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We tend to take our (limited) tolerance for ethanol, the alcohol in drinkable spirits, pretty much for granted, yet it is toxic to most organisms. Some scientists reason that the [...]

This article explores the topic of redundancy and offers guidance for individuals who have lost their jobs. It acknowledges the growing number of redundancies in Australia and globally, with a particular focus on the tech industry. The article explains the process of redundancy and outlines the entitlements that employees have, including redundancy pay based on their length of service. It also provides strategies for job searching based on different age groups. The article emphasizes the importance of maintaining a positive mindset and utilizing available resources during the transition period. Additionally, it discusses the significance of motivation in the hiring process, suggesting that candidates with strong motivation and passion may be more desirable than those with slightly more skills but less motivation. The article highlights the value of hiring individuals who are highly engaged and likely to stay with the organization for a longer period of time. [Extracted from the article]

The article discusses the rise of digital-only banks, known as neobanks, in Australia. It highlights the closure of traditional bank branches and the increasing reliance on digital and mobile banking services. While some neobanks have struggled to survive or have been acquired by traditional banks, others have thrived by partnering with established institutions. The advantages of neobanks include innovative and user-friendly services, transparency, and cost savings for customers. However, they may not offer the full range of banking products and some customers may prefer the safety and in-person experience of traditional banks. Neobanks appeal to younger, tech-savvy customers and are popular among those who spend a lot of time on their phones. The article concludes by noting the challenges of starting a neobank in a highly regulated and expensive industry. [Extracted from the article]

IMPORTANCE: High-dose trivalent compared with standard-dose quadrivalent influenza vaccine did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations in patients with high-risk cardiovascular disease in the INVESTED trial. Whether humoral immune response to influenza vaccine is associated with clinical outcomes is unknown. OBJECTIVE: To examine the antibody response to high-dose trivalent compared with standard-dose quadrivalent inactivated influenza vaccine and its associations with clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis is a prespecified analysis of the immune response substudy of the randomized, double-blind, active-controlled INVESTED trial, which was conducted at 157 sites in the United States and Canada over 3 influenza seasons between September 2016 and January 2019. Antibody titers were determined by hemagglutination inhibition assays at randomization and 4 weeks during the 2017-2018 and 2018-2019 seasons. Eligibility criteria included recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor. Data were analyzed from February 2023 to June 2023. MAIN OUTCOMES AND MEASURES: Mean antibody titer change, seroprotection (antibody titer level ≥1:40) and seroconversion (≥4-fold increase in titer) at 4 weeks, and the association between seroconversion status and the risk for adverse clinical outcomes. INTERVENTIONS: High-dose trivalent or standard-dose quadrivalent inactivated influenza vaccine, with revaccination up to 3 seasons. RESULTS: Antibody data were available for 658 of 5260 randomized participants (12.5%; mean [SD] age, 66.2 [11.4] years; 507 male [77.1%], 151 female [22.9%]; 348 with heart failure [52.9%]). High-dose vaccine was associated with an increased magnitude in antibody titers for A/H1N1, A/H3N2, and B-type antigens compared with standard dose. More than 92% of all participants achieved seroprotection for each of the contained antigens, while seroconversion rates were higher in participants who received high-dose vaccine. Seroconversion for any antigen was not associated with the risk for cardiopulmonary hospitalizations or all-cause mortality (hazard ratio, 1.09; 95% CI, 0.79-1.53; P = .59), irrespective of randomized treatment (P = .38 for interaction). CONCLUSIONS AND RELEVANCE: High-dose vaccine elicited a more robust humoral response in patients with heart failure or prior myocardial infarction enrolled in the INVESTED trial, with no association between seroconversion status and the risk for cardiopulmonary hospitalizations or all-cause mortality. Vaccination to prevent influenza remains critical in high-risk populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02787044

Drug substance development requires a range of analytical methods to be developed to generate process knowledge and to support in-process and release testing throughout a synthetic sequence. Analytical chemists are challenged to ensure these fit-for-purpose methods are reliably transferred and executed at external manufacturing sites. The performance and robustness will differ based on method complexity, experience, proximity to final drug substance, and by the clinical stage of development. Here, we share experiences with a wide variety of transfer challenges and our remediation strategy., In support of drug substance development, analytical methods are developed to generate process knowledge, monitor reactions, and assess quality of input materials, intermediates, and drug substances. During clinical stages of [...]

For decades, vapor degreasing was the cleaning technology of choice in the precision and finishing industries. This came to an end in the 1990s when the ozone issue forced the [...]

Almost any consideration of how humans have traditionally studied nature needs to go back to Aristotle. In the Greek philosopher's On the Parts of Animals and History of Animals, we [...]

For decades, vapor degreasing was the cleaning technology of choice in the precision and finishing industries. This came to an end in the 1990s when the ozone issue forced the [...]

HUMANS have developed naming things into an art. Of course, we are not the only animals to have names for objects and other organisms we encounter. For instance, prairie dogs [...]

For decades, vapor degreasing was the cleaning technology of choice in the precision and finishing industries. This came to an end in the 1990s, when the ozone issue forced the [...]

Leave the Armenian capital of Yerevan behind you in the shadow of looming Mount Ararat and drive fast for two hours southwest. The meandering road will take you across some [...]

An ever-growing fossil record has made it inescapable that hominid history has not been the received saga of a lone hero battling from primitiveness to sapient perfection over the eons, [...]

Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate, adriamycin (doxorubicin) and platinum (cisplatin). Due to the rarity of OS, the generation of relevant cell models as tools for drug discovery is paramount to tackling this issue. Four literature databases were systematically searched using pre-determined search terms to identify MAP resistant OS cell lines and patients. Drug exposure strategies used to develop cell models of resistance and the impact of these on the differential expression of resistance associated genes, proteins and non-coding RNAs are reported. A comparison to clinical studies in relation to chemotherapy response, relapse and metastasis was then made. The search retrieved 1891 papers of which 52 were relevant. Commonly, cell lines were derived from Caucasian patients with epithelial or fibroblastic subtypes. The strategy for model development varied with most opting for continuous over pulsed chemotherapy exposure. A diverse resistance level was observed between models (2.2–338 fold) with 63% of models exceeding clinically reported resistance levels which may affect the expression of chemoresistance factors. In vitro p-glycoprotein overexpression is a key resistance mechanism; however, from the available literature to date this does not translate to innate resistance in patients. The selection of models with a lower fold resistance may better reflect the clinical situation. A comparison of standardised strategies in models and variants should be performed to determine their impact on resistance markers. Clinical studies are required to determine the impact of resistance markers identified in vitro in poor responders to MAP treatment, specifically with respect to innate and acquired resistance. A shift from seeking disputed and undruggable mechanisms to clinically relevant resistance mechanisms may identify key resistance markers that can be targeted for patient benefit after a 40-year wait.

To decide whether to remain underground or to emerge from overwintering, fossorial ectotherms simultaneously process environmental, gravitational and circannual migratory cues. Here, we provide an experimental framework to study the behaviour of fossorial ectotherms during soil temperature inversion – a phenomenon that marks the transition between winter and spring – based on three non-mutually exclusive hypotheses (thermoregulation, negative geotaxis and migration restlessness). Using a vertical thermal gradient, we evaluated how temperature selection (Tsel), activity and vertical position selection differed under simulated soil temperature inversion (contrasting the active versus overwintering thermal gradients) in the spotted salamander (Ambystoma maculatum). Salamanders had different Tsel and activity levels between gradients, but selected similar heights regardless of thermal gradient orientation. Negative geotaxis may explain responses to changes in vertical thermal gradient orientation, with migratory restlessness contributing to differences in activity levels. Ultimately, our work should benefit those who aim to better understand the biology of fossorial ectotherms.

The article discusses the success and endurance of two major environmental groups in Australia: the Northern Rivers group and Stop Adani. The Northern Rivers group formed in response to the threat of gas extraction and successfully organized campaigns to keep the region gasfield-free. When floods hit the area, they shifted focus to resilience and mutual aid. Stop Adani, on the other hand, formed to oppose the Adani coal mine and successfully reduced its size but eventually lost momentum. The article highlights the importance of strong local roots, diverse representation, strategic planning, and positive framing in building successful and enduring climate groups. [Extracted from the article]

SMART TECH Virtual reality opens up a whole new world Virtual reality is one of those futuristic tech concepts that always seems as if it's just around the corner but never quite arrives. Destination Tilba Five things to do 1. From $509.99 Pros: The cheapest and most accessible way to get a decent VR experience in your own home, this device lets you play some 200 games alongside using other apps, and you can also connect it to a PC to experience VR content running on your (more powerful) computer. [Extracted from the article]

Somatic mutations in UBA1 cause vacuoles, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory somatic (VEXAS) syndrome, an adult-onset inflammatory disease with an overlap of hematologic manifestations. VEXAS syndrome is characterized by a high mortality rate and significant clinical heterogeneity. We sought to determine independent predictors of survival in VEXAS and to understand the mechanistic basis for these factors. We analyzed 83 patients with somatic pathogenic variants in UBA1 at p.Met41 (p.Met41Leu/Thr/Val), the start codon for translation of the cytoplasmic isoform of UBA1 (UBA1b). Patients with the p.Met41Val genotype were most likely to have an undifferentiated inflammatory syndrome. Multivariate analysis showed ear chondritis was associated with increased survival, whereas transfusion dependence and the p.Met41Val variant were independently associated with decreased survival. Using in vitro models and patient-derived cells, we demonstrate that p.Met41Val variant supports less UBA1b translation than either p.Met41Leu or p.Met41Thr, providing a molecular rationale for decreased survival. In addition, we show that these 3 canonical VEXAS variants produce more UBA1b than any of the 6 other possible single-nucleotide variants within this codon. Finally, we report a patient, clinically diagnosed with VEXAS syndrome, with 2 novel mutations in UBA1 occurring in cis on the same allele. One mutation (c.121 A>T; p.Met41Leu) caused severely reduced translation of UBA1b in a reporter assay, but coexpression with the second mutation (c.119 G>C; p.Gly40Ala) rescued UBA1b levels to those of canonical mutations. We conclude that regulation of residual UBA1b translation is fundamental to the pathogenesis of VEXAS syndrome and contributes to disease prognosis.

Shaping Humanity How Science, Art, and Imagination Help Us Understand Our Origins by John Gurche Yale University Press, 2013; 363 pages, $49.95 For professional and amateur alike, comprehending the long [...]

For long-time readers of Natural History, Stephen Jay Gould needs no introduction. His column, 'This View of Life,' was a mainstay of the magazine, starting in January 1974 with 'Size [...]

Some people think that plants respond to talking, the playing of music, and other forms of human attention. And although plants more than likely do not process human language, they [...]

Debt recycling is a strategy that allows individuals to replace non-tax-deductible debt on their primary residence with tax-deductible debt from investments. By refinancing their home and using the equity to fund an income-generating asset, individuals can accelerate their home loan repayment and potentially grow their property portfolios. However, there are risks involved, such as the investment not increasing in value as expected and interest rates rising. It is important to seek professional advice from experts in lending, tax, and finance before undertaking this strategy. [Extracted from the article]