Discussion of: A statistical analysis of multiple temperature proxies: Are reconstructions of surface temperatures over the last 1000 years reliable?

Discussion of "A statistical analysis of multiple temperature proxies: Are reconstructions of surface temperatures over the last 1000 years reliable?" by B.B. McShane and A.J. Wyner [arXiv:1104.4002]Comment: Published in at http://dx.doi.org/10.1214/10-AOAS398F the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Joint analysis of stressors and ecosystem services to enhance restoration effectiveness

With increasing pressure placed on natural systems by growing human populations, both scientists and resource managers need a better understanding of the relationships between cumulative stress from human activities and valued ecosystem services. Societies often seek to mitigate threats to these services through large-scale, costly restoration projects, such as the over one billion dollar Great Lakes Restoration Initiative currently underway. To help inform these efforts, we merged high-resolution spatial analyses of environmental stressors with mapping of ecosystem services for all five Great Lakes. Cumulative ecosystem stress is highest in near-shore habitats, but also extends offshore in Lakes Erie, Ontario, and Michigan. Variation in cumulative stress is driven largely by spatial concordance among multiple stressors, indicating the importance of considering all stressors when planning restoration activities. In addition, highly stressed areas reflect numerous different combinations of stressors rather than a single suite of problems, suggesting that a detailed understanding of the stressors needing alleviation could improve restoration planning. We also find that many important areas for fisheries and recreation are subject to high stress, indicating that ecosystem degradation could be threatening key services. Current restoration efforts have targeted high-stress sites almost exclusively, but generally without knowledge of the full range of stressors affecting these locations or differences among sites in service provisioning. Our results demonstrate that joint spatial analysis of stressors and ecosystem services can provide a critical foundation for maximizing social and ecological benefits from restoration investments. www.pnas.org/lookup/suppl/doi:10.1073/pnas.1213841110/-/DCSupplementa

Prime beef cuts : culinary images for thinking 'men'

The paper contributes to scholarship theorising the sociality of the brand in terms of subject positions it makes possible through drawing upon the generative context of circulating discourses, in this case of masculinity, cuisine and celebrity. Specifically, it discusses masculinity as a socially constructed gender practice (Bristor and Fischer, 1993), examining materialisations of such practice in the form of visualisations of social relations as resources for 'thinking gender' or 'doing gender'. The transformative potential of the visualisations is illuminated by exploring the narrative content choreographed within a series of photographic images positioning the market appeal of a celebrity chef through the medium of a contemporary lifestyle cookery book. We consider how images of men 'doing masculinity'are not only channelled into reproducing existing gender hierarchy and compulsory heterosexuality in the service of commercial ends, but also into disrupting such enduring stereotyping through subtle reframing. We acknowledge that masculinity is already inscribed within conventionalised representations of culinary culture. In this case we consider how traces of masculinity are exploited and reinscribed through contemporary images that generate resources for rethinking masculine roles and identities, especially when viewed through the lens of stereotypically feminised pursuits such as shopping, food preparation, cooking, and the communal intimacy of food sharing. We identify unsettling tensions within the compositions, arguing that they relate to discursive spaces between the gendered positions written into the images and the popular imagination they feed off. Set against landscapes of culinary culture, we argue that the images invoke a brand of naively roughish "laddishness" or "blokishness", rendering it in domesticated form not only as benign and containable, but fashionable, pliable and, importantly, desirable. We conclude that although the images draw on stereotypical premeditated notions of a feral, boisterous and untamed heterosexual masculinity, they also set in motion gender-blending narratives

Translabyrinthine resection of NF2 associated vestibular schwannoma with cochlear implant insertion

The authors present the case of a 24-year-old female with neurofibromatosis type 2. Growth of the left vestibular schwannoma and progressive hearing loss prompted the decision to proceed to translabyrinthine resection with cochlear nerve preservation and cochlear implant insertion. Complete resection with preservation of the facial and cochlear nerves was achieved. The patient had grade 1 facial function and was discharged on postoperative day 4 following suturing of a minor CSF leak. This case highlights the feasibility of cochlear nerve preservation and cochlear implant insertion in appropriately selected patients, offering a combination of effective tumor control and hearing rehabilitation. The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID2112

Risk factors for severe outcomes in patients with systemic vasculitis & COVID‐19: a bi‐national registry‐based cohort study

OBJECTIVE: COVID-19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and so may be at risk of severe outcomes following COVID-19. It is important to establish the risk factors for severe COVID-19 outcomes in these patients, including the impact of immunosuppressive therapies. METHODS: A multi-centre cohort was developed through the participation of centres affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes were described. Logistic regression was used to evaluate associations between potential risk factors and severe COVID-19 outcome, defined as a requirement for advanced oxygen therapy, invasive ventilation, or death. RESULTS: Sixty-five cases of patients with systemic vasculitis who developed COVID-19 were reported (median age 70 years, 49% female) of whom 25 (38%) experienced a severe outcome. Most cases (55/65, 85%) had ANCA-associated vasculitis (AAV). Almost all patients required hospitalization (59/65, 91%), 7 patients (11%) were admitted to intensive care and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcome (adjusted odds ratio [aOR] 3.7 (1.1-14.9, p=0.047)) as was comorbid respiratory disease (aOR 7.5 (1.9-38.2, p=0.006)). Vasculitis disease activity and non-glucocorticoid immunosuppression were not associated with severe outcome. CONCLUSION: In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID-19. These data can inform clinical decision making relating to risk of severe COVID-19 in this vulnerable patient group

Combinatorial quorum sensing allows bacteria to resolve their social and physical environment

Quorum sensing (QS) is a cell–cell communication system that controls gene expression in many bacterial species, mediated by diffusible signal molecules. Although the intracellular regulatory mechanisms of QS are often well-understood, the functional roles of QS remain controversial. In particular, the use of multiple signals by many bacterial species poses a serious challenge to current functional theories. Here, we address this challenge by showing that bacteria can use multiple QS signals to infer both their social (density) and physical (mass-transfer) environment. Analytical and evolutionary simulation models show that the detection of, and response to, complex social/physical contrasts requires multiple signals with distinct half-lives and combinatorial (nonadditive) responses to signal concentrations. We test these predictions using the opportunistic pathogen Pseudomonas aeruginosa and demonstrate significant differences in signal decay betweeallyn its two primary signal molecules, as well as diverse combinatorial responses to dual-signal inputs. QS is associated with the control of secreted factors, and we show that secretome genes are preferentially controlled by synergistic “AND-gate” responses to multiple signal inputs, ensuring the effective expression of secreted factors in high-density and low mass-transfer environments. Our results support a new functional hypothesis for the use of multiple signals and, more generally, show that bacteria are capable of combinatorial communication

Plasmodium knowlesi Genome Sequences from Clinical Isolates Reveal Extensive Genomic Dimorphism.

Plasmodium knowlesi is a newly described zoonosis that causes malaria in the human population that can be severe and fatal. The study of P. knowlesi parasites from human clinical isolates is relatively new and, in order to obtain maximum information from patient sample collections, we explored the possibility of generating P. knowlesi genome sequences from archived clinical isolates. Our patient sample collection consisted of frozen whole blood samples that contained excessive human DNA contamination and, in that form, were not suitable for parasite genome sequencing. We developed a method to reduce the amount of human DNA in the thawed blood samples in preparation for high throughput parasite genome sequencing using Illumina HiSeq and MiSeq sequencing platforms. Seven of fifteen samples processed had sufficiently pure P. knowlesi DNA for whole genome sequencing. The reads were mapped to the P. knowlesi H strain reference genome and an average mapping of 90% was obtained. Genes with low coverage were removed leaving 4623 genes for subsequent analyses. Previously we identified a DNA sequence dimorphism on a small fragment of the P. knowlesi normocyte binding protein xa gene on chromosome 14. We used the genome data to assemble full-length Pknbpxa sequences and discovered that the dimorphism extended along the gene. An in-house algorithm was developed to detect SNP sites co-associating with the dimorphism. More than half of the P. knowlesi genome was dimorphic, involving genes on all chromosomes and suggesting that two distinct types of P. knowlesi infect the human population in Sarawak, Malaysian Borneo. We use P. knowlesi clinical samples to demonstrate that Plasmodium DNA from archived patient samples can produce high quality genome data. We show that analyses, of even small numbers of difficult clinical malaria isolates, can generate comprehensive genomic information that will improve our understanding of malaria parasite diversity and pathobiology

Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation

yesInflammation of adipose tissue in obesity is associated with increased IL-1β, IL-6 and TNF-α secretion and proposed to contribute to insulin resistance. AMP-activated protein kinase (AMPK) regulates nutrient metabolism and is reported to have anti-inflammatory actions in adipose tissue, yet the mechanisms underlying this remain poorly characterised. The effect of AMPK activation on cytokine-stimulated proinflammatory signalling was therefore assessed in cultured adipocytes. AMPK activation inhibited IL-1β-stimulated CXCL10 secretion, associated with reduced interleukin-1 receptor associated kinase-4 (IRAK4) phosphorylation and downregulated MKK4/JNK and IKK/IκB/NFκB signalling. AMPK activation inhibited TNF-α-stimulated IKK/IκB/NFκB signalling but had no effect on JNK phosphorylation. The JAK/STAT3 pathway was also suppressed by AMPK after IL-6 stimulation and during adipogenesis. Adipose tissue from AMPKα1−/− mice exhibited increased JNK and STAT3 phosphorylation, supporting suppression of these distinct proinflammatory pathways by AMPK in vivo. The inhibition of multiple pro-inflammatory signalling pathways by AMPK may underlie the reported beneficial effects of AMPK activation in adipose tissue.British Heart Foundatio