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Increasing evidence suggests that total intravenous anaesthesia (TIVA) may be the preferred anaesthetic for cancer resection surgery. To assist the preparation of a randomised controlled trial (RCT) examining Volatile (versus TIVA) Anaesthesia and Perioperative Outcomes Related to Cancer (VAPOR-C) we developed an 18-question electronic survey to investigate practice patterns and perspectives (emphasising indications, barriers, and impact on cancer outcomes) of TIVA versus inhalational general anaesthesia in Australasia. The survey was emailed to 1,000 (of 5,300 active Fellows) randomly selected Australian and New Zealand College of Anaesthetists (ANZCA) Fellows. The response rate was 27.5% (n=275). Of the respondents, 18% use TIVA for the majority of cases. In contrast, 46% use TIVA 20% of the time or less. Respondents described indications for TIVA as high risk of nausea, neurosurgery, and susceptibility to malignant hyperthermia. Lack of equipment, lack of education and cost were not considered barriers to TIVA use, and a significant proportion (41%) of respondents would use TIVA more often if setup were easier. Of the respondents, 43% thought that TIVA was associated with less cancer recurrence than inhalational anaesthesia, while 46% thought that there was no difference. Yet, only 29% of respondents reported that they use TIVA often or very often for cancer surgery. In Australasia, there is generally a low frequency of TIVA use despite a perception of benefit when compared with inhalational anaesthesia. Anaesthetists are willing to use TIVA for indications where sufficient evidence supports a meaningful level of improvement in clinical outcome. The survey explores attitudes towards use of TIVA for cancer surgery and demonstrates equipoise in anaesthetists' opinions regarding this indication. The inconsistent use of TIVA in Australasia, minimal barriers to its use, and the equipoise in anaesthetists' opinions regarding the effect of TIVA versus inhalational anaesthesia on cancer outcomes support the need for a large prospective RCT.

While cognitive decline and memory loss are the major clinical manifestations of Alzheimer’s disease (AD), they are now recognized as late features of the disease. Recent failures in clinical drug trials highlight the importance of evaluating and treating patients with AD as early as possible and the difficulties in developing effective therapies once the disease progresses. Since the pathological hallmarks of AD including the abnormal aggregation of amyloid-beta and tau can occur decades before any significant cognitive decline in the preclinical stage of AD, it is important to identify the earliest clinical manifestations of AD and elucidate their underlying cellular and molecular mechanisms. Importantly, metabolic and non-cognitive manifestations of AD such as weight loss and alterations of peripheral metabolic signals can occur before the onset of cognitive symptoms and worsen with disease progression. Accumulating evidence suggests that the major culprit behind these early metabolic and non-cognitive manifestations of AD is AD pathology causing dysfunction of the hypothalamus, a brain region critical for integrating peripheral signals with essential homeostatic physiological functions. Here, we aim to highlight recent developments that address the role of AD pathology in the development of hypothalamic dysfunction associated with metabolic and non-cognitive manifestations seen in AD. Understanding the mechanisms underlying hypothalamic dysfunction in AD could give key new insights into the development of novel biomarkers and therapeutic targets.

After the domestication of animals and crops in the Near East some 11,000 years ago, farming had reached much of central Europe by 7500 years before the present. The extent to which these early European farmers were immigrants or descendants of resident hunter-gatherers who had adopted farming has been widely debated. We compared new mitochondrial DNA (mtDNA) sequences from late European hunter-gatherer skeletons with those from early farmers and from modern Europeans. We find large genetic differences between all three groups that cannot be explained by population continuity alone. Most (82%) of the ancient hunter-gatherers share mtDNA types that are relatively rare in central Europeans today. Together, these analyses provide persuasive evidence that the first farmers were not the descendants of local hunter-gatherers but immigrated into central Europe at the onset of the Neolithic.

Glioblastoma: large-scale genomics and a lab model The Cancer Genome Atlas, a large-scale genomics project to catalogue cancer-linked mutations, is starting to produce results. Glioblastoma, the most common brain cancer, was the first target for the project and the initial results, published AOP on 4 September, are now in print. Genes newly implicated in glioblastoma include tumour suppressors ( NF1 , RB1 , ATM and APC ) and several tyrosine kinase genes. Glioblastoma is extremely resistant to therapy, hence the potential importance of the development of a possible model system. Zheng et al . report that mice lacking the tumour suppressors p53 and Pten develop tumours resembling human glioblastomas, associated with increased Myc protein levels. As well as offering a potential system for testing therapeutics, this points to c-Myc as a possible drug target. In a mouse model, it is found that the loss of the tumour suppressors p53 and Pten leads to the development of tumours resembling human primary glioblastomas, and both p53 and PTEN are frequently lost in the human cancer. Loss of these tumour suppressors impairs the differentiation of neural stem cells, due to upregulation of Myc by the concerted action of p53 and PTEN loss. Glioblastoma (GBM) is a highly lethal brain tumour presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as a high-grade disease that typically harbours mutations in EGFR, PTEN and INK4A/ARF (also known as CDKN2A ), and the secondary GBM subtype evolves from the slow progression of a low-grade disease that classically possesses PDGF and TP53 events 1 , 2 , 3 . Here we show that concomitant central nervous system (CNS)-specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute-onset high-grade malignant glioma phenotype with notable clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted TP53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of TP53 as well as the expected PTEN mutations. Integrated transcriptomic profiling, in silico promoter analysis and functional studies of murine neural stem cells (NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives increased Myc protein levels and its associated signature. Functional studies validated increased Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of NSCs doubly null for p53 and Pten ( p53 -/-  Pten -/- ) as well as tumour neurospheres (TNSs) derived from this model. Myc also serves to maintain robust tumorigenic potential of p53 -/-  Pten -/- TNSs. These murine modelling studies, together with confirmatory transcriptomic/promoter studies in human primary GBM, validate a pathogenetic role of a common tumour suppressor mutation profile in human primary GBM and establish Myc as an important target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal and tumorigenic potential.

Researchers have long been interested in how an executive's self-concept affects his or her behaviors, but have lacked a theoretically grounded, validated construct for conducting systematic inquires. The concept of 'core self-evaluation' (CSE), which has been recently validated in the psychology literature, concisely encompasses and consolidates the common, overlapping portions of four previously unconnected personality dimensions: self-esteem, self-efficacy, locus of control, and emotional stability. CSE has great potential to provide substantial leverage for research on executive self-concept. We review and reconcile prior research on related constructs in executive settings (including narcissism, hubris, and overconfidence) and argue that CSE should be adopted as a robust, well-validated umbrella construct for research on executive self-concept. Indeed, a very high level of CSE, or hyper-CSE, aligns closely with what is often colloquially called 'hubris.' We anticipate that hyper-CSE executives--who possess supreme levels of self-confidence, self-potency, and conviction that they will prevail--will manifest this trait in their job behaviors. We develop a set of integrated propositions that describe the implications of CSE for strategic decision processes, strategic choices, and organizational performance. Finally, we propose additional avenues for research.

Since the \"summer of migration\" in 2015, LGBT organizations have been actively involved in migration work, particularly in creating safer spaces for queer asylum seekers and refugees. This involvement marks a shift as these organizations previously had limited engagement with queer people of color. German LGBT organizations focus on providing support, security, and community for queer asylum seekers and refugees, drawing upon the concept of safer spaces. While existing literature addresses LGBT organizations in development and the challenges faced by queer asylum seekers, there is limited research on the creation of safer spaces. Research suggests a predominant focus on spatial separation as a means of ensuring safety. This article aims to fill this research gap by exploring how German LGBT organizations are adapting and institutionalizing the concept of safer spaces. It investigates the role of spatial separation, control mechanisms, and potential essentialist and cultural biases in shaping safer spaces. The study contextualizes this within the framework of homonationalism in Germany, followed by a theoretical exploration of safer spaces and an empirical analysis of how LGBT organizations conceptualize them. Drawing on expert interviews with spokespersons of German LGBT organizations and an extensive analysis of their websites, my study shows the ways in which the LGBT organizations construct themselves as saviors of vulnerable queer asylum seekers and migrants, while constructing the non-queer asylum seekers and migrants as a threat through othering. Following the logics of these safer space concepts, spatial separation appears as the ultimate solution to offer safety to queer migrants and refugees. In contrast, I also observe alternative safer spaces offered by LGBT organizations, which, in addition to their purely protective function, also create spaces for caring practices and peer-to-peer empowerment through storytelling.

Changing trends in foodborne disease are influenced by many factors, including temperature. Globally and in Australia, warmer ambient temperatures are projected to rise if climate change continues. Salmonella spp. are a temperature-sensitive pathogen and rising temperature can have a substantial effect on disease burden affecting human health. We examined the relationship between temperature and Salmonella spp. and serotype notifications in Adelaide, Australia. Time-series Poisson regression models were fit to estimate the effect of temperature during warmer months on Salmonella spp. and serotype cases notified from 1990 to 2012. Long-term trends, seasonality, autocorrelation and lagged effects were included in the statistical models. Daily Salmonella spp. counts increased by 1·3% [incidence rate ratio (IRR) 1·013, 95% confidence interval (CI) 1·008–1·019] per 1 °C rise in temperature in the warm season with greater increases observed in specific serotype and phage-type cases ranging from 3·4% (IRR 1·034, 95% CI 1·008–1·061) to 4·4% (IRR 1·044, 95% CI 1·024–1·064). We observed increased cases of S. Typhimurium PT9 and S. Typhimurium PT108 notifications above a threshold of 39 °C. This study has identified the impact of warm season temperature on different Salmonella spp. strains and confirms higher temperature has a greater effect on phage-type notifications. The findings will contribute targeted information for public health policy interventions, including food safety programmes during warmer weather.

Guillain–Barré syndrome and neuralgic amyotrophy have been associated with hepatitis E virus (HEV) genotype 3 infections, while myasthenia gravis (MG) has been associated with HEV genotype 4 infections. However, whether chronic inflammatory demyelinating polyneuropathy (CIDP) is associated with HEV infections has not been conclusively clarified yet. 102 CIDP patients, 102 age- and sex-matched blood donors, 61 peripheral neuropathy patients (non-CIDP patients), and 26 MG patients were tested for HEV and anti-HEV IgM and IgG. Sixty-five of the 102 (64%) CIDP patients tested positive for anti-HEV IgG and one (1%) for anti-HEV IgM. No other patient tested positive for ati-HEV IgM. In the subgroup of CIDP patients with initial diagnosis (without previous IVIG treatment), 30/54 (56%) tested positive for anti-HEV IgG. Anti-HEV rates were significantly lower in blood donors (28%), non-CIDP peripheral neuropathy patients (20%), and MG patients (12%). No subject tested positive for HEV viremia. CSF tested negative for in 61 CIDP patients (54 patients with primary diagnosis). The development of CIDP but not non-CIDP polyneuropathy may be triggered by HEV exposure in an HEV genotype 3 endemic region. The increased anti-HEV seroprevalence in CIDP patients is not a consequence of IVIG therapy.

Superconducting Tunnel Junctions (STJs) are used as high-resolution quantum sensors to search for evidence of sterile neutrinos in the electron capture decay of 7 Be. We are developing spatially resolved Monte Carlo simulations of the energy relaxation in superconductors to understand electron escape after the 7 Be decay and distinguish details in the STJ response function from a possible sterile neutrino signal. Simulations of the charge generation and the Fano factor for different materials agree with the literature values. Initial simulations of the escape tail are consistent with observations and contain fine structure in the line shape. The line shape will be refined as better experimental data become available.

As an extension of earlier work on QED, we construct a BRST-invariant Lagrangian for SU(N) Yang–Mills theory with fundamental matter, regulated by the inclusion of massive Pauli–Villars (PV) gluons and PV quarks. The underlying gauge symmetry for massless PV gluons is generalized to accommodate the PV-index-changing currents that are required by the regularization. Auxiliary adjoint scalars are used, in a mechanism due to Stueckelberg, to attribute mass to the PV gluons and the PV quarks. The addition of Faddeev–Popov ghosts then establishes a residual BRST symmetry. Although there are drawbacks to the approach, in particular the computational load of a large number of PV fields and a nonlocal interaction of the ghost fields, this formulation could provide a foundation for renormalizable nonperturbative solutions of light-front QCD in an arbitrary covariant gauge.