A rare case of orbital angioleiomyoma.

A 65-year old woman presented with 3-year history of painless, gradual swelling of the right upper eyelid associated with proptosis. Computed tomography (CT) and magnetic resonance imaging (MRI) of the orbit showed a well circumscribed soft tissue mass in the supero-lateral orbit. An excision biopsy of the lesion was performed via lateral orbitotomy. Histopathology examination and immunochemistry staining confirmed the diagnosis of cavernous angioleiomyoma. The tumour was excised completely. Orbital angioleiomyoma is a rare benign tumour and the lesion can cause visual morbidity, particularly when intraconal. Despite sophisticated imaging modalities, histopathological analysis is essential for diagnosis. Angioleiomyoma should be included in the differential diagnosis of well-defined orbital lesions. Complete surgical excision carries a low risk of recurrence.

Phacoemulsification cataract surgery in the loggerhead turtle (Caretta caretta): surgical technique and outcomes in 10 cases.

Cataract removal using phacoemulsification was performed in 10 loggerhead turtles being rehabilitated after stranding. All turtles had significant systemic abnormalities and had cataracts either at the time of rescue or developed them during rehabilitation. Surgical difficulties encountered included an extremely soft globe that did not allow for a partial thickness corneal incision, incomplete topical anesthesia of the ocular surface with proparacaine, inability to dilate the pupil pharmacologically, a markedly shallow anterior chamber, a thick posterior capsular plaque in most cases, and difficulty creating a watertight closure with sutures. Minimal to no intraocular inflammation was seen in all cases following surgery, but all cases in which corneal sutures were used developed a marked inflammatory reaction surrounding the sutures and appeared uncomfortable until sutures were removed or sloughed. All turtles appeared to have improved vision following surgery and were eventually released. Two turtles were re-encountered a year or more after release. Both showed signs of normal growth and the ability to capture prey in the wild. This report documents successful outcomes associated with cataract surgery in loggerhead turtles, but also presents significant surgical challenges that should be taken into account before attempting this procedure in this species.

Survey of Ocular Prosthetics Rehabilitation in the United Kingdom, Part 1: Anophthalmic Patients' Aetiology, Opinions, and Attitudes.

PURPOSE: Ocular prostheses are constructed to aid cosmetic, functional, and psychological rehabilitation of anophthalmic patients. Part-1 of this study aimed to evaluate anophthalmic patients' opinions, attitudes, and experience about aspects related to their postfit ocular prostheses. METHODS: One hundred sixty questionnaires were delivered to anophthalmic patients inquiring about different information such as age, gender, occupation, eye-loss cause, prosthesis type, prosthesis-wearing frequency, prosthesis-cleaning frequency, and problems encountered. A total of 126 questionnaires were returned (response rate was 78.8%). Data was analyzed using SPSS software (P <0.05). RESULTS: The patients were 74 males and 52 females (57.55 years ±â€Š17.57). Almost 50% of the patients lost their eye due to trauma that was the highest among other causes (P <0.05). High proportion clean their prosthesis daily (37.4%) which was the highest among other cleaning regimes (P <0.05). Almost 30.3% experienced having problems with their prosthetic eye. Patients who clean their prosthetic eye every 6 months have experienced more problems (P <0.05). Majority of patients wear their prosthetic eyes 24 hours (92%) (P <0.05). Half of patients who received a prosthetic eye for the first time experienced problems with it (P <0.05) such as excess discharge (45%), infection (25%), and soreness (20%). However, the problems were independent of prosthesis-type (P >0.05). CONCLUSIONS: Trauma is the most common cause of anophthalmic patients in the North-West of England. Anophthalmic patients are likely to experience problems with their prosthetic eye if they have lost their natural eye due to disease; it is their first prosthesis; or if they clean it once every 6 months.

Survey of Ocular Prosthetics Rehabilitation in the United Kingdom, Part 2: Anophthalmic Patients' Satisfaction and Acceptance.

AIM: Ocular prostheses are integral for anophthalmic patients. Part 1 of this study reported that patients' aetiology, opinions, and attitudes significantly affected their prosthetic eyes experience. Part 2 investigates the patient satisfaction and acceptance in light of some of the aetiological demographics reported in Part 1. METHODOLOGY: One hundred sixty questionnaires were delivered to anophthalmic patients attending oculoplastic clinic. Etiological aspects presented in the questionnaire were disseminated in part 1. Patient satisfaction was assessed through 8 closed-end statements reflecting aspects concerning patient's views on prosthesis comfort and appearance; patient's expectations, self-esteem, and perception; and cooperation with ocularist. Each statement had 3 categories as agree, moderately agree, and disagree. A total of 126 questionnaires were returned (response rate was 78.8%). Data was analyzed using SPSS software. Association coefficients and correlations between variables were also analyzed. RESULTS: Total number of responses for the 8 statements was 888, averaging of 111 (expected 126) respondent per statement. Overall, 95.4% of our patients agreed with all satisfaction statements presented echoing very high satisfaction rate with their ocular prosthetics. Having an eye replacement that covers the defect is associated with high satisfaction among patients regardless of ocular prosthetic type. Patient acceptance of prosthesis in relation to employment status was high but not the same among the different categories (P > 0.05). High satisfaction with ocular prosthetics was prevalent among both genders, but there were no statistically significant differences in percentages of agreement in all statements (P > 0.05). Satisfaction and acceptance with ocular prosthetics was the same among all age groups of 12 to 85 years old (P > 0.05). CONCLUSIONS: The patient satisfaction is associated with the interplay of different variables that is related to ocular prosthesis design and its ability to disguise disfigurement (ie, prosthesis shape, resemblance to existing contra-lateral eye, etc.); patients themselves (ie, gender, age, occupation, marital status, etc); and psychological well-being and social support provided. Anophthalmic patients of the north west of England are significantly happy with their ocular prosthetic rehabilitation and support they receive from their regional hospital. Ocular prosthetics enhances their psychological well-being and social interaction and factors like patients' sex, age, employment status, and type of ocular prosthesis have no effect on their acceptance and satisfaction.

Reliability and Effectiveness of the Manchester Orbital Exenteration Wound Assessment Tool: Inter-Observer Agreement.

AIM: To evaluate the inter-observer agreement of the Manchester Orbital Exenteration Wound Assessment Tool (MOEWAT), a tool designed to facilitate grading of healing in exenterated sockets, scores from clinical photographs of exenterated sockets. METHODS: Existing MOEWAT system was modified to allow grading of clinical photographs. Photographs of 36 different patients at different stages of healing following exenteration were identified. Scores for two masked observers, who independently graded the photographs were compared. The inter-observer agreement of scores was assessed using a Bland-Altman plot, with the average agreement and 95% confidence interval around the mean computed. RESULTS: The average age of the 36 patients was 66 ± 29 years. Photographs were taken 32 ± 16 months after exenteration. Across all photographs, the averages score given by the first observer (4.3 ± 2.2) and second observer (3.4 ± 1.5) were similar (t = -1.9; p = 0.07). From the Bland-Altman plot, the mean difference in score (0.8 ± 1.8) was close to zero, with 95% confidence limits for agreement are indicated by the dashed lines and spanning from -2.6 to 4.3. CONCLUSION: MOEWAT can be successfully used to stage wound healing in exenterated sockets, with good inter-observer agreement.

The ability of people with Parkinson's disease to modify dual-task performance in response to instructions during simple and complex walking tasks.

Gait impairments are a common and consequential motor symptom in Parkinson's disease (PD). A cognitive strategy that incorporates instructions to concentrate on specific parameters of walking is an effective approach to gait rehabilitation for persons with PD during single-task and simple dual-task walking conditions. This study examined the ability to modify dual-task walking in response to instructions during a complex walking task in people with PD compared to healthy older adults (HOA). Eleven people with PD and twelve HOA performed a cognitive task while walking with either a usual base or a narrow base of support. Dual-task walking and cognitive task performance were characterized under two conditions-when participants were instructed focus on walking and when they were instructed to focus on the cognitive task. During both usual base and narrow base walking, instructions affected cognitive task response latency, with slower performance when instructed to focus on walking compared to the cognitive task. Regardless of task or instructions, cognitive task performance was slower in participants with PD compared to HOA. During usual base walking, instructions influenced gait speed for both people with PD and HOA, with faster gait speed when instructed to focus on walking compared to the cognitive task. In contrast, during the narrow base walking, instructions affected gait speed only for HOA, but not for people with PD. This suggests that among people with PD the ability to modify walking in response to instructions depends on the complexity of the walking task.

Processing anomalous anaphors.

Previous researchers have demonstrated that readers may engage in shallow, or incomplete, processing when the semantic overlap between current information and previously encountered information is high. The present study investigated whether these effects would occur during processing of unambiguous noun phrase anaphors, for which there was only a single possible antecedent. Participants read passages containing anaphors that were correct, incorrect but highly related, or incorrect and low-related, with respect to previously encountered information. The time required to process the anaphor was a function of the goodness of fit between the anaphor and the antecedent; anaphors that were incorrect but highly related to the antecedent were processed more quickly than those that were incorrect and low-related. This occurred regardless of the distance between the anaphor and the antecedent. However, reading times results from a spillover sentence indicated that readers subsequently validated the anaphor against the information in memory, resulting in continued processing difficulty for both the incorrect-high- and -low-related anaphor conditions. The results are consistent with a three-stage comprehension model in which information is activated, integrated on the basis of its goodness of fit with the contents of working memory, and then validated against information in long-term memory.

Revisiting effects of contextual strength on the subordinate bias effect: evidence from eye movements.

In this study, we examined two issues regarding the role of context in ambiguity resolution: whether access to the contextually appropriate meaning is exhaustive or selective, and whether the contextually inappropriate meaning is inhibited. Participants read texts in which a biased ambiguous word was encountered twice while their eye movements were measured. The context preceding the first encounter varied in the extent to which the subordinate meaning was supported; the context preceding the second encounter always supported the dominant meaning. The findings suggest that lexical access is exhaustive but can be influenced by context, and that the subsequent accessibility of the contextually inappropriate meaning is unaffected by previous selection processes. The results were interpreted in terms of the assumptions of the reordered-access model and activation mechanisms that operate during reading.

Spiritual awakening and transformation in scientists and academics.

The purpose of this study was to document both quantitatively and qualitatively the characteristics of spiritual awakenings and their transformational effects in scientists and academics who reported having experienced this phenomenon; it also aimed to explore barriers these individuals perceived to sharing their experiences with others within society. METHODS: An interview questionnaire was used to collect detailed descriptions of both the physical and metaphysical experiences of 54 scientists and academics having had a spiritually transformative experience (STE) (e.g., spontaneous energetic awakenings, awakenings occurring through near-death experiences (NDEs), and through spiritual practices). RESULTS AND CONCLUSIONS: Participants reported the STE as a mystical experience involving feelings of expansion (including conscious awareness leaving the body), energy rising up the spine, a sense of being enveloped in light, love or part of a unified energetic field. Principle triggers for these experiences included concentrating on spiritual matters, the presence of a spiritually developed person, and intense meditation or prayer. Transformational changes in participants included increased sensory sensitivity, creativity, and changes in beliefs, including a desire to serve others, a sense of unity with all, and the immortality of the spirit. Effects on career ranged from incorporating their new worldview and spiritual insights into the way they interacted with others within their current career, to radically changing their career to focus on questions related to the fundamental nature of consciousness or to serve others from this new perspective. Among barriers to sharing experiences, participants noted their concern that they would be misunderstood or ridiculed by others.

Reflections on extraordinary knowing: Insight into the nature of the mind.

Scientists have spent considerable time and effort studying and mapping the geography of the brain, with the expectation that this understanding will lead to insights related to the nature of the mind. This article discusses evidence that, while the mind utilizes sensory information processed by the brain, awareness is not limited to these structures. Research studies give evidence supporting the mind's ability to expand awareness to include perception of objects and events not available to the five senses. This awareness also extends to moments in the future, including the mind's ability to access information seconds or even days in advance of the occurrence. A major brain filter that limits this capacity for expanded awareness is the Default Mode Network (DMN). We summarize research showing that when the DMN activity is reduced, e.g., through meditation, ingestion of neuromodulatory drugs, or NDEs, filtering within the brain is reduced, there is a concomitant development of new connectivity, and these neural changes are correlated with access to expanded awareness.

Worldviews and environmental ethics: Contributions of brain processing networks.

Research suggests that worldviews define our relationship to the environment, including our responsibility to the environment and our planet. This paper examines two specific worldviews and their potential environmental impact: the materialist worldview, considered to be the dominant worldview of Western society, and the so-called post-materialist worldview. We believe that changing the worldview of both individuals and society is key to changing environmental ethics, specifically attitudes, beliefs, and actions towards the environment. Recent neuroscience research suggests that brain filters and networks contribute to concealing an expanded nonlocal awareness. This creates self-referential thinking and contributes to the limited conceptual framework characteristic of a materialist worldview. We discuss the underlying concepts of both materialist and post-materialist worldviews including their impact on environmental ethics, then explore the various types of neural filters and processing networks that contribute to a materialist worldview, and finally explore methods for modifying neural filters and changing worldviews.

Factors Predicting Long-term Outcome and the Need for Surgery in Graves Orbitopathy: Extended Follow-up From the CIRTED Trial.

Graves orbitopathy is both disabling and disfiguring. Medical therapies to reduce inflammation are widely used, but there is limited trial data beyond 18 months of follow-up. METHODS: Three-year follow-up of a subset of the CIRTED trial (N = 68), which randomized patients to receive high-dose oral steroid with azathioprine/placebo and radiotherapy/sham radiotherapy. RESULTS: Data were available at 3 years from 68 of 126 randomized subjects (54%). No additional benefit was seen at 3 years for patients randomized to azathioprine or radiotherapy with regard to a binary clinical composite outcome measure (BCCOM), modified European Group on Graves' Orbitopathy score, or Ophthalmopathy Index.Clinical Activity Score (CAS), Ophthalmopathy Index, and Total Eye Score improved over 3 years (P < .001). However, quality of life at 3 years remained poor. Of 64 individuals with available surgical outcome data, 24 of 64 (37.5%) required surgical intervention. Disease duration of greater than 6 months before treatment was associated with increased need for surgery [odds ratio (OR) 16.8; 95% CI 2.95, 95.0; P = .001]. Higher baseline levels of CAS, Ophthalmopathy Index, and Total Eye Score but not early improvement in CAS were associated with increased requirement for surgery. CONCLUSION: In this long-term follow-up from a clinical trial, 3-year outcomes remained suboptimal with ongoing poor quality of life and high numbers requiring surgery. Importantly, reduction in CAS in the first year, a commonly used surrogate outcome measure, was not associated with improved long-term outcomes.

Complete manuscript title: Neurological complications from sinugenic orbital cellulitis.

INTRODUCTION: This study was undertaken with an aim to identify any common factors or trends among patients of orbital cellulitis that developed neurological complications. METHODS: A 24-month retrospective review of patients was undertaken to include those showing clinical deterioration and neurological complications on radiological imaging, after being treated for orbital cellulitis at Manchester Royal Eye Hospital. The study specifically looked at the site of orbital collection, sinus involvement, types of neurological complications and whether these were detected at initial presentation, surgical input and microbiology findings. RESULTS: Nine patients (9/26) developed associated neurological complications during the study period. (February 2018 and January 2020) This included subdural empyema in six patients; leptomeningeal enhancement in two and septic emboli in one patient. All the patients had associated significant pan-sinusitis at initial presentation. Neurological complications were detected in three patients at the time of admission and after clinical deterioration and further investigations in the rest. CONCLUSION: A superior orbital abscess and Streptococcus mileri infection had higher risk of neurological complications. It is worth debating whether patients with chronic sinusitis who develop orbital cellulitis need earlier surgical input rather than a conservative treatment. Patients who fail to improve clinically need to be re-imaged to look for possible neurological complications.

Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, double-dummy, 2×2 partial factorial, randomised controlled trial.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance. METHODS AND ANALYSIS: We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance. ETHICS AND DISSEMINATION: Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines for ethical conduct of Research, including that for First Nations Australians. TRIAL REGISTRATION NUMBER: ACTRN12619000564156.

The pobA gene of Burkholderia cenocepacia encodes a group I Sfp-type phosphopantetheinyltransferase required for biosynthesis of the siderophores ornibactin and pyochelin.

The opportunistic pathogen Burkholderia cenocepacia produces the siderophores ornibactin and pyochelin under iron-restricted conditions. Biosynthesis of both siderophores requires the involvement of non-ribosomal peptide synthetases (NRPSs). Using a transposon containing the lacZ reporter gene, two B. cenocepacia mutants were isolated which were deficient in siderophore production. Mutant IW10 was shown to produce normal amounts of ornibactin but only trace amounts of pyochelin, whereas synthesis of both siderophores was abolished in AHA27. Growth of AHA27, but not IW10, was inhibited under iron-restricted conditions. In both mutants, the transposon had integrated into the pobA gene, which encodes a polypeptide exhibiting similarity to the Sfp-type phosphopantetheinyltransferases (PPTases). These enzymes are responsible for activation of NRPSs by the covalent attachment of the 4'-phosphopantetheine (P-pant) moiety of coenzyme A. Previously characterized PPTase genes from other bacteria were shown to efficiently complement both mutants for siderophore production when provided in trans. The B. cenocepacia pobA gene was also able to efficiently complement an Escherichia coli entD mutant for production of the siderophore enterobactin. Using mutant IW10, in which the lacZ gene carried by the transposon is inserted in the same orientation as pobA, it was shown that pobA is not appreciably iron-regulated. Finally, we confirmed that Sfp-type bacterial PPTases can be subdivided into two distinct groups, and we present the amino acid signature sequences which characterize each of these groups.

A translational research evaluation of the Stay Active and Independent for Life (SAIL) community-based fall prevention exercise and education program.

Falls in older adults are the leading cause of injury hospitalizations and fatalities in the United States; primary risk factors are muscle weakness, impaired mobility, and balance deficits. This article describes the 12-month translational research evaluation of the Stay Active and Independent for Life (SAIL) community-based public health, public domain fall prevention exercise and education program. Recruitment reached the target goal by 154%; 331 adults (mean age = 74.6) attended more than one class (mean classes attended = 24.8, SD = 26.6, range = 1-120) at nine community sites in one county in the 12-month period; 173 completed health and demographic forms, 132 completed program surveys, and 91 completed baseline and follow-up physical function tests. Physical function test results showed significant improvements in strength, balance, and mobility in those who were below normal limits at baseline, and in those who attended classes twice a week or more for more than 2 months. Survey results found that 93% of respondents reported improved performance of daily activities; 92% reported improved strength, balance, fitness, or flexibility; and 80% found the SAIL information guide education component helpful.

Burden of Care for Children with Bronchiectasis from Parents/Carers Perspective.

Bronchiectasis is a neglected chronic respiratory condition. In children optimal appropriate management can halt the disease process, and in some cases reverse the radiological abnormality. This requires many facets, including parental/carer bronchiectasis-specific knowledge, for which there is currently no such published data. Further, the importance of patient voices in guiding clinical research is becoming increasingly appreciated. To address these issues, we aimed to describe the voices of parents of children with bronchiectasis relating to (a) burden of illness and quality of life (QoL), (b) their major worries/concerns and (c) understanding/management of exacerbations. The parents of 152 children with bronchiectasis (median age = 5.8 years, range 3.5-8.4) recruited from the Queensland Children's Hospital (Australia) completed questionnaires, including a parent-proxy cough-specific QoL. We found that parents of children with bronchiectasis had impaired QoL (median 4.38, range 3.13-5.63) and a high disease burden with median 7.0 (range 4.0-10.0) doctor visits in 12-months. Parental knowledge varied with only 41% understanding appropriate management of an exacerbation. The highest worry/concern expressed were long-term effects (n = 42, 29.8%) and perceived declining health (n = 36, 25.5%). Our study has highlighted the need for improved education, high parental burden and areas of concern/worry which may inform development of a bronchiectasis-specific paediatric QoL tool.

Utility of a personalised Bronchiectasis Action Management Plan (BAMP) for children with bronchiectasis: protocol for a multicentre, double-blind parallel, superiority randomised controlled trial.

INTRODUCTION: Bronchiectasis is no longer considered rare or irreversible in children, yet it remains relatively under-researched and neglected in respiratory health globally. Bronchiectasis (including chronic suppurative lung disease) causes substantial morbidity for patients and significant impact on caregivers, especially during acute respiratory exacerbations. In other chronic respiratory diseases (eg, asthma), empowering consumers with an individualised plan for management of acute exacerbations improves clinical outcomes. However, in the absence of any such data specific to bronchiectasis, action management plans are rarely currently used in children or adults with bronchiectasis. We hypothesise that providing an individualised bronchiectasis action management plan (BAMP) to children with bronchiectasis reduces non-scheduled doctor consultations, compared with not having a BAMP. METHODS AND ANALYSIS: This multicentre, parallel, double-blind, randomised trial involving three urban Australian hospitals commenced in June 2018 and will include 198 children, aged <19 years with bronchiectasis who had 2 or more exacerbations in the previous 18 months. Children will be randomised to having an individualised BAMP or standard care (a decoy clinic letter). Primary caregivers will then be followed up monthly for 12 months. The primary outcome is the rate of acute non-scheduled doctor visits for respiratory exacerbations by 12 months. The main secondary outcomes are cough-specific quality of life scores at 6 and 12 months, overall exacerbation rate over 12 months, and proportion of children who received timely influenza vaccination by 30 May annually. ETHICS AND DISSEMINATION: The Human Research Ethics Committees of the Northern Territory Department of Health and Menzies School of Heath Research and Queensland Children's Hospital approved the study. The results of the trial will be submitted for publication and the BAMP made available free online. TRIAL REGISTRATION NUMBER: Australia and New Zealand Clinical Trials Register ACTRN12618000604202.

Duration of amoxicillin-clavulanate for protracted bacterial bronchitis in children (DACS): a multi-centre, double blind, randomised controlled trial.

BACKGROUND: Protracted bacterial bronchitis (PBB) is a leading cause of chronic wet cough in children. The current standard treatment in European and American guidelines is 2 weeks of antibiotics, but the optimal duration of therapy is unknown. We describe the first randomised controlled trial to assess the duration of antibiotic treatment in children with chronic wet cough and suspected PBB. We hypothesise that 4 weeks of amoxicillin-clavulanate is superior to 2 weeks for improving clinical outcomes. METHODS: Our parallel, double-blind, placebo-controlled, randomised controlled trial was completed in four Australian hospitals. Children aged 2 months to 19 years with chronic (>4 weeks duration) wet cough, and suspected PBB were randomly assigned (1:1) using permuted block randomisation (stratified by age and site) to 4 weeks of amoxicillin-clavulanate (25-35 mg/kg twice daily oral suspension; 4-week group) or 2 weeks of amoxicillin-clavulanate followed by 2 weeks of placebo (2-week group). The children, caregivers, all the study coordinators, and investigators were masked to treatment assignment until data analysis was completed. The primary outcome was clinical cure (cough resolution) by day 28. Secondary outcomes were recurrence of PBB at 6 months, time to next exacerbation, change in Parent-proxy Cough-Specific Quality-of-Life (PC-QoL) score from baseline to day 28 and from day 28 to 7 months, adverse events, nasal swab bacteriology, and antimicrobial resistance. Analyses followed the intention-to-treat principle. This trial is complete and registered with Australian/New Zealand Registry, ACTRN12616001725459. FINDINGS: Between March 8, 2017, and Sept 30, 2019, 106 children were randomly assigned (52 in the 4-week group, median age 2·2 years [IQR 1·3-4·1]; 54 in the 2-week group, median age 1·7 years [1·2-3·8]) with 90 children completing the 4-week treatment. By day 28, the primary endpoint of clinical cure in the 4-week group (32 [62%] of 52 patients) was not significantly different to the 2-week group (38 [70%] of 54 patients; adjusted relative risk 0·87 [95% CI 0·60 to 1·28]; p=0·49). Time to next wet cough exacerbation was significantly longer in the 4-week group than the 2-week group (median 150 days [IQR 38-181] vs 36 days [15-181]; adjusted hazard ratio 0·47 [0·25 to 0·90]; p=0·02). The rate of recurrence of PBB at 6 months was 17 (53%) of 32 patients in the 4-week group vs 28 (74%) of 38 patients in the 2-week group, but the difference between the groups was not significant (adjusted odds ratio 0·39 [0·14 to 1·04]; p=0·07). PC-QoL significantly improved from baseline to day 28 in both groups, but there was no significant difference between them (mean difference in change -0·2 [95% CI -1·0 to 0·6]; p=0·64). From day 28 to 7 months, median PC-QoL remained stable in both groups with no difference in change between them. Data on respiratory pathogens and antimicrobial resistance (paired swabs available for 48 children) were similar between groups. Adverse events occurred in 13 (25%) children in the 2-week group and ten (19%) in the 4-week group (p=0·57). INTERPRETATION: A 4-week course of amoxicillin-clavulanate for treating children with chronic wet cough and suspected PBB confers little advantage compared with a 2-week course in achieving clinical cure by 28 days. However, as a 4-week duration led to a longer cough-free period, identifying children who would benefit from a longer antibiotic course is a priority. FUNDING: Queensland Children's Hospital Foundation.

The roles of IL-12 and IL-23 in CD8+ T cell-mediated immunity against Listeria monocytogenes: Insights from a DC vaccination model.

Listeria monocytogenes infection induces a strong inflammatory response characterized by the production of IL-12 and IFN-gamma and protective immunity against this pathogen is dependent on CD8+ T cells (CTL). Recent studies have suggested that these inflammatory cytokines affect the rate of memory CD8+ T cell generation as well as the number of short-lived effector cells generated. The role of the closely related cytokine, IL-23, in this response has not been examined. We hypothesized that IL-12 and IL-23 produced by dendritic cells collectively enhance the generation and function of memory cells. To test this hypothesis, we employed a DC vaccination approach. Mice lacking IL-12 and IL-23 were vaccinated with wild-type (WT), IL-12(-/-), or IL-12/23(-/-) DC and protection to Lm was monitored. Mice vaccinated with WT and IL-12(-/-) DC were resistant to lethal challenge with Lm. Surprisingly, mice vaccinated with IL-12/23(-/-) DC exhibited significantly reduced protection when challenged. Protection correlated with the relative size of the memory pools generated. In summary, these data indicate that IL-23 can partially compensate for the lack of IL-12 in the generation protective immunity against Lm.