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First nationwide full-genome characterisation of human-derived Andes virus in Chile: a retrospective genomic epidemiology study.

BACKGROUND: Andes virus (ANDV) is the only hantavirus known to transmit between humans and causes hantavirus cardiopulmonary syndrome in Chile and Argentina. In Chile, ANDV genomic diversity remains incompletely characterised. This study aimed to characterise the genetic diversity, geographical structure, and molecular signatures of ANDV using human clinical samples collected over a 13-year period (2011-24). METHODS: We conducted a retrospective genomic epidemiology study of ANDV infections in Chile. Clinical samples from patients with confirmed ANDV, collected between March 9, 2011, and June 27, 2024, were analysed and sequenced. Clinical and epidemiological data were obtained from diagnostic laboratories and surveillance programmes. Consensus sequences for the S, M, and L segments were generated, and genetic clustering and divergence were assessed using phylogenetic inference and variant calling. FINDINGS: We analysed clinical samples from 58 infected individuals and identified two major genomic variants of ANDV with distinct geographical distributions, defined by regionally structured patterns of nucleotide and amino acid substitutions across the S, M, and L segments: ANDV Chi-North (central Chile) and ANDV-South (southern Chile). No consistent clustering by clinical severity was observed, and no recurrent non-synonymous substitutions were uniquely associated with severe disease. Substitutions previously associated with person-to-person transmission in outbreaks in Argentina were not consistently observed in Chilean sequences, including in four person-to-person transmission cases. Although some substitutions described in ANDV-like viruses were present in the Chi-North lineage, this lineage remained phylogenetically distinct and geographically restricted to central Chile. INTERPRETATION: To our knowledge, this study provides the first nationwide genomic characterisation of human-derived ANDV in Chile. The identification of geographically structured variants indicates that ANDV diversity in Chile is driven by regional diversification rather than clinical outcome. The absence of consistent amino acid signatures associated with disease severity or person-to-person transmission suggests that these phenotypes are unlikely to be explained by viral genetic variation alone. These findings refine current understanding of ANDV evolution and highlight the need for continued integrated genomic surveillance in endemic regions. FUNDING: Agencia Nacional de Investigación y Desarrollo de Chile and National Institutes of Health.

Humans↗

Surprising evolutionary predictions from enhanced ecological realism.

A focus on the eco-evolutionary feedback continually operating between a population's evolution and its environment helps to appreciate the generality of ESS theory. Here we illustrate, through a sequence of four examples, how respecting such feedback in the evolutionary dynamics of quantitative traits may result in qualitatively unexpected outcomes. Reviewing existing insights and complementing these with new results, we show (1) that evolutionary matrix games are fundamentally degenerate and allow a natural unfolding, (2) that selection-driven extinction may not be rare in nature, (3) that evolutionary epidemiology should not rely on R0 maximization, and (4) why the occurrence of Hardy-Weinberg proportions generically requires an evolutionary explanation.

Biological Evolution↗

Tissue management with a new gingival retraction material: a preliminary clinical report.

A new retraction material (Merocel) was evaluated in a clinical trial with 10 selected abutments. Each selected abutment required an anterior single unit. A comparison of probing attachment level, bleeding on probing, and plaque index demonstrated highly successful periodontal maintenance. The main advantage of Merocel retraction material is that it is capable of innocuously expanding the gingival sulcus. This preliminary study suggested that a Merocel strip was a predictable retraction material in conjunction with impression procedures. The material was also evaluated by scanning electron microscopy and demonstrated promise in this investigation. The Merocel strip shows potential for other applications, but limitations of this material indicated that evolution of atraumatic gingival retraction should continue.

Adult↗

[Evolving methods in immunohematology].

The immunogenic nature of erythrocyte polymorphism is in variance with the incompatible transfusion. Indeed, the fixing of an antibody on the corresponding antigen generally condemns the cell concerned with its destruction. Therefore, in order to ensure the immunohemolytic safety of the transfusions, it is necessary to avoid an in vivo encounter between antigens and antibodies, whose feasibility study in vitro is a determining element. Because of the requirement standards of such analyses and the preoccupation with the continuous improvement of transfusion safety, the evolution of the methods used in immunohematology is a constant concern for all those involved in the process. Thus, during the last few years, new technologies have been introduced which aim at improving performance and sometimes implementing alternatives to agglutination. This improvement is not limited to the search for an overall increase in specificity-sensitivity; it also takes into account the capability to detect "the clinically significant" as well as the limitations of human reliability, which justifies the introduction of automation and computerization. The whole of these methodological evolutions associated with that of the performance of reagents, legitimate the need to reconsider the realization of erythrocyte typing and the search for anti-erythrocyte antibodies.

Agglutination Tests↗

Folk biology and the anthropology of science: cognitive universals and cultural particulars.

This essay in the "anthropology of science" is about how cognition constrains culture in producing science. The example is folk biology, whose cultural recurrence issues from the very same domain-specific cognitive universals that provide the historical backbone of systematic biology. Humans everywhere think about plants and animals in highly structured ways. People have similar folk-biological taxonomies composed of essence-based, species-like groups and the ranking of species into lower- and higher-order groups. Such taxonomies are not as arbitrary in structure and content, nor as variable across cultures, as the assembly of entities into cosmologies, materials, or social groups. These structures are routine products of our "habits of mind," which may in part be naturally selected to grasp relevant and recurrent "habits of the world." An experiment illustrates that the same taxonomic rank is preferred for making biological inferences in two diverse populations: Lowland Maya and Midwest Americans. These findings cannot be explained by domain-general models of similarity because such models cannot account for why both cultures prefer species-like groups, although Americans have relatively little actual knowledge or experience at this level. This supports a modular view of folk biology as a core domain of human knowledge and as a special player, or "core meme," in the selection processes by which cultures evolve. Structural aspects of folk taxonomy provide people in different cultures with the built-in constraints and flexibility that allow them to understand and respond appropriately to different cultural and ecological settings. Another set of reasoning experiments shows that Maya, American folk, and scientists use similarly structured taxonomies in somewhat different ways to extend their understanding of the world in the face of uncertainty. Although folk and scientific taxonomies diverge historically, they continue to interact. The theory of evolution may ultimately dispense with the core concepts of folk biology, including species, taxonomy, and teleology; in practice, however, these may remain indispensable to doing scientific work. Moreover, theory-driven scientific knowledge cannot simply replace folk knowledge in everyday life. Folk-biological knowledge is not driven by implicit or inchoate theories of the sort science aims to make more accurate and perfect.

Aged↗

Designing therapeutic strategies for patients with a dominant left ventricle, discordant ventriculo-arterial connections, and unobstructed flow of blood to the lungs.

The palliation of the cyanotic child with a dominant morphologically left ventricle, discordant ventriculo-arterial connections, and obstruction to the pulmonary outflow tract has continued to evolve and mature. The evolution began in the early days of surgical palliation with the Blalock-Taussig shunt, extended to construction of cavopulmonary shunts, if required, and then to the Fontan procedure and its subsequent modifications. This journey took nearly 30 years to complete. There is increasing clinical data to document the beneficial effects of this approach, with ever-improving outcomes. Some aspects of the history of the cavopulmonary shunt have been previously reviewed in this journal and elsewhere, as have analysis of outcomes for some groups of patients considered for surgical completion of the Fontan circulation. While there has been some ongoing interest in ventricular septation since the early success of Sakakibara et al., this approach has largely been abandoned. Considerably more challenges and debate resonate in the surgical algorithms defined for patients whose hearts are characterized by a dominant left ventricle, discordant ventriculo-arterial connections, and unobstructed flow of blood to the lungs. This latter group will be the focus of this review, as will the aetiology of the myocardial hypertrophy that is particularly frequent in this group of patients, its clinical recognition, indeed its anticipation, and the multiple surgical strategies designed to prevent or treat it. All these manoeuvres are considered to optimise suitability for, and outcome from, creation of the Fontan circulation.

Cardiac Surgical Procedures↗

Characterization of Lactobacillus carbohydrate fermentation activity using immobilized cell technique.

A microbial bioreactor based on calcium alginate immobilized Lactobacillus cells coupled to a pH electrode was developed for quantitative determination of carbohydrate fermentation activity. A high biomass (10(10) cfu mL(-)(1)) and particular pregrowth conditions were needed. Reduction of catabolite repression by monosaccharides was achieved by pregrowth in lactose. The evolution of acid production in a continuous flow-stopped flow bioreactor was monitored for different sugar solutions in contact with the immobilized bacteria. The resulting slopes (DeltamV/Deltat) were used to quantify the fermentation capability for a defined sugar related to that of glucose, which was taken as 100%. The procedure is simple, being based on pH variation that can give quantitative results compared to other reported techniques for carbohydrate fermentation pattern from which only qualitative results are obtained. In addition, it offers reduction in time and costs and is a suitable tool for the rapid analysis of isolated strains and in studies of modifications of sugar metabolism in mutants.

Biomass↗

Children's rights: a decade of dispute.

AIM: This paper attempts to raise issues surrounding children's rights against a backdrop of ethical principles and their subsequent interpretation and application in practice. METHOD: Key words have been used to search a selection of electronic databases and a range of 'grey' literature has been reviewed. BACKGROUND: Over a decade ago the United Nations (1989) Convention on the Rights of the Child was ratified, with the exception of two member states (UNICEF 2000). The Human Rights Act (Department of Health 1998) became law in October 2000 in the United Kingdom (UK). Despite a decade of recommendations, guidelines and legislation, children's rights, particularly consent to health care, remain complex and inconsistent. As we move into a new era of human rights involving all members of society, it is timely for nurses in the UK to reflect on the challenges created in attempting to interpret the philosophy of such legislation because such complexity surrounds the interpretation of human rights for many other vulnerable clients within health care. FINDINGS: The interpretation of children's rights continues to be influenced by the evolution of the meanings of childhood. Adults view children's rights from multiple perspectives of best interest, which are determined by their beliefs about children's ability to understand and consent to health care and treatment. An ability and right to consent appears not to be balanced by the right to withhold consent. Inconsistency and ambiguity persist in the law and its interpretation. Adults need to develop a more pragmatic approach to children's rights. This requires better understanding of children and their experiences of health care. CONCLUSION: Until adults develop a more pragmatic ideology in relation to children's rights then a true respect for children's autonomy will not be achieved. Consent will therefore remain an adult and legal prerogative.

Child↗

Evaluation by respirometry of the degradability of retort water using a shale ash and overburden packed column.

Oil shale processing produces an aqueous wastewater stream known as retort water. The fate of the organic content of retort water from the Stuart oil shale project (Gladstone, Queensland) is examined in a proposed packed bed treatment system consisting of a 1:1 mixture of residual shale from the retorting process and mining overburden. The retort water had a neutral pH and an average unfiltered TOC of 2,900 mg 1(-1). The inorganic composition of the retort water was dominated by NH4+. Only 40% of the total organic carbon (TOC) in the retort water was identifiable, and this was dominated by carboxylic acids. In addition to monitoring influent and effluent TOC concentrations, CO2 evolution was monitored on line by continuous measurements of headspace concentrations and air flow rates. The column was run for 64 days before it blocked and was dismantled for analysis. Over 98% of the TOC was removed from the retort water. Respirometry measurements were confounded by CO2 production from inorganic sources. Based on predictions with the chemical equilibrium package PHREEQE, approximately 15% of the total CO2 production arose from the reaction of NH4+ with carbonates. The balance of the CO2 production accounted for at least 80% of the carbon removed from the retort water. Direct measurements of solid organic carbon showed that approximately 20% of the influent carbon was held-up in the top 20cm of the column. Less than 20% of this held-up carbon was present as either biomass or as adsorbed species. Therefore, the column was ultimately blocked by either extracellular polymeric substances or by a sludge that had precipitated out of the retort water.

Biodegradation, Environmental↗

Pneumococcal resistance in the UK.

The first case reports of infection with penicillin-resistant pneumococci (PRP, MIC > 0.1 mg/L) and multidrug-resistant pneumococci were made in Australia in 1967 and South Africa in 1977, respectively. Since this time these organisms have spread to become a worldwide problem. In Europe PRP prevalence rates of up to 40% have been reported from Spain and 58% from Hungary, although there has been considerable national, regional and local variation in these figures. Until recently the UK was considered to have low prevalence of PRP. As recently as 1990, 100% of 7255 strains of pneumococci from 61 centres across the UK were found to be penicillin sensitive. However, there have now been several reports of significant and rising levels of resistance nationwide. Erythromycin resistance has also risen from 2.8% to 8.6% between 1990 and 1995 in England and Wales. At the Northern Ireland Public Health Laboratory (NIPHL) 3171 strains of pneumococci were examined using the oxacillin screening test between 1988 and 1995, during which time the annual rate of penicillin resistance was found to increase from <1% to 10.6%. The proportion of PRP with high-level resistance (MIC > 1 mg/L) increased from 0% to 36% and levels of PRP cross-resistance to cephalosporins and ciprofloxacin were 89% and 78%, respectively, which are amongst the highest in the UK. Similar rates of penicillin resistance have now been reported from several geographically disparate regions in the UK including Liverpool, Manchester and London. The number of laboratories in England and Wales reporting the isolation of PRPs to the Central Public Health Laboratory increased from 23 (3%) in 1987 to 72 (21%) in 1991 and a recent study from this reference laboratory showed that the prevalence of pneumococcal resistance to penicillin had increased 2.5-fold between 1990 and 1995. Clearly both PRP and multidrug-resistant pneumococci are increasing in prevalence in the UK, and this increase is likely to continue. A recent model of the evolution of national PRP prevalence rates describes a slow emergence phase, followed by an exponential growth phase of around 10 years reaching a stationary phase when the proportion of PRP reaches 50%. It is possible that the UK is currently at the beginning of the exponential growth phase of PRP. This has implications for the future treatment of pneumococcal infections in this country and emphasizes the need for new anti-pneumococcal agents. The new quinolone grepafloxacin, which has an MIC90 of 0.25 mg/L for pneumococci, may represent a future alternative oral treatment for multidrug-resistant strains. The activity of this antibiotic against 70 PRPs is compared with that of two other quinolones and macrolides.

Anti-Bacterial Agents↗

Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin.

The prevalence of resistance to a range of antimicrobials was determined for isolates of Streptococcus pneumoniae examined in the PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance study (1999-2000) using NCCLS testing methods and interpretative criteria. Of 3362 pneumococcal isolates collected from 69 centres in 25 countries, 22.1% overall were resistant to penicillin G, with the highest rates of resistance found among isolates from Asia (53.4%), France (46.2%) and Spain (42.1%). Erythromycin A resistance occurred in 31.1% of isolates overall with the highest rates found in Asia (79.6%), France (57.6%), Hungary (55.6%) and Italy (42.9%). Marked geographical differences in the prevalence of both penicillin G (the Netherlands 0%; South Korea 71.5%) and erythromycin A (Sweden 4.7%; South Korea 87.6%) resistance were observed. Asia was characterized by the highest prevalence of resistance, overall, with only eight of 19 antimicrobials (co-amoxiclav, linezolid, vancomycin, teicoplanin, quinupristin/dalfopristin, levofloxacin, moxifloxacin and telithromycin) retaining high activity against isolates of S. pneumoniae from this region. Notable rates of resistance to clarithromycin, azithromycin, co-trimoxazole and tetracycline were observed in the majority of countries submitting isolates of S. pneumoniae to the PROTEKT surveillance study. Fluoroquinolone resistance was low (1%), overall, although 14.3% of 70 isolates from Hong Kong were resistant to levofloxacin and moxifloxacin, all but one of these isolates belonging to a single clone of the 23F serotype. Although, at present, apparently limited to pockets of clonal spread, continued vigilance with regard to the evolution of fluoroquinolone resistance is indicated. Telithromycin (MIC(90) 0.12 mg/L; 99.9% of isolates susceptible) and lin- ezolid (MIC(90) 2 mg/L; 100% of isolates susceptible) were the two most active oral agents tested, both compounds retaining activity against isolates of fluoroquinolone-resistant S. pneumoniae. The results of the PROTEKT surveillance study 1999-2000 emphasize the widespread evolution of resistance to a variety of antimicrobials amongst isolates of S. pneumoniae and demonstrate the potential of telithromycin as a therapeutic option for the treatment of community-acquired respiratory tract infections caused by this organism.

Anti-Bacterial Agents↗

Glaucomatous neurodegeneration and the concept of neuroprotection.

Glaucomatous neurodegeneration is a progressive pathological affair morphologically characterized by RGC death resulting in functional visual deterioration. Although a variety of primary insults ranging from mechanical trauma to ischemia to genetic susceptibility can initiate disease onset, apparently loss of trophic support and excitotoxin release remain the common themes responsible for neuronal damage and eventual cell death by apoptosis. The spread of this damage is perpetuated by secondary degeneration that allows directly injured neurons to release noxious and degenerative substances into the surrounding cells. Neuroprotection is a collective therapeutic approach the aim of which is to provide resilience to such neurons in an effort to prevent or delay progressive neuronal degeneration. At present, definitive neuroprotective therapy remains unachieved despite a variety of approaches having been defined and intensely pursued. However, the evolution in our understanding of glaucoma continues to offer reason for optimism. To this end, we remain unreservedly hopeful in the labor and committed work of dedicated investigators. We are all indebted to them.

Apoptosis↗

Developments in antiepileptic drug therapy.

Development of new antiepileptic drugs has continued to progress, with both the evolution of new drugs, as well as new formulations of old drugs. It is hoped that, with advances in the understanding of the molecular basis of epilepsy, novel antiepileptic drugs will come about through design rather than serendipity. This article concentrates on a selection of the more promising antiepileptic drugs and reviews their recent progress. Felbamate, lamotrigine, vigabatrin, zonisamide, and gabapentin are already in clinical use in certain countries. Stiripentol and other potential antiepileptic drugs are also reviewed. In addition, there have been strategies to improve the pharmacokinetics of currently used antiepileptic drugs and we have concentrated on controlled-release carbamazepine and oxcarbazepine, both available in certain countries. It is, however, increasingly apparent that good comparative studies are needed before definitive advice can be given in the drug treatment of epilepsy.

Anticonvulsants↗

Community-acquired pneumonia.

Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality worldwide and has significant financial implications for health-care systems. The epidemiology and fundamental biology of the disease has evolved, reflecting the human immunodeficiency virus pandemic, increasing world travel, and, as always, poverty. The promise held out by molecular diagnostic technology has yet to deliver in this arena, and antibiotic resistance continues to drive the quest for new antimicrobial agents. The emergence of multidrug-resistant Streptococcus pneumoniae, the microorganism most often implicated as a cause of CAP, continues to threaten treatment options. The evolution of this organism, the persistently high mortality rate associated with CAP, and increasing health-care costs have prompted the publication of guidelines by various authorities that can be used to assist in the initial assessment of the patient and then guide empirical antimicrobial therapy. It is unclear whether these guidelines will have significant impact on cost and mortality, although the trend toward a rational and evidence-based approach to antimicrobial therapy must be a goal to aspire to.

Anti-Bacterial Agents↗

Longitudinal Study of the National Kidney Foundation's (NKF) Kidney Early Evaluation Program (KEEP).

In 2000, the National Kidney Foundation implemented the Kidney Early Evaluation Program (KEEP 2.0) to increase awareness of kidney disease among those at highest risk, and improve outcomes through early detection and referral for care. The KEEP 2.0 screening program identified significant numbers of persons with reduced kidney function, with previously undetected kidney disease risk factors, and with inadequate risk factor control. These data support the evolution to KEEP 3.0, which will continue to identify individuals at high risk for kidney disease, and will address the educational needs of health care providers and consumers, given that preventing and managing kidney disease requires their joint effort. Consumers need to embrace lifestyle behaviors that reduce risk, and adhere to medical recommendations in managing their existing conditions. At the same time, providers need to ensure that the latest evidence-based guidelines in diagnosis and treatment are being implemented in their clinical practice. KEEP 3.0 participants will be randomly assigned to one of several educational programs that vary on whether they provide individually tailored or nontailored information, with long-term follow-up for evaluation of clinical outcomes. Tailored programs may be more successful in supporting behavioral change as these consider the individuals' "readiness to change." In addition, participant-identified providers will be randomly assigned to one of several educational protocols designed to provide evidence-based recommendations for clinical and pharmaceutical management of kidney disease and risk factors; these programs vary on whether they require active or passive participation of providers. Analytic evaluations will examine changes from baseline in participant kidney disease and risk factor status during follow-up, and estimate the influence of the various educational protocols on both process of care measures and clinical outcomes.

Cohort Studies↗

Male killing can select for male mate choice: a novel solution to the paradox of the lek.

In lekking species, intense directional selection is applied to aspects of the male genotype by female choice. Under conventional quantitative genetics theory, the expectation is that this will lead to a rapid loss in additive genetic variance for the trait in question. However, despite female choice, male variation is maintained and hence it pays females to continue choosing. This has been termed the 'paradox of the lek'. Here we present a theoretical analysis of a putative sex-role-reversed lek in the butterfly Acraea encedon. Sex-role reversal appears to have come about because of infection with a male-killing Wolbachia. The bacterium is highly prevalent in some populations, such that there is a dearth of males. Receptive females form dense aggregations, and it has been suggested that males preferentially select females uninfected with the bacterium. As with more conventional systems, this presents a theoretical problem exactly analogous to the lek paradox, namely what maintains female variation and hence why do males continue to choose? We model the evolution of a male choice gene that allows discrimination between infected and uninfected females, and show that the stable maintenance of both female variation and male choice is likely, so long as males make mistakes when discriminating between females. Furthermore, our model allows the maintenance, in a panmictic population, of a male killer that is perfectly transmitted. This is the first model to allow this result, and may explain the long-term persistence of a male killer in Hypolimnas bolina.

Animals↗