Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:

1. – high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;

2. – putative fossils on Mars will likely be ambiguous biomarkers for life;

3. – microbial contamination resulting from human habitation is unavoidable; and

4. – based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.

Some of the outstanding questions are:

1. – which interpretation of the hemispheric dichotomy of the planet is correct;

2. – to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;

3. – in what abundance are carbonates formed by atmospheric processes;

4. – what properties of martian meteorites could be used to constrain their source locations;

5. – the origin(s) of organic macromolecules;

6. – was/is Mars inhabited;

7. – how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;

8. – how can we ensure that humans and microbes form a stable and benign biosphere; and

9. – should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?

Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.

Introduction: Despite an overall decline in opioid prescriptions in Canada, healthcare visits, hospitalizations, and deaths due to opioid-related harms continue to rise for children. Clinicians urgently require high quality synthesized evidence to inform personalized decisions regarding opioid use for children. The objective of this systematic review was to examine the association between short-term therapeutic exposure to opioids and development of opioid use disorder. Methods: A medical librarian conducted a comprehensive search of 10 databases from inception to May 2019. Two authors independently assessed studies for inclusion. Studies were eligible if they reported primary research in English or French, and study participants had short (<14 days) or non-specific duration of therapeutic exposure to opioids before age 18 years. Primary outcome was the development of an opioid use disorder; secondary outcomes included opioid addiction, dependence, misuse, and abuse. Data extraction involved two independent reviewers utilizing a standardized form. Methodological quality was assessed using the NIH tools for observational studies. Results are described narratively. Results: The search identified 4,072 unique citations; 82 were selected for review, and 17 were included (3 retrospective cohort, 4 prospective cohort, and 10 cross-sectional). All studies took place in the USA. A total of 1,562,503 participants were analyzed. Nine studies were administered in schools, 3 used administrative data. While most settings were non-specific, 1 study examined opioid use in dentistry, 1 in trauma, and 1 in organized sports. One comparative study showed an association between short-term therapeutic use and opioid misuse. Two studies showed opioid related adverse events (e.g., overdose) among cohorts exposed to short-term use. The remaining 14 studies did not specify duration of exposure; therefore, confirming whether misuse was due to short-term therapeutic exposure was not possible. Conclusion: A small number of studies in this review suggest an association between short-term opioid use and opioid misuse; however, further analysis is underway with consideration of methodological limitations of the individual studies (final results pending). Careful consideration of the risk and benefits of short-term opioid use should be undertaken prior to prescribing opioids. PROSPERO Registration Number: 122681.

Background: Since January 1, 2016 2358 people have died from opioid poisoning in Alberta. Buprenorphine/naloxone (bup/nal) is the recommended first line treatment for opioid use disorder (OUD) and this treatment can be initiated in emergency departments and urgent care centres (EDs). Aim Statement: This project aims to spread a quality improvement intervention to all 107 adult EDs in Alberta by March 31, 2020. The intervention supports clinicians to initiate bup/nal for eligible individuals and provide rapid referrals to OUD treatment clinics. Measures & Design: Local ED teams were identified (administrators, clinical nurse educators, physicians and, where available, pharmacists and social workers). Local teams were supported by a provincial project team (project manager, consultant, and five physician leads) through a multi-faceted implementation process using provincial order sets, clinician education products, and patient-facing information. We used administrative ED and pharmacy data to track the number of visits where bup/nal was given in ED, and whether discharged patients continued to fill any opioid agonist treatment (OAT) prescription 30 days after their index ED visit. OUD clinics reported the number of referrals received from EDs and the number attending their first appointment. Patient safety event reports were tracked to identify any unintended negative impacts. Evaluation/Results: We report data from May 15, 2018 (program start) to September 31, 2019. Forty-nine EDs (46% of 107) implemented the program and 22 (45% of 49) reported evaluation data. There were 5385 opioid-related visits to reporting ED sites after program adoption. Bup/nal was given during 832 ED visits (663 unique patients): 7 visits in the 1st quarter the program operated, 55 in the 2nd, 74 in the 3rd, 143 in the 4th, 294 in the 5th, and 255 in the 6th. Among 505 unique discharged patients with 30 day follow up data available 319 (63%) continued to fill any OAT prescription after receiving bup/nal in ED. 16 (70%) of 23 community clinics provided data. EDs referred patients to these clinics 440 times, and 236 referrals (54%) attended their first follow-up appointment. Available data may under-report program impact. 5 patient safety events have been reported, with no harm or minimal harm to the patient. Discussion/Impact: Results demonstrate effective spread and uptake of a standardized provincial ED based early medical intervention program for patients who live with OUD.

The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.

Introduction: Given the current opioid crisis, caregivers have mounting fears regarding use of opioid medication in their children. Since caregivers are often the gatekeepers to their children's pain management, understanding their perspectives on analgesics is essential. For caregivers of children with acute injury presenting to the pediatric emergency department (PED), we aimed to determine caregivers’: a) willingness to accept opioids from emergency care providers, b) reasons for refusing opioids, and c) past experiences with opioids. Methods: A novel 31-item electronic survey was offered, via tablet device, to caregivers of children aged 4-16 years who had a musculoskeletal injury <7 days old and presented to one of two Canadian PEDs between March and November 2017. Primary outcome was caregiver willingness to accept opioids for moderate pain for their children. Results: 517 caregivers completed the survey; mean age was 40.9 +/−7 years with 70.0% (362/517) being mothers. Children included 62.2% (321/516) males with an overall mean age of 10 +/−3.6 years. 49.6% of caregivers (254/512) reported willingness to accept opioids for moderate pain that persisted after non-opioid analgesia, while 37.1% (190/512) were unsure what they would do. Only 33.2% (170/512) of caregivers stated they would accept opioid analgesia upon discharge while 45.5% (233/512) were unsure about at-home use. Caregivers were primarily concerned about side effects, overdose, addiction, and masking of diagnosis. Caregiver fear of addiction (OR 1.12, 95% CI 1.01-1.25) and side effects (OR 1.25, 95% CI 1.11-1.42) increased the odds of rejecting opioids in the emergency department, while fears of addiction (OR 1.19, 95% CI 1.07-1.32) and overdose (OR 1.15, 95% CI 1.04-1.27) increased the odds of rejecting opioids for at-home use. Conclusion: Only half of caregivers reported that they would accept opioids for moderate pain, despite ongoing pain following non-opioid analgesics. Caregiver fears of addiction, side effects, overdose, and masking their child's diagnosis influence their behaviours. These findings are a first step in understanding caregiver decision-making and can guide healthcare providers in their conversations about acute pain treatment with families.

Introduction: Competence in procedural skills is vital within the emergency department. Challenging procedures such as cricothyroidotomy are difficult to master as they are rare and hard to train for. Additionally, common procedures such as chest tube insertions require practice to become sufficiently competent. Opportunities to hone these skills are essential in residency training. This project aimed to create instructional video modules for specific emergency medicine (EM) procedures and gauge their utility as adjunctive resources for procedural learning in the EM residency curriculum. Methods: Tutorial videos for clamshell thoracotomy, cricothyroidotomy, and chest tube insertion were filmed within a cadaver lab with step-by-step instructions. The footage was edited and overlaid with a pre-prepared audio narration using Camtasia®/Apple® Video Editing software. These videos were embedded within modules that included foundational knowledge relevant to the procedures, including anatomy, physiology and pathophysiology. The modules were peer-edited by licensed EM staff physicians and distributed to EM residents and staff physicians for analysis. Qualitative and quantitative analysis relied upon participants’ answers to questions and a Modified Task Value Scale, respectively. Results: Ten participants were included in the analysis, including EM residents (n = 6) and staff emergency physicians (n = 4). Qualitative feedback suggested that positive aspects of the modules included visuals, content, narration, and review of anatomy. Negative aspects included the lack of indications for procedures, technical details, real patient examples, and a speed up function. Quantitative feedback resulted in scores of 4 and above out of 5 on the Motivated Task Value Scale across all aspects for all the modules. Furthermore, analysis revealed an average score of 3.9 for inclination to access more modules such as these, and a score of 4.4 for overall perception of the modules. Conclusion: Participants found the video modules valuable to their learning, both qualitatively and quantitatively. This study was limited by a small sample size of modules and a low number of participants. Furthermore, a more detailed analysis with further measures, including self-efficacy and self-confidence, would yield more comprehensive conclusions. However, video-based modules provide an effective and easily accessible adjunctive tool to acquire skill and confidence with EM procedures, for medical learners and staff physicians.

Three-dimensional (3D) printing technology is a promising method for bone tissue engineering applications. For enhanced bone regeneration, it is important to have printable ink materials with appealing properties such as construct interconnectivity, mechanical strength, controlled degradation rates, and the presence of bioactive materials. In this respect, we develop a composite ink composed of polycaprolactone (PCL), poly(D,L-lactide-co-glycolide) (PLGA), and hydroxyapatite particles (HAps) and 3D print it into porous constructs. In vitro study revealed that composite constructs had higher mechanical properties, surface roughness, quicker degradation profile, and cellular behaviors compared to PCL counterparts. Furthermore, in vivo results showed that 3D-printed composite constructs had a positive influence on bone regeneration due to the presence of newly formed mineralized bone tissue and blood vessel formation. Therefore, 3D printable ink made of PCL/PLGA/HAp can be a highly useful material for 3D printing of bone tissue constructs.

Introduction: Inadequate pain management in children is ubiquitous in the emergency department (ED). As the current national opioid crisis has highlighted, physicians are caught between balancing pain management and the risk of long term opioid dependence. This study aimed to describe pediatric emergency physicians (PEPs) willingness to prescribe opioids to children in the ED and at discharge. Methods: A unique survey tool was created using published methodology guidelines. Information regarding practices, knowledge, attitudes, perceived barriers, facilitators and demographics were collected. The survey was distributed to all physician members of Pediatric Emergency Research Canada (PERC), using a modified Dillmans Tailored Design method, from October to December 2017. Results: The response rate was 49.7% (124/242); 53% (57/107) were female, mean age was 43.6 years (+/− 8.7), and 58% (72/124) had pediatric emergency subspecialty training. The most common first line ED pain medication was ibuprofen for mild, moderate and severe musculoskeletal injury (MSK-I)-related pain (94.4% (117/124), 89.5% (111/124), and 62.9% (78/124), respectively). For moderate and severe MSK-I, intranasal fentanyl was the most common opioid for first (35.5% (44/124) and 61.3% (76/124), respectively) and second line pain management (41.1% (51/124) and 20.2% (25/124), respectively). 74.8% (89/119) of PEPs reported that an opioid protocol would be helpful, specifically for morphine, fentanyl, and hydromorphone. Using a 0-100 scale, physicians minimally worried about physical dependence (13.3 +/−19.3), addiction (16.6 +/−19.8), and diversion of opioids (32.8+/−26.4) when prescribing short-term opioids to children. They reported that the current opioid crisis minimally influenced their willingness to prescribe opioids (30.0 +/−26.2). Physicians reported rarely (36%; 45/125) or never (28%; 35/125) completing a screening risk assessment prior to prescribing opioids. Conclusion: Ibuprofen remains the most common medication recommended for MSK-I pain in the ED and at discharge. Intranasal fentanyl was the top opioid for all pain intensities. PEPs are minimally concerned regarding dependence, addiction, and the current opioid crisis when prescribing short-term opioids to children. There is an urgent need for robust evidence regarding the dependence and addiction risk for children receiving short term opioids in order to create knowledge translation tools for ED physicians. Opioid specific protocols for both in the ED and at discharge would likely improve physician comfort in responsible and adequate pain management for children.

Introduction: Active substance use and unstable housing are both associated with increased emergency department (ED) utilization. This study examined ED health care costs among a cohort of substance using and/or homeless adults following an index ED visit, relative to a control ED population. Methods: Consecutive patients presenting to an inner-city ED between August 2010 and November 2011 who reported unstable housing and/or who had a chief presenting complaint related to acute or chronic substance use were evaluated. Controls were enrolled in a 1:4 ratio. Participants’ health care utilization was tracked via electronic medical record for six months after the index ED visit. Costing data across all EDs in the region was obtained from Alberta Health Services and calculated to include physician billing and the cost of an ED visit excluding investigations. The cost impact of ED utilization was estimated by multiplying the derived ED cost per visit by the median number of visits with interquartile ranges (IQR) for each group during follow up. Proportions were compared using non-parametric tests. Results: From 4679 patients screened, 209 patients were enrolled (41 controls, 46 substance using, 91 unstably housed, 31 both unstably housed and substance using (UHS)). Median costs (IQR) per group over the six-month period were $0 ($0-$345.42) for control, $345.42 ($0-$1139.89) for substance using, $345.42 ($0-$1381.68) for unstably housed and $1381.68 ($690.84-$4248.67) for unstably housed and substance using patients (p<0.05). Conclusion: The intensity of excess ED costs was greatest in patients who were both unstably housed and presenting with a chief complaint related to substance use. This group had a significantly larger impact on health care expenditure relative to ED users who were not unstably housed or who presented with a substance use related complaint. Further research into how care or connection to community resources in the ED can reduce these costs is warranted.

Introduction: Emergency department visits related to substance use are becoming more serious and increasingly costly in Canada. Emergency physicians must be able to effectively screen, manage, refer, and advocate for these complex patients. This study sought to describe the current state of addiction medicine training in Canadian emergency medicine (EM) residency programs and to assess the need for a formal curriculum. Methods: All Royal College and College of Family Physicians EM Program Directors (PDs) were asked to participate in a ten-question needs assessment survey on addiction medicine training for residents. Questions were developed through consensus after reviewing the relevant literature and conducting a formal pilot survey with staff physicians experienced in survey methodology. Responses were collected securely using the Research Electronic Data Capture (REDCap) database. Results: 19 out of 31 (62%) eligible PDs completed the survey. The importance of addiction medicine training received a median score of 69.5 (IQR=74.0) on a scale of 1-100. Most programs devoted two hours or less per year of formalized teaching on individual topics (such as opioids, alcohol, harm reduction) over the past two academic years. The two most common teaching modalities used were didactic lectures (15/19, 78.9%) and case-based tutorials (12/19, 63.2%). Case-based tutorials were identified as the most effective teaching method (12/19, 63.2%). Topics highlighted as most important to include in a curriculum were: screening for substance use disorders and referral for further treatment (14/19, 73.7%), social determinants of health (14/19, 73.7%), alcohol, opioid, and stimulant intoxication and/or withdrawal (14/19, 73.7% each), and management of patients on opioid agonist therapy (14/19, 73.7%). The most commonly perceived barriers to implementing such a curriculum were insufficient curriculum time (10/19, 52.6%) and lack of qualified teaching staff (7/19, 36.8%). Conclusion: This needs assessment provides an understanding of the current state of addiction medicine training for EM residents in Canada. A case-based addiction medicine workshop is currently being developed to address identified curriculum gaps. Integrating this curriculum longitudinally into a time-constrained academic schedule is an important next step.

It has been demonstrated that microRNAs (miRNAs) play important roles in the control of melanogenesis and hair color in mammals. By comparing miRNA expression profiles between brown and white alpaca skin, we previously identified miR508-3p as a differentially expressed miRNA suggesting its potential role in melanogenesis and hair color formation. The present study was conducted to determine the role of miR508-3p in melanogenesis in alpaca melanocytes. In situ hybridization showed that miR508-3p is abundantly present in the cytoplasma of alpaca melanocytes. miR508-3p was predicted to target the gene encoding microphthalmia transcription factor (MITF) and a luciferase reporter assay indicated that miR508-3p regulates MITF expression by directly targeting its 3′UTR. Overexpression of miR508-3p in alpaca melanocytes down-regulated MITF expression both at the messenger RNA and protein level and resulted in decreased expression of key melanogenic genes including tyrosinase and tyrosinase-related protein 2. Overexpression of miR508-3p in melanocytes also resulted in decreased melanin production including total alkali-soluble melanogenesis, eumelanogenesis and pheomelanogenesis. Results support a functional role of miR508-3p in regulating melanogenesis in alpaca melanocytes by directly targeting MITF.

Introduction: Substance use and unstable housing are associated with heavy use of the Emergency Department (ED). This study examined the impact of substance use and unstable housing on the probability of future ED use. Methods: Case-control study of patients presenting to an urban ED. Patients were eligible if they were unstably housed for the past 30 days, and/or if their chief complaint was related to substance use. Following written informed consent, patients completed a baseline survey and health care use was tracked via electronic medical records for the next six months. Controls were enrolled in a 1:4 ratio. More than 2 ED visits during the follow-up was pre-specified as a measure of excess ED use. Descriptive analyses included proportions and medians with interquartile ranges (IQR). Binomial logistic regression models were used to estimate the impact of housing status, high-risk alcohol use (AUDIT) and drug use (DUDIT), and combinations of these factors on subsequent acute care system contacts (ED visits + admissions). We controlled for age, gender, comorbidities at baseline, and baseline presenting acuity. Results: 41 controls, 46 substance using, 91 unstably housed, and 31 both unstably housed and substance using patients were enrolled (n = 209). Median ED visits during follow up were 0 (IQR: 0-1.0) for controls, 1.0 (IQR: 0-3.3) for substance using, 1.0 (IQR: 0-4.0) for unstably housed and 4 (IQR: 2-12.3) for unstably housed and substance using patients. The median acute care system contacts over the same period was 1.0 (IQR 0-2.0) for controls, 1.0 (IQR: 0-4.0) for substance using, 1.0 (IQR: 0-5.0) for unstably housed and 4.5 (IQR: 2.8-14.3) for unstably housed and substance using patients. Being unstably housed was the factor most strongly associated with having > 2 ED visits (b=3.288, p<0.005) followed by high-risk alcohol and drug use (b=2.149, p<0.08); high risk alcohol use alone was not significantly associated with ED visits (b=1.939, p<0.1). The number of comorbidities present at baseline was a small but statistically significant additional risk factor (b=0.478, p<0.05). The model correctly predicted 70.1% of patients’ ED utilization status. Conclusion: Unstable housing is a substantial risk factor for ED use; high-risk alcohol and drug use, and comorbidities at baseline increased this risk. The intensity of excess ED use was greatest in patients who were unstably housed and substance using.

Introduction: Patients who are homeless and/or using substances rely heavily on emergency departments (ED) for medical care, and present with complex medical and social needs. Negative physician attitudes towards this population undermine the therapeutic relationship, compromising the quality of medical care provided. The objective of this study was to determine the attitudes of emergency physicians towards homeless and substance-using patients. Methods: Using a Modified Total Design approach, we conducted a cross-sectional survey of emergency physicians at five different healthcare locations in Calgary, Alberta, Canada. Attitudes were assessed using two validated measures, the Health Care Providers Attitudes Towards the Homeless Inventory (HPATHI), and the Short Understanding of Substance Use Scale (SUSS). Surveys were self-administered by respondents between March and December 2013. Results: A total of 117 physicians completed the survey (response rate 48%). 28% of respondents resented the amount of time it takes to see homeless patients, and 32% believed caring for homeless patients was not financially viable; 57% felt overwhelmed by the complexity of problems that homeless people have. Physicians with extra training in addiction medicine or health care for the homeless had more positive attitudes than physicians with no extra training; physician attitudes worsened over time towards both populations. Conclusion: Physicians feel overwhelmed when caring for patients who are homeless and/or substance using and negative attitudes worsened over time. Extra training in addiction medicine or healthcare for the homeless is associated with more positive attitudes. Possible strategies to improve attitudes should include a multifaceted approach addressing individual physician knowledge deficits, as well as expanded access to resources in the ED and community, designed to deal with the complex needs of these populations.