A constraint on historic growth in global photosynthesis due to increasing CO2.

The global terrestrial carbon sink is increasing1-3, offsetting roughly a third of anthropogenic CO2 released into the atmosphere each decade1, and thus serving to slow4 the growth of atmospheric CO2. It has been suggested that a CO2-induced long-term increase in global photosynthesis, a process known as CO2 fertilization, is responsible for a large proportion of the current terrestrial carbon sink4-7. The estimated magnitude of the historic increase in photosynthesis as result of increasing atmospheric CO2 concentrations, however, differs by an order of magnitude between long-term proxies and terrestrial biosphere models7-13. Here we quantify the historic effect of CO2 on global photosynthesis by identifying an emergent constraint14-16 that combines terrestrial biosphere models with global carbon budget estimates. Our analysis suggests that CO2 fertilization increased global annual photosynthesis by 11.85 ± 1.4%, or 13.98 ± 1.63 petagrams carbon (mean ± 95% confidence interval) between 1981 and 2020. Our results help resolve conflicting estimates of the historic sensitivity of global photosynthesis to CO2, and highlight the large impact anthropogenic emissions have had on ecosystems worldwide.

A surge of light at the birth of a supernova.

It is difficult to establish the properties of massive stars that explode as supernovae. The electromagnetic emission during the first minutes to hours after the emergence of the shock from the stellar surface conveys important information about the final evolution and structure of the exploding star. However, the unpredictable nature of supernova events hinders the detection of this brief initial phase. Here we report the serendipitous discovery of a newly born, normal type IIb supernova (SN 2016gkg), which reveals a rapid brightening at optical wavelengths of about 40 magnitudes per day. The very frequent sampling of the observations allowed us to study in detail the outermost structure of the progenitor of the supernova and the physics of the emergence of the shock. We develop hydrodynamical models of the explosion that naturally account for the complete evolution of the supernova over distinct phases regulated by different physical processes. This result suggests that it is appropriate to decouple the treatment of the shock propagation from the unknown mechanism that triggers the explosion.

Non-pharmaceutical interventions to reduce COVID-19 transmission in the UK: a rapid mapping review and interactive evidence gap map.

BACKGROUND: Non-pharmaceutical interventions (NPIs) were crucial in the response to the COVID-19 pandemic, although uncertainties about their effectiveness remain. This work aimed to better understand the evidence generated during the pandemic on the effectiveness of NPIs implemented in the UK. METHODS: We conducted a rapid mapping review (search date: 1 March 2023) to identify primary studies reporting on the effectiveness of NPIs to reduce COVID-19 transmission. Included studies were displayed in an interactive evidence gap map. RESULTS: After removal of duplicates, 11 752 records were screened. Of these, 151 were included, including 100 modelling studies but only 2 randomized controlled trials and 10 longitudinal observational studies.Most studies reported on NPIs to identify and isolate those who are or may become infectious, and on NPIs to reduce the number of contacts. There was an evidence gap for hand and respiratory hygiene, ventilation and cleaning. CONCLUSIONS: Our findings show that despite the large number of studies published, there is still a lack of robust evaluations of the NPIs implemented in the UK. There is a need to build evaluation into the design and implementation of public health interventions and policies from the start of any future pandemic or other public health emergency.

The independent and joint risks of alcohol consumption, smoking, and excess weight on morbidity and mortality: a systematic review and meta-analysis exploring synergistic associations.

OBJECTIVE: Alcohol consumption, smoking, and excess weight independently increase the risk of morbidity/mortality. Less is known about how they interact. This research aims to quantify the independent and joint associations of these exposures across health outcomes and identify whether these associations are synergistic. STUDY DESIGN: The protocol for this systematic review and meta-analysis was pre-registered (PROSPERO CRD42021231443). METHODS: Medline and Embase were searched between 1 January 2010 and 9 February 2022. Eligible peer-reviewed observational studies had to include adult participants from Organisation for Co-Operation and Development countries and report independent and joint associations between at least two eligible exposures (alcohol, smoking, and excess weight) and an ICD-10 outcome (or equivalent). For all estimates, we calculated the synergy index (SI) to identify whether joint associations were synergistic. Meta-analyses were conducted for outcomes with sufficiently homogenous data. RESULTS: The search returned 26,290 studies, of which 98 were included. Based on 138,130 participants, the combined effect (SI) of alcohol and smoking on head and neck cancer death/disease was 3.78 times greater than the additive effect of each exposure (95% confidence interval [CI] = 2.61, 5.48). Based on 2,603,939 participants, the combined effect of alcohol and excess weight on liver disease/death was 1.55 times greater than the additive effect of each exposure (95% CI = 1.33, 1.82). CONCLUSION: Synergistic associations suggest the true population-level risk may be underestimated. In the absence of bias, individuals with multiple risks would experience a greater absolute risk reduction from an intervention that targets a single exposure than individuals with a single risk.

Experimental testing of a prototype cantilevered liquid-nitrogen-cooled silicon mirror.

This report presents testing of a prototype cantilevered liquid-nitrogen-cooled silicon mirror. This mirror was designed to be the first mirror for the new soft X-ray beamlines to be built as part of the Advanced Light Source Upgrade. Test activities focused on fracture, heat transfer, modal response and distortion, and indicated that the mirror functions as intended.

Osteoarthritis consumers as co-researchers: identifying consumer insights to improve osteoarthritis management by co-designing translational research solutions.

INTRODUCTION: Co-design is a consumer-driven approach that facilitates consumer participation in creating meaningful solutions to complex problems. Poor uptake of core management strategies for osteoarthritis suggests there is a missing link in translation between research and practice. We partnered with osteoarthritis consumers as 'co-researchers' to identify translational research solutions to improve uptake of core management strategies that are grounded in lived experiences. OBJECTIVE: To transparently describe a theory-driven, generative co-design approach using an integrated conceptual framework to collaborate with consumers at the equal partnership level. DESIGN: We used co-design workshops with a non-hierarchical participatory framework. Three workshops with six co-researchers [2 female, mean age 68.7 (9.8) years, 3-30 years symptom duration] were conducted using activities to encourage creative thinking, promote deep reflection on personal/societal beliefs and minimise sensitivities around sharing personal beliefs (e.g., establishing a safe space, prompting questions, perspective-taking, counter-stereotypical exemplars). RESULTS: All six co-researchers actively participated in the workshops. Achievement of an equal collaborative partnership was evidenced by co-researchers challenging a project proposed by the research team and making alternative recommendations that have been implemented in prospective decision-making - representing a complete change in research focus driven by consumer input. A key suggested solution was to develop a scalable knowledge translation intervention that targets misconceptions about osteoarthritis and its management at the societal-level. CONCLUSIONS: Through an innovative co-design approach in partnership with co-researchers, we identified meaningful areas on which to focus translational research for osteoarthritis. Discordance between existing research priorities and novel solutions proposed by co-researchers highlights the value of co-design.

Computer simulation of carbonization and graphitization of coal.

This study describes computer simulations of carbonization and graphite formation, including the effects of hydrogen, nitrogen, oxygen, and sulfur. We introduce a novel technique to simulate carbonization, 'Simulation of Thermal Emission of Atoms and Molecules (STEAM)', designed to elucidate volatile outgassing and density variations in the intermediate material during carbonization. The investigation analyzes the functional groups that endure through high-temperature carbonization and examines the graphitization processes in carbon-rich materials containing non-carbon impurity elements. The physical, vibrational, and electronic attributes of impure amorphous graphite are analyzed, and the impact of nitrogen on electronic conduction is investigated.

A prospective observational study of the effects of sugammadex on peri-operative oestrogen and progesterone levels in women who take hormonal contraception.

Pharmacokinetic modelling suggests that sugammadex may interact with endogenous progesterone and reduce levels by 34% in patients taking hormonal contraception. Due to this potential interaction that may be equivalent to missing one dose of an oral contraceptive pill, both the manufacturer and professional anaesthesia organisations recommend counselling patients to use additional non-hormonal contraception after administration of sugammadex. We performed a prospective observational study examining the changes in serum oestrogen and progesterone concentrations in premenopausal adult women undergoing an operative procedure. Sixty participants who were on hormonal contraception received sugammadex. Two additional control groups were recruited, consisting of 30 participants who were not on hormonal contraception and did not receive sugammadex, and 32 who were not on hormonal contraception and did receive sugammadex. Three blood samples were taken: before sugammadex; 15 min post-sugammadex; and 240 min post-sugammadex or end of operating theatre time. Median oestrogen levels decreased from baseline by around 40% at 240 min in all three groups (p ≤ 0.001). Progesterone levels rose significantly at 15 min (p = 0.002) in patients on contraception then decreased non-significantly to 20% below baseline at 240 min. The decrease in oestrogen and the rise in progesterone could both act to minimise the risk of ovulation and thus protect contraception in this population. We found no evidence of a change in hormone levels that might threaten contraceptive efficacy in women on hormonal contraception receiving sugammadex.

A clinical and electrophysiological case study of a child with a novel frame shift mutation in the CACNA1F and missense variation of RIMS1 genes.

PURPOSE: The purpose of this paper is to present a case study illustrating the importance of electrophysiological investigation in the diagnosis and serial monitoring of isolated congenital nystagmus. RESULTS: Serial electophysiological monitoring was undertaken in the male proband over a 9-year period commencing with initial assessment at 12 weeks of age: Skin electroretinograms (sERGs) were initially absent but subsequently revealed low-amplitude responses, electronegative morphologies and notched flicker responses suggestive of incomplete congenital stationary night blindness (CSNB2), but with an absent dark-adapted rod-specific response, while flash visual evoked potentials (fVEPs) demonstrated persistent crossed asymmetry, typical of albinoid misrouting of the optic nerves. Molecular investigation confirmed a novel hemizygous frame shift mutation in the CACNA1F gene, considered to be pathogenic and causative of X-linked CSNB2; additionally, a novel heterozygous missense variation in one copy of the RIMS1 gene was identified, pathogenic mutations of which underpin late-onset autosomal dominant cone-rod dystrophy (type 7). Segregation studies confirmed maternal inheritance of both mutations in the clinically asymptomatic mother in whom depressed rod-specific responses were confirmed on sERG. The child's visual acuity has remained stable as have the sERGs which have been verified by recordings using scleral electrodes. CONCLUSIONS: The importance of recording ERGs as part of evaluating infants who present with nystagmus, even with a normal fundus appearance, is supported. Further, sERGs were able to distinguish an apparent variant of CSNB2 and could give consistent results over many years. FVEP results add to the evidence that albinoid misrouting of the optic nerves may occur in cases of CSNB2. ERGs and fVEPs can provide valuable information in discriminating the relative diagnostic importance of multiple genetic abnormalities.

Unilateral diaphragmatic paresis following supracostal post-percutaneous nephrolithotomy.

Unilateral acquired diaphragmatic paresis is a known complication of thoracic surgeries. Direct mechanical injury to the phrenic nerve during surgery results in this complication. However its occurrence post-percutaneous nephrolithotomy (PCNL) has not been described. We report a 43-year-old man who underwent prone PCNL for endourological management of left complete staghorn calculus. Access via the 10th left intercostal space, under fluoroscopy, was carried out to remove the calculus. Post-operative, the routine chest radiograph revealed left hemidiaphragmatic blunting. Computerized tomography of the chest confirmed left hemidiaphragmatic elevation, suggesting unilateral diaphragmatic paresis. He did not have any respiratory symptoms, was managed conservatively with chest physiotherapy and incentive spirometry and responded extremely well. The absence of reported cases of diaphragmatic paresis post PCNL lends to a dearth in knowledge regarding recognition and management. This case report aims to acquaint urologists with this rare complication associated with supracostal PCNL and provide a rational management plan.

Topographic Control of Order in Quasi-2D Granular Phase Transitions.

We experimentally investigate the nature of 2D phase transitions in a quasi-2D granular fluid. Using a surface decorated with periodically spaced dimples we observe interfacial tension between coexisting granular liquid and crystal phases. Measurements of the orientational and translational order parameters and associated susceptibilities indicate that the surface topography alters the order of the phase transition from a two-step continuous one to a first-order liquid-solid one. The interplay of boundary inelasticity and geometry, either order promoting or inhibiting, controls whether it is the granular crystal or the granular fluid which makes contact with the edge. This order induced wetting has important consequences, determining how coexisting phases separate spatially.

Type I interferon response and vascular alteration in chilblain-like lesions during the COVID-19 outbreak.

BACKGROUND: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. OBJECTIVES: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus. METHODS: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included. RESULTS: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL. CONCLUSIONS: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.

Robustness of convolutional neural networks to physiological electrocardiogram noise.

The electrocardiogram (ECG) is a widespread diagnostic tool in healthcare and supports the diagnosis of cardiovascular disorders. Deep learning methods are a successful and popular technique to detect indications of disorders from an ECG signal. However, there are open questions around the robustness of these methods to various factors, including physiological ECG noise. In this study, we generate clean and noisy versions of an ECG dataset before applying symmetric projection attractor reconstruction (SPAR) and scalogram image transformations. A convolutional neural network is used to classify these image transforms. For the clean ECG dataset, F1 scores for SPAR attractor and scalogram transforms were 0.70 and 0.79, respectively. Scores decreased by less than 0.05 for the noisy ECG datasets. Notably, when the network trained on clean data was used to classify the noisy datasets, performance decreases of up to 0.18 in F1 scores were seen. However, when the network trained on the noisy data was used to classify the clean dataset, the decrease was less than 0.05. We conclude that physiological ECG noise impacts classification using deep learning methods and careful consideration should be given to the inclusion of noisy ECG signals in the training data when developing supervised networks for ECG classification. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry.

Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 × 10-8) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy.

Fossils with Feathers and Philosophy of Science.

The last half century of paleornithological research has transformed the way that biologists perceive the evolutionary history of birds. This transformation has been driven, since 1969, by a series of exciting fossil discoveries combined with intense scientific debate over how best to interpret these discoveries. Ideally, as evidence accrues and results accumulate, interpretive scientific agreement forms. But this has not entirely happened in the debate over avian origins: the accumulation of scientific evidence and analyses has had some effect, but not a conclusive one, in terms of resolving the question of avian origins. Although the majority of biologists have come to accept that birds are dinosaurs, there is lingering and, in some quarters, strident opposition to this view. In order to both understand the ongoing disagreement about avian origins and generate a prediction about the future of the debate, here we use a revised model of scientific practice to assess the current and historical state of play surrounding the topic of bird evolutionary origins. Many scientists are familiar with the metascientific scholars Sir Karl Popper and Thomas Kuhn, and these are the primary figures that have been appealed to so far, in prior attempts to assess the dispute. But we demonstrate that a variation of Imre Lakatos's model of progressive versus degenerative research programmes provides a novel and productive assessment of the debate. We establish that a refurbished Lakatosian account both explains the intractability of the dispute and predicts a likely outcome for the debate about avian origins. In short, here, we offer a metascientific tool for rationally assessing competing theories-one that allows researchers involved in seemingly intractable scientific disputes to advance their debates.

Abdominoperineal excision in Australasia: clinical outcomes, predictive factors and recent trends of nonrestorative rectal cancer surgery.

AIM: The decision to perform an abdominoperineal excision (APR) rather than restorative bowel resection relies on a number of clinical factors. There remains great variability in APR rates internationally. The aim of this study was to demonstrate trends of APR surgery in low rectal cancer (< 6 cm from the anal verge) in Australasia and identify predictors of nonrestoration. METHOD: This study reviewed a prospectively maintained colorectal registry - the Binational Colorectal Cancer Audit (BCCA) - from general/colorectal surgical units across Australia and New Zealand. Data were analysed to determine factors predictive of nonrestorative resection. Patients were analysed based on the presence (control) or absence (comparison) of a primary anastomosis. RESULTS: Of 3628 patients with rectal cancer, 2096 were diagnosed with low rectal cancer between 2007 and 2017. The incidence of APR remained constant over the study period, with 58% of all resections of low rectal cancer being APR. The majority of resections were performed by consultants in urban hospitals (86% vs 14%). Tumours ≤ 3 cm from the anal verge, T4, M1 disease and neoadjuvant therapy were the greatest predictors of APR (P < 0.001). A significantly increased rate of restorative surgery was observed in public hospital settings (59% vs 41%, P < 0.05). The rate of positive circumferential resection margin (CRM) was 7.95%, with significantly increased rates in patients undergoing APR (12.2% vs 6.2%, P < 0.001). CRM positivity was increased in open approaches, T4, N2 and M1 staged disease and in an emergency/urgent setting (P < 0.001 and P < 0.045, respectively). Significantly increased wound and pulmonary complications were observed in the APR cohort (P < 0.01). CONCLUSION: The rates of APR in Australia and New Zealand remain high but are comparable to international figures, with one-third of rectal cancers being treated by APR. The main determinants of APR are tumour height, T stage and neoadjuvant therapy requirement. CRM positivity was higher in APR patients.

Outcomes of extended radical resections for locally advanced and recurrent pelvic malignancy involving the aortoiliac axis.

AIM: Currently, there is no clear consensus on the role of extended pelvic resections for locally advanced or recurrent disease involving major vascular structures. The aims of this study were to report the outcomes of consecutive patients undergoing extended resections for pelvic malignancy involving the aortoiliac axis. METHODS: Prospective data were collected on patients having extended radical resections for locally advanced or recurrent pelvic malignancies, with aortoiliac axis involvement, requiring en bloc vascular resection and reconstruction, at a single institution between 2014 and 2018. RESULTS: Eleven patients were included (median age 60 years; range 31-69 years; seven women). The majority required resection of both arterial and venous systems (n = 8), and the technique for vascular reconstruction was either interposition grafts or femoral-femoral crossover grafts. The median operative time was 510 min (range 330-960 min). Clear resection margins (R0) were achieved in nine patients. The median length of stay was 25 days (range 7-83 days). Seven patients did not suffer an early complication. There was one serious complication (Clavien-Dindo ≥ 3), an arterial graft occlusion secondary to thrombus in the immediate postoperative period, requiring a return to theatre and thrombectomy. The median length of follow-up in this study was 22 months (range 4-58 months). CONCLUSION: This series demonstrates that en bloc major vascular resection and reconstruction can be performed safely and can achieve clear resection margins in selected patients with locally advanced or recurrent pelvic malignancy at specialist surgery centres.

Robotic multivisceral pelvic resection: experience from an exenteration unit.

BACKGROUND: Pelvic exenteration remains a viable and effective treatment option for the management of locally advanced or recurrent pelvic malignancy. The aim of this study was to present an early experience of robotic multivisceral resection of pelvic malignancy, and to compare this experience with similar series through a systematic review of the literature. METHODS: A retrospective study was performed on patients who had robotic-assisted multi-visceral resection for pelvic malignancy at a single Colorectal Surgical unit based between two tertiary academic hospitals. Primary outcomes observed included operation type, operation time, perioperative complications, and hospital length of stay. Secondary outcomes included R0 resection status, lymph node harvest, and rate of recurrence at clinical follow-up. RESULTS: Eight cases of robotic multivisceral resection were performed for primary locally advanced pelvic malignancy involving a rectal resection as part of their operative management. The median age of patients undergoing resection was 56 years (range 29-83 years). The male:female ratio was 6:2. The mean total operating time was 8.3 h (range 6-10 h). Perioperative blood transfusion requirements were minimal. Mean hospital length of stay was 15 days (range 7-26 days). No patients experienced any serious postoperative morbidity or mortality. All patients had clear margins on histological assessment and no patients have recurrence at 12-month follow-up. CONCLUSIONS: Robotic multivisceral resection for malignant disease of the pelvis is a safe and feasible minimally invasive approach in highly selected cases.

Large herbivore assemblages in a changing climate: incorporating water dependence and thermoregulation.

The coexistence of different species of large herbivores (ungulates) in grasslands and savannas has fascinated ecologists for decades. However, changes in climate, land-use and trophic structure of ecosystems increasingly jeopardise the persistence of such diverse assemblages. Body size has been used successfully to explain ungulate niche differentiation with regard to food requirements and predation sensitivity. But this single trait axis insufficiently captures interspecific differences in water requirements and thermoregulatory capacity and thus sensitivity to climate change. Here, we develop a two-dimensional trait space of body size and minimum dung moisture content that characterises the combined food and water requirements of large herbivores. From this, we predict that increased spatial homogeneity in water availability in drylands reduces the number of ungulate species that will coexist. But we also predict that extreme droughts will cause the larger, water-dependent grazers as wildebeest, zebra and buffalo-dominant species in savanna ecosystems - to be replaced by smaller, less water-dependent species. Subsequently, we explore how other constraints such as predation risk and thermoregulation are connected to this two-dimensional framework. Our novel framework integrates multiple simultaneous stressors for herbivores and yields an extensive set of testable hypotheses about the expected changes in large herbivore community composition following climate change.