Fatal meningitis in a previously healthy young adult caused by Streptococcus pneumoniae serotype 38: an emerging serotype?

BACKGROUND: In December 2001, a fatal case of pneumococcal meningitis in a Marine Corps recruit was identified. As pneumococcal vaccine usage in recruit populations is being considered, an investigation was initiated into the causative serotype. CASE PRESENTATION: Traditional and molecular methods were utilized to determine the serotype of the infecting pneumococcus. The pneumococcal isolate was identified as serotype 38 (PS38), a serotype not covered by current vaccine formulations. The global significance of this serotype was explored in the medical literature, and found to be a rare but recognized cause of carriage and invasive disease. CONCLUSION: The potential of PS38 to cause severe disease is documented in this report. Current literature does not support the hypothesis that this serotype is increasing in incidence. However, as we monitor the changing epidemiology of pneumococcal illness in the US in this conjugate era, PS38 might find a more prominent and concerning niche as a replacement serotype

Disparities in the Prevalence of Osteoporosis and Osteopenia in Men and Women Living in Sub-Saharan Africa, the UK, and the USA

PURPOSE: To review the rising prevalence of osteopenia and osteoporosis in sub-Saharan Africa and the challenges this poses to governments and healthcare services. Using existing studies, we compare the prevalence of osteopenia and osteoporosis in men and women from sub-Saharan Africa to US and UK cohorts. Context-specific disparities in healthcare are discussed particularly the challenges in diagnosis and treatment of osteoporosis. RECENT FINDINGS: There are few epidemiological data describing the burden of osteoporosis in sub-Saharan Africa. In the studies and cohorts presented here, osteoporosis prevalence varies by sex, country and area of residence, but is generally higher in African populations, than has previously been appreciated. Risk factors contributing to poorer bone health include HIV, malnutrition and "inflammaging." Reprioritization towards care of ageing populations is urgently required. Equitable access to implementable preventative strategies, diagnostic services, treatments and pathways of care for bone health (for example embedded within HIV services) need now to be recognized and addressed by policy makers

Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.

Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs). Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system

Early mortality experience in a large military cohort and a comparison of mortality data sources

<p>Abstract</p> <p>Background</p> <p>Complete and accurate ascertainment of mortality is critically important in any longitudinal study. Tracking of mortality is particularly essential among US military members because of unique occupational exposures (e.g., worldwide deployments as well as combat experiences). Our study objectives were to describe the early mortality experience of Panel 1 of the Millennium Cohort, consisting of participants in a 21-year prospective study of US military service members, and to assess data sources used to ascertain mortality.</p> <p>Methods</p> <p>A population-based random sample (n = 256,400) of all US military service members on service rosters as of October 1, 2000, was selected for study recruitment. Among this original sample, 214,388 had valid mailing addresses, were not in the pilot study, and comprised the group referred to in this study as the invited sample. Panel 1 participants were enrolled from 2001 to 2003, represented all armed service branches, and included active-duty, Reserve, and National Guard members. Crude death rates, as well as age- and sex-adjusted overall and age-adjusted, category-specific death rates were calculated and compared for participants (n = 77,047) and non-participants (n = 137,341) based on data from the Social Security Administration Death Master File, Department of Veterans Affairs (VA) files, and the Department of Defense Medical Mortality Registry, 2001-2006. Numbers of deaths identified by these three data sources, as well as the National Death Index, were compared for 2001-2004.</p> <p>Results</p> <p>There were 341 deaths among the participants for a crude death rate of 80.7 per 100,000 person-years (95% confidence interval [CI]: 72.2,89.3) compared to 820 deaths and a crude death rate of 113.2 per 100,000 person-years (95% CI: 105.4, 120.9) for non-participants. Age-adjusted, category-specific death rates highlighted consistently higher rates among study non-participants. Although there were advantages and disadvantages for each data source, the VA mortality files identified the largest number of deaths (97%).</p> <p>Conclusions</p> <p>The difference in crude and adjusted death rates between Panel 1 participants and non-participants may reflect healthier segments of the military having the opportunity and choosing to participate. In our study population, mortality information was best captured using multiple data sources.</p

Complex Consequences of Herbivory and Interplant Cues in Three Annual Plants

Information exchange (or signaling) between plants following herbivore damage has recently been shown to affect plant responses to herbivory in relatively simple natural systems. In a large, manipulative field study using three annual plant species (Achyrachaena mollis, Lupinus nanus, and Sinapis arvensis), we tested whether experimental damage to a neighboring conspecific affected a plant's lifetime fitness and interactions with herbivores. By manipulating relatedness between plants, we assessed whether genetic relatedness of neighboring individuals influenced the outcome of having a damaged neighbor. Additionally, in laboratory feeding assays, we assessed whether damage to a neighboring plant specifically affected palatability to a generalist herbivore and, for S. arvensis, a specialist herbivore. Our study suggested a high level of contingency in the outcomes of plant signaling. For example, in the field, damaging a neighbor resulted in greater herbivory to A. mollis, but only when the damaged neighbor was a close relative. Similarly, in laboratory trials, the palatability of S. arvensis to a generalist herbivore increased after the plant was exposed to a damaged neighbor, while palatability to a specialist herbivore decreased. Across all species, damage to a neighbor resulted in decreased lifetime fitness, but only if neighbors were closely related. These results suggest that the outcomes of plant signaling within multi-species neighborhoods may be far more context-specific than has been previously shown. In particular, our study shows that herbivore interactions and signaling between plants are contingent on the genetic relationship between neighboring plants. Many factors affect the outcomes of plant signaling, and studies that clarify these factors will be necessary in order to assess the role of plant information exchange about herbivory in natural systems

Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world\u27s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km² resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-km² pixels (summarized from 8500 unique temperature sensors) across all the world’s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

The Lancet Global Health Commission on Global Eye Health: vision beyond 2020

Eye health and vision have widespread and profound implications for many aspects of life, health, sustainable development, and the economy. Yet nowadays, many people, families, and populations continue to suffer the consequences of poor access to high-quality, affordable eye care, leading to vision impairment and blindness. In 2020, an estimated 596 million people had distance vision impairment worldwide, of whom 43 million were blind. Another 510 million people had uncorrected near vision impairment, simply because of not having reading spectacles. A large proportion of those affected (90%), live in low-income and middle-income countries (LMICs). However, encouragingly, more than 90% of people with vision impairment have a preventable or treatable cause with existing highly cost-effective interventions. Eye conditions affect all stages of life, with young children and older people being particularly affected. Crucially, women, rural populations, and ethnic minority groups are more likely to have vision impairment, and this pervasive inequality needs to be addressed. By 2050, population ageing, growth, and urbanisation might lead to an estimated 895 million people with distance vision impairment, of whom 61 million will be blind. Action to prioritise eye health is needed now. This Commission defines eye health as maximised vision, ocular health, and functional ability, thereby contributing to overall health and wellbeing, social inclusion, and quality of life. Eye health is essential to achieve many of the Sustainable Development Goals (SDGs). Poor eye health and impaired vision have a negative effect on quality of life and restrict equitable access to and achievement in education and the workplace. Vision loss has substantial financial implications for affected individuals, families, and communities. Although high-quality data for global economic estimates are scarce, particularly for LMICs, conservative assessments based on the latest prevalence figures for 2020 suggest that annual global productivity loss from vision impairment is approximately US$410·7 billion purchasing power parity. Vision impairment reduces mobility, affects mental wellbeing, exacerbates risk of dementia, increases likelihood of falls and road traffic crashes, increases the need for social care, and ultimately leads to higher mortality rates. By contrast, vision facilitates many daily life activities, enables better educational outcomes, and increases work productivity, reducing inequality. An increasing amount of evidence shows the potential for vision to advance the SDGs, by contributing towards poverty reduction, zero hunger, good health and wellbeing, quality education, gender equality, and decent work. Eye health is a global public priority, transforming lives in both poor and wealthy communities. Therefore, eye health needs to be reframed as a development as well as a health issue and given greater prominence within the global development and health agendas. Vision loss has many causes that require promotional, preventive, treatment, and rehabilitative interventions. Cataract, uncorrected refractive error, glaucoma, age-related macular degeneration, and diabetic retinopathy are responsible for most global vision impairment. Research has identified treatments to reduce or eliminate blindness from all these conditions; the priority is to deliver treatments where they are most needed. Proven eye care interventions, such as cataract surgery and spectacle provision, are among the most cost-effective in all of health care. Greater financial investment is needed so that millions of people living with unnecessary vision impairment and blindness can benefit from these interventions. Lessons from the past three decades give hope that this challenge can be met. Between 1990 and 2020, the age-standardised global prevalence of blindness fell by 28·5%. Since the 1990s, prevalence of major infectious causes of blindness—onchocerciasis and trachoma—have declined substantially. Hope remains that by 2030, the transmission of onchocerciasis will be interrupted, and trachoma will be eliminated as a public health problem in every country worldwide. However, the ageing population has led to a higher crude prevalence of age-related causes of blindness, and thus an increased total number of people with blindness in some regions. Despite this progress, business as usual will not keep pace with the demographic trends of an ageing global population or address the inequities that persist in each country. New threats to eye health are emerging, including the worldwide increase in diabetic retinopathy, high myopia, retinopathy of prematurity, and chronic eye diseases of ageing such as glaucoma and age-related macular degeneration. With the projected increase in such conditions and their associated vision loss over the coming decades, urgent action is needed to develop innovative treatments and deliver services at a greater scale than previously achieved. Good eye health at the community and national level has been marginalised as a luxury available to only wealthy or urban areas. Eye health needs to be urgently brought into the mainstream of national health and development policy, planning, financing, and action. The challenge is to develop and deliver comprehensive eye health services (promotion, prevention, treatment, rehabilitation) that address the full range of eye conditions within the context of universal health coverage. Accessing services should not bring the risk of falling into poverty and services should be of high quality, as envisaged by the WHO framework for health-care quality: effective, safe, people-centred, timely, equitable, integrated, and efficient. To this framework we add the need for services to be environmentally sustainable. Universal health coverage is not universal without eye care. Multiple obstacles need to be overcome to achieve universal coverage for eye health. Important issues include complex barriers to availability and access to quality services, cost, major shortages and maldistribution of well-trained personnel, and lack of suitable, well maintained equipment and consumables. These issues are particularly widespread in LMICs, but also occur in underserved communities in high-income countries. Strong partnerships need to be formed with natural allies working in areas affected by eye health, such as non-communicable diseases, neglected tropical diseases, healthy ageing, children's services, education, disability, and rehabilitation. The eye health sector has traditionally focused on treatment and rehabilitation, and underused health promotion and prevention strategies to lessen the impact of eye disease and reduce inequality. Solving these problems will depend on solutions established from high quality evidence that can guide more effective implementation at scale. Evidence-based approaches will need to address existing deficiencies in the supply and demand. Strategic investments in discovery research, harnessing new findings from diverse fields, and implementation research to guide effective scale up are needed globally. Encouragingly, developments in telemedicine, mobile health, artificial intelligence, and distance learning could potentially enable eye care professionals to deliver higher quality care that is more plentiful, equitable, and cost-effective. This Commission did a Grand Challenges in Global Eye Health prioritisation exercise to highlight key areas for concerted research and action. This exercise has identified a broad set of challenges spanning the fields of epidemiology, health systems, diagnostics, therapeutics, and implementation. The most compelling of these issues, picked from among 3400 suggestions proposed by 336 people from 118 countries, can help to frame the future research agenda for global eye health. In this Commission, we harness lessons learned from over two decades, present the growing evidence for the life-transforming impact of eye care, and provide a thorough understanding of rapid developments in the field. This report was created through a broad consultation involving experts within and outside the eye care sector to help inform governments and other stakeholders about the path forward for eye health beyond 2020, to further the SDGs (including universal health coverage), and work towards a world without avoidable vision loss. The next few years are a crucial time for the global eye health community and its partners in health care, government, and other sectors to consider the successes and challenges encountered in the past two decades, and at the same time to chart a way forward for the upcoming decades. Moving forward requires building on the strong foundation laid by WHO and partners in VISION 2020 with renewed impetus to ultimately deliver high quality universal eye health care for all