A RANGE-WIDE ECTOPARASITE SURVEY FOR ALLEGHENY WOODRATS (NEOTOMA MAGISTER).

Allegheny woodrats (Neotoma magister) are karst-specializing rodents that are rare or in conservation need in many states within their current range. Parasitism and habitat fragmentation have been suggested as primary reasons for declining populations. The presence, prevalence, and impact of ectoparasites, including fleas, ticks, and bots, is not fully understood rangewide. We collected Allegheny woodrat ectoparasites across 8 states in their range, identifying parasites via morphological and genetic means. Across contributions from 8 states, we discovered 2 woodrat-specific fleas parasitizing Allegheny woodrats: Orchopeas pennsylvanicus (all contributing states, n = 228) and Epitedia cavernicola (Indiana only, n = 9). The former was a new state record in New Jersey and Ohio. Woodrat specialists Ixodes woodi were morphologically identified as the dominant tick species (n = 38), and our contributions to genetic databases may ease confusion in future efforts. Three generalist species of ticks representing 8 individuals were identified as Dermacentor variabilis, Amblyomma americanum, and Ixodes scapularis. Only 2 bot fly species were recognized in Allegheny woodrats: 1 squirrel bot (Cuterebra emasculator) and 10 individuals of Cuterebra sp. not genetically conspecific to any known eastern U.S. rodent bot. The host specificity for fleas is not surprising, given that previous small-scale surveys and ticks primarily appear to be a mix of genus-specific (Ixodes woodi) and generalist species. There remains uncertainty with bots via morphological and genetic analyses. Our survey presents a wide-ranging baseline survey for Allegheny woodrats across their range, emphasizing the diversity (or specificity) of parasite groups for this species. An understanding of Allegheny woodrats and the health impact of ectoparasites is imperative because they face myriad challenges rangewide, especially considering the bot-driven demise of 1 woodrat in our study. Ectoparasites can have a marked impact on already-declining woodrat populations across their range and should not be overlooked in future surveys.

Sex- and Race-Based Differences in the Treatment of Interstitial Lung Diseases in North America and Australasia.

BACKGROUND: Biological sex, gender, and race are important considerations in patients with interstitial lung diseases (ILDs). RESEARCH QUESTION: Does a patient's sex assigned at birth, and race, influence ILD treatment initiation? STUDY DESIGN AND METHODS: Patients with ILD from three longitudinal prospective registries were compared in this observational study. ILD-related medications included antifibrotics and immunomodulating medications. Race was dichotomized as "White" vs "non-White." Time to treatment initiation was determined from the date of the initial ILD registry visit to the date of first medication initiation. Proportions of treated patients were compared between groups by χ2 test. Cox proportional analysis was used to determine how sex and race were associated with time to treatment initiation stratified by ILD diagnosis. RESULTS: A total of 4,572 patients were included across all cohorts. The proportion of men who received treatment was higher than for women in the Canadian cohort (47% vs 40%; P < .001), and the proportion of White patients who received treatment was also higher compared with non-White patients (46% vs 36%; P < .001). In contrast, the proportion of treated men in the Chicago cohort was lower compared with women (56% vs 64%; P = .005), and that of White patients was lower compared with non-White patients (56% vs 69%; P < .001). No sex- or race-based differences in proportions of patients treated were found in the Australasian cohort. White race was significantly associated with earlier treatment initiation compared with non-White race across diagnoses in the Canadian cohort, whereas the opposite association was found in the Australasian cohort. INTERPRETATION: Sex- and race-based differences exist in the initiation of ILD treatment, with variability across different cohorts in different countries. Reasons for these differences need to be further explored in future studies.

Pulmonary involvement in Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis: A single centre case series.

Anti-Neutrophil Cytoplasmic Antibody associated Vasculitides (AAV) comprise a rare group of disorders in which respiratory tract involvement is variable and often severe. The rarity and heterogeneity of AAV makes this a challenging condition to diagnose and manage. In this single-centre case series of 44 patients with AAV-associated respiratory disease, we provide an overview of disease manifestations, management aspects and treatment outcomes. Data from this case series highlight the real-world diagnostic and therapeutic challenges of the AAV respiratory disease spectrum; including uncertainties in the management of fibrosing interstitial lung disease, tracheobronchial stenosis and diffuse alveolar haemorrhage.

Crowdsourcing biocuration: The Community Assessment of Community Annotation with Ontologies (CACAO).

Experimental data about gene functions curated from the primary literature have enormous value for research scientists in understanding biology. Using the Gene Ontology (GO), manual curation by experts has provided an important resource for studying gene function, especially within model organisms. Unprecedented expansion of the scientific literature and validation of the predicted proteins have increased both data value and the challenges of keeping pace. Capturing literature-based functional annotations is limited by the ability of biocurators to handle the massive and rapidly growing scientific literature. Within the community-oriented wiki framework for GO annotation called the Gene Ontology Normal Usage Tracking System (GONUTS), we describe an approach to expand biocuration through crowdsourcing with undergraduates. This multiplies the number of high-quality annotations in international databases, enriches our coverage of the literature on normal gene function, and pushes the field in new directions. From an intercollegiate competition judged by experienced biocurators, Community Assessment of Community Annotation with Ontologies (CACAO), we have contributed nearly 5,000 literature-based annotations. Many of those annotations are to organisms not currently well-represented within GO. Over a 10-year history, our community contributors have spurred changes to the ontology not traditionally covered by professional biocurators. The CACAO principle of relying on community members to participate in and shape the future of biocuration in GO is a powerful and scalable model used to promote the scientific enterprise. It also provides undergraduate students with a unique and enriching introduction to critical reading of primary literature and acquisition of marketable skills.

Diagnosis and management of connective tissue disease-associated interstitial lung disease in Australia and New Zealand: A position statement from the Thoracic Society of Australia and New Zealand.

Pulmonary complications in CTD are common and can involve the interstitium, airways, pleura and pulmonary vasculature. ILD can occur in all CTD (CTD-ILD), and may vary from limited, non-progressive lung involvement, to fulminant, life-threatening disease. Given the potential for major adverse outcomes in CTD-ILD, accurate diagnosis, assessment and careful consideration of therapeutic intervention are a priority. Limited data are available to guide management decisions in CTD-ILD. Autoimmune-mediated pulmonary inflammation is considered a key pathobiological pathway in these disorders, and immunosuppressive therapy is generally regarded the cornerstone of treatment for severe and/or progressive CTD-ILD. However, the natural history of CTD-ILD in individual patients can be difficult to predict, and deciding who to treat, when and with what agent can be challenging. Establishing realistic therapeutic goals from both the patient and clinician perspective requires considerable expertise. The document aims to provide a framework for clinicians to aid in the assessment and management of ILD in the major CTD. A suggested approach to diagnosis and monitoring of CTD-ILD and, where available, evidence-based, disease-specific approaches to treatment have been provided.

Double-Triggering During Noninvasive Ventilation in a Simulated Lung Model.

BACKGROUND: Double-triggering is a well-recognized form of patient-ventilator asynchrony in noninvasive ventilation (NIV). This benchtop simulated lung study aimed to determine under which patient and device-specific conditions double-triggering is more prevalent, and how this influences the delivery of NIV. METHODS: Two commonly used proprietary NIV devices were tested using a benchtop lung model. Lung compliance, airway resistance, respiratory effort, and breathing frequency were manipulated, and the frequency of double-triggering was assessed. A lung model of very low lung compliance (15 mL/cm H2O) was then used to assess the frequency of double-triggering when breathing frequency and respiratory effort were varied, along with basic NIV settings, including inspiratory pressure and expiratory pressure. Minute ventilation and total inspiratory work (as calculated by the simulated lung model) were also correlated with frequency of double-triggering. RESULTS: In both devices, double-triggering was observed with reduced lung compliance (P = .02 and P < .001 for the two devices, respectively). Reduced airway resistance was associated with double-triggering with the one device only (P = .02). Respiratory effort and breathing frequency were not independent predictors of double-triggering across all lung models. In the lung model of very low lung compliance, both devices showed increased double-triggering at a lower breathing frequency (P < .001 and P < .001), higher respiratory effort (P = .03 and P < .001), and greater pressure support (P = .044, P < .001). Importantly, double-triggering was associated with reduced minute ventilation (P = .007) with one device and increased inspiratory work (P < .001) with the other device. CONCLUSIONS: Both simulated-patient and device characteristics influenced the frequency of double-triggering in NIV, resulting in meaningful consequences in a simulated lung model.

Clinical management practices of life-threatening asthma: an audit of practices in intensive care.

OBJECTIVE: Lack of management guidelines for lifethreatening asthma (LTA) risks practice variation. This study aims to elucidate management practices of LTA in the intensive care unit (ICU). DESIGN: A retrospective cohort study. SETTING: Thirteen participating ICUs in Australia between July 2010 and June 2013. PARTICIPANTS: Patients with the principal diagnosis of LTA. MAIN OUTCOME MEASURES: Clinical history, ICU management, patient outcomes, ward education and discharge plans. RESULTS: Of the 270 (267 patients) ICU admissions, 69% were female, with a median age of 39 years (interquartile range [IQR], 26-53 years); 119 (44%) were current smokers; 89 patients (33%) previously required ICU admission, of whom 23 (25%) were intubated. The median ICU stay was 2 days (IQR, 2-4 days). Three patients (1%) died. Seventy-nine patients (29%) received non-invasive ventilation, with 11 (14%) needing subsequent invasive ventilation. Sixty-eight patients (25%) were intubated, with the majority of patients receiving volume cycled synchronised intermittent mechanical ventilation (n = 63; 93%). Drugs used included ß2-agonist by intravenous infusion (n = 69; 26%), inhaled adrenaline (n = 15; 6%) or an adrenaline intravenous infusion (n = 23; 9%), inhaled anticholinergics (n = 238; 90%), systemic corticosteroids (n = 232; 88%), antibiotics (n = 126; 48%) and antivirals (n = 22; 8%). When suitable, 105 patients (n = 200; 53%) had an asthma management plan and 122 (n = 202; 60%) had asthma education upon hospital discharge. Myopathy was associated with hyperglycaemia requiring treatment (odds ratio [OR], 31.6; 95% CI, 2.1-474). Asthma education was more common under specialist thoracic medicine care (OR, 3.0; 95% CI, 1.61-5.54). CONCLUSION: In LTA, practice variation is common, with opportunities to improve discharge management plans and asthma education.

Treatment associated Mantle Cell Lymphoma with Cyclophosphamide therapy for Granulomatosis with Polyangiitis.

We present a case of a 68-year-old woman who developed mantle cell lymphoma in the setting of long-term cyclophosphamide therapy and relapsing granulomatosis with polyangiitis (Wegener's granulomatosis, GPA). Adverse outcomes associated with cyclophosphamide therapy are well documented; however, the development of non-Hodgkin's lymphoma appears rare. Cumulative dose of cyclophosphamide (>36 g) is a significant risk factor in the development of serious long-term adverse outcomes and is particularly relevant to this case in which maintenance cyclophosphamide therapy was continued, following induction, for 2 years total, on account of patient preference. This case study will highlight the patient's initial diagnosis, treatment response, relapse and subsequent complications of therapy.

Parasite predators exhibit a rapid numerical response to increased parasite abundance and reduce transmission to hosts.

Predators of parasites have recently gained attention as important parts of food webs and ecosystems. In aquatic systems, many taxa consume free-living stages of parasites, and can thus reduce parasite transmission to hosts. However, the importance of the functional and numerical responses of parasite predators to disease dynamics is not well understood. We collected host-parasite-predator cooccurrence data from the field, and then experimentally manipulated predator abundance, parasite abundance, and the presence of alternative prey to determine the consequences for parasite transmission. The parasite predator of interest was a ubiquitous symbiotic oligochaete of mollusks, Chaetogaster limnaei limnaei, which inhabits host shells and consumes larval trematode parasites. Predators exhibited a rapid numerical response, where predator populations increased or decreased by as much as 60% in just 5 days, depending on the parasite:predator ratio. Furthermore, snail infection decreased substantially with increasing parasite predator densities, where the highest predator densities reduced infection by up to 89%. Predators of parasites can play an important role in regulating parasite transmission, even when infection risk is high, and especially when predators can rapidly respond numerically to resource pulses. We suggest that these types of interactions might have cascading effects on entire disease systems, and emphasize the importance of considering disease dynamics at the community level.

Outcomes in patients with gram-negative sepsis treated with gentamicin.

OBJECTIVE: Recent changes to therapeutic drug monitoring (TDM) of gentamicin have been advocated in Australia. It remains uncertain whether these will have an effect on hard clinical endpoints. The aim of this study was to determine clinical outcomes in patients with gram-negative infections treated with gentamicin. METHODS: Microbiology results of patients with confirmed gram-negative cultures were retrospectively reviewed and those treated with gentamicin included. Medical records were reviewed and patient demographics, diagnosis, renal function, comorbidities, gentamicin doses, duration, monitoring, concomitant antibiotics, antimicrobial sensitivity and clinical and microbiological outcomes recorded. RESULTS: A total of 100 patients were included in the study: 52% were male, median age 64 years (17-97). Total body weight was recorded in 56% (median 74.5 kg, range 35-134 kg). Most patients had two or more important comorbidities. A total of 72% received empiric and 28% directed treatment. The organism was identified on blood culture in 45%, urine culture in 43% and aspiration of liver abscess in 12%; 95% of organisms were sensitive to gentamicin. Baseline renal function was normal in 62%. Mean gentamicin dose was 3.9 ± 0.9 mg/kg and mean duration 2.9 ± 2.5 days. Only 21% had optimal TDM. Clinical outcome was favourable in 90%. There were no cases of preventable serious toxicity. CONCLUSIONS: Despite the modest doses of gentamicin used in an elderly population with comorbidities, as well as the absence of optimal TDM, outcomes were favourable without preventable serious toxicity.

LPLRFamide causes anorexigenic effects in broiler chicks and Bobwhite quail.

Although LPLRFamide was the first member of the RFamide family to be isolated from a vertebrate species, its effects on hunger and satiety-related processes are poorly documented. Thus, we intracerebroventricularly administered LPLRFamide (3.0-15.0 nmol) to both Cobb-500 (a broiler type of Gallus gallus) and Bobwhite quail (Colinus virginianus) chicks and measured their food intake. The threshold of anorexigenic response was 7.0 nmol in Cobb-500 chicks and the effect had diminished by 30 min post-injection. In Bobwhite quail all doses of LPLRFamide tested caused anorexia that remained throughout the 60 min observation period. A comprehensive behavior analysis was conducted and Cobb-500 chicks had increased food pecks early in the observation period and spent a greater amount of time in deep rest. Although food pecks were increased pecking efficiency was decreased. In Bobwhite quail, feeding pecks and the number of jumps were reduced after LPLRFamide treatment. We judged that these behaviors in both species were likely not competitive with ingestion and thus did not secondarily contribute to anorexia. These results demonstrate that LPLRFamide is associated with satiety-related processes in Cobb-500 chicks and Bobwhite quail, while threshold of responses are different.