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Mental health conditions confer considerable global disease burden in young adults, who are also the highest demographic to work shifts, and of whom 20% meet criteria for a sleep disorder. We aimed to establish the relationship between the combined effect of shift work and sleep disorders, and mental health. The Raine Study is the only longitudinal, population-based birth cohort in the world with gold-standard, Level 1 measurement of sleep (polysomnography, PSG) collected in early adulthood. Participants (aged 22y) underwent in-laboratory PSG and completed detailed sleep questionnaires. Multivariable adjusted robust linear regression models were conducted to explore associations with anxiety (GAD7) and depression (PHQ9), adjusted for sex, health comorbidities, and work hours/week. Data were from 660 employed young adults (27.3% shift workers). At least one clinically significant sleep disorder was present in 18% of shift workers (day, evening and night shifts) and 21% of non-shift workers ( p  = 0.51); 80% were undiagnosed. Scores for anxiety and depression were not different between shift and non-shift workers ( p  = 0.29 and p  = 0.82); but were higher in those with a sleep disorder than those without ( Md(IQR) anxiety: 7.0(4.0–10.0) vs 4.0(1.0–6.0)), and depression: (9.0(5.0–13.0) vs 4.0(2.0–6.0)). Considering evening and night shift workers only (i.e. excluding day shift workers) revealed an interaction between shift work and sleep disorder status for anxiety ( p  = 0.021), but not depression ( p  = 0.96), with anxiety scores being highest in those shift workers with a sleep disorder ( Md(IQR) 8.5(4.0–12.2). We have shown that clinical sleep disorders are common in young workers and are largely undiagnosed. Measures of mental health do not appear be different between shift and non-shift workers. These findings indicate that the identification and treatment of clinical sleep disorders should be prioritised for young workers as these sleep disorders, rather than shift work per se , are associated with poorer mental health. These negative mental health effects appear to be greatest in those who work evening and/or night shift and have a sleep disorder.

\"Planck's Law, an equation used by physicists to determine the radiation leaking from any object in the universe, was described by Albert Einstein as 'the basis of all twentieth-century physics.' Max Planck is credited with being the father of quantum theory, and his work laid the foundation for our modern understanding of matter and energetic processes. But Planck's story is not well known, especially in the United States. A German physicist working during the first half of the twentieth century, his library, personal journals, notebooks, and letters were all destroyed with his home in World War II. What remains, other than his contributions to science, are handwritten letters in German shorthand, and tributes from other scientists of the time, including his close friend Albert Einstein. In Planck : Driven by Vision, Broken by War, Brandon R. Brown interweaves the voices and writings of Planck, his family, and his contemporaries--with many passages appearing in English for the first time--to create a portrait of a groundbreaking physicist working in the midst of war. Planck spent much of his adult life grappling with the identity crisis of being an influential German with ideas that ran counter to his government. During the later part of his life, he survived bombings and battlefields, surgeries and blood transfusions, all the while performing his influential work amidst a violent and crumbling Nazi bureaucracy. When his son was accused of treason related to a bombing, Planck tried to use his standing as a German 'national treasure,' and wrote direct letters to Hitler to spare his son's life. Brown tells the story of Planck's friendship with the far more outspoken Albert Einstein, and shows how his work fits within the explosion of technology and science that occurred during his life. The story of a brilliant man living in a dangerous time, Brandon Brown gives Max Planck his rightful place in the history of science, and shows how war-torn Germany deeply impacted his life and work\"-- Provided by publisher.

Advances in fluorescence microscopy enable monitoring larger brain areas in-vivo with finer time resolution. The resulting data rates require reproducible analysis pipelines that are reliable, fully automated, and scalable to datasets generated over the course of months. We present CaImAn, an open-source library for calcium imaging data analysis. CaImAn provides automatic and scalable methods to address problems common to pre-processing, including motion correction, neural activity identification, and registration across different sessions of data collection. It does this while requiring minimal user intervention, with good scalability on computers ranging from laptops to high-performance computing clusters. CaImAn is suitable for two-photon and one-photon imaging, and also enables real-time analysis on streaming data. To benchmark the performance of CaImAn we collected and combined a corpus of manual annotations from multiple labelers on nine mouse two-photon datasets. We demonstrate that CaImAn achieves near-human performance in detecting locations of active neurons. The human brain contains billions of cells called neurons that rapidly carry information from one part of the brain to another. Progress in medical research and healthcare is hindered by the difficulty in understanding precisely which neurons are active at any given time. New brain imaging techniques and genetic tools allow researchers to track the activity of thousands of neurons in living animals over many months. However, these experiments produce large volumes of data that researchers currently have to analyze manually, which can take a long time and generate irreproducible results. There is a need to develop new computational tools to analyze such data. The new tools should be able to operate on standard computers rather than just specialist equipment as this would limit the use of the solutions to particularly well-funded research teams. Ideally, the tools should also be able to operate in real-time as several experimental and therapeutic scenarios, like the control of robotic limbs, require this. To address this need, Giovannucci et al. developed a new software package called CaImAn to analyze brain images on a large scale. Firstly, the team developed algorithms that are suitable to analyze large sets of data on laptops and other standard computing equipment. These algorithms were then adapted to operate online in real-time. To test how well the new software performs against manual analysis by human researchers, Giovannucci et al. asked several trained human annotators to identify active neurons that were round or donut-shaped in several sets of imaging data from mouse brains. Each set of data was independently analyzed by three or four researchers who then discussed any neurons they disagreed on to generate a ‘consensus annotation’. Giovannucci et al. then used CaImAn to analyze the same sets of data and compared the results to the consensus annotations. This demonstrated that CaImAn is nearly as good as human researchers at identifying active neurons in brain images. CaImAn provides a quicker method to analyze large sets of brain imaging data and is currently used by over a hundred laboratories across the world. The software is open source, meaning that it is freely-available and that users are encouraged to customize it and collaborate with other users to develop it further.

\"All across the world, legends are appearing. Great Beasts--once the most powerful beings in Erdas--are being summoned as spirit animals. Bonded to special kids, they unite the human and animal worlds. But a mysterious stranger is hunting these legends, just as they are reborn, and he's rushing anyone who stands in his way. These are the stories of those stolen legends, and of the young heroes who will stop at nothing to get them back\"--Page 4 of cover.

Sleep disorders are common, and largely undiagnosed in early-career workers. The combination of sleep disorders and shift work has implications for mental health, workplace safety, and productivity. Early identification and management of sleep disorders is likely to be beneficial to workers, employers and the community more broadly. We assessed the feasibility and acceptability of a tailored sleep disorder screening and management pathway for individuals with future shift work requirements. Paramedic students were invited to complete an online sleep health survey, which included validated sleep disorder screening questionnaires for insomnia, obstructive sleep apnea and restless legs syndrome. Participants were able to express interest in participating in a sleep monitoring and management study. Participants at risk for a sleep disorder were identified, contacted by the study physician (RJA), notified of their sleep disorder screening results and provided with information regarding management options. Feasibility of the screening and management pathways were determined by completion of the 12 week follow-up, and ability to engage with health services for diagnostic testing or treatment. Acceptability of these pathways was assessed with a semi-structured interview on completion of the study at 12 weeks. Screening was completed in thirty participants (mean age 22.5 ± 6.7, 63% female), 17 of whom were ‘at-risk’ for a sleep disorder and offered a management pathway. All participants engaged with the study physician (RJA), with 16 completing the study (94% completion rate). Three participants with excessive daytime sleepiness received feedback from the study physician (RJA) and no further care required. Of the remaining 14 participants, 11 (78%) engaged with health services after speaking with the study physician (RJA). Those who engaged with diagnostic and management services reported that a structured pathway with online screening was convenient and easy to follow. Facilitating screening and management of sleep disorders in students with future shift work requirements is both feasible and acceptable. These findings can inform the development of a preventive strategy for sleep disorders and ideally, a health services feasibility trial for future shift workers.

The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals 1 . Unlike most medications for the treatment of substance use disorders, anecdotal reports suggest that ibogaine has the potential to treat addiction to various substances, including opiates, alcohol and psychostimulants. The effects of ibogaine—like those of other psychedelic compounds—are long-lasting 2 , which has been attributed to its ability to modify addiction-related neural circuitry through the activation of neurotrophic factor signalling 3 , 4 . However, several safety concerns have hindered the clinical development of ibogaine, including its toxicity, hallucinogenic potential and tendency to induce cardiac arrhythmias. Here we apply the principles of function-oriented synthesis to identify the key structural elements of the potential therapeutic pharmacophore of ibogaine, and we use this information to engineer tabernanthalog—a water-soluble, non-hallucinogenic, non-toxic analogue of ibogaine that can be prepared in a single step. In rodents, tabernanthalog was found to promote structural neural plasticity, reduce alcohol- and heroin-seeking behaviour, and produce antidepressant-like effects. This work demonstrates that, through careful chemical design, it is possible to modify a psychedelic compound to produce a safer, non-hallucinogenic variant that has therapeutic potential. Psychedelic alkaloids served as lead structures for the development of tabernanthalog, a non-hallucinogenic and non-toxic analogue that reduces alcohol- and heroin-seeking behaviour and produces antidepressant-like effects in rodents.

The therapeutic efficacy of systemic drug-delivery vehicles depends on their ability to evade the immune system, cross the biological barriers of the body and localize at target tissues. White blood cells of the immune system—known as leukocytes—possess all of these properties and exert their targeting ability through cellular membrane interactions. Here, we show that nanoporous silicon particles can successfully perform all these actions when they are coated with cellular membranes purified from leukocytes. These hybrid particles, called leukolike vectors, can avoid being cleared by the immune system. Furthermore, they can communicate with endothelial cells through receptor–ligand interactions, and transport and release a payload across an inflamed reconstructed endothelium. Moreover, leukolike vectors retained their functions when injected in vivo , showing enhanced circulation time and improved accumulation in a tumour. Camouflaging nanoporous silicon particles by functionalizing them with membranes isolated from white blood cells can delay their removal from the body and improve their accumulation in tumours.

Health disparities adversely affect millions of people living in disadvantaged communities, resisting public health interventions that do not address the specific conditions, driving forces, or health problems in these communities. Drawing from the underutilized science of deliberative methods, we introduce the innovative citizens’ panels for health equity approach—a novel methodology that engages public expertise and knowledge of community health needs, risks, and priorities to tailor public health research and interventions for greater relevance and impact on disadvantaged communities. By engaging affected residents and stakeholders in informed deliberation and decision-making about community health disparities, citizens’ panels provide important guidance for (1) designing research studies to target the major health disparities affecting disadvantaged communities and (2) tailoring evidence-based interventions to the perspectives, practices, and preferences of disadvantaged residents. Employed as the primary methodology in 2 federally funded projects conducted in California and Arkansas between 2017 and 2019, citizens’ panels offer a systematic method for obtaining rich community insight into health disparities, shaping community-informed solutions, and affording disadvantaged communities influence over public health decision-making to stimulate grassroots change and health equity.

For many organisms the ability to transduce light into cellular signals is crucial for survival. Light stimulates DNA repair and metabolism changes in bacteria, avoidance responses in single-cell organisms, attraction responses in plants, and both visual and nonvisual perception in animals. Despite these widely differing responses, in all of nature there are only six known families of proteins that can transduce light. Although the roundworm Caenorhabditis elegans has none of the known light transduction systems, we show here that C. elegans strongly accelerates its locomotion in response to blue or shorter wavelengths of light, with maximal responsiveness to ultraviolet light. Our data suggest that C. elegans uses this light response to escape the lethal doses of sunlight that permeate its habitat. Short-wavelength light drives locomotion by bypassing two critical signals, cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG), that neurons use to shape and control behaviors. C. elegans mutants lacking these signals are paralyzed and unresponsive to harsh physical stimuli in ambient light, but short-wavelength light rapidly rescues their paralysis and restores normal levels of coordinated locomotion. This light response is mediated by LITE-1, a novel ultraviolet light receptor that acts in neurons and is a member of the invertebrate Gustatory receptor (Gr) family. Heterologous expression of the receptor in muscle cells is sufficient to confer light responsiveness on cells that are normally unresponsive to light. Our results reveal a novel molecular solution for ultraviolet light detection and an unusual sensory modality in C. elegans that is unlike any previously described light response in any organism.