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The influence of the epistemological beliefs of parents on the development of comprehensive scientific reasoning abilities was investigated in a five-wave longitudinal study from kindergarten to elementary school. The 161 German 5-10-year-olds (89 girls, 72 boys) were assessed yearly on their scientific reasoning abilities using comprehensive measures for experimentation and data-interpretation skills, as well as understanding of the nature of science. The children were also tested on their language abilities and intelligence. Their parents completed a sociodemographics questionnaire and answered ten questions about their epistemological beliefs regarding (1) the interpretive nature of science, (2) the tentative nature of knowledge, and (3) the role of scientific framework theories. The personal epistemology of the parents significantly predicted the scientific reasoning development of their children regardless of the parents' education level and the children's general cognitive abilities. However, the effect of the epistemology of parents on their children's scientific reasoning was limited to the intercepts, suggesting that the epistemic understanding of parents affects how scientific reasoning develops in their children, but not the development speed. Although parental epistemology exerts substantial effects on scientific reasoning of their children, it did not affect their reading ability, suggesting an involvement of science-specific mechanisms rather than generalized family-based influences. These findings highlight the importance of family as a variable in the development of scientific reasoning, which is an area lacking in research, and it suggests that early interventions targeted at the epistemic understanding of caregivers can provide useful ways for promoting the reasoning of children.

Abstract Background In 2018, the Dutch government initiated the Solid Start program to provide each child with the best start in life. Key program elements are a biopsychosocial perspective on pregnancy and children’s development and stimulating local collaborations between social and health domains, with a specific focus on (future) families in vulnerable situations. Two programs for interprofessional collaboration between maternity and social care professionals to optimize care for pregnant women in vulnerable situations were developed and implemented, in Groningen in 2017 and in South Limburg in 2021. This paper describes the extent of implementation of these programs and the perceptions of involved professionals about determinants that influence program implementation. Methods We conducted a mixed-methods study in 2021 and 2022 in two Dutch regions, Groningen and South Limburg. Questionnaires were sent to primary care midwives, hospital-based midwives, obstetricians (i.e. maternity care professionals), (coordinating) youth health care nurses and social workers (i.e. social care professionals), involved in the execution of the programs. Semi-structured interviews were held with involved professionals to enrich the quantitative data. Quantitative and qualitative data were collected and analyzed using Fleuren's implementation model. Results The findings of the questionnaire (n = 60) and interviews (n = 28) indicate that professionals in both regions are generally positive about the implemented programs. However, there was limited knowledge and use of the program in Groningen. Promoting factors for implementation were mentioned on the determinants for the innovation and the user. Maternity care professionals prefer a general, conversational way to identify vulnerabilities that connects to midwives’ daily practice. Low-threshold, personal contact with clear agreements for referral and consultation between professionals contributes to implementation. Professionals agree that properly identifying vulnerabilities and referring women to appropriate care is an important task and contributes to better care. On the determinants of the organization, professionals indicate some preconditions for successful implementation, such as clearly described roles and responsibilities, interprofessional training, time and financial resources. Conclusions Areas for improvement for the implementation of interprofessional collaboration between maternity care and social care focus mainly on determinants of the organization, which should be addressed both regionally and nationally. In addition, sustainable implementation requires continuous awareness of influencing factors and a process of evaluation, adaptation and support of the target group.

Abstract Tick-borne encephalitis virus (TBEV) vaccine breakthrough (VBT) infections are not uncommon in endemic areas. The clinical and immunological outcomes have been poorly investigated. We assessed the magnitude and specificity of virus-specific antibody and T cell responses after TBE in previously vaccinated subjects and compared the results with those of unvaccinated TBE patients and study subjects that received vaccination without VBT infection. Symptomatic TBEV infection of unvaccinated study subjects induced virus-specific antibody responses to the E protein and non-structural protein 1 (NS1) as well as T cell responses to structural and other non-structural (NS) proteins. After VBT infections, significantly impaired NS1-specific antibody responses were observed, while the virus-specific T cell responses to the NS proteins were relatively strong. VBT infection caused predominantly moderate to severe disease during hospitalization. The level of TBEV EDIII- and NS1-specific antibodies in unvaccinated convalescent patients inversely correlated with TBE severity and neurological symptoms early after infection.

Although scientific reasoning is not a formal, independent school subject, it is an increasingly important skill, especially for student learning in science, technology, engineering, and mathematics (STEM) subjects. To promote scientific reasoning effectively, it is important to know its influencing factors. While cognitive influences have been investigated, affective-motivational factors, particularly self-efficacy, have rarely been considered in studies on scientific reasoning. To examine, for the first time, whether self-efficacy can be measured in a task-specific way and whether self-efficacy correlates with students' scientific reasoning performance, the study assessed performance in scientific reasoning and self-efficacy (academic and task-specific) in a sample of 140 fourth graders and 148 eighth graders. As expected, higher correlations emerged for task-specific self-efficacy in both grades. A hierarchical cluster analysis showed that the correlational patterns were not the same across grade levels, with differences in self-estimated performance prevailing between the two grade levels: The largest cluster in Grade 4 (41%) comprised children who significantly overestimated their performance, whereas the largest cluster in Grade 8 (39%) comprised students who gave a realistic estimate of their own performance in scientific reasoning. This cluster was not present in Grade 4. Additional clusters of students who overestimated or underestimated their performance emerged in both grades. The results support the conclusion that self-efficacy expectations are important to consider when fostering scientific reasoning, and the large number of elementary school students who overestimated their performance suggests that not all students might benefit from interventions targeted at increasing self-efficacy.

Daylight is essential for ecosystems and for the physical and mental well-being of people. In densely populated cities, only a small proportion of total daylight is available to support urban greenery and most people have little daily exposure to natural daylight. Despite this, many cities have followed a strategy of densification as a way of preventing urban sprawl and reducing energy consumption. In this article, we review the biological importance of daylight and show that urban densification leads to a reduction in the daylight available for both people and nature. We conclude that daylight in cities should be treated as a limiting resource that needs to be planned and managed carefully, much like water or energy. We suggest elements for a policy framework aimed at optimizing urban daylight, including how to determine daylight needs, how to determine the maximum viable urban density, and policy options for built and unbuilt areas.

Abstract The European Scientific Working Group on Influenza (ESWI) held the 9th ESWI Influenza Conference in Valencia from 17—20 September 2023. Here we provide a summary of twelve key presentations, covering major topics on influenza virus, respiratory syncytial virus (RSV) and SARS coronavirus 2 (SARS-CoV-2) including: infection processes beyond acute respiratory disease, long COVID, vaccines against influenza and RSV, the implications of the potential extinction of influenza B virus Yamagata lineage, and the threats posed by zoonotic highly pathogenic avian influenza viruses.

Abstract Monoclonal antibodies are an increasingly important tool for prophylaxis and treatment of acute virus infections like SARS-CoV-2 infection. However, their use is often restricted due to the time required for development, variable yields and high production costs, as well as the need for adaptation to newly emerging virus variants. Here we use the genetically modified filamentous fungus expression system Thermothelomyces heterothallica (C1), which has a naturally high biosynthesis capacity for secretory enzymes and other proteins, to produce a human monoclonal IgG1 antibody (HuMab 87G7) that neutralises the SARS-CoV-2 variants of concern (VOCs) Alpha, Beta, Gamma, Delta, and Omicron. Both the mammalian cell and C1 produced HuMab 87G7 broadly neutralise SARS-CoV-2 VOCs in vitro and also provide protection against VOC Omicron in hamsters. The C1 produced HuMab 87G7 is also able to protect against the Delta VOC in non-human primates. In summary, these findings show that the C1 expression system is a promising technology platform for the development of HuMabs in preventive and therapeutic medicine.

Abstract Animal migration is one of nature's most spectacular phenomena, but migratory animals and their journeys are imperilled across the globe. Migratory birds are among the most well‐studied animals on Earth, yet relatively little is known about in‐flight behaviour during nocturnal migration. Because many migrating bird species vocalize during flight, passive acoustic monitoring shows great promise for facilitating widespread monitoring of bird migration. Here, we present Nighthawk, a deep learning model designed to detect and identify the vocalizations of nocturnally migrating birds. We trained Nighthawk on the in‐flight vocalizations of migratory birds using a diverse dataset of recordings from across the Americas. Our results demonstrate that Nighthawk performs well as a nocturnal flight call detector and classifier for dozens of avian taxa, both at the species level and for broader taxonomic groups (e.g. orders and families). It achieves an average precision score above 0.80 for 50 species and a mean average precision of 0.96 across 4 orders. The model accurately quantified nightly nocturnal migration intensity (80% variation explained) and species phenology (78% variation explained) and performed well on data from across North America. Incorporating modest amounts of additional annotated audio (50–120 h) into model training yielded high performance on target datasets from both North and South America (average precision on order Passeriformes >0.99). By monitoring the vocalizations of actively migrating birds, Nighthawk provides a detailed window onto nocturnal bird migration that is not presently attainable by other means (e.g. radar or citizen science). Scientists, managers and practitioners could use acoustic monitoring with Nighthawk for a number of applications, including: monitoring migration passage at wind farms; studying airspace usage during migratory flights; monitoring the changing migrations of species susceptible to climate change; and revealing previously unknown migration routes and behaviours. Overall, this work will empower diverse stakeholders to efficiently monitor migrating birds across the Western Hemisphere and collect data in aid of science and conservation.

Kinetoplastid organisms, including Trypanosoma brucei, are a significant health burden in many tropical and semitropical countries. Much of their metabolism is poorly understood. To better study kinetoplastid metabolism, chemical probes that inhibit kinetoplastid enzymes are needed. To discover chemical probes, we have developed a high-throughput flow cytometry screening assay that simultaneously measures multiple glycolysis-relevant metabolites in live T. brucei bloodstream form parasites. We transfected parasites with biosensors that measure glucose, ATP, or glycosomal pH. The glucose and ATP sensors were FRET biosensors, while the pH sensor was a GFP-based biosensor. The pH sensor exhibited a different fluorescent profile from the FRET sensors, allowing us to simultaneously measure pH and either glucose or ATP. Cell viability was measured in tandem with the biosensors using thiazole red. We pooled sensor cell lines, loaded them onto plates containing a compound library, and then analyzed them by flow cytometry. The library was analyzed twice, once with the pooled pH and glucose sensor cell lines and once with the pH and ATP sensor cell lines. Multiplexing sensors provided some internal validation of active compounds and gave potential clues for each compound's target(s). We demonstrated this using the glycolytic inhibitor 2-deoxyglucose and the alternative oxidase inhibitor salicylhydroxamic acid. Individual biosensor-based assays exhibited a Z′-factor value acceptable for high-throughput screening, including when multiplexed. We tested assay performance in a pilot screen of 14,976 compounds from the Life Chemicals Compound Library. We obtained hit rates from 0.2 to 0.4% depending on the biosensor, with many compounds impacting multiple sensors. We rescreened 44 hits, and 28 (64%) showed repeatable activity for one or more sensors. One compound exhibited EC50 values in the low micromolar range against two sensors. We expect this method will enable the discovery of glycolytic chemical probes to improve metabolic studies in kinetoplastid parasites.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease caused by RVF virus (RVFV). RVFV infections in humans are usually asymptomatic or associated with mild febrile illness, although more severe cases of haemorrhagic disease and encephalitis with high mortality also occur. Currently, there are no licensed human vaccines available. The safety and efficacy of a genetically engineered four-segmented RVFV variant (hRVFV-4s) as a potential live-attenuated human vaccine has been tested successfully in mice, ruminants, and marmosets though the correlates of protection of this vaccine are still largely unknown. In the present study, we have assessed hRVFV-4s-induced humoral and cellular immunity in a mouse model of RVFV infection. Our results confirm that a single dose of hRVFV-4s is highly efficient in protecting naïve mice from developing severe disease following intraperitoneal challenge with a highly virulent RVFV strain and data show that virus neutralizing (VN) serum antibody titres in a prime-boost regimen are significantly higher compared to the single dose. Subsequently, VN antibodies from prime-boost-vaccinated recipients were shown to be protective when transferred to naïve mice. In addition, hRVFV-4s vaccination induced a significant virus-specific T cell response as shown by IFN-γ ELISpot assay, though these T cells did not provide significant protection upon passive transfer to naïve recipient mice. Collectively, this study highlights hRVFV-4s-induced VN antibodies as a major correlate of protection against lethal RVFV infection.

ABSTRACTTick-borne encephalitis virus (TBEV) infection may cause acute central nervous system inflammation varying in clinical manifestations and severity. A possible correlation of TBEV-specific antibody and cell-mediated immune responses, shortly after infection, with clinical manifestations, severity and long-term outcome has been poorly investigated. In a cohort of thirty early tick-borne encephalitis (TBE) patients, we assessed the magnitude, specificity and functional properties of TBEV-specific T-cell and antibody responses. These responses early during disease were assessed in view of clinical manifestations, severity and long-term outcome. TBEV-specific T-cell responses to C, E, NS1, and NS5 proteins were significantly lower in patients with severe acute illness than in patients with mild TBE. Lower T-cell responses to E, NS1, and NS5 proteins also correlated with the development of meningoencephalomyelitis. Virus-specific antibody titres early after infection did not correlate with disease severity, clinical manifestations, or long-term outcome in this study, possibly due to the small number of patients of which matching serum and peripheral blood mononuclear cells were available. The findings suggest that virus-specific T cells afford a certain degree of protection against the development of severe TBEV-induced disease.

This 6-wave longitudinal study (2014-2018) of 161 German 5- to 10-year-olds from a midsized city and rural area in southern Germany (89 females, 72 males; predominantly White; mostly middle class) found that scientific-reasoning abilities first develop at 6 years. Abilities were highly stable, with the kindergarten score predicting 25% of end-of-elementary-school variance. Individual but not developmental differences were related to language abilities (0.39), mindreading skills (0.33), and parental education (0.36). In early elementary school, mindreading skills predicted scientific reasoning (0.15), but not vice versa; in late elementary school, bidirectional associations emerged (0.11-0.33). Our findings suggest that mindreading is a precursor for the development of scientific reasoning and that older children use scientific reasoning to revise their advanced theories of mind.

Are there categorically distinct parenting behaviours that differ between families with children with and without disabilities (mild intellectual disability [MID], deaf or hard of hearing children [DHH])? A study involving 719 children and their families assessed mothers' responses to the Parenting Styles and Dimensions Questionnaire and children's language skills at 8 and 9 years. A latent class analysis revealed three discrete classes of parenting behaviours: (1) authoritative; (2) mildly authoritative; and (3) inconsistent or neglecting. The latter class comprised around 10% of the mothers, across all groups. The behaviours that were associated with this class, however, differed across groups: In families with children without disability, it was characterized by inconsistent (authoritarian and permissive) behaviours; in families with children with disabilities, it is best described as neglecting. A high level of education was related to better parenting behaviours, and in children with DHH, neglecting parenting was associated with poor language development.

Introduction: This study explored the impact of synchronous professional development regarding Nemeth Code Within Unified English Braille (UEB) Contexts on the knowledge and skills of 17 teachers of students with visual impairments. Methods: Participants attended the professional development sessions in June 2022 and submitted a pretest, posttest, final assignment, and posttraining survey. Results: Sixteen out of 17 participants scored higher on their posttest with a mean difference of 5.53. None of the participants submitted an error-free assignment. Total numbers of errors ranged from 8 to 60, and the categories with the highest percentage of errors were formatting, use of opening and terminating switch indicators, and Nemeth Code symbols. Discussion: In order to successfully progress in the general education curriculum, students who read braille must have access to timely, accurately prepared materials in all content areas including mathematics. Direct examination of the final assignment submitted by the 17 participants revealed similar error patterns to previous research. In addition, some of the participants struggled to correctly use Nemeth Code switch indicators. Implications for Practitioners: Teachers of students with visual impairments should continue to build their skills for Nemeth Code within UEB Contexts. Additional resources and professional development are urgently needed.

This article presents and discusses the lessons learned from the monitoring of 25 integrated daylighting and electric lighting international case study projects. The case studies consist of real occupied buildings that have been monitored as part of the International Energy Agency (IEA) SHC Task 61/EBC Annex 77 Programme. The general goal of the case studies was to balance lighting energy use with occupants’ visual and non-visual requirements. This was achieved using innovative solutions for daylighting and electric lighting with advanced controls, but also implementing simple and out-of-the-box strategies. The findings suggest that energy demands for lighting can significantly be reduced by combining sensible daylight provision, efficient lighting sources, and advances in controls. Yet, the effective achievement of project goals requires adequate monitoring, fine-tuning, and verification. The findings also suggest that the adoption of “integrative” lighting – that is, lighting systems that address both visual and non-visual responses – is getting increasingly popular. Catering to non-visual requirements will likely drive further innovation in lighting technology. Currently, there is limited investment available for developing daylighting systems for integrative lighting, and the current related electric strategies often come at the risk of energy rebound effects. Overall, providing daylighting and understanding user requirements are fundamental steps towards achieving quality projects, with potential benefits beyond saving energy.

Over the past few decades, dengue fever has emerged as a significant global health threat, affecting tropical and moderate climate regions. Current vaccines have practical limitations, there is a strong need for safer, more effective options. This study introduces novel vaccine candidates covering all four dengue virus (DENV) serotypes using virus-like particles (VLPs), a proven vaccine platform. The dengue virus envelope protein domain III (EDIII), the primary target of DENV-neutralizing antibodies, was either genetically fused or chemically coupled to bacteriophage-derived AP205-VLPs. To facilitate the incorporation of the large EDIII domain, AP205 monomers were dimerized, resulting in sterically optimized VLPs with 90 N- and C-termini. These vaccines induced high-affinity/avidity antibody titers in mice, and confirmed their protective potential by neutralizing different DENV serotypes in vitro. Administration of a tetravalent vaccine induced high neutralizing titers against all four serotypes without producing enhancing antibodies, at least not against DENV2. In conclusion, the vaccine candidates, especially when administered in a combined fashion, exhibit intriguing properties for potential use in the field, and exploring the possibility of conducting a preclinical challenge model to verify protection would be a logical next step.

Investigating scientific reasoning comprehensively with large sample sizes is a challenge, especially in young children where there is little evidence showing that paper-and-pencil instruments can be used to reliably measure competencies. The present study with 122 third graders compares three test modalities: an established interview (Science-K Interview), a novel group test (Science-K Group Test), and an established paper-and-pencil test (Science-P Reasoning Inventory), asking how scientific reasoning can be reliably measured in primary school. The children were presented with 15 items from the Science-K Interview, 15 parallel items from the Science-K Group Test, and 5 items from the Science-P Reasoning Inventory. The interview was presented first, followed by the group test and Science-P items. The Rasch model revealed a good fit of 23 items to the unidimensional model indicating that there is a single underlying ability involved in primary-school scientific reasoning that can be measured with both interview and group test. Although students performed significantly better in the group test than in the interview, the difference was not substantial and might partially be explained by the sequence of the tests. As expected, children solved more Science-K items correctly compared to the Science-P items, which assesses more advanced aspects of scientific reasoning. The important finding of the study is that group tests can reliably capture scientific reasoning in third graders. The use of group tests in primary school can facilitate conducting studies with large sample sizes and can be used for diagnostic purposes, especially in the context of science education in schools.

First-order theory of mind (ToM) development has shown to conform to a Guttman scale, with desire reasoning developing before belief reasoning. There have been attempts to test for internal consistency and scalability in advanced ToM, but not over a broad age range and only with a limited set of tasks. This 2-year longitudinal study (N = 155; M[subscript age] = 4.2; SD = 0.85 months; 68 girls, 87 boys) tests for the scalability of a broader range of ToM tasks, and we model the developmental "transition" from first-order to advanced ToM in 4- to 6-year-olds. Rasch analyses showed that psychometrically sound and developmentally sequenced scales emerge when measures of morally relevant and second-order false belief, as well as mental verb understanding, metacognition, and recognition of nonliteral speech are included. Individual differences were moderately stable over time, and there were systematic transitions from failure to success in children's performance, suggesting that conceptual continuity exists between first-order and advanced ToM.

The ability to correctly interpret data is an important skill in modern knowledge societies. The present study investigates adults' ability to interpret covariation data presented in bar graphs. Drawing on previous findings that show that the problem context influences the interpretation of contingency tables (grounded and concrete problems are easier than abstract ones) and based on findings from the literature on motivated reasoning (confirming problems are easier than disconfirming ones), we present N = 111 undergraduates with bar graphs in either grounded (confirming or disconfirming) or abstract contexts. Our results show that only grounded problems in confirming contexts are easier than abstract ones; grounded problems in disconfirming contexts are more challenging than abstract ones. Overall, the interpretation of bar graphs is difficult: Even in our sample of educated college students, correct performance did not exceed 50%. Our results support earlier findings regarding the context dependency of data-interpretation skills, and they suggest that relatively minor task variations have an impact on reasoners' interpretations of bar graphs.

Recent reports documenting sporadic infections in carnivorous mammals worldwide with highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b have raised concerns about the potential risk of adaptation to sustained transmission in mammals, including humans. We report H5N1 clade 2.3.4.4b infection of two grey seals (Halichoerus grypus) from coastal waters of The Netherlands and Germany in December 2022 and February 2023, respectively. Histological and immunohistochemical investigations showed in both animals a non-suppurative and necrotising encephalitis with viral antigen restricted to the neuroparenchyma. Whole genome sequencing showed the presence of HPAIV H5N1 clade 2.3.4.4b strains in brain tissue, which were closely related to sympatric avian influenza viruses. Viral RNA was also detected in the lung of the seal from Germany by real-time quantitative PCR. No other organs tested positive. The mammalian adaptation PB2-E627K mutation was identified in approximately 40% of the virus population present in the brain tissue of the German seal. Retrospective screening for nucleoprotein-specific antibodies, of sera collected from 251 seals sampled in this region from 2020 to 2023, did not show evidence of influenza A virus-specific antibodies. Similarly, screening by reverse transcription PCR of tissues of 101 seals that had died along the Dutch coast in the period 2020–2021, did not show evidence of influenza virus infection. Collectively, these results indicate that individual seals are sporadically infected with HPAIV-H5N1 clade 2.3.4.4b, resulting in an encephalitis in the absence of a systemic infection, and with no evidence thus far of onward spread between seals.

Both theory of mind (ToM) and executive functioning have been related to children's academic abilities. In a longitudinal study with 112 children, we investigated the influence of these two abilities on children's math and reading performance at 7 years of age. We found that math performance was predicted by concurrent working memory as well as by preschool numerical abilities and ToM. Reading performance was predicted by concurrent working memory and verbal IQ at 6 years. This corroborates earlier research demonstrating the importance of executive functioning (working memory) and ToM for later academic abilities. We argue that ToM may be an important developmental precursor of math performance because both require an understanding of representations.

Abstract Background Since its first appearance in the USA in 1999, West Nile virus (WNV) has spread in the Western hemisphere and continues to represent an important public health concern. In the absence of effective treatment, there is a medical need for the development of a safe and efficient vaccine. Live attenuated WNV vaccines have shown promise in preclinical and clinical studies but might carry inherent risks due to the possibility of reversion to more virulent forms. Subunit vaccines based on the large envelope (E) glycoprotein of WNV have therefore been explored as an alternative approach. Although these vaccines were shown to protect from disease in animal models, multiple injections and/or strong adjuvants were required to reach efficacy, underscoring the need for more immunogenic, yet safe DIII-based vaccines. Results We produced a conjugate vaccine against WNV consisting of recombinantly expressed domain III (DIII) of the E glycoprotein chemically cross-linked to virus-like particles derived from the recently discovered bacteriophage AP205. In contrast to isolated DIII protein, which required three administrations to induce detectable antibody titers in mice, high titers of DIII-specific antibodies were induced after a single injection of the conjugate vaccine. These antibodies were able to neutralize the virus in vitro and provided partial protection from a challenge with a lethal dose of WNV. Three injections of the vaccine induced high titers of virus-neutralizing antibodies, and completely protected mice from WNV infection. Conclusions The immunogenicity of DIII can be strongly enhanced by conjugation to virus-like particles of the bacteriophage AP205. The superior immunogenicity of the conjugate vaccine with respect to other DIII-based subunit vaccines, its anticipated favourable safety profile and low production costs highlight its potential as an efficacious and cost-effective prophylaxis against WNV.

Abstract Background Dengue disease severity is usually classified using criteria set up by the World Health Organization (WHO). We aimed to assess the diagnostic accuracy of the WHO classification system and modifications to this system, and evaluated their potential practical usefulness. Methods Patients, admitted consecutively to the hospital with severe dengue, were classified using the WHO classification system and modifications to this system. Treating physicians were asked to classify patients immediately after discharge. We calculated the sensitivity of the various classification systems for the detection of shock and the agreement between the various classification systems and the treating physician's classification. Results Of 152 patients with confirmed dengue, sixty-six (43%) had evidence of circulatory failure. The WHO classification system had a sensitivity of 86% (95%CI 76–94) for the detection of patients with shock. All modifications to the WHO classification system had a higher sensitivity than the WHO classification system (sensitivity ranging from 88% to 99%). The WHO classification system was in only modest agreement with the intuitive classification by treating physicians whereas several modified classification systems were in good agreement. Conclusion The use of the WHO classification system to classify dengue disease severity is to be questioned, because it is not accurate in correctly classifying dengue disease severity and it lacks sufficient agreement with clinical practice.

Tick-borne encephalitis (TBE) is a serious neurological disease caused by TBE virus (TBEV). Because antiviral treatment options are not available, vaccination is the key prophylactic measure against TBEV infections. Despite the availability of effective vaccines, cases of vaccination breakthrough infections have been reported. The multienzymatic non-structural protein 3 (NS3) of orthoflaviviruses plays an important role in polyprotein processing and virus replication. In the present study, we evaluated NS3 of TBEV as a potential vaccine target for the induction of protective immunity. To this end, a recombinant modified vaccinia virus Ankara that drives the expression of the TBEV NS3 gene (MVA-NS3) was constructed. MVA-NS3 was used to immunize C57BL/6 mice. It induced NS3-specific immune responses, in particular T cell responses, especially against the helicase domain of NS3. However, MVA-NS3-immunized mice were not protected from subsequent challenge infection with a lethal dose of the TBEV strain Neudoerfl, indicating that in contrast to immunity to prME and NS1, NS3-specific immunity is not an independent correlate of protection against TBEV in this mouse model.

An adult male Bell’s hinge-back tortoise (Kinixys belliana) was admitted to a veterinary clinic due to a swelling in the oral cavity. Physical examination revealed an approximately 2.5 × 1.5 cm sized, irregularly shaped tissue mass with villiform projections extending from its surface located in the oropharyngeal cavity. An initial biopsy was performed, and the lesion was diagnosed as squamous papilloma. Swabs taken for virological examination tested negative with specific PCRs for papillomavirus and herpesvirus. Further analysis of the oropharyngeal mass via metagenomic sequencing revealed sequence reads corresponding to a member of the family Adintoviridae. The tissue mass was removed one week after the initial examination. The oral cavity remained unsuspicious in follow-up examinations performed after one, five and twenty weeks. However, a regrowth of the tissue was determined 23 months after the initial presentation. The resampled biopsy tested negative for sequence reads of Adintoviridae. Conclusively, this report presents the diagnostic testing and therapy of an oral cavity lesion of unknown origin. The significance of concurrent metagenomic determination of adintovirus sequence reads within the tissue lesion is discussed.

Abstract Background Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations. Whether the insertion/deletion (4G/5G) polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death from dengue is unknown. We, therefore, investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue. Methods A total of 194 patients admitted to the Dr. Kariadi Hospital in Semarang, Indonesia, with clinical suspected severe dengue virus infection were enrolled. Blood samples were obtained on day of admission, days 1, 2 and 7 after admission and at a 1-month follow-up visit. Plasma concentrations of PAI-1 were measured using a sandwich ELISA kit. The PAI-1 4G/5G polymorphism was typed by allele-specific PCR analysis. Results Concentrations of PAI-1 on admission and peak values of PAI-1 during admission were higher than the values measured in healthy controls. Survival was significantly worse in patients with PAI-1 concentrations in the highest tertile (at admission: OR 4.7 [95% CI 0.9–23.8], peak value during admission: OR 6.3 [95%CI 1.3–30.8]). No association was found between the PAI-1 4G/5G polymorphism, and PAI-1 plasma concentrations, dengue disease severity and mortality from dengue. Conclusion These data suggest that the 4G/5G polymorphism has no significant influence on PAI-1 concentrations in dengue virus infected patients and is not associated with the risk of death from dengue. Other factors contributing to the variability of PAI-1 plasma concentrations in patients with dengue need to be explored.

The Eurasian lynx (Lynx lynx) represents an endangered species with only small populations remaining in Central Europe. Knowledge about the threat posed by potential infectious agents to these animals is crucial for informing ongoing protection measures. Canine distemper virus (CDV) is known to have a wide host range with infection reported in many mammalian species including several lynx species (Lynx pardinus, Lynx canadensis, Lynx rufus), but is an extremely rare finding in the Eurasian lynx. The present report describes a case of a Eurasian lynx showing central nervous signs, including apathy and ataxia. A CT scan revealed multiple hypodense areas in different localizations within the brain as well as enlarged liquid filled areas, leading to the suspicion of a degenerative process. Due to clinical deterioration, the animal was euthanized and submitted for macroscopical and histological investigations. Histological investigations revealed multifocal demyelinations in the cerebellum, brain stem and cervical spinal cord as well as a multifocal, perivascular, lymphohistiocytic meningoencephalitis. A CDV infection was confirmed by immunohistochemistry and RT-PCR analyses. This CDV infection of a Eurasian lynx resembles a classical chronic manifestation of distemper in dogs and highlights the threat posed by canine distemper to this species.

IntroductionTick-borne encephalitis virus (TBEV) is one of the most relevant tick-transmitted neurotropic arboviruses in Europe and Asia and the causative agent of tick-borne encephalitis (TBE). Annually more than 10,000 TBE cases are reported despite having vaccines available. In Europe, the vaccines FSME-IMMUN® and Encepur® based on formaldehyde-inactivated whole viruses are licensed. However, demanding vaccination schedules contribute to sub-optimal vaccination uptake and breakthrough infections have been reported repeatedly. Due to its immunogenic properties as well as its role in viral replication and disease pathogenesis, the non-structural protein 1 (NS1) of flaviviruses has become of interest for non-virion based flavivirus vaccine candidates in recent years.MethodsTherefore, immunogenicity and protective efficacy of TBEV NS1 expressed by neuraminidase (NA)-deficient Influenza A virus (IAV) or Modified Vaccinia virus Ankara (MVA) vectors were investigated in this study.ResultsWith these recombinant viral vectors TBEV NS1-specific antibody and T cell responses were induced. Upon heterologous prime/boost regimens partial protection against lethal TBEV challenge infection was afforded in mice.DiscussionThis supports the inclusion of NS1 as a vaccine component in next generation TBEV vaccines.

Abstract A pol-fragment of simian immunodeficiency virus (SIV) that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus) was detected in two mandrills (Mandrillus sphinx) from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely to be hybrids. Their mitochondrial haplotype suggested that they descended from founder animals in Cameroon or northern Gabon, close to the habitat of the drill. SIVdrl has once before been found in a wild-caught mandrill from the same region, indicating that mandrills are naturally infected with a SIVdrl-like virus. This suggests that mandrills are the first primate species to be infected with three strains of SIV: SIVmnd1, SIVmnd2, and SIVdrl.

Within the Great Plains region of North America, oxbow wetlands were lost as streams were channelized and straightened to allow for agricultural use of the landscape. Topeka Shiner, which rely on these oxbow wetlands, have declined in abundance, currently occupy 20% of their historical geographic range, and are now an endangered species. A large emphasis has been placed on restoring oxbow wetlands to recover Topeka Shiner populations. As the number of oxbow restorations has increased, so has the number of monitoring projects focused on these habitats. Currently, conservation practitioners rely on the presence of Topeka Shiner to determine the success of an oxbow restoration. Given the rarity of the species, this method is likely ineffective. Within this study we attempt to create a model that can be used to determine the success of an oxbow restoration that will benefit the Topeka Shiner without relying on the presence of the species in the wetland. We used multiple fish community metrics and modelling strategies to determine the best model for predicting Topeka Shiner CPUE and presence/absence within oxbows. We determined that the top models were ineffective at predicting Topeka Shiner CPUE and presence/absence. Our findings illustrate the random nature by which fish communities become established within oxbows, and the island-like nature of oxbows in terms of how fish communities may become established and change over time. These findings indicate that the success of oxbow restoration for Topeka Shiner needs to be defined at a larger scale than for individual oxbows. Furthermore, our findings corroborate the inability of previous studies to determine reproducible associations of Topeka Shiner with various fish community metrics., INTRODUCTION Human land use and resulting declines in aquatic ecosystem habitat abundance and quality have led to declines in freshwater fish abundance and species diversity (Jelks el al., 2008; Gido, [...]