Artificial intelligence-based detection of paediatric appendicular skeletal fractures: performance and limitations for common fracture types and locations.

BACKGROUND: Research into artificial intelligence (AI)-based fracture detection in children is scarce and has disregarded the detection of indirect fracture signs and dislocations. OBJECTIVE: To assess the diagnostic accuracy of an existing AI-tool for the detection of fractures, indirect fracture signs, and dislocations. MATERIALS AND METHODS: An AI software, BoneView (Gleamer, Paris, France), was assessed for diagnostic accuracy of fracture detection using paediatric radiology consensus diagnoses as reference. Radiographs from a single emergency department were enrolled retrospectively going back from December 2021, limited to 1,000 radiographs per body part. Enrolment criteria were as follows: suspected fractures of the forearm, lower leg, or elbow; age 0-18 years; and radiographs in at least two projections. RESULTS: Lower leg radiographs showed 607 fractures. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were high (87.5%, 87.5%, 98.3%, 98.3%, respectively). Detection rate was low for toddler's fractures, trampoline fractures, and proximal tibial Salter-Harris-II fractures. Forearm radiographs showed 1,137 fractures. Sensitivity, specificity, PPV, and NPV were high (92.9%, 98.1%, 98.4%, 91.7%, respectively). Radial and ulnar bowing fractures were not reliably detected (one out of 11 radial bowing fractures and zero out of seven ulnar bowing fractures were correctly detected). Detection rate was low for styloid process avulsions, proximal radial buckle, and complete olecranon fractures. Elbow radiographs showed 517 fractures. Sensitivity and NPV were moderate (80.5%, 84.7%, respectively). Specificity and PPV were high (94.9%, 93.3%, respectively). For joint effusion, sensitivity, specificity, PPV, and NPV were moderate (85.1%, 85.7%, 89.5%, 80%, respectively). For elbow dislocations, sensitivity and PPV were low (65.8%, 50%, respectively). Specificity and NPV were high (97.7%, 98.8%, respectively). CONCLUSIONS: The diagnostic performance of BoneView is promising for forearm and lower leg fractures. However, improvement is mandatory before clinicians can rely solely on AI-based paediatric fracture detection using this software.

Listening to the Voices of Health Care Workers During the COVID-19 Pandemic: A Qualitative Study Providing In-Depth Insights Into Ethical and Individual Challenges.

In their daily practice, health care workers (HCWs) experience the effects of tensions between professional ethos and work realities, which can lead to ethical dilemmas. We aim to explore the ethical dilemmas that affected HCWs in Germany during the COVID-19 pandemic and to understand these in the context of the German health system. Between April and December 2022, we interviewed HCWs from various levels of care and key informants responsible for decisions related to HCWs in Germany. Three themes were identified in the data analyzed from 78 participants. The first highlighted the potency of pre-existing health system problems during the COVID-19 pandemic. The second captured the ethical dilemmas that were described as having arisen due to the tension between professional ethos and structural constraints. The third included factors related to increasing or diminishing the implications of ethical dilemmas. A lack of opportunities for HCWs to participate in political and managerial decisions was suggested to result in policies that do not meet the needs of HCWs and patients. Positive interpersonal interactions were described as helpful when coping with dilemmatic decision-making situations. In order to avoid negative consequences caused by unresolved ethical dilemmas, including moral distress, among HCWs, staff shortages and decision-making in the German health system urgently need to be addressed. HCWs' working conditions regularly evoke ethical dilemmas, particularly during public health emergencies. Together with HCWs, decision-makers must develop new models for working in health care settings that are in line with HCWs' professional ethos.

Caregiver acceptance of malaria vaccination for children under 5 years of age and associated factors: cross-sectional household survey, Guinea and Sierra Leone, 2022.

BACKGROUND: Malaria is a leading cause of death and reduced life span in Guinea and Sierra Leone, where plans for rolling out the malaria vaccine for children are being made. There is little evidence about caregiver acceptance rates to guide roll-out policies. To inform future vaccine implementation planning, this analysis aimed to assess potential malaria vaccine acceptance by caregivers and identify factors associated with acceptance in Guinea and Sierra Leone. METHODS: A cross-sectional household survey using lot quality assurance sampling was conducted in three regions per country between May 2022 and August 2022. The first survey respondent in each household provided sociodemographic information. A household member responsible for childcare shared their likelihood of accepting a malaria vaccine for their children under 5 years and details about children's health. The prevalence of caregiver vaccine acceptance was calculated and associated factors were explored using multivariable logistic regression modelling calculating adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Caregivers in 76% of 702 sampled households in Guinea and 81% of 575 households in Sierra Leone were accepting of a potential vaccine for their children. In both countries, acceptance was lower in remote areas than in urban areas (Guinea: aOR 0.22 [95%CI 0.09-0.50], Sierra Leone: 0.17 [0.06-0.47]). In Guinea, acceptance was lower among caregivers living in the richest households compared to the poorest households (0.10 [0.04-0.24]), among those whose children were tested for malaria when febrile (0.54 [0.34-0.85]) and in households adopting more preventative measures against malaria (0.39 [0.25-0.62]). Better knowledge of the cause of malaria infection was associated with increased acceptance (3.46 [1.01-11.87]). In Sierra Leone, vaccine acceptance was higher among caregivers living in households where the first respondent had higher levels of education as compared to lower levels (2.32 [1.05-5.11]). CONCLUSION: In both countries, malaria vaccine acceptance seems promising for future vaccine roll-out programmes. Policy makers might consider regional differences, sociodemographic factors, and levels of knowledge about malaria for optimization of implementation strategies. Raising awareness about the benefits of comprehensive malaria control efforts, including vaccination and other preventive measures, requires attention in upcoming campaigns.

The pathways between natural disasters and violence against children: a systematic review.

BACKGROUND: Natural disasters are increasingly affecting a larger segment of the world's population. These highly disruptive events have the potential to produce negative changes in social dynamics and the environment which increase violence against children. We do not currently have a comprehensive understanding of how natural disasters lead to violence against children despite the growing threat to human populations and the importance of violence as a public health issue. The mapping of pathways to violence is critical in designing targeted and evidence-based prevention services for children. We systematically reviewed peer-reviewed articles and grey literature to document the pathways between natural disasters and violence against children and to suggest how this information could be used in the design of future programming. METHODS: We searched 15 bibliographic databases and six grey literature repositories from the earliest date of publication to May 16, 2018. In addition, we solicited grey literature from humanitarian agencies globally that implement child-focused programming after natural disasters. Peer-reviewed articles and grey literature that presented original quantitative or qualitative evidence on how natural disasters led to violence against children were included. The authors synthesized the evidence narratively and used thematic analysis with a constant comparative method to articulate pathways to violence. RESULTS: We identified 6276 unduplicated publications. Nine peer-reviewed articles and 17 grey literature publications met the inclusion criteria. The literature outlined five pathways between natural disasters and violence, including: (i) environmentally induced changes in supervision, accompaniment, and child separation; (ii) transgression of social norms in post-disaster behavior; (iii) economic stress; (iv) negative coping with stress; and (v) insecure shelter and living conditions. CONCLUSIONS: Service providers would benefit from systematic documentation to a high-quality standard of all possible pathways to violence in tailoring programming after natural disasters. The identified pathways in this review provide a foundation for designing targeted prevention services. In addition, the positive coping strategies within certain affected families and communities can be leveraged in implementing strength-based approaches to violence prevention.

An Insect Counteradaptation against Host Plant Defenses Evolved through Concerted Neofunctionalization.

Antagonistic chemical interactions between herbivorous insects and their host plants are often thought to coevolve in a stepwise process, with an evolutionary innovation on one side being countered by a corresponding advance on the other. Glucosinolate sulfatase (GSS) enzyme activity is essential for the Diamondback moth, Plutella xylostella, to overcome a highly diversified secondary metabolite-based host defense system in the Brassicales. GSS genes are located in an ancient cluster of arylsulfataselike genes, but the exact roles of gene copies and their evolutionary trajectories are unknown. Here, we combine a functional investigation of duplicated insect arylsulfatases with an analysis of associated nucleotide substitution patterns. We show that the Diamondback moth genome encodes three GSSs with distinct substrate spectra and distinct expression patterns in response to glucosinolates. Contrary to our expectations, early functional diversification of gene copies was not indicative of a coevolutionary arms race between host and herbivore. Instead, both copies of a duplicated arylsulfatase gene evolved concertedly in the context of an insect host shift to acquire novel detoxifying functions under positive selection, a pattern of duplicate gene retention that we call "concerted neofunctionalization."

Integration of PET-imaging into radiotherapy treatment planning for low-grade meningiomas improves outcome.

PURPOSE: Meningiomas have an excellent survival prognosis, and radiotherapy (RT) is a central component of interdisciplinary treatment. During treatment planning, the definition of the target volume remains challenging using MR and CT imaging alone. This is the first study to analyze the impact of additional PET-imaging on local control (LC) and overall survival (OS) after high-precision RT. METHODS: We analyzed 339 meningiomas treated between 2000 and 2018. For analyses, we divided the patients in low-grade (n = 276) and high-grade (n = 63) cases. We performed RT in an adjuvant setting due to subtotal resection or later due to recurrent tumor growth. The target volumes were delineated based on diagnostic CT and MRI and, if available, additional PET-imaging (low-grade: n = 164, 59.4%; high-grade: n = 39, 61.9%) with either 68Ga-Dotanoc/Dotatoc, 18F-fluoroethyltyrosine or 11C-methionine tracer. Patients were treated with fractionated stereotactic RT with a median total dose and dose per fraction of 54 Gy and 1.8 Gy, respectively. RESULTS: Median follow-up was 5.6 years. For low-grade meningiomas, mean OS was 15.6 years and mean LC was 16.9 years; for high-grade cases mean OS was 11.6 years, and mean LC was 11.1 years. In univariate analyses, PET-imaging had a significant impact on OS (p = 0.035) and LC (p = 0.041) for low-grade meningiomas and remained significant (p = 0.015) for LC in the multivariate analysis. For high-grade cases, PET did not influence both OS and LC. Further prognostic factors could be identified. CONCLUSIONS: For low-grade meningiomas, we showed that the addition of PET-imaging for target volume definition led to a significantly enhanced LC. Thus, PET improves the detection of tumor cells and helps distinguish between healthy tissue and meningioma tissue, especially during the treatment planning process.

Molecular signatures of selection associated with host plant differences in Pieris butterflies.

Adaptive traits that enable organisms to conquer novel niches and experience subsequent diversification are ecologically and evolutionarily important. The larvae of Pieris butterflies express nitrile-specifier proteins (NSPs), a key innovation for overcoming the glucosinolate (GLS)-myrosinase-based defence system of their Brassicales host plants. Nitrile-specifier proteins are a member of the NSP-like gene family, which includes the major allergen (MA) protein, a paralog of NSP with a GLS-disarming function, and a single domain major allergen (SDMA) protein, whose function is unknown. The arms-race between GLS-based defences and the NSP-like gene family is suggested to mediate diversification in both Pierid butterflies and Brassicales plants. Here, we tested whether the expected strong selection on NSP-like gene family correlates with shifts in host plant spectra among Pierid butterflies. We combined feeding experiments using 25 Brassicaceae plants and five Pieris species with larval transcriptome data to investigate the patterns of selection acting on NSP-like gene family members. Although we observed significantly elevated nonsynonymous to synonymous substitution rate ratios in NSPs on branches associated with changes in patterns of host plant usage, no such pattern was observed in MAs or SDMAs. Furthermore, we found evidence for positive selection of NSP at a phylogenetic branch which reflects different host plant spectra. Our data indicate that the NSP-related gene members have evolved differently: NSPs have accumulated more amino acid changes in response to shifting preferences for host plants, whereas MAs and SDMAs appear to be more conserved. Further detailed functional assays of these genes would provide important insights to understand their role in the chemical arms-race between Pieris butterflies and their Brassicales host plants.

The butterfly plant arms-race escalated by gene and genome duplications.

Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits.

High-precision radiotherapy for meningiomas : Long-term results and patient-reported outcome (PRO).

OBJECTIVE: To evaluate long-term outcome after high-precision radiotherapy (RT) of meningioma patients in terms of survival and side effects. METHODS: We analyzed 275 meningioma cases: 147 low-grade and 43 high-grade meningiomas (WHO II: n = 40, III: n = 3). In all, 85 patients had no pathologically confirmed histology but were determined as low-grade based on multimodal imaging. Surgery was performed in 183 cases. RT was delivered as either radiosurgery (RS, n = 16), fractionated stereotactic radiotherapy (FSRT, n = 241), or intensity-modulated radiation therapy (IMRT, n = 18). Of 218 patients contacted for patient-reported-outcome (PRO), 207 responded (95%). RESULTS: Median follow-up was 7.2 years. For low-grade meningioma the survival rate (OS) was 97% at 3 years, 85% at 10 years, and 64% at 15 years, for atypical meningioma 91% at 3 years, 62% at 10 years, and 50% at 15 years. Local control rate (PFS) for low-grade meningioma was 91% at 3 years, 87% at 5 years, and 86% at 10 years, for atypical cases 67% at 3 years and 55% at 5 years. Of all, 3.0% of patients reported worsened or new symptoms grade ≥3 during RT and the first 6 months thereafter; 17.5% reported a deterioration after more than 2 years. We found the prognostic factors tumor volume and age significantly influencing OS and PFS. CONCLUSION: Complemented by PRO, we found long-term low toxicity rates in addition to excellent local control. Thus, due to the beneficial risk-benefit profile of benign and high-risk meningiomas, RT should be performed as adjuvant treatment and should not be postponed until tumor progression.

Fractionated vs. single-fraction stereotactic radiotherapy in patients with vestibular schwannoma : Hearing preservation and patients' self-reported outcome based on an established questionnaire.

BACKGROUND: Stereotactic radiotherapy (RT) has been established as a valid treatment alternative in patients with vestibular schwannoma (VS). There is ongoing controversy regarding the optimal fractionation. Hearing preservation may be the primary goal for patients with VS, followed by maintenance of quality of life (QoL). METHODS: From 2002 to 2015, 184 patients with VS were treated with radiosurgery (RS) or fractionated stereotactic radiotherapy (FSRT). A survey on current symptoms and QoL was conducted between February and June 2016. RESULTS: Median follow-up after RT was 7.5 years (range 0-14.4 years). Mean overall survival (OS) after RT was 31.1 years, with 94 and 87% survival at 5 and 10 years, respectively [corrected]. Mean progression-free survival (PFS) was 13.3 years, with 5­ and 10-year PFS of 92%. Hearing could be preserved in RS patients for a median of 36.3 months (range 2.3-13.7 years). Hearing worsened in 17 (30%) cases. Median hearing preservation for FSRT was 48.7 months (range 0.0-13.8 years); 29 (23%) showed hearing deterioration. The difference in hearing preservation was not significant between RS and FSRT (p = 0.3). A total of 123/162 patients participated in the patient survey (return rate 76%). The results correlate well with the information documented in the patient files for tinnitus and facial and trigeminal nerve toxicity. Significant differences appeared regarding hearing impairment, gait uncertainty, and imbalance. CONCLUSION: These data confirm that RS and FSRT are comparable in terms of local control for VS. RS should be reserved for smaller lesions, while FSRT can be offered independently of tumor size. Patient self-reported outcome during follow-up is of high value. The established questionnaire could be validated in the independent cohort.

Strategies to foster community engagement for epidemic and pandemic preparedness and response in sub-Saharan Africa: a scoping review protocol.

INTRODUCTION: The surge of public health emergencies over the past decade has disproportionately affected sub-Saharan Africa. These include outbreaks of infectious diseases such as Ebola, Monkeypox and COVID-19. Experience has shown that community participation is key to the successful implementation of infection control activities. Despite the pivotal role community engagement plays in epidemic and pandemic preparedness and response activities, strategies to engage communities have been underexplored to date, particularly in sub-Sahara Africa. Furthermore, reviews conducted have not included evidence from the latest pandemic, COVID-19. This scoping review aims to address these gaps by documenting through available literature, the strategies for community engagement for epidemic and pandemic preparedness and response in sub-Sahara Africa. METHODS AND ANALYSIS: We will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews and the methodological framework for scoping reviews from Arksey and O'Malley to guide the review. Two reviewers will develop a systematic search strategy to identify articles published from January 2014 to date. We will retrieve peer-reviewed research published in the English language from databases including Embase, EBSCO-host, PubMed, Global Health, CINAHL, Google Scholar and Web of Science. Additionally, we will search for relevant grey literature from the websites of specific international organisations, public health institutes and Government Ministries of Health in African countries. After the removal of duplicates, the two reviewers will independently screen all titles, abstracts and full articles to establish the relevance of each study for inclusion in the review. We will extract data from the included articles using a data extraction tool and present the findings in tabular form with an accompanying narrative to aid comprehension. ETHICS AND DISSEMINATION: Ethical approval is not required for the conduct of scoping reviews. We plan to disseminate the findings from this review through publications in a peer-reviewed journal, presentations at conferences and meetings with policy-makers.

Policy responses to the COVID-19 pandemic in West Africa: a scoping review protocol.

INTRODUCTION: Four years after the devastating Ebola outbreak, governments in West Africa were quick to implement non-pharmaceutical interventions (NPIs) in response to the rapid spread of SARS-CoV-2. The NPIs implemented included physical distancing, closure of schools and businesses, restrictions on public gatherings and mandating the use of face masks among others. In the absence of widely available vaccinations, NPIs were the only known means to try to slow the spread of COVID-19. While numerous studies have assessed the effectiveness of these NPIs in high-income countries, less is known about the processes that lead to the adoption of policies and the factors that influence their implementation and adherence in low-income and middle-income countries. The objective of this scoping review is to understand the extent and type of evidence in relation to the policy formulation, decision-making and implementation stages of NPIs in West Africa. METHODS AND ANALYSIS: A scoping review will be undertaken following the guidance developed by Arskey and O'Malley, the Joanna Briggs Institute (JBI) methodology for scoping reviews and the PRISMA guidelines for Scoping Reviews. Both peer-reviewed and grey literature will be searched using Web of Science, Embase, Scopus, APA PsycInfo, WHO Institutional Repository for Information Sharing, JSTOR and Google Advanced Search, and by searching the websites of the WHO, and the West African Health Organisation. Screening will be conducted by two reviewers based on inclusion and exclusion criteria, and data will be extracted, coded and narratively synthesised. ETHICS AND DISSEMINATION: We started this scoping review in May 2023, and anticipate finishing by April 2024. Ethics approval is not required since we are not collecting primary data. This protocol was registered at Open Science Framework (https://osf.io/gvek2/). We plan to disseminate this research through publications, conference presentations and upcoming West African policy dialogues on pandemic preparedness and response.

Dog Owners' Perceptions of Canine Body Composition and Effect of Standardized Education for Dog Owners on Body Condition Assessment of Their Own Dogs.

Overweight in dogs is an increasing problem, with a prevalence of about 30% in Sweden. To prevent the negative health effects of overweight, it is important to identify and treat canine overweight. Dog owners are essential for such interventions. The aim of this study was to evaluate dog owners' perceptions of various canine body compositions via indirect assessment based on photos and direct assessment of their own dogs. A second aim was to evaluate the effect of a standardized practical education for dog owners on body condition score (BCS) assessment of their own dogs. The 9-point BCS scale was used, and two study samples were recruited: one was a survey sample where 564 dog owners assessed the BCS of dogs using photos, and one sample was a separate clinical sample where 82 dogs were assessed by their owners and by veterinary health care personnel. The initial BCS assessment by the dog owners in the clinical sample (mean ± SD) was significantly lower (4.6 ± 1.0) than the BCS assessed by the veterinary health care personnel (5.2 ± 1.1), but the owners improved significantly after receiving the standardized education (5.1 ± 1.0) (both p < 0.0001) and performed as accurately as the veterinary health care personnel (p = 0.99). The results should be verified in the broader dog owner population based on a randomized selection of participants. "Weight blindness", defined here as an underassessment of normal-weight dogs and an inability to identify overweight dogs, is likely to have a negative impact on canine overweight prevalence. Deeper knowledge about dog owners' perceptions can inform the development of new strategies to help prevent and manage canine overweight, whereof standardized practical education on BCS assessment is shown here to be one example.

Technical feasibility and clinical success of direct "free hand" EUS-guided gastroenterostomy in patients with gastric outlet obstruction.

Background and study aims Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) with lumen-apposing metal stents (LAMS) appears to be a promising intervention in management of gastroduodenal out obstruction (GOO), particularly for patients for whom surgery is high risk or in a palliative setting. This study aimed to evaluate the technical feasibility, procedure-associated adverse events (AEs), and clinical outcome of direct "free hand" EUS-GE. Patients and methods This retrospective two-center study included patients who underwent direct "free hand" EUS-GE (April 2017 to March 2021) investigating technical success (correctly placed LAMS), clinical outcome (successful oral nutrition), and management of procedure-associated AEs. "Free hand" was defined as the use of the electrocautery enhanced stent delivery system alone without additional guidewire-assistance for EUS-GE creation. Results Forty-five patients (58 % women/42 % men; mean age 65 years) with malignant (n = 39), benign (n = 4) or unclear (n = 2) GOO underwent direct "free hand" EUS-GE. The technical success rate was 98 % (44/45). Of the patients, 95% (42/44) had less vomiting and increased ability to tolerate oral food intake after the intervention. In one patient, a second EUS-GE was necessary to achieve sufficient clinical improvement. Procedure-associated AEs were observed in 24 % (11/45) of cases including stent misplacement (n = 7), leakage (n = 1), development of a gastrojejunocolic fistula (n = 1), and bleeding (n = 2), which could be all managed endoscopically. Conclusions Direct EUS-GE has a favorable risk-benefit profile for patients with GOO, showing high technical success rates, manageable AEs, and rapid symptom relief.

Tmem160 contributes to the establishment of discrete nerve injury-induced pain behaviors in male mice.

Chronic pain is a prevalent medical problem, and its molecular basis remains poorly understood. Here, we demonstrate the significance of the transmembrane protein (Tmem) 160 for nerve injury-induced neuropathic pain. An extensive behavioral assessment suggests a pain modality- and entity-specific phenotype in male Tmem160 global knockout (KO) mice: delayed establishment of tactile hypersensitivity and alterations in self-grooming after nerve injury. In contrast, Tmem160 seems to be dispensable for other nerve injury-induced pain modalities, such as non-evoked and movement-evoked pain, and for other pain entities. Mechanistically, we show that global KO males exhibit dampened neuroimmune signaling and diminished TRPA1-mediated activity in cultured dorsal root ganglia. Neither these changes nor altered pain-related behaviors are observed in global KO female and male peripheral sensory neuron-specific KO mice. Our findings reveal Tmem160 as a sexually dimorphic factor contributing to the establishment, but not maintenance, of discrete nerve injury-induced pain behaviors in male mice.

Microevolutionary dynamics of a macroevolutionary key innovation in a Lepidopteran herbivore.

BACKGROUND: A molecular population genetics understanding is central to the study of ecological and evolutionary functional genomics. Population genetics identifies genetic variation and its distribution within and among populations, it reveals the demographic history of the populations studied, and can provide indirect insights into historical selection dynamics. Here we use this approach to examine the demographic and selective dynamics acting of a candidate gene involved in plant-insect interactions. Previous work documents the macroevolutionary and historical ecological importance of the nitrile-specifier protein (Nsp), which facilitated the host shift of Pieridae butterflies onto Brassicales host plants approximately 80 Myr ago. RESULTS: Here we assess the microevolutionary dynamics of the Nsp gene by studying the within and among-population variation at Nsp and reference genes in the butterfly Pieris rapae (Small Cabbage White). Nsp exhibits unexpectedly high amounts of amino acid polymorphism, unequally distributed across the gene. The vast majority of genetic variation exists within populations, with little to no genetic differentiation among four populations on two continents. A comparison of synonymous and nonsynonymous substitutions in 70 randomly chosen genes among P. rapae and its close relative Pieris brassicae (Large Cabbage White) finds Nsp to have a significantly relaxed functional constraint compared to housekeeping genes. We find strong evidence for a recent population expansion and no role for strong purifying or directional selection upon the Nsp gene. CONCLUSIONS: The microevolutionary dynamics of the Nsp gene in P. rapae are dominated by recent population expansion and variation in functional constraint across the repeated domains of the Nsp gene. While the high amounts of amino acid diversity suggest there may be significant functional differences among allelic variants segregating within populations, indirect tests of selection could not conclusively identify a signature of historical selection. The importance of using this information for planning future studies of potential performance and fitness consequences of the observed variation is discussed.

Phylogenetic relatedness and host plant growth form influence gene expression of the polyphagous comma butterfly (Polygonia c-album).

BACKGROUND: The mechanisms that shape the host plant range of herbivorous insect are to date not well understood but knowledge of these mechanisms and the selective forces that influence them can expand our understanding of the larger ecological interaction. Nevertheless, it is well established that chemical defenses of plants influence the host range of herbivorous insects. While host plant chemistry is influenced by phylogeny, also the growth forms of plants appear to influence the plant defense strategies as first postulated by Feeny (the "plant apparency" hypothesis). In the present study we aim to investigate the molecular basis of the diverse host plant range of the comma butterfly (Polygonia c-album) by testing differential gene expression in the caterpillars on three host plants that are either closely related or share the same growth form. RESULTS: In total 120 genes were identified to be differentially expressed in P. c-album after feeding on different host plants, 55 of them in the midgut and 65 in the restbody of the caterpillars. Expression patterns could be confirmed with an independent method for 14 of 27 tested genes. Pairwise similarities in upregulation in the midgut of the caterpillars were higher between plants that shared either growth form or were phylogenetically related. No known detoxifying enzymes were found to be differently regulated in the midgut after feeding on different host plants. CONCLUSION: Our data suggest a complex picture of gene expression in response to host plant feeding. While each plant requires a unique gene regulation in the caterpillar, both phylogenetic relatedness and host plant growth form appear to influence the expression profile of the polyphagous comma butterfly, in agreement with phylogenetic studies of host plant utilization in butterflies.

Evolutionary origins of a novel host plant detoxification gene in butterflies.

Chemical interactions between plants and their insect herbivores provide an excellent opportunity to study the evolution of species interactions on a molecular level. Here, we investigate the molecular evolutionary events that gave rise to a novel detoxifying enzyme (nitrile-specifier protein [NSP]) in the butterfly family Pieridae, previously identified as a coevolutionary key innovation. By generating and sequencing expressed sequence tags, genomic libraries, and screening databases we found NSP to be a member of an insect-specific gene family, which we characterized and named the NSP-like gene family. Members consist of variable tandem repeats, are gut expressed, and are found across Insecta evolving in a dynamic, ongoing birth-death process. In the Lepidoptera, multiple copies of single-domain major allergen genes are present and originate via tandem duplications. Multiple domain genes are found solely within the brassicaceous-feeding Pieridae butterflies, one of them being NSP and another called major allergen (MA). Analyses suggest that NSP and its paralog MA have a unique single-domain evolutionary origin, being formed by intragenic domain duplication followed by tandem whole-gene duplication. Duplicates subsequently experienced a period of relaxed constraint followed by an increase in constraint, perhaps after neofunctionalization. NSP and its ortholog MA are still experiencing high rates of change, reflecting a dynamic evolution consistent with the known role of NSP in plant-insect interactions. Our results provide direct evidence to the hypothesis that gene duplication is one of the driving forces for speciation and adaptation, showing that both within- and whole-gene tandem duplications are a powerful force underlying evolutionary adaptation.

Violence against children and natural disasters: A systematic review and meta-analysis of quantitative evidence.

OBJECTIVES: Reviews of violence against children in disaster settings focus on armed conflict. Little is understood about natural disasters which has implications in planning humanitarian response. We examined the magnitude and direction of the association between exposure to natural disasters and physical, emotional, and sexual violence against children, and assessed the quality of the evidence. METHODS: We searched 15 health and social science databases from first record until May 16, 2018. Publications describing all types of quantitative study design were eligible for inclusion. We presented study characteristics and quality in a narrative form and generated pooled estimates using a three-level random effects model. We evaluated Cochrane's Q with p-values below 0.10 and radial plots to assess heterogeneity. Planned subgroup analyses explored differential results by violence form, study design, and analysis method. RESULTS: 11 publications met inclusion criteria. The majority were cross-sectional studies examining physical or sexual violence in the United States. We found no evidence of a consistent association or directional influence between natural disasters and violence against children. Combined categorical violence outcomes had substantial heterogeneity [Q (df = 66) = 252.83, p < 0.001]. Subgroups without evidence of heterogeneity had confidence intervals that included a possible null effect. Our findings were mainly limited by inconsistencies in operational definitions of violence, a lack of representative sampling, and unclear establishment of temporal order between natural disaster exposure and violence outcomes. CONCLUSIONS: Based on the available evidence, we cannot confidently conclude that natural disasters increase the level or severity of violence against children above non-disaster settings, however heterogeneity and study quality hamper our ability to draw firm conclusions. More nuanced and rigorous research is needed to inform practice and policy as natural disasters increasingly affect human populations.