War and disaster are forcing a major rethink around mass casualty management.

Mass casualty events (MASCAL) do not follow the same rules as typical major incidents. In the West at least, the latter often occur in stable, networked trauma systems, whereas MASCAL are characterised by overwhelming numbers of patients, compounded by protracted scene and transport times, decompensated response systems and significant disruption to infrastructure, command and control.This paper describes the 8Ds approach being taken by the UK Defence Medical Services and the North Atlantic Treaty Organization Emergency Medicine Panel framework to approach MASCAL. The eight domains were derived from literature about management of casualties in the World Wars, and also from approaches taken by civilian health systems as they struggle to manage increasing demand. They are: distribute; decompress; delay; delegate; deliver faster and deliver better; dynamic levels of care; and de-escalate These domains will allow a structured approach to research and innovate around MASCAL, informing better guidelines for their management.

Measurements of pulse rate using facial video cameras from smart devices in patients diagnosed with atrial fibrillation.

Clinical applications of passive long-term heart rate (HR) monitoring in patients with cardiac arrhythmias include adequate drug titration of atrioventricular (AV) nodal drugs and assessment of medical compliance with treatment. A majority of patients treated with beta-blockers, especially patients with atrial fibrillation (AF), require some degree of drug titration during the first 6 months of treatment to ensure that adequate HR control and medicine compliance has been achieved. Failing to achieve adequate rate control in patients with AF can lead to worsening symptoms, heart failure exacerbations, and potentially tachycardia-induced cardiomyopathy. Enabling video-based monitoring during telehealth patient visits could facilitate providers to measure heart rate (HR) without the need for a dedicated home device (smartwatch, SPO2 device, or others). Videoplethysmography (VPG) is a monitoring technology that measures pulse rate by utilizing front-facing cameras embedded in smart devices. VPG provides a remote and contactless cardiac monitoring solution. We conducted a clinical experiment to evaluate the accuracy of VPG in measuring HR while running on two portable devices: Samsung S10 smartphones and S3 tablets. We used a single­lead ECG to measure the heart rate at the time of the VPG recordings in AF patients. We employed the Bland-Altman method to measure the level of agreement between videoplethysmography and ECG-based measurements of HR. The findings reveal that the mean difference in videoplethysmography and ECG-based heart rate was inferior to 1 bpm across the 2 devices with confidence intervals ranging from 3 to 12 BPM. Our facial video-based HR monitoring solution could assist providers in measuring heart rates in their patients with AF during remote telehealth visits.

Meeting Summary: Global Vaccine and Immunization Research Forum, 2021.

The 2021 Global Vaccine and Immunization Research Forum highlighted the considerable advances and recent progress in research and development for vaccines and immunization, critically reviewed lessons learned from COVID-19 vaccine programs, and looked ahead to opportunities for this decade. For COVID-19, decades of investments in basic and translational research, new technology platforms, and vaccines targeting prototype pathogens enabled a rapid, global response. Unprecedented global coordination and partnership have played an essential role in creating and delivering COVID-19 vaccines. More improvement is needed in product attributes such as deliverability, and in equitable access to vaccines. Developments in other priority areas included: the halting of two human immunodeficiency virus vaccine trials due to lack of efficacy in preventing infection; promising efficacy results in Phase 2 trials of two tuberculosis vaccines; pilot implementation of the most advanced malaria vaccine candidate in three countries; trials of human papillomavirus vaccines given in single-dose regimens; and emergency use listing of a novel, oral poliomyelitis type 2 vaccine. More systematic, proactive approaches are being developed for fostering vaccine uptake and demand, aligning on priorities for investment by the public and private sectors, and accelerating policy making. Participants emphasized that addressing endemic disease is intertwined with emergency preparedness and pandemic response, so that advances in one area create opportunities in the other. In this decade, advances made in response to the COVID-19 pandemic should accelerate availability of vaccines for other diseases, contribute to preparedness for future pandemics, and help to achieve impact and equity under Immunization Agenda 2030.

Accelerating access for all through research and innovation in immunization: Recommendations from Strategic Priority 7 of the Immunization Agenda 2030.

Research and innovation have been fundamental to many of the successes in immunization thus far, and will play important roles in the future success of Immunization Agenda 2030 (IA2030). Strategic Priority 7 (SP7) of IA2030, which addresses research and innovation, is explicitly informed by country needs and priorities, and aims to strengthen the innovation ecosystem through capacity building and collaboration at country, regional, and global levels. SP7 identifies four key focus areas: (1) "needs-based innovation", (2) "new and improved products, services, and practices", (3) "evidence for implementation", and (4) "local capacity". Strategic interventions in these key focus areas apply the lessons of the Global Vaccine Action Plan and the "Decade of Vaccines" to emphasize local innovation, promote the use of research by countries to improve program performance and impact, and encourage capacity building for the development and implementation of innovations. The proposed approach will maintain a focus on the development of new vaccines and the improvement of existing vaccines, and increase attention to innovation in service delivery. Monitoring and evaluation will foster evidence-based priority setting at the country level and help to ground the global research and development (R&D) agenda in the needs of communities. Together, these approaches are intended to harness the power of research and innovation more effectively, to meet the challenges of the future and achieve the ambitious goals of IA2030.

Mutant clones in normal epithelium outcompete and eliminate emerging tumours.

Human epithelial tissues accumulate cancer-driver mutations with age1-9, yet tumour formation remains rare. The positive selection of these mutations suggests that they alter the behaviour and fitness of proliferating cells10-12. Thus, normal adult tissues become a patchwork of mutant clones competing for space and survival, with the fittest clones expanding by eliminating their less competitive neighbours11-14. However, little is known about how such dynamic competition in normal epithelia influences early tumorigenesis. Here we show that the majority of newly formed oesophageal tumours are eliminated through competition with mutant clones in the adjacent normal epithelium. We followed the fate of nascent, microscopic, pre-malignant tumours in a mouse model of oesophageal carcinogenesis and found that most were rapidly lost with no indication of tumour cell death, decreased proliferation or an anti-tumour immune response. However, deep sequencing of ten-day-old and one-year-old tumours showed evidence of selection on the surviving neoplasms. Induction of highly competitive clones in transgenic mice increased early tumour removal, whereas pharmacological inhibition of clonal competition reduced tumour loss. These results support a model in which survival of early neoplasms depends on their competitive fitness relative to that of mutant clones in the surrounding normal tissue. Mutant clones in normal epithelium have an unexpected anti-tumorigenic role in purging early tumours through cell competition, thereby preserving tissue integrity.

Worldwide prevalence of suicidal ideation and suicide plan among people with schizophrenia: a meta-analysis and systematic review of epidemiological surveys.

Schizophrenia is a severe psychiatric disorder with high premature mortality rates. This is a meta-analysis and systematic review of the prevalence of suicidal ideation (SI) and suicide plan (SP) among people with schizophrenia. PubMed, Web of Science, Embase, and PsycINFO were systematically searched from their respective inception to October 10, 2020. Data on prevalence of SI and/or SP were synthesized using the random effects model. Twenty-six studies covering 5079 people with schizophrenia were included for meta-analysis. The lifetime and point prevalence of SI were 34.5% (95% CI: 28.2-40.9%), and 29.9% (95% CI: 24.2-35.6%), respectively. The lifetime prevalence of SP was 44.3% and the point prevalence of SP ranged between 6.4 and 13%. Subgroup and meta-regression analyses revealed that source of patients, survey countries, and sample size were significantly associated with the point prevalence of SI, while male proportion and quality assessment scores were significantly associated with the lifetime and point prevalence of SI. Survey time and mean age were significantly associated with lifetime prevalence of SI. Both SI and SP are common in people living with schizophrenia, especially in males and inpatients. Routine screening and effective interventions for SI and SP should be implemented in this population.

Knowledge and awareness of COVID-19 among Indonesian migrant workers in the Greater China Region.

OBJECTIVES: Migrant workers are one of the most vulnerable population groups during the coronavirus disease 2019 (COVID-19) pandemic. This study investigated knowledge and awareness of COVID-19 among Indonesian migrant workers (IMWs) in Macao (SAR), Hong Kong (SAR), and Taiwan. STUDY DESIGN: This was a cross-sectional study. METHODS: Data were collected through an online survey in February and March 2020 to gain information on (1) participants' sociodemographic characteristics, (2) experience and awareness regarding COVID-19 information, and (3) knowledge and understanding of COVID-19. A series of Chi-squared, t-test, and logistic regression analyses were conducted. RESULTS: The survey was completed by 491 participants (92.1% female). Knowledge of COVID-19 was obtained from multiple sources, including a large proportion from online social media. However, participants who obtained information from their employer, local social networks, and migrant organisations answered a greater number of questions correctly. One-third of participants reported receiving hoax, fake news, and incorrect information and obtained information from unverified sources. Participants were most interested in information about how to cure COVID-19, and 57.8% knew that no specific drug or vaccine was currently available. Almost all participants correctly identified fever and wearing a facemask as the main COVID-19 symptom and prevention strategy, respectively. Participants with senior high school or higher education and who worked as domestic or care workers had a greater knowledge of COVID-19 than their counterparts. CONCLUSIONS: Public health communication strategies using multiple channels, including employers and community organisations, would help to minimise COVID-19 knowledge gaps. In addition, it is recommended that digital literacy content is added to public health campaigns.

Second surgery for progressive glioblastoma: a multi-centre questionnaire and cohort-based review of clinical decision-making and patient outcomes in current practice.

PURPOSE: Glioblastoma prognosis is poor. Treatment options are limited at progression. Surgery may benefit, but no quality guidelines exist to inform patient selection. We sought to describe variations in surgical management at progression, highlight where further evidence is needed, and build towards a consensus strategy. METHODS: Current practice in selection of patients with progressive GBM for second surgery was surveyed online amongst specialists in the UK and Europe. We complemented this with an assessment of practice in a retrospective cohort study from six United Kingdom neurosurgical units. We used descriptive statistics to analyse the data. RESULTS: 234 questionnaire responses were received. Maintaining or improving patient quality of life was key to decision making, with variation as to whether patient age, performance status or intended extent of resection was relevant. MGMT methylation status was not important. Half considered no minimum time after first surgery. 288 patients were reported in the cohort analysis. Median time to second surgery from first surgery 390 days. Median overall survival 815 days, with no association between time to second surgery and time to death (p = 0.874). CONCLUSIONS: This is the most wide-ranging examination of contemporaneous practice in management of GBM progression. Without evidence-based guidelines, the variation is unsurprising. We propose consensus guidelines for consideration, to reduce heterogeneity in decision making, support data collection and analysis of factors influencing outcomes, and to inform clinical trials to establish whether second surgery improves patient outcomes, or simply selects to patients already performing well.

Understanding vaccine-elicited protective immunity against pre-erythrocytic stage malaria in endemic regions.

Recent malaria vaccine trials in endemic areas have yielded disparate results compared to studies conducted in non-endemic areas. A workshop was organized to discuss the differential pre-erythrocytic stage malaria vaccine (Pre-E-Vac) efficacies and underlying protective immunity under various conditions. It was concluded that many factors, including vaccine technology platforms, host genetics or physiologic conditions, and parasite and mosquito vector variations, may all contribute to Pre-E-Vac efficacy. Cross-disciplinary approaches are needed to decipher the multi-dimensional variables that contribute to the observed vaccine hypo-responsiveness. The malaria vaccine community has an opportunity to leverage recent advances in immunology, systems vaccinology, and high dimensionality data science methodologies to generate new clinical datasets with unprecedented levels of functional resolution as well as capitalize on existing datasets for comprehensive and aggregate analyses. These approaches would help to unlock our understanding of Pre-E-Vac immunology and to translate new candidates from the laboratory to the field more predictably.

Meeting report: Global vaccine and immunization research forum, 2018.

Every two years, the Global Vaccine and Immunization Research Forum takes stock of global research in vaccines and immunization. As in prior years, the 2018 meeting addressed vaccine discovery, development, decision-making, and deployment. This time, however, it also featured two overarching themes: "Innovating for Equity" and "End-to-End Integration." Significant advances have been made in the last two years, but participants noted that some important goals of the Global Vaccine Action Plan are not being met and called urgently for innovation in improving access to vaccines. Two factors were highlighted as crucial to improving coverage: a focus on equity and sustainability throughout the immunization ecosystem, and an enabling political environment that prioritizes health and immunization.

A feasibility randomised controlled trial to evaluate the role of computed tomography in adults with atypical right iliac fossa pain.

BACKGROUND: In patients with right iliac fossa pain, the need for surgery is largely determined by the likelihood of appendicitis. Patients often undergo ultrasound scanning despite a low diagnostic accuracy for appendicitis. This study aimed to determine the feasibility of a larger trial of computed tomography in the evaluation of patients with atypical right iliac fossa pain. MATERIALS AND METHODS: A single-centre, unblinded, parallel randomised controlled trial of computed tomography in the assessment of patients with atypical right iliac fossa pain. After a retrospective evaluation, standard care was defined as serial examination with or without ultrasound. Atypical right iliac fossa pain was defined as no firm diagnosis after initial senior review. Simple descriptions of the risks and benefits of computed tomography were devised for patients to consider. Primary objectives were to assess feasibility and acceptability of the study procedures. RESULTS: A total of 71 patients were invited to participate and 68 were randomised. Final analysis included 31 participants in the standard care arm and 33 in the computed tomography arm, with comparable demographics. Computed tomography was associated with superior diagnostic accuracy, with 100% positive and negative predictive value. The proportion of scans that positively influenced management was 73% for computed tomography and 0% for ultrasound. In the computed tomography arm, there was a trend towards a shorter length of stay (2.3 vs 3.1 days) and a lower negative laparoscopy rate (2 of 11 vs 4 of 9). CONCLUSION: A large randomised trial to evaluate the use of unenhanced computed tomography in atypical right iliac fossa pain appears feasible and justified.

Increase in CFC-11 emissions from eastern China based on atmospheric observations.

The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons1. The atmospheric concentration of trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s2. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased3,4. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown3. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 ± 3.0 (±1 standard deviation) gigagrams per year higher in 2014-2017 than in 2008-2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010.

Targeted TNF-α Overexpression Drives Salivary Gland Inflammation.

Chronic inflammation of the salivary glands from pathologic conditions such as Sjögren's syndrome can result in glandular destruction and hyposalivation. To understand which molecular factors may play a role in clinical cases of salivary gland hypofunction, we developed an aquaporin 5 (AQP5) Cre mouse line to produce genetic recombination predominantly within the acinar cells of the glands. We then bred these mice with the TNF-αglo transgenic line to develop a mouse model with salivary gland-specific overexpression of TNF-α; which replicates conditions seen in sialadenitis, an inflammation of the salivary glands resulting from infection or autoimmune disorders such as Sjögren's syndrome. The resulting AQP5-Cre/TNF-αglo mice display severe inflammation in the salivary glands with acinar cell atrophy, fibrosis, and dilation of the ducts. AQP5 expression was reduced in the salivary glands, while tight junction integrity appeared to be disrupted. The immune dysregulation in the salivary gland of these mice led to hyposalivation and masticatory dysfunction.

Radiological Kinetics of Brain Metastases and Clinical Implications for Patients Treated With Stereotactic Radiosurgery.

AIMS: Select patients with brain metastases receive stereotactic radiosurgery (SRS) with the objective of improving survival and intracranial disease control. Brain metastases number and volume are prognostic factors used to inform patient selection. The aim of this study was to assess the rate of change of brain metastases size and number (growth kinetics) between the diagnostic and day of SRS magnetic resonance imaging (MRI) scans. MATERIALS AND METHODS: All patients treated with Gamma Knife SRS between October 2015 and April 2017 were included in this single-centre retrospective analysis. Brain metastases number and diameter were recorded at diagnosis and treatment. For patients with multiple brain metastases, the largest lesion was the index lesion. Distant intracranial control and overall survival were reported from the date of SRS. RESULTS: In total, 146 patients received 156 episodes of SRS. The median interval between diagnostic and SRS MRI was 20 days (range 1-68). Interval growth in the index lesion of at least 3 mm or the development of a new brain metastasis was noted in 60.2% of patients. This was associated with age less than 60 years (P = 0.001), Eastern Cooperative Oncology Group (ECOG) performance status 2 or above (P = 0.04), non-small cell lung carcinoma (NSCLC) (P = 0.03) or melanoma histologies (P = 0.05) and uncontrolled extracranial disease (P = 0.05). These patients were also more likely to develop distant intracranial recurrence (P = 0.046). Clinically significant growth was not associated with scan interval or differences in overall survival. The Kaplan-Meier estimate of probability of survival at 12 months was 59.3% (95% confidence interval 46.7-75.2%) for all patients. CONCLUSION: Intracranial progression between diagnosis and day of SRS is common. Risk factors are uncontrolled extracranial disease, poorer performance status, NSCLC or melanoma histologies and age less than 60 years. These patients would benefit from an MRI closer to treatment to inform patient selection and target delineation for SRS planning.

Identifying patients at risk for urinary retention following inguinal herniorrhaphy: a single institution study.

PURPOSE: We aim to identify patients at risk for post-operative urinary retention (POUR) and factors associated with POUR. METHODS: Males who underwent inguinal hernia repair (IHR) from June 2010 to September 2014 at a single institution were grouped according to the presence (symptomatic) or absence (asymptomatic) of preoperative urogenital symptoms (UGS). Patients ≤ 18 years of age were excluded. POUR was defined as the need to catheterize a patient who had not voided 6 h after surgery. Data were examined using IBM SPSS v23.0. RESULTS: Of the 60 asymptomatic and 30 symptomatic patients identified, no differences were seen in age (55 vs. 65, p = 0.13), length of stay > 1 day (3% vs. 13%, p = 0.09), bilateral inguinal herniation (23% vs. 23%, p = 1.00), or laparoscopic approach (70% vs. 69%, p = 1.00); however, significant differences were seen in POUR (5% vs. 27%, p = 0.01) and α-blocker utilization (50% vs. 80%, p = 0.01). When age-matched, neither POUR (10% vs. 27%, p = 0.10) or α-blocker utilization (57% vs. 80%, p = 0.05) significantly differed between asymptomatic and symptomatic patients, respectively. Logistic regression analysis demonstrated that only bilateral inguinal herniation (OR 6.55, p = 0.03) and symptoms (OR 6.78, p = 0.02) were associated with POUR. Asymptomatic patients with a unilateral hernia have a 4.3% risk of POUR, whereas symptomatic patients with a bilateral inguinal hernia have at 57.1% risk. CONCLUSIONS: We demonstrate that bilateral inguinal herniation and UGS independently increase the risk of POUR, whereas α-blockers do not. For the general surgical population, α-blockers should not be routinely prescribed to all patients and instead should be limited to high-risk patients.

An evaluation of a common elements treatment approach for youth in Somali refugee camps.

BACKGROUND: This paper reports on: (1) an evaluation of a common elements treatment approach (CETA) developed for comorbid presentations of depression, anxiety, traumatic stress, and/or externalizing symptoms among children in three Somali refugee camps on the Ethiopian/Somali border, and (2) an evaluation of implementation factors from the perspective of staff, lay providers, and families who engaged in the intervention. METHODS: This project was conducted in three refugee camps and utilized locally validated mental health instruments for internalizing, externalizing, and posttraumatic stress (PTS) symptoms. Participants were recruited from either a validity study or from referrals from social workers within International Rescue Committee Programs. Lay providers delivered CETA to youth (CETA-Youth) and families, and symptoms were re-assessed post-treatment. Providers and families responded to a semi-structured interview to assess implementation factors. RESULTS: Children who participated in the CETA-Youth open trial reported significant decreases in symptoms of internalizing (d  =  1.37), externalizing (d  =  0.85), and posttraumatic stress (d  =  1.71), and improvements in well-being (d  =  0.75). Caregivers also reported significant decreases in child symptoms. Qualitative results were positive toward the acceptability and appropriateness of treatment, and its feasibility. CONCLUSIONS: This project is the first to examine a common elements approach (CETA: defined as flexible delivery of elements, order, and dosing) with children and caregivers in a low-resource setting with delivery by lay providers. CETA-Youth may offer an effective treatment that is easier to implement and scale-up versus multiple focal interventions. A fullscale randomized clinical trial is warranted.

Meeting report: Global vaccine and immunization research forum.

Building on the success of the first Global Vaccine and Immunization Research Forum (GVIRF), the World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health in the United States of America, and the Bill & Melinda Gates Foundation convened the second GVIRF in March 2016. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific advances and innovative technologies to design and deliver vaccines as well as novel tools and approaches to increase the uptake of vaccines throughout the world. This report summarizes the discussions and conclusions from the forum participants.

Activation of a novel p70 S6 kinase 1-dependent intracellular cascade in the basolateral nucleus of the amygdala is required for the acquisition of extinction memory.

Repeated presentations of a previously conditioned stimulus lead to a new form of learning known as extinction, which temporarily alters the response to the original stimulus. Previous studies have shown that the consolidation of extinction memory requires de novo protein synthesis. However, the role of specific nodes of translational control in extinction is unknown. Using auditory threat conditioning in mice, we investigated the role of mechanistic target of rapamycin complex 1 (mTORC1) and its effector p70 S6 kinase 1 (S6K1) in the extinction of auditory threat conditioning. We found that rapamycin attenuated the consolidation of extinction memory. In contrast, genetic deletion and pharmacological inhibition of S6K1, a downstream effector of mTORC1, blocked within-session extinction, indicating a role for S6K1 independent of protein synthesis. Indeed, the activation of S6K1 during extinction required extracellular signal-regulated kinase (ERK) activation in the basolateral nucleus of the amygdala (BLA) and was necessary for increased phosphorylation of the GluA1 (Thr840) subunit of the AMPA receptor following extinction training. Mice exposed to brief uncontrollable stress showed impaired within-session extinction as well as a downregulation of ERK and S6K1 signaling in the amygdala. Finally, using fiber photometry we were able to record calcium signals in vivo, and we found that inhibition of S6K1 reduces extinction-induced changes in neuronal activity of the BLA. These results implicate a novel ERK-S6K1-GluA1 signaling cascade critically involved in extinction.