Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19.

Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a limited range of other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad range of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers. In particular, CAST/EiJ, a wild-derived strain, developed high lung viral burdens, more severe lung pathology than seen in other CC strains, and a dysregulated cytokine profile resulting in morbidity and mortality. These inbred mouse strains may serve as a valuable platform to evaluate therapeutic countermeasures against severe COVID-19 and other coronavirus pandemics in the future.

COVID-19 preparedness and response in the Pitcairn Islands: keeping one of the world's smallest and most isolated populations safe in a pandemic.

Problem: While the COVID-19 pandemic threatened the entire world, the extremely remote Pitcairn Islands faced unique vulnerabilities. With only a physician and a nurse to care for an ageing population of fewer than 40 residents, and with very limited referral pathways, Pitcairn encountered distinct challenges in preparing for and responding to the COVID-19 pandemic. Context: The Pitcairn Islands is an overseas territory of United Kingdom of Great Britain and Northern Ireland consisting of four islands in the South Pacific: Pitcairn, Henderson, Ducie and Oeno. Pitcairn is the only inhabited island with a local resident population of approximately 31 people, around half of whom were over 60 years old in 2023. The islands are only accessible by sea and are located more than 2000 km from the nearest referral hospital in French Polynesia. Actions: Pitcairn's Island Council took aggressive action to delay the importation of SARS-CoV-2, vaccinate its small population and prepare for the potential arrival of the virus. Outcomes: As of May 2024, Pitcairn was one of the only jurisdictions in the world not to have had a single COVID-19 hospitalization or death. Nevertheless, the pandemic presented the islands' population with many economic, social and health challenges. Discussion: Pitcairn's population avoided COVID-19-related hospitalizations and deaths despite its elderly population's vulnerability to COVID-19, a significant level of comorbidities, and limited clinical management capabilities and options for emergency referrals. The pandemic highlighted some of the population's health vulnerabilities while also underscoring some of their innate strengths.

Fifteen-minute consultation: a guide to paediatric major haemorrhage.

Major trauma is a principal cause of morbidity and mortality in children. Severe haemorrhage is the second-leading cause of death in paediatric trauma, preceded by traumatic brain injury. Major haemorrhage protocols (MHPs), also known as 'code red' and 'massive transfusion protocols', are used to make large volumes of blood products rapidly available. Most recommendations for paediatric MHPs are extrapolated from adult data because of a lack of large, high-quality, prospective paediatric studies. However, applying adult data in a paediatric context requires caution due to differences in injury mechanisms and physiological responses between adults and children. Since major haemorrhage is a high-acuity low-occurrence event, MHP requires effective training, collaboration and communication among a large multidisciplinary team.In this 15-minute consultation, we provide an evidence-based synthesis of the management principles of paediatric major haemorrhage.

Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques.

The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.

Tonga national emergency medical team response to the 2022 Hunga Tonga-Hunga Ha'apai volcanic eruption and tsunami: the first deployment of the Tonga Emergency Medical Assistance Team (TEMAT).

Problem: The undersea Hunga Tonga-Hunga Ha'apai volcano erupted on 15 January 2022, causing a tsunami that affected Tonga as well as other countries around the Pacific rim. Tonga's international borders were closed at the time due to the coronavirus disease pandemic, but clinical surge support was needed to respond to this disaster. Context: Tonga's Ministry of Health formed the Tonga Emergency Medical Assistance Team (TEMAT) in 2018 to provide clinical care and public health assistance during disasters, outbreaks and other health emergencies. TEMAT was activated for the first time in January 2022 to respond to medical and public health needs following the eruption and tsunami. Action: On 16 January 2022, a five-person TEMAT advance team was deployed to conduct initial damage assessments and provide casualty care. Subsequently, TEMAT rotations were deployed to provide clinical care and public health support across the Ha'apai island group for over 2 months. Outcome: TEMAT deployed to the islands most affected by the volcanic eruption and tsunami within 24 hours of the event, providing emergency clinical, psychosocial and public health services across four islands. TEMAT reported daily to the Ministry of Health and National Emergency Management Office, providing critical information for response decision-making. All TEMAT actions were documented, and an after-action review was conducted following the deployment. Discussion: TEMAT's deployment in response to the 2022 volcanic eruption and tsunami highlighted the importance of national emergency medical teams that are prepared to respond to a range of emergency events.

Epidemiology of dengue reported in the World Health Organization's Western Pacific Region, 2013-2019.

The global burden of dengue, an emerging and re-emerging mosquito-borne disease, increased during the 20-year period ending in 2019, with approximately 70% of cases estimated to have been in Asia. This report describes the epidemiology of dengue in the World Health Organization's Western Pacific Region during 2013-2019 using regional surveillance data reported from indicator-based surveillance systems from countries and areas in the Region, supplemented by publicly available dengue outbreak situation reports. The total reported annual number of dengue cases in the Region increased from 430 023 in 2013 to 1 050 285 in 2019, surpassing 1 million cases for the first time in 2019. The reported case-fatality ratio ranged from 0.19% (724/376 972 in 2014 and 2030/1 050 285 in 2019) to 0.30% (1380/458 843 in 2016). The introduction or reintroduction of serotypes to specific areas caused several outbreaks and rare occurrences of local transmission in places where dengue was not previously reported. This report reinforces the increased importance of dengue surveillance systems in monitoring dengue across the Region.

Implementation and use of a national electronic dashboard to guide COVID-19 clinical management in Fiji.

Problem: From April to September 2021, Fiji experienced a second wave of coronavirus disease (COVID-19) precipitated by the Delta variant of concern, prompting a need to strengthen existing data management of positive COVID-19 cases. Context: With COVID-19 cases peaking at 1405 a day and many hospital admissions, the need to develop a better way to visualize data became clear. Action: The Fiji Ministry of Health and Medical Services, the World Health Organization and the United Nations Office for the Coordination of Humanitarian Affairs collaborated to develop an online clinical dashboard to support better visualization of case management data. Outcome: The dashboard was used across Fiji at national, divisional and local levels for COVID-19 management. At the national level, it provided real-time reports describing the surge pattern, severity and management of COVID-19 cases across the country during daily incident management team meetings. At the divisional level, it gave the divisional directors access to timely information about hospital and community isolation of cases. At the hospital level, the dashboard allowed managers to monitor trends in isolated cases and use of oxygen resources. Discussion: The dashboard replaced previous paper-based reporting of statistics with delivery of trends and real-time data. The team that developed the tool were situated in different locations and did not meet physically, demonstrating the ease of implementing this online tool in a resource-constrained setting. The dashboard is easy to use and could be used in other Pacific island countries and areas.

How the Commonwealth of the Northern Mariana Islands stalled COVID-19 for 22 months and managed its first significant community transmission.

Objective: The Commonwealth of the Northern Mariana Islands (CNMI) is a remote Pacific island territory with a population of 47 329 that successfully prevented the significant introduction of coronavirus disease (COVID-19) until late 2021. This study documents how the response to the introduction of COVID-19 in CNMI in 2021 was conducted with limited resources without overwhelming local clinical capacity or compromising health service delivery for the population. Methods: Data from COVID-19 case investigations, contact tracing, the Commonwealth's immunization registry and whole genome sequencing were collated and analysed as part of this study. Results: Between 26 March 2020 and 31 December 2021, 3281 cases and 14 deaths due to COVID-19 were reported in CNMI (case fatality rate, 0.4%). While notification rates were highest among younger age groups, hospitalization and mortality rates were disproportionately greater among those aged > 50 years and among the unvaccinated. The first widespread community transmission in CNMI was detected in October 2021, with genomic epidemiology and contact tracing data indicating a single introduction event involving the AY.25 lineage and subsequent rapid community spread. Vaccination coverage was high before widespread transmission occurred in October 2021 and increased further over the study period. Discussion: Robust preparedness and strong leadership generated resilience within the public health sector such that COVID-19 did not overwhelm CNMI's health system as it did in other jurisdictions and countries around the world. At no point was hospital capacity exceeded, and all patients received adequate care without the need for health-care rationing.

The roles of emergency medical teams in response to Samoa's 2019 measles outbreak.

Problem: On 15 November 2019, Samoa's Government declared a state of emergency in response to a rapidly worsening measles outbreak. The outbreak overwhelmed Samoa's health system, necessitating international assistance, including from emergency medical teams (EMTs). Context: Measles spread globally throughout 2019, with cases rising by more than 300% in the first quarter of 2019, as compared with 2018. Given Samoa's low immunization coverage with a measles-containing vaccine at the time, at 40% for the first dose and 28% for the second, the country was soon overwhelmed with measles cases, hospitalizations and deaths. Action: Following a request for international assistance, 18 EMTs from around the world deployed to Samoa, bringing more than 550 additional clinical, public health and logistics personnel to the country's measles response. Working alongside Samoan health workers, EMTs provided critical surge assistance in clinical management, vaccination, surveillance, infection prevention and control, risk communication and community engagement, and mental health and psychosocial support. Outcome: A total of 1867 hospitalized measles patients were treated from 30 September 2019 to 13 January 2020, with 83 measles-related deaths recorded. EMTs provided essential surge support across Samoa's health system during the most acute phase of the response, helping to care for the ill and control the outbreak. Discussion: Samoa's measles response triggered a large-scale and unique EMT activation, with teams integrated into Samoa's hospitals and health centres. The response demonstrated the critical role that EMTs can play in outbreak response and the importance of strong coordination to ensure optimal use of international clinical surge support by a health system in crisis.

Examining the challenges of hospital discharge for patients with a urinary catheter.

BACKGROUND: Patient discharge between acute and secondary care will be viewed differently based on the stakeholder groups involved. Examining these different perceptions may help improve the discharge process and the patient journey from hospital to home. AIMS: To determine the perceptions of community and hospital nursing staff regarding the challenges that exist with the general hospital discharge process for patients with a urinary catheter. METHODS: A survey was created and sent to a wide range of acute and community nurses and the subscriber list of Journal of Community Nursing, Journal of General Practice Nursing and Wound Care Today. FINDINGS: Compared with hospital staff, the opinions of community staff were more negative around the discharge process and post-discharge care and materials. CONCLUSIONS: Results of this survey provide insight into the perceptions of nursing staff into general patient discharge for those with a urinary catheter and help identify the challenges that exist on the patient journey from hospital to home.

Leptomeningeal Carcinomatosis Secondary to Adenocarcinoma of the Breast: A Cadaveric Case Report.

A rare complication of metastatic breast cancer, leptomeningeal carcinomatosis (LC) was discovered during routine cadaveric dissection of a 57-year-old Caucasian female who died from breast cancer metastasis to the brain. This pathology develops in only 5% of patients with metastatic breast cancer and presents with a number of neurological deficits. Progressive neurologic dysfunction is fatal, with a median survival of 10 to 15 weeks. In this case study, we examine the gross and microscopic features of LC and document the infiltration of metastatic cells into the brain parenchyma along the Virchow-Robin spaces.

Spin controlled surface chemistry: alkyl desorption from Si(100)-2×1 by nonadiabatic hydrogen elimination.

An understanding of the role that spin states play in semiconductor surface chemical reactions is currently limited. Herein, we provide evidence of a nonadiabatic reaction involving a localized singlet to triplet thermal excitation of the Si(100) surface dimer dangling bond. By comparing the ß-hydrogen elimination kinetics of ethyl adsorbates probed by thermal desorption experiments to electronic structure calculation results, we determined that a coverage-dependent change in mechanism occurs. At low coverage, a nonadiabatic, inter-dimer mechanism is dominant, while adiabatic mechanisms become dominant at higher coverage. Computational results indicate that the spin crossover is rapid near room temperature and the nonadiabatic path is accelerated by a barrier that is 40 kJ mol-1 less than the adiabatic path. Simulated thermal desorption reactions using nonadiabatic transition state theory (NA-TST) for the surface dimer intersystem crossing are in close agreement with experimental observations.

Risk factors for loss of bone mineral density after curative esophagectomy.

Micronutrient and fat malabsorption and altered enteroendocrine signaling occur after esophagectomy for cancer; however, the impact of malnutrition on bone health in this cohort has not been previously investigated. In this study, the prevalence of osteoporosis increased after curative surgery, associated with disease-specific, treatment-related, and population risk factors. PURPOSE: Improved oncologic outcomes in esophageal cancer (EC) have resulted in increased survivorship and a focus on long-term quality of life. Malnutrition and micronutrient malabsorption are common among patients with EC, but the effect on bone metabolism is not known. The aim of this study was to characterize changes in bone mineral density (BMD) following curative esophagectomy. METHODS: Consecutive disease-free patients who underwent esophagectomy with gastric conduit for pathologically node-negative disease from 2000 to 2014 were included. BMD was assessed at vertebral levels T12-L5 by computed tomography using a simple trabecular region-of-interest attenuation technique, and serum markers of nutritional status and bone metabolism were examined. Independent risk factors for osteoporosis were identified by multivariable logistic regression. RESULTS: Seventy-five consecutive patients were studied. Osteoporosis was present in 25% at diagnosis. BMD declined at 1 and 2 years postoperatively (144.3 ± 45.8 versus 128.6 ± 46.2 and 122.7 ± 43.5 Hounsfield Units (HU), P < 0.0001), with increased osteoporosis prevalence to 38% and 44% (P = 0.049), respectively. No significant postoperative change in vitamin D, calcium, or phosphate was observed, but alkaline phosphatase increased significantly (P < 0.001). While female sex (P = 0.004) and ASA grade (P = 0.043) were independently associated with osteoporosis at diagnosis, age (P = 0.050), female sex (P = 0.023), smoking (P = 0.024), and pathologic T stage (P = 0.023) were independently predictive of osteoporosis at 1 year postoperatively. CONCLUSIONS: Osteoporosis is prevalent among disease-free patients post-esophagectomy for EC, associated with disease-specific, treatment-related, and population risk factors. Strategies which minimize BMD decline should be considered to avoid fragility fractures in this cohort.

Ebola epidemic--Liberia, March-October 2014.

On March 21, 2014, the Guinea Ministry of Health reported the outbreak of an illness characterized by fever, severe diarrhea, vomiting and a high fatality rate (59%), leading to the first known epidemic of Ebola virus disease (Ebola) in West Africa and the largest and longest Ebola epidemic in history. As of November 2, Liberia had reported the largest number of cases (6,525) and deaths (2,697) among the three affected countries of West Africa with ongoing transmission (Guinea, Liberia, and Sierra Leone). The response strategy in Liberia has included management of the epidemic through an incident management system (IMS) in which the activities of all partners are coordinated. Within the IMS, key strategies for epidemic control include surveillance, case investigation, laboratory confirmation, contact tracing, safe transportation of persons with suspected Ebola, isolation, infection control within the health care system, community engagement, and safe burial. This report provides a brief overview of the progression of the epidemic in Liberia and summarizes the interventions implemented.

Review article: Emergency department assessment and management of stab wounds to the neck.

A stab wound to neck is an infrequent but highly important presentation to the ED in Australasia. Injuries to the two large neurovascular bundles that are vital to life might occur with associated injuries to midline aerodigestive structures. A literature review was undertaken to discuss the assessment and management of this injury in the emergency medicine setting.