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Burning fossil fuels has resulted in a prominent yet unintended manipulation of the global sulfur cycle. Emissions of sulfur dioxide and reactive sulfur to the atmosphere have caused widespread health and environmental impacts and have led, ultimately, to calls to decrease sulfur emissions. However, anthropogenic modification of the sulfur cycle is far from over. Using four contrasting case studies from across the United States, we show how high levels of sulfur are added to croplands as fertilizers and pesticides and constitute a major yet under-studied environmental perturbation. Long-term sulfur additions to crops probably cause similar consequences for the health of soil and downstream aquatic ecosystems as those observed in regions historically impacted by acid rain, yet the cascade of effects has not been broadly explored. A new wave of research on the sulfur cycle will require studies that examine the integrated roles of climate, hydrology and other element cycles in modifying sulfur processes and flows within and downgradient of agricultural source areas. Such research must include not only scientists, but also farmers, regulating authorities and land managers who are engaged in developing approaches to monitor and mitigate environmental and human health impacts.Deliberate application of sulfur onto croplands as fertilizer and pesticide probably causes environmental damage similar to historical acid rain events, according to a literature review and four case studies from the United States.

Streams and rivers can substantially modify organic carbon (OC) inputs from terrestrial landscapes, and much of this processing is the result of microbial respiration. While carbon dioxide (CO2) is the major end-product of ecosystem respiration, methane (CH4) is also present in many fluvial environments even though methanogenesis typically requires anoxic conditions that may be scarce in these systems. Given recent recognition of the pervasiveness of this greenhouse gas in streams and rivers, we synthesized existing research and data to identify patterns and drivers of CH4, knowledge gaps, and research opportunities. This included examining the history of lotie CH4 research, creating a database of concentrations and fluxes (MethDB) to generate a global-scale estimate of fluvial CH4 efflux, and developing a conceptual framework and using this framework to consider how human activities may modify fluvial CH4 dynamics. Current understanding of CH4 in streams and rivers has been strongly influenced by goals of understanding OC processing and quantifying the contribution of CH4 to ecosystem C fluxes. Less effort has been directed towards investigating processes that dictate in situ CH4 production and loss. CH4 makes a meager contribution to watershed or landscape C budgets, but streams and rivers are often significant CH4 sources to the atmosphere across these same spatial extents. Most fluvial systems are supersaturated with CH4 and we estimate an annual global emission of 26.8 Tg CH4, equivalent to ∼15-40% of wetland and lake effluxes, respectively. Less clear is the role of CH4 oxidation, methanogenesis, and total anaerobic respiration to whole ecosystem production and respiration. Controls on CH4 generation and persistence can be viewed in terms of proximate controls that influence methanogenesis (organic matter, temperature, alternative electron acceptors, nutrients) and distal geomorphic and hydrologie drivers. Multiple controls combined with its extreme redox status and low solubility result in high spatial and temporal variance of CH4 in fluvial environments, which presents a substantial challenge for understanding its larger-scale dynamics. Further understanding of CH4 production and consumption, anaerobic metabolism, and ecosystem energetics in streams and rivers can be achieved through more directed studies and comparison with knowledge from terrestrial, wetland, and aquatic disciplines.

Subjective Cognitive Complaints (SCCs) may represent one of the earliest stages of preclinical dementia. The objective of the present study was to extend previous work by our group to examine the relationship between participant-reported and informant-reported memory and non-memory SCCs, cognitive decline and incident dementia, over a six-year period. Participants were 873 community dwelling older adults (Mage = 78.65, SD = 4.79) without dementia and 843 informants (close friends or family) from the Sydney Memory and Ageing Study. Comprehensive neuropsychological testing and diagnostic assessments were carried out at baseline and biennially for six years. Linear mixed models and Cox proportional hazard models were performed to determine the association of SCCs, rate of cognitive decline and risk of incident dementia, controlling demographics and covariates of mood and personality. Participant and informant memory-specific SCCs were associated with rate of global cognitive decline; for individual cognitive domains, participant memory SCCs predicted decline for language, while informant memory SCCs predicted decline for executive function and memory. Odds of incident dementia were associated with baseline participant memory SCCs and informant memory and non-memory SCCs in partially adjusted models. In fully adjusted models, only informant SCCs were associated with increased risk of incident dementia. Self-reported memory-specific cognitive complaints are associated with decline in global cognition over 6-years and may be predictive of incident dementia, particularly if the individual is depressed or anxious and has increased neuroticism or decreased openness. Further, if and where possible, informants should be sought and asked to report on their perceptions of the individual's memory ability and any memory-specific changes that they have noticed as these increase the index of diagnostic suspicion.

Objectives. To test the construct validity of the short‐form version of the Depression anxiety and stress scale (DASS‐21), and in particular, to assess whether stress as indexed by this measure is synonymous with negative affectivity (NA) or whether it represents a related, but distinct, construct. To provide normative data for the general adult population. Design. Cross‐sectional, correlational and confirmatory factor analysis (CFA). Methods. The DASS‐21 was administered to a non‐clinical sample, broadly representative of the general adult UK population (N=1,794). Competing models of the latent structure of the DASS‐21 were evaluated using CFA. Results. The model with optimal fit (RCFI = 0.94) had a quadripartite structure, and consisted of a general factor of psychological distress plus orthogonal specific factors of depression, anxiety, and stress. This model was a significantly better fit than a competing model that tested the possibility that the Stress scale simply measures NA. Conclusions. The DASS‐21 subscales can validly be used to measure the dimensions of depression, anxiety, and stress. However, each of these subscales also taps a more general dimension of psychological distress or NA. The utility of the measure is enhanced by the provision of normative data based on a large sample.

Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS activity. Plexiform neurofibromas (PN) are peripheral nerve sheath tumors that develop in patients with NF1 and are associated with substantial morbidity and for which, until recently, the only treatment was surgical resection. However, surgery carries several risks and a proportion of PN are considered inoperable. Understanding the genetic underpinnings of PN led to the investigation of targeted therapies as medical treatment options, and the MEK1/2 inhibitor selumetinib has shown promising efficacy in pediatric patients with NF1 and symptomatic, inoperable PN. In a phase I/II trial, most children (approximately 70%) achieved reduction in tumor volume accompanied by improvements in patient-reported outcomes (decreased tumor-related pain and improvements in quality of life, strength, and range of motion). Selumetinib is currently the only licensed medical therapy indicated for use in pediatric patients with symptomatic, inoperable NF1-PN, with approval based on the results of this pivotal clinical study. Several other MEK inhibitors (binimetinib, mirdametinib, trametinib) and the tyrosine kinase inhibitor cabozantinib are also being investigated as medical therapies for NF1-PN. Careful consideration of multiple aspects of both disease and treatments is vital to reduce morbidity and improve outcomes in patients with this complex and heterogeneous disease, and clinicians should be fully aware of the risks and benefits of available treatments. There is no single treatment pathway for patients with NF1-PN; surgery, watchful waiting, and/or medical treatment are options. Treatment should be individualized based on recommendations from a multidisciplinary team, considering the size and location of PN, effects on adjacent tissues, and patient and family preferences. This review outlines the treatment strategies currently available for patients with NF1-PN and the evidence supporting the use of MEK inhibitors, and discusses key considerations in clinical decision-making.

Arthropod endosymbiont Wolbachia pipientis is part of a global biocontrol strategy to reduce the replication of mosquito-borne RNA viruses such as alphaviruses. We previously demonstrated the importance of a host cytosine methyltransferase, DNMT2, in Drosophila and viral RNA as a cellular target during pathogen-blocking. Here we report a role for DNMT2 in Wolbachia -induced alphavirus inhibition in Aedes species. Expression of DNMT2 in mosquito tissues, including the salivary glands, is elevated upon virus infection. Notably, this is suppressed in Wolbachia- colonized animals, coincident with reduced virus replication and decreased infectivity of progeny virus. Ectopic expression of DNMT2 in cultured Aedes cells is proviral, increasing progeny virus infectivity, and this effect of DNMT2 on virus replication and infectivity is dependent on its methyltransferase activity. Finally, examining the effects of Wolbachia on modifications of viral RNA by LC-MS show a decrease in the amount of 5-methylcytosine modification consistent with the down-regulation of DNMT2 in Wolbachia colonized mosquito cells and animals. Collectively, our findings support the conclusion that disruption of 5-methylcytosine modification of viral RNA is a vital mechanism operative in pathogen blocking. These data also emphasize the essential role of epitranscriptomic modifications in regulating fundamental alphavirus replication and transmission processes.

The mainstay treatment for Degenerative Cervical Myelopathy (DCM) is surgical decompression. Not all cases, however, are suitable for surgery. Recent international guidelines advise surgery for moderate to severe disease as well as progressive mild disease. The goal of this study was to examine the factors in current practice that drive the decision to operate in DCM. Retrospective cohort study. 1 year of cervical spine MRI scans (N = 1123) were reviewed to identify patients with DCM with sufficient clinical documentation (N = 39). Variables at surgical assessment were recorded: age, sex, clinical signs and symptoms of DCM, disease severity, and quantitative MRI measures of cord compression. Bivariate correlations were used to compare each variable with the decision to offer the patient an operation. Subsequent multivariable analysis incorporated all significant bivariate correlations. Of the 39 patients identified, 25 (64%) were offered an operation. The decision to operate was significantly associated with narrower non-pathological canal and cord diameters as well as cord compression ratio, explaining 50% of the variance. In a multivariable model, only cord compression ratio was significant (p = 0.017). Examination findings, symptoms, functional disability, disease severity, disease progression, and demographic factors were all non-significant. Cord compression emerged as the main factor in surgical decision-making prior to the publication of recent guidelines. Newly identified predictors of post-operative outcome were not significantly associated with decision to operate.

Streams and rivers are active processors of carbon, leading to significant emissions of CO2 and possibly CH4 to the atmosphere. Patterns and controls of CH4 in fluvial ecosystems remain relatively poorly understood. Furthermore, little is known regarding how major human impacts to fluvial ecosystems may be transforming their role as CH4 producers and emitters. Here, we examine the consequences of two distinct ecosystem changes as a result of human land use: increased nutrient loading (primarily as nitrate), and increased sediment loading and deposition of fine particles in the benthic zone. We did not find support for the hypothesis that enhanced nitrate loading down-regulates methane production via thermodynamic or toxic effects. We did find strong evidence that increased sedimentation and enhanced organic matter content of the benthos lead to greater methane production (diffusive + ebullitive flux) relative to pristine fluvial systems in northern Wisconsin (upper Midwest, USA). Overall, streams in a human-dominated landscape of southern Wisconsin were major regional sources of CH4 to the atmosphere, equivalent to ∼20% of dairy cattle emissions, or ∼50% of a landfill's annual emissions. We suggest that restoration of the benthic environment (reduced fine deposits) could lead to reduced CH4 emissions, while decreasing nutrient loading is likely to have limited impacts to this ecosystem process.

Objectives: To evaluate the reliability and validity of the PANAS (Watson, Clark, & Tellegen, 1988b) and provide normative data. Design: Cross‐sectional and correlational. Method: The PANAS was administered to a non‐clinical sample, broadly representative of the general adult UK population (N = 1,003). Competing models of the latent structure of the PANAS were evaluated using confirmatory factor analysis. Regression and correlational analysis were used to determine the influence of demographic variables on PANAS scores as well as the relationship between the PANAS with measures of depression and anxiety (the HADS and the DASS). Results: The best‐fitting model (robust comparative fit index = .94) of the latent structure of the PANAS consisted of two correlated factors corresponding to the PA and NA scales, and permitted correlated error between items drawn from the same mood subcategories (Zevon & Tellegen, 1982). Demographic variables had only very modest influences on PANAS scores and the PANAS exhibited measurement invariance across demographic subgroups. The reliability of the PANAS was high, and the pattern of relationships between the PANAS and the DASS and HADS were consistent with tripartite theory. Conclusion: The PANAS is a reliable and valid measure of the constructs it was intended to assess, although the hypothesis of complete independence between PA and NA must be rejected. The utility of this measure is enhanced by the provision of large‐scale normative data.

Magnetic resonance imaging (MRI) is gold-standard for investigating Degenerative Cervical Myelopathy (DCM), a disabling disease triggered by compression of the spinal cord following degenerative changes of adjacent structures. Quantifiable compression correlates poorly with disease and language describing compression in radiological reports is un-standardised. Retrospective chart review. 1) Identify terminology in radiological reporting of cord compression and elucidate relationships between language and quantitative measures 2) Evaluate language's ability to distinguish myelopathic from asymptomatic compression 3) Explore correlations between quantitative or qualitative features and symptom severity 4) Investigate the influence of quantitative and qualitative measures on surgical referrals. From all cervical spine MRIs conducted during one year at a tertiary centre (N = 1123), 166 patients had reported cord compression. For each spinal level deemed compressed by radiologists (N = 218), four quantitative measurements were calculated: 'Maximum Canal Compromise (MCC); 'Maximum Spinal Cord Compression' (MSCC); 'Spinal Canal Occupation Ratio' (SCOR) and 'Compression Ratio' (CR). These were compared to associated radiological reporting terminology. 1) Terminology in radiological reports was varied. Objective measures of compromise correlated poorly with language. \"Compressed\" was used for more severe cord compromise as measured by MCC (p<0.001), MSCC (p<0.001), and CR (p = 0.002). 2) Greater compromise was seen in cords with a myelopathy diagnosis across MCC (p<0.001); MSCC (p = 0.002) and CR (p<0.001). \"Compress\" (p<0.001) and \"Flatten\" (p<0.001) were used more commonly for myelopathy-diagnosis levels. 3) Measurements of cord compromise (MCC: p = 0.304; MSCC: p = 0.217; SCOR: p = 0.503; CR: p = 0.256) and descriptive terms (p = 0.591) did not correlate with i-mJOA score. 4) The only variables affecting spinal surgery referral were increased MSCC (p = 0.001) and use of 'Compressed' (p = 0.045). Radiological reporting in DCM is variable and language is not fully predictive of the degree of quantitative cord compression. Additionally, terminology may influence surgical referrals.