In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.

The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.

Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.

Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).

Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.

We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.

The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.

We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.

Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.

Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.

Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).

Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.

Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Whole-genome sequencing (WGS) shotgun metagenomics (metagenomics) attempts to sequence the entire genetic content straight from the sample. Diagnostic advantages lie in the ability to detect unsuspected, uncultivatable, or very slow-growing organisms.

To evaluate the clinical and economic effects of using WGS and metagenomics for outbreak management in a large metropolitan hospital.

Cost-effectiveness study.

Intensive care unit and burn unit of large metropolitan hospital.

Simulated intensive care unit and burn unit patients.

We built a complex simulation model to estimate pathogen transmission, associated hospital costs, and quality-adjusted life years (QALYs) during a 32-month outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB). Model parameters were determined using microbiology surveillance data, genome sequencing results, hospital admission databases, and local clinical knowledge. The model was calibrated to the actual pathogen spread within the intensive care unit and burn unit (scenario 1) and compared with early use of WGS (scenario 2) and early use of WGS and metagenomics (scenario 3) to determine their respective cost-effectiveness. Sensitivity analyses were performed to address model uncertainty.

On average compared with scenario 1, scenario 2 resulted in 14 fewer patients with CRAB, 59 additional QALYs, and $75,099 cost savings. Scenario 3, compared with scenario 1, resulted in 18 fewer patients with CRAB, 74 additional QALYs, and $93,822 in hospital cost savings. The likelihoods that scenario 2 and scenario 3 were cost-effective were 57% and 60%, respectively.

The use of WGS and metagenomics in infection control processes were predicted to produce favorable economic and clinical outcomes.

To understand the transmission dynamics of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in a hospital outbreak to inform infection control actions.

Retrospective cohort study.

General medical and elderly inpatient wards in a hospital in England.

Coronavirus disease 2019 (COVID-19) patients were classified as community or healthcare associated by time from admission to onset or positivity using European Centre for Disease Prevention and Control definitions. COVID-19 symptoms were classified as asymptomatic, nonrespiratory, or respiratory. Infectiousness was calculated from 2 days prior to 14 days after symptom onset or positive test. Cases were defined as healthcare-associated COVID-19 when infection was acquired from the wards under investigation. COVID-19 exposures were calculated based on symptoms and bed proximity to an infectious patient. Risk ratios and adjusted odds ratios (aORs) were calculated from univariable and multivariable logistic regression.

Of 153 patients, 65 were COVID-19 patients and 45 of these were healthcare-associated cases. Exposure to a COVID-19 patient with respiratory symptoms was associated with healthcare-associated infection irrespective of proximity (aOR, 3.81; 95% CI, 1.6.3–8.87). Nonrespiratory exposure was only significant within 2.5 m (aOR, 5.21; 95% CI, 1.15–23.48). A small increase in risk ratio was observed for exposure to a respiratory patient for >1 day compared to 1 day from 2.04 (95% CI, 0.99–4.22) to 2.36 (95% CI, 1.44–3.88).

Respiratory exposure anywhere within a 4-bed bay was a risk, whereas nonrespiratory exposure required bed distance ≤2.5 m. Standard infection control measures required beds to be >2 m apart. Our findings suggest that this may be insufficient to stop SARS-CoV-2 transmission. We recommend improving cohorting and further studies into bed distance and transmission factors.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.

Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.

Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.

These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.