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Edited by
David Mabey, London School of Hygiene and Tropical Medicine,Martin W. Weber, World Health Organization,Moffat Nyirenda, London School of Hygiene and Tropical Medicine,Dorothy Yeboah-Manu, Noguchi Memorial Institute for Medical Research, University of Ghana,Jackson Orem, Uganda Cancer Institute, Kampala,Laura Benjamin, University College London,Michael Marks, London School of Hygiene and Tropical Medicine,Nicholas A. Feasey, Liverpool School of Tropical Medicine
Despite declining trends, pneumonia remains the most important infectious cause of serious illness and death in young children globally. It is estimated that pneumonia causes almost 800,000 deaths in children under 5 years of age each year, nearly all of which are preventable. Pneumonia is generally a more common cause of death in those countries that have the highest infant mortality rates. Risk factors are malnutrition, HIV infection or exposure and indoor or outdoor air pollution. Lack of access to basic medical care is behind most pneumonia deaths (UNICEF & World Health Organization 2013). This remains a problem in many African countries. Untreated, the case-fatality rate is particularly high in the first year of life.
Edited by
David Mabey, London School of Hygiene and Tropical Medicine,Martin W. Weber, World Health Organization,Moffat Nyirenda, London School of Hygiene and Tropical Medicine,Dorothy Yeboah-Manu, Noguchi Memorial Institute for Medical Research, University of Ghana,Jackson Orem, Uganda Cancer Institute, Kampala,Laura Benjamin, University College London,Michael Marks, London School of Hygiene and Tropical Medicine,Nicholas A. Feasey, Liverpool School of Tropical Medicine
The mortality rate of children less than 5 years of age has decreased by 60% since 1990, with the Millennium Development Goals having been a powerful drive for improvement. However, the reduction has not been evenly distributed throughout the world (UN IGME 2020). Sub-Saharan Africa remains the region with the highest under-5 mortality rate in the world, where 1 child in every 13 dies before celebrating their 5th birthday (UN IGME 2020).
Duchenne muscular dystrophy is a devastating neuromuscular disorder characterized by the loss of dystrophin, inevitably leading to cardiomyopathy. Despite publications on prophylaxis and treatment with cardiac medications to mitigate cardiomyopathy progression, gaps remain in the specifics of medication initiation and optimization.
Method:
This document is an expert opinion statement, addressing a critical gap in cardiac care for Duchenne muscular dystrophy. It provides thorough recommendations for the initiation and titration of cardiac medications based on disease progression and patient response. Recommendations are derived from the expertise of the Advance Cardiac Therapies Improving Outcomes Network and are informed by established guidelines from the American Heart Association, American College of Cardiology, and Duchenne Muscular Dystrophy Care Considerations. These expert-derived recommendations aim to navigate the complexities of Duchenne muscular dystrophy-related cardiac care.
Results:
Comprehensive recommendations for initiation, titration, and optimization of critical cardiac medications are provided to address Duchenne muscular dystrophy-associated cardiomyopathy.
Discussion:
The management of Duchenne muscular dystrophy requires a multidisciplinary approach. However, the diversity of healthcare providers involved in Duchenne muscular dystrophy can result in variations in cardiac care, complicating treatment standardization and patient outcomes. The aim of this report is to provide a roadmap for managing Duchenne muscular dystrophy-associated cardiomyopathy, by elucidating timing and dosage nuances crucial for optimal therapeutic efficacy, ultimately improving cardiac outcomes, and improving the quality of life for individuals with Duchenne muscular dystrophy.
Conclusion:
This document seeks to establish a standardized framework for cardiac care in Duchenne muscular dystrophy, aiming to improve cardiac prognosis.
A rock cairn, with two matchbooks buried beneath, was found on the summit of the highest hill on Thomas Island, Bunger Hills, East Antarctica. The matchbooks are most likely from United States World War II-era ration packs, which were distributed to various military and civilian expeditions from the mid-1940s into the 1950s. Bunger Hills was first visited by United States Navy ‘Operation Highjump’ in February 1947, when a seaplane most likely landed on a marine inlet, rather than a lake as reported previously. Thomas Island was first visited by United States Navy ‘Operation Windmill’ in January 1948, when a survey point was established, and it is probably this location that is marked by the rock cairn. The matchbooks were replaced beneath the cairn and the rocks replaced. Just over 76 years had elapsed between burial of the matchbooks, construction of the cairn and their rediscovery.
We conducted a quantitative analysis of the microbial burden and prevalence of epidemiologically important pathogens (EIP) found on long-term care facilities (LTCF) environmental surfaces.
Methods:
Microbiological samples were collected using Rodac plates (25cm2/plate) from resident rooms and common areas in five LTCFs. EIP were defined as MRSA, VRE, C. difficile and multidrug-resistant (MDR) Gram-negative rods (GNRs).
Results:
Rooms of residents with reported colonization had much greater EIP counts per Rodac (8.32 CFU, 95% CI 8.05, 8.60) than rooms of non-colonized residents (0.78 CFU, 95% CI 0.70, 0.86). Sixty-five percent of the resident rooms and 50% of the common areas were positive for at least one EIP. If a resident was labeled by the facility as colonized with an EIP, we only found that EIP in 30% of the rooms. MRSA was the most common EIP recovered, followed by C. difficile and MDR-GNR.
Discussion:
We found frequent environmental contamination with EIP in LTCFs. Colonization status of a resident was a strong predictor of higher levels of EIP being recovered from his/her room.
Tetralogy of Fallot patients face an elevated risk of developing chylothorax and pleural effusions post-surgery. This patient group exhibits risk factors known to compromise the lymphatic system, such as elevated central venous pressure, pulmonary flow changes, and hypoxia. This study investigates the morphology and function of the lymphatic system in tetralogy of Fallot patients through lymphatic magnetic resonance imaging and near-infrared fluorescence imaging, respectively.
Methods:
Post-repair tetralogy of Fallot patients aged 6–18 years were recruited, along with age and gender-matched controls. Magnetic resonance imaging was used to assess the morphology of the thoracic lymphatic vessels and the thoracic, while near-infrared fluorescence imaging was used to assess lymphatic activity utilising lymph rate, velocity, and pressure.
Results:
Nine patients and 10 controls were included. Echocardiography revealed that 2/3 of the patients had moderate-severe pulmonary regurgitation, while none displayed signs of elevated central venous pressure. Magnetic resonance imaging identified three patients with type 3 (out of 4 types) lymphatic abnormalities, while controls had none. The thoracic ducts showed severe (one patient) and moderate (one patient) tortuosity. Mean thoracic duct diameters were 3.3 mm ±1.1 in patients and 3.0 mm ± 0.8 in controls (p-value = 0.53). Near-infrared fluorescence imaging revealed no anomalous patterns.
Conclusion:
Despite no presence of clinical lymphatic disease, 3/9 of the repaired tetralogy of Fallot patients exhibited lymphatic morphological abnormalities. The significance of these anomalies remains uncertain currently. Further research is needed to determine whether these lymphatic alterations in this patient cohort are a result of congenital malformations, haemodynamic shifts, or prenatal and early-life saturation levels.
Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. We investigated the association of retinal microvascular function, a proxy for microvascular function in the brain, with incidence and trajectories of clinically relevant depressive symptoms.
Methods
Longitudinal data are from The Maastricht Study of 5952 participants (59.9 ± 8.5 years/49.7% women) without clinically relevant depressive symptoms at baseline (2010–2017). Central retinal arteriolar equivalent and central retinal venular equivalent (CRAE and CRVE) and a composite score of flicker light-induced retinal arteriolar and venular dilation were assessed at baseline. We assessed incidence and trajectories of clinically relevant depressive symptoms (9-item Patient Health Questionnaire score ⩾10). Trajectories included continuously low prevalence (low, n = 5225 [87.8%]); early increasing, then chronic high prevalence (early-chronic, n = 157 [2.6%]); low, then increasing prevalence (late-increasing, n = 247 [4.2%]); and remitting prevalence (remitting, n = 323 [5.4%]).
Results
After a median follow-up of 7.0 years (range 1.0–11.0), 806 (13.5%) individuals had incident clinically relevant depressive symptoms. After full adjustment, a larger CRAE and CRVE were each associated with a lower risk of clinically relevant depressive symptoms (hazard ratios [HRs] per standard deviation [s.d.]: 0.89 [95% confidence interval (CI) 0.83–0.96] and 0.93 [0.86–0.99], respectively), while a lower flicker light-induced retinal dilation was associated with a higher risk of clinically relevant depressive symptoms (HR per s.d.: 1.10 [1.01–1.20]). Compared to the low trajectory, a larger CRAE was associated with lower odds of belonging to the early-chronic trajectory (OR: 0.83 [0.69–0.99]) and a lower flicker light-induced retinal dilation was associated with higher odds of belonging to the remitting trajectory (OR: 1.23 [1.07–1.43]).
Conclusions
These findings support the hypothesis that cerebral microvascular dysfunction contributes to the development of depressive symptoms.
Tight focusing with very small f-numbers is necessary to achieve the highest at-focus irradiances. However, tight focusing imposes strong demands on precise target positioning in-focus to achieve the highest on-target irradiance. We describe several near-infrared, visible, ultraviolet and soft and hard X-ray diagnostics employed in a ∼1022 W/cm2 laser–plasma experiment. We used nearly 10 J total energy femtosecond laser pulses focused into an approximately 1.3-μm focal spot on 5–20 μm thick stainless-steel targets. We discuss the applicability of these diagnostics to determine the best in-focus target position with approximately 5 μm accuracy (i.e., around half of the short Rayleigh length) and show that several diagnostics (in particular, 3$\omega$ reflection and on-axis hard X-rays) can ensure this accuracy. We demonstrated target positioning within several micrometers from the focus, ensuring over 80% of the ideal peak laser intensity on-target. Our approach is relatively fast (it requires 10–20 laser shots) and does not rely on the coincidence of low-power and high-power focal planes.
In 2015, the United Nations articulated the ambition to move toward a prosperous, socially inclusive, and environmentally sustainable future for all by adopting the Sustainable Development Goals (SDGs). However, little is known about the pathways that could lead to their concurrent achievement. We provide an overview of the current literature on quantitative pathways toward the SDGs, indicate the commonly used methods and indicators, and identify the most comprehensive pathways that have been published to date. Our results indicate that there is a need for more scenarios toward the full set of SDGs, using a wider range of underlying narratives.
Technical Summary
Quantitative goal-seeking scenario studies could help to explore the needed systems' transformations to implement the 2030 Agenda for Sustainable Development by identifying enabling conditions and accounting for the synergies and trade-offs between the SDGs. Given that the SDGs were adopted some time ago, here, we review the existing global scenario literature to determine what it can offer in this context. We found only a few scenarios that address a large set of SDGs, while many more deal with specific clusters of 2–6 SDGs. We identified the most frequent clusters and compared the results of the most comprehensive sustainable development scenarios. The latter is complicated because of the diversity of methods, indicators, and assumptions used. Therefore, we suggest that an effort is needed to develop a wider set of scenarios that would achieve multiple SDGs, using a more standardized framework of targets and indicators.
Social Media Summary
This study reviews the current global pathways toward the SDGs and shows the need for a broader set of SDG scenarios.
We performed a literature review to describe the risk of surgical-site infection (SSI) in minimally invasive surgery (MIS) compared to standard open surgery. Most studies reported decreased SSI rates among patients undergoing MIS compared to open procedures. However, many were observational studies and may have been affected by selection bias. MIS is associated with reduced risk of surgical-site infection compared to standard open surgery and should be considered when feasible.
Spatially resolved transcriptomics (SRT) is a growing field that links gene expression to anatomical context. SRT approaches that use next-generation sequencing (NGS) combine RNA sequencing with histological or fluorescent imaging to generate spatial maps of gene expression in intact tissue sections. These technologies directly couple gene expression measurements with high-resolution histological or immunofluorescent images that contain rich morphological information about the tissue under study. While broad access to NGS-based spatial transcriptomic technology is now commercially available through the Visium platform from the vendor 10× Genomics, computational tools for extracting image-derived metrics for integration with gene expression data remain limited. We developed VistoSeg as a MATLAB pipeline to process, analyze and interactively visualize the high-resolution images generated in the Visium platform. VistoSeg outputs can be easily integrated with accompanying transcriptomic data to facilitate downstream analyses in common programing languages including R and Python. VistoSeg provides user-friendly tools for integrating image-derived metrics from histological and immunofluorescent images with spatially resolved gene expression data. Integration of this data enhances the ability to understand the transcriptional landscape within tissue architecture. VistoSeg is freely available at http://research.libd.org/VistoSeg/.
To promote equity for intersectionally disaster-vulnerable individuals and address three literature gaps: (1) incremental effects of collective and self-efficacy as preparedness predictors, (2) differentiation of fear and perceived severity of a disaster, and (3) clarification of the relationship between fear and preparedness.
Methods:
Due to infection risks associated with communal housing, early in the coronavirus disease (COVID-19) pandemic, many universities permitted students to remain in campus housing only if they were housing insecure, including many international students. We surveyed intersectionally-vulnerable students and their partners at a southeast US university, N = 54, who were international (77.8%), Asian (55.6%), and/or housing insecure at baseline (79.6%). In 14 waves from May–October 2020, we assessed pandemic preparedness/response behaviors (PPRBs) and potential PPRB predictors.
Results:
We examined within- and between-person effects of fear, perceived severity, collective efficacy, and self-efficacy on PPRBs. Within-person perceived severity and collective efficacy both significantly, positively predicted greater PPRBs. All effects of fear and self-efficacy were not significant.
Conclusions:
Perceived severity and confidence that one’s actions positively impact one’s community fluctuated throughout the pandemic and are linked to greater PPRB engagement. Public health messages and interventions to improve PPRB may benefit from emphasizing collective efficacy and accuracy over fear.
Diagnosing the evolution of laser-generated high energy density (HED) systems is fundamental to develop a correct understanding of the behavior of matter under extreme conditions. Talbot–Lau interferometry constitutes a promising tool, since it permits simultaneous single-shot X-ray radiography and phase-contrast imaging of dense plasmas. We present the results of an experiment at OMEGA EP that aims to probe the ablation front of a laser-irradiated foil using a Talbot–Lau X-ray interferometer. A polystyrene (CH) foil was irradiated by a laser of 133 J, 1 ns and probed with 8 keV laser-produced backlighter radiation from Cu foils driven by a short-pulse laser (153 J, 11 ps). The ablation front interferograms were processed in combination with a set of reference images obtained ex situ using phase-stepping. We managed to obtain attenuation and phase-shift images of a laser-irradiated foil for electron densities above ${10}^{22}\;{\mathrm{cm}}^{-3}$. These results showcase the capabilities of Talbot–Lau X-ray diagnostic methods to diagnose HED laser-generated plasmas through high-resolution imaging.
Viruses are the most numerically abundant biological entities on Earth. As ubiquitous replicators of molecular information and agents of community change, viruses have potent effects on the life on Earth, and may play a critical role in human spaceflight, for life-detection missions to other planetary bodies and planetary protection. However, major knowledge gaps constrain our understanding of the Earth's virosphere: (1) the role viruses play in biogeochemical cycles, (2) the origin(s) of viruses and (3) the involvement of viruses in the evolution, distribution and persistence of life. As viruses are the only replicators that span all known types of nucleic acids, an expanded experimental and theoretical toolbox built for Earth's viruses will be pivotal for detecting and understanding life on Earth and beyond. Only by filling in these knowledge and technical gaps we will obtain an inclusive assessment of how to distinguish and detect life on other planetary surfaces. Meanwhile, space exploration requires life-support systems for the needs of humans, plants and their microbial inhabitants. Viral effects on microbes and plants are essential for Earth's biosphere and human health, but virus–host interactions in spaceflight are poorly understood. Viral relationships with their hosts respond to environmental changes in complex ways which are difficult to predict by extrapolating from Earth-based proxies. These relationships should be studied in space to fully understand how spaceflight will modulate viral impacts on human health and life-support systems, including microbiomes. In this review, we address key questions that must be examined to incorporate viruses into Earth system models, life-support systems and life detection. Tackling these questions will benefit our efforts to develop planetary protection protocols and further our understanding of viruses in astrobiology.
We compared the effectiveness of 4 sampling methods to recover Staphylococcus aureus, Klebsiella pneumoniae and Clostridioides difficile from contaminated environmental surfaces: cotton swabs, RODAC culture plates, sponge sticks with manual agitation, and sponge sticks with a stomacher. Organism type was the most important factor in bacterial recovery.