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We present the serendipitous radio-continuum discovery of a likely Galactic supernova remnant (SNR) G305.4–2.2. This object displays a remarkable circular symmetry in shape, making it one of the most circular Galactic SNRs known. Nicknamed Teleios due to its symmetry, it was detected in the new Australian Square Kilometre Array Pathfinder (ASKAP) Evolutionary Map of the Universe (EMU) radio–continuum images with an angular size of 1 320$^{\prime\prime}$$\times$1 260$^{\prime\prime}$ and PA = 0$^\circ$. While there is a hint of possible H$\alpha$ and gamma-ray emission, Teleios is exclusively seen at radio–continuum frequencies. Interestingly, Teleios is not only almost perfectly symmetric, but it also has one of the lowest surface brightnesses discovered among Galactic SNRs and a steep spectral index of $\alpha$=–0.6$\pm$0.3. Our best estimates from Hi studies and the $\Sigma$–D relation place Teleios as a type Ia SNR at a distance of either $\sim$2.2 kpc (near-side) or $\sim$7.7 kpc (far-side). This indicates two possible scenarios, either a young (under 1 000 yr) or a somewhat older SNR (over 10 000 yr). With a corresponding diameter of 14/48 pc, our evolutionary studies place Teleios at the either early or late Sedov phase, depending on the distance/diameter estimate. However, our modelling also predicts X-ray emission, which we do not see in the present generation of eROSITA images. We also explored a type Iax explosion scenario that would point to a much closer distance of $\lt$1 kpc and Teleios size of only $\sim$3.3 pc, which would be similar to the only known type Iax remnant SN1181. Unfortunately, all examined scenarios have their challenges, and no definitive Supernova (SN) origin type can be established at this stage. Remarkably, Teleios has retained its symmetrical shape as it aged even to such a diameter, suggesting expansion into a rarefied and isotropic ambient medium. The low radio surface brightness and the lack of pronounced polarisation can be explained by a high level of ambient rotation measure (RM), with the largest RM being observed at Teleios’s centre.
Sulfur stable isotope ratios (δ34S) have become increasingly common in archaeology for studying paleodiet, especially in occasions where there is a need to identify aquatic resource consumption more accurately. This is particularly relevant in the Baltic Sea region, where brackish conditions tend to mask “typical” marine carbon isotopic signals. Here we report new δ34S values for 126 human bone collagen samples which will be analyzed together with previously published data to investigate the potential of sulfur isotopes as an alternative proxy for aquatic resource consumption in historic period Estonia (ca. AD 1100‒1800). Bayesian statistical programming was used to provide quantitative dietary estimates, suggesting that the diet of the general population was predominantly terrestrial. The inclusion of δ34S as an additional dietary proxy produced generally comparable model results to the scenario that excluded δ34S. A sub-selection of samples was also radiocarbon dated and calibrated to take into account potential reservoir effects. For burials of commoners, the average contribution of 10% fish to dietary carbon does not significantly alter calibrated date ranges, even in the occasion where data on local reservoir effects is insufficient. This study has demonstrated both the potential and the pitfalls of using δ34S in this temporo-spatial context, and the new stable isotope and 14C data have shed light onto individual site-histories but also to broader cultural processes and changes that occurred during these turbulent times in this region.
Depression, a leading cause of global disability, arises from a multifaceted combination of genetic and environmental components. This study explores the relationship between major depressive disorder (MDD) polygenic scores (PGS), characteristics and symptoms of depression, and community-shared socioeconomic factors derived from postal code data in a cohort of 12,646 individuals from the Australian Genetics of Depression Study (AGDS). Our findings reveal that people living in areas with relatively higher socioeconomic advantages and education/occupation scores are more likely to report experiencing fewer depressive symptoms during their worst depressive period, as well as fewer number of lifetime episodes. Additionally, participants who reported depression onset later in life tend to currently reside in wealthier areas. Interestingly, no significant interaction between genetic and socioeconomic factors was observed, suggesting their independent contribution to depression outcomes. This research underscores the importance of integrating socioeconomic factors into psychiatric evaluation and care, and points to the critical role of public policy in addressing mental health disparities driven by socioeconomic factors. Future research should aim to further elucidate the causal relationships within these associations and explore the potential for integrated genetic and socioeconomic approaches in mental health interventions.
Measurements of the radiocarbon (14C) content of subannual wood cellulose samples over the 1963 bomb spike have revealed an apparent delay between the increase in atmospheric radiocarbon content and that of wood cellulose. This delay is apparent in both coniferous and deciduous tree species and is of a magnitude of approximately 4 weeks. The delay in wood cellulose 14C change as measured in a Sitka spruce from Washington state, USA, was previously used to estimate the relative influence of tree physiological effects contra environmental effects. We repeated the measurements with the increased measurement precision of today’s AMS systems and compare the new results to the ones of a Scots pine tree from Trondheim, central Norway and a white oak from Oregon state, USA. The results challenge the assumption that the 14C tree ring records directly show the atmospheric 14C concentration of a homogeneous, zonally well-mixed atmosphere. Instead, the apparent 1963 delay reflects local influences of the ecosystem and tree physiology. The 1963/1964 data allows for exploratory modeling of the effects of biospheric decay CO2 and local environmental influences assuming the absence of stored photosynthates from the previous year. Compared to the 10–30% contribution from biospheric CO2, the effects of delayed incorporation of carbon into the wood cellulose and the effect of stored photosynthate are small in the conifers. Highly detailed 14C records of stem cellulose can, in combination with stable isotope studies, contribute to our understanding of variability of the local carbon cycle, climate, and the environment.
The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
There is a substantial difference between the housing that older Americans prefer and the housing that the market supplies. While market failures and seniors’ resource constraints explain part of this mismatch, zoning laws, Medicare and Medicaid reimbursement policies, and health law also loom large. Older Americans strongly prefer to age in place, in home-like environments. This chapter focuses on two types of housing that facilitate that manner of aging: Green House nursing homes and accessory dwelling units. The chapter discusses the substantial benefits for seniors who rely on others for care, and those who can live independently, in these respective kinds of housing. These benefits include substantial health and quality-of-life advantages as well as the ability to maintain connectedness within existing social networks. The chapter further examines the legal impediments to the proliferation of these housing types and the measures that some forward-looking jurisdictions are taking to facilitate their growth.
A major subglacial lake, Lake Snow Eagle (LSE), was identified in East Antarctica by airborne geophysical surveys. LSE, contained within a subglacial canyon, likely hosts a valuable sediment record of the geological and glaciological changes of interior East Antarctica. Understanding past lake activity is crucial for interpreting this record. Here, we present the englacial radiostratigraphy in the LSE area mapped by airborne ice-penetrating radar, which reveals a localized high-amplitude variation in ice unit thickness that is estimated to be ∼12 ka old. Using an ice-flow model that simulates englacial stratigraphy, we investigate the origin of this feature and its relationship to changes in ice dynamical boundary conditions. Our results reveal that local snowfall redistribution initiated around the early Holocene is likely the primary cause, resulting from a short-wavelength (∼10 km) high-amplitude (∼20 m) ice surface slope variation caused by basal lubrication over a large subglacial lake. This finding indicates an increase in LSE water volume during the Holocene, illustrating the sensitivity in volume of a major topographically constrained subglacial lake across a single glacial cycle. This study demonstrates how englacial stratigraphy can provide valuable insight into subglacial hydrological changes before modern satellite observations, both for LSE and potentially at other locations.
Objectives/Goals: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer (BC) with limited treatment options. Mortality rate is especially high in African American (AA) women of reproductive age. High levels of intracellular calcium (Ca2+) have been shown in TNBC cells. This study is to investigate Ca2+ channel blockers (CCBs) as therapy for TNBC. Methods/Study Population: Two human TNBC cell lines obtained from ATCC – HCC1806, and MDA-MB-453 are treated with CCBs, Cilnidipine (Cil), and Mibefradil (Mib), in a concentration- and time-dependent manner. Cell proliferation assays are performed by the MTS cell viability assay. Intracellular Ca2+ levels are measured using the fluorescent dye: Fluro 4-AM. Apoptosis is determined by flow cytometry using Annexin V staining and mitochondrial permeability will be assessed by the Mito JC-1 assay. Expression of Ca2+ signaling genes will be quantitated by real-time polymerase chain reaction (RT-PCR). Potential pathways of CCB efficacy will be identified by ingenuity pathway analysis (IPA). Results/Anticipated Results: Our findings show both CCBs decrease cell proliferation in a concentration- and time-dependent manner to a maximum of 80% vs. control in both TNBC cells. Flow cytometry findings on both TNBC cells treated with both drugs at 20 µM for 24 hours depicts late apoptosis. Interestingly, Mib did not change the intracellular Ca2+ level in HCC1806 cells yet decreased in MDA-MB-453 cells by fivefold, while Cil increased the intracellular Ca2+ level in both cells almost twofold. It is anticipated that Mito JC-1 assay depict decreased mitochondrial potential in both cells. For reverse transcription polymerase chain reaction, it is anticipated that CCB treatment will increase transient receptor potential Ca2+ channels and decrease voltage-gated Ca2+ channels in both cells. IPA analysis is expected to show apoptotic pathways are involved in TNBC via CCB treatment. Discussion/Significance of Impact: TNBC lacks the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Treatment options for TNBC remain severely limited. Our findings that both Cil and Mib can inhibit proliferation of human breast cancer cell lines indicate repurposing CCBs as treatment for TNBC warrants further investigation.
This paper studies reversibility and transitivity of semigroups acting on homogeneous spaces. Properties of the reversor set of a subsemigroup acting on homogeneous spaces are presented. Let G be a topological group and L a subgroup of G. Assume that S is a subsemigroup of G with nonempty interior. It is presented a study of the reversibility of the S-action on $G/L$ in terms of the actions of S and L on homogeneous spaces of G. The results relate the reversibility and the transitivity of S in $G/L$ with the minimality of the action of L on homogeneous spaces of G. In addition, sufficient conditions for S to be right reversible in G if S is reversible in $G/L$ are presented.
Increasing daylight exposure might be a simple way to improve mental health. However, little is known about daylight-symptom associations in depressive disorders.
Methods
In a subset of the Australian Genetics of Depression Study (N = 13,480; 75% female), we explored associations between self-reported number of hours spent in daylight on a typical workday and free day and seven symptom dimensions: depressive (overall, somatic, psychological); hypo-manic-like; psychotic-like; insomnia; and daytime sleepiness. Polygenic scores for major depressive disorder (MDD); bipolar disorder (BD); and schizophrenia (SCZ) were calculated. Models were adjusted for age, sex, shift work status, employment status, season, and educational attainment. Exploratory analyses examined age-stratified associations (18–24 years; 25–34 years; 35–64 years; 65 and older). Bonferroni-corrected associations (p < 0.004) are discussed.
Results
Adults with depression reported spending a median of one hour in daylight on workdays and three hours on free days. More daylight exposure on workdays and free days was associated with lower depressive (overall, psychological, somatic) and insomnia symptoms (p’s<0.001), but higher hypo-manic-like symptoms (p’s<0.002). Genetic loading for MDD and SCZ were associated with less daylight exposure in unadjusted correlational analyses (effect sizes were not meaningful). Exploratory analyses revealed age-related heterogeneity. Among 18–24-year-olds, no symptom dimensions were associated with daylight. By contrast, for the older age groups, there was a pattern of more daylight exposure and lower insomnia symptoms (p < 0.003) (except for 25–34-year-olds on free days, p = 0.019); and lower depressive symptoms with more daylight on free days, and to some extent workdays (depending on the age-group).
Conclusions
Exploration of the causal status of daylight in depression is warranted.
While national rules regarding the scope, availability and issuance of utility models vary from country to country, most utility model regimes offer protection for tangible products, with many, but not all, jurisdictions excluding processes, biological materials and computer software from the scope of protection. The duration of utility model protection ranges from five to fifteen years, with most countries offering ten years of protection. In most countries, utility model applications are not formally examined and must simply disclose the product in question. Given the lack of examination, obtaining utility models is generally viewed as faster and cheaper than obtaining patents. This combination of speed and cost, in theory, makes utility models potentially attractive to small and medium enterprises (SMEs) that cannot afford to obtain full patent protection. Similar considerations have also been raised as advantageous to innovators in low-income countries.
In laboratory testing, a novel hydrogen peroxide gas plasma endoscope sterilizer consistently reduced vegetative organisms, but not bacterial spores, to undetectable levels in the presence of high organism load (≥6.5 log10) and organic material and salts. These findings highlight the importance of meticulous cleaning of endoscopes prior to sterilization.
Procedure duration is an important predictor of patient outcomes in surgery. However, the relationship between procedure duration and adverse events in congenital cardiac catheterization is largely unexplored.
Methods:
All cases entered into the Congenital Cardiac Catheterization Project on Outcomes from 2014 to 2017 were included. Cases were ordered from shortest to longest case length, minus time spent managing adverse events, for each case type. The outcomes, Level 3bc/4/5 and 4/5 adverse event rates, were calculated for cases above and below the 75th percentile for case length. To identify an independent relationship between case length and outcomes, the case length percentile was added to the CHARM II risk model.
Results:
Among 14,704 catheterizations, longer cases (>75th percentile for case length) had Level 4/5 rates that were 2.2% and 2.7% compared to cases ≤75th percentile with adverse event rates of 0.9% and 1.4% for diagnostic and interventional cases, respectively. Level 3bc/4/5 rates were 5.0% and 8.4% in longer cases compared to 2.4% and 5.4% for diagnostic and interventional cases, respectively. After adding case length to the CHARM II risk model, case length 50th–75th percentile had an odds ratio (OR) of 1.4, 75th–90th percentile an OR of 1.56, and >90th percentile an OR of 2.24 as compared to cases with case length <50th percentile (p ≤ 0.001 for all).
Conclusions:
Longer case lengths are associated with clinically important and life-threatening adverse events in congenital cardiac catheterization, even after accounting for known risk factors. Case length may be an important target for future quality improvement work.
The strategy method (SM) is, in practice, subject to a possibly severe economic-theoretical bias. Although many studies utilize SM to examine responses to rare or off-equilibrium behaviors unattainable through direct elicitation (DE), they ignore the fact that the strategic equivalence between SM and DE holds for the monetary payoff game but not the game participants actually play, which is in terms of utilities. We report three results. First, failing to account for estimation bias when decisions at one information set can influence utility at another may result in significant differences in decision-making. Second, the magnitude of this bias can be substantial, comparable to other measured treatment effects. Third, minor interventions targeting salience can amplify these differences similarly, causing treatment effects to differ significantly between SM and DE, even reversing in direction. These findings emphasize the need for reconsideration of the SM’s reliability for economic research.
This article highlights a potential and significant economic–theoretical bias in the widely used strategy method (SM) technique. Although SM is commonly employed to analyze numerous observations per subject regarding rare or off-equilibrium behaviors unattainable through direct elicitation (DE), researchers often overlook a critical distinction. The strategic equivalence between SM and DE is applicable in the context of monetary payoff games, but not in the actual utility-based games played by participants. This oversight may lead to inaccurate conclusions and demand a reevaluation of existing research in the field. We formalize the mapping from the monetary payoff game to this actual game and delineate necessary and sufficient conditions for strategic equivalence to apply.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Disruptions of antipsychotic therapy lead to greater symptoms and increased likelihood of relapse. One way to improve medication adherence has been with long-acting formulations, usually administered by injection. Implantable technology has been used to support medication continuity in a few therapeutic areas, e.g., contraception. Despite the potential benefits from implants, this modality is not yet available for maintenance treatment of schizophrenia. Delpor, Inc. is developing an investigational risperidone implant (DLP-114) that releases therapeutic drug levels for up to 12-months. Initial clinical findings are reported below.
Methods
The DLP-114 implant is a titanium cylinder approximately 4-5 cm long and 5 mm in diameter. It has membranes mounted on each end and is loaded with a proprietary formulation of risperidone.
The clinical study (NCT04418466) was an open-label study in stable schizophrenia patients to evaluate the safety, tolerability, and pharmacokinetics (PK) of switching from oral risperidone to DLP-114. Schizophrenia patients (N=28), stable on a 2-3 mg dose of oral risperidone for ≥2 weeks were randomized to receive either 6- or 12-month DLP-114 implant devices. Each patient received two DLP-114 devices implanted in the abdomen. Device placements were conducted through a 10-minute procedure using local anesthetic and a custom placement tool. Plasma levels of risperidone and 9-hydroxyrisperidone were tracked over the treatment period, and patients were clinically monitored for signs of relapse. Patient safety (including local tolerance and emergent AEs) and PK were the principal endpoints. Secondary clinical endpoints included PANSS and CGI scores.
Results
The placement and removal procedures were well tolerated. Of 28 enrolled patients, two were lost to follow up and one asked to have the implant removed prior to the end of the dosing period. One nonrelated SAE (pulmonary embolism) was reported. Treatment-related AEs were generally mild, and included implant site pain/soreness/tenderness, drowsiness, ecchymosis, increased appetite, insomnia, and headache. The PK profile in both groups followed near zero-order kinetics with both dosing periods until the end of study. The average steady-state plasma concentration ranged between 7-13 ng/mL. One patient was removed from the study with signs of impending relapse. All other patients were clinically stable for the study duration, with average PANSS scores from 50-60 and CGI-I scores from 3-4. PANSS and CGI-I scores were comparable between the oral and the implant phases of the study.
Conclusions
DLP-114 was well tolerated for up to 12 months. Average PANSS and CGI-I scores were similar between the oral and implant treatment phases, suggesting that, for most patients, DLP-114 provided a comparable therapeutic benefit to 2-3 mg of daily oral risperidone over time. Plasma concentrations of risperidone and 9-hydroxyrisperidone were substantially constant for 6-12 months, but values for steady-state Cave fell slightly below the target of 10-14 ng/mL.
Funding
Research reported in this poster was supported by Delpor, Inc. and by the National Institute of Mental Health of the National Institutes of Health under award number R44MH094036.
Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.
Aims
To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.
Method
The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5–0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and ‘inner tension’ item 3 of the Montgomery–Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment (n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).
Results
In cohort 1 (n = 68) the reduction in HAM-A score was not statistically significant: −1.4 (95% CI [−8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 (n = 106) of −4.0 (95% CI [−10.6, −1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 (P = 0.026) but not cohort 1 (P = 0.96).
Conclusion
Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.