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Objectives: To identify and review key research advances from the literature published between 2019 and 2023 on the diagnosis and microbiology of otitis media (OM) including acute otitis media (AOM), recurrent AOM (rAOM), otitis media with effusion (OME), chronic suppurative otitis media (CSOM) and AOM complications (mastoiditis)., Data Sources: PubMed database of the National Library of Medicine., Review Methods: All relevant original articles published in Medline in English between July 2019 and February 2023 were identified. Studies that were reviews, case studies, relating to OM complications (other than mastoiditis), and studies focusing on guideline adherence, and consensus statements were excluded. Members of the panel drafted the report based on these search results., Main Findings: For the diagnosis section, 2294 unique records screened, 55 were eligible for inclusion. For the microbiology section 705 unique records were screened and 137 articles were eligible for inclusion. The main themes that arose in OM diagnosis were the need to incorporate multiple modalities including video-otoscopy, tympanometry, telemedicine and artificial intelligence for accurate diagnoses in all diagnostic settings. Further to this, was the use of new, cheap, readily available tools which may improve access in rural and lowmiddle income (LMIC) settings. For OM aetiology, PCR remains the most sensitive method for detecting middle ear pathogens with microbiome analysis still largely restricted to research use. The global pandemic response reduced rates of OM in children, but post-pandemic shifts should be monitored., Implication for Practice and Future Research: Cheap, easy to use multi-technique assessments combined with artificial intelligence and/or telemedicine should be integrated into future practice to improve diagnosis and treatment pathways in OM diagnosis. Longitudinal studies investigating the in-vivo process of OM development, timings and in-depth interactions between the triad of bacteria, viruses and the host immune response are still required. Standardized methods of collection and analysis for microbiome studies to enable inter-study comparisons are required. There is a need to target underlying biofilms if going to effectively prevent rAOM and OME and possibly enhance ventilation tube retention., Competing Interests: Declaration of competing interest No conflict., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Video otoscopy plays an important role in improving access to ear health services. This study investigated the clinician-rated quality of video otoscopy recordings and still images, and compared their suitability for asynchronous diagnosis of middle-ear disease., Methods: Two hundred and eighty video otoscopy image-recording pairs were collected from 150 children (aged six months to 15 years) by an ear, nose, and throat (ENT) specialist, audiologists, and trained research assistants, and independently rated by an audiologist and ENT surgeon. On a five-point scale, clinicians rated the cerumen amount, field of view, quality, focus, light, and gave an overall rating, and asked whether they could make an accurate diagnosis for both still images and recordings., Results: More video otoscopy recordings were rated as 'good' or 'excellent' compared to still images across all domains. The mean difference between the two otoscopic procedures ratings was significant across almost all domains ( p  < 0.05), except 'cerumen amount'. The suitability to make a diagnosis significantly improved when using recordings (p<0.05). Younger participant age was found to have a significant, negative impact on the ratings across all domains ( p  < 0.03). The role of the tester conducting video otoscopy did not have a significant impact on the ratings., Discussion: Video otoscopy recordings were found to provide clearer views of the tympanic membrane and increase the ability to make diagnoses, compared to still images, for both audiologists and ENT surgeons. Research assistants with limited practice were able to obtain video otoscopy images and recordings that were comparable to the ones obtained by clinicians.

Aspergillus fumigatus is a serious human pathogen causing life-threatening Aspergillosis in immunocompromised patients. Secondary metabolites (SMs) play an important role in pathogenesis, but the products of many SM biosynthetic gene clusters (BGCs) remain unknown. In this study, we have developed a heterologous expression platform in Aspergillus nidulans , using a newly created genetic dereplication strain, to express a previously unknown BGC from A. fumigatus and determine its products. The BGC produces sartorypyrones, and we have named it the spy BGC. Analysis of targeted gene deletions by HRESIMS, NMR, and microcrystal electron diffraction (MicroED) enabled us to identify 12 products from the spy BGC. Seven of the compounds have not been isolated previously. We also individually expressed the polyketide synthase (PKS) gene spyA and demonstrated that it produces the polyketide triacetic acid lactone (TAL), a potentially important biorenewable platform chemical. Our data have allowed us to propose a biosynthetic pathway for sartorypyrones and related natural products. This work highlights the potential of using the A. nidulans heterologous expression platform to uncover cryptic BGCs from A. fumigatus and other species, despite the complexity of their secondary metabolomes., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Purpose: The aim of this research note is to encourage child language researchers and clinicians to give careful consideration to the use of domain-specific tests as a proxy for language; particularly in the context of large-scale studies and for the identification of language disorder in clinical practice., Method: We report on data leveraged through the prospective Raine Study cohort. Participants included 1626 children aged 10 years ( n  = 104 with developmental language disorder [DLD] and n  = 1522 without DLD). We assessed the predictive utility of common language measures including subtests of a standardised omnibus language assessment, non-verbal intelligence, and a domain-specific receptive vocabulary test., Result: Children with DLD performed within the average range on a measure of non-verbal intelligence ( z  = -0.86) and receptive vocabulary ( z  = -0.38), as well as two out of the six subtests on the omnibus language assessment ( z s > -1.50). The magnitude of the predictive relationship between language assessments and the likelihood of a child meeting criteria for DLD at 10 years was assessed using a logistic regression model, which was significant: χ 2 (8) = 16.91, p =  0.031. Semantic Relationships (OR = 1.13, CI = 1.04 - 1.23, p = .004), Formulated Sentences (OR = 1.07, CI = 1.01 - 1.13, p = .028), Recalling Sentences (OR = 1.20, CI = 1.15 - 1.26, p < .001), and Sentence Assembly (OR = 1.17, CI = 1.07 - 1.30, p = .001) were significant predictors of DLD., Conclusion: Domain-specific language assessments, particularly those testing receptive vocabulary, may overestimate the language ability of children with DLD. Caution is urged when using such tests by clinicians and researchers, especially those measuring language skills of children at scale. Future directions for measuring the functional impact of DLD are presented.

Hearing and vision impairments are common globally. They are often considered separately in research, and in planning and delivering services. However, they can occur concurrently, termed dual sensory impairment (DSI). The prevalence and impact of hearing and vision impairment have been well-examined, but there has been much less consideration of DSI. The aim of this scoping review was to determine the nature and extent of the evidence on prevalence and impact of DSI. Three databases were searched: MEDLINE, Embase and Global Health (April 2022). We included primary studies and systematic reviews reporting the prevalence or impact of DSI. No limits were placed on age, publication dates, or country. Only studies where the full text was available in English were included. Two reviewers independently screened titles, abstract, full texts. Data were charted by two reviewers independently using a pre-piloted form. The review identified 183 reports of 153 unique primary studies and 14 review articles. Most evidence came from high-income countries (86% of reports). Prevalence varied across reports, as did age groups of participants and definitions used. The prevalence of DSI increased with age. Impact was examined across three broad groups of outcomes-psychosocial, participation, and physical health. There was a strong trend towards poorer outcomes for people with DSI across all categories compared to people with one or neither impairment, including activities of daily living (worse for people with DSI in 78% of reports) and depression (68%). This scoping review highlights that DSI is a relatively common condition with substantial impact, particularly among older adults. There is a gap in evidence from low and middle-income countries. There is a pressing need for a consensus position on the definition(s) of DSI and standardisation of reporting age groups to enable reliable estimates to be ascertained and compared and responsive services developed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bright et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The present study aims to investigate the association between an early history of recurrent otitis media (OM) with or without ventilation tube insertion (VTI) and later behavioural problems in childhood and adolescence., Methods: Parental reports in a longitudinal pregnancy cohort were used to classify children into three groups; recurrent OM without VTI (rOM group; n = 276), recurrent OM with VTI (VTI group; n = 62), and no history of early-life recurrent OM as a reference group (n = 1485). The Child Behaviour Checklist (CBCL) was administered at ages 5, 8, 10, and 13 years and data were analysed for psychological wellbeing. Mixed-effects regression modelling was used to investigate the associations between a history of rOM and CBCL T-scores across all ages for rOM and VTI groups compared to the reference group. All analyses were controlled for a wide range of confounding variables., Results: The analyses revealed a significant association between recurrent OM and behavioural problems. While there was a general decline in scores (i.e. improvement) observed over the duration of the follow-up period, children in the rOM group displayed significantly higher scores for internalising and externalising behaviours at ages five, eight and 10 years. Attention scores were significantly higher across all ages in the rOM group. A transient increase in internalising behaviour was observed in the VTI group at ages eight and 10 years. Logistic regression models showed an increased overall likelihood for the rOM group only to fall within the abnormal clinical range for internalising and externalising behaviours., Conclusion: Early-life recurrent OM with and without VTI was associated with increased behavioural and attention problems in early and late childhood. This suggests that recurrent OM can have a significant impact on children's behaviour and attention that can persist into early adolescence., Competing Interests: Declaration of interest statement The authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: Australian Aboriginal and/or Torres Strait Islander children in rural/remote areas suffer high rates of persistent otitis media (OM) from early infancy. We aimed to determine the proportion of Aboriginal infants living in an urban area who have OM and investigate associated risk factors., Methods: Between 2017 and 2020, the Djaalinj Waakinj cohort study enrolled 125 Aboriginal infants at 0-12 weeks of age in the Perth South Metropolitan region, Western Australia. Proportion of children with OM based on tympanometry at ages 2, 6 and 12 months was evaluated, type B tympanogram indicating middle ear effusion. Potential risk factors were investigated by logistic regression with generalised estimating equations., Results: The proportion of children with OM was 35% (29/83) at 2 months, 49% (34/70) at 6 months and 49% (33/68) at 12 months of age. About 70% (16/23) of those with OM at ages 2 and/or 6 months had OM at 12 months compared with 20% (3/15) if no prior OM (relative risk = 3.48, 95% confidence interval (CI): 1.22-40.1). On multivariate analysis, infants living in houses with ≥1 person/room were at increased risk of OM (odds ratio = 1.78, 95% CI: 0.96-3.32)., Conclusion: Approximately half of Aboriginal infants enrolled into the South Metropolitan Perth project have OM by the age of 6 months and early onset of disease strongly predicts subsequent OM. Early surveillance for OM in urban areas is needed for early detection and management to reduce the risk of long-term hearing loss which can have serious developmental, social, behavioural, educational and economic consequences., (© 2023 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Introduction: Shortage of ear, nose, and throat specialists in public hospitals can result in delays in the detection and management of otitis media. This study introduced a new hospital-based telehealth service, named the Ear Portal, and investigated its role in improving access to specialist care., Methods: The study included 87 children (aged 6 months to 6 years) referred to a tertiary children's hospital due to otitis media-related concerns. A specialist multidisciplinary team met fortnightly to review pre-recorded data and provide care plans., Results: The service resulted in a median waiting time of 28 days to receive a diagnosis and care plan by the multidisciplinary team, compared to a mean waiting time of 450 days for a reference group receiving standard healthcare services. Most children (90.3%) received bilateral ear diagnosis. Normal findings were found in 43.9%. However, the majority required further ear, nose, and throat with or without audiology face-to-face follow-up due to a diagnosis of middle-ear disease, unknown hearing status, or concerns not related to ears. The mean time required for clinical assessments completion by research assistants and multidisciplinary team review was 37.6 and 5.1 min per participant, respectively., Discussion: Children in the Ear Portal service received a diagnosis and care plan in a median of 28 days, which is within the clinically recommended timeframes. With sufficient clinical information, this service can provide faster access to specialist care than the standard healthcare pathway. The service can reduce the time required by the specialist to provide a diagnosis and care plan which may help increase the specialists' capacity.

Aim: This study sought to determine the prevalence of Developmental Language Disorder (DLD) in Australian school-aged children and associated potential risk factors for DLD at 10 years., Methods: This study used a cross-sectional design to estimate the prevalence of DLD in Generation 2 of the prospective Raine Study. Participants included 1626 children aged 10 years with available language data. Primary outcomes included variables matching diagnostic criteria for DLD. Associations of other potential prenatal and environmental variables were analysed as secondary outcomes., Results: The prevalence of DLD in this sample was 6.4% (n = 104) at 10 years. This sub-cohort comprised 33.7% (n = 35) with expressive language deficits, 20.2% (n = 21) with receptive language deficits, and 46.2% (n = 48) with receptive-expressive deficits. No significant difference in sex distribution was observed (52.9% male, p = 0.799). Children who were exposed to smoke in utero at 18 weeks gestation were at increased risk of DLD at 10 years (OR = 2.56, CI = 1.23-5.35, p = 0.012)., Conclusions: DLD is a relatively prevalent condition in Australian children, even when assessed in middle childhood years. These findings can inform future research priorities, and public health and educational policy which account for the associations with potential risk factors., (© 2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Objective: To compare the asynchronous assessment of video otoscopic still images to recordings by an audiologist and ear, nose and throat surgeon (ENT) for diagnostic reliability and agreement in identifying middle-ear disease., Design: A prospective cross-sectional study, asynchronously assessing video otoscopy, tympanometry and case history (Dx1). A subset was re-diagnosed (Dx2)., Study Sample: Video otoscopy and data from 146 children recruited at two public community events; a sub-set of 47 were re-assessed., Results: The intra-rater diagnostic agreement between Dx1 and Dx2 was moderate ( k  = 0.445-0.552) for the ENT surgeon, and almost-perfect ( k  = 0.928) for the audiologist, in both procedures. The agreement between the two procedures was substantial ( k  = 0.624) and moderate ( k  = 0.416) for the ENT surgeon in Dx1 and Dx2 respectively, and almost-perfect for the audiologist ( k  = 0.854-0.978) in both rounds. In Dx1, the inter-rater agreement between the clinicians was substantial using still images ( k  = 0.672) and moderate using recordings ( k  = 0.593); in Dx2 it was moderate using both procedures ( k  = 0.477-0.488)., Conclusion: Both video otoscopic procedures, in addition to tympanometry and case history information, can be reliably used for asynchronous diagnosis of childhood middle-ear disease. An audiologist has a potential role in triaging children with middle-ear abnormalities and, therefore, improving access to ear-health services.

Purpose: Children who are Deaf and Hard of Hearing (DHH), their parents, Teachers of the Deaf, and other community stakeholders were involved in co-designing a web-based resource to support students' social-emotional well-being. The resource was designed to provide families and teachers with strategies to enhance the social and emotional well-being of Grade 4-6 students who are DHH. This study reports outcomes of a pilot study of the web-based resource intervention., Method: A pre-post pilot study was conducted to quantitatively examine reported anxiety, well-being, social relationships, school experience, student-teacher relationship, and parent and teacher self-efficacy. A total of 37 students, their parents ( n = 37), and their classroom teachers ( n = 40) participated in the intervention program and were provided access to the resource., Results: In total, 19 students, 22 parents, and 17 teachers completed both pre- and postsurvey measures. Paired t tests revealed that there was a statistically significant increase in parents' self-efficacy scores from pre- to posttest. Multivariate analysis of covariance revealed a significant association between parent use of the website and student-reported improved peer support and reduced school loneliness. No other statistically significant differences were found., Conclusions: The use of a web-based resource codeveloped with students who are DHH, their parents, and teachers could potentially be beneficial for the well-being of students who are DHH as well as parents' self-efficacy. Further research is needed to confirm the benefits.

This paper describes the design, synthesis, characterization, and performance of a novel semiconductive crystalline coordination network, synthesized using 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) ligands interconnected with bismuth ions, toward chemiresistive gas sensing. Bi(HHTP) exhibits two distinct structures upon hydration and dehydration of the pores within the network, Bi(HHTP)-α and Bi(HHTP)-β, respectively, both with unprecedented network topology (2,3-c and 3,4,4,5-c nodal net stoichiometry, respectively) and unique corrugated coordination geometries of HHTP molecules held together by bismuth ions, as revealed by a crystal structure resolved via microelectron diffraction (MicroED) (1.00 Å resolution). Good electrical conductivity (5.3 × 10 -3 S·cm -1 ) promotes the utility of this material in the chemical sensing of gases (NH 3 and NO) and volatile organic compounds (VOCs: acetone, ethanol, methanol, and isopropanol). The chemiresistive sensing of NO and NH 3 using Bi(HHTP) exhibits limits of detection 0.15 and 0.29 parts per million (ppm), respectively, at low driving voltages (0.1-1.0 V) and operation at room temperature. This material is also capable of exhibiting unique and distinct responses to VOCs at ppm concentrations. Spectroscopic assessment via X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopic methods (i.e., attenuated total reflectance-infrared spectroscopy (ATR-IR) and diffuse reflectance infrared Fourier transformed spectroscopy (DRIFTS)), suggests that the sensing mechanisms of Bi(HHTP) to VOCs, NO, and NH 3 comprise a complex combination of steric, electronic, and protic properties of the targeted analytes.

Topochemical polymerization reactions hold the promise of producing ultra-high molecular weight crystalline polymers. However, the totality of topochemical polymerization reactions has failed to produce ultra-high molecular weight polymers that are both soluble and display variable functionality, which are restrained by the crystal-packing and reactivity requirements on their respective monomers in the solid state. Herein, we demonstrate the topochemical polymerization reaction of a family of para-azaquinodimethane compounds that undergo facile visible light and thermally initiated polymerization in the solid state, allowing for the first determination of a topochemical polymer crystal structure resolved via the cryoelectron microscopy technique of microcrystal electron diffraction. The topochemical polymerization reaction also displays excellent functional group tolerance, accommodating both solubilizing side chains and reactive groups that allow for post-polymerization functionalization. The thus-produced soluble ultra-high molecular weight polymers display superior capacitive energy storage properties. This study overcomes several synthetic and characterization challenges amongst topochemical polymerization reactions, representing a critical step toward their broader application., (© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

We examined the association between otitis media (OM) and educational attainment in a retrospective population cohort of Western Australian children who participated in the grade 3 National Assessment Program-Literacy and Numeracy in 2012 ( N = 19,262). Literacy and numeracy scores were linked to administrative hospital and emergency department data to identify secondary care episodes for OM. Results of multivariate multilevel models showed that children with OM episodes had increased odds of poor performance on literacy and numeracy tests, compared to children without OM episodes (46-79% increase in odds for Aboriginal children; 20-31% increase in odds for non-Aboriginal children). There were no significant effects found for age at the first episode, nor for OM episode frequency (all p s > 0.05). Regardless of the timing or frequency of episodes, children with OM episodes are at risk of poor literacy and numeracy attainment. Aboriginal children with OM appeared to be particularly at risk of poor literacy and numeracy achievement. Intervention to reduce the prevalence of otitis media in young children, and early treatment of OM, are important for limiting the negative effects on academic outcomes.

Objectives The aim of this study was to generate a conceptual framework describing which aspects of children and adolescents' lives are affected by chronic tinnitus. Design Views and experiences of 32 participants from two participant groups informed this study: (a) a tinnitus group, consisting of adults who had experienced tinnitus during childhood and/or adolescence and primary carers of children/adolescents with tinnitus, and (b) a clinicians' group, consisting of clinicians who provided care for children/adolescents with tinnitus. Participants produced statements describing aspects of children/adolescents' lives that may be affected by chronic tinnitus. Key concepts were identified through the processes of sorting the statements and rating them for degree of associated impact. Result Participants identified 118 unique aspects of the lives of children/adolescents who may be affected by chronic tinnitus. These were clustered into four concepts: (a) emotional well-being, (b) academic performances, (c) social/relationa, and (d) auditory/cognitive processing. At a group level, participants rated the impact of tinnitus as above a slight degree but below a moderate degree of impact. However, individual participant's ratings indicated a range of perceived impact for each statement. Conclusions The experience of chronic tinnitus during childhood and adolescence extends beyond the mere perception of sound. The perception of tinnitus may impact a child's emotional well-being, academic performances, social/relational, and auditory/cognitive processing. The impact of tinnitus in one aspect of a child's life may influence other aspects of their life. While at a group level, participants regarded the impact of tinnitus as "somewhat more than mild" to "less than moderate"; individual participant's ratings indicate that the impact from chronic tinnitus may be highly individual and highlighted the importance of individual assessment and management. Clinically, tinnitus management during childhood and adolescence may be improved if clinicians consider the impact and manifestation of tinnitus within each child's daily life and tailor tinnitus education and management strategies accordingly.

Background: Atopic diseases are the most common chronic conditions of childhood. The apparent rise in food anaphylaxis in young children over the past three decades is of particular concern, owing to the lack of proven prevention strategies other than the timely introduction of peanut and egg. Due to reported in vitro differences in the immune response of young infants primed with whole-cell pertussis (wP) versus acellular pertussis (aP) vaccine, we systematically appraised and synthesised evidence on the safety and the potential allergy preventive benefits of wP, to inform recommendation for future practice and research., Objectives: To assess the efficacy and safety of wP vaccinations in comparison to aP vaccinations in early infancy for the prevention of atopic diseases in children., Search Methods: We searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, and grey literature. The date of the search was 7 September 2020., Selection Criteria: We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) that reported the occurrence of atopic diseases, and RCTs only to assess safety outcomes. To be included studies had to have at least six months follow-up, and involve children under 18 years old, who received a first dose of either wP (experimental intervention) or aP (comparator) before six months of age., Data Collection and Analysis: Two review authors independently screened studies for eligibility, extracted the data, and assessed risk of bias using standard Cochrane methods. We assessed the certainty of the evidence using GRADE. Our primary outcomes were diagnosis of IgE-mediated food allergy and all-cause serious adverse events (SAEs). Secondary outcomes included: diagnosis of not vaccine-associated anaphylaxis or urticaria, diagnosis of asthma, diagnosis of allergic rhinitis, diagnosis of atopic dermatitis and diagnosis of encephalopathy. Due to paucity of RCTs reporting on the atopic outcomes of interest, we assessed a broader outcome domain (cumulative incidence of atopic disease) as specified in our protocol. We summarised effect estimates as risk ratios (RR) and 95% confidence intervals (CI). Where appropriate, we pooled safety data in meta-analyses using fixed-effect Mantel-Haenszel methods, without zero-cell corrections for dichotomous outcomes., Main Results: We identified four eligible studies reporting on atopic outcomes, representing 7333 children. Based on a single trial, there was uncertain evidence on whether wP vaccines affected the risk of overall atopic disease (RR 0.85, 95% CI 0.62 to 1.17) or asthma only (RR 1.04, 95% CI 0.59 to 1.82; 497 children) by 2.5 years old.Three NRSIs were judged to be at serious or critical risk of bias due to confounding, missing data, or both, and were ineligible for inclusion in a narrative synthesis.  We identified 21 eligible studies (137,281 children) that reported the safety outcomes of interest. We judged seven studies to be at high risk of bias and those remaining, at unclear risk.  The pooled RR was 0.94 for all-cause SAEs (95% CI 0.78 to 1.15; I 2 = 0%; 15 studies, 38,072 children). For every 1000 children primed with a first dose of wP, 11 had an SAE. The corresponding risk with aP was 12 children (95% CI 9 to 13). The 95% CI around the risk difference ranged from three fewer to two more events per 1000 children, and the certainty of the evidence was judged as moderate (downgraded one level for imprecision). No diagnoses of encephalopathy following vaccination were reported (95% CI around the risk difference - 5 to 12 per 100,000 children; seven primary series studies; 115,271 children). The certainty of the evidence was judged as low, since this is a serious condition, and we could not exclude a clinically meaningful difference., Authors' Conclusions: There is very low-certainty evidence that a first dose of wP given early in infancy, compared to a first dose of aP, affects the risk of atopic diseases in children. The incidence of all-cause SAEs in wP and aP vaccinees was low, and no cases of encephalopathy were reported. The certainty of the evidence was judged as moderate for all-cause SAEs, and low for encephalopathy. Future studies should use sensitive and specific endpoints of clinical relevance, and should be conducted in settings with high prevalence of IgE-mediated food allergy. Safety endpoints should prioritise common vaccine reactions, parental acceptability, SAEs and their potential relatedness to the dose administered., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Solid-state packing plays a defining role in the properties of a molecular organic material, but it is difficult to elucidate in the absence of single crystals that are suitable for X-ray diffraction. Herein, we demonstrate the coupling of divergent synthesis with microcrystal electron diffraction (MicroED) for rapid assessment of solid-state packing motifs, using a class of chiral nanocarbons-expanded helicenes-as a proof of concept. Two highly selective oxidative dearomatizations of a readily accessible helicene provided a divergent route to four electron-deficient analogues containing quinone or quinoxaline units. Crystallization efforts consistently yielded microcrystals that were unsuitable for single-crystal X-ray diffraction, but ideal for MicroED. This technique facilitated the elucidation of solid-state structures of all five compounds with <1.1 Å resolution. The otherwise-inaccessible data revealed a range of notable packing behaviors, including four different space groups, homochirality in a crystal for a helicene with an extremely low enantiomerization barrier, and nanometer scale cavities., (© 2020 Wiley-VCH GmbH.)

Purpose The aim of the study was to examine whether otitis media (OM) in early childhood has an impact on language development in later childhood. Methods We analyzed data from 1,344 second-generation (Generation 2) participants in the Raine Study, a longitudinal pregnancy cohort established in Perth, Western Australia, between 1989 and 1991. OM was assessed clinically at 6 years of age. Language development was measured using the Peabody Picture Vocabulary Test-Revised (PPVT-R) at 6 and 10 years of age and the Clinical Evaluation of Language Fundamentals-Third Edition at 10 years of age. Logistic regression analysis accounted for a wide range of social and environmental covariates. Results There was no significant relationship between bilateral OM and language ability at 6 years of age (β = -0.56 [-3.78, 2.66], p = .732). However, while scores were within the normal range for the outcome measures at both time points, there was a significant reduction in the rate of receptive vocabulary growth at 10 years of age (PPVT-R) for children with bilateral OM at 6 years of age (β = -3.17 [-6.04, -0.31], p = .030), but not for the combined unilateral or bilateral OM group (β = -1.83 [-4.04, 0.39], p = .106). Conclusions Children with OM detected at 6 years of age in this cohort had average language development scores within the normal range at 6 and 10 years of age. However, there was a small but statistically significant reduction in the rate of receptive vocabulary growth at 10 years of age (on the PPVT-R measure only) in children who had bilateral OM at 6 years of age after adjusting for a range of sociodemographic factors.

Small peptides containing combinations of cysteine, tyrosine, histidine, and serine residues react with octafluorocyclopentene (OFCP) to afford atypically structured macrocycles through successive vinylic substitutions. The reactions proceed rapidly in air at 0 °C and are tolerant of spectating tryptophan, asparagine, glutamine, and threonine residues. Hexapeptides of consensus sequence YXCXXC displace four fluorine atoms from OFCP to generate fluorinated macrobicyclic compounds that display dual-turn surfaces. The method provides facile access to a wide range of previously unknown heterocyclic structures., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Here we apply microcrystal electron diffraction (MicroED) to the structural determination of transition-metal complexes. We find that the simultaneous use of 300 keV electrons, very low electron doses, and an ultrasensitive camera allows for the collection of data without cryogenic cooling of the stage. This technique reveals the first crystal structures of the classic zirconocene hydride, colloquially known as "Schwartz's reagent", a novel Pd(II) complex not amenable to solution-state NMR or X-ray crystallography, and five other paramagnetic and diamagnetic transition-metal complexes., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

In the many scientific endeavors that are driven by organic chemistry, unambiguous identification of small molecules is of paramount importance. Over the past 50 years, NMR and other powerful spectroscopic techniques have been developed to address this challenge. While almost all of these techniques rely on inference of connectivity, the unambiguous determination of a small molecule's structure requires X-ray and/or neutron diffraction studies. In practice, however, X-ray crystallography is rarely applied in routine organic chemistry due to intrinsic limitations of both the analytes and the technique. Here we report the use of the electron cryo-microscopy (cryoEM) method microcrystal electron diffraction (MicroED) to provide routine and unambiguous structural determination of small organic molecules. From simple powders, with minimal sample preparation, we could collect high-quality MicroED data from nanocrystals (∼100 nm, ∼10 -15 g) resulting in atomic resolution (<1 Å) crystal structures in minutes., Competing Interests: The authors declare no competing financial interest.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline (MPPG) represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiation requires specific training, skills, and techniques as described in each document. As the review of the previous version of AAPM Professional Policy (PP)-17 (Scope of Practice) progressed, the writing group focused on one of the main goals: to have this document accepted by regulatory and accrediting bodies. After much discussion, it was decided that this goal would be better served through a MPPG. To further advance this goal, the text was updated to reflect the rationale and processes by which the activities in the scope of practice were identified and categorized. Lastly, the AAPM Professional Council believes that this document has benefitted from public comment which is part of the MPPG process but not the AAPM Professional Policy approval process. The following terms are used in the AAPM's MPPGs: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances., (© 2018 American Association of Physicists in Medicine. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: This review examined (a) the current evidence from studies on teleaudiology applications for rehabilitation of adults with hearing impairment with hearing aids and (b) whether it is sufficient to support the translation into routine clinical practice., Method: A search strategy and eligibility criteria were utilized to include articles specifically related to hearing aid fitting and follow-up procedures that are involved in consultations for the rehabilitation of adults, where the service was provided by the clinician by teleaudiology. A search using key words and Medical Subject Headings (MeSH) was conducted on the main electronic databases that index health-related studies. The included studies were assessed using validated evaluation tools for methodological quality, level of evidence, and grade recommendations for application into practice., Results: Fourteen studies were identified as being within the scope of this review. The evaluation tools showed that none of these studies demonstrated either a strong methodological quality or high level of evidence. Analysis of evidence identified 19 activities, which were classified into service outcomes categories of feasibility, barriers, efficiency, quality, and effectiveness. Recommendations could be made regarding the (a) feasibility, (b) barriers, and (c) efficiency of teleaudiology for the rehabilitation of hearing loss with hearing aids., Conclusion: This review provides up-to-date evidence for teleaudiology hearing aid services in new and experienced hearing aid users in different practice settings. Findings direct future research priorities to strengthen evidence-based practice. There is a need for further studies of many aspects of teleaudiology services for rehabilitation with hearing aids to support their implementation into clinical practice., Supplemental Material: https://doi.org/10.23641/asha.6534473.

Objective: To examine whether self-reported hearing difficulty is an accurate measure of hearing loss compared with standard hearing screening with pure tone audiometry in rural and urban communities., Design: Convenience sampling., Setting: Urban and rural areas of Western Australia., Participants: A total of 2090 participants (923 men; 1165 women; 2 unknown) aged 20-100 years presenting for community-based hearing screening in urban (982) and rural (1090) areas., Interventions: Self-reported hearing difficulty assessed with the Hearing Handicap Inventory for the Elderly - Screening questionnaire. Hearing loss defined as average hearing thresholds >25 dB in the better ear using screening audiometry conducted at 500, 1000, 2000 and 4000 Hz., Main Outcome Measures: Nil., Results: The Hearing Handicap Inventory for the Elderly - Screening was sensitive (≥60 years = 76.69%; <60 years = 71.67%) but not specific (≥60 years = 45.15%; <60 years = 49.63%) for identifying hearing loss. The <60 age group had a hearing loss prevalence of 25.6%, and a false-positive rate of 67.12% compared with a prevalence of 69.12% and false-positive rate of 29.77% for the ≥60 age group. For all ages, rural participants were more likely to have a disabling hearing loss (odds ratio 2.04 (95% confidence interval, 1.55-2.67); χ(2)(1) = 27.28; P < 0.001), but there were no significant differences in hearing aid uptake., Conclusions: Patients in rural areas presenting for hearing screenings are more likely to suffer hearing loss than adults in urban areas. We suggest rural health practitioners incorporate a self-reported hearing loss questionnaire into health check-ups for adults, particularly patients aged ≥60 years due to the high prevalence of hearing loss in this group., (© 2015 National Rural Health Alliance Inc.)

The fragrant heartwood oil of West Australian sandalwood (Santalum spicatum) contains a mixture of sesquiterpene olefins and alcohols, including variable levels of the valuable sesquiterpene alcohols, α- and β-santalol, and often high levels of E,E-farnesol. Transcriptome analysis revealed sequences for a nearly complete set of genes of the sesquiterpenoid biosynthetic pathway in this commercially valuable sandalwood species. Transcriptome sequences were produced from heartwood xylem tissue of a farnesol-rich individual tree. From the assembly of 12,537 contigs, seven different terpene synthases (TPSs), several cytochromes P450, and allylic phosphatases were identified, as well as transcripts of the mevalonic acid and methylerythritol phosphate pathways. Five of the S. spicatum TPS sequences were previously unknown. The full-length cDNA of SspiTPS4 was cloned and the enzyme functionally characterized as a multi-product sesquisabinene B synthase, which complements previous characterization of santalene and bisabolol synthases in S. spicatum. While SspiTPS4 and previously cloned sandalwood TPSs do not explain the prevalence of E,E-farnesol in S. spicatum, the genes identified in this and previous work can form a basis for future studies on natural variation of sandalwood terpenoid oil profiles., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: To describe the prevalence and risk factors of recurrent otitis media (rOM) in an urban Australian population at 3 years of age., Methods: Cross-sectional examination of prevalence and risk factors of rOM in 2280 participants from the Raine Study enrolled from public and private hospitals in Perth, Western Australia, between 1989 and 1991. Parental report questionnaires at 3 years of age were used for rOM identification, with secondary confirmation by otoscopic examination at 1, 2 or 3 years of age., Results: The prevalence of parent-reported rOM was 26.8% (611/2280) and 5.5% (125/2280) for severe rOM in the Study. Independent associations were found between rOM and the presence of older siblings, attendance at day care and the introduction of other milk products at ≤4 months of age. Independent associations for severe rOM were the presence of allergies and attendance at day care., Conclusions: Prevalence rates of rOM within the Raine Study children are similar to a number of other known cohorts. Parity, presence of allergies, attendance at day care and introduction of other milk products at ≤4 months are highlighted as specific risk factors for rOM in this population and presence of allergies and attendance at day care being risk factors for severe rOM. Diagnosis of rOM by parent report and the delay between data collection and reporting are limitations of this study. However, as there is very limited data on OM in urban, non-Indigenous Australian children, this study improves our understanding of OM for this group., (© 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)