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Negative symptoms of schizophrenia manifest as reduced motivation and pleasure (MAP) and impaired emotional expressivity (EXP). These can occur as primary phenomena, but have also been suggested to occur secondary to other clinical factors, including antipsychotic-induced sedation. However, this relationship has not been established formally. Here, we examined the effect of antipsychotic-induced sedation (assessed via the proxy of total daily sleep duration) on MAP and EXP in a cohort of 187 clozapine-treated patients with schizophrenia followed for over 2 years on average, using multilevel regression and mediation models. MAP, but not EXP, was adversely influenced by sedation, independently of the severity of psychosis or depression. Moreover, clozapine impaired MAP indirectly by worsening sedation, but after accounting for clozapine-induced sedation, clozapine improved MAP. Our results highlight the importance of addressing sedative side-effects of antipsychotics to improve clinical outcomes.
The convergence of free-energy calculations based on importance sampling depends heavily on the choice of collective variables (CVs), which in principle, should include the slow degrees of freedom of the biological processes to be investigated. Autoencoders (AEs), as emerging data-driven dimension reduction tools, have been utilised for discovering CVs. AEs, however, are often treated as black boxes, and what AEs actually encode during training, and whether the latent variables from encoders are suitable as CVs for further free-energy calculations remains unknown. In this contribution, we review AEs and their time-series-based variants, including time-lagged AEs (TAEs) and modified TAEs, as well as the closely related model variational approach for Markov processes networks (VAMPnets). We then show through numerical examples that AEs learn the high-variance modes instead of the slow modes. In stark contrast, time series-based models are able to capture the slow modes. Moreover, both modified TAEs with extensions from slow feature analysis and the state-free reversible VAMPnets (SRVs) can yield orthogonal multidimensional CVs. As an illustration, we employ SRVs to discover the CVs of the isomerizations of N-acetyl-N′-methylalanylamide and trialanine by iterative learning with trajectories from biased simulations. Last, through numerical experiments with anisotropic diffusion, we investigate the potential relationship of time-series-based models and committor probabilities.
Both neuroscientists and literary translators aim to understand how invariance of meaning can arise across different forms. But literary translators must render experiences that are more subtle, more contextual, more entire, than a glimpse of a cat’s tail. Thus, for the neuroscientist who seeks to understand invariances, the goals of literary translation match the highest levels of scientific aspiration. From a neuroscientific perspective, it is fascinating that literary translation is possible at all.
Weakly collisional plasmas are subject to nonlinear relaxation processes, which can operate at rates much faster than the particle collision frequencies. This causes the plasma to respond like a magnetised fluid despite having long particle mean free paths. In this Letter the effective collisional mechanisms are modelled in the plasma kinetic equation to produce density, pressure and magnetic-field responses to compare with spacecraft measurements of the solar wind compressive fluctuations at 1 AU. This enables a measurement of the effective mean free path of the solar wind protons, found to be ${\approx }4 \times 10^{5}$ km, which is approximately $10^{3}$ times shorter than the collisional mean free path. These measurements are shown to support the effective fluid behaviour of the solar wind at scales above the proton gyroradius and demonstrate that effective collision processes alter the thermodynamics and transport of weakly collisional plasmas.
Air dispersal of respiratory viruses other than SARS-CoV-2 has not been systematically reported. The incidence and factors associated with air dispersal of respiratory viruses are largely unknown.
Methods:
We performed air sampling by collecting 72,000 L of air over 6 hours for pediatric and adolescent patients infected with parainfluenza virus 3 (PIF3), respiratory syncytial virus (RSV), rhinovirus, and adenovirus. The patients were singly or 2-patient cohort isolated in airborne infection isolation rooms (AIIRs) from December 3, 2021, to January 26, 2022. The viral load in nasopharyngeal aspirates (NPA) and air samples were measured. Factors associated with air dispersal were investigated and analyzed.
Results:
Of 20 singly isolated patients with median age of 30 months (range, 3 months–15 years), 7 (35%) had air dispersal of the viruses compatible with their NPA results. These included 4 (40%) of 10 PIF3-infected patients, 2 (66%) of 3 RSV-infected patients, and 1 (50%) of 2 adenovirus-infected patients. The mean viral load in their room air sample was 1.58×103 copies/mL. Compared with 13 patients (65%) without air dispersal, these 7 patients had a significantly higher mean viral load in their NPA specimens (6.15×107 copies/mL vs 1.61×105 copies/mL; P < .001). Another 14 patients were placed in cohorts as 7 pairs infected with the same virus (PIF3, 2 pairs; RSV, 3 pairs; rhinovirus, 1 pair; and adenovirus, 1 pair) in double-bed AIIRs, all of which had air dispersal. The mean room air viral load in 2-patient cohorts was significantly higher than in rooms of singly isolated patients (1.02×104 copies/mL vs 1.58×103 copies/mL; P = .020).
Conclusion:
Air dispersal of common respiratory viruses may have infection prevention and public health implications.
In March 2020, New York City became the epicenter of the coronavirus disease 2019 (COVID-19) pandemic in the United States. Because healthcare facilities were overwhelmed with patients, the Jacob K. Javits Convention Center was transformed into the nation’s largest alternate care site: Javits New York Medical Station (hereafter termed Javits). Protecting healthcare workers (HCWs) during a global shortage of personal protective equipment (PPE) in a nontraditional healthcare setting posed unique challenges. We describe components of the HCW safety program implemented at Javits.
Setting:
Javits, a large convention center transformed into a field hospital, with clinical staff from the US Public Health Service Commissioned Corps and the US Department of Defense.
Methods:
Key strategies to ensure HCW safety included ensuring 1-way flow of traffic on and off the patient floor, developing a matrix detailing PPE required for each work activity and location, PPE extended use and reuse protocols, personnel training, and monitoring adherence to PPE donning/doffing protocols when entering or exiting the patient floor. Javits staff who reported COVID-19 symptoms were immediately isolated, monitored, and offered a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) reverse-transcriptase polymerase chain reaction (RT-PCR) test.
Conclusions:
A well-designed and implemented HCW safety plan can minimize the risk of SARS-CoV-2 infection for HCWs. The lessons learned from operating the nation’s largest COVID-19 alternate care site can be adapted to other environments during public health emergencies.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding about the remaining options to achieve the Paris Agreement goals, through overcoming political barriers to carbon pricing, taking into account non-CO2 factors, a well-designed implementation of demand-side and nature-based solutions, resilience building of ecosystems and the recognition that climate change mitigation costs can be justified by benefits to the health of humans and nature alone. We consider new insights about what to expect if we fail to include a new dimension of fire extremes and the prospect of cascading climate tipping elements.
Technical summary
A synthesis is made of 10 topics within climate research, where there have been significant advances since January 2020. The insights are based on input from an international open call with broad disciplinary scope. Findings include: (1) the options to still keep global warming below 1.5 °C; (2) the impact of non-CO2 factors in global warming; (3) a new dimension of fire extremes forced by climate change; (4) the increasing pressure on interconnected climate tipping elements; (5) the dimensions of climate justice; (6) political challenges impeding the effectiveness of carbon pricing; (7) demand-side solutions as vehicles of climate mitigation; (8) the potentials and caveats of nature-based solutions; (9) how building resilience of marine ecosystems is possible; and (10) that the costs of climate change mitigation policies can be more than justified by the benefits to the health of humans and nature.
Social media summary
How do we limit global warming to 1.5 °C and why is it crucial? See highlights of latest climate science.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
Design:
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
Methods:
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Results:
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
Conclusions:
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
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.
Mind–body dualism is often considered to be incompatible with modern psychiatry for two reasons. First, it is claimed that dualism is falsified by recent advances in neuroscience. Second, dualism is thought to lead to an unhelpful attitude towards patients and their illnesses. I reflect on and challenge both lines of thought and argue that there is no inherent conflict between dualism and psychiatry.
The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias.
Methods
We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain.
Results
A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges' gs = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects.
Conclusions
High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.
Gonorrhoea cases in women have been rising in Australia in the 2010s but the cause of the increase is not well understood. This cross-sectional study aimed to describe the characteristics of genital gonorrhoea infection in women attending the Melbourne Sexual Health Centre, Australia. Gonorrhoea cases were diagnosed by nucleic acid amplification test (NAAT) and/or culture. Genitourinary specimens were obtained in 12 869 clinic visits in women aged 16 years or above between August 2017 and August 2018. Genital gonorrhoea was detected in 142 (1.1%) of the visits. Almost half of the cases were asymptomatic, 47.9% [95% confidence interval (CI) 39.8–56.1%]; yellow, green or pus-like vaginal discharge was present in 11.3% (95% CI 7.0–17.6%) and other genital symptoms in 40.8% (95% CI 33.1–49.1%) of the cases. The mean time between last sexual contact and onset of symptoms was 7.3 days and between the onset of symptoms to presentation to the clinic was 12.1 days. Half of the cases of genital gonorrhoea among women are asymptomatic and these cases would have been missed by testing of only symptomatic women. Further epidemiological and behavioural research is required to understand the temporal changes in sexual practices among women in Australia.
The typical marine animal has increased in biovolume by more than two orders of magnitude since the beginning of the Cambrian, but the causes of this trend remain unknown. We test the hypothesis that the efficiency of intra-organism oxygen delivery is a major constraint on body-size evolution in marine animals. To test this hypothesis, we compiled a dataset comprising 13,723 marine animal genera spanning the Phanerozoic. We coded each genus according to its respiratory medium, circulatory anatomy, and feeding mode. In extant genera, we find that respiratory medium and circulatory anatomy explain more of the difference in size than feeding modes. Likewise, we find that most of the Phanerozoic increase in mean biovolume is accounted for by size increase in taxa that accomplish oxygen delivery through closed circulatory systems. During the Cambrian, water-breathing animals with closed circulatory systems were smaller, on average, than contemporaries with open circulatory systems. However, genera with closed circulatory systems superseded in size genera with open circulatory systems by the Middle Ordovician, as part of their Phanerozoic-long trend of increasing size. In a regression analysis, respiratory and circulatory anatomy explain far more size variation in the living fauna than do feeding modes, even after accounting for taxonomic affinity at the class level. These findings suggest that ecological and environmental drivers of the Phanerozoic increase in the mean size of marine animals operated within strong, anatomically determined constraints.
Simultaneous Disasters in Southeast Asia: Is Risk Outpacing Resilience?
Since Southeast Asian leaders signed the ASEAN Agreement on Disaster Management and Emergency Response (AADMER) in 2005, the region has prioritized developing national and regional disaster management capabilities to respond to disasters. However, the recent back-to-back disasters that occurred between July and August 2018 tested the response capacities of national governments and the humanitarian community. Parts of Myanmar, Vietnam, Laos, Cambodia and the Philippines battled floods of varying severity induced by seasonal monsoon rains, tropical storms and a dam collapse on a tributary of the Mekong River. Meanwhile, Indonesia's Lombok Island, West Nusa Tenggara was hit by multiple earthquakes and aftershocks between 29 July and 19 August. The ASEAN Coordinating Centre for Humanitarian Assistance on disaster management (AHA Centre) reported that at the peak of these disasters, over 588,000 people were displaced and more than 5.2 million people in Southeast Asia were affected. Against the backdrop of recent disasters generating simultaneous responses, this chapter makes key observations on Southeast Asia's ability to meet the immediate needs of disasteraffected communities while building greater disaster resilience for the future. It assesses the (i) institutionalization of disaster management in ASEAN; (ii) localization of disaster response; and (iii) opportunities for financial risk management for building disaster-resilient communities.
ASEAN in the Eye of the Storm—Institutionalization of Disaster Management in ASEAN
In assessing current and future disaster management capabilities, this chapter focuses on the floods in Laos and Cambodia after the collapse of a saddle dam of the Xe Pian-Xe Nam Noy hydropower project, floods in Myanmar caused by heavy monsoon rainfall and a breached dam in the Bago region, and the earthquakes and aftershocks in Lombok, West Nusa Tenggara, Indonesia. It identifies the evolution of a regional mechanism to respond to disasters grounded in the legallybinding AADMER. This agreement was ratified by all ASEAN member states and came into force in 2009 and represented ASEAN's regional commitment to respond to disasters. Its objectives are to provide effective disaster management mechanisms and to have ASEAN member states “jointly respond to disaster emergencies” through regional cooperation. AADMER's most significant contribution has been to institutionalize disaster management within and between ASEAN member states.