Transitioning children using home invasive mechanical ventilation from hospital to home: Discharge criteria, disparities, and ethical considerations.

Children using home invasive mechanical ventilation (HIMV), a valuable therapeutic option for chronic respiratory failure, constitute a growing population. Transitioning children using HIMV from hospital to home care is a complex process that requires a multidisciplinary approach involving healthcare professionals, caregivers, and community resources. Medical stability, caregiver competence, and home environment suitability are essential factors in determining discharge readiness. Caregiver education and training play a pivotal role in ensuring safe and effective home care. Simulation training and staged education progression are effective strategies for equipping caregivers with necessary skills. Resource limitations, inadequate home nursing support, and disparities in available community resources are common obstacles to successful HIMV discharge. International perspectives shed light on diverse healthcare systems and challenges faced by caregivers worldwide. While standardizing guidelines for HIMV discharge may be complex, collaboration among healthcare providers and the development of evidence-based regional guidelines can improve outcomes for children using HIMV and their caregivers. This review seeks to synthesize literature, provide expert guidance based on experience, and highlight components to safely discharge children using HIMV. It further assesses disparities and divergences within regional and international healthcare systems while addressing relevant ethical considerations.

A Functional Magnetic Resonance Imaging Meta-Analysis of Childhood Trauma.

BACKGROUND: Traumatic experiences during childhood significantly impact the developing brain and contribute to the development of numerous physical and mental health problems. To date, however, a comprehensive understanding of the functional impairments within the brain associated with childhood trauma histories does not exist. Previous functional magnetic resonance imaging (fMRI) meta-analytical tools required homogeneity of task types and the clinical populations studied, thus preventing the comprehensive pooling of brain-based deficits present in children who have trauma histories. We hypothesized that the use of the novel, data-driven Bayesian author-topic model approach to fMRI meta-analyses would reveal deficits in brain networks that span fMRI task types in children with trauma histories. METHODS: To our knowledge, this is the first study to use the Bayesian author-topic model approach to fMRI meta-analyses within a clinical population. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we present data-driven results obtained by combining activation patterns across heterogeneous tasks from 1428 initially screened studies and combining data from 14 studies that met study criteria (285 children with trauma histories, 297 healthy control children). RESULTS: Altered brain activity was revealed within 2 clusters in children with trauma histories compared to control children: the default mode/affective network/posterior insula and the central executive network. Our identified clusters were associated with tasks pertaining to cognitive processing, emotional/social stress, self-referential thought, memory, unexpected stimuli, and avoidance behaviors in youths who have experienced childhood trauma. CONCLUSIONS: Our results reveal disturbances in children with trauma histories within the modulation of the default mode and central executive networks-but not the salience network-regardless of whether children also presented with posttraumatic stress symptoms.

Bayesian multi-level modelling for predicting single and double feature visual search.

Performance in visual search tasks is frequently summarised by "search slopes" - the additional cost in reaction time for each additional distractor. While search tasks with a shallow search slopes are termed efficient (pop-out, parallel, feature), there is no clear dichotomy between efficient and inefficient (serial, conjunction) search. Indeed, a range of search slopes are observed in empirical data. The Target Contrast Signal (TCS) Theory is a rare example of quantitative model that attempts to predict search slopes for efficient visual search. One study using the TCS framework has shown that the search slope in a double-feature search (where the target differs in both colour and shape from the distractors) can be estimated from the slopes of the associated single-feature searches. This estimation is done using a contrast combination model, and a collinear contrast integration model was shown to outperform other options. In our work, we extend TCS to a Bayesian multi-level framework. We investigate modelling using normal and shifted-lognormal distributions, and show that the latter allows for a better fit to previously published data. We run a new fully within-subjects experiment to attempt to replicate the key original findings, and show that overall, TCS does a good job of predicting the data. However, we do not replicate the finding that the collinear combination model outperforms the other contrast combination models, instead finding that it may be difficult to conclusively distinguish between them.

A novel Shiga toxin 2a neutralizing antibody therapeutic with low immunogenicity and high efficacy.

Shiga toxin-producing Escherichia coli infections are difficult to treat due to the risk of antibiotic-induced stress upregulating the production of toxins, medical treatment is consequently limited to supportive care to prevent the development of hemolytic uremic syndrome (HUS). Here, we introduce a potentially therapeutic humanized mouse monoclonal antibody (Hu-mAb 2-5) targeting Stx2a, the most common Shiga toxin subtype identified from outbreaks. We demonstrate that Hu-mAb 2-5 has low immunogenicity in healthy adults ex vivo and high neutralizing efficacy in vivo, protecting mice from mortality and HUS-related tissue damage.

SwrA-mediated Multimerization of DegU and an Upstream Activation Sequence Enhance Flagellar Gene Expression in Bacillus subtilis.

The earliest genes in bacterial flagellar assembly are activated by narrowly-conserved proteins called master regulators that often act as heteromeric complexes. A complex of SwrA and the response-regulator transcription factor DegU is thought to form the master flagellar regulator in Bacillus subtilis but how the two proteins co-operate to activate gene expression is poorly-understood. Here we find using ChIP-Seq that SwrA interacts with a subset of DegU binding sites in the chromosome and does so in a DegU-dependent manner. Using this information, we identify a DegU-specific inverted repeat DNA sequence in the Pflache promoter region and show that SwrA synergizes with DegU phosphorylation to increase binding affinity. We further demonstrate that the SwrA/DegU footprint extends from the DegU binding site towards the promoter, likely through SwrA-induced DegU multimerization. The location of the DegU inverted repeat was critical and moving the binding site closer to the promoter impaired transcription by disrupting a previously-unrecognized upstream activation sequence (UAS). Thus, the SwrA-DegU heteromeric complex likely enables both remote binding and interaction between the activator and RNA polymerase. Small co-activator proteins like SwrA may allow selective activation of subsets of genes where activator multimerization is needed. Why some promoters require activator multimerization and some require UAS sequences is unknown.

SwrA extends DegU over an UP element to activate flagellar gene expression in Bacillus subtilis.

SwrA activates flagellar gene expression in Bacillus subtilis to increase the frequency of motile cells in liquid and elevate flagellar density to enable swarming over solid surfaces. Here we use ChIP-seq to show that SwrA interacts with many sites on the chromosome in a manner that depends on the response regulator DegU. We identify a DegU-specific inverted repeat DNA sequence and show that SwrA synergizes with phosphorylation to increase DegU DNA binding affinity. We further show that SwrA increases the size of the DegU footprint expanding the region bound by DegU towards the promoter. The location of the DegU inverted repeat was critical and moving the binding site closer to the promoter impaired transcription more that could be explained by deactivation. We conclude that SwrA/DegU forms a heteromeric complex that enables both remote binding and interaction between the activator and RNA polymerase in the context of an interceding UP element. We speculate that multimeric activators that resolve cis-element spatial conflicts are common in bacteria and likely act on flagellar biosynthesis loci and other long operons of other multi-subunit complexes. IMPORTANCE: In Bacteria, the sigma subunit of RNA polymerase recognizes specific DNA sequences called promoters that determine where gene transcription begins. Some promoters also have sequences immediately upstream called an UP element that is bound by the alpha subunit of RNA polymerase and is often necessary for transcription. Finally, promoters may be activated by transcription factors that bind DNA specific sequences and help recruit RNA polymerase to weak promoter elements. Here we show that the promoter for the 32 gene long flagellar operon in Bacillus subtilis requires an UP element and is activated by a heteromeric transcription factor of DegU and SwrA. Our evidence suggests that SwrA oligomerizes DegU over the DNA to allow RNA polymerase to interact with DegU and the UP element simultaneously. Heteromeric activator complexes are known but poorly-understood in bacteria and we speculate they may be needed to resolve spatial conflicts in the DNA sequence.

Development of Thermally Stable Nanobodies for Detection and Neutralization of Staphylococcal Enterotoxin B.

In this study, sixteen unique staphylococcal enterotoxin B (SEB)-reactive nanobodies (nbs), including ten monovalent and six bivalent nbs, were developed. All characterized nbs were highly specific for SEB and did not cross-react with other staphylococcal enterotoxins (SE). Several formats of highly sensitive enzyme-linked immunosorbent assays (ELISAs) were established using SEB nbs and a polyclonal antibody (pAb). The lowest limit of detection (LOD) reached 50 pg/mL in PBS. When applied to an ELISA to detect SEB-spiked milk (a commonly contaminated foodstuff), a LOD as low as 190 pg/mL was obtained. The sensitivity of ELISA was found to increase concurrently with the valency of nbs used in the assay. In addition, a wide range of thermal tolerance was observed among the sixteen nbs, with a subset of nbs, SEB-5, SEB-9, and SEB-62, retaining activity even after exposure to 95 °C for 10 min, whereas the conventional monoclonal and polyclonal antibodies exhibited heat-labile properties. Several nbs demonstrated a long shelf-life, with one nb (SEB-9) retaining 93% of its activity after two weeks of storage at room temperature. In addition to their usage in toxin detection, eleven out of fifteen nbs were capable of neutralizing SEB's super-antigenic activity, demonstrated by their inhibition on IL-2 expression in an ex vivo human PBMC assay. Compared to monoclonal and polyclonal antibodies, the nbs are relatively small, thermally stable, and easy to produce, making them useful in applications for sensitive, specific, and cost-effective detection and management of SEB contamination in food products.

Varying benefits of generalist and specialist camouflage in two versus four background environments.

Background-matching camouflage is a well-established strategy to reduce detection, but implementing this on heterogeneous backgrounds is challenging. For prey with fixed color patterns, solutions include specializing on a particular visual microhabitat, or adopting a compromise or generalist appearance, matching multiple backgrounds less well. Existing studies suggest both approaches can succeed, but most consider relatively simple scenarios, where artificial prey appear against two backgrounds differing in a single visual characteristic. Here, we used computer-based search tasks with human participants to test the relative benefits of specializing and generalizing for complex targets, displayed on either two or four types of naturalistic backgrounds. Across two background types, specialization was beneficial on average. However, the success of this strategy varied with search duration, such that generalist targets could outperform specialists over short search durations due to the presence of poorly matched specialists. Over longer searches, the remaining well-matched specialists had greater success than generalists, leading to an overall benefit of specialization at longer search durations. Against four different backgrounds, the initial cost to specialization was greater, so specialists and generalists ultimately experienced similar survival. Generalists performed better when their patterning was a compromise between backgrounds that were more similar to each other than when backgrounds were more different, with similarity in luminance more relevant than pattern differences. Time dependence in the relative success of these strategies suggests that predator search behavior may affect optimal camouflage in real-world situations.

Correction: Foraging as sampling without replacement: A Bayesian statistical model for estimating biases in target selection.

[This corrects the article DOI: 10.1371/journal.pcbi.1009813.].

A Bayesian Statistical Model Is Able to Predict Target-by-Target Selection Behaviour in a Human Foraging Task.

Foraging refers to search involving multiple targets or multiple types of targets, and as a model task has a long history in animal behaviour and human cognition research. Foraging behaviour is usually operationalized using summary statistics, such as average distance covered during target collection (the path length) and the frequency of switching between target types. We recently introduced an alternative approach, which is to model each instance of target selection as random selection without replacement. Our model produces estimates of a set of foraging biases, such as a bias to select closer targets or targets of a particular category. Here we apply this model to predict individual target selection events. We add a new start position bias to the model, and generate foraging paths using the parameters estimated from individual participants' pre-existing data. The model predicts which target the participant will select next with a range of accuracy from 43% to 69% across participants (chance is 11%). The model therefore explains a substantial proportion of foraging behaviour in this paradigm. The situations where the model makes errors reveal useful information to guide future research on those aspects of foraging that we have not yet explained.

Emergency treatment of anaphylaxis: concise clinical guidance.

Anaphylaxis is a serious systemic hypersensitivity reaction that is usually rapid in onset and may cause death. It is characterised by the rapid development of airway and/or breathing and/or circulation problems. Intramuscular adrenaline is the most important treatment, although, even in healthcare settings, many patients do not receive this intervention contrary to guidelines. The Resuscitation Council UK published an updated guideline in 2021 with some significant changes in recognition, management, observation and follow-up of patients with anaphylaxis. This is a concise version of the updated guideline.

Nest sanitation as an effective defence against brood parasitism.

Egg rejection is a crucial defence strategy against brood parasitism that requires the host to correctly recognise the foreign egg. Rejection behaviour has, thus, evolved in many hosts, facilitated by the visual differences between the parasitic and host eggs, and driving hosts to rely on colour and pattern cues. On the other hand, the need to recognise non-egg-shaped objects to carry out nest sanitation led birds to evolve the ability to discriminate and eject objects using mainly shape cues. However, little is known regarding the evolutionary significance of rejection behaviour in general and the cognitive processes underlying it. Here, we investigated the response of the barn swallow (Hirundo rustica) during pre-laying and laying stages to four objects types that differed in shape (eggs vs stars) and colour/pattern (mimetic vs non-mimetic) to investigate (1) what cognitive mechanisms are involved in object discrimination and (2) whether egg rejection is a direct defence against brood parasitism, or simply a product of nest sanitation. We found that swallows ejected stars more often than eggs in both stages, indicating that swallows possess a template for the shape of their eggs. Since the effect of colour/pattern on ejection decisions was minor, we suggest that barn swallows have not evolved a direct defence against brood parasitism but instead, egg ejection might be a product of their well-developed nest sanitation behaviour. Nonetheless, the fact that mimetic eggs were ejected especially in the pre-laying stage shows that nest sanitation could be an effective defence against poorly timed brood parasitism.

Foraging as sampling without replacement: A Bayesian statistical model for estimating biases in target selection.

Foraging entails finding multiple targets sequentially. In humans and other animals, a key observation has been a tendency to forage in 'runs' of the same target type. This tendency is context-sensitive, and in humans, it is strongest when the targets are difficult to distinguish from the distractors. Many important questions have yet to be addressed about this and other tendencies in human foraging, and a key limitation is a lack of precise measures of foraging behaviour. The standard measures tend to be run statistics, such as the maximum run length and the number of runs. But these measures are not only interdependent, they are also constrained by the number and distribution of targets, making it difficult to make inferences about the effects of these aspects of the environment on foraging. Moreover, run statistics are underspecified about the underlying cognitive processes determining foraging behaviour. We present an alternative approach: modelling foraging as a procedure of generative sampling without replacement, implemented in a Bayesian multilevel model. This allows us to break behaviour down into a number of biases that influence target selection, such as the proximity of targets and a bias for selecting targets in runs, in a way that is not dependent on the number of targets present. Our method thereby facilitates direct comparison of specific foraging tendencies between search environments that differ in theoretically important dimensions. We demonstrate the use of our model with simulation examples and re-analysis of existing data. We believe our model will provide deeper insights into visual foraging and provide a foundation for further modelling work in this area.

Adapting and validating the Autism Diagnostic Observation Schedule Version 2 for use with deaf children and young people.

We report a Delphi Consensus modification and first validation study of the Autism Diagnostic Observation Schedule - 2 with deaf children and young people (ADOS-2 Deaf adaptation). Validation included 122 deaf participants (aged 2-18 years), 63 with an Autism Spectrum Disorder (ASD). This was compared to a National Institute for Health and Clinical Excellence (NICE) guideline standard clinical assessment by blinded independent specialist clinicians. Results showed overall sensitivity 73% (95%CI 60%, 83%); specificity 71% (95%CI 58%, 82%), and for the more common modules 1-3 (combined as in previous studies) sensitivity 79% (95% CI 65-89%); specificity 79% (95% CI 66-89%) suggesting this instrument will be a helpful addition for use with deaf children and young people.

Determined to improve: An exploration of therapist perspectives about their development.

Scholars note that therapist performance is one of many factors that contribute to client treatment outcomes. Given that the performance of therapists matters, researchers have identified several methods and models for improving therapist effectiveness. However, scholars have yet to explore highly effective therapists' perspectives on their motivation to develop, the methods they use, and the impact of their efforts to develop. The present study used a consensual qualitative research (Hill & Knox, 2021) approach to explore dynamics underlying therapist development of expertise. Semistructured interviews were conducted with 12 therapists whose outcome data placed them in the top 25% of clinicians of their respective clinics, according to their supervisors. The researchers reached consensus at each stage of analysis as they organized data into domains, core ideas, and cross-analysis. Domains and corresponding subdomains were: (a) struggle with personal, external, and response to barriers subdomains, (b) therapist characteristics with striving, presence, skills, and values subdomains, and (c) development with early career, formal, feedback, relational, personal/identity subdomains. Implications for practice and areas for future research are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Generalist camouflage can be more successful than microhabitat specialisation in natural environments.

BACKGROUND: Crypsis by background-matching is a critical form of anti-predator defence for animals exposed to visual predators, but achieving effective camouflage in patchy and variable natural environments is not straightforward. To cope with heterogeneous backgrounds, animals could either specialise on particular microhabitat patches, appearing cryptic in some areas but mismatching others, or adopt a compromise strategy, providing partial matching across different patch types. Existing studies have tested the effectiveness of compromise strategies in only a limited set of circumstances, primarily with small targets varying in pattern, and usually in screen-based tasks. Here, we measured the detection risk associated with different background-matching strategies for relatively large targets, with human observers searching for them in natural scenes, and focusing on colour. Model prey were designed to either 'specialise' on the colour of common microhabitat patches, or 'generalise' by matching the average colour of the whole visual scenes. RESULTS: In both the field and an equivalent online computer-based search task, targets adopting the generalist strategy were more successful in evading detection than those matching microhabitat patches. This advantage occurred because, across all possible locations in these experiments, targets were typically viewed against a patchwork of different microhabitat areas; the putatively generalist targets were thus more similar on average to their various immediate surroundings than were the specialists. CONCLUSIONS: Demonstrating close agreement between the results of field and online search experiments provides useful validation of online citizen science methods commonly used to test principles of camouflage, at least for human observers. In finding a survival benefit to matching the average colour of the visual scenes in our chosen environment, our results highlight the importance of relative scales in determining optimal camouflage strategies, and suggest how compromise coloration can succeed in nature.

Evidence update for the treatment of anaphylaxis.

The Resuscitation Council UK has updated its Guideline for healthcare providers on the Emergency treatment of anaphylaxis. As part of this process, an evidence review was undertaken by the Guideline Working Group, using an internationally-accepted approach for adoption, adaptation, and de novo guideline development based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence to decision (EtD) framework, referred to as GRADE-ADOLOPMENT. A number of significant changes have been made, which will be reflected in the updated Guideline. These include: emphasis on repeating intramuscular adrenaline doses after 5 min if symptoms of anaphylaxis do not resolve; corticosteroids (e.g. hydrocortisone) no longer being routinely recommended for the emergency treatment of anaphylaxis; interventions for reactions which are refractory to initial treatment with adrenaline; a recommendation against the use of antihistamines for the acute management of anaphylaxis; and guidance relating to the duration of observation following anaphylaxis, and timing of discharge.

A new global ice sheet reconstruction for the past 80 000 years.

The evolution of past global ice sheets is highly uncertain. One example is the missing ice problem during the Last Glacial Maximum (LGM, 26 000-19 000 years before present) - an apparent 8-28 m discrepancy between far-field sea level indicators and modelled sea level from ice sheet reconstructions. In the absence of ice sheet reconstructions, researchers often use marine δ18O proxy records to infer ice volume prior to the LGM. We present a global ice sheet reconstruction for the past 80 000 years, called PaleoMIST 1.0, constructed independently of far-field sea level and δ18O proxy records. Our reconstruction is compatible with LGM far-field sea-level records without requiring extra ice volume, thus solving the missing ice problem. However, for Marine Isotope Stage 3 (57 000-29 000 years before present) - a pre-LGM period - our reconstruction does not match proxy-based sea level reconstructions, indicating the relationship between marine δ18O and sea level may be more complex than assumed.