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School closures because of the COVID-19 pandemic affected over a billion young people worldwide and presented a threat to long-term learning, particularly for public school students in low socioeconomic situations. This article offers quasi-experimental evidence on a low-cost strategy for distance learning applied in the Republic of Panama to minimize the negative consequences of the pandemic on public elementary school children's reading levels. We conducted a 12-week intervention that utilized mobile phone technology and dissemination of reading material through WhatsApp, a cross-platform messaging freeware service, to maintain and improve children's reading levels during the pandemic school shutdown. The objective was to determine the feasibility of using WhatsApp as a digital tool to facilitate education and inform evolving practice and policy responses. Results among 292 students between the second and sixth grades indicated overall mean gains of up to 10.3% in the number of words read per minute, with statistically significant improvements overall and higher gains among the second and third grades. In addition, the adoption rate was high, with a reported average of 84% completion of the daily readings. The results of this low-tech intervention have immediate and longer-term implications for using mobile technology as a supplemental or complementary learning tool, especially for developing regions and during school closures or school vacations.

We reconstruct the phenotype of Balto, the heroic sled dog renowned for transporting diphtheria antitoxin to Nome, Alaska, in 1925, using evolutionary constraint estimates from the Zoonomia alignment of 240 mammals and 682 genomes from dogs and wolves of the 21st century. Balto shares just part of his diverse ancestry with the eponymous Siberian husky breed. Balto's genotype predicts a combination of coat features atypical for modern sled dog breeds, and a slightly smaller stature. He had enhanced starch digestion compared with Greenland sled dogs and a compendium of derived homozygous coding variants at constrained positions in genes connected to bone and skin development. We propose that Balto's population of origin, which was less inbred and genetically healthier than that of modern breeds, was adapted to the extreme environment of 1920s Alaska.

Introduction: Access to emergency care is an essential part of the health system. Improving access to emergency services in low- and middle-income countries (LMIC) decreases mortality and reduces global disparities; however, few studies have assessed emergency services resources in LMICs. To guide future improvements in care, we performed a comprehensive assessment of the emergency services capacity of a rural community in Guatemala serving a mostly indigenous population.Methods: We performed an exhaustively sampled cross-sectional survey of all healthcare facilities providing urgent and emergent care in the four largest cities surrounding Lake Atitlán using the Emergency Services Resource Assessment Tool (ESRAT). Results: Of 17 identified facilities, 16 agreed to participate and were surveyed: nine private hospitals; four public clinics; and three public hospitals, including the region’s public departmental hospital. All facilities provided emergency services 24/7, and a dedicated emergency unit was available at 67% of hospitals and 75% of clinics. A dedicated physician was present in the emergency unit during the day at 67% of hospitals and 75% of clinics. Hospitals had a significantly higher percentage of available equipment compared to clinics (85% vs 54%, mean difference 31%; 95% confidence interval (CI) 23-37%; P = 0.004). There was no difference in availability of laboratory tests between public and private hospitals or between cities. Private hospitals had access to a significantly higher percentage of medications compared to clinics (56% vs 27%, mean difference 29%; 95% CI 9-49%; P = 0.024). Conclusion: We found a high availability of emergency services and universal availability of personal protective equipment but a severe shortage of critical medications in clinics, and widespread shortage of pediatric equipment.

Abstract Participants judged the risk of an infection during a face to face conversation at different interpersonal distances from a SARS-CoV-2 infected person who wore a face mask or not, and in the same questionnaire answered questions about Corona related issues. Keeping a distance to an infected person serves as a protective measure against an infection. When an infected person moves closer, risk of infection increases. Participants were aware of this fact, but underestimated the rate at which the risk of infection increases when getting closer to an infected person, e.g., from 1.5 to 0.5 m (perceived risk increase = 3.33 times higher, objective = 9.00 times higher). This is alarming because it means that people can take risks of infection that they are not aware of or want to take, when they approach another possibly virus infected person. Correspondingly, when an infected person moves away the speed of risk decrease was underestimated, meaning that people are not aware of how much safer they will be if they move away from an infected person. The perceived risk reducing effects of a face mask were approximately correct. Judgments of infection risk at different interpersonal distances (with or without a mask) were unrelated to how often a person used a mask, avoided others or canceled meetings during the COVID-19 pandemic. Greater worry in general and in particular over COVID-19, correlated positively with more protective behavior during the pandemic, but not with judgments of infection risk at different interpersonal distances. Participants with higher scores on a cognitive numeracy test judged mask efficiency more correctly, and women were more worried and risk avoiding than men. The results have implications for understanding behavior in a pandemic, and are relevant for risk communications about the steep increase in risk when approaching a person who may be infected with an airborne virus.

Abstract The inefficient distribution of fertilizers, nutrients, and pesticides on crops is a major challenge in modern agriculture that leads to reduced productivity and environmental pollution. Nanoformulation of agrochemicals is an attractive approach to enable the selective delivery of agents into specific plant organs, their release in those tissues, and improve their efficiency. Already commercialized nanofertilizers utilize the physiochemical properties of metal nanoparticles such as size, charge, and the metal core to overcome biological barriers in plants to reach their target sites. Despite their wide application in human diseases, lipid nanoparticles are rarely used in agricultural applications and a systematic screening approach to identifying efficacious formulations has not been reported. Here, we developed a quantitative metal-encoded platform to determine the biodistribution of different lipid nanoparticles in plant tissues. In this platform lanthanide metal complexes were encapsulated into four types of lipid nanoparticles. Our approach was able to successfully quantify payload accumulation for all the lipid formulations across the roots, stem, and leaf of the plant. Lanthanide levels were 20- to 57-fold higher in the leaf and 100- to 10,000-fold higher in the stem for the nanoparticle encapsulated lanthanide complexes compared to the unencapsulated, free lanthanide complex. This system will facilitate the discovery of nanoparticles as delivery carriers for agrochemicals and plant tissue-targeting products.

Clinical studies have demonstrated that local expression of the cytokine IL-12 drives interferon-gamma expression and recruits T cells to the tumor microenvironment, ultimately yielding durable systemic T cell responses. Interrogation of longitudinal biomarker data from our late-stage melanoma trials identified a significant on-treatment increase of intratumoral CXCR3 transcripts that was restricted to responding patients, underscoring the clinical relevance of tumor-infiltrating CXCR3+ immune cells. In this study, we sought to understand if the addition of DNA-encodable CXCL9 could augment the anti-tumor immune responses driven by intratumoral IL-12. We show that localized IL-12 and CXCL9 treatment reshapes the tumor microenvironment to promote dendritic cell licensing and CD8+ T cell activation. Additionally, this combination treatment results in a significant abscopal anti-tumor response and provides a concomitant benefit to anti-PD-1 therapies. Collectively, these data demonstrate that a functional tumoral CXCR3/CXCL9 axis is critical for IL-12 anti-tumor efficacy. Furthermore, restoring or amplifying the CXCL9 gradient in the tumors via intratumoral electroporation of plasmid CXCL9 can not only result in efficient trafficking of cytotoxic CD8+ T cells into the tumor but can also reshape the microenvironment to promote systemic immune response.

The search for efficient antimicrobial therapies that can alleviate suffering caused by infections from resistant bacteria is more urgent than ever before. Infections caused by multi-resistant pathogens represent a significant and increasing burden to healthcare and society and researcher are investigating new classes of bioactive compounds to slow down this development. Antimicrobial peptides from the innate immune system represent one promising class that offers a potential solution to the antibiotic resistance problem due to their mode of action on the microbial membranes. However, challenges associated with pharmacokinetics, bioavailability and off-target toxicity are slowing down the advancement and use of innate defensive peptides. Improving the therapeutic properties of these peptides is a strategy for reducing the clinical limitations and synthetic mimics of antimicrobial peptides are emerging as a promising class of molecules for a variety of antimicrobial applications. These compounds can be made significantly shorter while maintaining, or even improving antimicrobial properties, and several downsized synthetic mimics are now in clinical development for a range of infectious diseases. A variety of strategies can be employed to prepare these small compounds and this review describes the different compounds developed to date by adhering to a minimum pharmacophore based on an amphiphilic balance between cationic charge and hydrophobicity. These compounds can be made as small as dipeptides, circumventing the need for large compounds with elaborate three-dimensional structures to generate simplified and potent antimicrobial mimics for a range of medical applications. This review highlight key and recent development in the field of small antimicrobial peptide mimics as a promising class of antimicrobials, illustrating just how small you can go.

The present study aims to characterise the pharmacokinetics of rifampicin (RIF) in tuberculosis (TB) patients with and without HIV co-infection, considering the formation of 25-O-desacetyl-rifampicin (desRIF). It is hypothesised that the metabolite formation, HIV co-infection and drug formulation may further explain the interindividual variation in the exposure to RIF. Pharmacokinetic, clinical, and demographic data from TB patients with (TB-HIV+ group; n = 18) or without HIV (TB-HIV− group; n = 15) who were receiving RIF as part of a four-drug fixed-dose combination (FDC) regimen (RIF, isoniazid, pyrazinamide, and ethambutol) were analysed, along with the published literature data on the relative bioavailability of different formulations. A population pharmacokinetic model, including the formation of desRIF, was developed and compared to a model based solely on the parent drug. HIV co-infection does not alter the plasma exposure to RIF and the desRIF formation does not contribute to the observed variability in the RIF disposition. The relative bioavailability and RIF plasma exposure were significantly lower than previously reported for the standard regimen with FDC tablets. Furthermore, participants weighting less than 50 kg do not reach the same RIF plasma exposure as compared to those weighting >50 kg. In conclusion, as no covariate was identified other than body weight on CL/F and Vd/F, low systemic exposure to RIF is likely to be caused by the low bioavailability of the formulation.

Abstract The intestinal epithelial receptor Guanylyl Cyclase C (GUCY2C) is a tumor-associated cell surface antigen expressed across gastrointestinal malignancies that can serve as an efficacious target for colorectal cancer immunotherapy. Here, we describe a yeast surface-display approach combined with an orthogonal peptide-based mapping strategy to identify the GUCY2C binding epitope of a novel anti-GUCY2CxCD3 bispecific antibody (BsAb) that recently advanced into the clinic for the treatment of cancer. The target epitope was localized to the N-terminal helix H2 of human GUCY2C, which enabled the determination of the crystal structure of the minimal GUCY2C epitope in complex with the anti-GUCY2C antibody domain. To understand if this minimal epitope covers the entire antibody binding region and to investigate the impact of epitope position on the antibody’s activity, we further determined the structure of this interaction in the context of the full-length extracellular domain (ECD) of GUCY2C. We found that this epitope is positioned on the protruding membrane-distal helical region of GUCY2C and that its specific location on the surface of GUCY2C dictates the close spatial proximity of the two antigen arms in a diabody arrangement essential to the tumor killing activity of GUCY2CxCD3 BsAb.

Introduction Fragmentation in immunisation reporting systems pose challenges in measuring vaccine coverage for First Nations children in Canada. Some Nations have entered into data-sharing agreements with the province of Alberta’s health ministry, enabling novel opportunities to calculate coverage.Methods Partnering with a First Nations community in Alberta, this retrospective cohort study calculated routine childhood vaccine coverage. Administrative data for vaccines delivered within and outside the community were linked to calculate partial and complete immunisation coverage in 2013–2019 at ages 2 and 7 years for children living in the community. We also compared vaccine coverage each year for (a) children who were and were not continuous community residents and (b) children who received or not their first vaccine at the on-reserve community health centre. We also calculated the mean complete coverage across all study years with 95% CIs.Results For most vaccines, coverage was higher (p

Over the past twenty years, many sectors have used capacity diagnostics for mapping and analyzing the skills needed for national development at individual, organizational and institutional levels. These diagnostics, also sometimes referred to as "needs assessments" or "gap analyses," are systematic investigations carried out prior to or during an ongoing program, project or productive activity as a means to gaining insight on discrepancies between current and desired conditions with a view to improving performance, designing new processes, and/or correcting deficiencies. This article presents a model for adapting capacity diagnostics to assess higher education for (1) documentation of existing resources in specific institutions or disciplines, and (2) quantification of labor market perceptions of current assets and gaps, with a view to facilitating planning for and development of required curricular, research and personnel capacities. The model is illustrated with a case study from the Republic of Panama where the National Secretariat for Science, Technology and Innovation (SENACYT) conducted a study with Tulane University to assess the country's higher education and research in the social sciences. This article further explores the potential for this higher education diagnostic to serve as a tool for academia supply-labor market demand gap analysis elsewhere, which has far-reaching implications for countries and states in terms of competitiveness at national and global levels--particularly for developing regions.

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.

The COVID-19 pandemic has led to rapid scientific progress in wastewater-based surveillance of community infections. Measuring levels of RNA from SARS-CoV-2 in sewage samples began to be used as a [...]

School closures because of the COVID-19 pandemic affected over a billion young people worldwide and presented a threat to long-term learning, particularly for public school students in low socioeconomic situations. This article offers quasi-experimental evidence on a low-cost strategy for distance learning applied in the Republic of Panama to minimize the negative consequences of the pandemic on public elementary school children’s reading levels. We conducted a 12-week intervention that utilized mobile phone technology and dissemination of reading material through WhatsApp, a cross-platform messaging freeware service, to maintain and improve children’s reading levels during the pandemic school shutdown. The objective was to determine the feasibility of using WhatsApp as a digital tool to facilitate education and inform evolving practice and policy responses. Results among 292 students between the second and sixth grades indicated overall mean gains of up to 10.3% in the number of words read per minute, with statistically significant improvements overall and higher gains among the second and third grades. In addition, the adoption rate was high, with a reported average of 84% completion of the daily readings. The results of this low-tech intervention have immediate and longer-term implications for using mobile technology as a supplemental or complementary learning tool, especially for developing regions and during school closures or school vacations.

Abstract Background During the COVID-19 pandemic people were asked to keep interpersonal distance, wash their hands and avoid gatherings of people. But, do people understand how much a change of the distance to a virus infected person means for the exposure to that person’s virus? To answer this question, we studied how people perceive virus exposure from an infected person at different distances and lengths of a conversation. Method An online questionnaire was distributed to 101 participants drawn from the general US population. Participants judged perceived virus exposure at different interpersonal distances to an infected person in a face to face conversation of different lengths of time. A model based on empirical and theoretical studies of dispersion of particles in the air was used to estimate a person’s objective virus exposure during different times and distances from a virus source. The model and empirical data show that exposure changes with the square of the distance and linearly with time. Results A majority (78%) of the participants underestimated the effects on virus exposure following a change of interpersonal distance. The dominating bias was assuming that exposure varies linearly with distance. To illustrate, an approach to a virus source from 6 to 2 feet was judged to give a 3 times higher exposure but, objectively it is 9 times. By way of contrast, perceptions of exposure as a function of the duration of a conversation were unbiased. The COVID-19 pandemic caused by the SARS-CoV2 virus is likely to be followed by other pandemics also caused by airborne Corona or other viruses. Therefore, the results are important for administrators when designing risk communications to the general public and workers in the health care sector about social distancing and infection risks. Conclusions People quite drastically underestimate the increase in virus exposure following an approach to a virus infected person. They also overestimate exposure after a move away from an infected person. For public health reasons, the correct function connecting distance with virus exposure should be communicated to the general public to avoid deliberate violations of recommended interpersonal distances.

Wastewater monitoring of SARS-CoV-2 enables early detection and monitoring of the COVID-19 disease burden in communities and can track specific variants of concern. We determined proportions of the Omicron and Delta variants across 30 municipalities covering >75% of the province of Alberta (population 4.5 million), Canada, during November 2021–January 2022. Larger cities Calgary and Edmonton exhibited more rapid emergence of Omicron than did smaller and more remote municipalities. Notable exceptions were Banff, a small international resort town, and Fort McMurray, a medium-sized northern community that has many workers who fly in and out regularly. The integrated wastewater signal revealed that the Omicron variant represented close to 100% of SARS-CoV-2 burden by late December, before the peak in newly diagnosed clinical cases throughout Alberta in mid-January. These findings demonstrate that wastewater monitoring offers early and reliable population-level results for establishing the extent and spread of SARS-CoV-2 variants.

To make good decisions, employees must manage their own intuitions and be able to anticipate decision-making in their work environment. How well this is accomplished has significant consequences for the workplace. A closer examination indicates that individuals utilize various types of intuition. People’s work context is frequently omitted from studies on the use of intuition, resulting in a literature that omits vital aspects of decision-making. To assist applicable research in the workplace, our contribution to the management literature is a comprehensive overview of intuitive decision-making types. Current psychological assessment scales constitute a mature discipline, but they frequently lack the professional applications needed in business administration and economics. Considering this, the primary objective of this article is to assemble and assess many types of intuition and combine them into a new lens for research in the theory and practice of business using a multidimensional approach. It is comprised of rational choice theory, classical intuitive decision making, emotional decisions (gut feelings), fast heuristic decisions, unconscious thought, and anticipation. The overview of several scientifically proven measuring scales produces a theoretical foundation for future empirical study in business administration and economics based on these findings.

[This corrects the article DOI: 10.1038/s42003-018-0226-0.].

[This corrects the article DOI: 10.1038/s42003-018-0226-0.].

Abstract Objectives To examine the comparative performance of EuroQol EQ-5D-5L and Center for Disease Control Healthy Days measures in assessing population health. Methods Using data from 2014 Alberta Community Health Survey, a cross-sectional population-based survey (N = 7559), conducted in Alberta, Canada, we examined construct validity of the measures as indicators of population health. Differences in EQ-5D-5L index score, visual analogue scale (EQ-VAS), and CDC unhealthy days index across socio-demographic subgroups were tested by Mann–Whitney and Kruskal–Wallis tests using known-groups approach. Results EQ-5D-5L and CDC Healthy Days provided comparable assessments of population health in this sample. Both measures discriminated between subgroups defined by self-perceived health status, level of education, and material deprivation. The discriminative ability of CDC Healthy Days was limited in capturing variability in health among age groups compared to the EQ-5D-5L. Among participants who reported 0 unhealthy days, the proportion of those with level 3 problems in pain/discomfort varied from 1.1% for participants aged 18–24 to 19.2% for those over 75 years. Conclusions EQ-5D-5L demonstrated better construct validity than CDC Healthy Days in assessing health in a population-based sample of adults.

Clinical studies have demonstrated that local expression of the cytokine IL-12 drives interferon-gamma expression and recruits T cells to the tumor microenvironment, ultimately yielding durable systemic T cell responses. Interrogation of longitudinal biomarker data from our late-stage melanoma trials identified a significant on-treatment increase of intratumoral CXCR3 transcripts that was restricted to responding patients, underscoring the clinical relevance of tumor-infiltrating CXCR3+ immune cells. In this study, we sought to understand if the addition of DNA-encodable CXCL9 could augment the anti-tumor immune responses driven by intratumoral IL-12. We show that localized IL-12 and CXCL9 treatment reshapes the tumor microenvironment to promote dendritic cell licensing and CD8+ T cell activation. Additionally, this combination treatment results in a significant abscopal anti-tumor response and provides a concomitant benefit to anti-PD-1 therapies. Collectively, these data demonstrate that a functional tumoral CXCR3/CXCL9 axis is critical for IL-12 anti-tumor efficacy. Furthermore, restoring or amplifying the CXCL9 gradient in the tumors via intratumoral electroporation of plasmid CXCL9 can not only result in efficient trafficking of cytotoxic CD8+ T cells into the tumor but can also reshape the microenvironment to promote systemic immune response.

Abstract Bloodstream infections are among the most serious and frequent infections, and the people most exposed are patients in the Intensive Care Unit (ICU). ESBL (extended-spectrum beta-lactate) are resistant bacteria to penicillins, cephalosporins and monobactams. It´s necessary to know how often and which microorganisms are involved, checking their susceptibility. This study was carried out at the University Hospital. Data collection was performed in the Adult and Newborn ICUs, with assessment of microorganisms and their resistance profile. During six-month period, 156 samples were studied, and 42 were positive with microorganism isolation. Isolated species include Staphylococcus aureus, Staphylococcus epidermidis and Klebsiella pneumoniae. Many resistant to carbapenem.

We attempted to strengthen an evidence-based, peer-mediated, first-grade reading program (First Grade Peer-Assisted Learning Strategies [PALS]) by modestly revising its content and adding a repeated-reading (RR) component. In a cluster-randomized trial, we conducted a component analysis of the revised program by creating two versions of it. "PALS+Fluency" represented the modified program with an RR component, whereas "PALS-Only" represented the same program without RR. We tested the efficacy of the two PALS versions together against controls and against each other to determine if peer-mediated RR had "value added." With moderator analyses, we further explored whether the PALS programs benefited weaker and stronger readers alike. Thirty-three first-grade classroom teachers (and 491 students) from eight urban schools were randomly assigned to the three study groups within their schools. The PALS-Only and PALS+Fluency programs ran for 22 weeks. Multilevel modeling showed that the combined effects of the two PALS programs on phonological awareness (PA), word reading, and reading fluency were superior to those of controls. Students' pretreatment PA moderated combined program effects on PA and word reading, indicating stronger effects for students with weaker PA. PALS-Only students improved PA skills (over PALS+Fluency students) with stronger effects for those with weaker pretreatment PA.