Overriding water table control on managed peatland greenhouse gas emissions.

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland3-5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems6. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTDe could reduce the net warming impact of CO2 and CH4 emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO2 per hectare per year, until WTDe is less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTDe is within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDe in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.

Factors influencing general practice nurse's implementation of culturally responsive care, using normalization process theory: A cross-sectional study.

AIMS: To explore levers and barriers to providing culturally responsive care for general practice nurses (GPNs) using normalization process theory. DESIGN: A self-administered online cross-sectional survey. METHODS: A participatory co-designed adapted version of the normalization of complex interventions measure (NoMAD) validated tool was distributed to a convenience sample of GPNs between December 2022 and February 2023. The sample comprised of GPNs working in general practice services in Ireland (n = 122). Data were analysed using descriptive and analytical statistics (Pearson correlations) and principles of content analysis. This study was conducted and reported in line with the Consensus-Based Checklist for Reporting of Survey Studies (CROSS). RESULTS: GPNs in this study indicated their familiarity with, acknowledged the importance of and were committed to, providing culturally responsive care. However, implementing culturally responsive care in daily practice was problematic due to insufficient education and training, scarcity of resources and supports and a lack of organizational leadership. Subsequently, GPNs experience difficulties adapting everyday practices to respond appropriately to the care needs of culturally and linguistically diverse (CaLD) patients. CONCLUSION: This analysis highlights the necessity of exploring the intricacies of factors that influence capabilities and capacity for providing culturally responsive care. Despite demonstrating awareness of the importance of providing nursing care that responds to the needs of CaLD patients, GPNs do not have full confidence or capacity to integrate culturally responsive care into their daily work practices. IMPACT: Using normalization process theory, this study elucidates for the first time how GPNs in Ireland make sense of, legitimize, enact and sustain culturally responsive care as a routine way of working. It illuminates the multitude of micro-level (individual), meso-level (organizational) and macro-level (structural) factors that require attention for normalizing culturally responsive care in general practice services. PATIENT OR PUBLIC CONTRIBUTION: The study question was identified in a participatory research prioritization for Irish research about migrant health that involved migrants in the process.

Infliximab improves vascular stiffness in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have increased cardiovascular mortality. Tumour necrosis factor alpha (TNFalpha)-blocking therapy has been shown to reduce RA disease activity measures and joint damage progression. Some observational studies suggest that TNFalpha blockade reduces mortality and incidence of first cardiovascular events. The mechanisms contributing to these outcomes are unclear. This study assessed the effects of infliximab treatment on vascular stiffness and structure in patients with RA. METHODS: A post hoc analysis of longitudinal data from a randomised placebo controlled study evaluated the effect of infliximab on vascular assessments. 26 patients received intravenous infliximab (3 mg/kg) at weeks 0, 2, 6 and every 8 weeks thereafter to week 54. Patients were followed up to 56 weeks of infliximab therapy with assessments of RA disease activity, cardiovascular risk factors, vascular stiffness (pulse wave velocity (PWV)), carotid intima media thickness (CIMT) and carotid artery plaque (CAP). Univariate analyses of changes over time by repeated measures analysis of variance (ANOVA) were followed by multivariate time-series regression analysis (TSRA) if changes were seen. RESULTS: PWV was significantly lower (better) after 56 weeks of treatment with infliximab (ANOVA p<0.01, TSRA p<0.01). However, CIMT (ANOVA p = 0.50) and CAP (chi(2) = 4.13, p = 0.88) did not change over the study period. Multiple cardiovascular risk measures did not change with treatment and did not correlate with changes in measures of vascular structure. CONCLUSIONS: Arterial stiffness improves with infliximab treatment in RA. This change may help explain the improved cardiovascular disease survival in patients with RA receiving TNFalpha-blocking therapy.

Gully hotspot contribution to landscape methane (CH4) and carbon dioxide (CO2) fluxes in a northern peatland.

Peatlands are long term carbon catchments that sink atmospheric carbon dioxide (CO(2)) and source methane (CH(4)). In the uplands of the United Kingdom ombrotrophic blanket peatlands commonly exist within Calluna vulgaris (L.) dominated moorland ecosystems. These landscapes contain a range of topographical features that influence local hydrology, climate and plant community composition. In this study we examined the variation in ecosystem CO(2) respiration and net CH(4) fluxes from typical plant-soil systems in dendritic drainage gullies and adjacent blanket peat during the growing season. Typically, Eriophorum spp., Sphagnum spp. and mixed grasses occupied gullies while C. vulgaris dominated in adjacent blanket peat. Gross CO(2) respiration was highest in the areas of Eriophorum spp. (650+/-140 mg CO(2) m(-2) h(-1)) compared to those with Sphagnum spp. (338+/-49 mg CO(2) m(-2) h(-1)), mixed grasses (342+/-91 mg CO(2) m(-2) h(-1)) and C. vulgaris (174+/-63 mg CO(2) m(-2) h(-1)). Measurements of the net CH(4) flux showed higher fluxes from the Eriophorum spp (2.2+/-0.6 mg CH(4) m(-2) h(-1)) locations compared to the Sphagnum spp. (0.6+/-0.4 mg CH(4) m(-2) h(-1)), mixed grasses (0.1+/-0.1 mg CH(4) m(-2) h(-1)) and a negligible flux detected from C. vulgaris (0.0+/-0.0 mg CH(4) m(-2) h(-1)) locations. A GIS approach was applied to calculate the contribution of gullies to landscape scale greenhouse gas fluxes. Findings from the Moor House National Nature Reserve in the UK showed that although gullies occupied only 9.3% of the total land surface, gullies accounted for 95.8% and 21.6% of the peatland net CH(4) and CO(2) respiratory fluxes, respectively. The implication of these findings is that the relative contribution of characteristic gully systems need to be considered in estimates of landscape scale peatland greenhouse gas fluxes.

Direct isotopic evidence of biogenic methane production and efflux from beneath a temperate glacier.

The base of glaciers and ice sheets provide environments suitable for the production of methane. High pressure conditions beneath the impermeable 'cap' of overlying ice promote entrapment of methane reserves that can be released to the atmosphere during ice thinning and meltwater evacuation. However, contemporary glaciers and ice sheets are rarely accounted for as methane contributors through field measurements. Here, we present direct field-based evidence of methane production and release from beneath the Icelandic glacier Sólheimajökull, where geothermal activity creates sub-oxic conditions suited to methane production and preservation along the meltwater flow path. Methane production at the glacier bed (48 tonnes per day, or 39 mM CH4 m-2 day-1), and evasion to the atmosphere from the proglacial stream (41 tonnes per day, or 32 M CH4 m-2 day-1) indicates considerable production and release to the atmosphere during the summer melt season. Isotopic signatures (-60.2‰ to -7.6‰ for δ13CCH4 and -324.3‰ to +161.1‰ for DCH4), support a biogenic signature within waters emerging from the subglacial environment. Temperate glacial methane production and release may thus be a significant and hitherto unresolved contributor of a potent greenhouse gas to the atmosphere.

Nucleosomal arrangement of HIV-1 DNA: maps generated from an integrated genome and an EBV-based episomal model.

ACH-2 cells, an immortalized human T-cell line, contain a single integrated copy of the HIV-1 provirus. Here, the structure of HIV-1 chromatin was probed using a DNA cleavage reagent. Nuclei were isolated from ACH-2 cells and treated with methidiumpropyl-EDTA (MPE)-iron(II) to produce limited DNA cleavage. Primers were selected at approximately 300 bp intervals along the HIV-1 DNA, and sites of preferential cleavage were mapped by carrying out 50 cycles of primer extension using a thermo-stable DNA polymerase in the presence of [32P]dATP. By comparing the resulting cleavage pattern with patterns derived from human cell lines not containing HIV-1 sequences, it was possible to map the arrangement of nucleosomes across the integrated HIV-1 genome. Particularly regular spacing was seen in the 3' end of the pol and env coding regions, and several extended blocks spared of nucleosomes were found in gag and pol, the largest being an approximately 450 bp region in gag. For comparison, and to examine nucleosome placement on HIV-1 DNA when it is not integrated, overlapping segments of HIV-1 DNA were cloned into an EBV-oriP plasmid, grown as stable episomes in a human B lymphoblastoid cell line, and the same analysis using MPE-iron(II) cleavage and primer extension carried out. The major features of nucleosome placement on these EBV/HIV minichromosomes was very similar to that observed in the integrated HIV-1 genome arguing for a strong sequence dependence for nucleosome placement along HIV-1 DNA.

The effects of time course after anterior cruciate ligament injury in correlation with meniscal and cartilage loss.

In this study, 130 consecutive patients with anterior cruciate ligament insufficiency who were undergoing ligament reconstruction underwent arthroscopic examination at the time of reconstruction, and any loss of meniscal or chondral integrity was documented in a systematic fashion. In these patients, a greater proportion of the medial meniscus was lost compared with the lateral meniscus (16% versus 5%). On average, 6 cm2 of the articular cartilage was damaged (5.2 cm2) or lost (0.8 cm2), with the area of damage and loss greatest on the medial femoral condyle. Patients whose injuries had occurred more than 2 years before the examination had more than sixfold greater cartilage loss and damage compared with those whose injuries had occurred within the past 2 months. Meniscal loss was associated with a threefold increase in cartilage damage or loss. The group of patients with meniscal loss whose initial anterior cruciate ligament injury occurred more than 2 years before examination exhibited 18 times the amount of cartilage loss or damage as did the group that had no meniscal loss and whose injury occurred less than 1 month before examination.

Arthroscopic estimation of the extent of chondropathy.

INTRODUCTION: Arthroscopy has been used to evaluate articular cartilage (AC) pathology in osteoarthritis (OA) for outcome measurement and validation of non-invasive imaging. However, many fundamental aspects of arthroscopic assessment remain un-validated. OBJECTIVES: This study evaluated arthroscopic estimates of extent of chondropathy. METHODS: Serial arthroscopic assessments were performed in a group of 15 sheep before and after bilateral stifle medial meniscectomy (MMx). Post-mortem assessments were performed in un-MMx sheep and 4 and 16 weeks post-MMx. Arthroscopic assessments of the extent of each grade of chondropathy were compared with a non-arthroscopic hybrid assessment that incorporated biomechanical, thickness and macroscopic assessments. RESULTS: Arthroscopy evaluated only 36% of AC and missed significant pathological changes, softening and chondro-osteophyte, occurring in peripheral regions. The patterns of change in arthroscopic assessments were similar to those of the non-arthroscopic assessment but there was a very strong tendency to over-estimate the extent of softened AC after MMx. In spite of these limitations arthroscopic assessments were responsive to change. Estimates of the extent of normal and softened AC were most responsive to change over time followed by estimates of superficial and deep fibrillation. Arthroscopy was as an excellent discriminator between normal and OA. Assessments of chondro-osteophyte and exposed bone were not responsive to change. CONCLUSIONS: Arthroscopic estimates of extent of chondropathy are prone to substantial error. While experience and training may reduce these errors other approaches may more effectively improve performance.

Arthroscopy -- a potential "gold standard" for the diagnosis of the chondropathy of early osteoarthritis.

OBJECTIVES: The aims of this study were to: 1. Evaluate the performance of arthroscopy for the diagnosis of chondropathy and to compare it to that of direct non-arthroscopic assessments; 2. Determine intra-observer reliability of arthroscopic assessments; 3. Evaluate the effects of the arthroscopic video quality and probing upon diagnostic performance. DESIGN: The ovine medial meniscectomy (MMx) model of early osteoarthritis (OA) was used assuming that pre-MMx articular cartilage (AC) was "normal" and post-MMx AC "chondropathic". Video recordings of arthroscopic assessments of each stifle compartment were evaluated. Scores were given for the quality of the video and the amount of probing. The diagnostic performances of dynamic shear modulus (G), light microscopic assessment and superficial zone collagen birefringence assessments were evaluated and compared to that of arthroscopy. Intra-observer reliability of arthroscopic assessments was also evaluated. RESULTS: Arthroscopic assessments had high sensitivity (91-100%), specificity (62-88%) and accuracy (75-93%) for the diagnosis of chondropathy 16 weeks after MMx. Arthroscopy compared favourably with the direct non-arthroscopic assessments in the lateral compartment and was found to have extremely high intra-observer reliability (kappa 0.78-1.00). The quality of arthroscopic video recordings and the amount of probing did not significantly influence accuracy or reliability. CONCLUSIONS: Arthroscopy performs as well as direct non-arthroscopic assessments of AC for diagnosis of early OA. These results suggest that arthroscopy can be used as a "gold standard" for the validation of non-invasive assessments like magnetic resonance imaging and that arthroscopic diagnosis can be based on small amounts of video footage without AC probing.

Emergence and evolution of enfuvirtide resistance following long-term therapy involves heptad repeat 2 mutations within gp41.

The objective of this study was to track the evolution of sequence changes in both the heptad region 1 (HR1) and HR2 domains of gp41 associated with resistance to enfuvirtide (ENF) in a patient cohort receiving long-term ENF treatment. We studied 17 highly antiretroviral agent-experienced patients receiving long-term ENF treatment with virological rebound or a lack of suppression. Sixty-two samples obtained after between 5 and 107 weeks of ENF therapy were analyzed. Baseline samples from 15 of these 17 patients were available for analysis. Viruses from five samples from four patients were also sequenced after the cessation of ENF therapy. Drug susceptibilities were assessed by a pseudotype virus reporter assay. We identified HR1 and HR2 sequence changes over time in relation to the baseline sequences. Mutations in HR1 (amino acids 36 to 45) were noted in all cases, including previously unreported changes N42Q/H and N43Q. In addition to a range of HR2 sequence changes at polymorphic sites, isolates from 6 of 17 (35%) patients developed an S138A substitution in the HR2 domain at least 8 weeks after the start of ENF treatment and also subsequent to the first emergence of HR1 mutations. In most, but not all, cases the S138A mutation accompanied HR1 mutations at position 43. Molecular modeling demonstrates the close proximity of S138A with amino acids 40 and 45 in HR1. Of note, isolates in samples available from four patients demonstrated the loss of both the HR1 and the S138A HR2 mutations following the cessation of therapy. We show that the S138A HR2 mutation increased the level of resistance by approximately threefold over that conferred by the HR1 mutation N43D. Continual evolution of HR1 in the domain from amino acids 36 to 45 was observed during long-term ENF therapy. We have identified, for the first time, an ENF resistance-associated HR2 mutation, S138A, which appeared in isolates from 6 of 17 patients with virological failure and demonstrated its potential to contribute to drug resistance. We propose that this represents a possible secondary and/or compensatory mutation, particularly when it coexists with mutations at position 43 in HR-1.

Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro.

Enfuvirtide (ENF), a novel human immunodeficiency virus type 1 (HIV-1) fusion inhibitor, has potent antiviral activity against HIV-1 both in vitro and in vivo. Resistance to ENF observed after in vitro passaging was associated with changes in a three-amino-acid (aa) motif, GIV, at positions 36 to 38 of gp41. Patients with ongoing viral replication while receiving ENF during clinical trials acquired substitutions within gp41 aa 36 to 45 in the first heptad repeat (HR-1) of gp41 in both population-based plasma virus sequences and proviral DNA sequences from isolates showing reduced susceptibilities to ENF. To investigate their impact on ENF susceptibility, substitutions were introduced into a modified pNL4-3 strain by site-directed mutagenesis, and the susceptibilities of mutant viruses and patient-derived isolates to ENF were tested. In general, susceptibility decreases for single substitutions were lower than those for double substitutions, and the levels of ENF resistance seen for clinical isolates were higher than those observed for the site-directed mutant viruses. The mechanism of ENF resistance was explored for a subset of the substitutions by expressing them in the context of a maltose binding protein chimera containing a portion of the gp41 ectodomain and measuring their binding affinity to fluorescein-labeled ENF. Changes in binding affinity for the mutant gp41 fusion proteins correlated with the ENF susceptibilities of viruses containing the same substitutions. The combined results support the key role of gp41 aa 36 to 45 in the development of resistance to ENF and illustrate that additional envelope regions contribute to the ENF susceptibility of fusion inhibitor-naïve viruses and resistance to ENF.

Impact of selective cyclooxygenase-2 inhibitors on anti-ulcer medication and non-steroidal anti-inflammatory drug use in patients with rheumatic disease.

BACKGROUND: Anti-inflammatory medications are the most common treatment for rheumatic disease in Australia. Recent years have seen large increases in the use of selective cyclooxygenase-2 (COX-2) inhibitors. Predictors of use, costs and benefits of the new medications have not been evaluated. AIMS: To determine trends in selective COX-2 inhibitor, non-steroidal anti-inflammatory drug (NSAID) and anti-ulcer medication (AUM) prescription following the introduction of selective COX-2 inhibitors; to determine predictors of selective COX-2 inhibitor, NSAID and AUM prescribing and to perform a limited evaluation of the costs and benefits associated with the introduction of selective COX-2 inhibitors. METHODS: Groups of consecutive patients attending a hospital rheumatology clinic, private rooms of consulting rheumatologists and a dermatology outpatient clinic were surveyed by investigator-administered questionnaire on three separate occasions. Information was sought about AUM, NSAID and selective COX-2 use and about factors likely to influence selective COX-2 prescribing. Sampling was carried out at 3, 10 and 16 months after the release of COX-2 selective inhibitors in Australia. The final survey was 3 months after Pharmaceutical Benefits Scheme (PBS) listing of celecoxib in Australia. Costs of treatment were calculated from survey findings of frequency of drug use as well as published drug prices and hospitalisation costs. RESULTS: Four-hundred and fifty-eight patients were surveyed. From the 3 months post-release to the 3 months post-PBS listing, a period of 13 months, COX-2 use in rheumatology patients increased from 18 to 57%. De novo prescription of selective COX-2 inhibitors increased from 42 to 61%. During the same period there was a fall in both NSAID (43-20%) and AUM use (41-27%). Neither selective COX-2 inhibitor nor NSAID prescription was related to risk factors for gastro-intestinal (GI) complications, but AUM use was found to correlate strongly to histories of gastroscopy, GI ulceration or GI bleed. The calculated increase in the cost of treatment was $1 033 002/10 000 patients per year. The net cost per serious GI event prevented was $71 736, compared with the normal cost of treatment of $2004. CONCLUSIONS: Among rheumatology patients, selective COX-2 inhibitors have largely replaced NSAIDs and have resulted in a reduction in AUM consumption, but prescribing patterns for selective COX-2 inhibitors have not been related clearly to risk factors for GI complications. The introduction of selective COX-2 inhibitors has been associated with a significant increase in expenditure.

Electroconvulsive therapy in old-old patients.

The authors compared falls, cardiovascular factors, confusion, gastrointestinal, pulmonary, and metabolic side effects for "old-old" (>75 years) patient groups treated with either electroconvulsive therapy (ECT) or pharmacotherapy. A subset of a pharmacotherapy patient group was selected to match for age, sex, and diagnosis in a case-control design. Side effects were recorded from each selected patient's medical record and compared between groups. Patients receiving ECT showed fewer cardiovascular and gastrointestinal side effects. Patients receiving ECT had longer lengths of stay and more favorable outcomes. Overall, there was a tendency for ECT to result in fewer side effects and better treatment outcomes. ECT appears to be relatively safe and more effective than pharmacotherapy for major depressive disorders in old-old patients.

Reduction in dissociation due to aging and cognitive deficit.

Our objective was to investigate whether dissociative experiences occur less frequently in older psychiatric patients than in younger adult patients, and to examine the role of cognitive deficits in the frequency of dissociative events. Fifty-two outpatients 60 years and older were administered the Dissociative Experiences Scale (DES) and the Mini-Mental State Exam (MMSE). Their scores were compared with those of 50 outpatients 35 to 55 years old. Each group included patients sampled from the Mental Health Center (MHC) and University Medical Center clinics. Older patients showed significantly lower DES and MMSE median scores than younger patients. Cognitive deficit reflected by reduced MMSE scores also was associated with reduced DES scores for younger and older patients. Older patients with little or no cognitive deficit continued to show reduced DES scores. Decreases in dissociativity continue well beyond the fourth decade and do not rely on age-related cognitive deficit. Factors related to the aging process seem to mediate reductions in dissociativity independent of reductions mediated by cognitive deficit. The use of the DES for screening without adjusting for age and cognitive status is questioned.

Red cell exchange in sickle cell disease.

Red cell exchange transfusion is frequently of use in the management of patients with sickle cell disease either electively or therapeutically. Modern cell separators allow this procedure to be performed rapidly, effectively and safely. These machines have a number of advantages over manual exchange procedures. The patient remains isovolaemic, there is little loss of plasma or platelets, the procedure is relatively short and in elective circumstances can be performed on an outpatient basis. In this series 66 exchanges were performed on 21 patients with an overall increase in HbA of 70%. The COBE Spectra gave a mean increase in HbA of 77%, with the majority of patients achieving an HbA of > 90% post exchange. Automated redcell exchange was well tolerated by most patients, and adverse effects were limited to symptoms of hypocalcaemia which were easily treated, and to transfusion reactions. Cell separators can therefore be recommended for exchange transfusion in patients with sickle cell disease, who require an increase in HbA levels either prophylactically or therapeutically. They are safe, effective, easy and quick to use.