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ABSTRACT Introduction The term “Mediterranean lifestyle” has gained increasing prominence in recent years, yet a specific definition remains elusive. In response, the Mediterranean Lifestyle Medicine Institute Board of Directors convened a multidisciplinary panel comprising international experts and leaders in lifestyle medicine. Their goal was to review existing literature and formulate a consensus definition of the “traditional Mediterranean lifestyle (tMedL),” referring to the historical way of living of the people in the Mediterranean region. This paper presents the agreed consensus statement and a comprehensive holistic definition of the term “traditional Mediterranean lifestyle.” Methods Major medical and social sciences electronic databases from inception to February 2023 were searched, employing keywords relevant to the Mediterranean lifestyle and its constituent elements (diet, physical activity, sleep, stress, socialization). Subsequently, definitions for each pillar were created and synthesized to derive a comprehensive definition of the “traditional Mediterranean lifestyle.” Results This proposed definition received ratification from the Mediterranean Lifestyle Medicine Institute's expert working group during the First International Mediterranean Lifestyle Medicine Conference held in June 2023 on the island of Leros, Greece. “The traditional Mediterranean lifestyle is characterized by its diverse and adaptable nature. Key facets encompass conviviality, lifelong social connectedness, purposeful living, strong community and familial bonds, harmony with nature and the environment, profound spirituality, adherence to religious practices, preservation of local customs, resilience cultivated through adversity, and a commitment to moderation across all spheres of life.” Conclusions This definition comprehensively outlines the primary lifestyle factors ingrained in Mediterranean inhabitants across generations. Its holistic nature furnishes a crucial conceptual framework for directing lifestyle medicine practitioners in assisting patients to mitigate diseases, promote overall well‐being, devise research initiatives to investigate the health ramifications of this lifestyle, and inform curriculum development.

The most common source of Radiofrequency Electromagnetic Field (RF-EMF) exposures during sleep includes digital devices, yet there are no studies investigating the impact of multi-night exposure to electromagnetic fields emitted from a baby monitor on sleep under real-world conditions in healthy adults. Given the rise in the number of people reporting to be sensitive to manmade electromagnetic fields, the ubiquitous use of Wi-Fi enabled digital devices and the lack of real-world data, we investigated the effect of 2.45 GHz radiofrequency exposure during sleep on subjective sleep quality, and objective sleep measures, heart rate variability and actigraphy in healthy adults. This pilot study was a 4-week randomised, double-blind, crossover trial of 12 healthy adults. After a one-week run-in period, participants were randomised to exposure from either an active or inactive (sham) baby monitor for 7 nights and then crossed over to the alternate intervention after a one-week washout period. Subjective and objective assessments of sleep included the Pittsburgh Insomnia Rating Scale (PIRS-20), electroencephalography (EEG), actigraphy and heart rate variability (HRV) derived from electrocardiogram. Sleep quality was reduced significantly (p

Background:. Tiny arteriovenous (AV) shunts of 10–150 µm (0.01–0.15 mm) are documented in the hands and feet. Larger shunts up to 0.5 mm (500 µm) have been discovered by the authors in the inner canthus and the human eye. This study seeks their possible existence in the upper limb. Methods:. Radiographic lead oxide cadaver injection and dissection studies of 14 archival and six new upper limbs were examined. Results:. AV shunts of 0.1–0.5 mm were discovered between the brachial, ulnar, and radial arteries and their venae comitantes and between their arterial perforators and the subcutaneous veins. Conclusion:. This pilot study provides insight into the possible function of these large AV shunts associated with blood flow variation in temperature, blood pressure, tissue transfer, flap prefabrication, and flap necrosis.

The intracellular symbiont Wolbachia pipientis evolved after the divergence of arthropods and nematodes, but it reached high prevalence in many of these taxa through its abilities to infect new hosts and their germlines. Some strains exhibit long-term patterns of co-evolution with their hosts, while other strains are capable of switching hosts. This makes strain selection an important factor in symbiont-based biological control. However, little is known about the ecological and evolutionary interactions that occur when a promiscuous strain colonizes an infected host. Here, we study what occurs when two strains come into contact in host cells following horizontal transmission and infection. We focus on the faithful wMel strain from Drosophila melanogaster and the promiscuous wRi strain from Drosophila simulans using an in vitro cell culture system with multiple host cell types and combinatorial infection states. Mixing D. melanogaster cell lines stably infected with wMel and wRi revealed that wMel outcompetes wRi quickly and reproducibly. Furthermore, wMel was able to competitively exclude wRi even from minuscule starting quantities, indicating that this is a nearly deterministic outcome, independent of the starting infection frequency. This competitive advantage was not exclusive to wMel's native D. melanogaster cell background, as wMel also outgrew wRi in D. simulans cells. Overall, wRi is less adept at in vitro growth and survival than wMel and its in vivo state, revealing differences between the two strains in cellular and humoral regulation. These attributes may underlie the observed low rate of mixed infections in nature and the relatively rare rate of host-switching in most strains. Our in vitro experimental framework for estimating cellular growth dynamics of Wolbachia strains in different host species and cell types provides the first strategy for parameterizing endosymbiont and host cell biology at high resolution. This toolset will be crucial to our application of these bacteria as biological control agents in novel hosts and ecosystems.

The detection of known signals in colored Gaussian noise typically involves applying a matched filter to prewhitened data samples in the discrete-time domain. This is achieved by sampling the continuous-time data and applying a prewhitener before applying a matched filter. An alternative approach switches the order of sampling and whitening; whitens the data using an analog prewhitener before sampling. These two methods have been widely regarded as equivalent when sampling at the Nyquist or a higher rate. In this study, we demonstrate that these approaches are indeed equivalent when all Nyquist or higher rate samples are utilized. However, when performing detection using only a subset of the Nyquist samples, the equivalence breaks down. We show that for sparse signal detection, these approaches diverge; the implementation utilizing an analog prewhitener followed by a sampler is both computationally feasible and superior in terms of detection performance.

Abstract Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin’s efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that the inhibition of cathepsins, a protein family of the host organism, by calpeptin is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections.

Background: Natural products are widely used for primary insomnia (PI). This systematic review with trial sequential analysis (TSA) aimed to summarize evidence pertaining to the effectiveness and safety of Zao Ren An Shen (ZRAS) prescription, a commercial Chinese polyherbal preparation, for treating PI.Methods: Controlled clinical trials appraising ZRAS compared to controls or as an add-on treatment were systematically searched across seven databases until January 2024. Cochrane ROB 2.0 and ROBINS-I tools were adopted to determine risk of bias. Quality of evidence was assessed using the GRADE framework.Results: We analyzed 22 studies, involving 2,142 participants. The effect of ZRAS in reducing Pittsburgh Sleep Quality Index scores was found to be comparable to benzodiazepines [MD = 0.39, 95%CI (−0.12, 0.91), p = 0.13] and superior to Z-drugs [MD = −1.31, 95%CI (−2.37, −0.24), p = 0.02]. The addition of ZRAS to hypnotics more significantly reduced polysomnographically-recorded sleep onset latency [MD = −4.44 min, 95%CI (−7.98, −0.91), p = 0.01] and number of awakenings [MD = −0.89 times, 95%CI (−1.67, −0.10), p = 0.03], and increased total sleep time [MD = 40.72 min, 95%CI (25.14, 56.30), p < 0.01], with fewer adverse events than hypnotics alone. TSA validated the robustness of these quantitative synthesis results. However, the quality of evidence ranged from very low to low. The limited data available for follow-up did not support meta-synthesis.Conclusion: While ZRAS prescription shows promising effectiveness in treating PI, the overall quality of evidence is limited. Rigorously-designed randomized control trials are warranted to confirm the short-term efficacy of ZRAS and explore its medium-to-long-term efficacy.Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=471497), identifier (CRD42023471497).

A remarkable new species, Microselia lorien, from northern coastal New South Wales, Australia is described and illustrated. This is the first record of the genus Microselia in Australia. With the previously described species occurring in the Afrotropical (6), Neotropical (1), Palaearctic (7), Nearctic (1) regions (Systema Dipterorum, 2022). The species discovered in Australia is new to science.

By placing an antiferromagnet next to a heavy metal such as platinum, magnetic excitations in the antiferromagnet drive a spin current in the heavy metal, leading to terahertz emission. Here, Kholid et al study the terahertz emission of two antiferromagnets, KCoF3 and KNiF3 with very different magnon frequencies, and find that the opening of a gap in the magnon density of states drastically alters the spin-transfer efficiency.

BackgroundClinical practice guidelines (CPGs) are used to guide decision-making, especially regarding complementary and alternative medicine (CAM) therapies that are unfamiliar to orthodox healthcare providers. This systematic review aimed to critically review and summarise CAM recommendations associated with anxiety management included in the existing CPGs.MethodsSeven databases, websites of six international guidelines developing institutions, and the National Centre for Complementary and Integrative Health website were systematically searched. Their reporting and methodological quality were evaluated using the Reporting Items for practice Guidelines in Healthcare checklist and the Appraisal of Guidelines for Research and Evaluation (2nd version) instrument, respectively.ResultsTen CPGs were included, with reporting rates between 51.4 and 88.6%. Seven of these were of moderate to high methodological quality. Seventeen CAM modalities were implicated, involving phytotherapeutics, mind–body practice, art therapy, and homeopathy. Applied relaxation was included in 70% CPGs, which varied in degree of support for its use in the treatment of generalised anxiety disorder. There were few recommendations for other therapies/products. Light therapy was not recommended for use in generalised anxiety disorder, and St John’s wort and mindfulness were not recommended for use in social anxiety disorder in individual guidelines. Recommendations for the applicability of other therapies/products for treating a specific anxiety disorder were commonly graded as “unclear, unambiguous, or uncertain”. No CAM recommendations were provided for separation anxiety disorder, specific phobia or selective mutism.ConclusionAvailable guidelines are limited in providing logically explained graded CAM recommendations for anxiety treatment and care. A lack of high-quality evidence and multidisciplinary consultation during the guideline development are two major reasons. High quality and reliable clinical evidence and the engagement of a range of interdisciplinary stakeholders are needed for future CPG development and updating.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373694, identifier CRD42022373694.

BackgroundComplementary and Alternative Medicine (CAM) interventions may prove to be an attractive option for the treatment of depression. The aim of this scientometric analysis is to determine the global scientific output of research regarding managing depression with CAM and identify the hotspots and frontiers within this theme.MethodsPublications regarding the utilization of CAM for treating depression were collected from the Web of Science Core Collection from 1993 to 2022, and analyzed and visualized by Bibliometrix R-package, VOSviewer, and CiteSpace.ResultsA total of 1,710 publications were acquired. The number of annual publications showed an overall rapid upward trend, with the figure peaking at 179 in 2021. The USA was the leading research center. Totally 2,323 distinct institutions involving 7,638 scholars contributed to the research theme. However, most of the cooperation was limited to within the same country, institution or research team. The Journal of Alternative and Complementary Medicine was the most productive periodical. The CAM therapies of most interest to researchers were acupuncture and body–mind techniques, such as yoga, meditation and mindfulness. Systematic review and meta-analysis are commonly used methods. “Inflammation,” “rating scale” and “psychological stress” were identified as the most studied trend topics recently.ConclusionManaging depression with evidence-based CAM treatment is gaining attention globally. Body–mind techniques and acupuncture are growing research hotspots or emerging trending topics. Future studies are predicted to potentially investigate the possible mechanisms of action underlying CAM treatments in reducing depression in terms of modulation of psychological stress and inflammation levels. Cross-countries/institutes/team research collaborations should be encouraged and further enhanced.

Admixture, the exchange of genetic information between distinct source populations, is thought to be a major source of adaptive genetic variation. Unlike mutation events, which periodically generate single alleles, admixture can introduce many selected alleles simultaneously. As such, the effects of linkage between selected alleles may be especially pronounced in admixed populations. However, existing tools for identifying selected mutations within admixed populations only account for selection at a single site, overlooking phenomena such as linkage among proximal selected alleles. Here, we develop and extensively validate a method for identifying and quantifying the individual effects of multiple linked selected sites on a chromosome in admixed populations. Our approach numerically calculates the expected local ancestry landscape in an admixed population for a given multi-locus selection model, and then maximizes the likelihood of the model. After applying this method to admixed populations of Drosophila melanogaster and Passer italiae, we found that the impacts between linked sites may be an important contributor to natural selection in admixed populations. Furthermore, for the situations we considered, the selection coefficients and number of selected sites are overestimated in analyses that do not consider the effects of linkage among selected sites. Our results imply that linkage among selected sites may be an important evolutionary force in admixed populations. This tool provides a powerful generalized method to investigate these crucial phenomena in diverse populations.

BackgroundThere is a need for evidence-informed guidance on the use of complementary and alternative medicine (CAM) for insomnia because of its widespread utilization and a lack of guidance on the balance of benefits and harms. This systematic review aimed to identify and summarize the CAM recommendations associated with insomnia treatment and care from existing comprehensive clinical practice guidelines (CPGs). The quality of the eligible guidelines was appraised to assess the credibility of these recommendations.MethodsFormally published CPGs incorporating CAM recommendations for insomnia management were searched for in seven databases from their inception to January 2023. The NCCIH website and six websites of international guideline developing institutions were also retrieved. The methodological and reporting quality of each included guideline was appraised using the AGREE II instrument and RIGHT statement, respectively.ResultsSeventeen eligible GCPs were included, and 14 were judged to be of moderate to high methodological and reporting quality. The reporting rate of eligible CPGs ranged from 42.9 to 97.1%. Twenty-two CAM modalities were implicated, involving nutritional or natural products, physical CAM, psychological CAM, homeopathy, aromatherapy, and mindful movements. Recommendations for these modalities were mostly unclear, unambiguous, uncertain, or conflicting. Logically explained graded recommendations supporting the CAM use in the treatment and/or care of insomnia were scarce, with bibliotherapy, Tai Chi, Yoga, and auriculotherapy positively recommended based on little and weak evidence. The only consensus was that four phytotherapeutics including valerian, chamomile, kava, and aromatherapy were not recommended for insomnia management because of risk profile and/or limited benefits.ConclusionsExisting guidelines are generally limited in providing clear, evidence-informed recommendations for the use of CAM therapies for insomnia management due to a lack of high-quality evidence and multidisciplinary consultation in CPG development. More well-designed studies to provide reliable clinical evidence are therefore urgently needed. Allowing the engagement of a range of interdisciplinary stakeholders in future updates of CPGs is also warranted.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369155, identifier: CRD42022369155.

Background and objectiveWhilst acupuncture is widely used for treating psychosomatic diseases, there is little high-quality evidence supporting its application in comorbid perimenopausal depression (PMD) and insomnia (PMI) which are common complaints during climacteric. This feasibility, patient-assessor-blinded, randomized, sham-controlled clinical trial addresses this gap by investigating the efficacy and safety of acupuncture on depressed mood and poor sleep in women with comorbid PMD and PMI.MethodsSeventy eligible participants were randomly assigned to either real-acupuncture (RA) or sham-acupuncture (SA) groups. Either RA or SA treatment were delivered in 17 sessions over 8 weeks. The primary outcomes for mood and sleep were changes on 17-items Hamilton Depression Rating Scale (HAM-D17) and Pittsburgh Sleep Quality Index (PSQI) scores, from baseline to 16-week follow-up. Secondary outcome measures involved anxiety symptoms, perimenopausal symptoms, quality of life, participants' experience of and satisfaction with the acupuncture treatment. Blood samples were taken to measure reproductive hormone levels. Intention-To-Treat and Per-Protocol analyses were conducted with linear mixed-effects models. The James' and Bang's blinding indices were used to assess the adequacy of blinding.ResultsSixty-five participants completed all treatment sessions, and 54 and 41 participants completed the eight- and 16-week follow-ups, respectively. At post-treatment and 8-week follow-up, the RA group showed a significantly greater reduction in PSQI scores than the SA group did; although the reduction of HAM-D17 scores in RA group was significant, the change was not statistically different from that of SA. There were no significant mean differences between baseline and 16-week follow-up in either HAM-D17 or PSQI in either group. There were no significant between-group differences in serum reproductive hormone levels. All treatments were tolerable and no serious adverse events were reported, and the blinding was successful.ConclusionAcupuncture is safe and can contribute to clinically relevant improvements in comorbid PMD and PMI, with satisfactory short-and medium-term effects. Whether the anti-depressive benefit of acupuncture is specific or non-specific remains to be determined. No evidence was found for any longer-term benefit of acupuncture compared to sham at 16 weeks. Further research is required to elucidate mechanisms underlying the short to medium term effects of acupuncture.

The Central Dogma highlights the mutualistic functions of protein and nucleic acid biopolymers, and this synergy appears prominently in the membraneless organelles widely distributed throughout prokaryotic and eukaryotic organisms alike. Ribonucleoprotein granules (RNPs), which are complex coacervates of RNA with proteins, are a prime example of these membranelles organelles and underly multiple essential cellular functions. Inspired by the highly dynamic character of these organelles and the recent studies that ATP both inhibits and templates phase separation of the fused in sarcoma (FUS) protein implicated in several neurodegenerative diseases, we explored the RNA templated ordering of a single motif of the Aβ peptide of Alzheimer’s disease. We now know that this strong cross-β propensity motif alone assembles through a liquid-like coacervate phase that can be externally templated to form distinct supramolecular assemblies. Now we provide evidence that structured phosphates, ranging from complex structures like double stranded and quadraplex DNA to simple trimetaphosphate, differentially impact the liquid to solid phase transition necessary for paracrystalline assembly. The results from this simple model illustrate the potential of ordered environmental templates in the transition to potentially irreversible pathogenic assemblies and provides insight into the ordering dynamics necessary for creating functional synthetic polymer co-assemblies.

Abstract Objective The SARS-CoV-2 pandemic has prompted one of the most extensive and expeditious genomic sequencing efforts in history. Each viral genome is accompanied by a set of metadata which supplies important information such as the geographic origin of the sample, age of the host, and the lab at which the sample was sequenced, and is integral to epidemiological efforts and public health direction. Here, we interrogate some shortcomings of metadata within the GISAID database to raise awareness of common errors and inconsistencies that may affect data-driven analyses and provide possible avenues for resolutions. Results Our analysis reveals a startling prevalence of spelling errors and inconsistent naming conventions, which together occur in an estimated ~ 9.8% and ~ 11.6% of “originating lab” and “submitting lab” GISAID metadata entries respectively. We also find numerous ambiguous entries which provide very little information about the actual source of a sample and could easily associate with multiple sources worldwide. Importantly, all of these issues can impair the ability and accuracy of association studies by deceptively causing a group of samples to identify with multiple sources when they truly all identify with one source, or vice versa.

Accurate simulation of complex biological processes is an essential component of developing and validating new technologies and inference approaches. As an effort to help contain the COVID-19 pandemic, large numbers of SARS-CoV-2 genomes have been sequenced from most regions in the world. More than 5.5 million viral sequences are publicly available as of November 2021. Many studies estimate viral genealogies from these sequences, as these can provide valuable information about the spread of the pandemic across time and space. Additionally such data are a rich source of information about molecular evolutionary processes including natural selection, for example allowing the identification of new variants with transmissibility and immunity evasion advantages. To our knowledge, there is no framework that is both efficient and flexible enough to simulate the pandemic to approximate world-scale scenarios and generate viral genealogies of millions of samples. Here, we introduce a new fast simulator VGsim which addresses the problem of simulation genealogies under epidemiological models. The simulation process is split into two phases. During the forward run the algorithm generates a chain of population-level events reflecting the dynamics of the pandemic using an hierarchical version of the Gillespie algorithm. During the backward run a coalescent-like approach generates a tree genealogy of samples conditioning on the population-level events chain generated during the forward run. Our software can model complex population structure, epistasis and immunity escape.

BackgroundThe globally growing demand for complementary and alternative medicine (CAM) has attracted educators' attention to integrate CAM into conventional nursing programs. This systematic review aimed to understand the status quo of nursing students (NSs)' overall rated knowledge of, attitude/belief toward, and practice/previous use or experience (KAP) of CAM in surveys, given these factors may influence NSs' receptivity to CAM curricula, and may be of value in guiding the development of effective teaching strategies.MethodsFormally published cross-sectional quantitative studies investigating the primary outcome of KAP toward CAM by NSs were searched for from eight databases from their inception through to 28 April 2022. PRISMA 2020 guidelines were followed.ResultsTwenty-six studies were included for analysis, 25 of which were judged to be of moderate to high quality. Despite limited and poorly informed knowledge of CAM therapies, the majority of NSs generally viewed them in a positive light. Furthermore, NSs usually reported an interest in further learning, and supported and welcomed the integration of CAM curricula, at least as elective modules, into existing nursing programs. Lack of evidence was perceived as a major barrier to the use or integration of CAM. Mass media and the internet were the main sources via which NSs access CAM information. Measurement of KAP in all included studies was via self-designed questionnaires/scales or adapted from previously developed questionnaires/scales.ConclusionsThe need for integrating and strengthening CAM curricula into current nursing education is identified. Besides theoretical knowledge and matched clinical placement, skills training in literature searching and evidence-based practice are advised to be included in the curricula design. The experiential learning mode is strongly recommended for delivering specific CAM modalities. In addition, a standard instrumentation for determining NSs' KAP toward CAM should be designed and examined for use in different cultural settings.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=300602, identifier: PROSPERO CRD42022300602.

We develop an optimization approach for the planning problem of configuring the positions of sensors within a sensor network for minimization of the travel length required to service the sensor locations. This is in contrast to existing approaches whereby the coverage of the sensor network is an objective of the optimization; in this new optimization approach the level of coverage is treated as a constraint. By beginning with an over-populated sensor network and then alternating between sensor repositioning and sensor removal, we create an optimization procedure that solves this difficult practical planning problem. A formal rule for switching between the repositioning and removal components of the optimization strategy is developed. Numerical example problems are presented to illustrate the method and show its performance against a heuristic optimization approach.

Abstract Paramedics working on a rotating shift are at an increased risk of developing chronic health issues due to continuous circadian rhythm disruption. The acute effects of shift rotation and objectively measured sleep have rarely been reported in paramedics. This study investigated the relationships between a rotating shift schedule and sleep (using actigraphy), subjective reports of sleepiness, mood, stress and fatigue. Galvanic Skin Response, energy expenditure and physical activity (BodyMedia SenseWear Armband) were also recorded across the shift schedule. Paramedics were monitored for a period of eight consecutive days across pre-shift, day shift, night shift, and 2 days off. Fifteen paramedics (M age = 39.5 and SD = 10.7 years) who worked rotational shifts experienced sleep restriction during night shift compared to pre-shift, day shift and days off (p

Pet–owner co-sleeping is increasingly common in some parts of the world. Adult owners often subjectively report benefits of co-sleeping with pets, although objective actigraphy reports conversely indicate sleep disruptions due to the pet. Because limited research is available regarding pet–owner co-sleeping in non-adult samples, the aim of this two-part study was to explore whether co-sleeping improves sleep quality in adolescents, an age group in which poor sleep patterns are well documented. In Study One, an online survey with 265 pet-owning 13-to-17-year-old participants found that over 78% co-slept with their pet. Average sleep quality scores for co-sleepers and non-co-sleepers indicated generally poor sleep, with no differences in sleep quality depending on age, gender, or co-sleeping status. Study Two consisted of two preliminary case studies, using actigraphy on dog–adolescent co-sleepers. In both cases, high sleep concordance was observed, but owners again experienced generally poor sleep quality. Future actigraphy research is needed, including larger sample sizes and a control group of non-co-sleepers, to validate the preliminary findings from this study, but our limited evidence suggests that co-sleeping with a pet may not impact sleep quality in adolescents.

A silver lining has emerged from the current COVID-19 pandemic that medical laboratory services across the Pacific have benefitted by. The pressures of COVID-19 exposed numerous deficiencies in our healthcare systems with a particular spotlight beamed onto national diagnostic testing capabilities. Consequently, laboratory services have been thrust into the centre of attention in biosecurity issues and become a high priority focus in the drive to ensure performance accuracy and diagnostic capacity is realised. Resources have been directed to ensure laboratories are prepared and responsive to early detection, but also prepared and ready for the recovery stages when borders re-open and new generation tourists are screened. An exciting development to come out of these uncertain times is the growing popularity of mobile laboratory facilities housed in shipping containers. They provide a convenient, cheap and timely solution to smaller Pacific Island nations by greatly enhancing their molecular technology platforms and containment facilities all in one box. A collaborated effort from Pacific partnership organisations has been instrumental in accelerating the establishment of these novel laboratory units and help address the need for testing facilities in geographically isolated sites.

Admixture is increasingly being recognized as an important factor in evolutionary genetics. The distribution of genomic admixture tracts, and the resulting effects on admixture linkage disequilibrium, can be used to date the timing of admixture between species or populations. However, the theory used for such prediction assumes selective neutrality despite the fact that many famous examples of admixture involve natural selection acting for or against admixture. In this paper, we investigate the effects of positive selection on the distribution of tract lengths. We develop a theoretical framework that relies on approximating the trajectory of the selected allele using a logistic function. By numerically calculating the expected allele trajectory, we also show that the approach can be extended to cases where the logistic approximation is poor due to the effects of genetic drift. Using simulations, we show that the model is highly accurate under most scenarios. We use the model to show that positive selection on average will tend to increase the admixture tract length. However, perhaps counter-intuitively, conditional on the allele frequency at the time of sampling, positive selection will actually produce shorter expected tract lengths. We discuss the consequences of our results in interpreting the timing of the introgression of EPAS1 from Denisovans into the ancestors of Tibetans.

Paramedics face many challenges while on duty, one of which is working different types of shifts. Shift work has been linked to a number of health issues such as insomnia, depression, and anxiety. Besides shift work, Saudi paramedics, a group that has not been investigated for sleep or mental health issues previously, may be facing more demands than Australian paramedics due to lower numbers of paramedics in comparison to the general population. The aim of this study was to investigate the prevalence of sleep and mental health disorders among paramedics in Saudi Arabia and Australia. Paramedics were invited to complete a survey to assess stress, post-traumatic stress disorder (PTSD), depression, anxiety, daytime sleepiness, insomnia, sleep quality, shift work disorder, obstructive sleep apnoea, fatigue, and general health. A total of 104 males Saudi paramedics (M age = 32.5 ± 6.1 years) and 83 males paramedics from Australia (M age = 44.1 ± 12.1 years) responded to the survey. Significantly higher rates of depression, PTSD, insomnia, and fatigue, along with significantly poorer physical functioning were observed among Saudi paramedics in comparison with Australian paramedics. However, Australian paramedics reported significantly poorer sleep quality and general health in comparison to Saudi paramedics. After removing the effect of driving and working durations, outcomes were no longer significant. The higher burden of depression and PTSD among Saudi paramedics may be explained by longer hours spent driving and longer work durations reported by this group. Taking into consideration the outcomes reported in this study, more investigations are needed to study their possible effects on paramedics’ cognition, performance, and safety.

BackgroundDue to concerns about risks associated with antidepressants and/or hypnotics, complementary therapies such as acupuncture have been sought by patients with active or previous depression to manage insomnia. This systematic review aimed to clarify if acupuncture is effective and safe enough to be recommended as an alternative or adjuvant therapy to standard care in ameliorating concomitant or residual insomnia, two types of insomnia associated with depression.MethodsRandomized controlled trials (RCTs) of depression-related insomnia (DI) treatment via acupuncture vs. waitlist-control or placebo-/sham-acupuncture and RCTs of DI treatment via acupuncture alone or combined with standard care [Western pharmacotherapy and/or cognitive-behavioral therapy (CBT)] vs. standard care alone were searched for from seven databases from inception to December 2021. Cochrane criteria were followed.ResultsTwenty-one studies involving 1,571 participants were analyzed. For insomnia as a major symptom of active depression, meta-analyses suggested that acupuncture significantly reduced the global scores of both the Pittsburg Sleep Quality Index (PSQI) [MD = −3.12, 95% CI (−5.16, −1.08), p < 0.01] and Hamilton Depression Scale (HAMD) [SMD = −2.67, 95% CI (−3.51, −1.84), p < 0.01], in comparison with placebo-acupuncture. When compared with conventional pharmacotherapy (antidepressants and/or hypnotics), the results favored acupuncture in decreasing PSQI [MD = −1.17, 95% CI (−2.26, −0.08), p = 0.03] and HAMD [SMD = −0.47, 95% CI (−0.91, −0.02), p = 0.04]. Acupuncture was comparable to conventional pharmacotherapy in reducing scores of each domain of PSQI. For insomnia as a residual symptom of previous or partially remitted depression, acupuncture conferred a very limited, non-significant therapeutic advantage against sham-/placebo-acupuncture. Whether acupuncture has an add-on effect to conventional pharmacotherapy in this type of insomnia has not been investigated. Also, no study was available to address the efficacy differences between acupuncture and CBT or the synergistic effect of these two therapies.ConclusionsThere is a low to moderate level of evidence supporting acupuncture as a safe and effective remedy alternative to or adjuvant to conventional pharmacotherapy (antidepressant and/or hypnotic) in improving insomnia and other depression symptoms among patients with active depression. Furthermore, the patients' complaint of disrupted sleep continuity is most likely to benefit from acupuncture. The benefit of acupuncture on residual insomnia associated with previous or partially remitted depression is limited. Future acupuncture studies need to consider applying optimal dosage and addressing deficiencies in trial quality.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021269880, PROSPERO, identifier: CRD42021269880.

Sequence simulators are fundamental tools in bioinformatics, as they allow us to test data processing and inference tools, and are an essential component of some inference methods. The ongoing surge in available sequence data is however testing the limits of our bioinformatics software. One example is the large number of SARS-CoV-2 genomes available, which are beyond the processing power of many methods, and simulating such large datasets is also proving difficult. Here, we present a new algorithm and software for efficiently simulating sequence evolution along extremely large trees (e.g. > 100, 000 tips) when the branches of the tree are short, as is typical in genomic epidemiology. Our algorithm is based on the Gillespie approach, and it implements an efficient multi-layered search tree structure that provides high computational efficiency by taking advantage of the fact that only a small proportion of the genome is likely to mutate at each branch of the considered phylogeny. Our open source software allows easy integration with other Python packages as well as a variety of evolutionary models, including indel models and new hypermutability models that we developed to more realistically represent SARS-CoV-2 genome evolution.

A new method is derived for finding the best positions in which to locate the sensors in a distributed sensor network in order to achieve a desired variation, or pattern, in spatial coverage over a specified domain. Such patterning is important in situations when there are not enough sensors to completely cover a region adequately. By providing coverage based on a desired pattern, this approach allows a user/designer to specify which sub-regions of the domain are more important to cover, and to what level that is desired. The method that is developed is novel in that it is an analytic approach, as opposed to existing numerical optimization approaches, and thus provides solutions rapidly and can also be applied to provide online repositioning for existing sensor networks to respond to changes in the environment. The method is based on deriving an expression for the probabilistic density of sensor locations that best matches the desired coverage under given spatially varying environmental conditions; and then samples from that sensor density to determine specific sensor locations. The performance of the method is demonstrated on numerical examples in both one-dimensional and two-dimensional settings. Comparisons are made between solutions found from this approach and solutions obtained by a numerical optimization technique.

This study examined the effects of a daytime nap on the retention of implicitly learnt “first-order conditional” (FOC) and “second-order conditional” (SOC) motor sequences. The implicit learning and retention of a motor sequence has been linked to the neural processes undertaken by the basal ganglia and primary motor cortex (i.e., procedural memory system). There is evidence, however, suggesting that SOC learning may further rely on the hippocampus-supported declarative memory system. Sleep appears to benefit the retention of information processed by the declarative memory system, but not the procedural memory system. Thus, it was hypothesized that sleep would benefit the retention of a SOC motor sequence but not a FOC sequence. The implicit learning and retention of these sequences was examined using the Serial Reaction Time Task. In this study, healthy adults implicitly learnt either a FOC (n = 20) or a SOC sequence (n = 20). Retention of both sequences was assessed following a daytime nap and period of wakefulness. Sleep was not found to improve the retention of the SOC sequence. There were no significant differences in the retention of a FOC or a SOC sequence following a nap or period of wakefulness. The study questions whether the declarative memory system is involved in the retention of implicitly learnt SOC sequences.

Background: Many women with perimenopausal depression (PMD) have sought alternative therapies such as acupuncture because of concerns about risks associated with antidepressant and hormone replacement therapy (HRT). This systematic review aimed to clarify if acupuncture is effective for PMD compared with waitlist control or placebo/sham acupuncture, and if acupuncture alone or combined with standard care (antidepressant and/or HRT) is more effective in ameliorating PMD in comparison with standard care alone.Methods: Randomized controlled trials (RCTs) of PMD treatment via acupuncture vs. waitlist control or placebo/sham acupuncture, and RCTs of PMD treatment via acupuncture alone or combined with Western pharmacotherapy vs. Western pharmacotherapy were searched for from seven databases from inception to December 2020. Cochrane criteria were followed.Results: Twenty-five studies involving 2,213 women were analyzed. Meta-analyses indicated that acupuncture significantly reduced the global scores of Hamilton Depression Scale (HAMD) [standardized mean difference (SMD) = −0.54, 95% CI (−0.91, −0.16), p < 0.01], compared with standard care. The therapeutic effect of acupuncture maintained at 2-, 4-, and 12-week follow-ups. Acupuncture combined with standard care was more effective than standard care alone in decreasing HAMD scores [SMD = −0.82, 95% CI (−1.07, −0.58), p < 0.01]. Too few RCTs were available to assess the clinical efficacy differences between acupuncture and placebo/sham acupuncture or HRT alone. Acupuncture also showed better effects in decreasing Kupperman index (KI) scores, whether compared with antidepressant alone [MD = −4.55, 95% CI (−8.46, −0.65), p = 0.02] or antidepressant combined with HRT [MD = −0.89, 95% CI (−1.34, −0.43), p < 0.01].Conclusions: In comparison with standard care, acupuncture alone or combined with standard care was associated with significant improvements in PMD and reductions of other menopausal symptoms. This finding suggests that acupuncture may be a useful addition to treatment for PMD.

The SARS-CoV-2 pandemic has led to unprecedented, nearly real-time genetic tracing due to the rapid community sequencing response. Researchers immediately leveraged these data to infer the evolutionary relationships among viral samples and to study key biological questions, including whether host viral genome editing and recombination are features of SARS-CoV-2 evolution. This global sequencing effort is inherently decentralized and must rely on data collected by many labs using a wide variety of molecular and bioinformatic techniques. There is thus a strong possibility that systematic errors associated with lab-or protocol-specific practices affect some sequences in the repositories. We find that some recurrent mutations in reported SARS-CoV-2 genome sequences have been observed predominantly or exclusively by single labs, co-localize with commonly used primer binding sites and are more likely to affect the protein-coding sequences than other similarly recurrent mutations. We show that their inclusion can affect phylogenetic inference on scales relevant to local lineage tracing, and make it appear as though there has been an excess of recurrent mutation or recombination among viral lineages. We suggest how samples can be screened and problematic variants removed, and we plan to regularly inform the scientific community with our updated results as more SARS-CoV-2 genome sequences are shared (https://virological.org/t/issues-with-sars-cov-2-sequencing-data/473 and https://virological.org/t/masking-strategies-for-sars-cov-2-alignments/480). We also develop tools for comparing and visualizing differences among very large phylogenies and we show that consistent clade- and tree-based comparisons can be made between phylogenies produced by different groups. These will facilitate evolutionary inferences and comparisons among phylogenies produced for a wide array of purposes. Building on the SARS-CoV-2 Genome Browser at UCSC, we present a toolkit to compare, analyze and combine SARS-CoV-2 phylogenies, find and remove potential sequencing errors and establish a widely shared, stable clade structure for a more accurate scientific inference and discourse.

Background/objectives: Emerging research suggests that face-to-face group mindfulness-based therapies are an effective intervention for insomnia. This pilot study examined the effectiveness of a mindfulness-based smartphone application for improving objectively-measured sleep, self-reported sleep, insomnia severity, pre-sleep arousal and daytime mood. Method: A community sample of 23 adults with subclinical to moderately severe symptoms of insomnia were randomized to either a mindfulness or progressive muscle relaxation (PMR) smartphone application for 40 or 60 days. Objective sleep outcomes assessed using actigraphy, and self-report measures of total wake time, cognitive and somatic pre-sleep arousal, and daytime positive and negative affect were assessed for 14 nights at baseline and post-intervention. Insomnia severity was recorded at baseline and post-intervention. Results: A greater reduction in sleep onset latency was observed in the mindfulness group over time, relative to the PMR group. The mindfulness group also reported medium effect size improvements for sleep efficiency. No significant interaction effects were found for self-reported sleep measures, however, main effects of time were found for both groups for total wake time, insomnia severity, cognitive pre-sleep arousal, and daytime positive and negative affect. Conclusions: These preliminary findings suggest that both mindfulness and PMR smartphone applications have the potential to improve symptoms of insomnia. In particular, this mindfulness-based smartphone application may improve sleep onset latency and reduce the duration of night-awakenings. Further research exploring digital therapeutics as a self-help option for those with insomnia is needed.

Bacterial symbionts bring a wealth of functions to the associations they participate in, but by doing so, they endanger the genes and genomes underlying these abilities. When bacterial symbionts become obligately associated with their hosts, their genomes are thought to decay towards an organelle-like fate due to decreased homologous recombination and inefficient selection. However, numerous associations exist that counter these expectations, especially in marine environments, possibly due to ongoing horizontal gene flow. Despite extensive theoretical treatment, no empirical study thus far has connected these underlying population genetic processes with long-term evolutionary outcomes. By sampling marine chemosynthetic bacterial-bivalve endosymbioses that range from primarily vertical to strictly horizontal transmission, we tested this canonical theory. We found that transmission mode strongly predicts homologous recombination rates, and that exceedingly low recombination rates are associated with moderate genome degradation in the marine symbionts with nearly strict vertical transmission. Nonetheless, even the most degraded marine endosymbiont genomes are occasionally horizontally transmitted and are much larger than their terrestrial insect symbiont counterparts. Therefore, horizontal transmission and recombination enable efficient natural selection to maintain intermediate symbiont genome sizes and substantial functional genetic variation.

Abstract In this paper, we study the “Session Reconstruction” problem which is the reconstruction of user interactions from recorded request/response logs of a session. The reconstruction is especially useful when the only available information about the session is its HTTP trace, as could be the case during a forensic analysis of an attack on a website. Solutions to the reconstruction problem do exist for “traditional” Web applications. However, these solutions cannot handle modern “Rich Internet Applications” (RIAS). Our solution is implemented in the context of RIAs in a tool called D-ForenRIA. Our tool is made of a proxy and a set of browsers. Browsers are responsible for trying candidate actions on each DOM, and the proxy, which contains the observed HTTP trace, is responsible for responding to browsers’ requests and validating attempted actions on each DOM. D-ForenRIA has a distributed architecture, a learning mechanism to guide the session reconstruction process efficiently, and can handle complex user-inputs, client-side randomness, and to some extents actions that do not generate any HTTP traffic. In addition, concurrent reconstruction makes the system scalable for real-world use. The results of our evaluation on several RIAs show that D-ForenRIA can efficiently reconstruct user-sessions in practice.

Beards are a sort of dwelling. Much like Heidegger's linguistic play with related etymologies of building and dwelling, beards are in a constant state of becoming, forever changing length, shape, and color. To the person—usually, but not always, a man—who grows a beard, the end product is always projected out into the future, like Heidegger’s concept of being. The beard is trimmed and groomed constantly; it is cultivated in a way that feels authentic to its wearer. But the same ontological problems that Heidegger applies to dwelling in a home also apply to beards. Long facial hair symbolizes wisdom in many cultures, but anyone who has grown a beard can attest to the existential dilemma of long facial hair. I didn’t recognize you with the beard, someone will say. Beards can serve as symbols of erudition, yes, but they are also masks for our social selves. The beard is, after all, is a curious appendage, as it is an extension of the self, but not the self per se. Herman Melville called beards “suburbs of the chin.” If, like Heidegger, we are to see being as not a fixed entity divorced from other beings, but a being-in-the-world, a set of relations among other beings, then beards are not simply static accessories or styles, but an example of the slippery nature of being itself.

Therapy for public speaking phobia using virtual reality exposure (VRE) has focused on distress arousal rather than distress habituation. Understanding habituation will help optimise session duration, making treatment more affordable and accessible. This pilot study utilised within-speech repeated measures to examine distress habituation during three brief public speaking scenarios in a non-clinical sample (n = 19; 18-76 years). VRE elicited significant distress in all three scenarios. Although within-scenario distress habituation was not observed, between-scenario habituation was partially supported. An increase in distress during the second scenario indicated that three consecutive speech performances were critical in achieving habituation. Brief repeated VRE scenarios using an agent audience were effective in eliciting public speaking distress, as well as habituation.

Phase change memories involve crystalline-to-amorphous transformations which require high current densities. Here, the authors introduce extended defects in GeTe crystals, reduce the current densities necessary for amorphization and obtain low-power, scalable memories with multiple resistance states.

Task-switching is an important cognitive skill that facilitates our ability to choose appropriate behavior in a varied and changing environment. Task-switching training studies have sought to improve this ability by practicing switching between multiple tasks. However, an efficacious training paradigm has been difficult to develop in part due to findings that small differences in task parameters influence switching behavior in a non-trivial manner. Here, for the first time we employ the Drift Diffusion Model (DDM) to understand the influence of feedback on task-switching and investigate how drift diffusion parameters change over the course of task switch training. We trained 316 participants on a simple task where they alternated sorting stimuli by color or by shape. Feedback differed in six different ways between subjects groups, ranging from No Feedback (NFB) to a variety of manipulations addressing trial-wise vs. Block Feedback (BFB), rewards vs. punishments, payment bonuses and different payouts depending upon the trial type (switch/non-switch). While overall performance was found to be affected by feedback, no effect of feedback was found on task-switching learning. Drift Diffusion Modeling revealed that the reductions in reaction time (RT) switch cost over the course of training were driven by a continually decreasing decision boundary. Furthermore, feedback effects on RT switch cost were also driven by differences in decision boundary, but not in drift rate. These results reveal that participants systematically modified their task-switching performance without yielding an overall gain in performance.

Using electrical and thermal measurements, we present a method for characterising the anomalous Nernst effect (ANE) within nanoscale devices implementing perpendicular anisotropy materials. Perpendicularly magnetised CoFeB/Pt nanowires were fabricated in close proximity to Pt heater elements on an electrically insulating substrate. The voltages induced within the magnetic material as a result of the ANE were recorded for increasing heater powers, and for both out-of-plane saturated states of the device. Scanning thermal probe microscopy was used to map the temperature distribution within the region of the device at a range of heater powers. By analysing the results from each thermography measurement, it was possible to correlate the temperature gradient induced at the magnetic nanowire against the anomalous Nernst voltage measured within the device. For the particular material, geometry and substrate used, a Nernst coefficient value KN = 2.3 μV(K.T)-1 was calculated. This combination of measurements can provide a powerful tool to characterise the ANE within a number of nanoscale systems, a necessary task for the future implementation and optimisation of the effect within spin-caloritronic devices.

We present new studies of the characteristics and detection ability of nanoscale sensors based on domain wall nucleation within perpendicularly magnetised ultrathin CoFeB/Pt films. A combination of MFM imaging and anomalous Hall effect transport measurements were used to verify and characterise the behaviour of fabricated devices. After initial characterisation, the influence of magnetic nanoparticles on device behaviour was studied using individual iron oxide (FeOx) particles mounted on modified atomic force microscopy probes. We demonstrate the successful detection of particles ranging in diameter between 2.8 μm and 100 nm. In the case of the 2.8 μm particle, we have mapped the signal amplitude produced at a variety of distances from the sensor. We find that the particle’s influence may be detected at separations up to 700 nm. Furthermore, we demonstrate a method for resolving the location of a particle with respect to the centre of the device, providing a lateral sensing ability.

Anxiety disorders are the most common type of mental disorder during adolescence, which is at least partly due to the resistance to extinction exhibited at this age. The dopaminergic system is known to be dysregulated during adolescence; therefore, we aimed to facilitate extinction in adolescent rats using the dopamine receptor 2 partial agonist aripiprazole (Abilify™), and examine the behavioral and neural outcomes. Adolescent rats were conditioned to fear a tone. The next day, rats received extinction 30 min after a systemic injection of either 5 mg/kg aripiprazole or vehicle, and then were tested the following day. For the immunohistochemistry experiment, naïve and “no extinction” conditions were added and rats were perfused either on the extinction day or test day. To assess the activation of neurons receiving dopaminergic input, c-Fos, and dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) labeled neurons were quantified in the amygdala and the medial prefrontal cortex (mPFC). Systemic treatment with aripiprazole at the time of extinction significantly reduced freezing at test the next day. This effect was not observed in rats that were fear conditioned but did not receive any extinction. Aripiprazole's facilitation of extinction was accompanied by increased activation of neurons in the mPFC. Taken together, aripiprazole represents a novel pharmacological adjunct to exposure therapy worthy of further examination. The effect of aripiprazole is related to enhanced activation of mPFC neurons receiving dopaminergic innervation.

Devices comprised of CoFeB nanostructures with perpendicular magnetic anisotropy and non-magnetic Ta channel were operated in thermal lateral spin valve (LSV) mode and studied by magnetotransport measurements and magnetic scanning gate microscopy (SGM). Due to the short spin diffusion length of Ta, the spin diffusion signal was suppressed, allowing the study of the contribution from the anomalous Nernst (ANE) and anomalous Hall effects (AHE). The magnetotransport measurements identified the switching fields of the CoFeB nanostructures and demonstrated a combination of AHE and ANE when the devices were operated in thermally-driven spin-injection mode. Modified scanning probe microscopy probes were fabricated by placing a NdFeB magnetic bead (MB) on the apex of a commercial Si probe. The dipole magnetic field distribution around the MB was characterized by using differential phase contrast technique and direct measurement of the switching field induced by the bead in the CoFeB nanodevices. Using SGM we demonstrate the influence of localized magnetic field on the CoFeB nanostructures near the non-magnetic channel. This approach provides a promising route towards the study of thermal and spin diffusion effects using local magnetic fields.

The Juan Fernández Archipelago (33°37'S, 78°51'W), an isolated group of islands 650 km west of continental Chile, has a high degree of endemism in its marine biota. Despite numerous scientific expeditions to these islands that have identified this high endemism, few studies have attempted to identify patterns of community structure in subtidal habitats. Using visual census, we surveyed fish and habitat associations at five sites located at two of the three islands of the archipelago. Given the isolation of the archipelago we asked: What is the composition of the reef fish fauna at these isolated islands? What habitats dominate subtidal environments? What influences the abundances of reef fishes? Our analysis confirms that fish communities at the archipielago are dominated by endemic species. The ichthyofauna is comprised of a mixture of subtropical and temperate taxa, with greater similarity to western than eastern South Pacific fauna. We identified different fish assemblages at wave-exposed and wave-sheltered sites. Brown and red macroalgae were correlated with the abundances of some reef fishes. Four broad trophic categories of reef fishes were present at the archipelago, with invertebrate consumers dominating abundance. To our knowledge, this is the first attempt to quantify patterns of community structure in subtidal environments at the Juan Fernández Archipelago.

Polyimide (PI, Kapton-H®) films are widely utilized in the spacecraft industry for their insulating properties, mechanical durability, light weight, and chemical resistance to radiation. Still PI materials remain exposed to a combination of high-energy electrons, protons, and ultraviolet (UV) photons, particles primarily responsible for radiation-induced damage in geosynchronous Earth orbit (GEO), which drastically change PI’s properties. This work reviews the effect of electron, proton, and UV photon irradiation on the material properties (morphology, absorption, mechanical properties, and charge transport) of PI. The different damaging mechanisms and chemical consequences that drive changes in the material properties of PI caused by each individual kind of irradiation will be discussed in detail.

Admixture-the mixing of genomes from divergent populations-is increasingly appreciated as a central process in evolution. To characterize and quantify patterns of admixture across the genome, a number of methods have been developed for local ancestry inference. However, existing approaches have a number of shortcomings. First, all local ancestry inference methods require some prior assumption about the expected ancestry tract lengths. Second, existing methods generally require genotypes, which is not feasible to obtain for many next-generation sequencing projects. Third, many methods assume samples are diploid, however a wide variety of sequencing applications will fail to meet this assumption. To address these issues, we introduce a novel hidden Markov model for estimating local ancestry that models the read pileup data, rather than genotypes, is generalized to arbitrary ploidy, and can estimate the time since admixture during local ancestry inference. We demonstrate that our method can simultaneously estimate the time since admixture and local ancestry with good accuracy, and that it performs well on samples of high ploidy-i.e. 100 or more chromosomes. As this method is very general, we expect it will be useful for local ancestry inference in a wider variety of populations than what previously has been possible. We then applied our method to pooled sequencing data derived from populations of Drosophila melanogaster on an ancestry cline on the east coast of North America. We find that regions of local recombination rates are negatively correlated with the proportion of African ancestry, suggesting that selection against foreign ancestry is the least efficient in low recombination regions. Finally we show that clinal outlier loci are enriched for genes associated with gene regulatory functions, consistent with a role of regulatory evolution in ecological adaptation of admixed D. melanogaster populations. Our results illustrate the potential of local ancestry inference for elucidating fundamental evolutionary processes.

Process operators face competing demands to maintain process safety, while at the same time meeting production targets. Since June 2015 the Seveso III directive replaces Seveso II with stricter standards for inspections by notified bodies and more effective enforcement of the rules for managing safety. Inspectors look for evidence of good practice in process safety, with reference to IEC 61511 as the benchmark. Many experienced operators of hazardous process plants already manage safety to some extent. However, IEC 61511 calls for structure and planning, to ensure that nothing goes un-checked. Records should show that plans were followed and any resulting corrective actions completed. Producing documents to show functional safety is well-managed can be challenging, when the inspector calls. Five key areas are investigated, and opportunities for improvement are explored. Three of these topics relate to the operational phase of the safety lifecycle, which is applicable to all plants, regardless of age, or of safety instrumented system (SIS) technology in use: Safety Requirements Specification (SRS), Technology Selection, Management of Safety System assets, Planning for Proof Test and Inspection, Management of overrides. Suggestions for improvements are made and thought-provoking impulses are given for each of the key areas resulting in a set of recommended best practices that are likely to improve safety at any plant without causing the need of major investments.

Current glaucoma management modalities are hindered by low patient compliance and adherence. This can be due to highly complex treatment strategies or poor patient understanding. Treatments focus on the management or reduction of intraocular pressure. This is most commonly done through the use of daily topical eye drops. Unfortunately, despite effective therapies, glaucoma continues to progress, possibly due to patients not adhering to their treatments. In order to mitigate these patient compliance issues, many sustained release treatments are being researched and are entering the clinic. Conjunctival, subconjunctival, and intravitreal inserts, punctal plugs, and drug depots are currently in clinical development. Each delivery system has hurdles, yet shows promise and could potentially mitigate the current problems associated with poor patient compliance.

Publish and Anguish: Reconsidering the Never Ending Crisis of the Humanities Russell Cobb This article reviews three books (Michael Bérubé. The Left at War. New York: New York University Press, 2009; Stanley Fish. Save the World on Your Own Time. Oxford: Oxford University Press, 2008; Louis Menand, The Marketplace of Ideas: Reform and Reaction in the American University. New York: W.W. Norton, 2010) in the larger context of the decline in funding and enrollment numbers in humanities departments. The article explores various responses to the crisis in the humanities in North America and ultimately agrees with Menand that reforms must be taken to make the humanities more relevant to fields outside the academy. The author disagrees with Fish that it is advisable or even possible to separate academic work from politics and also disagrees with Menand that the radical Left, or "Manichean" Left, represents a substantial problem in mainstream academic culture. Publier et s’angoisser: Reconsidérations sur la crise éternelle des sciences humaines Russell Cobb Cet article examine trois ouvrages récents (The Left at War par Michael Bérubé, New York: New York University Press, 2009; Save the World on Your Own Time, par Stanley Fish, Oxford: Oxford University Press, 2008; The Marketplace of Ideas: Reform and Reaction in the American University par Louis Menand, New York: W.W. Norton, 2010) dans la perspective du déclin du financement et des inscriptions au sein des départements de sciences humaines. L’auteur y passe en revue un certain nombre de positions adoptées jusqu’ici face à cette crise du point de vue nord-américain, pour finalement se ranger aux arguments de Menand selon lesquels une réforme est nécessaire en vue de rendre les sciences humaines plus compatibles avec des domaines extérieurs au monde académique. L’article s’oppose toutefois à Menand sur la prétendue nature problématique d’une intelligentsia radicale de gauche dans les universités, et prend le contrepied des propos de Fish quant au besoin de séparer la recherche fondamentale de la sphère politique.

Recognition of individuals by scent is widespread across animal taxa. Though animals can often discriminate chemical blends based on many compounds, recent work shows that specific protein pheromones are necessary and sufficient for individual recognition via scent marks in mice. The genetic nature of individuality in scent marks (e.g. coding versus regulatory variation) and the evolutionary processes that maintain diversity are poorly understood. The individual signatures in scent marks of house mice are the protein products of a group of highly similar paralogs in the major urinary protein (Mup) gene family. Using the offspring of wild-caught mice, we examine individuality in the major urinary protein (MUP) scent marks at the DNA, RNA and protein levels. We show that individuality arises through a combination of variation at amino acid coding sites and differential transcription of central Mup genes across individuals, and we identify eSNPs in promoters. There is no evidence of post-transcriptional processes influencing phenotypic diversity as transcripts accurately predict the relative abundance of proteins in urine samples. The match between transcripts and urine samples taken six months earlier also emphasizes that the proportional relationships across central MUP isoforms in urine is stable. Balancing selection maintains coding variants at moderate frequencies, though pheromone diversity appears limited by interactions with vomeronasal receptors. We find that differential transcription of the central Mup paralogs within and between individuals significantly increases the individuality of pheromone blends. Balancing selection on gene regulation allows for increased individuality via combinatorial diversity in a limited number of pheromones.