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Abstract Background Candidemia is an invasive mycosis with an increasing global incidence and high mortality rates in cancer patients. The production of biofilms by some strains of Candida constitutes a mechanism that limits the action of antifungal agents; however, there is limited and conflicting evidence about its role in the risk of death. This study aimed to determine whether biofilm formation is associated with mortality in cancer patients with candidemia. Methods This retrospective cohort study included patients treated at Peru’s oncologic reference center between June 2015 and October 2017. Data were collected by monitoring patients for 30 days from the diagnosis of candidemia until the date of death or hospital discharge. Statistical analyses evaluated the association between biofilm production determined by XTT reduction and mortality, adjusting for demographic, clinical, and microbiological factors assessed by the hospital routinary activities. Survival analysis and bivariate and multivariate Cox regression were used, estimating the hazard ratio (HR) as a measure of association with a significance level of p

Abstract Background Malaria remains a global health challenge, particularly in Peru's Loreto region. Despite ongoing efforts, high infection rates and asymptomatic cases perpetuate transmission. The Peruvian Ministry of Health’s “Zero Malaria Plan” targets elimination. This novel study combines microscopic, molecular, and serological techniques to assess transmission intensity, identify epidemiological risk factors, and characterize species-specific patterns across villages. The findings aim to inform targeted interventions and support broader malaria elimination efforts in line with the Zero Malaria Plan initiative. Methods A cross-sectional malaria survey was conducted in the Zungarococha community, comprising the villages Llanchama (LL), Ninarumi (NI), Puerto Almendra (PA), and Zungarococha (ZG), using microscopic, molecular, and serological techniques to evaluate malaria transmission intensity. Statistical analysis, including multivariate-adjusted analysis, seroprevalence curves, and spatial clustering analysis, were performed to assess malaria prevalence, exposure, and risk factors. Results The survey revealed a high prevalence of asymptomatic infections (6% by microscopy and 18% by PCR), indicating that molecular methods are more sensitive for detecting asymptomatic infections. Seroprevalence varied significantly between villages, reflecting the heterogeneous malaria transmission dynamics. Multivariate analysis identified age, village, and limited bed net use as significant risk factors for malaria infection and species-specific exposure. Seroprevalence curves demonstrated community-specific patterns, with Llanchama and Puerto Almendra showing the highest seroconversion rates for both Plasmodium species. Conclusions The study highlights the diverse nature of malaria transmission in the Loreto region, particularly nothing the pronounced heterogeneity as transmission rates decline, especially in residual malaria scenarios. The use of molecular and serological techniques enhances the detection of current infections and past exposure, aiding in the identification of epidemiological risk factors. These findings underscore the importance of using molecular and serological tools to characterize malaria transmission patterns in low-endemic areas, which is crucial for planning and implementing targeted interventions and elimination strategies. This is particularly relevant for initiatives like the Zero Malaria Plan in the Peruvian Amazon.

BackgroundRapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice.Methods and findingsWe assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza.ConclusionsCOVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like disease. The optimal algorithm is driven by country income level and health budgets, the level of suspicion that the patient may have COVID, and influenza prevalence. Further research to better characterize the unintended effects of corticosteroids, particularly on influenza cases, could improve decision making around the treatment of those with COVID-like symptoms in LMICs.

In this work, we present the novel basket2vec methodology to learn a rich retail basket representation in a latent space with an aim to preserve the co-occurrence relationship between items. We evaluate our methodology using real retail data consisting of millions of transactions; when compared with sparse approaches, our basket2vec methodology showed significant improved performance of at least an order of magnitude. We induced useful geometrical properties to structure the resulting latent space. Furthermore, we show how to use our basket2vec methodology for three applications: $\mathcal {K}$ -means clustering, item recommendation system, and generative modeling. Our basket2vec representation can be regarded as a general analytical tool, to be used in several retail applications, such as: next-item and -basket prediction, basket-level trend evolution analysis, and customer segmentation based on transactional data.

Hepatitis B virus (HBV) and Hepatitis E virus (HEV) are zoonotic pathogens posing significant health concerns in rural Amazonia, a region marked by high endemicity, poverty, and limited healthcare access. However, the epidemiology of HBV and HEV in this ecosystem remains underexplored. This study examines the circulation of HBV and HEV at the human–wildlife interface and identifies risk factors within an isolated Amazonian indigenous community reliant on hunting for subsistence. Antibodies against HBV core antigens (HBcAbs) were found in three wildlife species: Cuniculus paca (0.8%), Tayassu pecari (1.6%), and Mazama americana (4.1%), marking the first record of HBV antibodies in free-ranging wildlife in the Amazon. However, further research is necessary to identify circulating strains and their relation to human HBV. HBcAbs were also detected in 9.1% of human samples, confirming exposure to HBV in the region. HEV IgG antibodies were present in 17.1% of humans and were associated with higher age. All wildlife and domestic animal samples tested negative for HEV, but transmission through consumption of wild animals and contaminated water needs further investigation. The identified risk factors highlight the urgent need for measures to promote safer food handling, improved sanitation, hygiene, and practices related to contact with wild animals.

Abstract Background Rapid diagnostic testing may support improved treatment of COVID patients. Understanding COVID testing and care pathways is important for assessing the impact and cost-effectiveness of testing in the real world, yet there is limited information on these pathways in low-and-middle income countries (LMICs). We therefore undertook an expert consultation to better understand testing policies and practices, clinical screening, the profile of patients seeking testing or care, linkage to care after testing, treatment, lessons learnt and expected changes in 2023. Methods We organized a qualitative consultation with ten experts from seven LMICs (India, Indonesia, Malawi, Nigeria, Peru, South Africa, and Zimbabwe) identified through purposive sampling. We conducted structured interviews during six regional consultations, and undertook a thematic analysis of responses. Results Participants reported that, after initial efforts to scale-up testing, the policy priority given to COVID testing has declined. Comorbidities putting patients at heightened risk (e.g., diabetes) mainly relied on self-identification. The decision to test following clinical screening was highly context-/location-specific, often dictated by local epidemiology and test availability. When rapid diagnostic tests were available, public sector healthcare providers tended to rely on them for diagnosis (alongside PCR for Asian/Latin American participants), while private sector providers predominantly used polymerase chain reaction (PCR) tests. Positive test results were generally taken at ‘face value’ by clinicians, although negative tests with a high index of suspicion may be confirmed with PCR. However, even with a positive result, patients were not always linked to care in a timely manner because of reluctance to receiving care or delays in returning to care centres upon clinical deterioration. Countries often lacked multiple components of the range of therapeutics advised in WHO guidelines: notably so for oral antivirals designed for high-risk mild patients. Severely ill patients mostly received corticosteroids and, in higher-resourced settings, tocilizumab. Conclusions Testing does not always prompt enhanced care, due to reluctance on the part of patients and limited therapeutic availability within clinical settings. Any analysis of the impact or cost-effectiveness of testing policies post pandemic needs to either consider investment in optimal treatment pathways or constrain estimates of benefits based on actual practice.

Summary: In 2023, a series of climatological and political events unfolded, partly driving forward the global climate and health agenda while simultaneously exposing important disparities and vulnerabilities to climate-related events. On the policy front, a significant step forward was marked by the inaugural Health Day at COP28, acknowledging the profound impacts of climate change on health. However, the first-ever Global Stocktake showed an important gap between the current progress and the targets outlined in the Paris Agreement, underscoring the urgent need for further and decisive action. From a Latin American perspective, some questions arise: How do we achieve the change that is needed? How to address the vulnerabilities to climate change in a region with long-standing social inequities? How do we promote intersectoral collaboration to face a complex problem such as climate change? The debate is still ongoing, and in many instances, it is just starting.The renamed regional centre Lancet Countdown Latin America (previously named Lancet Countdown South America) expanded its geographical scope adding Mexico and five Central American countries: Costa Rica, El Salvador, Guatemala, Honduras, and Panama, as a response to the need for stronger collaboration in a region with significant social disparities, including research capacities and funding. The centre is an independent and multidisciplinary collaboration that tracks the links between health and climate change in Latin America, following the global Lancet Countdown's methodologies and five domains. The Lancet Countdown Latin America work hinges on the commitment of 23 regional academic institutions, United Nations agencies, and 34 researchers who generously contribute their time and expertise.Building from the first report, the 2023 report of the Lancet Countdown Latin America, presents 34 indicators that track the relationship between health and climate change up to 2022, aiming at providing evidence to public decision-making with the purpose of improving the health and wellbeing of Latin American populations and reducing social inequities through climate actions focusing on health.This report shows that Latin American populations continue to observe a growing exposure to changing climatic conditions. A warming trend has been observed across all countries in Latin America, with severe direct impacts. In 2022, people were exposed to ambient temperatures, on average, 0.38 °C higher than in 1986–2005, with Paraguay experiencing the highest anomaly (+1.9 °C), followed by Argentina (+1.2 °C) and Uruguay (+0.9 °C) (indicator 1.1.1). In 2013–2022, infants were exposed to 248% more heatwave days and people over 65 years old were exposed to 271% more heatwave days than in 1986–2005 (indicator 1.1.2). Also, compared to 1991–2000, in 2013–2022, there were 256 and 189 additional annual hours per person, during which ambient heat posed at least moderate and high risk of heat stress during light outdoor physical activity in Latin America, respectively (indicator 1.1.3). Finally, the region had a 140% increase in heat-related mortality from 2000–2009 to 2013–2022 (indicator 1.1.4).Changes in ecosystems have led to an increased risk of wildfires, exposing individuals to very or extremely high fire danger for more extended periods (indicator 1.2.1). Additionally, the transmission potential for dengue by Aedes aegypti mosquitoes has risen by 54% from 1951–1960 to 2013–2022 (indicator 1.3), which aligns with the recent outbreaks and increasing dengue cases observed across Latin America in recent months.Based on the 2023 report of the Lancet Countdown Latin America, there are three key messages that Latin America needs to further explore and advance for a health-centred climate-resilient development.Latin American countries require intersectoral public policies that simultaneously increase climate resilience, reduce social inequities, improve population health, and reduce greenhouse gas (GHG) emissions.The findings show that adaptation policies in Latin America remain weak, with a pressing need for robust vulnerability and adaptation (V&A) assessments to address climate risks effectively. Unfortunately, such assessments are scarce. Up to 2021, Brazil is the only country that has completed and officially reported a V&A to the 2021 Global Survey conducted by the World Health Organization (WHO). Argentina, Guatemala, and Panama have also conducted them, but they have not been reported (indicator 2.1.1). Similarly, efforts in developing and implementing Health National Adaptation Plans (HNAPs) are varied and limited in scope. Brazil, Chile, and Uruguay are the only countries that have an HNAP (indicator 2.1.2). Moreover, self-reported city-level climate change risk assessments are very limited in the region (indicator 2.1.3).The collaboration between meteorological and health sectors remains insufficient, with only Argentina, Brazil, Colombia, and Guatemala self-reporting some level of integration (indicator 2.2.1), hindering comprehensive responses to climate-related health risks in the region. Additionally, despite the urgent need for action, there has been minimal progress in increasing urban greenspaces across the region since 2015, with only Colombia, Nicaragua, and Venezuela showing slight improvements (indicator 2.2.2). Compounding these challenges is the decrease in funding for climate change adaptation projects in Latin America, as evidenced by the 16% drop in funds allocated by the Green Climate Fund (GCF) in 2022 compared to 2021. Alarmingly, none of the funds approved in 2022 were directed toward climate change and health projects, highlighting a critical gap in addressing health-related climate risks (indicator 2.2.3).From a vulnerability perspective, the Mosquito Risk Index (MoRI) indicates an overall decrease in severe mosquito-borne disease risk in the region due to improvements in water, sanitation, and hygiene (WASH) (indicator 2.3.1). Brazil and Paraguay were the only countries that showed an increase in this indicator. It is worth noting that significant temporal variation within and between countries still persists, suggesting inadequate preparedness for climate-related changes.Overall, population health is not solely determined by the health sector, nor are climate policies a sole responsibility of the environmental sector. More and stronger intersectoral collaboration is needed to pave development pathways that consider solid adaptation to climate change, greater reductions of GHG emissions, and that increase social equity and population health. These policies involve sectors such as finance, transport, energy, housing, health, and agriculture, requiring institutional structures and policy instruments that allow long-term intersectoral collaboration.Latin American countries need to accelerate an energy transition that prioritises people's health and wellbeing, reduces energy poverty and air pollution, and maximises health and economic gains.In Latin America, there is a notable disparity in energy transition, with electricity generation from coal increasing by an average of 2.6% from 1991–2000 to 2011–2020, posing a challenge to efforts aimed at phasing out coal (indicator 3.1.1). However, this percentage increase is conservative as it may not include all the fossil fuels for thermoelectric electricity generation, especially during climate-related events and when hydropower is affected (Panel 4). Yet, renewable energy sources have been growing, increasing by an average of 5.7% during the same period. Access to clean fuels for cooking remains a concern, with 46.3% of the rural population in Central America and 23.3% in South America lacking access to clean fuels in 2022 (indicator 3.1.2). It is crucial to highlight the concerning overreliance on fossil fuels, particularly liquefied petroleum gas (LPG), as a primary cooking fuel. A significant majority of Latin American populations, approximately 74.6%, rely on LPG for cooking. Transitioning to cleaner heating and cooking alternatives could also have a health benefit by reducing household air pollution-related mortality. Fossil fuels continue to dominate road transport energy in Latin America, accounting for 96%, although some South American countries are increasing the use of biofuels (indicator 3.1.3). Premature mortality attributable to fossil-fuel-derived PM2.5 has shown varied trends across countries, increasing by 3.9% from 2005 to 2020 across Latin America, which corresponds to 123.5 premature deaths per million people (indicator 3.2.1). The Latin American countries with the highest premature mortality rate attributable to PM2.5 in 2020 were Chile, Peru, Brazil, Colombia, Mexico, and Paraguay. Of the total premature deaths attributable to PM2.5 in 2020, 19.1% was from transport, 12.3% from households, 11.6% from industry, and 11% from agriculture.From emission and capture of GHG perspective, commodity-driven deforestation and expansion of agricultural land remain major contributors to tree cover loss in the region, accounting for around 80% of the total loss (indicator 3.3). Additionally, animal-based food production in Latin America contributes 85% to agricultural CO2 equivalent emissions, with Argentina, Brazil, Panama, Paraguay, and Uruguay ranking highest in per capita emissions (indicator 3.4.1). From a health perspective, in 2020, approximately 870,000 deaths were associated with imbalanced diets, of which 155,000 (18%) were linked to high intake of red and processed meat and dairy products (indicator 3.4.2).Energy transition in Latin America is still in its infancy, and as a result, millions of people are currently exposed to dangerous levels of air pollution and energy poverty (i.e., lack of access to essential energy sources or services). As shown in this report, the levels of air pollution, outdoors and indoors, are a significant problem in the whole region, with marked disparities between urban and rural areas. In 2022, Peru, Chile, Mexico, Guatemala, Colombia, El Salvador, Brazil, Uruguay, Honduras, Panama, and Nicaragua were in the top 100 most polluted countries globally. Transitioning to cleaner sources of energy, phasing out fossil fuels, and promoting better energy efficiency in the industrial and housing sectors are not only climate mitigation measures but also huge health and economic opportunities for more prosperous and healthy societies.Latin American countries need to increase climate finance through permanent fiscal commitments and multilateral development banks to pave climate-resilient development pathways.Climate change poses significant economic costs, with investments in mitigation and adaptation measures progressing slowly. In 2022, economic losses due to weather-related extreme events in Latin America were US$15.6 billion –an amount mainly driven by floods and landslides in Brazil–representing 0.28% of Latin America's Gross Domestic Product (GDP) (indicator 4.1.1). In contrast to high-income countries, most of these losses lack insurance coverage, imposing a substantial financial strain on affected families and governments. Heat-related mortality among individuals aged 65 and older in Latin America reached alarming levels, with losses exceeding the equivalent of the average income of 451,000 people annually (indicator 4.1.2). Moreover, the total potential income loss due to heat-related labour capacity reduction amounted to 1.34% of regional GDP, disproportionately affecting the agriculture and construction sectors (indicator 4.1.3). Additionally, the economic toll of premature mortality from air pollution was substantial, equivalent to a significant portion of regional GDP (0.61%) (indicator 4.1.4).On a positive note, clean energy investments in the region increased in 2022, surpassing fossil fuel investments. However, in 2020, all countries reviewed continued to offer net-negative carbon prices, revealing fossil fuel subsidies totalling US$23 billion. Venezuela had the highest net subsidies relative to current health expenditure (123%), followed by Argentina (10.5%), Bolivia (10.3%), Ecuador (8.3%), and Chile (5.6%) (indicator 4.2.1).Fossil fuel-based energy is today more expensive than renewable energy. Fossil fuel burning drives climate change and damages the environment on which people depend, and air pollution derived from the burning of fossil fuels causes seven million premature deaths each year worldwide, along with a substantial burden of disease. Transitioning to sustainable, zero-emission energy sources, fostering healthier food systems, and expediting adaptation efforts promise not only environmental benefits but also significant economic gains. However, to implement mitigation and adaptation policies that also improve social wellbeing and prosperity, stronger and solid financial systems are needed. Climate finance in Latin American countries is scarce and strongly depends on political cycles, which threatens adequate responses to the current and future challenges.Progress on the climate agenda is lagging behind the urgent pace required. While engagement with the intersection of health and climate change is increasing, government involvement remains inadequate. Newspaper coverage of health and climate change has been on the rise, peaking in 2022, yet the proportion of climate change articles discussing health has declined over time (indicator 5.1). Although there has been significant growth in the number of scientific papers focusing on Latin America, it still represents less than 4% of global publications on the subject (indicator 5.3). And, while health was mentioned by most Latin American countries at the UN General Debate in 2022, only a few addressed the intersection of health and climate change, indicating a lack of awareness at the governmental level (indicator 5.4).The 2023 Lancet Countdown Latin America report underscores the cascading and compounding health impacts of anthropogenic climate change, marked by increased exposure to heatwaves, wildfires, and vector-borne diseases. Specifically, for Latin America, the report emphasises three critical messages: the urgent action to implement intersectoral public policies that enhance climate resilience across the region; the pressing need to prioritise an energy transition that focuses on health co-benefits and wellbeing, and lastly, that need for increasing climate finance by committing to sustained fiscal efforts and engaging with multilateral development banks. By understanding the problems, addressing the gaps, and taking decisive action, Latin America can navigate the challenges of climate change, fostering a more sustainable and resilient future for its population.Spanish and Portuguese translated versions of this Summary can be found in Appendix B and C, respectively.The full translated report in Spanish is available in Appendix D.

Despite being cultivated with annual crops, marginal agricultural lands are usually more suitable for grasses, trees, or other perennial vegetation with persistent roots that are better adapted to unfavorable growth conditions. Replacing crops with perennial grassland vegetation (i.e., grassland restoration) on such marginal land can also contribute to realizing positive agroecological outcomes. However, while agroecological principles can guide multiple pathways and management practices, little work has explored the role of marginal agricultural land restoration in soil-based agroecological outcomes. Here we analyzed how soil properties linked with achieving three positive agroecological outcomes (enhanced soil health, higher recycling, and input reduction) are affected by marginal-land restoration and the plant traits of the established vegetation. To do this, we focused on changes in three indicators of these agroecological outcomes: active soil C (soil health), diversity of soil bacterial communities (recycling), and nutrient acquisition via total root biomass (input reduction) measured in three plant-cover types (forest, cropland, restored grassland) in 13 farms distributed in an agricultural landscape in southern Ontario, Canada. Active C and root biomass were highest in forests, intermediate in grasslands and lowest in croplands, while there were no differences in terms of soil bacterial diversity, indicating that restoring land can help achieve some positive agroecological outcomes. Using path analysis, we also found that two plant traits, leaf mass per area (LMA) and leaf dry matter content (LDMC), were key in mediating the link between grassland restoration and agroecological outcomes. Specifically, grassland restoration helped improve indicators of soil health and input reduction via the promotion of vegetation with conservative traits (high LMA and LDMC). Our analytical approach enabled the assessment of the agroecological outcomes after implementing restoration practices, while identifying the most important mechanistic paths mediated by plant traits.

Introduction Understanding human mobility’s role in malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission.Methods We measure community connectivity across the study area using a respondent driven sampling design among key informants who are at least 18 years of age. 45 initial communities will be selected: 10 in Brazil, 10 in Ecuador and 25 in Peru. Participants will be recruited in each initial node and administered a survey to obtain data on each community’s mobility patterns. Survey responses will be ranked and the 2–3 most connected communities will then be selected and surveyed. This process will be repeated for a third round of data collection. Community network matrices will be linked with each country’s malaria surveillance system to test the effects of mobility on disease risk.Ethics and dissemination This study protocol has been approved by the institutional review boards of Duke University (USA), Universidad San Francisco de Quito (Ecuador), Universidad Peruana Cayetano Heredia (Peru) and Universidade Federal Minas Gerais (Brazil). Results will be disseminated in communities by the end of the study.

Image segmentation of the corneal endothelium with deep convolutional neural networks (CNN) is challenging due to the scarcity of expert-annotated data. This work proposes a data augmentation technique via warping to enhance the performance of semi-supervised training of CNNs for accurate segmentation. We use a unique augmentation process for images and masks involving keypoint extraction, Delaunay triangulation, local affine transformations, and mask refinement. This approach accurately captures the natural variability of the corneal endothelium, enriching the dataset with realistic and diverse images. The proposed method achieved an increase in the mean intersection over union (mIoU) and Dice coefficient (DC) metrics of 17.2% and 4.8% respectively, for the segmentation task in corneal endothelial images on multiple CNN architectures. Our data augmentation strategy successfully models the natural variability in corneal endothelial images, thereby enhancing the performance and generalization capabilities of semi-supervised CNNs in medical image cell segmentation tasks.

Fc-mediated antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can contribute to the containment HIV-1 replication but whether such activities are sufficient for protection is unclear. We previously identified an antibody to the variable 2 (V2) apex of the HIV-1 Env trimer (PGT145) that potently directs the lysis of SIV-infected cells by NK cells but poorly neutralizes SIV infectivity. To determine if ADCC is sufficient for protection, separate groups of six rhesus macaques were treated with PGT145 or a control antibody (DEN3) by intravenous infusion followed five days later by intrarectal challenge with SIVmac239. Despite high concentrations of PGT145 and potent ADCC activity in plasma on the day of challenge, all animals became infected and viral loads did not differ between the PGT145- and DEN3-treated animals. To determine if PGT145 can protect against a neutralization-sensitive virus, two additional groups of six macaques were treated with PGT145 and DEN3 and challenged with an SIVmac239 variant with a single amino acid change in Env (K180S) that increases PGT145 binding and renders the virus susceptible to neutralization by this antibody. Although there was no difference in virus acquisition, peak and chronic phase viral loads were significantly lower and time to peak viremia was significantly delayed in the PGT145-treated animals compared to the DEN3-treated control animals. Env changes were also selected in the PGT145-treated animals that confer resistance to both neutralization and ADCC. These results show that ADCC is not sufficient for protection by this V2-specific antibody. However, protection may be achieved by increasing the affinity of antibody binding to Env above the threshold required for neutralization.

Extensive research showcases the extent and efficacy of humor-based messaging in general health promotion. However, the work describing humor’s use within testicular cancer (TC) awareness is less developed. The aim of this comparative critical review was to determine the impact of using humor-based messaging in TC awareness campaigns to achieve a baseline assessment from which future research can be modeled. A literature search was conducted using seven databases to locate relevant literature. Three research questions guided this investigation: (1) To what extent has humor been used in TC awareness campaigns? (2) What does the literature reveal about the use of humor-based messaging on relevant health outcomes? (3) What are the limitations within current TC awareness strategies? Six studies were included in the review, of which three directly assessed the use of humor in TC awareness vis-à-vis intervention designs. Humor-based strategies were implemented to enhance knowledge of TC and testicular self-examination (TSE) procedures, reduce anxiety surrounding detection threat, and promote TSE. The rhetoric provided to men via various health interventions relied on humor and slang to promote TSE among males. Despite the small sample size of the included studies, this review determined that humor may be useful in reducing uncomfortable feelings surrounding TSE, increasing awareness of TC, and promoting TSE. When using humor-based messaging, however, the audience and type of humor implemented must be considered. Limited research exists assessing the long-term impact humor in TC promotion on health behavioral changes, easing anxieties related to detection, and increased self-efficacy surrounding TSE.

Abstract Metabolic disorders are often linked to alterations in insulin signaling. Omega-3 (n-3) fatty acids modulate immunometabolic responses; thus, we examined the effects of peripartum n-3 on systemic and adipose tissue (AT)-specific insulin sensitivity, immune function, and the endocannabinoid system (ECS) in dairy cows. Cows were supplemented peripartum with saturated fat (CTL) or flaxseed supplement rich in alpha-linolenic acid (ALA). Blood immunometabolic biomarkers were examined, and at 5–8 d postpartum (PP), an intravenous glucose-tolerance-test (GTT) and AT biopsies were performed. Insulin sensitivity in AT was assessed by phosphoproteomics and proteomics. Peripartum n-3 reduced the plasma concentrations of Interleukin-6 (IL-6) and IL-17α, lowered the percentage of white blood cells PP, and reduced inflammatory proteins in AT. Systemic insulin sensitivity was higher in ALA than in CTL. In AT, the top canonical pathways, according to the differential phosphoproteome in ALA, were protein-kinase-A signaling and insulin-receptor signaling; network analysis and immunoblots validated the lower phosphorylation of protein kinase B (Akt), and lower abundance of insulin receptor, together suggesting reduced insulin sensitivity in ALA AT. The n-3 reduced the plasma concentrations of ECS-associated ligands, and lowered the abundances of cannabinoid-1-receptor and monoglycerol-lipase in peripheral blood mononuclear cells PP. Peripartum ALA supplementation in dairy cows improved systemic insulin sensitivity and immune function, reduced ECS components, and had tissue-specific effects on insulin-sensitivity in AT, possibly counter-balancing the systemic responses.

Abstract Crop domestication has led to the development of distinct trait syndromes, a series of constrained plant trait trade‐offs to maximize yield in high‐input agricultural environments, and potentially constrained trait plasticity. Yet, with the ongoing transition to organic and diversified agroecosystems, which create more heterogeneous nutrient availability, this constrained plasticity, especially in root functional traits, may be undesirable for nutrient acquisition. Such agricultural systems require a nuanced understanding of the soil‐crop continuum under organic amendments and with intercropping, and the role crop genetic resources play in governing nutrient management and design. In this study, we use a functional traits lens to determine if crops with a range of domestication histories express different functional trait plasticity and how this expression changes with soil amendments and intercropping. We utilize a common garden experiment including five wheat (Triticum aestivum) varietals with a range of domestication histories planted in a factorial combination with amendment type (organic and inorganic) and cropping design (monoculture or intercropped with soybean). We use bivariate, multivariate and trait space analyses to quantify trait variation and plasticity in five leaf and five root functional traits. Almost all leaf and root traits varied among varieties. Yet, amendment type was nearly inconsequential for explaining trait expression across varieties. However, intercropping was linked to significant differences in root acquisitive strategies, regardless of the varietals' distinct history. Our findings show substantial leaf and root trait plasticity, with roots expressing greater trait space occupation with domestication, but also the strong role of management in crop trait expression. We underscore the utility of a functional trait‐based approach to understand plant–soil dynamics with organic amendments, as well as the role of crop genetic histories in the successful transition to low‐input and diversified agroecosystems.

Toxoplasma gondii is a ubiquitous zoonotic protozoan parasite that infects a wide variety range of warm-blooded animals. This study describes the epidemiological scenario of T. gondii in an indigenous community that relies on subsistence hunting in a well-conserved and isolated area of the Peruvian Amazon. The high seropositivity against T. gondii in humans (83.3% IgG and 6.1% IgM), wild mammals (30.45%, 17 species), peri-domestic rodents (10.0% Rattus sp.), and domestic animals (94.1% dogs and 100% cats) indicates the existence of a sylvatic cycle in the community under study. Individual age was found to be positively associated with IgG detection against T. gondii but not with IgM. It is estimated that each family consumed 5.67 infected animals per year with terrestrial species having higher infective rates than arboreal species. The main risk factors included improper handling and cooking of wild meat, poor hygiene practices, and feeding uncooked offal to domestic animals. This scenario results in a continuous process of infection and reinfection within the indigenous community with cats, dogs, and peri-domestic animals becoming infected through the ingestion of infected raw viscera. Our results emphasize the need to promote safe food handling practices and disposal of waste materials from hunted animals in such communities.

Enzyme-linked immunoelectrotransfer blot (EITB) detects antibodies against seven Taenia solium larvae antigens in three protein families (GP50, T24/42, and 8-kDa) with different structures and functions. EITB banding patterns against these antigens in pigs provide information about the course of infection and may discriminate viable cysticercosis. We analyzed the banding patterns and infection outcomes (presence of viable cysts, degenerated cysts, and any cysts) of 512 rural pigs. Banding patterns were grouped into homogenous classes using latent class analysis, and relationships with infection outcomes were assessed. Four classes were identified: 1 (n = 308, EITB-negative or positive for the GP50 family), 2 (n = 127, positive for GP50 (GP50 family), GP42-39 and GP24 (T24/42 family), but negative for 8-kDa antigens), 3 (n = 22, positive for GP50 and T24/42 antigens (GP42-39 and GP24), as well as to 8-kDa bands GP13, GP14, and GP18, but negative for GP21), and 4 (n = 55, positive for GP50 and T24/42 antigens, as well as to 8-kDa antigens GP21 and GP18 in combination). Pigs in classes 3 and 4 were more likely to have viable cysts (72.6% and 96.4%, respectively) than pigs in classes 1 and 2 (0.7% and 27.6%, respectively; p < 0.001). The number of infections with any cysts was higher in classes 3 and 4 (77.3% and 98.2%, respectively) and lower in classes 2 and 1 (34.7% and 4.9%, respectively; p < 0.001). Pigs with viable cysts represented >90% of pigs with any cysts in classes 3 and 4 (94.1% and 98.2%, respectively), while degenerated cysts were frequent among pigs with any cysts in classes 1, 3, and 2 (86.7%, 47.1%, and 43.2%, respectively; p < 0.001). EITB banding patterns strongly correlate with cysticercosis infection status in rural pigs, with classes 3 and 4 being more predictive of viable infections.

Abstract The translation of promising preclinical research into successful trials often fails. One contributing factor is the “Princess and the Pea” problem, which refers to how an initially significant effect size dissipates as research transitions to more complex systems. This work aimed to quantify the effects of spreading variability on sample size requirements. Sample size estimates were performed by Monte Carlo simulation. To simulate the process of progressing from preclinical to clinical studies, nested sigmoidal dose–response transformations with modifiable input parameter variability were used. The results demonstrated that adding variabilty to the dose–response parameters substantially increases sample size requirements compared to standared calculations. Increasing the number of consecutive studies further increases the sample size. These results quantitatively demonstrate how the spread of variability in translational research, which is not typically accounted for, can result in drastic increases in the sample size required to maintain a desired study power.

Abstract Green roofs are promoted to contribute to more resilient cities by enhancing urban ecosystem services and food systems. Extensive, low‐maintenance green roofs experience frequent environmental stresses, which reduce plant survival and growth. Stress‐tolerant plants are therefore used to sustain well‐established services, such as building temperature regulation. However, transitioning extensive green roofs to provide other key urban services, such as food production, involves less tolerant plant species. Although facilitation exerted by stress‐tolerant species (nurses) has been proposed to improve the performance of stress‐intolerant species (protégés) in extensive green roofs, the conditions under which facilitation could occur are not well understood. Therefore, a comprehensive framework is needed that integrates current knowledge on how the performance of protégé species is affected by nurse plants across stress conditions. We present a framework for green roof research that results in a linear model that integrates (i) modern trait–environment theory and (ii) facilitation ecology in a refined stress‐gradient hypothesis (SGH) originally developed following study of other stressful environments. The model makes testable predictions on how phenotypic traits mediate the performance response of protégé species to nurse plants along stress gradients in extensive green roofs. This is not only useful for the analysis of eco‐physiological performance measures directly linked with multifunctionality and ecosystem services, but also demographic or ‘vital’ rates that drive species persistence and plant community maintenance. We discuss a range of applications related to key agricultural and ecological questions arising from contemporary extensive green roof research, such as enhancing conditions for crop production, weed management, plant invasions and biodiversity conservation. We also provide guidelines for the generation of appropriate data and for fitting this model using readily available statistical procedures. Our framework will allow researchers to assess under which environmental conditions nurse–protégé interactions are feasible. We expect the findings from such research to help develop strategies and guidelines for managing environmental conditions that optimize protégé performances that ultimately affect the delivery of ecosystem services in constructed urban green spaces.

Nonmelanoma skin cancer is the most common cancer in the world, and lung cancer is the leading cause of death from cancer. Histologically, squamous cell carcinoma (SCC) is the second most prevalent type of both skin and lung cancers. We report the case of a 38-year-old female with metastatic, poorly differentiated lung SCC detected on chest X-ray after she presented to the hospital with cough and dyspnea. She had had a 7.5 cm moderately differentiated well-circumscribed posterior scalp SCC completely excised eight years earlier. CT scan showed a large right lung mass, nodular filling defect in the left atrium (LA), and metastases to the adrenal glands and the first rib. Her pulmonary tumor extends to the LA via the right superior pulmonary vein, which is rarely reported in the literature. Ultrasound-guided biopsy of the rib mass showed poorly differentiated SCC. The patient received urgent radiotherapy, given superior vena cava and mainstem bronchus compression. Head CT showed no brain metastasis. A biopsy of the left adrenal initially reported an undifferentiated pleomorphic sarcoma; however, a second pathologist reported it as a poorly differentiated carcinoma of lung origin. At least three pathologists verified the specimen, and it had a PD-L1 test with a 1-49% score. An initial echocardiogram confirmed the LA mass. The patient received a Paclitaxel-Carboplatin-Pembrolizumab regimen as the first-line treatment for metastatic SCC. A repeat echocardiogram after cycle 1 showed a decrease in the size of the tumor in the LA. Almost five months after her initial visit, this young woman’s symptoms and performance status have improved post-palliative radiotherapy and chemo-immunotherapy. Follow-up CT showed smaller lung, nodal, adrenal, and costochondral masses, and evidence of necrosis. This case is clinically relevant because it represents a common problem presenting uncommonly. Moreover, it highlights that ultrasound-guided interventions and medical imaging are essential in directing metastatic cancer diagnosis, treatment, and follow-up, especially when pathology cannot confirm but only presume a specific diagnosis.

[This corrects the article DOI: 10.1371/journal.pntd.0009000.].

BackgroundBoth pulmonary and mental health are affected following hospitalization for COVID-19 pneumonia. Pulmonary rehabilitation therapy has demonstrated benefits in improving mental health, but no validated combined programs that include mental health have been proposed. ObjectiveThis article presents the design of a trial that aimed to assess whether the participation in a combined rehabilitation program that includes home-based respiratory physiotherapy and telephone-based psychological support is associated with a greater improvement of pulmonary and mental health outcomes 7-12 weeks after COVID-19 hospitalization discharge compared with posthospital usual care provided by a public Peruvian hospital. MethodsWAYRA (the word for air in the Quechua language) was an open-label, unblinded, two-arm randomized controlled trial. We recruited 108 participants aged 18-75 years who were discharged from the hospital after COVID-19 pneumonia that required >6 liters/minute of supplemental oxygen during treatment. Participants were randomly assigned at a 1:1 ratio to receive the combined rehabilitation program or usual posthospital care provided by a public Peruvian hospital. The intervention consisted of 12 at-home respiratory rehabilitation sessions and 6 telephone-based psychological sessions. The primary outcome was the 6-minute walk distance. Secondary outcomes included lung function, mental health status (depression, anxiety, and trauma), and quality of life. Outcomes were assessed at baseline (before randomization) and at 7 and 12 weeks after hospital discharge to assess the difference between arms. ResultsThis study was funded by the Peruvian National Council of Science Technology and Technology Innovation in July 2020. Ethics approval was obtained on September 2, 2020. Recruitment and data collection occurred between October 2020 and June 2021. Results are expected to be published by the end of 2022. ConclusionsWAYRA was the first randomized controlled trial evaluating combined pulmonary-mental health rehabilitation for hospitalized COVID-19 survivors in resource-limited settings, potentially providing a foundation for the cost-effective scale-up of similar multidisciplinary rehabilitation programs. Trial RegistrationClinicalTrials.gov NCT04649736; https://clinicaltrials.gov/ct2/show/NCT04649736 International Registered Report Identifier (IRRID)RR1-10.2196/36001

Measuring manual-labor performance has been a key element of work scheduling and resource management in many industries. It is performed using a standard data system called Time and Motion Study (TMS). Many industries still rely on direct human effort to execute the TMS methodology which can be time-consuming, error-prone, and expensive. In this paper, we introduce an automatic replacement of the TMS technique that works at two levels of abstraction: primitive and activity actions. We leverage on recent advancements in deep learning methods and employ an encoder-decoder based classifier to recognize primitives and a continuous-time hidden Markov model to recognize activities. We show that our system yields results competitive with those obtained with several common human action recognition models. We also show how our proposed system can help operational decisions by computing productivity indicators such as worker availability, worker performance, and overall labor effectiveness.

Abstract Background The high incidence of Plasmodium vivax infections associated with clinical severity and the emergence of chloroquine (CQ) resistance has posed a challenge to control efforts aimed at eliminating this disease. Despite conflicting evidence regarding the role of mutations of P. vivax multidrug resistance 1 gene (pvmdr1) in drug resistance, this gene can be a tool for molecular surveillance due to its variability and spatial patterns. Methods Blood samples were collected from studies conducted between 2006 and 2015 in the Northern and Southern Amazon Basin and the North Coast of Peru. Thick and thin blood smears were prepared for malaria diagnosis by microscopy and PCR was performed for detection of P. vivax monoinfections. The pvmdr1 gene was subsequently sequenced and the genetic data was used for haplotype and diversity analysis. Results A total of 550 positive P. vivax samples were sequenced; 445 from the Northern Amazon Basin, 48 from the Southern Amazon Basin and 57 from the North Coast. Eight non-synonymous mutations and three synonymous mutations were analysed in 4,395 bp of pvmdr1. Amino acid changes at positions 976F and 1076L were detected in the Northern Amazon Basin (12.8%) and the Southern Amazon Basin (4.2%) with fluctuations in the prevalence of both mutations in the Northern Amazon Basin during the course of the study that seemed to correspond with a malaria control programme implemented in the region. A total of 13 pvmdr1 haplotypes with non-synonymous mutations were estimated in Peru and an overall nucleotide diversity of π = 0.00054. The Northern Amazon Basin was the most diverse region (π = 0.00055) followed by the Southern Amazon and the North Coast (π = 0.00035 and π = 0.00014, respectively). Conclusion This study showed a high variability in the frequencies of the 976F and 1076L polymorphisms in the Northern Amazon Basin between 2006 and 2015. The low and heterogeneous diversity of pvmdr1 found in this study underscores the need for additional research that can elucidate the role of this gene on P. vivax drug resistance as well as in vitro and clinical data that can clarify the extend of CQ resistance in Peru.

Abstract Background Given the absence of consensus diagnostic criteria for giant cell arteritis, clinicians may encounter difficulty with identification of new-onset headache in patients older than age 50 years presenting with visual changes and elevated inflammatory markers, particularly if temporal artery biopsies are performed and negative. Case presentation We present a case of a 57-year-old white man with headache, diplopia, and jaw paresthesia initially diagnosed and managed as steroid-refractory biopsy-negative giant cell arteritis. Further investigation disclosed evidence of soft tissue infiltration into Meckel’s (trigeminal) cave bilaterally. Positron emission tomography suggested the presence of a lymphoproliferative disorder. Histology confirmed the diagnosis of diffuse large B cell lymphoma. Conclusions Metastatic involvement in Meckel’s cave in diffuse large B cell lymphoma is extremely rare and presents a diagnostic challenge. Patients with suspicion of giant cell arteritis should undergo advanced imaging, particularly those with negative biopsy, atypical features, or lack of response to standard therapy, in order to assess for the presence of large-vessel vasculitis or other mimicking pathologies.

Summary: Peru celebrates 200 years of independence in 2021. Over this period of independent life, and despite the turbulent socio-political scenarios, from internal armed conflict to economic crisis to political instability over the last 40 years, Peru has experienced major changes on its epidemiological and population health profile. Major advancements in maternal and child health as well as in communicable diseases have been achieved in recent decades, and today Peru faces an increasing burden of non-communicable diseases including mental health conditions. In terms of the configuration of the public health system, Peru has also strived to secure country-wide optimal health care, struggling in particular to improve primary health care and intercultural services. The science and technology infrastructure has also evolved, although the need for substantial investments remains if advancing science is to be a national priority. Climate change will also bring significant challenges to population health given Peru's geographical and microclimates diversity. Looking back over the 200-years of independence, we present a summary of key advances in selected health-related fields, thus serving as the basis for reflections on pending agendas and future challenges, in order to look forward to ensuring the future health and wellbeing of the Peruvian population. Resumen (translated abstract): El Perú cumple 200 años de independencia en 2021. Durante estos dos siglos de vida independiente, junto con periodos sociales y políticos turbulentos, incluyendo un conflicto armado interno, hiperinflación y la inestabilidad política de los últimos 40 años, el Perú ha experimentado importantes cambios en su perfil epidemiológico con repercusiones directas en la salud de la población. En las últimas décadas, los indicadores de salud materno-infantil y de las enfermedades transmisibles muestran mejoría importante, pero el país se enfrenta de manera simultánea a una carga cada vez mayor de enfermedades no transmisibles y de salud mental. En cuanto a los sistemas de salud pública, se han realizado esfuerzos por aumentar la cobertura y calidad de la atención de salud en todo el país, apostándose en particular por mejorar la atención primaria. La ciencia y tecnología relacionadas con la salud también han mejorado, aunque si se quiere que la ciencia sea una prioridad nacional, son necesarias inversiones sustanciales. El cambio climático traerá importantes desafíos para la salud de la población, dada la diversidad geográfica y de microclimas del país. Para conmemorar los 200 años de vida independiente del Perú, presentamos un resumen de avances clave en diversas áreas y temas relacionados con la salud. Este repaso sirve como base para reflexionar sobre agendas y desafíos pendientes y futuros, con el fin de asegurar la salud y el bienestar de la población peruana en las próximas décadas.

Leishmaniasis is a disease of public importance with a complex transmission cycle. A quantitative PCR was developed by using the small subunit of the ribosomal RNA gene (SSU rRNA) as a DNA target, which is conserved in all Leishmania species. A TaqMan ® probe was designed to have a high specificity. In all, 22 out of 23 (95.7%) ticks classified as R. microplus tested positive for Leishmania sp. The quantification was between 34.1 and 2197.1 parasites per tick in a range of 12 to 769 fg/uL. In addition, 9 out of 10 (90%) ticks classified as Amblyomma sabanerae tested positive for Leishmania sp. The quantification was between 448.6 and 5428.6 parasites per tick in a range of 157 to 1900 fg/µL. Leishmania sp. was identified in very high percentages in Rhipicephalus microplus and Amblyomma sabanerae from wild Pecari tajacu and Chelonoidis denticulata, in quantities of 34.1 and 5428.6 parasites per arthropod, and this could suggest that the ticks were parasitized by sucking blood from the animals from which they were collected. This is the first report about Leishmania parasites found in wild Rhipicephalus microplus and Amblyomma sabanerae, adding new information about the distribution and epidemiology of the parasite in sylvatic areas.

Perivascular adipose tissue (PVAT) may connect adiposity to hypertension because of its vasoactive functions and proximity to blood vessels. We hypothesized that immune cell changes in PVATs precede the development of high fat diet (HFD)-induced hypertension. Both sexes of Dahl S rat become equally hypertensive when fed a HFD. Further, both sexes would have similar immune cell composition in PVATs with the development and progression of hypertension. Male and female Dahl S rats were fed a regular (10% calories from fat; CD) diet or a HFD (60%) from weaning. PVATs from around the thoracic aorta (APVAT) and small mesenteric vessels (MRPVAT) were harvested at 10 weeks (pre-hypertensive), 17 weeks (onset), or 24 (hypertensive) weeks on diet. RNA-sequencing in MRPVAT at 24 weeks indicated sex-differences with HFD (>CD) and diet-differences in males (>females). The top 2 out of 7 immune processes with the maximum number of differentially expressed genes (DEGs) were associated with immune effector processes and leukocyte activation. Macrophages and T cells (and their activation status), neutrophils, mast, B and NK cells were measured by flow cytometry. Sex-specific changes in the number of CD4 memory T cells (males > females) and M2-like macrophages (females > males) in PVATs occur with a HFD before hypertension developed. Sex-differences became more prominent with the development and progression of hypertension, driven by the diet (HFD > CD). These findings suggest that though the magnitudes of increased blood pressure were equivalent in both sexes, the associated phenotypic changes in the immune subsets within the PVATs were different in the male vs. the female with the development and progression of hypertension.

The need for fast, inexpensive, and robust medical technology is now more crucial than ever [...]

The Peruvian-Brazilian border is a highly endemic tegumentary leishmaniasis region in South America. The interoceanic highway is a commercial route that connects Peru and Brazil through Madre de Dios and has raised concerns about its impact on previously undisturbed areas. In order to assess leishmaniasis transmission risk along this highway, we conducted a surveillance study of the sand fly populations in this area. Sand flies were collected between 2009 and 2010 along transects at 200 m, 600 m and 1000 m from six study sites located along the highway (Iberia, La Novia, Alto Libertad, El Carmen, Florida Baja, Mazuko and Mavila) and an undisturbed area (Malinowski). Collected specimens were identified based on morphology and non-engorged females of each species were pooled and screened by kinetoplast PCR to detect natural Leishmania infections. A total of 9,023 specimens were collected belonging to 54 different Lutzomyia species including the first report of Lu. gantieri in Peru. Four species accounted for 50% of all specimens (Lutzomyia carrerai carrerai, Lu. davisi, Lu. shawi and Lu. richardwardi). El Carmen, Alto Libertad, Florida Baja and Malinowski presented higher Shannon diversity indexes (H = 2.36, 2.30, 2.17 and 2.13, respectively) than the most human disturbed sites of Mazuko and La Novia (H = 1.53 and 1.06, respectively). PCR detected 10 positive pools belonging to Lu. carrerai carrerai, Lu. yuilli yuilli, Lu. hirsuta hirsuta, Lu. (Trichophoromyia) spp., and Lu. (Lutzomyia) spp. Positive pools from 1,000 m transects had higher infectivity rates than those from 600 m and 200 m transects (9/169 = 5.3% vs 0/79 = 0% and 1/127 = 0.8%, p = 0.018). El Carmen, accounted for eight out of ten positives whereas one positive was collected in Florida Baja and Mazuko each. Our study has shown differences in sand fly diversity, abundance and species composition across and within sites. Multiple clustered Lutzomyia pools with natural Leishmania infection suggest a complex, diverse and spotty role in leishmaniasis transmission in Madre de Dios, with increased risk farther from the highway.

Background: The 1997–98 El Niño/Southern Oscillation (ENSO) was one of the most important natural disasters in 20th century Peru, associated with heavy rainfall and flooding. It affected 502 000 people, ruined 944 km of roads, and damaged 580 health centres and 956 schools. Almost a quarter of all people affected (23%) came from Piura, in the northwest of Peru. In this study, we assessed the association between the 1997–98 ENSO and growth stunting in children younger than 5 years on Peru's north coast. Methods: We analysed Peruvian Demographic and Health Survey (DHS) data, from 1996 and 2000, using a double-difference approach. Our primary outcome was childhood growth stunting, and our exposure was the ENSO phenomenon. The exposed group was from Peru's Piura coast, and the unexposed group was from southern coastal regions, which were less affected by the events associated with ENSO 1997–98. First, we conducted a regional comparison. Secondly, we used propensity score matching (PSM) to explore similarities between the exposed and non-exposed groups. We then estimated adjusted prevalence ratios (PR) of childhood growth stunting using generalised linear models. Finally, we conducted a subanalysis by childhood age. Findings: We studied 2270 and 1349 children younger than 5 years from 1996 and 2000, respectively. Regression without matching showed a PR of 1·37 (95% CI 0·93–2·01), and a PSM regression 1-to-2 PR of 1·45 (0·66–3·18), obtaining a PR greater than 1 but with a confidence interval that included the null value. Furthermore, we found a possible effect on children aged 0–11 months. In the regressions without PSM, analysis for this age group showed a PR of 2·48 (1·11–5·54); whereas, after PSM 1-to-2, the PR was 2·69 (1·03–7·03); alternative PSM was also consistent with these results. Analysis of the other age groups yielded results that were not statistically significant. Interpretation: Our results suggest that the ENSO phenomenon could have increased childhood stunting on the coast of Piura. More specifically, children who were aged 0 to 11 months during the worst and most disruptive period of the El Niño phenomenon were at increased risk of growth stunting. Our results were consistent with and without PSM. Factors that might have contributed to our results include increased childhood morbidity with concurrent reductions in maternal and familial access to health care, and diminished household incomes due to El Niño's devastating effects during the disaster period. Our findings outline a need to prevent harm to people and their health during weather and natural events associated with ENSO. Specifically, there is a need for childhood-focused social protection systems, especially during critical stages of growth and development. Childhood-focused social protection and delivery systems will be instrumental in preventing downstream effects of similar climatic events. Funding: Fogarty 2D43 TW007393.

Wheat is the most widely grown food crop, with 761 Mt produced globally in 2020. To meet the expected grain demand by mid-century, wheat breeding strategies must continue to improve upon yield-advancing physiological traits, regardless of climate change impacts. Here, the best performing doubled haploid (DH) crosses with an increased canopy photosynthesis from wheat field experiments in the literature were extrapolated to the global scale with a multi-model ensemble of process-based wheat crop models to estimate global wheat production. The DH field experiments were also used to determine a quantitative relationship between wheat production and solar radiation to estimate genetic yield potential. The multi-model ensemble projected a global annual wheat production of 1050 ± 145 Mt due to the improved canopy photosynthesis, a 37% increase, without expanding cropping area. Achieving this genetic yield potential would meet the lower estimate of the projected grain demand in 2050, albeit with considerable challenges.

Abstract Malaria has steadily increased in the Peruvian Amazon over the last five years. This study aimed to determine the parasite prevalence and micro-geographical heterogeneity of Plasmodium vivax parasitaemia in communities of the Peruvian Amazon. Four cross-sectional active case detection surveys were conducted between May and July 2015 in four riverine communities in Mazan district. Analysis of 2785 samples of 820 individuals nested within 154 households for Plasmodium parasitaemia was carried out using light microscopy and qPCR. The spatio-temporal distribution of Plasmodium parasitaemia, dominated by P. vivax, was shown to cluster at both household and community levels. Of enrolled individuals, 47% had at least one P. vivax parasitaemia and 10% P. falciparum, by qPCR, both of which were predominantly sub-microscopic and asymptomatic. Spatial analysis detected significant clustering in three communities. Our findings showed that communities at small-to-moderate spatial scales differed in P. vivax parasite prevalence, and multilevel Poisson regression models showed that such differences were influenced by factors such as age, education, and location of households within high-risk clusters, as well as factors linked to a local micro-geographic context, such as travel and occupation. Complex transmission patterns were found to be related to human mobility among communities in the same micro-basin.

Malaria: Inhibiting parasite invasion of red blood cells A vaccine targeting a protein complex that allows malaria-causing parasite to enter red blood cells has been produced. Malaria caused by the parasite Plasmodium falciparum is an oft-deadly infectious disease without an effective vaccine. A team of researchers at the National Institutes of Health led by Prakash Srinivasan, currently at the Johns Hopkins Malaria Research Institute, United States, demonstrated the efficacy of a vaccine candidate that works by priming a host’s immune system to a parasitic protein complex required to form a junction with red blood cells, allowing entry and proliferation of the pathogen. The group’s vaccine conferred more effective protection in monkeys than prior candidates that targeted only one component of the parasitic protein complex. This research warrants a closer look into how this candidate, and others targeting the protein complex, can be used to prevent malaria in humans.

A brief introduction to the development of the homotopy perturbation method is given, and the main milestones are elucidated with more than 90 references. This paper further improves the method by constructing a homotopy equation with one or more auxiliary parameters embedding in the linear term with a clear advantage in accelerating and controlling the approximation convergence speed. Moreover, a revision of a recent amplitude-period approximation formula is presented providing an answer to an open problem related to the optimal approximation along with a new universal formula. Duffing equation is used as an example to illustrate the solution process for the homotopy perturbation method, and only one or few iterations are needed in practical applications, making the method much attractive. From the side of amplitude-period formulation, the nonlinear pendulum, the Duffing equation and an oscillator with discontinuity are analyzed providing an asymptotic exact equivalence for bigger parameter values in the case of Duffing’s system. This mini review gives a tutorial guideline for practical applications of the homotopy perturbation method, the references are not exhaustive.

ABSTRACT As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins. Thus, HIV-1 Env-specific antibodies do not typically cross-react with the Env proteins of SIVsmm/mac isolates. Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity. Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody. Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization. These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers. To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization. IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity. This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.

Urinary tract infections (UTIs) are a common human infection. Antibiotic resistance in extended-spectrum β-lactamase (ESBL)-producing uropathogenic E. coli (UPEC) is a major therapeutic challenge due to limited treatment alternatives. The aim was to characterize the antimicrobial resistance (AMR) and dynamics of ESBL-producing UPEC isolates from UTI cases seen at a local hospital in Cusco, Peru. Ninety-nine isolates from respective patients were characterized against 18 different antibiotics. Latent class analysis (LCA) was used to evaluate the dynamics across the study time according to resistance patterns. The median age of patients was 51 years old, and nearly half were women. ESBL-producing UPEC isolates were slightly more frequent in outpatient services than emergency rooms, and there were higher resistance rates in males compared to females. Half of the ESBL producers were resistant to aminoglycosides and nitrofurantoin. Cefoxitin and fosfomycin resistance was 29.3% and 14.1%, respectively. Resistance to carbapenems was not observed. All isolates were multidrug-resistant bacteria, and 16.2% (16/99) were also classified as extensively drug-resistant bacteria. The resistance patterns varied across the study time and differed regarding sex and healthcare service. The study revealed high levels of AMR to commonly used antimicrobials and a dynamic circulation of ESBL-producing UPEC isolates with varying resistance patterns.

Background: The parasite of the genus Leishmania causes a neglected disease known as leishmaniasis, which has different clinical aspects depending on the species that infects the person and the immune response of the patient. The objective was to determine, using molecular biology, the current circulating species of Leishmania in biopsies of different types of cutaneous leishmaniasis (CL) from the endemic district in the region of “Madre de Dios”, Peru. Methods: The study's 19 samples were obtained in the Huepethue district in the “Madre de Dios” region from patients who were diagnosed for suspected leishmaniasis infection with three clinical manifestations. These were analyzed using kDNA-PCR, Nested-PCR and HRM-PCR to identify the genus of an infecting parasite as well as its species. Results: kDNA-PCR detected all tests for the genus of Leishmania to be positive, while the Nested-PCR could not detect 20.9% of species (one L. (V.) braziliensis and three L. (V.) amazonensis), and the HRM-PCR detected all species presented in the samples. The most prevalent species was L. (V.) braziliensis (73.7%), and the clinical manifestations were ulcers (63.2%), superficial scabs (5.3%) and diffuse form (5.3%), followed by L. (V.) amazonensis (15.8%), manifesting ulcers (15.6%), and L. (V.) lainsoni (10.5%), manifesting superficial scabs (5.3%) and ulcers (5.3%). L. (V.) braziliensis, L. (V.) amazonensis and L. (V.) lainsoni were detected effectively using HRM-PCR in the samples with different clinical manifestations. Conclusions: Highlighting the findings of a high diversity of Leishmania species using High Resolution Melting PCR in biopsies with different clinical manifestations of cutaneous leishmaniasis. Keywords: Leishmania, Clinical manifestations, PCR, Genotyping, Cutaneous leishmaniasis

The conventional reading of the skin prick test (SPT) for diagnosing allergies is prone to inter- and intra-observer variations. Drawing the contours of the skin wheals from the SPT and scanning them for computer processing is cumbersome. However, 3D scanning technology promises the best results in terms of accuracy, fast acquisition, and processing. In this work, we present a wide-field 3D imaging system for the 3D reconstruction of the SPT, and we propose an automated method for the measurement of the skin wheals. The automated measurement is based on pyramidal decomposition and parametric 3D surface fitting for estimating the sizes of the wheals directly. We proposed two parametric models for the diameter estimation. Model 1 is based on an inverted Elliptical Paraboloid function, and model 2 on a super-Gaussian function. The accuracy of the 3D imaging system was evaluated with validation objects obtaining transversal and depth accuracies within ± 0.1 mm and ± 0.01 mm, respectively. We tested the method on 80 SPTs conducted in volunteer subjects, which resulted in 61 detected wheals. We analyzed the accuracy of the models against manual reference measurements from a physician and obtained that the parametric model 2 on average yields diameters closer to the reference measurements (model 1: -0.398 mm vs. model 2: -0.339 mm) with narrower 95% limits of agreement (model 1: [-1.58, 0.78] mm vs. model 2: [-1.39, 0.71] mm) in a Bland-Altman analysis. In one subject, we tested the reproducibility of the method by registering the forearm under five different poses obtaining a maximum coefficient of variation of 5.24% in the estimated wheal diameters. The proposed method delivers accurate and reproducible measurements of the SPT.

The co-occurrence between anxiety and depression symptoms among children with anxiety disorders is well-known, yet there is considerable heterogeneity in terms of explanatory factors. Although cognitive–affective processes have been hypothesized to play a prominent role, surprisingly, no research to date has examined the role of anxiety sensitivity in this co-occurrence. The present investigation examined the role of anxiety sensitivity in the co-occurrence of anxiety and depression symptoms among clinically anxious children. We expected that anxiety sensitivity would moderate the co-occurrence between anxiety and depression symptoms, such that higher anxiety would be related to higher depression among boys and girls with high (but not low) anxiety sensitivity. Participants ( N = 44, age range = 8–12 years; 52% female; 52% African American) were interviewed with the Anxiety Disorders Interview Schedule-IV: Children and Parent Versions and completed self-report measures of anxiety sensitivity, anxiety, and depression symptom severity. Controlling for child age, moderation analyses revealed that higher anxiety was related to higher depression only among girls with high anxiety sensitivity. Among girls with low anxiety sensitivity, the relation between anxiety and depression symptoms was not significant. Anxiety and depression symptoms were strongly correlated among clinically anxious boys irrespective of their levels of anxiety sensitivity. Anxiety sensitivity is an important factor related to anxiety–depression symptom co-occurrence among clinically anxious females in particular. Targeted interventions focused on anxiety sensitivity reduction may prove useful for reducing anxiety–depression symptom co-occurrence among clinically anxious girls. Future research should explore additional moderators that may explain the high correlation between anxiety and depressive symptoms observed among clinically anxious boys.

Training in Biomedical Informatics is essential to meet the challenges of a globalized world. However, the development of postgraduate training and research programs in this area are scarce in Latin America. Through QUIPU: Andean Center for Training and research in Iformatics for Global Health, has developed the first Certificate and Master’s Program on Biomedical Informatics in the Andean Region. The aim of this article is to describe the experience of the program. To date, 51 students from Peru, Chile, Ecuador, Colombia and Venezuela have participated; they come from health ministries, hospitals, universities, research centers, professional associations and private companies. Seventeen courses were offered with the participation of faculty from Argentina, Chile, Colombia, USA, Mexico and Peru. This program is already institutionalized at the School of Public Health and Administration from the Universidad Peruana Cayetano Heredia.

Cutaneous leishmaniasis (CL) is an important health problem in the New World affecting civilian and military populations that are frequently exposed in endemic settings. The Peruvian region of Madre de Dios located near the border with Brazil is one of the most endemic CL regions in South America with more than 4,451 reported cases between 2010 and 2015 according to the Peruvian epidemiology directorate. However, little is known regarding the diversity and distribution of sand fly vectors in this region. In this study, we aimed to characterize the sand fly fauna in this endemic setting and identify sand fly species naturally infected with Leishmania possibly involved in pathogen transmission.Sand fly collections were carried out during 2014 and 2015 in the communities of Flor de Acre, Villa Primavera, Mavila and Arca Pacahuara using CDC light traps and Shannon traps. Collected specimens were identified and non-blood-fed females were selected for Leishmania infection screening using kinetoplastid DNA-PCR (kDNA-PCR) and nested Real time PCR for species identification.A total of 10,897 phlebotomines belonging to the genus Lutzomyia (58 species) and Brumptomyia (2 species) were collected. Our study confirmed the widespread distribution and abundance of Lutzomyia (Trichophoromyia) spp. (24%), Lu. whitmani (19.4%) and Lu. yucumensis (15.8%) in the region. Analysis of Shannon diversity index indicates variability in sand fly composition across sites with Villa Primavera presenting the highest sand fly diversity and abundance. Leishmania screening by kDNA-PCR resulted in 45 positive pools collected from Flor de Acre (34 pools), Mavila (10 pools) and Arca Pacahuara (1 pool) and included 14 species: Lu. yucumensis, Lu. aragoi, Lu. sallesi, Lu. sherlocki, Lu. shawi, Lu. walkeri, Lu nevesi, Lu. migonei, Lu. davisi, Lu. carrerai, Lu. hirsuta, Lu. (Trichophoromyia) spp., Lu. llanosmartinsi and Lu. whitmani. Lutzomyia sherlocki, Lu. walkeri and Lu. llanosmartinsi had the highest infection rates (8%, 7% and 6%, respectively). We identified Leishmania guyanensis in two Lu. whitmani pools, and L. braziliensis in two Lu. llanosmartinsi pools and one Lu. davisi pool.Based on our collections there is high sand fly diversity in Madre de Dios, with differences in sand fly abundance and species composition across sites. We identified 14 sand fly species naturally infected with Leishmania spp., having detected natural infection with L. (V.) guyanensis and L. (V.) braziliensis in three sand fly species. These results suggest the presence of several potential vectors that vary in their spatial and geographical distribution, which could explain the high prevalence of CL cases in this region.

ABSTRACT Whole-genome sequencing (WGS) of microbial pathogens from clinical samples is a highly sensitive tool used to gain a deeper understanding of the biology, epidemiology, and drug resistance mechanisms of many infections. However, WGS of organisms which exhibit low densities in their hosts is challenging due to high levels of host genomic DNA (gDNA), which leads to very low coverage of the microbial genome. WGS of Plasmodium vivax, the most widely distributed form of malaria, is especially difficult because of low parasite densities and the lack of an ex vivo culture system. Current techniques used to enrich P. vivax DNA from clinical samples require significant resources or are not consistently effective. Here, we demonstrate that selective whole-genome amplification (SWGA) can enrich P. vivax gDNA from unprocessed human blood samples and dried blood spots for high-quality WGS, allowing genetic characterization of isolates that would otherwise have been prohibitively expensive or impossible to sequence. We achieved an average genome coverage of 24×, with up to 95% of the P. vivax core genome covered by ≥5 reads. The single-nucleotide polymorphism (SNP) characteristics and drug resistance mutations seen were consistent with those of other P. vivax sequences from a similar region in Peru, demonstrating that SWGA produces high-quality sequences for downstream analysis. SWGA is a robust tool that will enable efficient, cost-effective WGS of P. vivax isolates from clinical samples that can be applied to other neglected microbial pathogens. IMPORTANCE Malaria is a disease caused by Plasmodium parasites that caused 214 million symptomatic cases and 438,000 deaths in 2015. Plasmodium vivax is the most widely distributed species, causing the majority of malaria infections outside sub-Saharan Africa. Whole-genome sequencing (WGS) of Plasmodium parasites from clinical samples has revealed important insights into the epidemiology and mechanisms of drug resistance of malaria. However, WGS of P. vivax is challenging due to low parasite levels in humans and the lack of a routine system to culture the parasites. Selective whole-genome amplification (SWGA) preferentially amplifies the genomes of pathogens from mixtures of target and host gDNA. Here, we demonstrate that SWGA is a simple, robust method that can be used to enrich P. vivax genomic DNA (gDNA) from unprocessed human blood samples and dried blood spots for cost-effective, high-quality WGS.

The research community has made significant advances towards realizing self-tuning cloud caches; notwithstanding, existing products still require manual expert tuning to maximize performance. Cloud (software) caches are built to swiftly serve requests; thus, avoiding costly functionality additions not directly related to the request-serving control path is critical. We show that serverless computing cloud services can be leveraged to solve the complex optimization problems that arise during self-tuning loops and can be used to optimize cloud caches for free. To illustrate that our approach is feasible and useful, we implement SPREDS (Self-Partitioning REDiS), a modified version of Redis that optimizes memory management in the multi-instance Redis scenario. A cost analysis shows that the serverless computing approach can lead to significant cost savings: The cost of running the controller as a serverless microservice is 0.85% of the cost of the always-on alternative. Through this case study, we make a strong case for implementing the controller of autonomic systems using a serverless computing approach.

Background/Aims: we have investigated whether cultured cardiomyocytes of the cell line HL-1 have the ability to perform regulatory volume responses both in hypotonic and hypertonic conditions. Furthermore, we characterized those regulatory responses and studied the effects of bumetanide and DIDS in volume regulation of HL-1 cells. Methods: we used a light scattering system to measure the transient volume changes of HL-1 cells when subjected to osmotic challenge. Results: We found that HL-1 cells correct for their volume excess by undergoing regulatory volume decrease (RVD), and also respond to hypertonic stress with a regulatory volume increase (RVI). Rate of RVD was 0.08 ± 0.04 intensity/min, and rate of RVI was 0.09 ± 0.01 intensity/min. Volume recovery was 83.68 ± 5.73 % for RVD and 92.3 ± 2.3 % for RVI. Bumetanide 50 µM inhibited volume recovery, from 92.3 ± 2.3 % (control) to 24.6 ± 8.8 % and reduced the rate of RVI from 0.070 ± 0.020 intensity/min (control) to 0.010 ± 0.005 intensity/min. 50 µM DIDS reduced volume recovery to 42.93 ± 7.7 % and rate of RVI, to 0.03 ± 0.01 intensity/min. Conclusions: these results suggest that bumetanide- and DIDS-sensitive mechanisms are involved in the RVI of HL-1 cells, which points to the involvement of the Na+/K+/2Cl- cotransporter and Cl-/bicarbonate exchanger in RVI, respectively.