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The quenching of cluster satellite galaxies is inextricably linked to the suppression of their cold interstellar medium (ISM) by environmental mechanisms. While the removal of neutral atomic hydrogen (H i) at large radii is well studied, how the environment impacts the remaining gas in the centres of galaxies, which are dominated by molecular gas, is less clear. Using new observations from the Virgo Environment traced in CO survey (VERTICO) and archival H i data, we study the H i and molecular gas within the optical discs of Virgo cluster galaxies on 1.2-kpc scales with spatially resolved scaling relations between stellar ($\Sigma_{\star}$), H i ($\Sigma_{\text{H}\,{\small\text{I}}}$), and molecular gas ($\Sigma_{\text{mol}}$) surface densities. Adopting H i deficiency as a measure of environmental impact, we find evidence that, in addition to removing the H i at large radii, the cluster processes also lower the average $\Sigma_{\text{H}\,{\small\text{I}}}$ of the remaining gas even in the central $1.2\,$kpc. The impact on molecular gas is comparatively weaker than on the H i, and we show that the lower $\Sigma_{\text{mol}}$ gas is removed first. In the most H i-deficient galaxies, however, we find evidence that environmental processes reduce the typical $\Sigma_{\text{mol}}$ of the remaining gas by nearly a factor of 3. We find no evidence for environment-driven elevation of $\Sigma_{\text{H}\,{\small\text{I}}}$ or $\Sigma_{\text{mol}}$ in H i-deficient galaxies. Using the ratio of $\Sigma_{\text{mol}}$-to-$\Sigma_{\text{H}\,{\small\text{I}}}$ in individual regions, we show that changes in the ISM physical conditions, estimated using the total gas surface density and midplane hydrostatic pressure, cannot explain the observed reduction in molecular gas content. Instead, we suggest that direct stripping of the molecular gas is required to explain our results.
Lumateperone (LUMA) is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. An open-label study (Study 303) evaluated the safety and tolerability of LUMA in outpatients with stable schizophrenia who switched from previous antipsychotic (AP) treatment. This post hoc analysis of Study 303 investigated the safety and tolerability of LUMA stratified by previous AP in patients who switched to LUMA treatment for 6 weeks.
Methods
Adult outpatients (≥18 years) with stable schizophrenia were switched from previous AP to LUMA 42 mg once daily for 6 weeks followed by switching to another approved AP for 2 weeks follow-up. Post hoc analyses were stratified by most common previous AP: risperidone or paliperidone (RIS/PAL); quetiapine (QET); aripiprazole or brexpiprazole (ARI/BRE); olanzapine (OLA). Safety analyses included adverse events (AE), vital signs, and laboratory tests. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions-Severity (CGI-S) scale.
Results
The safety population comprised 301 patients, of which 235 (78.1%) were previously treated with RIS/PAL (n=95), QET (n=60), ARI/BRE (n=43), or OLA (n=37). Rates of treatment-emergent AEs (TEAEs) while on LUMA were similar between previous AP groups (44.2%-55.8%). TEAEs with incidences of ≥5% in any AP group were dry mouth, somnolence, sedation, headache, diarrhea, cough, and insomnia. Most TEAEs were mild or moderate in severity for all groups. Rates of serious TEAEs were low and similar between groups (0%–7.0%).
Statistically significant (P<.05) decreases from baseline were observed in the OLA group that switched to LUMA in total cholesterol and low-density lipoprotein cholesterol with significant decreases thereafter on LUMA. Statistically significant decreases in prolactin levels were observed in both the RIS/PAL (P<.0001) and OLA (P<.05) groups. Patients switched from RIS/PAL to LUMA showed significant (P<.05) decreases for body mass index, waist circumference, and weight. At follow-up, 2 weeks after patients switched back from LUMA to another AP, none of the decreases in laboratory parameters or body morphology observed while on LUMA maintained significance.
Those switching from QET had significant improvements from baseline at Day 42 in PANSS Total score (mean change from baseline −3.47; 95% confidence interval [CI] −5.27, −1.68; P<.001) and CGI-S Total score (mean change from baseline −0.24; 95% CI, −0.38, −0.10; P<.01).
Conclusion
In outpatients with stable schizophrenia, LUMA 42 mg treatment was well tolerated in patients switching from a variety of previous APs. Patients switching from RIS/PAL or OLA to LUMA had significant improvements in cardiometabolic and prolactin parameters. These data further support the favorable safety, tolerability, and efficacy of LUMA in patients with schizophrenia.
Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder as monotherapy and as adjunctive therapy with lithium or valproate. This post hoc analysis investigated the efficacy and tolerability of lumateperone in patients with schizophrenia via number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).
Methods
Data were pooled from three late-phase 4–6 week placebo-controlled studies of lumateperone 42 mg/day in adults with schizophrenia and an acute exacerbation of psychosis (Study 005 [NCT01499563], Study 301 [NCT02282761], Study 302 [NCT02469155]). NNT and NNH were calculated vs placebo for several different Positive and Negative Syndrome Scale [PANSS] Total score response cutoffs (percent reduction from baseline) and for adverse events (AEs), respectively.
Results
In the two informative studies (placebo, n=221; lumateperone, n=224), the NNT vs placebo for lumateperone was statistically significant for PANSS Total score reductions from baseline to 4 weeks/endpoint of ≥20% (NNT=9, 95% confidence interval [CI] 5–36) and ≥30% (NNT=8; 95%CI 5–21). In all studies pooled (placebo, n=412; lumateperone, n=406), study discontinuations due to AEs were uncommon and the NNH (389) was not statistically significant from placebo. The only AE with NNH vs placebo <10 was somnolence/sedation (NNH=8; 95%CI 6–12). With lumateperone treatment, weight gain ≥7% from baseline was similar to placebo (NNH=112) and fewer patients experienced akathisia than placebo. Lumateperone LHH ratios were >>1 for all AEs (range 13.6–48.6) except somnolence/sedation (LHH~1).
Conclusion
Lumateperone’s benefit-risk profile was favorable in late-phase schizophrenia trials.
Current treatments for schizophrenia are often associated with increased rates of metabolic syndrome (MetSy). MetSy is defined as meeting 3 of the following 5 criteria: waist circumference >40in (men) or >35in (women), triglycerides =150mg/dL, high density lipoprotein cholesterol (HDL) <40mg/dL (men) or <50mg/dL (women), systolic blood pressure (BP) =130mmHg or diastolic BP =85mmHg, fasting glucose =100mg/dL. Patients with MetSy have an elevated risk of developing type II diabetes and increased mortality due to cardiovascular disease. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA approved for the treatment of schizophrenia. This distinct pharmacological profile has been associated with favorable tolerability and a low risk of adverse metabolic effects in clinical trials. This post hoc analysis of 2 randomized, double-blind, placebo-controlled studies of patients with an acute exacerbation of schizophrenia compared rates of MetSy with lumateperone and risperidone. Data from an open-label long-term trial of lumateperone were also evaluated.
Method
The incidence and shift in MetSy were analyzed in data pooled from 2 short-term (4 or 6 week) placebo- and active-controlled (risperidone 4mg) studies of lumateperone 42mg (Studies 005 and 302). The pooled lumateperone data were compared with data for risperidone. Data from an open-label 1-year trial (Study 303) evaluated MetSy in patients with stable schizophrenia switched from prior antipsychotic (PA) treatment to lumateperone 42mg.
Results
In the acute studies (n=256 lumateperone 42mg, n=255 risperidone 4mg), rates of MetSy were similar between groups at baseline (16% lumateperone, 19% risperidone). At the end of treatment (EOT), MetSy was less common with lumateperone than with risperidone (13% vs 25%). More lumateperone patients (46%) compared with risperidone (25%) patients improved from having MetSy at baseline to no longer meeting MetSy criteria at EOT. Conversely, more patients on risperidone than on lumateperone developed MetSy during treatment (13% vs 5%). Differences in MetSy conversion rates were driven by changes in triglycerides and glucose. In the long-term study (n=602 lumateperone 42mg), 33% of patients had MetSy at PA baseline. Thirty-six percent of patients (36%) with MetSy at PA baseline improved to no longer meeting criteria at EOT. Fewer than half that percentage shifted from not meeting MetSy criteria to having MetSy (15%).
Conclusions
In this post hoc analysis, lumateperone 42mg patients had reduced rates of MetSy compared with risperidone patients. In the long-term study, patients with MetSy on PA switched to lumateperone 42mg had a reduction in the risk of MetSy. These results suggest that lumateperone 42mg is a promising new treatment for schizophrenia with a favorable metabolic profile.
The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, the neotoma R package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.
The History, Electrocardiogram (ECG), Age, Risk Factors, and Troponin (HEART) score is a decision aid designed to risk stratify emergency department (ED) patients with acute chest pain. It has been validated for ED use, but it has yet to be evaluated in a prehospital setting.
Hypothesis
A prehospital modified HEART score can predict major adverse cardiac events (MACE) among undifferentiated chest pain patients transported to the ED.
Methods
A retrospective cohort study of patients with chest pain transported by two county-based Emergency Medical Service (EMS) agencies to a tertiary care center was conducted. Adults without ST-elevation myocardial infarction (STEMI) were included. Inter-facility transfers and those without a prehospital 12-lead ECG or an ED troponin measurement were excluded. Modified HEART scores were calculated by study investigators using a standardized data collection tool for each patient. All MACE (death, myocardial infarction [MI], or coronary revascularization) were determined by record review at 30 days. The sensitivity and negative predictive values (NPVs) for MACE at 30 days were calculated.
Results
Over the study period, 794 patients met inclusion criteria. A MACE at 30 days was present in 10.7% (85/794) of patients with 12 deaths (1.5%), 66 MIs (8.3%), and 12 coronary revascularizations without MI (1.5%). The modified HEART score identified 33.2% (264/794) of patients as low risk. Among low-risk patients, 1.9% (5/264) had MACE (two MIs and three revascularizations without MI). The sensitivity and NPV for 30-day MACE was 94.1% (95% CI, 86.8-98.1) and 98.1% (95% CI, 95.6-99.4), respectively.
Conclusions
Prehospital modified HEART scores have a high NPV for MACE at 30 days. A study in which prehospital providers prospectively apply this decision aid is warranted.
Conifer wood, probably spruce (Picea sp.), of middle Wisconsinan age (29,200 ± 500 yr B.P.) was recovered from late-glacial lake sediments from Upper South Branch Pond, Maine. If the wood was derived from a local source, deglaciation of part of northern New England is suggested for this time. The occurrence also has implications for understanding the problem associated with radiocarbon dating of bulk lake sediment containing small amounts of organic matter.
Two broad aims drive weed science research: improved management and improved
understanding of weed biology and ecology. In recent years, agricultural
weed research addressing these two aims has effectively split into separate
subdisciplines despite repeated calls for greater integration. Although some
excellent work is being done, agricultural weed research has developed a
very high level of repetitiveness, a preponderance of purely descriptive
studies, and has failed to clearly articulate novel hypotheses linked to
established bodies of ecological and evolutionary theory. In contrast,
invasive plant research attracts a diverse cadre of nonweed scientists using
invasions to explore broader and more integrated biological questions
grounded in theory. We propose that although studies focused on weed
management remain vitally important, agricultural weed research would
benefit from deeper theoretical justification, a broader vision, and
increased collaboration across diverse disciplines. To initiate change in
this direction, we call for more emphasis on interdisciplinary training for
weed scientists, and for focused workshops and working groups to develop
specific areas of research and promote interactions among weed scientists
and with the wider scientific community.
Pollen influx and percentage diagrams were prepared from an 11.4 m core from Moulton Pond, Maine. The pond basin was deglaciated about 14,000 y. a., after which it was located on an island in a sea of subarctic character until about 12,400 y. a. when the surrounding area emerged from the sea. The terrestrial vegetation was tundra until about 10,000 y. a. A change in the tundra vegetation is synchronous with the emergence from the sea, but synchroneity with the Pineo Ridge glacial readvance, which reached its maximum 50 km to the east of the pond about 12,700 y. a., is also possible because of imprecision in the dating. Comparisons of the Moulton Pond results with late-glacial pollen sequences elsewhere in eastern United States and adjacent Canada reveal a lack of synchroneity in vegetational changes casting doubt on claims of major broad-scale climatic shifts over the entire area.
The tundra period at Moulton Pond ended with a transition of a few hundred years to partly open, relatively xeric forests of low diversity dominated by white pine, oak, and birch trees. There was no intervening boreal forest. In the postglacial period the vegetation was continually changing, including in the early portion a series of immigrations of temperate tree taxa which later became important in the forests. The transient nature of these assemblages is further indicated by their differences from the closest modern analogs. From about 7100 y. a. until settlement by Europeans 200 y. a., the forests were closed. A major decline of conifers centering about 4700 y. a. was followed by maxima of mesic hardwoods about a thousand years later. In the most recent 2000 yr, the pollen record suggests greater environmental severity, evidenced by increasing spruce. But for the entire postglacial period, the closest modern vegetational analogs are all in the conifer-hardwood region. Much of the postglacial pollen sequence is inexplicable in climatic terms, as evidenced by nonsynchronous behavior of hemlock and beech.
The pollen influx diagram is useful for distinguishing tundra from forest, but for the postglacial period it is difficult to interpret. Pollen influx data are strongly affected by shifts in the pattern of sedimentation in lakes. We propose that such shifts account for the major changes in influx in mid- and late-postglacial time at Moulton Pond and at Rogers Lake, Connecticut. This complicates the interpretation of influx data which otherwise are superior to percentage data.
This article reports on the fourth stage of an evolving study to develop a systems model for embedding education for sustainability (EfS) into preservice teacher education. The fourth stage trialled the extension of the model to a comprehensive state-wide systems approach involving representatives from all eight Queensland teacher education institutions and other key policy agencies and professional associations. Support for trialling the model included regular meetings among the participating representatives and an implementation guide. This article describes the first three stages of developing and trialling the model before presenting the case study and action research methods employed, four key lessons learned from the project, and the implications of the major outcomes for teacher education policies and practices. The Queensland-wide, multi-site case study revealed processes and strategies that can enable institutional change agents to engage productively in building capacity for embedding EfS at the individual, institutional, and state levels in preservice teacher education. Collectively, the project components provide a system-wide framework that offers strategies, examples, insights, and resources that can serve as a model for other states and/or territories wishing to implement EfS in a systematic and coherent fashion.
The Consortium to Investigate Vascular Impairment of Cognition (CIVIC) is a Canadian, multi-centre, clinic-based prospective cohort study of patients with Vascular Cognitive Impairment (VCI). We report its organization and the impact of diagnostic criteria on the study of VCI.
Methods:
Nine memory disability clinics enrolled patients and recorded their usual investigations and care. A case report form included all vascular dementia (VaD) individual criteria for each of four sets (National Institute of Neurological Disorders and Stroke (NINDS-AIREN), Alzheimer’s Disease Diagnostic Treatment Centers (ADDTC), the ICD-10 Classification of Mental and Behavioural Disorders (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)) of consensus-based diagnostic criteria and for the Hachinski Ischemia Score (HIS). Investigators, having completed the case report form, were asked to make a clinical judgement about the cognitive diagnosis based on the best available information, including neuroimaging.
Results:
Of 1,347 patients (mean age 72 years; 56% women), 846 (63%) were diagnosed with dementia and 324 (24%) were diagnosed with VCI. The proportion of patients diagnosed with VaD by the diagnostic criteria was: 23.9% (n=322) by DSM-IV, 10.2% (n=137) by HIS, 4.3% (n=58) by ICD-10, 3.8% (n=51) by ADTCC, and 3.6% (n=48) by NINDS-AIREN. Judged against a clinical diagnosis of VaD, the sensitivity/specificity of each was: DSM-IV (0.77/0.80); HIS (0.41/0.92); ICD-10 (0.29/0.98); ADTCC (0.24/0.98); NINDS-AIREN (0.42/0.995). Compared with a clinical diagnosis of VCI, sensitivities were lower for the diagnostic criteria, reflecting the exclusion of patients who did not have dementia.
Conclusions:
Consensus-based criteria for VaD omit patients who do not meet dementia criteria that are modeled on Alzheimer’s disease. Even for patients who do, the proportion identified with VaD varies widely. Criteria based on empirical analyses need to be developed and validated.
Standard health economics concentrates on the provision of care by medical professionals. Yet ‘care’ receives scant analysis; it is portrayed as a spillover effect or externality in the form of interdependent utility functions. In this context care can only be conceived as either acts of altruism or as social capital. Both conceptions are subject to considerable problems stemming from mainstream health economics’ reliance on a reductionist social model built around instrumental rationality and consequentialism. Subsequently, this implies a disregard for moral rules and duties and the compassionate aspects of behaviour. Care as an externality is a second-order concern relative to self-interested utility maximization, and is therefore crowded out by the parameters of the standard model. We outline an alternative relational approach to conceptualising care based on the social embeddedness of the individual that emphasises the ethical properties of care. The deontological dimension of care suggests that standard health economics is likely to undervalue the importance of care and caring in medicine.
This paper describes the system architecture of a newly constructed radio telescope – the Boolardy engineering test array, which is a prototype of the Australian square kilometre array pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a six-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least nine dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.
The ngwayir (western ringtail possum Pseudocheirus occidentalis) is an arboreal species endemic to south-western Australia. The range and population of this species have been significantly reduced through multiple anthropogenic impacts. Classified as vulnerable, the ngwayir is highly susceptible to extremes of temperature and reduced water intake. Ngwayir distribution was determined using three different species distribution models using ngwayir presence records related to a set of 19 bioclimatic variables derived from historical climate data, overlaid with 2050 climate change scenarios. MaxEnt was used to identify core habitat and demonstrate how this habitat may be impacted. A supplementary modelling exercise was also conducted to ascertain potential impacts on the tree species that are core habitat for ngwayir. All models predicted a reduction of up to 60% in the range of the ngwayir and its habitat, as a result of global warming towards the south-west of the project area, with a mean potential distribution of 10.3% of the total modelled area of 561 059 km2. All three tree species modelled (jarrah, marri and peppermint) were predicted to experience similar contractions in range throughout most of the predicted ngwayir range, although their distributions differed. Populations of ngwayir persisting outside core habitat may indicate potential conservation opportunities.