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Heart rate variability (HRV) is a proxy measure of autonomic function and can be used as an indicator of swine stress. While traditional linear measures are used to distinguish between stressed and unstressed treatments, inclusion of nonlinear HRV measures that evaluate data structure and organization shows promise for improving HRV interpretation. The objective of this study was to evaluate the inclusion of nonlinear HRV measures in response to an acute heat episode. Twenty 12- to 14-week-old growing pigs were individually housed for 7 days and acclimated to thermoneutral conditions (20.35°C ± 0.01°C; 67.6% ± 0.2% RH) before undergoing one of the two treatments: (1) thermoneutral control (TN; n = 10 pigs) or (2) acute heat stress (HS; n = 10 pigs; 32.6°C ± 0.1°C; 26.2% ± 0.1% RH). In Phase 1 of the experimental procedure (P1; 60 min), pigs underwent a baseline HRV measurement period in thermoneutral conditions before treatment [Phase 2; P2; 60 min once gastrointestinal temperature (Tg) reached 40.6°C], where HS pigs were exposed to heated conditions and TN pigs remained in thermoneutral conditions. After P2, all pigs were moved back to thermoneutral conditions (Phase 3; P3; 60 min). During each phase, Tg data were collected every 5 min and behavioural data were collected to evaluate the amount of time each pig spent in an active posture. Additionally, linear (time and frequency domain) and nonlinear [sample entropy (SampEn), de-trended fluctuation analysis, percentage recurrence, percentage determinism (%DET), mean diagonal line length in a recurrence plot] HRV measures were quantified. Heat stressed pigs exhibited greater Tg (P = 0.002) and spent less time in an active posture compared to TN pigs during P2 (P = 0.0003). Additionally, low frequency to high frequency ratio was greater in HS pigs during P3 compared to TN pigs (P = 0.02). SampEn was reduced in HS pigs during P2 (P = 0.01) and P3 (P = 0.03) compared to TN pigs. Heat stressed pigs exhibited greater %DET during P3 (P = 0.03) and tended to have greater %DET (P = 0.09) during P2 than TN pigs. No differences between treatments were detected for the remaining HRV measures. In conclusion, linear HRV measures were largely unchanged during P2. However, changes to SampEn and %DET suggest increased heat stress as a result of the acute heat episode. Future work should continue to evaluate the benefits of including nonlinear HRV measures in HRV analysis of swine heat stress.
Evidence on long-term influences of maternal vitamin B12 deficiency or concentrations on infant cognition is limited. We examined associations between maternal plasma vitamin B12 and cognitive development in 24-month-old infants. Maternal plasma vitamin B12 concentrations were measured at 26–28 weeks’ gestation; infant cognitive development was assessed with the Bayley Scales of Infant and Toddler Development-III at 24 months, for 443 mother–infant pairs from the Growing Up in Singapore Towards Healthy Outcomes cohort. Linear regressions adjusted for key confounders examined associations of maternal vitamin B12 with cognitive, receptive and expressive language, fine and gross motor subscales. Co-occurrence of maternal vitamin B12 with folate or vitamin B6 insufficiencies on child’s cognition was explored. Average maternal plasma vitamin B12 concentrations was 220·5 ± 80·5 pmol/l; 15 % and 41 % of mothers were vitamin B12 deficient (<148 pmol/l) and insufficient (148–220·9 pmol/l), respectively. Infants of mothers with vitamin B12 deficiency had 0·42 (95 % CI −0·70, −0·14) sd lower cognitive scores, compared with infants of mothers with sufficient vitamin B12. Co-occurrence of maternal vitamins B12 and B6 insufficiencies was associated with 0·37 (95 % CI −0·69, −0·06) sd lower cognitive scores in infants compared with infants of mothers sufficient in both vitamins. No significant associations were observed with other subscales. Study findings suggest the possible need to ensure adequate vitamin B12 during pregnancy. The impact of co-occurrence of maternal B-vitamins insufficiencies on early cognitive development warrants further investigation.
Guangxi, a province in southwestern China, has the second highest reported number of HIV/AIDS cases in China. This study aimed to develop an accurate and effective model to describe the tendency of HIV and to predict its incidence in Guangxi. HIV incidence data of Guangxi from 2005 to 2016 were obtained from the database of the Chinese Center for Disease Control and Prevention. Long short-term memory (LSTM) neural network models, autoregressive integrated moving average (ARIMA) models, generalised regression neural network (GRNN) models and exponential smoothing (ES) were used to fit the incidence data. Data from 2015 and 2016 were used to validate the most suitable models. The model performances were evaluated by evaluating metrics, including mean square error (MSE), root mean square error, mean absolute error and mean absolute percentage error. The LSTM model had the lowest MSE when the N value (time step) was 12. The most appropriate ARIMA models for incidence in 2015 and 2016 were ARIMA (1, 1, 2) (0, 1, 2)12 and ARIMA (2, 1, 0) (1, 1, 2)12, respectively. The accuracy of GRNN and ES models in forecasting HIV incidence in Guangxi was relatively poor. Four performance metrics of the LSTM model were all lower than the ARIMA, GRNN and ES models. The LSTM model was more effective than other time-series models and is important for the monitoring and control of local HIV epidemics.
The association between opportunistic infection (OI) and anaemia among HIV-infected patients remains to be studied. We investigated the prevalence and risk factors of anaemia in hospitalised HIV-infected patients to reveal the association between OI and anaemia. We conducted a retrospective study of HIV-positive hospitalised patients from June 2016 to December 2017 in Mengchao Hepatobiliary Hospital of Fujian Medical University. Patients’ information on socio-demographic and clinical characteristics were carefully collected. The comparison of anaemia prevalence between groups was conducted with χ2 test. A logistic regression model was carried out to analyse the predictors of anaemia. The total prevalence of anaemia in hospitalised HIV-infected patients was 55.15%. The prevalence of mild, moderate and severe anaemia was 41.42%, 11.08% and 2.64%, respectively. Predictors independently associated with anaemia were: CD4 counts <50 cells/μl (odds ratio (OR): 6.376, 95% confidence interval (CI) = 1.916–21.215, P = 0.003), CD4 counts 50–199 cells/μl (OR: 6.303, 95% CI = 1.874–21.203, P = 0.003), co-infection with tuberculosis (TB) (OR: 2.703, 95% CI = 1.349–5.414, P = 0.005) or Penicillium marneffei (PM) (OR: 7.162, 95% CI = 3.147–15.299, P < 0.001). In Fujian, China, more than half inpatients with HIV were anaemic, but severe anaemia is infrequent. Lower CD4 counts, co-infection with TB or PM were independent risk factors for anaemia. Chinese HIV patients especially with TB, PM infection and low CD4 level should be routinely detected for anaemia to improve therapy.
Necrotising enterocolitis (NEC) is a devastating disease that typically affects formula-fed premature infants, suggesting that dietary components may influence disease pathogenesis. TAG are the major fat components of infant formula, and their digestion requires pancreatic lipases, which may be naturally deficient in premature neonates. We hypothesise that NEC develops partly from the accumulation of incompletely digested long-chain TAG-containing unsaturated fatty acids within the intestinal epithelial cells, leading to oxidative stress and enterocyte damage. We further hypothesise that the administration of a formula that contains reduced TAG (‘pre-digested fat’) that do not require lipase action may reduce NEC severity. To test these hypotheses, we induced NEC in neonatal mice using three different fat formulations, namely ‘standard fat’, ‘pre-digested fat’ or ‘very low fat’, and determined that mice fed ‘standard fat’ developed severe NEC, which was significantly reduced in mice fed ‘pre-digested fat’ or ‘very low fat’. The expression level of the critical fat-digesting enzyme carboxyl ester lipase was significantly lower in the newborn compared with older pups, leading to impaired fat digestion. The accumulation of mal-digested fat resulted in the significant accumulation of fat droplets within the intestinal epithelium of the distal ileum, resulting in the generation of reactive oxygen species and intestinal inflammation. Strikingly, these changes were prevented in pups fed ‘pre-digested fat’ or ‘very low fat’ formulas. These findings suggest that nutritional formula containing a pre-digested fat system may overcome the natural lipase deficiency of the premature gut, and serve as a novel approach to prevent NEC.
Due to the lack of basic information on water required by maize (Zea mays L.) in Brazil, the large amount of water applied usually exceeds crop requirements, wasting water and energy. In this study, we measured crop evapotranspiration (ETc) as evaporative heat flux from a centre pivot-irrigated maize plantation in Southern Brazil during winter and summer seasons, using the Bowen ratio method to evaluate how the degree of canopy-atmosphere coupling affects crop water needs and irrigation management. Irrigation requirements were determined by comparing ETc with reference evapotranspiration (ETo), derived from the Penman–Monteith equation and expressed as the ETc/ETo (Kc) ratio. In this study, the average Kc values obtained were 1.31 and 0.90 for the winter and summer, respectively. Using aerodynamic and canopy resistance measurements, the decoupling factor (Ω) was computed. Ω values tending to zero (0.09 and 0.20 for winter and summer, respectively) showed that strong coupling of maize plants to the atmosphere and sensitivity to high air temperatures, vapour pressure deficits and wind speed caused variations in Kc in relation to ETo ranges. During the experimental period, the Kc value ranged from 0.92 when the ETo exceeded 4 mm d−1 to 1.64 when the ETo was less than 2 mm d−1.
This study investigates numerically the performance of applying aerospike nozzle in a hydrogen peroxide mono-propellant propulsion system. A set of governing equations, including continuity, momentum, energy and species conservation equations with extended k-ε turbulence equations, are solved using the finite-volume method. The hydrogen peroxide mono-propellant is assumed to be fully decomposed into water vapor and oxygen after flowing through a catalyst bed before entering the nozzle. The aerospike nozzle is expected to have high performance even in deep throttling cases due to its self-compensating characteristics in a wide range of ambient pressure environments. The results show that the thrust coefficient efficiency (Cf,η) of this work exceeds 90% of the theoretical value with a nozzle pressure ratio (PR) in the range of 20 ~ 45. Many complex gas dynamics phenomena in the aerospike nozzle are found and explained in the paper. In addition, performance of the aerospike nozzle is compared with that of the bell-shape nozzle.
Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that selectively infects dividing cancer cells, integrates into the genome and replicates due to immune defects in tumors. Toca 511 spreads through tumors and stably delivers the gene encoding an optimized yeast cytosine deaminase that converts the prodrug Toca FC (investigational, extended-release of 5-fluorocytosine) into 5-fluorouracil. In preclinical models, 5-fluorouracil kills infected dividing cancer cells, myeloid derived suppressor cells and tumor associated macrophages, enabling immune activation against the tumor. In this dose ascending Ph1 trial (NCT01470794), Toca 511 was injected into the resection cavity wall of patients with rHGG, followed by courses of oral Toca FC. Additional cohorts included combination with bevacizumab or lomustine. Across the Ph1 program, the safety profile remains favorable. Objective responses (ORs) were assessed by IRR using MRI scans prior to Toca FC treatment as baseline. ORs occurred 6-19 months after Toca 511 administration, suggesting an immunologic mechanism. The ORs were observed in 4 patients with IDH1-wildtype and 2 patients with IDH1-mutant tumors, including 5 complete responses (CRs) with the investigational therapy alone, and 1 CR in combination with bevacizumab. The median duration of response (mDoR) was 35.1+ months. As of AUG2017, all responders were CR and remain alive. In a 23-patient subgroup who received high doses of Toca 511 and met Ph3 trial criteria, mOS was 14.4 months, 3-year survival rate was 26.1%, and mDoR was 35.7+ months with a durable response rate of 21.7%. Data suggest a positive association of durable response with OS.
The increasing tropospheric ozone concentration [O3] strongly affects plant growth. However, the response of belowground processes in rice (Oryza sativa L.) systems to higher O3 is not well understood. The grain production, belowground biomass partitioning, root morphology and activity of rice (cv. Shanyou 63) were investigated in a free-air O3 enrichment platform at four key growth stages. Elevated O3 (EO3, 50% above the ambient O3) significantly decreased the grain yield and total biomass at the grain milky mature stage, root biomass at the tillering stage and root to shoot ratios (RRS) at the flowering and grain filling stages. The effects of EO3 on root morphology and activity varied among rice growth stage. EO3 significantly decreased root length, density, area, diameter and volume at the flowering stage, but EO3 significantly decreased various root morphological indices at the tillering, grain filling and milky mature stages. EO3 significantly increased the specific root respiration rate (root activity) and root respiration rate (autotrophic respiration) at grain filling and milky mature stages. Higher root autotrophic respiration and lower RRS in response to EO3 would reduce allocation of assimilated carbon to root growth, adversely affecting rice productivity. Our findings are critical for understanding the O3-induced impairment of belowground processes and carbon cycling in rice cropping systems and breeding of O3-tolerant cultivars under higher [O3] scenarios.
Introduction: Survival from cardiac arrest has been linked to the quality of resuscitation care. Unfortunately, healthcare providers frequently underperform in these critical scenarios, with a well-documented deterioration in skills weeks to months following advanced life support courses. Improving initial training and preventing decay in knowledge and skills are a priority in resuscitation education. The spacing effect has repeatedly been shown to have an impact on learning and retention. Despite its potential advantages, the spacing effect has seldom been applied to organized education training or complex motor skill learning where it has the potential to make a significant impact. The purpose of this study was to determine if a resuscitation course taught in a spaced format compared to the usual massed instruction results in improved retention of procedural skills. Methods: EMS providers (Paramedics and Emergency Medical Technicians (EMT)) were block randomized to receive a Pediatric Advanced Life Support (PALS) course in either a spaced format (four 210-minute weekly sessions) or a massed format (two sequential 7-hour days). Blinded observers used expert-developed 4-point global rating scales to assess video recordings of each learner performing various resuscitation skills before, after and 3-months following course completion. Primary outcomes were performance on infant bag-valve-mask ventilation (BVMV), intraosseous (IO) insertion, infant intubation, infant and adult chest compressions. Results: Forty-eight of 50 participants completed the study protocol (26 spaced and 22 massed). There was no significant difference between the two groups on testing before and immediately after the course. 3-months following course completion participants in the spaced cohort scored higher overall for BVMV (2.2 ± 0.13 versus 1.8 ± 0.14, p=0.012) without statistically significant difference in scores for IO insertion (3.0 ± 0.13 versus 2.7± 0.13, p= 0.052), intubation (2.7± 0.13 versus 2.5 ± 0.14, p=0.249), infant compressions (2.5± 0.28 versus 2.5± 0.31, p=0.831) and adult compressions (2.3± 0.24 versus 2.2± 0.26, p=0.728) Conclusion: Procedural skills taught in a spaced format result in at least as good learning as the traditional massed format; more complex skills taught in a spaced format may result in better long term retention when compared to traditional massed training as there was a clear difference in BVMV and trend toward a difference in IO insertion.
We present a generalisation of the Kármán–Howarth–Monin (K–H–M) equation to include variable-density (VD) effects. The derived equation (i) reduces to the original K–H–M equation when density is a constant and (ii) leads to a VD analogue of the
-law with the same value of constant (
) appearing as the prefactor of the dissipation rate. The equation is employed to understand negative turbulent kinetic energy production in a
turbulent round jet with an initial density ratio of 4.2. From a Reynolds-averaged Navier–Stokes (RANS) perspective, negative production means that the mean flow is strengthened at the expense of the energy of turbulent fluctuations. We show that the associated energy transfer is accomplished by the deformation of smaller turbulent eddies into large ones in the development region of the jet and is captured by the linear scale-by-scale energy transfer term in the VD K–H–M equation. The nonlinear transfer term of the VD K–H–M equation depicts a conventional forward cascade for all eddies having a size less than the Eulerian integral length scale, regardless of their orientation. The net effect is a retarded energy cascade in the non-Boussinesq jet that has not been accounted for by existing turbulence theories. Implications of this observation for turbulence modelling are discussed.
Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.
To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.
Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.
ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.
The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.
For treatment of patients diagnosed with schizophrenia, comparative
long-term effectiveness of antipsychotic drugs to reduce relapses when
minimising adverse effects is of clinical interest, hence prompting this
To evaluate the comparative long-term effectiveness of antipsychotic
We systematically searched electronic databases for reports of randomised
controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing
relapse risks in schizophrenia. We conducted network meta-analysis of 18
antipsychotics and placebo.
Studies of 10 177 patients in 56 reports were included; treatment
duration averaged 48 weeks (range 4–156). Olanzapine was significantly
more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI
0.14–0.88) or haloperidol (OR=0.50, 95% CI 0.30–0.82); and fluphenazine
decanoate was more effective than chlorpromazine (OR=0.31, 95% CI
0.11–0.88) in relapse reduction. Fluphenazine decanoate, haloperidol,
haloperidol decanoate and trifluoperazine produced more extrapyramidal
adverse effects than olanzapine or quetiapine; and olanzapine was
associated with more weight gain than other agents.
Except for apparent superiority of olanzapine and fluphenazine decanoate
over chlorpromazine, most agents showed intermediate efficacy for relapse
prevention and differences among them were minor. Typical antipsychotics
yielded adverse neurological effects, and olanzapine was associated with
weight gain. The findings may contribute to evidence-based treatment
selection for patients with chronic psychotic disorders.
The in vivo effects of administering free and microencapsulated Lactobacillus plantarum LIP-1 cells (2·0×109 colony-forming units/d) were evaluated in high-fat-diet-induced hyperlipidaemic rats. Results from real-time quantitative PCR targeting to LIP-1 cells showed a higher colon colonisation count of LIP-1 in the rats receiving microencapsulated cells compared with free cells (P<0·05). Moreover, the microencapsulated LIP-1 treatment resulted in a more obvious lipid-lowering effect (P<0·05). Meanwhile, their faecal samples had significantly less lipopolysaccharide-producing bacteria (especially Bilophila, Sutterella and Oscillibacter) and mucosa-damaging bacteria (Bilophila and Akkermansia muciniphila), whereas significantly more SCFA-producing bacteria (P<0·05) (namely Lactobacillus, Alloprevotella, Coprococcus, Eubacterium and Ruminococcus) and bacteria that potentially possessed bile salt hydrolase activity (Bacteroides, Clostridium, Eubacterium and Lactobacillus), and other beneficial bacteria (Alistipes and Turicibacter). Further, Spearman’s correlation analysis showed significant correlations between some of the modulated gut bacteria and the serum lipid levels. These results together confirm that microcapsulation enhanced the colon colonisation of LIP-1 cells, which subsequently exhibited more pronounced effects in improving the gut microbiota composition of hyperlipidaemic rats and lipid reduction.
Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3–4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4–29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.
The musk deer (Moschus berezovskii) is an economically important species from which musk is extracted and used in perfumes and medicines. Cestodes (parasitic flatworms) of the genus Moniezia are important parasites that infect this endangered species and can cause high mortality in young deer. In 1982, Moniezia (S.) sichuanensis sp. nov. was described from a specimen obtained from wild musk deer. The new species was distinct from the other described species of Moniezia by the sawtooth-shaped interproglottidal glands, the thick vagina and the absence of a cirrus spine. In the present study, 12 cestodes collected from musk deer were examined morphologically and confirmed to be M. sichuanensis. Molecular characterization was performed by amplifying and comparing the internal transcribed spacer 1 (ITS1) and 5.8S rRNA gene (ITS1–5.8S) of ribosomal DNA with available sequences from other Moniezia species. The amplified sequences ranged from 761 to 764 bp and similarity ranged from 98.7–100%, compared to 67.8–92.4% with other Moniezia spp. Construction of a phylogenetic tree using the neighbour-joining method indicated that all 12 ITS1–5.8S sequences formed a single clade, confirming M. sichuanensis as a separate species. This study provides novel molecular insight into M. sichuanensis that could prove useful for future diagnosis and control of monieziasis in musk deer.
Agriculture threatens biodiversity across the tropics, particularly in semi-natural grassland landscapes, where human populations are high, habitat is easily converted and agriculture is prone to intensification. Over the last 20 years intensive, commercial dry season rice cultivation has emerged as the dominant threat to the Bengal florican Houbaropsis bengalensis, a globally threatened bustard that breeds in the seasonally inundated grasslands of central Cambodia. Although floricans have been extensively monitored for 10 years, no socioeconomic research has been undertaken to examine how local livelihood activities interact with the florican. We conducted household questionnaires and focus groups in 21 villages in the Northern Tonle Sap Conservation Landscape to gather information on household demographics, rice farming and bird hunting in protected and unprotected areas of florican breeding habitat. We identified a significant increase in dry season rice adoption by local communities since 2005. Dry season rice cultivation was strongly associated with agrochemical use and rice fields directly overlapped with florican breeding habitat, reducing habitat availability throughout the breeding season. We identified a low but significant level of bird hunting in grassland households (8%) and revealed a demand for wild bird meat amongst local communities. Our findings suggest an urgent need for conservation interventions in unprotected farmland and emphasize the role of enforcement and community engagement in improving protection within protected areas. We highlight the potential of private sector initiatives such as the Sustainable Rice Platform in reconciling conservation and development for impoverished rural communities.
Introduction/Innovation Concept: Estimates suggest that up to eighty-seven percent of human trafficking victims have come into contact with a healthcare provider during their exploitation and yet less than ten percent of emergency medicine (EM) physicians feel confident in identifying a victim. When provided with the relevant tools, medical personnel can aid in the recognition of victims and take the necessary steps in providing appropriate care when they present to the emergency department. Identifying this need for increased awareness in the urgent care setting, a module on human trafficking was implemented into the undergraduate medical education and departmental grand rounds. Methods: After identifying gaps in current medical education regarding screening for victims of human trafficking, a literature review was completed on the topic in medical education and utilized in constructing a list of objectives. These were then reviewed by community organizations that aid victims of trafficking and the Canadian Alliance of Medical Students Against Human Trafficking. Undergraduate medical students completed surveys prior to and following the learning module, in order to evaluate improvement in acquired knowledge. Curriculum, Tool, or Material: A one-hour lecture from ACT Alberta was given to undergraduate medical students as well as to residents and staff in departmental grand rounds. The session met the following objectives: defining human trafficking, recognition of victims, and identification of next steps in providing care. Additionally, an online module from Fraser Health was made available as an additional resource with case studies specific to emergency departments. The surveys consisted of 13 questions evaluating students’ knowledge on human trafficking and its prevalence in emergency medicine. The questions were a combination of a Likert scale, multiple choice, and short answer. There was a large amount of positive feedback from the students and comparison of the surveys showed that their knowledge in identifying victims had significantly improved. Conclusion: Medical students, residents, and staff may come into contact with victims of trafficking in the emergency department and yet less than three percent of emergency physicians have had training on how to recognize a victim. Implementing human trafficking awareness will impact EM medical education by providing victims a greater chance of being recognized and offered help when they present to the emergency room.