We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP). The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) and open-label extension ADHERE+ (NCT04280718) trials (interim analysis cutoff: February 16, 2024) assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to efgartigimod or placebo for ≤48 weeks (stage-B). Participants with clinical deterioration in stage-B or who completed ADHERE entered ADHERE+. Week 36 changes from run-in baseline (CFB) in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength scores were evaluated. Results: Of 322 stage-A participants, 221 were randomized and treated in stage-B, and 99% entered ADHERE+. Mean CFB (SE) in aINCAT, I-RODS, and grip strength scores were -1.2 (0.15) and 8.8 (1.46) and 17.5 (2.02), respectively, at ADHERE+ Week 36 (N=150). Half the participants with clinical deterioration during ADHERE stage-B restabilized on efgartigimod from ADHERE+ Week 4. Conclusions: Interim results from ADHERE+ indicate long-term effectiveness of efgartigimod PH20 SC in clinical outcomes in participants with CIDP.
Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP), a rare, progressive, immune-mediated disease that can lead to irreversible disability. The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) trial assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to weekly efgartigimod or placebo for ≤48 weeks (stage-B). This posthoc analysis evaluated changes from run-in baseline (study enrollment) to stage-B last assessment and items of the Inflammatory Rasch-built Overall Disability Scale (I-RODS). Results: Of 322 participants who entered stage-A, 221 were randomized and treated in stage-B, and 191/221 had data for run-in baseline and post–stage-B timepoints. Mean (SE) I-RODS change at stage-B last assessment vs run-in baseline was 5.7 (1.88) and -4.9 (1.82) in participants randomized to efgartigimod and placebo, respectively. 37/97 (38.1%) and 24/92 (26.1%) participants randomized to efgartigimod and placebo, respectively, experienced ≥4-point improvements in I-RODS score. Efgartigimod-treated participants improved ≥1 point in I-RODS items of clinical interest. Conclusions: Participants who received efgartigimod in stage-B experienced improvements in I-RODS score from study enrollment to stage-B last assessment.
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
Methods
By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
Results
A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
Conclusions
Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
Natural zeolites may represent one of the greatest under-utilized resources of the mineral world. Even with their unique character and properties, issues of consistency, homogeneity and purity preclude them from many premium applications. We report a simple method to upgrade mineral sedimentary Na-chabazite from the well known Bowie, Arizona, deposit to near synthetic purity and consistency. During this alkaline-silicate digestion process, initially soft chabazite ore granules gain substantial mechanical strength. This may allow direct employment in adsorption and purification processes without the need for binding and forming. These granules manifest significantly improved adsorption properties, including enhanced water and CO2 adsorptivity.
Mineral chabazite has shown the unusual ability to surface template nanometal particles, especially Ag. A chabazite analog was synthesized from delaminated metakaolin. The chabazite formed retained the platy morphology of the base clay. This morphology is ideal for displaying surface-supported nanometal particles. The synthetic chabazite analog demonstrated the ability to form and support large concentrations of Ag nanoparticles, as observed in the related natural mineral. Due to greater Al content, the synthetic chabazite manifests significantly improved capacity for the formation of such Ag nanoparticles. As in the case of the mineral chabazite, surface Ag nanoparticles of high uniformity were observed in the range of 5–6 nm.
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:
240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:
In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:
These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
According to CEOWORLD Magazine‘s 2019 “Health Care Indicators” rating of 89 countries in the world, Taiwan ranks first in the world. The coverage of the National Health Insurance covers all necessary medical treatment, including outpatient, hospitalization, and prescription drugs etc. The psychiatrist was wondering which item with the highest service cost–performance (CP) ratio of the psychiatrist performance in a general hospital and used proportion of PPF as performance indicator. He used allocation to distribute the hours across job activities.
Objectives
The purpose of this study is to investigate items allocation proportion for outpatient and inpatient ward in a specific month, examining the distribution of performance and figure out an appropriate model to optimal medical service.
Methods
Demographic data were collected through PPF projects included 15 outpatient items and 19 inpatient ward items from the third-month of the psychiatrist’s employment in the general hospital, as shown in Table 1. Items related to physiological examination has been excluded. The performance is calculated by combining outpatient and inpatient wards.
Results
Demographic data analysis found that proportion of inpatient ward PPF (67.01%) was significantly greater than proportion of outpatient PPF (32.99%) (Figure 1). The inpatient ward performance was 2 times the outpatient performance. This result showed that most performance came from inpatient ward. Among all items of the proportion of PPF unit, the highest two for inpatient ward items were general hospital bed inpatient consultation (32.58%) and special treatment for psychiatric inpatients (14.35%), and for outpatient, the highest was psychiatric outpatient consultation - more than two (11.31%) (Table 1).
Image:
Image 2:
Conclusions
National Health Insurance is an important system to assist in epidemic prevention during the COVID-19 period. The most PPF of psychiatrist service in a general hospital came from the service of inpatient ward items, including the general hospital bed inpatient consultation with the highest CP ratio. These findings may suggest that the inpatient service could offer psychiatrists fair PPF, and the hospital environment could be favorable for recruitment.
Despite emerging evidence suggesting the efficacy of psilocybin in the treatment of mood disorders such as depression, the exact mechanisms by which psilocybin is able to elicit these antidepressant effects remains unknown.
Objectives
As the use of psilocybin as a treatment modality for depression has garnered increasing interest, this study aims to summarize the existing evidence of the mechanism of action with which psilocybin alleviates depressive symptoms, focusing specifically on the neurobiological effects of psilocybin in human subjects.
Methods
Four databases (Ovid MEDLINE, EMBASE, psychINFO, and Web of Science) were searched using a combination of MeSH terms and free text keywords in September 2021. The original search included both human and animal studies and must have included testing of the mechanism of action of psilocybin. Only antidepressant effects were considered, with no other mood disorders or psychiatric diagnoses included. Two independent researchers screened at every stage of the review, with a third researcher resolving any conflicts. Though a full systematic review outlining the current literature on the complete mechanisms of action of psilocybin on depression was conducted, this abstract will focus specifically on the nine papers that included human subjects, disregarding the five animal models. PROSPERO registration number: 282710.
Results
After removing duplicates, the search identified 2193 papers and forty-nine were selected for full text review. Out of nine papers outlining the mechanisms of action of psilocybin use in human subjects, three papers investigated psilocybin’s effect on serotonin or glutamate receptor activity, two found an increase in synaptogenesis in regions such as the medial frontal cortex and hippocampus. Four found variation in blood flow to the amygdala, two found altered blood flow to the prefrontal cortex, and one found a reduction in delta power during sleep. Four papers found changes in functional connectivity or neurotransmission, most commonly in the hippocampus or prefrontal cortex.
Conclusions
Overall, the exact mechanism of psilocybin’s potential antidepressant effect remains unclear. Multiple pathways may be involved, including alterations in serotonin and glutamate receptor activity, as well as shifts in amygdala activity, neurogenesis, and functional connectivity in various brain regions. The relative lack of studies, and the variety of neurobiological modalities and endpoints used challenged the consolidation of data into consensus findings. Further studies are needed to better characterize psilocybin’s mechanism of action and to better understand the clinical effects of the use of psilocybin in the treatment of depression.
Bipolar disorder (BD) is a severe psychotic disease repeats depression, hypomania or mania. Using mobile applications to record emotions can help BD patients to self-manage and reduce emotional symptoms. Gamification applied in health-manage applications can improve the using frequency and satisfaction. Nurturing and horticultural therapy could increase the using frequency and alleviate the depression and anxiety.
Objectives
This study chose plants-nurturing to add to a self-management application, and explored the users’ experiences.
Methods
A one-group pretest-posttest design with qualitative interview was used. Analysis included the frequency of usage, emotional changes, and users’ feedback of the plants-nurturing in the first three months and after three months.。
Results
A total of 26 participants were included. In the frequency of usage, the times and ratio of days were increased but no significant difference. The emotional symptoms were no significant difference. Positive experiences were novelty and interesting, while negative experiences were the slow rate of growth.Table 1.
Demographics (N=26)
Range
Mean (SD)
Age
20-62
37.0(11.35)
n
Percentage
Gender
Female
15
57.7
Educational level
University
14
53.8
Employment situation
Employment
14
53.8
Image:
Image 2:
Image 3:
Conclusions
There was a preliminary increase when adding plants-nurturing to the self-manage application, whereas the effect should be examined by further research. The more delicate elements of gamification could be included in self-manage application, considered the users’ other sensory perception in the future. Meanwhile, to improve the frequency of usage and self-management in BD patients, the subjective experiences should be explored in-depth.
Most of the research explored the attrition rate and predictive factors for the smartphone application of emotion monitoring in bipolar disorder patients. However, there is less focus on the efficacy of maintaining the retention rate if the incentive system is employed.
Objectives
The aim of our research is to evaluate the efficacy of two different kinds of incentive systems on improving frequency of using the Smartphone Mood Relapse Warning application (MRW-APP) (Su et al., 2021) in bipolar patients.
Methods
A one-group pretest-posttest pilot study was conducted. Participants with bipolar disorder (n = 63) recorded their moods and symptoms through MRW-APP for 29 weeks with the attrition rate of 44%. Two different kinds of incentive systems, reward and lottery, were implemented. To know whether incentive implementation could play a role in motivating the participants to better adhere to the app, we used Friedman’s test and paired sample t-test to analyze the participants’ app-using frequency in the corresponding weeks.
Results
There was no significant difference in the participants’ app-using frequency (p>.05) before and after we implemented the first incentive system, reward (n=63). For the second incentive system, lottery (n=41), a significant difference in app-using frequency was still not observed (p>.05) after the intervention. But, for those who both had experienced two kinds of incentive systems (n=35), there were significant changes in their app-using frequency (p<.05).Table 1.
Demographics (n=63)
Variables
All (n=63)
Mean
SD
Age (n=55)
36.4025.27
11.10
Onset age (n=48)
9.35
n
%
Gender (n=54)
Female
33
61.1
Educational level (n=54)
Above undergraduates
40
74.1
SD= Standard deviation
Image:
Image 2:
Conclusions
This research found the two incentive systems, award and lottery, may help increase the using frequency of the smartphone monitoring app for participants with bipolar disorder. The results from our study can be a reference for mood monitoring apps development in the future, and it also suggested that incentive system has its potential on encouraging patients’ adherence to e-healthcare.
In Taiwan, National Health Insurance has been implemented for 27 years and continues to receive international recognition. People pay part of the quota at the time of medical treatment, and the rest of the medical expenses will be paid by the national health insurance. In this study, the researcher, a psychiatrist in the general hospital, investigated the correlation between service and revenue. He has started to work in this hospital since November 1st, 2021, without any other psychiatrist peers.
Objectives
This study used proportion of PPF as performance indicator and aimed to observe the changes of PPF unit from November 1st, 2021, to January 31st, 2022, examining the trend of PPF growth. The purpose is to figure out an appropriate model to optimize medical services and performance outcomes.
Methods
Demographic data were collected through PPF projects, consisting of 17 inpatient ward items and 14 outpatient items from November 1st, 2021, to January 31st, 2022, and items with no performance or related to physiological examination has been excluded. In addition, items with a ratio of greater than 1.5% are presented in the bar graphs, as shown in Figure 2 and 3. The performance proportion of inpatient ward and outpatient were calculated separately.
Results
Demographic data found PPF rises significantly over time (Figure 1). The 2nd month PPF unit (27.09%) was 2.5 times the 1st month PPF unit (10.70%), and the 3rd month PPF unit (62.21%) was 2.2 times the 2nd month PPF unit (27.085%). The highest proportion of PPF items were general hospital bed inpatient consultation fee for inpatient ward item (Figure 2) and psychiatric outpatient consultation fee for outpatient item (Figure 3). Furthermore, only the proportion of psychiatric outpatient consultation – more than two consecutive transfers increased continuously and the proportion of psychiatric outpatient consultation – adjusted by the hospital decreased, the other items has not changed significantly.
Image:
Image 2:
Image 3:
Conclusions
In the first three months of the psychiatrist employment, the performance showed an increasing trend. These findings may suggest that the psychiatrist could be competent in a general hospital with patients’ confidence. In addition, under an optimal model of PPF and medical service, psychiatrists would more like to work in the general hospital, to serve acute psychiatric patients in need.
We present the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY) Pilot Phase I Hi kinematic models. This first data release consists of Hi observations of three fields in the direction of the Hydra and Norma clusters, and the NGC 4636 galaxy group. In this paper, we describe how we generate and publicly release flat-disk tilted-ring kinematic models for 109/592 unique Hi detections in these fields. The modelling method adopted here—which we call the WALLABY Kinematic Analysis Proto-Pipeline (WKAPP) and for which the corresponding scripts are also publicly available—consists of combining results from the homogeneous application of the FAT and 3DBarolo algorithms to the subset of 209 detections with sufficient resolution and $S/N$ in order to generate optimised model parameters and uncertainties. The 109 models presented here tend to be gas rich detections resolved by at least 3–4 synthesised beams across their major axes, but there is no obvious environmental bias in the modelling. The data release described here is the first step towards the derivation of similar products for thousands of spatially resolved WALLABY detections via a dedicated kinematic pipeline. Such a large publicly available and homogeneously analysed dataset will be a powerful legacy product that that will enable a wide range of scientific studies.
We present WALLABY pilot data release 1, the first public release of H i pilot survey data from the Wide-field ASKAP L-band Legacy All-sky Blind Survey (WALLABY) on the Australian Square Kilometre Array Pathfinder. Phase 1 of the WALLABY pilot survey targeted three $60\,\mathrm{deg}^{2}$ regions on the sky in the direction of the Hydra and Norma galaxy clusters and the NGC 4636 galaxy group, covering the redshift range of $z \lesssim 0.08$. The source catalogue, images and spectra of nearly 600 extragalactic H i detections and kinematic models for 109 spatially resolved galaxies are available. As the pilot survey targeted regions containing nearby group and cluster environments, the median redshift of the sample of $z \approx 0.014$ is relatively low compared to the full WALLABY survey. The median galaxy H i mass is $2.3 \times 10^{9}\,{\rm M}_{{\odot}}$. The target noise level of $1.6\,\mathrm{mJy}$ per 30′′ beam and $18.5\,\mathrm{kHz}$ channel translates into a $5 \sigma$ H i mass sensitivity for point sources of about $5.2 \times 10^{8} \, (D_{\rm L} / \mathrm{100\,Mpc})^{2} \, {\rm M}_{{\odot}}$ across 50 spectral channels (${\approx} 200\,\mathrm{km \, s}^{-1}$) and a $5 \sigma$ H i column density sensitivity of about $8.6 \times 10^{19} \, (1 + z)^{4}\,\mathrm{cm}^{-2}$ across 5 channels (${\approx} 20\,\mathrm{km \, s}^{-1}$) for emission filling the 30′′ beam. As expected for a pilot survey, several technical issues and artefacts are still affecting the data quality. Most notably, there are systematic flux errors of up to several 10% caused by uncertainties about the exact size and shape of each of the primary beams as well as the presence of sidelobes due to the finite deconvolution threshold. In addition, artefacts such as residual continuum emission and bandpass ripples have affected some of the data. The pilot survey has been highly successful in uncovering such technical problems, most of which are expected to be addressed and rectified before the start of the full WALLABY survey.
The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.
Method
Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.
Results
Prospective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.
Conclusions
We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
This study aimed to elucidate whether molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea.
Method
Twenty patients with mild obstructive sleep apnoea (control group) and 40 patients with moderate to severe obstructive sleep apnoea (obstructive sleep apnoea group) who desired uvulopalatopharyngoplasty were recruited for the study. After uvulopalatopharyngoplasty, surgical specimens of the uvula were subjected to haematoxylin and eosin, Masson's trichrome and immunohistochemical staining. Western blot and reverse transcriptase-polymerase chain reaction were used to evaluate the protein and messenger RNA expressions.
Results
The obstructive sleep apnoea group showed more severe inflammation, increased collagen deposition and higher immunohistochemical staining intensity for TGF-ß and MMP-9 as well as higher protein and messenger RNA expression of MMP-9, VEGF, TGF-ß, p38 MAPK, SMAD 2/3, AKT and JNK in the uvula than control group.
Conclusion
Patients with obstructive sleep apnoea demonstrated more severe inflammation, increased airway remodelling, and increased protein and messenger RNA expression of pro-inflammatory and pro-fibrotic cytokines in the uvula than control participants.
The risk of antipsychotic-associated cardiovascular and metabolic events may differ among countries, and limited real-world evidence has been available comparing the corresponding risks among children and young adults. We, therefore, evaluated the risks of cardiovascular and metabolic events in children and young adults receiving antipsychotics.
Methods
We conducted a multinational self-controlled case series (SCCS) study and included patients aged 6–30 years old who had both exposure to antipsychotics and study outcomes from four nationwide databases of Taiwan (2004–2012), Korea (2010–2016), Hong Kong (2001–2014) and the UK (1997–2016) that covers a total of approximately 100 million individuals. We investigated three antipsychotics exposure windows (i.e., 90 days pre-exposure, 1–30 days, 30–90 days and 90 + days of exposure). The outcomes were cardiovascular events (stroke, ischaemic heart disease and acute myocardial infarction), or metabolic events (hypertension, type 2 diabetes mellitus and dyslipidaemia).
Results
We included a total of 48 515 individuals in the SCCS analysis. We found an increased risk of metabolic events only in the risk window with more than 90-day exposure, with a pooled IRR of 1.29 (95% CI 1.20–1.38). The pooled IRR was 0.98 (0.90–1.06) for 1–30 days and 0.88 (0.76–1.02) for 31–90 days. We found no association in any exposure window for cardiovascular events. The pooled IRR was 1.86 (0.74–4.64) for 1–30 days, 1.35 (0.74–2.47) for 31–90 days and 1.29 (0.98–1.70) for 90 + days.
Conclusions
Long-term exposure to antipsychotics was associated with an increased risk of metabolic events but did not trigger cardiovascular events in children and young adults.
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.
Wide-ranging outcomes have been reported for surgical and non-surgical management of T3 laryngeal carcinomas. This study compared the outcomes of T3 tumours treated with laryngectomy or (chemo)radiotherapy in the northeast of England.
Methods
The outcomes of T3 laryngeal carcinoma treatment at three centres (2007–2016) were retrospectively analysed using descriptive statistics and survival curves.
Results
Of 179 T3 laryngeal carcinomas, 68 were treated with laryngectomies, 57 with chemoradiotherapy and 32 with radiotherapy. There was no significant five-year survival difference between treatment with laryngectomy (34.1 per cent) and chemoradiotherapy (48.6 per cent) (p = 0.184). The five-year overall survival rate for radiotherapy (12.5 per cent) was significantly inferior compared to laryngectomy and chemoradiotherapy (p = 0.003 and p < 0.001, respectively). The recurrence rates were 22.1 per cent for laryngectomy, 17.5 per cent for chemoradiotherapy and 50 per cent for radiotherapy. There were significant differences in recurrence rates when laryngectomy (p = 0.005) and chemoradiotherapy (p = 0.001) were compared to radiotherapy.
Conclusion
Laryngectomy and chemoradiotherapy had significantly higher five-year overall survival and lower recurrence rates compared with radiotherapy alone. Laryngectomy should be considered in patients unsuitable for chemotherapy, as it may convey a significant survival advantage over radiotherapy alone.
Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum.
Methods
The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components).
Results
Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions.
Conclusions
The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.
The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.