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Healthcare contributes to environmental harm. Trainee-led Research and Audit in Anaesthesia for Sustainable Healthcare (TRA2SH) is an Australasian network focused on sustainable anaesthesia practice. TRA2SH hypothesised that trainee-led audits alongside education presented on a scheduled national day, called Operation Clean Up, can improve engagement with sustainability initiatives. This paper aims to describe the first two years of Operation Clean Up in terms of goals, achievements and data collected so far. Environmental themes for Operation Clean Up were chosen based on available evidence (life cycle analyses and observational studies). The first Operation Clean Up (OCU 2020) focused on reducing the unnecessary use of single-use disposable absorbent pads (known as ‘blueys’ in Australia, ‘greenies’ in New Zealand). OCU 2021 included: refuse desflurane, reduce bluey use, reuse drug trays, and recycle paper and cardboard. TRA2SH provided an information pack to trainees who presented educational material to their department and fed back procurement figures to quantify each item. Descriptive statistics were used to analyse de-identified pooled data submitted to a centralised database.Eight departments submitted data for OCU 2020 and six provided follow-up data. Bluey use was reduced from a median of 37 to 34 blueys per ten surgical encounters. Fifteen departments submitted pre-campaign data for OCU 2021 with follow-up data to be collected during OCU 2022. Baseline data showed a median bluey use of 31 per ten surgical encounters. Volatile-related emissions were calculated; desflurane’s proportion was 70% of these emissions yet was 11% of volatile procurement. Two participating departments removed desflurane from their formulary following OCU 2021. Operation Clean Up is a practical model for implementing sustainability initiatives using trainees as eco-leaders.

Anaesthetic agents have various financial and environmental impacts. Climate change is one of the biggest threats to human health, and anaesthetic gases contribute to global heating by acting as greenhouse gases. The primary aim of this study was to quantify the financial and environmental impacts of anaesthesia maintenance agents used during surgery in an Australian university teaching hospital. The volume of desflurane, sevoflurane, isoflurane and propofol purchased by a university teaching hospital between 2010 and 2020 was analysed and described in terms of financial and environmental impact. Estimated carbon emissions and financial costs of each agent per annum were calculated using the volumes purchased for each agent. A model of ideal anaesthetic agent usage was used to hypothesise the financial and environmental impact of replacing desflurane (the most environmentally damaging and expensive agent) with alternative agents. Using 2019 as an example year at our health service, replacing desflurane with low flow sevoflurane would save greenhouse gas emissions equivalent to driving over 1.4 million kilometres in an average petrol car. Removing desflurane from machines at our institution could save an estimated A$14,630 per annum through reduced machine testing alone. Our findings and calculations indicate that reducing the use of desflurane would have both financial and environmental benefits for healthcare.

The liver is bathed in bacterial products, including lipopolysaccharide transported from the intestinal portal vasculature, but maintains a state of tolerance that is exploited by persistent pathogens and tumours1–4. The cellular basis mediating this tolerance, yet allowing a switch to immunity or immunopathology, needs to be better understood for successful immunotherapy of liver diseases. Here we show that a variable proportion of CD8+T cells compartmentalized in the human liver co-stain for CD14 and other prototypic myeloid membrane proteins and are enriched in close proximity to CD14highmyeloid cells in hepatic zone 2. CD14+CD8+T cells preferentially accumulate within the donor pool in liver allografts, among hepatic virus-specific and tumour-infiltrating responses, and in cirrhotic ascites. CD14+CD8+T cells exhibit increased turnover, activation and constitutive immunomodulatory features with high homeostatic IL-10 and IL-2 production ex vivo, and enhanced antiviral/anti-tumour effector function after TCR engagement. This CD14+CD8+T cell profile can be recapitulated by the acquisition of membrane proteins—including the lipopolysaccharide receptor complex—from mononuclear phagocytes, resulting in augmented tumour killing by TCR-redirected T cells in vitro. CD14+CD8+T cells express integrins and chemokine receptors that favour interactions with the local stroma, which can promote their induction through CXCL12. Lipopolysaccharide can also increase the frequency of CD14+CD8+T cells in vitro and in vivo, and skew their function towards the production of chemotactic and regenerative cytokines. Thus, bacterial products in the gut–liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8+T cells with immunomodulatory ability.

Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1–3. Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs. 4–11), would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T cells, including those against the early transcribed replication–transcription complex (RTC)12,13, in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2 (ref. 14), suggesting abortive infection. RNA polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA polymerase was preferentially targeted (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. Enriched pre-existing RNA-polymerase-specific T cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T cells as targets for vaccines against endemic and emerging Coronaviridae.

The efficacy of bevacizumab (BEV) in elderly patients with glioblastoma remains unclear. We evaluated the effect of BEV on survival in this patient population using the Survival, Epidemiology, and End Results (SEER)-Medicare database.

Aim:To compare the overall survival of anaplastic lymphoma kinase-positive non-small-cell lung cancer patients who received alectinib with those who received ceritinib. Materials & methods:Two treatment arms (alectinib [n  183] and ceritinib [n  67]) were extracted from clinical trials and an electronic health record database, respectively. Propensity scores were applied to balance baseline characteristics. Kaplan–Meier and multivariate Cox regression were conducted. Results:After propensity score adjustment, baseline characteristics were balanced. Alectinib had a prolonged median overall survival (alectinib  24.3 months and ceritinib  15.6 months) and lower risk of death (hazard ratio: 0.65; 95 CI: 0.48–0.88). Conclusion:Alectinib was associated with prolonged overall survival versus ceritinib, which is consistent with efficacy evidence from clinical trials.

The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)–infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-betloEomesloBlimp-1hiHobitlo T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69+CD103+ CXCR6+CXCR3+). These tissue-resident memory T cells (TRM) are preferentially expanded in patients with partial immune control of HBV infection and can remain in the liver after the resolution of infection, including compartmentalized responses against epitopes within all major HBV proteins. Sequential IL-15 or antigen exposure followed by TGFβ induces liver-adapted TRM, including their signature high expression of exhaustion markers PD-1 and CD39. We suggest that these inhibitory molecules, together with paradoxically robust, rapid, cell-autonomous IL-2 and IFNγ production, equip liver CD8 TRM to survive while exerting local noncytolytic hepatic immunosurveillance.

ABSTRACTA successful pregnancy depends on the intricate and timely interactions of maternal and fetal cells. Placental extravillous cytotrophoblast invasion involves a cellular transition from an epithelial to mesenchymal phenotype. Villous cytotrophoblasts undergo a partial epithelial to mesenchymal transition (EMT) when differentiating into extravillous cytotrophoblasts and gain the capacity to migrate and invade. This review summarizes our current knowledge regarding known regulators of EMT in the human placenta, including the inducers of EMT, upstream transcription factors that control EMT and the downstream effectors, cell adhesion molecules and their differential expression and functions in pregnancy pathologies, preeclampsia (PE) and fetal growth restriction (FGR). The review also describes the research strategies that were used for the identification of the functional role of EMT targets in vitro. A better understanding of molecular pathways driven by placental EMT and further elucidation of signaling pathways underlying the developmental programs may offer novel strategies of targeted therapy for improving feto-placental growth in placental pathologies including PE and FGR.

A better understanding of mechanisms that regulate CD8+T cell responses to therapeutic vaccines is needed to develop approaches to enhance vaccine efficacy for chronic viral infections and cancers. We show here that NK cell depletion enhanced antigen-specific T cell responses to chimp adenoviral vector (ChAdOx) vaccination in a mouse model of chronic HBV infection (CHB). Probing the mechanism underlying this negative regulation, we observed that CHB drove parallel up-regulation of programmed cell death ligand 1 (PD-L1) on liver-resident NK cells and programmed cell death 1 (PD-1) on intrahepatic T cells. PD-L1–expressing liver-resident NK cells suppressed PD-1hiCD8+T cells enriched within the HBV-specific response to therapeutic vaccination. Cytokine activation of NK cells also induced PD-L1, and combining cytokine activation with PD-L1 blockade resulted in conversion of NK cells into efficient helpers that boosted HBV-specific CD8+T cell responses to therapeutic vaccination in mice and to chronic infection in humans. Our findings delineate an immunotherapeutic combination that can boost the response to therapeutic vaccination in CHB and highlight the broader importance of PD-L1–dependent regulation of T cells by cytokine-activated NK cells.

With the growing appreciation of tissue-resident immunity, studying tissue-specific immune cells contributing to both homeostasis and disease is imperative. Here, we provide a protocol for the isolation of human intrahepatic leukocyte (IHL) maximizing viability, purity, and yield. Our protocol is scalable by tissue weight, allowing for reproducible and efficient IHL liberation suitable for functional characterization, cell isolation, and profiling by flow (or mass) cytometry. Furthermore, we provide a “guide” to determine an expected IHL yield per gram of tissue processed.

The Agilent 2100 Bioanalyzer enables small-scale gel electrophoretic separation of nucleic acids on a microfluidic chip; however, a shortage of chips and an excess of reagents are common issues. Here we explore the compatibility of two commonly used Bioanalyzer reagents with three Bioanalyzer chip types. Microfluidic electrophoretic separation of DNA and RNA using DNA High Sensitivity and RNA 6000 Nano reagents, respectively, was successfully performed on multiple chip types following the assay-specific protocols. For RNA quality and next-generation sequencing (NGS) library length estimation, the Bioanalyzer chips we tested can be used interchangeably. These findings will be valuable for any laboratory using the Agilent Bioanalyzer in a shared facility.

Presents information on the Sheltered Work Opportunities Project of Bournemouth, England-based Cherry Tree Nursery. Skills involved in working in a nursery; Facilities of the Cherry Tree Nursery; Work skills acquired by volunteers.

Reports that cork oak growers in southern Europe are starting to gain a seal of approval for sustainable management. Decline of demand for wine corks in the face of competition from synthetic wine stoppers and screwcaps.

The author reflects on the advantages and disadvantages of single-sex schools. She says students are not learning social skills necessary later in life, but they also gain confidence. She notes the environment may be less distracting because there are fewer disruptive outbursts. There is no competition for who goes out with the most attractive or popular person of the opposite sex.

The article presents the author's views on the television advertising market. It is stated that market takes on another dimension at Christmas and the advertising is a huge part of that. Suggestions are offered on creating formats for advertising campaigns including formats, industry standard metrics, and adding layers to video.

The article presents the views offered by Jamie West, the director of Sky AdSmart and commercial, at the Future TV advertising forum in London, England. West said that Sky's advertising product AdSmart will not cannibalise the existing TV advertising but provide a powerful new route to market for advertisers.

The article reports that television programs have been watched by 76 percent of people due to positive feedback from Twitter.

The article reports that positive feedback from Twitter has resulted in 76 percent of people watching television programs.

The article reports that according to Google's head of mobile and social, EMEA, Ian Carrington, Internet searching on mobile communication devices will overtake desktop Internet searching in the next few years. Carrington cited Debenhmans as a retailer that has seen significant sales increases following its mobile site development, seeing conversion rates double after building its first mobile site.

The article reports on the launch of an online subscription platform by the Labs programme of BBC Worldwide Ltd. which have been designed specifically for students in Great Britain. The negotiations between BBC Worldwide and Flooved about potential integration opportunities are highlighted. According to BBC Worldwide co-founder Hamish Brocklebank, the platform aims to help universities and professors in keeping pace with the trends concerning the use of digital devices among college students.

The article reports on the deal between virtual world start-up for kids MiniMonos and children's publisher Egmont UK Ltd in Great Britain. It notes that the virtual world start-up is working with Egmont to produce content for the publisher's products which include the Toxic magazine. Melissa Clark-Reynolds, founder and chief executive officer (CEO) of MiniMonos, believes that the brands produced by Egmont are suitable to the start-ups ethical brand goals.

The article reports on the growth of publisher Vice Media Inc.'s global referral traffic through the aid of social networks. It is inferred that over half of the company's global referral traffic comes from social networks Twitter and Facebook, instead of search engines. Moreover, the company has also revealed a 75% surge since it relaunched its mobile-optimised site in July 2012.

The article reports on the plan of BBC Worldwide Ltd. to assess the monetary contribution of social media to business. It notes mobile as one of the biggest opportunities open for digital start-ups. Executive Karla Geci points out Facebook Inc.'s commitment in developing sophisticated mobile tool kits for developers who want to incorporate their mobile propositions with the network. It reveals the plan of Google Inc. to integrate its Google+ with the other products for unification.

The article reports on the launch of the personalised targeted advertising service InStream by commercial radio network Absolute Radio to third-party mobile applications including Radioplayer in Great Britain. It is inferred that the move will enable users to receive fewer and personally targeted ads on Radioplayer. The launch is expected to result in a commercial revenue share model.

The article reports on the launch of the personalised targeted advertising service InStream by commercial radio network Absolute Radio to third-party mobile applications including Radioplayer in Great Britain. It is inferred that the move will enable users to receive fewer and personally targeted ads on Radioplayer. The launch is expected to result in a commercial revenue share model.

The article reports that a series of data-driven advertising targeting packages will be launched by Channel 4 in 2013 as part of the company's continued strategy to deliver more value to registered users and advertisers.

The article offers brief information on Virgin TV Anywhere, a cloud-based entertainment service from Virgin Media Inc., letting subscribers access live and on-demand TV and film content via online and mobile devices.

An interview with Rakuten Inc. marketing director Adam Stewart is presented. He explains the launch of an online marketplace for Play.com in Great Britain and other businesses. He stresses that their business model focuses on empowering the merchants to develop customer relationships. He stresses the commitment of the company to produce more product and content discovery for consumers.

The article reports on the move of the publisher Guardian News & Media Ltd. to tie up with music video platform Muzu to explore third-party video syndication as part of its digital-first strategy. The move will provide Guardian access to Muzu's 100,000-catalague of official music videos to incorporate into its music-dedicated pages. Dipesh Morjaria, the publisher's business director of multimedia, streses the goal of the publisher to covert editorial interest into commerical value.

The article reports on the launch of the Thinkbox Ltd.'s first free iPad application aimed at the advertising industry in Great Britain. The free application was designed as a resource for advisers, creative agencies and media planners and buyers. The company aims to provide a content-rich table experience and to ensure it continues educating people about the market opportunities.

The article reports on the launch of the EE brand of fourth generation (4G) network by mobile operator Everything Everywhere Ltd. (EE) in Great Britain. It is inferred that the service will be offering mobile services up to four times faster than the third generation (3G) network. Issues addressed by EE chief executive officer (CEO) Olaf Swantee are highlighted.

The article reports on the plan of charitable organization Action for Children to create a personalized web experience aimed at boosting data-driven techniques in the U.S. According to Action for Children digital communications officer Darren Robertson, the misconceptions about the deployment costs are barriers that prevented charitable institutions from embracing it. Moreover, it also developed mobile-optimized platforms to furnish curated content from its primary to the fundraising site.

The article offers brief information on the micropayment-based television (TV) catch-up player from ITV.

The article reports on the team-up of Channel 4 and social television analytics firm SecondSync to track social media activity around its shows. It states that the broadcaster will monitor social media conversations with the view of exploring the associations with its BARB audience ratings. It also highlights the plan of Kellogg's to launch second-screen television campaign on Channel 4 to promote Krave brand.

The article reports on the launch of ITV PLC's synchronized, dual-screen ad format. It states that Rimmel London is planning to use ITV's synchronized dual screen ad format. It notes that the ad format, called Ad Sync will operate on smartphone and tablet iOS applications, developed by FremantleMedia UK Interactive with the linear broadcast advertisement during "The X Factor." It notes that the format was launched by ITV's managing director of online and commercial Fru Hazlitt.

The article reports on the launch of the video content to the network Guardian Select of Guardian News & Media Ltd. in Great Britain. It is inferred that the access to video content would facilitate an increase in digital revenue streams. A brief overview on the Guardian Select which comprises of 150 blogging and publishing network is provided.

The article reports that BBC Worldwide is to launch its first Ultraviolet-enabled DVD and Blu-Rays for Doctor Who and Top Gear in Great Britain. The commercial arm of the BBC will issue Ultraviolet-enabled versions of a selection of content, including "Doctor Who Series 7: Part 1," a new Top Gear commission, and "Attenborough: 60 Years in the Wild," the forthcoming retrospective on Sir David Attenborough's 60 years in natural history broadcasting.

The article reports that YouTube has added 60 more television channels in its content of 100 channels. As mentioned, these channels includes BBC Worldwide Americas Inc., Fremantlemedia and All3Media. It states that the content will include various categories including food, health and comedy. It mentions that YouTube will also include two channels related to nature and topical science.

The article offers brief information on the comedy show "YappFactor" on Zeebox application from Zeebox.