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\"Music and Sonic Environments in Video Games brings together a range of perspectives that explore how music and sound in video games interact with virtual and real environments, often in innovative and unexpected ways\"-- Provided by publisher.

The global nitrogen (N) cycle at the beginning of the 21st century has been shown to be strongly influenced by the inputs of reactive nitrogen (Nr) from human activities, including combustion-related NOx, industrial and agricultural N fixation, estimated to be 220 Tg N yr-1 in 2010, which is approximately equal to the sum of biological N fixation in unmanaged terrestrial and marine ecosystems. According to current projections, changes in climate and land use during the 21st century will increase both biological and anthropogenic fixation, bringing the total to approximately 600 Tg N yr-1 by around 2100. The fraction contributed directly by human activities is unlikely to increase substantially if increases in nitrogen use efficiency in agriculture are achieved and control measures on combustion-related emissions implemented. Some N-cycling processes emerge as particularly sensitive to climate change. One of the largest responses to climate in the processing of Nr is the emission to the atmosphere of NH3, which is estimated to increase from 65 Tg N yr-1 in 2008 to 93 Tg N yr-1 in 2100 assuming a change in global surface temperature of 5 degree C in the absence of increased anthropogenic activity. With changes in emissions in response to increased demand for animal products the combined effect would be to increase NH3 emissions to 135 Tg N yr-1. Another major change is the effect of climate changes on aerosol composition and specifically the increased sublimation of NH4NO3 close to the ground to form HNO3 and NH3 in a warmer climate, which deposit more rapidly to terrestrial surfaces than aerosols. Inorganic aerosols over the polluted regions especially in Europe and North America were dominated by (NH4)2SO4 in the 1970s to 1980s, and large reductions in emissions of SO2 have removed most of the SO42- from the atmosphere in these regions. Inorganic aerosols from anthropogenic emissions are now dominated by NH4NO3, a volatile aerosol which contributes substantially to PM10 and human health effects globally as well as eutrophication and climate effects. The volatility of NH4NO3 and rapid dry deposition of the vapour phase dissociation products, HNO3 and NH3, is estimated to be reducing the transport distances, deposition footprints and inter-country exchange of Nr in these regions. There have been important policy initiatives on components of the global N cycle. These have been regional or country-based and have delivered substantial reductions of inputs of Nr to sensitive soils, waters and the atmosphere. To date there have been no attempts to develop a global strategy to regulate human inputs to the nitrogen cycle. However, considering the magnitude of global Nr use, potential future increases, and the very large leakage of Nr in many forms to soils, waters and the atmosphere, international action is required. Current legislation will not deliver the scale of reductions globally for recovery from the effects of Nr deposition on sensitive ecosystems, or a decline in N2O emissions to the global atmosphere. Such changes would require substantial improvements in nitrogen use efficiency across the global economy combined with optimization of transport and food consumption patterns. This would allow reductions in Nr use, inputs to the atmosphere and deposition to sensitive ecosystems. Such changes would offer substantial economic and environmental co-benefits which could help motivate the necessary actions.

\"On your mark, get set--Teen Titans GO! You don't have to be over 18 to be a superhero! Robin, Beast Boy, Raven, Cyborg and Starfire are back fighting bad guys and eating pizza in these six epic tales. Rock 'n' roll zombies. Killer video games. A gigantic green monster. An evil book. The return of Red X. The Teen Titans swap powers. Multiplying villains! What more could you ask for? The teen superheroes from Jump City tackle all this and more in this exciting all-ages graphic novel\"-- Provided by publisher.

Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma have high survival when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with cetuximab—an antibody against the epidermal growth factor receptor—can preserve high survival and reduce treatment toxicity is unknown. We investigated whether cetuximab would maintain a high proportion of patient survival and reduce acute and late toxicity. RTOG 1016 was a randomised, multicentre, non-inferiority trial at 182 health-care centres in the USA and Canada. Eligibility criteria included histologically confirmed HPV-positive oropharyngeal carcinoma; American Joint Committee on Cancer 7th edition clinical categories T1–T2, N2a–N3 M0 or T3–T4, N0–N3 M0; Zubrod performance status 0 or 1; age at least 18 years; and adequate bone marrow, hepatic, and renal function. We randomly assigned patients (1:1) to receive either radiotherapy plus cetuximab or radiotherapy plus cisplatin. Randomisation was balanced by using randomly permuted blocks, and patients were stratified by T category (T1–T2 vs T3–T4), N category (N0–N2a vs N2b–N3), Zubrod performance status (0 vs 1), and tobacco smoking history (≤10 pack-years vs >10 pack-years). Patients were assigned to receive either intravenous cetuximab at a loading dose of 400 mg/m2 5–7 days before radiotherapy initiation, followed by cetuximab 250 mg/m2 weekly for seven doses (total 2150 mg/m2), or cisplatin 100 mg/m2 on days 1 and 22 of radiotherapy (total 200 mg/m2). All patients received accelerated intensity-modulated radiotherapy delivered at 70 Gy in 35 fractions over 6 weeks at six fractions per week (with two fractions given on one day, at least 6 h apart). The primary endpoint was overall survival, defined as time from randomisation to death from any cause, with non-inferiority margin 1·45. Primary analysis was based on the modified intention-to-treat approach, whereby all patients meeting eligibility criteria are included. This study is registered with ClinicalTrials.gov, number NCT01302834. Between June 9, 2011, and July 31, 2014, 987 patients were enrolled, of whom 849 were randomly assigned to receive radiotherapy plus cetuximab (n=425) or radiotherapy plus cisplatin (n=424). 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were subsequently eligible. After median follow-up duration of 4·5 years, radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival (hazard ratio [HR] 1·45, one-sided 95% upper CI 1·94; p=0·5056 for non-inferiority; one-sided log-rank p=0·0163). Estimated 5-year overall survival was 77·9% (95% CI 73·4–82·5) in the cetuximab group versus 84·6% (80·6–88·6) in the cisplatin group. Progression-free survival was significantly lower in the cetuximab group compared with the cisplatin group (HR 1·72, 95% CI 1·29–2·29; p=0·0002; 5-year progression-free survival 67·3%, 95% CI 62·4–72·2 vs 78·4%, 73·8–83·0), and locoregional failure was significantly higher in the cetuximab group compared with the cisplatin group (HR 2·05, 95% CI 1·35–3·10; 5-year proportions 17·3%, 95% CI 13·7–21·4 vs 9·9%, 6·9–13·6). Proportions of acute moderate to severe toxicity (77·4%, 95% CI 73·0–81·5 vs 81·7%, 77·5–85·3; p=0·1586) and late moderate to severe toxicity (16·5%, 95% CI 12·9–20·7 vs 20·4%, 16·4–24·8; p=0·1904) were similar between the cetuximab and cisplatin groups. For patients with HPV-positive oropharyngeal carcinoma, radiotherapy plus cetuximab showed inferior overall survival and progression-free survival compared with radiotherapy plus cisplatin. Radiotherapy plus cisplatin is the standard of care for eligible patients with HPV-positive oropharyngeal carcinoma. National Cancer Institute USA, Eli Lilly, and The Oral Cancer Foundation.

Atmospheric nitrogen (N) deposition is a recognized threat to plant diversity in temperate and northern parts of Europe and North America. This paper assesses evidence from field experiments for N deposition effects and thresholds for terrestrial plant diversity protection across a latitudinal range of main categories of ecosystems, from arctic and boreal systems to tropical forests. Current thinking on the mechanisms of N deposition effects on plant diversity, the global distribution of G200 ecoregions, and current and future (2030) estimates of atmospheric N-deposition rates are then used to identify the risks to plant diversity in all major ecosystem types now and in the future. This synthesis paper clearly shows that N accumulation is the main driver of changes to species composition across the whole range of different ecosystem types by driving the competitive interactions that lead to composition change and/or making conditions unfavorable for some species. Other effects such as direct toxicity of nitrogen gases and aerosols, long-term negative effects of increased ammonium and ammonia availability, soil-mediated effects of acidification, and secondary stress and disturbance are more ecosystem- and site-specific and often play a supporting role. N deposition effects in mediterranean ecosystems have now been identified, leading to a first estimate of an effect threshold. Importantly, ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase, in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas. Critical loads are effect thresholds for N deposition, and the critical load concept has helped European governments make progress toward reducing N loads on sensitive ecosystems. More needs to be done in Europe and North America, especially for the more sensitive ecosystem types, including several ecosystems of high conservation importance. The results of this assessment show that the vulnerable regions outside Europe and North America which have not received enough attention are ecoregions in eastern and southern Asia (China, India), an important part of the mediterranean ecoregion (California, southern Europe), and in the coming decades several subtropical and tropical parts of Latin America and Africa. Reductions in plant diversity by increased atmospheric N deposition may be more widespread than first thought, and more targeted studies are required in low background areas, especially in the G200 ecoregions.

Background:Giant Cell Arteritis (GCA) is a large vessel vasculitis associated with severe morbidity and requiring prompt assessment and treatment. The National Early Inflammatory Arthritis Audit (NEIAA) is a mandated audit of rheumatology care in England and Wales. In April 2023 GCA was added to the list of conditions included in NEIAA to characterise variation in care quality.Objectives:We describe the characteristics of people with GCA enrolled in NEIAA including age, gender, ethnicity and work status. We report data on indicators of disease status and care quality: time from referral to rheumatology assessment, time to diagnosis and symptom duration at first review. These data are compared against patients with rheumatoid arthritis (RA).Methods:We obtained NEIAA data for GCA and RA patients enrolled from April to November 2023. We used descriptive statistics (counts/percentages, medians/interquartile ranges [IQRs], means/standard deviations [sd]) to summarise the characteristics of each diagnostic group: age, gender, ethnicity (Asian, black, mixed, other or white), and work status (in paid work >20 hours per week or not). The primary outcome was time from referral to rheumatology assessment. Secondary outcomes were time from referral to diagnosis and patient reported duration of symptoms prior to assessment (<1 month, 1-3 months or >3months). The number of patients with GCA assessed within 1 day and within 3 days were reported. Patient numbers of less than 5 were redacted to reduce the risk of identification via small counts.Results:2308 patients were recruited (61 with GCA [2.6%], 2223 with RA [96%]); (Table 1). GCA patients were older (median 76 years, IQR [69,81]; 8% of patients <60 years) than RA,(median 61, IQR[50,71]; 49% of patients <60). GCA patients were more likely to be female (69% vs 64%) and white (97% vs 80%), and less likely to be in work (20% vs 45%). Time to assessment was shorter for GCA (median 6 days, IQR [2,15]; mean 14 days, sd 19) than for RA (median 18 days, IQR [11,23]); mean 28 days, sd 34). 6 GCA patients (10%) were assessed by rheumatology within 1 day of referral, and 20 patients (33%) within 3 days. Figure 1 shows the more prompt assessment of GCA patients compared to RA, but also that a small proportion of GCA patients wait longer than 30 days for review. GCA patients experienced less delay from referral to diagnosis (mean 16 days, sd 33; median 7, IQR [1,21] against 36 days, sd 116, for RA [median 27, IQR {15,47}]. People with GCA typically reported shorter duration of symptoms (52% had symptoms <1 month) than those with RA (8%).Conclusion:Enrolment of GCA patients into NEIAA has commenced, with evidence of uptake amongst many clinicians. Recruitment rates are less than expected for the estimated incidence of the condition in the UK, perhaps reflecting lack of awareness of the new requirements for data entry. The patient demographic broadly reflects the known epidemiology of GCA, though fewer non-white patients are present in this small cohort than might be expected. Times to assessment and diagnosis of GCA were shorter than for RA, likely indicating prioritisation of patients with possible GCA symptoms. However, on average these times are still longer than is desirable in the management of a potentially sight-threatening condition. This may reflect delayed outpatient assessment of patients managed initially in hospital, inadequate referral triage or high service pressures. Substantial numbers of patients report prolonged symptoms, suggesting limited public awareness of GCA, difficulty accessing healthcare, or delayed referral from primary care. Our findings offer a reminder to maintain robust GCA pathways and to audit performance robustly to bolster our understanding of patient care.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Edward Alveyn: None declared, Sarah Mackie Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SLM is supported in part by the NIHR Leeds Biomedical Research Centre. The views expressed in this article are those of the authors and not necessarily those of the NIHR, the NIHR Leeds Biomedical Research Centre, the National Health Service or the UK Department of Health and Social Care., Max Yates Advisory board work for BioGen, Financial support from AbbVie and UCB to attend international conferences., James Galloway JG has received honoraria from AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB., JG has received honoraria from AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB.

Background:Systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies (IIM) and systemic sclerosis (SSc) are complex multi-system diseases with substantial risk of hospitalisation and morbidity. The introduction of targeted therapies has improved prognosis for patients; however, it remains unclear whether this has impacted on hospitalisations for these conditions.Objectives:To describe trends in acute hospital admissions due to SLE, IIM and SSc in England between April 1998 to March 2023.Methods:An ecological study was performed to evaluate temporal trends in hospital admissions (emergency vs. day-case admissions) and lengths of admissions with primary diagnoses of SLE, IIM or SSc using the Hospital Episode Statistics dataset, which contains data on all admissions to National Health Service (NHS) hospitals in England. Data collected was specific to cases coded in which the cause of admission was directly attributed to the underlying disease (rather than an admission resulting from an infection or alternative cause for acute presentation in the context of known systemic autoimmune rheumatic disease).Results:As showing in Figure 1A, emergency admissions due to SLE decreased by 36% in England between April 1998 and March 2023, from 1.89 to 1.21 admissions per 100,000 population (p<0.001). Similarly, there was a 25% reduction in emergency admissions from IIM (from 0.56 to 0.42 admissions per 100,000 population, p<0.001), and 63% reduction in SSc admissions (from 0.61 to 0.22 admissions per 100,000 population, p<0.001). The number of attributable hospital bed-days per 100,000 population decreased by 56%, 44% and 78% for SLE, IIM and SSc, respectively (Figure 1B). Marked decreases in emergency admissions were observed for SLE and SSc, but not IIM, in the first year of the COVID-19 pandemic. In contrast to the observed decreases in emergency admissions, day-case admissions per 100,000 population for SLE, IIM and SSc increased by 209%, 535% and 169%, respectively, over the study period (Figure 1C).Conclusion:Acute admissions due to SLE, IIM and SSc have decreased markedly in England over the last 25 years. This may be a result of improved early recognition and aggressive treatment of flares of these diseases. Furthermore, a substantial number of targeted therapies/ biologics have been licensed for therapy for these conditions in the last 25 years. In contrast, day-case admissions increased manyfold, which likely reflects how advances in the treatment of these conditions (often delivered through these day-case admission) have resulted in improved outcomes and reduced costly unplanned emergency admissions. The decrease in emergency admission in year 2019 to 2020 is attributed to COVID-19 pandemic as patients with these conditions are more likely to have reservations to present to hospital as they are often on immunosuppressive therapies.Figure 1.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Melissa Ong: None declared, Mark Russell has received honoraria from AbbVie, Lilly, Galapagos, Menarini and Viforpharma, advisory board fees from Biogen, and support for attending educational meetings from Lilly, Pfizer, Janssen and UCB., James Galloway has received honoraria from Abbvie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB., Chris Wincup has received honoraria from UCB; research funding from AstraZeneca; support for attending educational meetings from Abbvie.

Increasing quantities of atmospheric anthropogenic fixed nitrogen entering the open ocean could account for up to about a third of the ocean's external (nonrecycled) nitrogen supply and up to ∼30% of the annual new marine biological production, ∼0.3 petagram of carbon per year. This input could account for the production of up to ∼1.6 teragrams of nitrous oxide ($\\text{N}_{2}\\text{O}$) per year. Although ∼10% of the ocean's drawdown of atmospheric anthropogenic carbon dioxide may result from this atmospheric nitrogen fertilization, leading to a decrease in radiative forcing, up to about two-thirds of this amount may be offset by the increase in$\\text{N}_{2}\\text{O}$emissions. The effects of increasing atmospheric nitrogen deposition are expected to continue to grow in the future.

Background:Sarcoidosis is a rare systemic inflammatory disorder of unknown aetiology, characterised by the formation of non-caseating granulomas. Clinical manifestations vary enormously, depending on the organ involved. Management can be challenging due to the suboptimal efficacy and toxic side effects associated with conventional treatments such as corticosteroids and second line immunosuppressants. Third-line therapies, including biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs), have emerged as promising alternatives.Objectives:The aim of this systematic review was to examine the efficacy b/tsDMARDs in the treatment of sarcoidosis. Meta-analyses focused on i) studies meeting their primary outcome and ii) studies measuring change in forced vital capacity (FVC).Methods:A systematic search of the MEDLINE, EMBASE, and ClinicalTrials.gov databases were performed to identify placebo controlled and single arm studies reporting on the efficacy of b/tsDMARDs in sarcoidosis patients. Data were manually extracted. Study quality was assessed using the Cochrane risk-of-bias tool and the Newcastle-Ottawa Scale. Meta-analyses of primary outcome data from placebo-controlled trials were performed using random-effects models and reported as odds ratios (OR) with 95% confidence intervals (CI). Meta-analyses of change in FVC from placebo controlled and single arm studies were performed using fixed-effects models and reported as change in FVC % predicted with 95% CI. Heterogeneity was assessed using the I2 statistic.Results:Seventeen studies were included, assessing 9 bDMARDs across 15 trials and one tsDMARD in two trials (Table 1). We found relatively abundant yet inconsistent support for infliximab; potential efficacy of tofacitinib, limited yet consistent support for adalimumab, rituximab and anakinra; inefficacy of golimumab, ustekinumab, and efzofitimod; and inconclusive results for sarilumab. Four randomised controlled trials (RCTs) were eligible for inclusion in the meta-analysis of studies meeting their primary outcome. Pooled estimates suggest no statistically significant difference between the number of patients meeting the primary outcome in the treatment groups compared to the control groups (OR: 1.03, 95% CI: 0.33-3.20) (Figure 1a). Three RCTs and three single-arm trials were eligible for inclusion in the meta-analysis of the change in FVC % predicted. There was a small and clinically non-significant increase in FVC% predicted from baseline following treatment (pooled change in FVC% predicted: 1.80, 95% CI: 0.26-3.34) (Figure 1b).Conclusion:b/tsDMARDs studies in sarcoidosis have demonstrated potential efficacy of infliximab, adalimumab, anakinra, rituximab, and tofacitinib. Meta-analyses of b/tsDMARDs placebo controlled trial data suggests an overall inefficacy in meeting studies primary outcomes, whilst pooled data from placebo controlled and single arm studies examining lung function has demonstrated a small and clinically non-significant increase in FVC%. Limited studies warrant caution in interpreting these findings. Further research involving larger sample sizes and a set of standardised outcome measures is imperative to substantiate these findings.Table 1. Characteristics of the included studies.Figure 1.Meta-analysis of a) studies meeting their primary outcome and b) studies measuring change in forced vital capacity (FVC).REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.