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The results of SeaCH4NGE include a detailed analysis of the chemical composition of seaweeds, including heavy metals and nutritional composition. This elucidated that iodine was the main concern prior to feeding trials. Chemical analysis of the compounds that may be responsible for methane reduction showed that for the seaweeds investigated the reduction seen in-vitro was likely due to compounds called phlorotannins rather than bromoform. The in-vitro screening of the seaweeds showed a some reduction of methane, but the reduction was seaweed species dependent. The reduction was dose dependent, i.e. higher amount of seaweed inclusion resulted in larger methane reduction in-vitro. The same two seaweed species were used for a Rusitec experiment (in-vitro) which is a very comprehensive analysis which provides additional information. The in-vivo trial carried out showed that feeding A. nodosum and Fucus vesiculosus to cattle has a relatively small effect on methane emission or yield. However, phlorotannins are known to have other beneficial effects when consumed by ruminants. The report further contains responses from a questionnaire to UK cattle farmers regarding their stance on seaweed supplementation and environmental matters. This report is closed until 31.12.2023. ____ Niðurstöður SeaCH4NGE fela í sér ítarlega greiningu á efnasamsetningu þangs, þ.m.t þungmálma og næringarsamsetningu. Joð styrkur reyndist helsti takmarkandi þáttur varðandi þang sem fóðurbæti. Líklegt er að sú metan minnkun sem sást með tilraunum á metanframleiðslu á rannsóknarstofu (in vitro) væri vegna efnasambanda sem kallast flórótannín frekar en brómóforms sem er þekkt efni sem getur minnkað metanframleiðslu jórturdýra. In vitro skimun þangsins sýndi hóflega minnkun metans, en lægri metanframleiðsla var háð þangtegundum. Lækkunin var skammtaháð, þ.e.a.s. með því að nota meira magn af þangi mátti sjá meiri metan minnkun in vitro. Sömu tvær þangtegundirnar voru notaðar við Rusitec tilraun (in vitro) sem er mjög yfirgripsmikil greining sem veitir frekari upplýsingar. In-vivo rannsókn á kúm sýndi að fóðrun nautgripa með A. nodosum og Fucus vesiculosus hefur tiltölulega lítil áhrif á losun metans. Hins vegar er vitað að flórótannín hafa önnur jákvæð áhrif þegar þau eru neytt af jórturdýrum. Skýrslan inniheldur einnig könnun sem var gerð á viðhorfi breskra kúabænda til þörungagjafar og loftslagsmála. Þessari skýrsla er lokað til 31.12.2023., Funding: EIT Food

The COVID-19 pandemic had and continues to have profound effects on the travel industry, creating many risks and unknowns, especially for international travel. Using consumer risk theory and protection motivation theory as a framework, this study explores the relationships between international travel plans in 2023 and 2024–2025 and the likelihood of purchasing travel insurance (i. e., cancellation/interruption, emergency medical, baggage) with a sample of 1,264 US residents. Travel companion(s) and household income are examined as potential moderators and travel risk and sufficient household income as mediators. Results reveal a likelihood to purchase all three travel insurance types, and travelers are twice as likely to buy insurance for international travel for 2024–2025 compared to 2023. Likelihood to purchase travel insurance is also influenced by travel risk and having sufficient financial resources where sufficient financial resources partially mediates the relationships in question. Results suggest a new era of travel where risk is inherent and if travelers have sufficient financial resources, they will purchase travel insurance to mitigate risks of potentially suffering financial losses. This is a new finding with implications for the travel insurance industry, which should find ways to partner with travel providers, such as wholesalers and group tours, to offer insurance to international travelers. Although COVID-19 has been downgraded, other diseases are surfacing (e. g., monkeypox), leaving public health an important consideration. This and subsequent research will remain important to monitor how other outbreaks and risks impact the travel industry and travelers' methods to protect themselves.

The Healthy Life Trajectories Initiative, an international consortium developed in partnership with the World Health Organization, is addressing childhood obesity from a life-course perspective. It hypothesises that an integrated complex intervention from preconception, through pregnancy, infancy and early childhood, will reduce childhood adiposity and non-communicable disease risk, and improve child development. As part of the Healthy Life Trajectories Initiative in South Africa, the Bukhali randomised controlled trial is being conducted with 18–28-year-old women in Soweto, where young women face numerous challenges to their physical and mental health. The aims of this paper were to describe the intervention development process (including adaptations), intervention components, and process evaluation; and to highlight key lessons learned. Intervention materials have been developed according to the life-course stages: preconception (Bukhali), pregnancy (Bukhali Baby), infancy (Bukhali Nana; birth—2 years), and early childhood (Bukhali Mntwana, 2–5 years). The intervention is delivered by community health workers, and includes the provision of health literacy resources, multi-micronutrient supplementation, in-person health screening, services and referral, nutrition risk support, SMS-reminders and telephonic contacts to assist with behaviour change goals. A key adaption is the incorporation of principles of trauma-information care, given the mental health challenges faced by participants. The Bukhali process evaluation is focussing on context, implementation and mechanisms of impact, using a mixed methods approach. Although the completion of the trial is still a number of years away, the documentation of the intervention development process and process evaluation of the trial can provide lessons for the development, implementation, and evaluation of such complex life-course trials.

Objective: The purpose of this case series was to evaluate the efficacy of a synthetic biodegradable temporising matrix (BTM; PolyNovo Biomaterials Pty Ltd, Australia) and compare the outcome of BTM patients with and without negative pressure wound therapy (NPWT). Method: A retrospective chart review was conducted on patients admitted with deep full-thickness burns, traumatic or complex wound injuries treated with BTM. Electronic medical records and images were evaluated by a team of clinical professionals. Endpoints included: the measure of successful BTM integration; and comparison between patients treated with and without NPWT. Additional measures were BTM total surface area, BTM sites, timeliness of BTM application and any complications. Results: A total of 28 patients were evaluated and 23 (82.1%) demonstrated overall successful BTM integration. Patients treated with BTM in conjunction with NPWT (n=16) demonstrated a significantly higher (p=0.046) integration rate compared to patients treated without NPWT (n=12) (93.8% versus 58.3%, respectively). Patients treated with BTM with NPWT continued to successfully integrate and sustain favourable outcomes despite the presence of severe infection or the development of haematomas. Conclusion: A significantly higher integration rate was demonstrated when BTM was used in conjunction with NPWT. The results of this study further support the efficacy of successful integration of BTM as a replacement for tissue loss in the treatment of deep, full-thickness burns, traumatic and complex wound injuries, and particularly favourable outcomes with the use of NPWT. To the best of our knowledge, this is the first reported case series comparing the clinical outcomes of BTM with and without the use of NPWT.

Many difficult behaviors are rooted in a lack of executive function (EF) skills. EF includes a variety of skills including attention, persistence, and regulating emotions, among others. It is important for all students to learn the skills that contribute to developing appropriate EF skills, but it is especially important for students with disabilities to learn these skills to be successful in school. This article includes a summary of the variety of specific EF skills, existing music research in these skill areas, and strategies teachers can use to improve EF skills in inclusive music classrooms.

Purpose The intravenous (IV) medication compounding workflow has long been associated with preventable medication errors. This has led to the development of technologies designed to enhance the safety of IV compounding workflows. Digital image capture is a component of this technology about which there is relatively limited published literature. This study evaluates image capture implemented within an electronic health record’s existing first-party IV workflow solution. Methods A retrospective case-control study was conducted to measure IV preparation times before and after digital imaging implementation. Preparations during 3 periods (preimplementation, ≤1 month post implementation, and >1 month post implementation) were matched for 5 variables. A less stringent analysis with matching for 2 variables, as well as an unmatched analysis, were performed post hoc. An employee survey assessed satisfaction with the digital imaging workflow, and revised orders were reviewed to identify new problems introduced by image capture. Results A total of 134,969 IV dispenses were available for analysis. Median preparation time in the preimplementation and >1 month post implementation cohorts was unchanged in the 5-variable matched analysis (6.87 minutes vs 6.58 minutes, P = 0.14) and increased in the 2-variable matched analysis (6.98 minutes vs 7.35 minutes, P < 0.001) and unmatched analysis (6.55 minutes vs 8.02 minutes, P < 0.001). A large majority of survey respondents (92%) felt that image capture improved patient safety. Of the 105 postimplementation preparations identified as requiring revisions by the checking pharmacist, 24 (22.9%) required revisions directly related to camera functionality. Conclusion Implementation of digital image capture likely increased preparation times. Most IV room staff felt that image capture increased preparation times and were satisfied with how the technology improved patient safety. Image capture introduced camera-specific issues that led to preparations requiring revisions.

Dioecy, the separation of sexes into different male and female plants, can enable sexes to independently develop optimal strategies for the sex-linked allocation of reproductive resources. Understanding how dioecious species vary as conditions become more or less favourable may affect conservation and revegetation efforts in arid environments. Our study investigated sex-related resource allocation in the Australian native shrub, Pimelea microcephala subsp. microcephala (Thymelaeaceae) at four sites across an annual rainfall gradient of 250-390 mm in semi-arid South Australia. The study measured 25 male and 25 female individuals for plant height, plant diameter, the number of inflorescences per plant, number of flowers per inflorescence and the ratio of reproductive to vegetative biomass. Significant differences in the ratio of biomass allocated to reproduction between sexes (p < 0.05) were detected at three of the four sites, with sex-related differences increasing with decreased annual rainfall. Female reproductive allocation was two to five times greater, and was less variable than males at all sites except the highest rainfall site (p < 0.05), while male reproductive allocation decreased with average annual rainfall (p < 0.05). Growth outcomes of males and females were equal and female reproductive traits were mostly consistent between sites and were not associated with rainfall, therefore population structure may remain stable for P. microcephala subsp. microcephala as habitats become drier, so long as pollen limitation does not occur. Refereed/Peer-reviewed

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

Purpose: The efficacy of cetuximab is poor in metastatic head and neck squamous cell carcinoma (HNSCC). Cetuximab initiates natural killer (NK) cell–mediated antibody-dependent cellular cytotoxicity, with resultant recruitment of immune cells and suppression of antitumor immunity. We hypothesized that adding an immune-checkpoint inhibitor (ICI) could overcome this and lead to an enhanced antitumor response. Patients and Methods: A phase II study of cetuximab and durvalumab in metastatic HNSCC was conducted. Eligible patients had measurable disease. Patients who had received both cetuximab and an ICI were excluded. The primary endpoint was objective response rate (ORR) by RECIST 1.1 at 6 months. Results: As of April 2022, 35 patients enrolled, of whom 33 received at least 1 dose of durvalumab and were included in the response analysis. Eleven patients (33%) had received prior platinum-based chemotherapy, 10 an ICI (30%), and 1 patient (3%) cetuximab. ORR was 39% (13/33) with a median duration of response of 8.6 months [95% confidence interval (CI): 6.5–16.8]. Median progression-free and overall survivals were 5.8 months (95% CI: 3.7–14.1) and 9.6 months (95% CI: 4.8–16.3), respectively. There were 16 grade 3 treatment-related adverse events (TRAE) and one grade 4 TRAE, with no treatment-related deaths. Overall and progression-free survival did not correlate with PD-L1 status. NK cell cytotoxic activity was increased by cetuximab and further increased with the addition of durvalumab in responders. Conclusions: The combination of cetuximab and durvalumab demonstrated durable activity with a tolerable safety profile in metastatic HNSCC and warrants further investigation.

Objective: To characterize the features of aged care users who died by suicide and examine the use of mental health services and psychopharmacotherapy in the year before death. Design: Population-based, retrospective exploratory study Setting and participants: Individuals who died while accessing or waiting for permanent residential aged care (PRAC) or home care packages in Australia between 2008 and 2017. Measurements: Linked datasets describing aged care use, date and cause of death, health care use, medication use, and state-based hospital data collections. Results: Of 532,507 people who died, 354 (0.07%) died by suicide, including 81 receiving a home care package (0.17% of all home care package deaths), 129 in PRAC (0.03% of all deaths in PRAC), and 144 approved for but awaiting care (0.23% of all deaths while awaiting care). Factors associated with death by suicide compared to death by another cause were male sex, having a mental health condition, not having dementia, less frailty, and a hospitalization for self-injury in the year before death. Among those who were awaiting care, being born outside Australia, living alone, and not having a carer were associated with death by suicide. Those who died by suicide more often accessed Government-subsidized mental health services in the year before their death than those who died by another cause. Conclusions: Older men, those with diagnosed mental health conditions, those living alone and without an informal carer, and those hospitalized for self-injury are key targets for suicide prevention efforts.

Limb thrombus formation is a complication that can occur after endovascular aortic repair (EVAR), and its clinical significance has continued to be debated. Our objective was to report the incidence of limb thrombus after EVAR and determine the association of specific demographic, anatomic, and/or graft variables.A retrospective analysis of EVAR patients at a single tertiary center between January 2010 and December 2018 was performed to determine the limb thrombus rate. Demographic, graft, and anatomic variables were analyzed for an association with limb thrombus.A total of 301 patients were included. The average follow-up was 27.6 ± 4.9 months. The mean age was 76.5 ± 0.5 years, and 85% were men. Limb thrombus occurred in 22 patients (7.3%). Of these 22 patients, 11 (50.0%) had had occlusive limb thrombus, 14 (63.6%) were symptomatic, and 17 (77.3%) had required intervention. The patients with limb thrombus were younger (69.8 ± 1.3 years vs 77.1 ± 0.5 years; P .0001) and more likely to be smokers (10.2% vs 5.2%; P = .10). The incidence of limb thrombus with the Alpha graft (10.7%; Cook Medical Inc, Bloomington, IN) was compared with that with non-Cook grafts (4.0%; P = .07). The average common iliac artery diameter for patients with and without limb thrombus was 14.1 mm and 16.1 mm, respectively (P .01). Right-sided limb thrombus was more likely in smaller right iliac arteries (14.7 ± 0.9 cm vs 17.0 ± 0.6 cm; P .05), with a similar finding on the left (13.6 ± 0.9 cm vs 15.2 ± 0.4 cm; P = .13). Unilateral limb thrombus was almost twice as likely on the main body side than on the contralateral side (11 vs 6). Limb thrombus was not associated with aortoiliac disease (odds ratio [OR], 1.31; 95% confidence interval [CI], 0.37-4.62), limb extension (OR, 0.47; 95% CI, 0.06-3.62), or nonmatching limb heights (OR, 1.36; 95% CI, 0.54-3.43). Limb thrombus was also not associated with increased 30-day mortality (P.05).Limb thrombus formation is a complication that can occur after EVAR (7.3%). In our study, limb thrombus was seen more frequently in younger patients and those who smoked. Cook Alpha grafts had a thrombus formation rate of 10.7%, which was not significantly higher than that with other brands. Limb thrombus was more likely in smaller iliac arteries and on the main body side.

Several authors of articles in the special issue came together for an asynchronous discussion of the articles, surfacing several tensions and opportunities for future work. This summary of the discussion offers a glimpse into these insights.

Fluorescent polyesters have been prepared using ring-opening copolymerization by adding a fluorescent monomer to the reaction. The coloured polymers have been depolymerized and white polymer resynthesized from the recovered monomers.

Introduction: Checkpoint inhibitors (CPI) have significantly improved survival among patients with various cancer types. Prior studies have shown a correlation between immune cell infiltration and poorly differentiated cancers. This study evaluated the impact of poorly differentiated histology on survival in patients with advanced gastrointestinal cancers treated with immunotherapy. Methods: This study was a retrospective, single-center analysis of patients with gastrointestinal cancers treated with CPIs between 2016 and 2021. Univariate and multivariable analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor and patient characteristics, progression-free survival, and overall survival. Results: A total of 123 patients were eligible and included in the analysis. Median age was 66 years (23–88 years). Majority had stage IV disease (89%), were white (65.5%), and were male (64.5%). Most common diagnoses were hepatocellular carcinoma (30.5%), gastric adenocarcinoma (16.5%), esophageal adenocarcinoma (17%), and colorectal cancer (19.8%). About 32% of the tumors were microsatellite instability-high (MSI-High/dMMR), with BRAF V600E mutation rate of 10%. About 25% of the patients received CPIs as initial treatment, while 35.5% had received two or more prior lines of therapy. Compared with well and moderately differentiated histology, patients with poorly differentiated tumors had a shorter median overall survival (mOS) (not reached [NR] vs. NR vs. 9.3 months, p = 0.0264). There was no statistically significant difference in median progression-free survival (mPFS) between histology types (2.5 vs. 4.2 vs. 2 months, p = 0.1314). On univariate survival analysis, moderately differentiated tumors correlated with a significantly longer mOS (HR: 0.48, CI: 0.24–0.93, p = 0.030) and mPFS (HR: 0.62, 95% CI: 0.38–1.00, p = 0.048) compared to poorly differentiated histology. Female patients (HR: 0.55, 95% CI: 0.34–0.90, p = 0.018) and the Eastern Cooperative Oncology Group (ECOG) of 1 (vs. ≥2) had significantly longer mPFS (HR: 0.58, 95% CI: 0.35–0.97, p = 0.036). ECOG of 1 also correlated with longer mOS (HR: 0.47, 95% CI: 0.23–0.94, p = 0.034). Microsatellite stable (MSS) tumors had significantly shorter mPFS (HR: 5.74, 95% CI: 2.41–13.63, p < 0.001) and mOS (HR: 5.45, 95% CI: 1.64–18.12, p = 0.006). The number of prior systemic therapies was also associated with shorter mPFS (HR: 1.19, 95% CI: 1.03–1.39, p = 0.022) and mOS (HR: 1.23, 95% CI: 1.01–1.50, p = 0.045). On multivariable analyses, ECOG status of 0/1 versus ≥2 and MSI-High/dMMR versus MSS remained significantly associated with longer mPFS and mOS. There was no correlation with histologic differentiation status, race, or mutations such as BRAF V600E or KRAS. Conclusion: Results from this study demonstrate that poorly differentiated histology was associated with shorter mOS but was not associated with improved PFS in patients treated with CPI. Treatment-naïve patients, moderately differentiated tumors, female gender, ECOG 1, and MSI-High/dMMR were most likely to benefit from CPI.

Amniotic band syndrome (ABS) and limb body wall complex (LBWC) have an overlapping phenotype of multiple congenital anomalies and their etiology is unknown. We aimed to determine the prevalence of ABS and LBWC in Europe from 1980 to 2019and to describe the spectrum of congenital anomalies. In addition, we investigated maternal age and multiple birth as possible risk factors for the occurrence of ABS and LBWC. We used data from the European surveillance of congenital anomalies (EUROCAT) network including data from 30 registries over 1980–2019. We included all pregnancy outcomes, including live births, stillbirths, and terminations of pregnancy for fetal anomalies. ABS and LBWC cases were extracted from the central EUROCAT database using coding information responses from the registries. In total, 866 ABS cases and 451 LBWC cases were included in this study. The mean prevalence was 0.53/10,000 births for ABS and 0.34/10,000 births for LBWC during the 40 years. Prevalence of both ABS and LBWC was lower in the 1980s and higher in the United Kingdom. Limb anomalies and neural tube defects were commonly see in ABS, whereas in LBWC abdominal and thoracic wall defects and limb anomalies were most prevalent. Twinning was confirmed as a risk factor for both ABS and LBWC. This study includes the largest cohort of ABS and LBWC cases ever reported over a large time period using standardized EUROCAT data. Prevalence, clinical characteristics, and the phenotypic spectrum are described, and twinning is confirmed as a risk factor. info:eu-repo/semantics/publishedVersion

Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine-specific antibody responses upon homologous boosting is modest compared with other technologies. Here, we describe a system enabling modular decoration of adenovirus capsid surfaces with antigens and demonstrate potent induction of humoral immunity against these displayed antigens. Ligand attachment via a covalent bond was achieved using a protein superglue, DogTag/DogCatcher (similar to SpyTag/SpyCatcher), in a rapid and spontaneous reaction requiring only co-incubation of ligand and vector components. DogTag was inserted into surface-exposed loops in the adenovirus hexon protein to allow attachment of DogCatcher-fused ligands on virus particles. Efficient coverage of the capsid surface was achieved using various ligands, with vector infectivity retained in each case. Capsid decoration shielded particles from vector neutralizing antibodies. In prime-boost regimens, adenovirus vectors decorated with the receptor-binding domain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike induced >10-fold higher SARS-CoV-2 neutralization titers compared with an undecorated vector encoding spike. Importantly, decorated vectors achieved equivalent or superior T cell immunogenicity against encoded antigens compared with undecorated vectors. We propose capsid decoration using protein superglues as a novel strategy to improve efficacy and boostability of adenovirus-based vaccines and therapeutics.

Charge detection mass spectrometry (CDMS) was used to analyze recombinant adeno-associated virus serotype 8 (rAAV8) vectors after incubation at elevated temperatures. rAAV8 vectors with a range of genomes of interest (GOIs) from 2.22 to 4.84 kb were investigated. For the shorter GOIs, GOI release occurred at surprisingly low temperatures (15 min at 45°C for cytomegalovirus [CMV]-GFP). The released DNA and intermediates with the GOI extruded from the capsid were detected. The temperature required to release the short GOIs is well below the 65°C incubation temperature required to disassemble the empty rAAV8 capsid. The temperature for GOI release increased with its GOI length. With the longer GOIs, the GOI stabilized the capsid so that it remained intact under conditions that would disassemble the empty particle. After incubation at 65°C, the main species in the CDMS mass distributions for the longer GOIs was the vector with the GOI. However, for GOIs longer than the wild-type genome (∼4.7 kb), the stability diminished, and genome release occurred at a lower temperature. Heterogeneous DNA fragments from the host cells or plasmids is released at a lower temperature than the longer GOIs, suggesting that the GOIs have a feature that resists early release.

It is well established that human pluripotent stem cells (hPSCs) can acquire genetic and epigenetic changes during culture in vitro. Given the increasing use of hPSCs in research and therapy and the vast expansion in the number of hPSC lines available for researchers, the International Society for Stem Cell Research has recognized the need to reassess quality control standards for ensuring the genetic integrity of hPSCs. Here, we summarize current knowledge of the nature of recurrent genetic and epigenetic variants in hPSC culture, the methods for their detection, and what is known concerning their effects on cell behavior in vitro or in vivo. We argue that the potential consequences of low-level contamination of cell therapy products with cells bearing oncogenic variants are essentially unknown at present. We highlight the key challenges facing the field with particular reference to safety assessment of hPSC-derived cellular therapeutics.

Within the National Weather Service’s Unified Forecast System (UFS), snow depth and snow cover observations are assimilated once daily using a rule-based method designed to correct for gross errors. While this approach improved the forecasts over its predecessors, it is now quite outdated and is likely to result in suboptimal analysis. We have then implemented and evaluated a snow data assimilation using the 2D optimal interpolation (OI) method, which accounts for model and observation errors and their spatial correlations as a function of distances between the observations and model grid cells. The performance of the OI was evaluated by assimilating daily snow depth observations from the Global Historical Climatology Network (GHCN) and the Interactive Multisensor Snow and Ice Mapping System (IMS) snow cover data into the UFS, from October 2019 to March 2020. Compared to the control analysis, which is very similar to the method currently in operational use, the OI improves the forecast snow depth and snow cover. For instance, the unbiased snow depth root-mean-squared error (ubRMSE) was reduced by 45 mm and the snow cover hit rate increased by 4%. This leads to modest improvements to globally averaged near-surface temperature (an average reduction of 0.23 K in temperature bias), with significant local improvements in some regions (much of Asia, the central United States). The reduction in near-surface temperature error was primarily caused by improved snow cover fraction from the data assimilation. Based on these results, the OI DA is currently being transitioned into operational use for the UFS. Significance Statement Weather and climate forecasting systems rely on accurate modeling of the evolution of atmospheric, oceanic, and land processes. In addition, model forecasts are substantially improved by continuous incorporation of observations to models, through a process called data assimilation. In this work, we upgraded the snow data assimilation used in the U.S. National Weather Service (NWS) global weather prediction system. Compared to the method currently in operational use, the new snow data assimilation improves both the forecasted snow quantity and near-surface air temperatures over snowy regions. Based on the positive results obtained in the experiments presented here, the new snow data assimilation method is being implemented in the NWS operational forecast system.

In the late nineteenth century, the prognosis of late-life melancholia was believed to be poor. The medical casebooks of 40 patients aged 60+years, admitted to two Hospitals for the Insane in New South Wales with melancholia between 1871 and 1905, were examined. Psychosis (87.5%), depressed mood (80%), suicidal behaviour (55%), physical ill health (55%), restlessness (50%) and fears of harm to self (50%) were identified. Main outcomes were discharge (40%) and death (37.5%). Victoria’s Kew Hospital patient register for 1872–88 revealed 669 melancholia admissions with 30 aged 60+. Outcomes worsened significantly with age (chi square = 16.19, df = 4, p < 0.005), mainly due to higher mortality. Nineteenth-century late-life melancholia was a severe disorder despite many cases recovering.

There are many models for structuring peer interactions in the music classroom. From peer mentoring to peer tutoring, to other structured interaction models that have emerged from other areas of education, music teachers have many options when considering how to include structured peer interaction activities. This article describes the various models of structured peer interaction activities that can be used in music classrooms and provides strategies for implementing these activities in ways that support students with disabilities.

Objective: To review studies reporting on the effectiveness of psychiatry service delivery for older people and people with dementia in hospital and residential aged care. Methods: A systematic search of four databases was conducted to obtain peer-reviewed literature reporting original research published since June 2004 evaluating a psychiatry service for older people (aged 60 years and over) or people with dementia in inpatient or residential aged care settings. Results: From the 38 included studies, there was consistent low-to-moderate quality evidence supporting the effectiveness of inpatient older persons’ mental health wards ( n = 14) on neuropsychiatric symptoms, mood, anxiety and quality of life. Inpatient consultation/liaison old age psychiatry services ( n = 9) were not associated with improved depression, quality of life or mortality in high-quality randomised studies. However, low-quality evidence demonstrated improved patient satisfaction with care and reduced carer stress. The highest quality studies demonstrated no effect of psychiatric in-reach services to residential aged care ( n = 9) on neuropsychiatric symptoms but a significant reduction in depressive symptoms among people with dementia. There was low-quality evidence that long-stay intermediate care wards ( n = 6) were associated with reduced risk for dangerous behavioural incidents and reduced costs compared to residential aged care facilities. There was no effect of these units on neuropsychiatric symptoms or carer stress. Conclusions and implications: The scarcity of high-quality studies examining the effectiveness of old age psychiatry services leaves providers and policy-makers to rely on low-quality evidence when designing services. Future research should consider carefully which outcomes to include, given that staff skill and confidence, length of stay, recommendation uptake, patient- and family-reported experiences, and negative outcomes (i.e. injuries, property damage) are as important as clinical outcomes.

The return of authoritarian great powers, the slowing of the democratic wave, and outright reversion to authoritarian rule pose important questions for international theory. What are the implications of an international system populated with more autocracies? This question was posed by a diverse array of social scientists, public intellectuals, and policy analysts in response to the autocratic wave in Europe in the 1920s and 1930s. We show that a series of conversations emanating from quite diverse intellectual priors – from Christian realists to international lawyers and disaffected Marxists – converged on the risks these autocratic regimes posed to democratic regimes and the international order they sought to forge. These risks included unconstrained rulers, an inability to sustain international commitments and political processes that undermined rational deliberation at home and spread disinformation abroad. The reading of this work suggests an under-appreciated strand of liberal international relations theory, and these debates have direct implications for liberal arguments about the democratic peace. Rather than theorizing why democracies avoid war, they underscore the importance of understanding why authoritarian and democratic countries are particularly prone to conflict.

Purpose In the last 20 years, concussion has received increased attention in the media, with distinct recognition of sports-related concussion (SRC). Much of this attention has centred on the paediatric population, due to concerns over adolescent brain development and the high numbers of teenagers playing contact sport. This qualitative study explored (1) what experts in the field of concussion perceive regarding trends in paediatric concussion awareness and management, and (2) how responses to these questions differ by country (US vs. NZ) and by discipline (research vs. sports coaching vs. sports medicine). Methods After the development of a semi-structured interview template, questions were coded for interviews of six (N = 6) experts in academia, medicine, and coaching: three in the United States (N = 3) and three in New Zealand (N = 3). Interviews were then transcribed and qualitatively analysed using a thematic narrative analysis. Emergent themes included concussion knowledge, management, and unanswered questions. Results Findings showed general commonalities on the importance of concussion education, the improvement of concussion awareness, compliance to concussion protocols, and the need to research long-term outcomes. Fewer commonalities were found regarding the level of concussion reporting, the impact of multiple concussions, whether paediatric and adult concussion should be treated similarly, and the utility of concussion tests. Conclusions Concussion experts agree on many areas; however, divergent opinions were apparent. Further original research is required within the paediatric population to analyse the efficacy of current concussion guidelines.