The Ighmbp2D564N mouse model is the first SMARD1 model to demonstrate respiratory defects.

Spinal muscular atrophy with respiratory distress type I (SMARD1) is a neurodegenerative disease defined by respiratory distress, muscle atrophy and sensory and autonomic nervous system defects. SMARD1 is a result of mutations within the IGHMBP2 gene. We have generated six Ighmbp2 mouse models based on patient-derived mutations that result in SMARD1 and/or Charcot-Marie Tooth Type 2 (CMT2S). Here we describe the characterization of one of these models, Ighmbp2D564N (human D565N). The Ighmbp2D564N/D564N mouse model mimics important aspects of the SMARD1 disease phenotype, including motor neuron degeneration and muscle atrophy. Ighmbp2D564N/D564N is the first SMARD1 mouse model to demonstrate respiratory defects based on quantified plethysmography analyses. SMARD1 disease phenotypes, including the respiratory defects, are significantly diminished by intracerebroventricular (ICV) injection of ssAAV9-IGHMBP2 and the extent of phenotypic restoration is dose-dependent. Collectively, this model provides important biological insight into SMARD1 disease development.

Does diet quality moderate the long-term effects of discrete but extreme PM2.5 exposure on respiratory symptoms? A study of the Hazelwood coalmine fire.

In 2014, a fire at an open cut coalmine in regional Victoria, Australia burned for 6 weeks. Residents of the nearby town of Morwell were exposed to smoke, which included high levels of fine particulate matter (PM2.5). We investigated whether the long-term effects of PM2.5 on respiratory health were moderated by diet quality. A cross-sectional analysis was conducted of data collected 8.5 years after the mine fire from 282 residents of Morwell and 166 residents from the nearby unexposed town of Sale. Primary outcomes were respiratory symptoms. Exposure was coalmine fire-related PM2.5 and diet quality was assessed as Australian Recommended Food Score (ARFS) derived using the Australian Eating Survey (AES). The moderating effect of diet quality on respiratory outcomes associated with PM2.5 was assessed using logistic regression models, adjusting for potential confounders. Diet quality was poor in this sample, with 60% in the lowest category of overall diet quality. Overall diet quality and fruit and vegetable quality significantly attenuated the association between PM2.5 and prevalence of chronic cough and phlegm. Sauce/condiment intake was associated with a greater effect of PM2.5 on COPD prevalence. No other moderating effects were significant. The moderating effects of overall diet quality and vegetable and fruit intake aligned with a priori hypotheses, suggesting potential protective benefits. While more evidence is needed to confirm these findings, improving diets, especially fruit and vegetable intake, may provide some protection against the effects of smoke exposure from fire events.

Long-term effects of extreme smoke exposure on COVID-19: A cohort study.

BACKGROUND: In 2014, the Hazelwood coalmine fire shrouded the regional Australian town of Morwell in smoke and ash for 6 weeks. One of the fire's by-products, PM2.5 , is associated with an increased risk of COVID-19 and severe disease. However, it is unclear whether the effect persisted for years after exposure. In this study, we surveyed a cohort established prior to the pandemic to determine whether PM2.5 from the coalmine fire increased long-term vulnerability to COVID-19 and severe disease. METHODS: From August to December 2022, 612 members of the Hazelwood Health Study's adult cohort, established in 2016/17, participated in a follow-up survey that included standardized items to capture COVID-19 cases, as well as questions about hospitalization and vaccinations. Associations were evaluated in crude and adjusted logistic regression models. RESULTS: A total of 268 (44%) participants self-reported or met symptom criteria for having had COVID-19 at least once. All models found a positive association, with odds of COVID-19 increasing by between 4% and 30% for a 10 µg/m3 increase in coalmine fire-related PM2.5 exposure. However, the association was significant in only 2 of the 18 models. There were insufficient hospitalizations to examine severity (n = 7; 1%). CONCLUSION: The findings are inconclusive on the effect of coalmine fire-related PM2.5 exposure on long-term vulnerability to COVID-19. Given the positive association that was robust to modelling variations as well as evidence for a causal mechanism, it would be prudent to treat PM2.5 from fire events as a long-term risk factor until more evidence accumulates.

Association between PM2.5 from a coal mine fire and FeNO concentration 7.5 years later.

BACKGROUND AND AIM: There are few long-term studies of respiratory health effects of landscape fires, despite increasing frequency and intensity due to climate change. We investigated the association between exposure to coal mine fire PM2.5 and fractional exhaled nitric oxide (FeNO) concentration 7.5 years later. METHODS: Adult residents of Morwell, who were exposed to the 2014 Hazelwood mine fire over 6 weeks, and unexposed residents of Sale, participated in the Hazelwood Health Study Respiratory Stream in 2021, including measurements of FeNO concentration, a marker of eosinophilic airway inflammation. Individual exposure to coal mine fire PM2.5 was modelled and mapped to time-location diaries. The effect of exposure to PM2.5 on log-transformed FeNO in exhaled breath was investigated using multivariate linear regression models in the entire sample and stratified by potentially vulnerable subgroups. RESULTS: A total of 326 adults (mean age: 57 years) had FeNO measured. The median FeNO level (interquartile range [IQR]) was 17.5 [15.0] ppb, and individual daily exposure to coal mine fire PM2.5 was 7.2 [13.8] µg/m3. We did not identify evidence of association between coal mine fire PM2.5 exposure and FeNO in the general adult sample, nor in various potentially vulnerable subgroups. The point estimates were consistently close to zero in the total sample and subgroups. CONCLUSION: Despite previous short-term impacts on FeNO and respiratory health outcomes in the medium term, we found no evidence that PM2.5 from the Hazelwood coal mine fire was associated with any long-term impact on eosinophilic airway inflammation measured by FeNO levels.

Long-term impact of the 2014 Hazelwood coal mine fire on emergency department presentations in Australia.

BACKGROUND: In 2014, wildfires ignited a coal mine in Australia, burning for 6 weeks, releasing large amounts of fine particulate matter ≤2.5 µm in diameter (PM2.5). We investigated the association between individual PM2.5 exposure and emergency department presentations (EDPs) within 5 years post-fire. METHODS: Survey and exposure data for 2725 residents from an exposed and unexposed town were linked with ED administrative data from 2009 to 2019. The association between individual PM2.5 and EDPs was assessed using recurrent survival analysis. RESULTS: A 10 µg/m3 increase in PM2.5 was associated with a 10% increase in respiratory EDPs (HR = 1.10; 95%CI:1.00-1.22) over 5 years post-fire. Increased risks of EDPs for ischaemic heart disease (HR = 1.39; 95%CI:1.12-1.73), atherothrombotic disease (HR = 1.27; 95%CI:1.08-1.50), and cardiovascular disease (HR = 1.10, 95%CI:0.99-1.22) were evident within 2.5 years. CONCLUSION: PM2.5 exposure from a 6-week mine fire increased the 5-year risk of respiratory conditions. An increased risk of CVD within 2.5 years post-fire subsided after this time.

Somatic symptoms, psychological distress and trauma after disasters: lessons from the 2014 Hazelwood mine fire and 2019-20 Black Summer bushfires.

BACKGROUND: Wildfires cause significant physical and mental ill-health. How physical and mental symptoms interact following wildfire smoke exposure is unclear, particularly in the context of repeated exposures. In this cross-sectional study we investigated how posttraumatic stress and general psychological distress associated with somatic symptoms in a community exposed to multiple smoke events. METHODS: A random weighted sample of 709 adults exposed to smoke during the 2014 Hazelwood coal mine fire in south-eastern Australia completed a survey in 2020. The survey coincided with the Black Summer wildfires that caused a similar period of smoke haze in the region. Participants self-reported somatic symptoms (PHQ-15) and mine fire-related posttraumatic stress (IES-R) experienced over the previous week, general psychological distress (K10) experienced over the previous four weeks, lifetime health diagnoses and demographic information. Associations between posttraumatic stress, general psychological distress, and each PHQ-15 somatic symptom were analysed using ordinal logistic regression models. RESULTS: Overall, 36.2% of participants reported moderate- or high-level somatic symptomology. The most frequent somatic symptoms were fatigue, limb pain, trouble sleeping, back pain, headaches, and shortness of breath. After controlling for confounding factors, general psychological distress and posttraumatic stress were independently associated with all somatic symptoms (except menstrual problems in females for posttraumatic stress). CONCLUSIONS: Results highlight the high prevalence of somatic symptoms and their association with general psychological distress and posttraumatic stress within a community in the midst of a second large-scale smoke event. It is essential that healthcare providers and public health authorities consider the interconnections of these conditions when supporting communities affected by climate-related disasters.

Sociodemographic circumstances, health, and life experience shape posttraumatic distress trajectories among individuals exposed to smoke during a large-scale coal mine fire.

The 2014 Hazelwood coal mine fire in the Latrobe Valley, Australia, distributed toxic smoke into surrounding communities over 45 days. This study investigated risk and protective factors associated with four trajectories of posttraumatic distress (resilient, recovery, delayed-onset, chronic) among exposed adults. Participants (N = 709) completed surveys in 2016-2017 and 2019-2020 assessing mine fire-related particulate matter (PM2.5 ) exposure; sociodemographic, physical, and mental health variables; and exposure to other traumatic and recent stressful events. Mine fire-related posttraumatic distress was measured using the IES-R; trajectories were determined according to established clinical significance thresholds. Relative risk ratios (RRRs) were generated from multivariate multinomial regressions. The resilient trajectory was most common (77.0%). The chronic trajectory (8.5%) was associated with loneliness, RRR = 2.59, 95% CI [1.30, 5.16], and physical health diagnoses, RRR = 2.31, 95% CI [1.32, 4.02]. The delayed-onset trajectory (9.1%) was associated with multiple recent stressful events, RRR = 2.51, 95% CI [1.37, 4.59]; mental health diagnoses, RRR = 2.30, 95% CI [1.25, 4.24]; loneliness, RRR = 2.05, 95% CI [1.09, 3.88]; and male gender, RRR = 2.01, 95% CI [1.18, 3.44]. Socioeconomic advantage protected against chronic, RRR = 0.68, 95% CI [0.53, 0.86], and delayed-onset trajectory membership, RRR = 0.68, 95% CI [0.50, 0.94]; social support protected against chronic trajectory membership, RRR = 0.67, 95% CI [0.49, 0.92]. PM2.5 exposure did not determine trajectory. These findings enhance understanding of longer-term posttraumatic responses to large-scale smoke events and can inform mental health initiatives within at-risk communities.

Divergent receptor utilization is necessary for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections.

Intrapleural injection of cholera toxin B conjugated to saporin (CTB-SAP) mimics respiratory motor neuron death and respiratory deficits observed in rat models of neuromuscular diseases. Seven-day CTB-SAP rats elicit enhanced phrenic long-term facilitation (pLTF) primarily through TrkB and PI3K/Akt-dependent mechanisms [i.e., Gs-pathway, which can be initiated by adenosine 2A (A2A) receptors in naïve rats], whereas 28-day CTB-SAP rats elicit moderate pLTF though BDNF- and MEK-/ERK-dependent mechanisms [i.e., Gq-pathway, which is typically initiated by serotonin (5-HT) receptors in naïve rats]. Here, we tested the hypothesis that pLTF following CTB-SAP is 1) A2A receptor-dependent at 7 days and 2) 5-HT receptor-dependent at 28 days. Adult Sprague-Dawley male rats were anesthetized, paralyzed, ventilated, and exposed to acute intermittent hypoxia (AIH; 3-, 5-min bouts of 10.5% O2) following bilateral, intrapleural injections at 7 days and 28 days of 1) CTB-SAP (25 µg) or 2) unconjugated CTB and SAP (control). Intrathecal C4 delivery included either the 1) A2A receptor antagonist (MSX-3; 10 µM; 12 µL) or 2) 5-HT receptor antagonist (methysergide; 20 mM; 15 µL). pLTF was abolished with A2A receptor inhibition in 7-day, not 28-day, CTB-SAP rats versus controls (P < 0.05), whereas pLTF was abolished following 5-HT receptor inhibition in 28-day, not 7-day, CTB-SAP rats versus controls (P < 0.05). In addition, 5-HT2A receptor expression was unchanged in CTB-SAP rats versus controls, whereas 5-HT2B receptor expression was decreased in CTB-SAP rats versus controls (P < 0.05). This study furthers our understanding of the contribution of differential receptor activation to pLTF and its implications for breathing following respiratory motor neuron death.NEW & NOTEWORTHY The current study investigates underlying receptor-dependent mechanisms contributing to phrenic long-term facilitation (pLTF) following CTB-SAP-induced respiratory motor neuron death at 7 days and 28 days. We found that A2A receptors are required for enhanced pLTF in 7-day CTB-SAP rats, whereas 5-HT receptors are required for moderate pLTF in 28-day CTB-SAP rats. Targeting these time-dependent mechanisms have implications for breathing maintenance over the course of many neuromuscular diseases.

Are e-cigarette use and vaping associated with increased respiratory symptoms and poorer lung function in a population exposed to smoke from a coal mine fire?

BACKGROUND AND OBJECTIVE: E-cigarette use has become increasingly prevalent, but there is some evidence demonstrating potential harms with frequent use. We aimed to identify the profiles of e-cigarette users from a regional community in Australia and investigate the associations of e-cigarettes with respiratory symptoms and lung function. METHODS: A total of 519 participants completed a cross-sectional study. Exposure to e-cigarettes was collected via a validated questionnaire. Respiratory symptoms were evaluated via a self-reported questionnaire and lung function measured with spirometry and forced oscillation technique (FOT). Linear and logistic regression models were fitted to investigate the associations between e-cigarettes and outcomes, while controlling for confounders such as tobacco smoking. RESULTS: Of the 519 participants, 46 (9%) reported e-cigarette use. Users tended to be younger (mean ± SD 45.2 ± 14.5 vs. 55.3 ± 16.0 years in non-users), concurrently using tobacco products (63% vs. 12% in non-users), have a mental health diagnosis (67% vs. 37% in non-users) and have self-reported asthma (63% vs. 42% in non-users). After controlling for known confounders, chest tightness (OR = 2.4, 95% CI 1.2-4.9, p = 0.02) was associated with e-cigarette use. Spirometry was not different after adjustment for confounding. However, FOT showed more negative reactance and a greater area under the reactance curve in e-cigarette users than non-users. CONCLUSION: E-cigarette use was associated with increased asthma symptoms and abnormal lung mechanics in our sample, supporting a potential health risk posed by these products. Vulnerable populations such as young adults and those with mental health conditions have higher usage, while there is high concurrent tobacco smoking.

Amblyomma maculatum-associated rickettsiae in vector tissues and vertebrate hosts during tick feeding.

Rickettsia parkeri, a causative agent of spotted fever rickettsiosis, is transmitted by Amblyomma maculatum (Gulf Coast tick), a tick that may also carry a non-pathogenic spotted fever group Rickettsia, "Candidatus Rickettsia andeanae". Here, we evaluated R. parkeri and "Candidatus R. andeanae" in tissues from A. maculatum prior to, during, and after blood feeding on rabbits. Using colony-reared A. maculatum that were capillary-fed uninfected cells, R. parkeri, "Candidatus R. andeanae", or both rickettsiae, we detected higher levels of Rickettsia spp. in the respective treatment groups. Rickettsial levels increased during blood feeding for both R. parkeri and "Candidatus R. andeanae", with a greater increase in R. parkeri in co-infected ticks compared to singly-infected ticks. We detected transovarial transmission of "Candidatus R. andeanae" in egg and larval cohorts and confirmed vertical transmission of R. parkeri in one group of larvae. Rabbits from all Rickettsia-exposed groups seroconverted on immunofluorescent antibody testing using R. parkeri antigen. Visualization of "Candidatus R. andeanae" in tick salivary glands suggested potential transmission via tick feeding. Here, rickettsial levels in artificially infected ticks demonstrate changes during feeding and transovarial transmission that may be relevant for interpreting rickettsial levels detected in wild A. maculatum.

Associations of atopy and asthma during aging of an adult population over a 20-year follow-up.

OBJECTIVE: Atopy is associated with asthma, but cross-sectional studies suggest this association may be weaker in older adults. It remains unclear if atopy predicts asthma later in adult life. We aimed to investigate whether atopy in young adults predicted asthma 20 years later and to quantify the contemporaneous relationship of atopy and asthma as adults age. METHODS: Participants of the European Community Respiratory Health Survey (ECRHS) in Melbourne aged 20-44 years were followed for 20 years and completed questionnaires, skin prick tests (SPT) and allergen specific immunoglobulin E measurement at a baseline and two subsequent surveys. Using logistic regression and generalized estimating equations, we tested if atopy at baseline predicted current asthma later in life and estimated the association between current atopy measured at each survey and current asthma, while adjusting for potential confounders. RESULTS: The analysis included 220 participants: 50.9% male. Mean (SD) age at baseline was 35.7 (5.7) years. Asthma and atopy prevalence remained stable over 20 years. Baseline atopy (SPT) was associated with current asthma (OR 9.74, 95%CI 4.22, 22.5) over 20 years, and current atopy (SPT) with concurrent asthma (3.12; 1.70, 5.74). CONCLUSIONS: Atopy remains strongly associated with current asthma in 40 to 64 year-old adults, both prospectively and contemporaneously, but the prospective association is stronger.

Use of mobile and cordless phones and change in cognitive function: a prospective cohort analysis of Australian primary school children.

BACKGROUND: Some previous studies have suggested an association between children's use of mobile phones (MPs)/cordless phones (CPs) and development of cognitive function. We evaluated possible longitudinal associations between the use of MPs and CPs in a cohort of primary school children and effects on their cognitive function. METHODS: Data on children's socio-demographics, use of MPs and CPs, and cognitive function were collected at baseline (2010-2012) and follow-up (2012-2013). Cognitive outcomes were evaluated with the CogHealth™ test battery and Stroop Color-Word test. The change in the number of MP/CP voice calls weekly from baseline to follow-up was dichotomized: "an increase in calls" or a "decrease/no change in calls". Multiple linear regression analyses, adjusting for confounders and clustering by school, were performed to evaluate the associations between the change in cognitive outcomes and change in MP and CP exposures. RESULTS: Of 412 children, a larger proportion of them used a CP (76% at baseline and follow-up), compared to a MP (31% at baseline and 43% at follow-up). Of 26 comparisons of changes in cognitive outcomes, four demonstrated significant associations. The increase in MP usage was associated with larger reduction in response time for response inhibition, smaller reduction in the number of total errors for spatial problem solving and larger increase in response time for a Stroop interference task. Except for the smaller reduction in detection task accuracy, the increase in CP usage had no effect on the changes in cognitive outcomes. CONCLUSION: Our study shows that a larger proportion of children used CPs compared to MPs. We found limited evidence that change in the use of MPs or CPs in primary school children was associated with change in cognitive function.

A Prospective Randomized Clinical Trial in Total Hip Arthroplasty-Comparing Early Results Between the Direct Anterior Approach and the Posterior Approach.

BACKGROUND: We report a prospective randomized study comparing early clinical results between the direct anterior approach (DAA) and posterior approach (PA) in primary hip arthroplasty. METHODS: Surgeries were performed by 2 senior hip arthroplasty surgeons. Seventy-two patients with complete data were assessed preoperatively 2, 6, and 12 weeks postoperatively. The primary outcomes were the Western Ontario McMasters Arthritis Index and Oxford Hip Scores. Secondary outcome measures included the EuroQoL, 10-meter walk test, and clinical and radiographic parameters. RESULTS: Data analyses showed no difference between DAA (n = 35) and PA (n = 37) groups when comparing total scores for primary outcomes. No significant differences were observed for 10-meter walk test, EuroQoL, and radiographic analyses. Subgroup analysis for surgeon 1 identified that the DAA group had shorter acute hospital stay, less postoperative opiate requirements, and smaller wounds. However, this was offset by increased operative time, higher intraoperative blood loss, and weaker hip flexion at 2 and 6 weeks. Subgroup analysis of items on the Western Ontario McMasters Arthritis Index and Oxford Hip Score identified that hip flexion activity favored the DAA group up to 6 weeks postoperatively. There was an 83% incidence of lateral cutaneous nerve of thigh neuropraxia at the 12-week mark in the DAA group. No neuropraxias occurred in the PA group. One dislocation occurred in each group. A single patient from the DAA group required reoperation for leg-length discrepancy. CONCLUSION: DAA total hip arthroplasty (THA) has comparable results with PA THA. Choice of surgical approach for THA should be based on patient factors, surgeon preference, and experience.

Use of mobile and cordless phones and cognition in Australian primary school children: a prospective cohort study.

BACKGROUND: Use of mobile (MP) and cordless phones (CP) is common among young children, but whether the resulting radiofrequency exposure affects development of cognitive skills is not known. Small changes have been found in older children. This study focused on children's exposures to MP and CP and cognitive development. The hypothesis was that children who used these phones would display differences in cognitive function compared to those who did not. METHODS: We recruited 619 fourth-grade students (8-11 years) from 37 schools around Melbourne and Wollongong, Australia. Participants completed a short questionnaire, a computerised cognitive test battery, and the Stroop colour-word test. Parents completed exposure questionnaires on their child's behalf. Analysis used multiple linear regression. The principal exposure-metrics were the total number of reported MP and CP calls weekly categorised into no use ('None'); use less than or equal to the median amount ('Some'); and use more than the median ('More'). The median number of calls/week was 2.5 for MP and 2.0 for CP. RESULTS: MP and CP use for calls was low; and only 5 of 78 comparisons of phone use with cognitive measures were statistically significant. The reaction time to the response-inhibition task was slower in those who used an MP 'More' compared to the 'Some' use group and non-users. For CP use, the response time to the Stroop interference task was slower in the 'More' group versus the 'Some' group, and accuracy was worse in visual recognition and episodic memory tasks and the identification task. In an additional exploratory analysis, there was some evidence of a gender effect on mean reaction times. The highest users for both phone types were girls. CONCLUSIONS: Overall, there was little evidence cognitive function was associated with CP and MP use in this age group. Although there was some evidence that effects of MP and CP use on cognition may differ by gender, this needs further exploration. CP results may be more reliable as parents estimated children's phone use and the CPs were at home; results for CP use were broadly consistent with our earlier study of older children.

Assessing Rat Diaphragm Motor Unit Connectivity Outcome Measures as Quantitative Biomarkers of Phrenic Motor Neuron Degeneration and Compensation.

Loss of ventilatory muscle function is a consequence of motor neuron injury and neurodegeneration (e.g., cervical spinal cord injury and amyotrophic lateral sclerosis, respectively). Phrenic motor neurons are the final link between the central nervous system and muscle, and their respective motor units (groups of muscle fibers innervated by a single motor neuron) represent the smallest functional unit of the neuromuscular ventilatory system. Compound muscle action potential (CMAP), single motor unit potential (SMUP), and motor unit number estimation (MUNE) are established electrophysiological approaches that enable the longitudinal assessment of motor unit integrity in animal models over time but have mostly been applied to limb muscles. Therefore, the objectives of this study are to describe an approach in preclinical rodent studies that can be used longitudinally to quantify the phrenic MUNE, motor unit size (represented as SMUP), and CMAP, and then to demonstrate the utility of these approaches in a motor neuron loss model. Sensitive, objective, and translationally relevant biomarkers for neuronal injury, degeneration, and regeneration in motor neuron injury and diseases can significantly aid and accelerate experimental research discoveries to clinical testing.

Evaluating the impact of Hazelwood mine fire event on students' educational development with Bayesian interrupted time-series hierarchical meta-regression.

BACKGROUND: Environmental disasters such as wildfires, floods and droughts can introduce significant interruptions and trauma to impacted communities. Children and young people can be disproportionately affected with additional educational disruptions. However, evaluating the impact of disasters is challenging due to difficulties in establishing studies and recruitment post-disasters. OBJECTIVES: We aimed to (1) develop a Bayesian model using aggregated school-level data to evaluate the impact of environmental disasters on academic achievement and (2) evaluate the impact of the 2014 Hazelwood mine fire (a six-week fire event in Australia). METHODS: Bayesian hierarchical meta-regression was developed to evaluate the impact of the mine fire using easily accessible aggregated school-level data from the standardised National Assessment Program-Literacy and Numeracy (NAPLAN) test. NAPLAN results and school characteristics (2008-2018) from 69 primary/secondary schools with different levels of mine fire-related smoke exposure were used to estimate the impact of the event. Using an interrupted time series design, the model estimated immediate effects and post-interruption trend differences with full Bayesian statistical inference. RESULTS: Major academic interruptions across NAPLAN domains were evident in high exposure schools in the year post-mine fire (greatest interruption in Writing: 11.09 [95%CI: 3.16-18.93], lowest interruption in Reading: 8.34 [95%CI: 1.07-15.51]). The interruption was comparable to a four to a five-month delay in educational attainment and had not fully recovered after several years. CONCLUSION: Considerable academic delays were found as a result of a mine fire, highlighting the need to provide educational and community-based supports in response to future events. Importantly, this work provides a statistical method using readily available aggregated data to assess the educational impacts in response to other environmental disasters.

An overview of clustering methods with guidelines for application in mental health research.

Cluster analyzes have been widely used in mental health research to decompose inter-individual heterogeneity by identifying more homogeneous subgroups of individuals. However, despite advances in new algorithms and increasing popularity, there is little guidance on model choice, analytical framework and reporting requirements. In this paper, we aimed to address this gap by introducing the philosophy, design, advantages/disadvantages and implementation of major algorithms that are particularly relevant in mental health research. Extensions of basic models, such as kernel methods, deep learning, semi-supervised clustering, and clustering ensembles are subsequently introduced. How to choose algorithms to address common issues as well as methods for pre-clustering data processing, clustering evaluation and validation are then discussed. Importantly, we also provide general guidance on clustering workflow and reporting requirements. To facilitate the implementation of different algorithms, we provide information on R functions and libraries.

Nonsteroidal anti-inflammatory drug (ketoprofen) delivery differentially impacts phrenic long-term facilitation in rats with motor neuron death induced by intrapleural CTB-SAP injections.

Intrapleural injections of cholera toxin B conjugated to saporin (CTB-SAP) selectively eliminates respiratory (e.g., phrenic) motor neurons, and mimics motor neuron death and respiratory deficits observed in rat models of neuromuscular diseases. Additionally, microglial density increases in the phrenic motor nucleus following CTB-SAP. This CTB-SAP rodent model allows us to study the impact of motor neuron death on the output of surviving phrenic motor neurons, and the underlying mechanisms that contribute to enhancing or constraining their output at 7 days (d) or 28d post-CTB-SAP injection. 7d CTB-SAP rats elicit enhanced phrenic long-term facilitation (pLTF) through the Gs-pathway (inflammation-resistant in naïve rats), while pLTF is elicited though the Gq-pathway (inflammation-sensitive in naïve rats) in control and 28d CTB-SAP rats. In 7d and 28d male CTB-SAP rats and controls, we evaluated the effect of cyclooxygenase-1/2 enzymes on pLTF by delivery of the nonsteroidal anti-inflammatory drug, ketoprofen (IP), and we hypothesized that pLTF would be unaffected by ketoprofen in 7d CTB-SAP rats, but pLTF would be enhanced in 28d CTB-SAP rats. In anesthetized, paralyzed and ventilated rats, pLTF was surprisingly attenuated in 7d CTB-SAP rats and enhanced in 28d CTB-SAP rats (both p < 0.05) following ketoprofen delivery. Additionally in CTB-SAP rats: 1) microglia were more amoeboid in the phrenic motor nucleus; and 2) cervical spinal inflammatory-associated factor expression (TNF-α, BDNF, and IL-10) was increased vs. controls in the absence of ketoprofen (p < 0.05). Following ketoprofen delivery, TNF-α and IL-10 expression was decreased back to control levels, while BDNF expression was differentially affected over the course of motor neuron death in CTB-SAP rats. This study furthers our understanding of factors (e.g., cyclooxygenase-1/2-induced inflammation) that contribute to enhancing or constraining pLTF and its implications for breathing following respiratory motor neuron death.

Axon and Myelin Sheath Segmentation in Electron Microscopy Images using Meta Learning.

Various neurological diseases affect the morphology of myelinated axons. Quantitative analysis of these structures and changes occurring due to neurodegeneration or neuroregeneration is of great importance for characterization of disease state and treatment response. This paper proposes a robust, meta-learning based pipeline for segmentation of axons and surrounding myelin sheaths in electron microscopy images. This is the first step towards computation of electron microscopy related bio-markers of hypoglossal nerve degeneration/regeneration. This segmentation task is challenging due to large variations in morphology and texture of myelinated axons at different levels of degeneration and very limited availability of annotated data. To overcome these difficulties, the proposed pipeline uses a meta learning-based training strategy and a U-net like encoder decoder deep neural network. Experiments on unseen test data collected at different magnification levels (i.e, trained on 500X and 1200X images, and tested on 250X and 2500X images) showed improved segmentation performance by 5% to 7% compared to a regularly trained, comparable deep learning network.