Emerging Adult Resilience to the Early Stages of the COVID-Pandemic: A Systematic Scoping Review.

Human resilience to COVID-19 related stressors remains a pressing concern following the aftereffects of the pandemic and in the face of probable future pandemics. In response, we systematically scoped the available literature (n = 2030 records) to determine the nature and extent of research on emerging adults' adaptive responses to COVID-19 stressors in the early stages of the pandemic. Using a multisystem resilience framework, our narrative review of 48 eligible studies unpacks the personal, relational, institutional and/or physical ecological resources that enabled positive emerging adult outcomes to COVID-18 stressors. We found that there is a geographical bias in studies on this topic, with majority world contexts poorly represented. Resources leading to positive outcomes foregrounded psychological and social support, while institutional and ecological supports were seldom mentioned. Multisystemic combinations of resources were rarely considered. This knowledge has valuable implications for understanding resilience in the context of other large-scale adverse conditions.

Sensory processing profiles and autistic symptoms as predictive factors in autism spectrum disorder and Williams syndrome.

BACKGROUND: Unusual sensory responses were included in the diagnostic criteria for autism spectrum disorder (ASD), yet they are also common among individuals with other neurodevelopmental disorders, including Williams syndrome (WS). Cross-syndrome comparisons of sensory atypicalities and the evaluation of their syndrome specificity however have rarely been undertaken. We aimed to (1) examine and compare the sensory profiles in ASD and WS groups and (2) investigate whether autistic symptoms, including sensory processing scores, can predict a group membership. METHODS: Parents of 26 children with ASD and intellectual disability, 30 parents of children with ASD (no intellectual disability) and 26 with WS aged between 4 and 16 years were recruited. Parents completed the Sensory Profile to provide information about their children's sensory experiences and the Social Responsiveness Scale - Second Edition (SRS-2) to assess the degree of social impairment in their children. RESULTS: No significant differences were found in sensory processing scores between the three groups. Binary logistic regression analyses were undertaken with sensory quadrants and SRS-2 total score as factors. Models significantly predicted group membership, with Low Registration, Sensory Sensitivity and SRS-2 total score being significant predictors. CONCLUSIONS: The findings suggest that high rates of sensory atypicalities are a common neurodevelopmental characteristic that do not reliably distinguish between WS and ASD groups. Low Registration and Sensory Sensitivity-related behaviours might, however, be more specific to ASD. Further work is needed to explore what behaviours within sensory profiles can discriminate between neurodevelopmental disorders and should be included in diagnostic classifications.

Establishing and prioritizing research questions for the prevention, diagnosis and treatment of hair loss (excluding alopecia areata): the Hair Loss Priority Setting Partnership.

BACKGROUND: Hair and scalp problems are common. Unfortunately, many uncertainties exist around the most effective management and treatment strategies for these disorders. OBJECTIVES: To identify uncertainties in hair-loss management, prevention, diagnosis and treatment that are important to both people with hair loss and healthcare professionals. METHODS: A Hair Loss Priority Setting Partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in hair loss. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants; following exclusions 884 uncertainties relating to hair loss (excluding alopecia areata) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that was taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for hair loss (excluding alopecia areata) to guide researchers and funding bodies to support studies important to both patients and clinicians.

Establishing and prioritizing research questions for the treatment of alopecia areata: the Alopecia Areata Priority Setting Partnership.

BACKGROUND: Alopecia areata (AA) is a common hair loss disorder that results in patchy to complete hair loss. Many uncertainties exist around the most effective treatments for this condition. OBJECTIVES: To identify uncertainties in AA management and treatment that are important to both service users (people with hair loss, carers and relatives) and healthcare professionals. METHODS: An AA priority setting partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in AA. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants, of which 1012 uncertainties relating to AA (and variants) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that were taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for AA to guide researchers and funding bodies to support studies important to both patients and clinicians.

Genetic Diversity of Campylobacter jejuni and Campylobacter coli Isolates from Conventional Broiler Flocks and the Impacts of Sampling Strategy and Laboratory Method.

The genetic diversity of Campylobacter jejuni and Campylobacter coliisolates from commercial broiler farms was examined by multilocus sequence typing (MLST), with an assessment of the impact of the sample type and laboratory method on the genotypes of Campylobacter isolated. A total of 645C. jejuniand 106C. coli isolates were obtained from 32 flocks and 17 farms, with 47 sequence types (STs) identified. The Campylobacter jejuniisolates obtained by different sampling approaches and laboratory methods were very similar, with the same STs identified at similar frequencies, and had no major effect on the genetic profile of Campylobacter population in broiler flocks at the farm level. ForC. coli, the results were more equivocal. While some STs were widely distributed within and among farms and flocks, analysis of molecular variance (AMOVA) revealed a high degree of genetic diversity among farms forC. jejuni, where farm effects accounted for 70.5% of variance, and among flocks from the same farm (9.9% of variance for C. jejuni and 64.1% forC. coli). These results show the complexity of the population structure of Campylobacterin broiler production and that commercial broiler farms provide an ecological niche for a wide diversity of genotypes. The genetic diversity of C. jejuni isolates among broiler farms should be taken into account when designing studies to understand Campylobacter populations in broiler production and the impact of interventions. We provide evidence that supports synthesis of studies on C. jejuni populations even when laboratory and sampling methods are not identical.

Parent insights into atypicalities of social approach behaviour in Williams syndrome.

BACKGROUND: Individuals with Williams syndrome have been reported to show high levels of social interest and a desire to interact with others irrespective of their familiarity. This high social motivation, when combined with reduced intellectual capacity and a profile of atypical social behaviour, is important in terms of social vulnerability of individuals with the disorder. Therefore, social approach to unfamiliar people and the role of this behaviour within the Williams syndrome (WS) social phenotype warrant further research to inform social skills' intervention design. METHODS: The current study used parent interviews (n = 21) to probe aspects of social behaviour and interactions with strangers, as well as the impact of such behaviour on the family. Using thematic analysis, it was possible to explore themes that emerged from the interviews, offering qualitatively rich insight into the variability of social approach behaviour in WS. RESULTS: Thematic analysis confirmed a significant desire to interact with strangers as well as a lack of awareness of appropriate social boundaries. However, parental reports about their child's social approach behaviour varied considerably. The within-syndrome variability of the sample was emphasised in parental reports of their child's personality characteristics (e.g. levels of impulsiveness), as well as the level of parental supervision employed. CONCLUSIONS: These in-depth parent insights can help target the needs of individuals with WS and emphasise that an individual approach to intervention will be essential because of the heterogeneity of the WS social profile.

Downmodulation of key inflammatory cell markers with a topical Janus kinase 1/2 inhibitor.

BACKGROUND: INCB018424 is a novel, potent Janus kinase (JAK)1/JAK2 inhibitor that blocks signal transduction of multiple proinflammatory cytokines. OBJECTIVES: To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of topical INCB018424 phosphate cream in patients with plaque psoriasis. METHODS: Topical INCB018424 phosphate 1·0% or 1·5% cream was applied once daily (QD) or twice daily (BID) for 4 weeks to 2-20% body surface area in five sequential cohorts of five patients aged 18-65 years. Target lesions were scored on a scale of 0-4 for erythema, scaling and thickness. Additionally, the overall disease activity in each patient was measured using Physician's Global Assessment. INCB018424 concentrations were measured in plasma, and cytokine stimulated phosphorylated signal transducer and activator of transcription 3 phosphorylation (pSTAT3) levels in peripheral blood cells were evaluated. Pretreatment and post-treatment skin biopsies were compared with healthy skin, including evaluation of histopathology, immunohistochemistry and mRNA expression. RESULTS: Treatment with INCB018424 phosphate cream either 1·0% QD or 1·5% BID resulted in improvements in lesion scores. No significant inhibition of pSTAT3 in peripheral blood cells was observed following topical application, consistent with the generally low steady-state plasma concentrations of INCB018424 measured. Transcriptional markers of immune cell lineage/activation in lesional skin were reduced by topical INCB018424, with correlations observed between clinical improvement and decreases in markers of T helper 17 lymphocyte activation, dendritic-cell activation and epidermal hyperplasia. INCB018424 treatment reduced epidermal hyperplasia and dermal inflammation in most patient samples, with reductions in CD3, CD11c, Ki67 and keratin 16 observed by immunohistochemical analysis. CONCLUSIONS: Topical INCB018424 dosed for 28 days QD or BID is pharmacologically active in patients with active psoriasis and modulates proinflammatory cytokines in the pathogenesis of psoriatic lesions.

Bayesian analysis of culture and PCR methods for detection of Campylobacter spp. in broiler caecal samples.

The objective of this study was to estimate the sensitivity and specificity of a culture method and a polymerase chain reaction (PCR) method for detection of two Campylobacter species: C. jejuni and C. coli. Data were collected during a 3-year survey of UK broiler flocks, and consisted of parallel sampling of caeca from 436 batches of birds by both PCR and culture. Batches were stratified by season (summer/non-summer) and whether they were the first depopulation of the flock, resulting in four sub-populations. A Bayesian approach in the absence of a gold standard was adopted, and the sensitivity and specificity of the PCR and culture for each Campylobacter subtype was estimated, along with the true C. jejuni and C. coli prevalence in each sub-population. Results indicated that the sensitivity of the culture method was higher than that of PCR in detecting both species when the samples were derived from populations infected with at most one species of Campylobacter. However, from a mixed population, the sensitivity of culture for detecting both C. jejuni or C. coli is reduced while PCR is potentially able to detect both species, although the total probability of correctly identifying at least one species by PCR is similar to that of the culture method.

Exploring the prevalence and phenomenology of repetitive behaviours and abnormal sensory processing in children with Williams Syndrome.

BACKGROUND: A small amount of research with individuals who have Williams Syndrome (WS) suggests that children with the condition may be vulnerable to sensory processing abnormalities and present with repetitive and restricted behaviours. METHODS: Parents of 21 children with WS aged 6-15 years completed a semi-structured interview designed to elicit the form, frequency, impact and developmental course of a range of sensory processing abnormalities and repetitive behaviours. RESULTS: Findings indicate that sensory processing difficulties are predominantly characterised by hypersensitivities, particularly in relation to vestibular, auditory, gustatory and proprioceptive functioning. Parents also reported the presence of a range of restricted and repetitive behaviours, which were often associated with their child's sensory symptoms. CONCLUSIONS: This study makes a significant contribution to our understanding of sensory functioning and repetitive behaviours in WS. It also highlights the need for a multidisciplinary assessment of the difficulties experienced by children with the disorder.

Imaging African trypanosomes.

Trypanosoma brucei are extracellular kinetoplastid parasites transmitted by the blood-sucking tsetse fly. They are responsible for the fatal disease human African trypanosomiasis (HAT), also known as sleeping sickness. In late-stage infection, trypanosomes cross the blood-brain barrier (BBB) and invade the central nervous system (CNS) invariably leading to coma and death if untreated. There is no available vaccine and current late-stage HAT chemotherapy consists of either melarsoprol, which is highly toxic causing up to 8% of deaths, or nifurtimox-eflornithine combination therapy (NECT), which is costly and difficult to administer. There is therefore an urgent need to identify new late-stage HAT drug candidates. Here, we review how current imaging tools, ranging from fluorescent confocal microscopy of live immobilized cells in culture to whole-animal imaging, are providing insight into T. brucei biology, parasite-host interplay, trypanosome CNS invasion and disease progression. We also consider how imaging tools can be used for candidate drug screening purposes that could lead to new chemotherapies.

Finding out what matters: validity of quality of life measurement in young people with ASD.

BACKGROUND: Compared with other conditions there has been a lack of focus on quality of life (QoL) as an outcome measure for children and young people with Autism Spectrum Disorder (ASD). This pilot study aimed to evaluate the validity of existing QoL questionnaires for use with children with ASD aged 8-12 years. METHODS: A literature review (1990-2011) identified the PedsQL (Pediatric Quality of Life Inventory) and Kidscreen as robust measures used with children with neurodevelopmental disorders. These measures were completed by 10 children and 11 parents. In addition semi-structured interviews were conducted with 10 parents and four children to explore their experience of completing the QoL questionnaires. RESULTS: Young people with ASD, and their parents, report lower child QoL compared with a normative sample. Framework analysis of the data highlighted six key themes which may affect the validity of generic QoL measures when administered within an ASD sample and which warrant further investigation. CONCLUSIONS: Our results indicate that a new condition-specific measure of QoL, grounded in ASD children's own perspectives of their lives, is needed and that such a measure should assess experiences of anxiety and access to special interests when measuring QoL of children with ASD. Active involvement of young people and their families is critical for the development of a theoretical framework for QoL within ASD, and any future development of an ASD-specific measure.

UK-wide risk factor study of broiler carcases highly contaminated with Campylobacter.

Campylobacter is a major cause of food poisoning and is typically the most common cause of gastroenteritis in the UK. Data collected at broiler farm and abattoir level, for slaughter batches that were sampled for UK-wide monitoring, were used to generate two epidemiological risk factor models. A total of 483 batches slaughtered between January 2016 and March 2017 were used in the analysis, coming from 19 abattoirs representing more than 85% of UK broiler production. For each selected slaughter batch, one carcase was sampled after primary chilling and 10 randomly sampled birds had caecal samples collected at the evisceration point. Samples were used for Campylobacter identification and quantification. Two multivariable mixed-effects models were designed, one with the binary outcome for the detection of a highly contaminated (>1000 colony forming units (CFU)/g) Campylobacter-positive carcase, whereas the other used the Campylobacter colony count (CFU/g) carcase outcome. The results suggest that caecal colonization within the batch was a key factor for the occurrence of Campylobacter on carcases, and many factors that were identified in the model were also likely to be related to colonization or related to the risk of introduction of Campylobacter from partial depopulation (referred to as thinning) of ~30% of the flock approximately 1 week before full flock depopulation events. The amount of neck skin in the sample was another key factor identified and was included in both models as a risk factor. The models have also identified other factors which may be related to the general health and husbandry on-farm (use of prebiotics or vaccines, and identification of the product used for drinking line cleaning), whereas the other factors may identify control points related to transmission within a farm. The identification of these variables could help focus control efforts on-farm, especially for relatively easy improvements, such as improving the provision of house-specific bird-weighing buckets/cages in houses.

Investigation of prevalence and risk factors for Campylobacter in broiler flocks at slaughter: results from a UK survey.

During 2007-2009 a UK-wide, 3-year stratified randomized survey of UK chicken broiler flocks was conducted to estimate the prevalence of Campylobacter-infected batches of birds at slaughter. Thirty-seven abattoirs, processing 88·3% of the total UK slaughter throughput, were recruited at the beginning of the survey. Of the 1174 slaughter batches sampled, 79·2% were found to be colonized with Campylobacter, the majority of isolates being C. jejuni. Previous partial depopulation of the flock [odds ratio (OR) 5·21], slaughter in the summer months (categorized as June, July and August; OR 14·27) or autumn months (categorized as September, October and November; OR 1·70) increasing bird age (40-41 days, OR 3·18; 42-45 days, OR 3·56; ⩾46 days, OR 13·43) and higher recent mortality level in the flock (1·00-1·49% mortality, OR 1·57; ⩾1·49% mortality, OR 2·74) were all identified as significant risk factors for Campylobacter colonization of the birds at slaughter. Time in transit to the slaughterhouse of more than 2·5 h was identified as a protective factor (OR 0·52).

The prevalence of Campylobacter spp. in broiler flocks and on broiler carcases, and the risks associated with highly contaminated carcases.

A baseline survey on the prevalence of Campylobacter spp. in broiler flocks and Campylobacter spp. on broiler carcases in the UK was performed in 2008 in accordance with Commission Decision 2007/516/EC. Pooled caecal contents from each randomly selected slaughter batch, and neck and breast skin from a single carcase were examined for Campylobacter spp. The prevalence of Campylobacter in the caeca of broiler batches was 75·8% (303/400) compared to 87·3% (349/400) on broiler carcases. Overall, 27·3% of the carcases were found to be highly contaminated with Campylobacter (≥1000 c.f.u./g). Slaughter in the summer months (June, July, August) [odds ratio (OR) 3·50], previous partial depopulation of the flock (OR 3·37), and an increased mortality at 14 days (≥1·25% to <1·75%) (OR 2·54) were identified as significant risk factors for the most heavily Campylobacter-contaminated carcases. Four poultry companies and farm location were also found to be significantly associated with highly contaminated carcases.

A single case study of a family-centred intervention with a young girl with cerebral palsy who is a multimodal communicator.

BACKGROUND: This paper describes the impact of a family-centred intervention that used video to enhance communication in a young girl with cerebral palsy. This single case study describes how the video-based intervention worked in the context of multimodal communication, which included high-tech augmentative and alternative communication (AAC) device use. This paper includes the family's perspective of the video intervention and they describe the impact of it on their family. METHODS: This single case study was based on the premise that the video interaction guidance intervention would increase attentiveness between participants during communication. It tests a hypothesis that eye gaze is a fundamental prerequisite for all communicative initiatives, regardless of modality in the child. Multimodality is described as the range of communicative behaviours used by the child and these are coded as AAC communication, vocalizations (intelligible and unintelligible), sign communication, nodding and pointing. Change was analysed over time with multiple testing both pre and post intervention. Data were analysed within INTERACT, a computer software to analyse behaviourally observed data. Behaviours were analysed for frequency and duration, contingency and co-occurrence. RESULTS: Results indicated increased duration of mother's and girl's eye gaze, increased frequency and duration in AAC communication by the girl and significant change in frequency [χ(2) (5, n = 1) = 13.25, P < 0.05] and duration [χ(2) (5, n = 1) = 12.57, P < 0.05] of the girl's multimodal communicative behaviours. Contingency and co-occurrence analysis indicated that mother's eye gaze followed by AAC communication was the most prominent change between the pre- and post-intervention assessments. CONCLUSIONS: There was a trend for increased eye gaze in both mum and girl and AAC communication in the girl following the video intervention. The family's perspective concurs with the results.

Responses of Lyngbya wollei to exposures of copper-based algaecides: the critical burden concept.

The formulation of a specific algaecide can greatly influence the bioavailability, uptake, and consequent control of the targeted alga. In this research, three copper-based algaecide formulations were evaluated in terms of copper sorption to a specific problematic alga and amount of copper required to achieve control. The objectives of this study were (1) to compare the masses of copper required to achieve control of Lyngbya wollei using the algaecide formulations Algimycin-PWF, Clearigate, and copper sulfate pentahydrate in laboratory toxicity experiments; (2) to relate the responses of L. wollei to the masses of copper adsorbed and absorbed (i.e., dose) as well as the concentrations of copper in the exposure water; and (3) to discern the relation between the mass of copper required to achieve control of a certain mass of L. wollei among different algaecide formulations. The critical burden of copper (i.e., threshold algaecide concentration that must be absorbed or adsorbed to achieve control) for L. wollei averaged 3.3 and 1.9 mg Cu/g algae for Algimycin-PWF and Clearigate, respectively, in experiments with a series of aqueous copper concentrations, water volumes, and masses of algae. With reasonable exposures in these experiments, control was not achieved with single applications of copper sulfate despite copper sorption >13 mg Cu/g algae in one experiment. Factors governing the critical burden of copper required for control of problematic cyanobacteria include algaecide formulation and concentration, volume of water, and mass of algae. By measuring the critical burden of copper from an algaecide formulation necessary to achieve control of the targeted algae, selection of an effective product and treatment rate can be calculated at a given field site.

Hair MDMA samples are consistent with reported ecstasy use: findings from a study investigating effects of ecstasy on mood and memory.

AIMS: Our group has conducted several Internet investigations into the biobehavioural effects of self-reported recreational use of MDMA (3,4-methylenedioxymethamphetamine or Ecstasy) and other psychosocial drugs. Here we report a new study examining the relationship between self-reported Ecstasy use and traces of MDMA found in hair samples. METHODS: In a laboratory setting, 49 undergraduate volunteers performed an Internet-based assessment which included mood scales and the University of East London Drug Use Questionnaire, which asks for history and current drug use. They also provided a hair sample for determination of exposure to MDMA over the previous month. RESULTS: Self-report of Ecstasy use and presence in hair samples were consistent (p < 0.00001). Both subjective and objective measures predicted lower self-reported ratings of happiness and higher self-reported stress. Self-reported Ecstasy use, but not presence in hair, was also associated with decreased tension. CONCLUSION: Different psychoactive drugs can influence long-term mood and cognition in complex and dynamically interactive ways. Here we have shown a good correspondence between self-report and objective assessment of exposure to MDMA. These data suggest that the Internet has potentially high utility as a useful medium to complement traditional laboratory studies into the sequelae of recreational drug use.

Maternally transmitted antigens are codominantly expressed by mouse cells containing two kinds of mitochondrial DNA.

Mtf, a cytoplasmic, probably mitochondrial factor, controls Mta polymorphism. We tested for dominance between two forms of Mtf to determine whether Mta is controlled by positive or negative genetic mechanisms. We fused Mtf-disparate cells containing distinct mtDNA markers and selected for hybrids containing both. Such mtDNA heteroplasmons codominantly and stably express alternative Mta antigens. Stable codominance excludes negative genetic mechanisms as well as a model of induced nuclear compensation, and implies Mtf controls Mta expression through a positive genetic mechanism.

H-2M3a violates the paradigm for major histocompatibility complex class I peptide binding.

The major histocompatibility (MHC) class I-b molecule H-2M3a binds and presents N-formylated peptides to cytotoxic T lymphocytes. This requirement potentially places severe constraints on the number of peptides that M3a can present to the immune system. Consistent with this idea, the M3a-Ld MHC class I chimera is expressed at very low levels on the cell surface, but can be induced significantly by the addition of specific peptides at 27 degrees C. Using this assay, we show that M3a binds many very short N-formyl peptides, including N-formyl chemotactic peptides and canonical octapeptides. This observation is in sharp contrast to the paradigmatic size range of peptides of 8-10 amino acids binding to most class I-a molecules and the class I-b molecule Qa-2. Stabilization by fMLF-benzyl amide could be detected at peptide concentrations as low as 100 nM. While N-formyl peptides as short as two amino acids in length stabilized expression of M3a-Ld, increasing the length of these peptides added to the stability of peptide-MHC complexes as determined by 27-37 degrees C temperature shift experiments. We propose that relaxation of the length rule may represent a compensatory adaptation to maximize the number of peptides that can be presented by H-2M3a.

Availability of endogenous peptides limits expression of an M3a-Ld major histocompatibility complex class I chimera.

Taking advantage of our understanding of the peptide specificity of the major histocompatibility complex class I-b molecule M3a, we sought to determine why these molecules are poorly represented on the cell surface. To this end we constructed a chimeric molecule with the alpha 1 and alpha 2 domains of M3a and alpha 3 of Ld thereby allowing use of available monoclonal antibodies to quantify surface expression. Transfected, but not control, B10.CAS2 (H-2M3b) cells were lysed readily by M3a-restricted monoclonal cytotoxic T lymphocytes. Thus, the chimera bound, trafficked, and presented endogenous mitochondrial peptides. However, despite high levels of M3a-Ld mRNA, transfectants were negative by surface staining. This finding was consistent with inefficient trafficking to the cell surface. Incubation at 26 degrees C, thought to permit trafficking of unoccupied heavy (H) chains, resulted in detectable cell surface expression of chimeric molecules. Incubation with exogenous peptide at 26 degrees C (but not at 37 degrees C) greatly enhanced expression of M3a-Ld molecules in a dose-dependent manner, suggesting stabilization of unoccupied molecules. Stable association of beta 2-microglobulin with the chimeric H chain was observed in labeled cell lysates only in the presence of exogenous specific peptide, indicating that peptide is required for the formation of a ternary complex. These results indicate that surface expression of M3a-Ld is limited largely by the steady-state availability of endogenous peptides. Since most known M3a-binding peptides are N-formylated, native M3a may normally be expressed at high levels only during infection by intracellular bacteria.