confirmed that in hypoxic mice inhibition of estrogen receptor alpha also has a therapeutic effect specifically in females. Female rodent lung displays increased aromatase and decreased BMPR2 and Id1 expression compared to male. Anastrozole treatment reversed the impaired BMPR2 pathway in females. Increased aromatase expression was also detected in female human pulmonary artery smooth muscle cells compared to male. Conclusions: The unique phenotype of female pulmonary arteries facilitates the therapeutic effects of anastrozole in experimental PH confirming a role for endogenous estrogen in the disease pathogenesis in females and suggests aromatase inhibitors may have therapeutic potential

Femoral Nerve Block Intervention in Neck of Femur Fracture (FINOF): a randomized controlled trial

Objective Fractured neck of femur is a severely painful condition with significant mortality and morbidity. We investigated whether early and continuous use of femoral nerve block can improve pain on movement and mobility after surgery in older participants with fragility neck of femur fracture. Design Prospective single centre, randomised controlled pragmatic trial. Setting Secondary care, acute NHS Trust, UK. Participants Participants admitted with a history and examination suggesting fractured neck of femur. Intervention Immediate continuous femoral nerve block via catheter or standard analgesia. Results One hundred and forty one participants were recruited, with 23 excluded. No significant difference was detected between cumulative dynamic pain scores (standard care (n = 56) vs 4 intervention (n = 55) 20 (IQR 15-24) vs 20 (15-23) p=0.51) or cumulated ambulation scores (standard care vs intervention 6 (5-9) vs 7 (5-10) p=0.76). There were no statistically different differences in secondary outcomes except cumulative pain at rest: 5 (0.5-6.5) in the standard care group and 2 (0-5) in the intervention group (p=0.043). Conclusions Early application of continuous femoral nerve block compared with standard systemic analgesia did not result in improved dynamic pain scores or superior post-operative ambulation. This technique may provide superior pain relief at rest. Continuous femoral nerve block did not delay initial control of pain, or mobilisation after surgery

FMDV replicons encoding green fluorescent protein are replication competent

The study of replication of viruses that require high bio-secure facilities can be accomplished with less stringent containment using non-infectious 'replicon' systems. The FMDV replicon system (pT7rep) reported by Mclnerney et al. (2000) was modified by the replacement of sequences encoding chloramphenicol acetyl-transferase (CAT) with those encoding a functional L proteinase (Lpro) linked to a bi-functional fluorescent/antibiotic resistance fusion protein (green fluorescent protein/puromycin resistance, [GFP-PAC]). Cells were transfected with replicon-derived transcript RNA and GFP fluorescence quantified. Replication of transcript RNAs was readily detected by fluorescence, whilst the signal from replication-incompetent forms of the genome was >2-fold lower. Surprisingly, a form of the replicon lacking the Lpro showed a significantly stronger fluorescence signal, but appeared with slightly delayed kinetics. Replication can, therefore, be quantified simply by live-cell imaging and image analyses, providing a rapid and facile alternative to RT-qPCR or CAT assays

Nationwide seagrass mapping using analysis-ready Sentinel-2 and PlanetScope data to support the Nationally Determined Contributions of Seychelles

There is a notable lack of spatially-explicit knowledge on seagrass meadows in many parts of the world, which hinders seagrass research, conservation, and carbon accounting efforts. With the recent introduction of the pan-tropical PlanetScope basemaps onto the Google Earth Engine (GEE) cloud platform through the Planet & Norway’s International Climate and Forests Initiative (NICFI), anyone can now freely access and process the entire pan-tropical archive of the PlanetScope between 2015 and today. In comparison to other public optical satellite archives available within GEE, like the Sentinel-2, Planet’s imagery has a shorter global revisit interval of 30.3 h, a better spatial resolution of 4.77m, but a worse spectral resolution of only the blue, green, red and near infrared bands. Despite the NICFI’s focus on terrestrial forest monitoring in the tropics, a vast pan-tropical area of optically shallow coastal waters is included in the cloud-native public archives. This paves the way for high-resolution seamless pan-tropical seagrass mapping with large time and cost efficiency. Here, we adapt our multitemporal composition approach on GEE, initially developed for Sentinel-2, to the six-year PlanetScope archive, to map the nationwide seagrass meadows in Seychelles. We compare the feasibility and performance of the PlanetScope data to Sentinel-2 in national seagrass mapping, leveraging the synergy of cloud computing, artificial intelligence, and open reference data. The development of this approach could and will provide a comprehensive blueprint seagrass mapping and monitoring system to quantify national seagrass blue carbon stocks for the Nationally Determined Contributions, both within and beyond Seychelles

Identification of common genetic variation that modulates alternative splicing

Alternative splicing of genes is an efficient means of generating variation in protein function. Several disease states have been associated with rare genetic variants that affect splicing patterns. Conversely, splicing efficiency of some genes is known to vary between individuals without apparent ill effects. What is not clear is whether commonly observed phenotypic variation in splicing patterns, and hence potential variation in protein function, is to a significant extent determined by naturally occurring DNA sequence variation and in particular by single nucleotide polymorphisms (SNPs). In this study, we surveyed the splicing patterns of 250 exons in 22 individuals who had been previously genotyped by the International HapMap Project. We identified 70 simple cassette exon alternative splicing events in our experimental system; for six of these, we detected consistent differences in splicing pattern between individuals, with a highly significant association between splice phenotype and neighbouring SNPs. Remarkably, for five out of six of these events, the strongest correlation was found with the SNP closest to the intron-exon boundary, although the distance between these SNPs and the intron-exon boundary ranged from 2 bp to greater than 1,000 bp. Two of these SNPs were further investigated using a minigene splicing system, and in each case the SNPs were found to exert cis-acting effects on exon splicing efficiency in vitro. The functional consequences of these SNPs could not be predicted using bioinformatic algorithms. Our findings suggest that phenotypic variation in splicing patterns is determined by the presence of SNPs within flanking introns or exons. Effects on splicing may represent an important mechanism by which SNPs influence gene function

Field-induced canting of magnetic moments in GdCo5 at finite temperature : first-principles calculations and high-field measurements

We present calculations and experimental measurements of the temperature-dependent magnetization of a single crystal of GdCo5 in magnetic fields of order 60 T. At zero temperature the calculations, based on density-functional theory in the disordered-local-moment picture, predict a field-induced transition from an antiferromagnetic to a canted alignment of Gd and Co moments at 46.1 T. At higher temperatures the calculations find this critical field to increase along with the zerofield magnetization. The experimental measurements observe this transition to occur between 44–48 T at 1.4 K. Up to temperatures of at least 100 K, the experiments continue to observe the transition; however, at variance with the calculations, no strong temperature dependence of the critical field is apparent. We assign this difference to the inaccurate description of the zero-field magnetization of the calculations at low temperatures, due to the use of classical statistical mechanics. Correcting for this effect, we recover a consistent description of the high-field magnetization of GdCo5 from theory and experiment

Serious mental health diagnoses in children on the child protection register: a record linkage study.

Children with experience of maltreatment, abuse or neglect are known to have a higher prevalence of poor mental health. Child Protection Services identify children most at risk of harm and in need of intervention. Mental healthcare usage in this population is not well understood as registration data is not routinely linked to health records. We undertook data linkage to describe the population on the register, their mental healthcare usage and to calculate age- and sex-specific incidence rates of mental health outcomes. We analysed records from the Aberdeen City Council Child Protection Register and for mental health prescribing and referrals to child and adolescent mental health services (CAMHS) for the NHS Grampian region between 1st January 2012 and 31st December 2022. We identified 1,498 individuals with a Child Protection Register registration, of which 70% were successfully matched to health records. 20% of registrations occurred before birth and the median age of registration was 3 years. 10.1% of children with a registration ever received a mental health prescription, 5.1% for treatment of attention deficit hyperactivity disorder and 1.7% for treatment of depression. 18.9% received a referral to specialist outpatient Child and Adolescent Mental Health Services. Age- and sex- standardised incidence rates for mental health prescribing and referrals are higher for children with a child protection registration compared to the general population. Children identified as being at significant risk of harm and involved with child protection services are at greater risk of seeking or receiving professional mental health support than their peers. Clinical services should investigate additional ways to support this population’s mental well-being as a priority. Efforts to reduce the exposure of children to potentially harmful environments at a societal level should also be pursued

Firm finances, weather derivatives and geography

This paper considers some intellectual, practical and political dimensions of collaboration between human and physical geographers exploring how firms are using relatively new financial products – weather derivatives – to displace any costs of weather-related uncertainty and risk. The paper defines weather derivatives and indicates how they differ from weather insurance products before considering the geo-political, cultural and economic context for their creation. The paper concludes by reflecting on the challenges of research collaboration across the human–physical geography divide and suggests that while such initiatives may be undermined by a range of institutional and intellectual factors, conversations between physical and human geographers remain and are likely to become increasingly pertinent. The creation of a market in weather derivatives raises a host of urgent political and regulatory questions and the confluence of natural and social knowledges, co-existing within and through the geography academy, provides a constructive and creative basis from which to engage with this new market and wider discourses of uneven economic development and climate change