Fire, Hurricane and Carbon Dioxide: Effects on Net Primary Production of a Subtropical Woodland

Disturbance affects most terrestrial ecosystems and has the potential to shape their responses to chronic environmental change. Scrub-oak vegetation regenerating from fire disturbance in subtropical Florida was exposed to experimentally elevated carbon dioxide (CO2) concentration (+350ll-1) using open-top chambers for 11yr, punctuated by hurricane disturbance in year 8. Here, we report the effects of elevated CO2 on aboveground and belowground net primary productivity (NPP) and nitrogen (N) cycling during this experiment. The stimulation of NPP and N uptake by elevated CO2 peaked within 2yr after disturbance by fire and hurricane, when soil nutrient availability was high. The stimulation subsequently declined and disappeared, coincident with low soil nutrient availability and with a CO2-induced reduction in the N concentration of oak stems. These findings show that strong growth responses to elevated CO2 can be transient, are consistent with a progressively limited response to elevated CO2 interrupted by disturbance, and illustrate the importance of biogeochemical responses to extreme events in modulating ecosystem responses to global environmental change

LIM kinase function and renal growth: potential role for LIM kinases in fetal programming of kidney development

Aims Maternal dietary restriction during pregnancy impairs nephron development and results in offspring with fewer nephrons. Cell turnover in the early developing kidney is altered by exposure to maternal dietary restriction and may be regulated by the LIM-kinase family of enzymes. We set out to establish whether disturbance of LIM-kinase activity might play a role in the impairment of nephron formation. Main methods E12.5 metanephric kidneys and HK2 cells were grown in culture with the pharmacological LIM-kinase inhibitor BMS5. Organs were injected with DiI, imaged and cell numbers measured over 48 h to assess growth. Cells undergoing mitosis were visualised by pH 3 labelling. Key findings Growth of cultured kidneys reduced to 83% of controls after exposure to BMS5 and final cell number to 25% of control levels after 48 h. Whilst control and BMS5 treated organs showed cells undergoing mitosis (100 ± 11 cells/field vs 113 ± 18 cells/field respectively) the proportion in anaphase was considerably diminished with BMS5 treatment (7.8 ± 0.8% vs 0.8 ± 0.6% respectively; P < 0.01). This was consistent with effects on HK2 cells highlighting a severe impact of BMS5 on formation of the mitotic spindle and centriole positioning. DiI labelled cells migrated in 100% of control cultures vs 0% BMS5 treated organs. The number of nephrogenic precursor cells appeared depleted in whole organs and formation of new nephrons was blocked by exposure to BMS5. Significance Pharmacological blockade of LIM-kinase function in the early developing kidney results in failure of renal development. This is likely due to prevention of dividing cells from completion of mitosis with their resultant loss

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

Increase in invasive Streptococcus pyogenes M1 infections with close evolutionary genetic relationship, Iceland and Scotland, 2022 to 2023

Group A Streptococcus isolates of the recently described M1UK clade have emerged to cause human infections in several European countries and elsewhere. Full-genome sequence analysis of M1 isolates discovered a close genomic relationship between some isolates from Scotland and the majority of isolates from Iceland causing serious infections in 2022 and 2023. Phylogenetic analysis strongly suggests that an isolate from or related to Scotland was the precursor to an M1UK variant responsible for almost all recent M1 infections in Iceland

Indirect effects of the COVID-19 pandemic on paediatric healthcare use and severe disease: a retrospective national cohort study

OBJECTIVES: To determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020. DESIGN: National retrospective cohort study. SETTING: Emergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records. PARTICIPANTS: 273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years. MAIN OUTCOME MEASURES: Rates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016–2019. RESULTS: The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016–2019. CONCLUSIONS: National lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Gaining access to agency and structure in industrial marketing theory : a critical pluralist approach.

This article is concerned with gaining greater insight into the interplay between agency and structure in industrial marketing (IM) scholarship. The article’s intent is to embed Midgley’s notion of critical pluralism within this endeavour. The article commends the movement towards increased deployment of critical realism, but cautions against the dangers of creating further atomism in marketing theory by generating another paradigm of thought with strongly defended boundaries, impervious to outside influence. The article advances a case for critical pluralism within IM scholarship and offers a three-dimensional (theoretical, methodological and methodical) framework to aid this. The discussion demonstrates how critical pluralism can be deployed to gain insights into agency and structure using a number of ‘integrative’ theoretical perspectives

Outcomes after urgent thyroidectomy following rapid control of thyrotoxicosis in Graves’ disease are similar to those after elective surgery in well-controlled disease

Background Surgery for Graves’ disease (GD) is usually performed after adequate control with medical treatment. Occasionally, rapid pre-operative optimization is required. The primary objective was to compare the outcomes of patients undergoing elective surgery for well-controlled GD with those undergoing rapid pre-operative treatment. We also propose a formal treatment protocol for future use. Methods A retrospective cohort study in a tertiary referral centre included 247 patients with well-controlled GD undergoing elective surgery and 19 patients with poorly controlled disease undergoing surgery after rapid optimization. The latter group did not respond well to thionamides (carbimazole and/or propylthiouracil) or had intolerance or side effects to thionamides and were treated with a range of non-thionamide drugs, including Lugol’s iodine, cholestyramine, beta blockers and steroids (with or without thionamides), and closely monitored for 1–2 weeks before surgery. Outcome measures included thyroid storm, hypoparathyroidism and recurrent laryngeal nerve palsy. Results In total, 266 patients with male-to-female ratio of 1:6 and median (interquartile range) age of 39 (31–51) were included. Overall, long-term recurrent laryngeal palsy and hypoparathyroidism occurred in 1 (0.38%) and 13 (4.9%) patients, respectively. No patient had thyroid storm. There was no significant difference in hypoparathyroidism (p = 1), vocal cord palsy (p = 0.803) and post-operative bleeding (p = 0.362), between elective surgery and rapid optimization groups. Conclusion Rapid pre-operative treatment is effective, safe and is associated with similar outcomes compared to usual treatment. A rapid pre-operative optimization protocol is proposed

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes