Geometry of the ideal free distribution: individual behavioural variation and annual reproductive success in aggregations of a social ungulate.

Variation in social environment can mitigate risks and rewards associated with occupying a particular patch. We aim to integrate Ideal Free Distribution (IFD) and Geometry of the Selfish Herd (GSH) to address an apparent conflict in their predictions of equal mean fitness between patches (IFD) and declining fitness benefits within a patch (GSH). We tested these hypotheses in a socio-spatial context using individual caribou that were aggregated or disaggregated during calving and varied in their annual reproductive success (ARS). We then tested individual consistency of these spatial tactics. We reveal that two socio-spatial tactics accorded similar mean ARS (IFD); however, ARS for aggregated individuals declined near the periphery (GSH). Individuals near the aggregation periphery exhibited flexibility, whereas others were consistent. The integration of classical theories through a contemporary lens of consistent individual differences provides evidence for an integrated GSH and IFD strategy that may represent an evolutionary stable state.

Spatiotemporal heterogeneity in prey abundance and vulnerability shapes the foraging tactics of an omnivore.

Prey abundance and prey vulnerability vary across space and time, but we know little about how they mediate predator-prey interactions and predator foraging tactics. To evaluate the interplay between prey abundance, prey vulnerability and predator space use, we examined patterns of black bear (Ursus americanus) predation of caribou (Rangifer tarandus) neonates in Newfoundland, Canada using data from 317 collared individuals (9 bears, 34 adult female caribou, 274 caribou calves). During the caribou calving season, we predicted that landscape features would influence calf vulnerability to bear predation, and that bears would actively hunt calves by selecting areas associated with increased calf vulnerability. Further, we hypothesized that bears would dynamically adjust their foraging tactics in response to spatiotemporal changes in calf abundance and vulnerability (collectively, calf availability). Accordingly, we expected bears to actively hunt calves when they were most abundant and vulnerable, but switch to foraging on other resources as calf availability declined. As predicted, landscape heterogeneity influenced risk of mortality, and bears displayed the strongest selection for areas where they were most likely to kill calves, which suggested they were actively hunting caribou. Initially, the per-capita rate at which bears killed calves followed a type-I functional response, but as the calving season progressed and calf vulnerability declined, kill rates dissociated from calf abundance. In support of our hypothesis, bears adjusted their foraging tactics when they were less efficient at catching calves, highlighting the influence that predation phenology may have on predator space use. Contrary to our expectations, however, bears appeared to continue to hunt caribou as calf availability declined, but switched from a tactic of selecting areas of increased calf vulnerability to a tactic that maximized encounter rates with calves. Our results reveal that generalist predators can dynamically adjust their foraging tactics over short time-scales in response to changing prey abundance and vulnerability. Further, they demonstrate the utility of integrating temporal dynamics of prey availability into investigations of predator-prey interactions, and move towards a mechanistic understanding of the dynamic foraging tactics of a large omnivore.

Hyperglycemic Hyperosmolar State During Induction Chemotherapy for Acute Lymphoblastic Leukemia.

We present the case of a 16-year-old boy who presented with fatigue, polyuria, and polydipsia while on chemotherapy for his relapsed acute lymphoblastic leukemia (ALL). Blood gas examination confirmed the diagnosis of hyperosmolar hyperglycemic state. The etiology for his hyperglycemia was most likely a result of oral glucocorticoid therapy combined with asparaginase therapy-both are a cornerstone of induction chemotherapy for ALL. The patient was aggressively rehydrated with saline, and medications were administered to correct his hyperkalemia. He was then slowly brought to euglycemia with a continuous infusion of insulin. Although hyperosmolar hyperglycemic state is rare during the treatment of ALL, frontline providers should be aware of this diagnosis because of the significant risk of hypovolemic shock and death if correction of hyperglycemia occurs prior to complete fluid resuscitation.

Phase-dependent climate-predator interactions explain three decades of variation in neonatal caribou survival.

Climate can have direct and indirect effects on population dynamics via changes in resource competition or predation risk, but this influence may be modulated by density- or phase-dependent processes. We hypothesized that for ungulates, climatic conditions close to parturition have a greater influence on the predation risk of neonates during population declines, when females are already under nutritional stress triggered by food limitation. We examined the presence of phase-dependent climate-predator (PDCP) interactions on neonatal ungulate survival by comparing spatial and temporal fluctuations in climatic conditions, cause-specific mortality and per capita resource limitation. We determined cause-specific fates of 1384 caribou (Rangifer tarandus) from 10 herds in Newfoundland, spanning more than 30 years during periods of numerical increase and decline, while exposed to predation from black bears (Ursus americanus) and coyotes (Canis latrans). We conducted Cox proportional hazards analysis for competing risks, fit as a function of weather metrics, to assess pre- and post-partum climatic influences on survival on herds in population increase and decline phases. We used cumulative incidence functions to compare temporal changes in risk from predators. Our results support our main hypothesis; when caribou populations increased, weather conditions preceding calving were the main determinants of cause-specific mortality, but when populations declined, weather conditions during calving also influenced predator-driven mortality. Cause-specific analysis showed that weather conditions can differentially affect predation risk between black bears and coyotes with specific variables increasing the risk from one species and decreasing the risk from the other. For caribou, nutritional stress appears to increase predation risk on neonates, an interaction which is exacerbated by susceptibility to climatic events. These findings support the PDCP interactions framework, where maternal body condition influences susceptibility to climate-related events and, subsequently, risk from predation.

In vivo enhancer analysis of human conserved non-coding sequences.

Identifying the sequences that direct the spatial and temporal expression of genes and defining their function in vivo remains a significant challenge in the annotation of vertebrate genomes. One major obstacle is the lack of experimentally validated training sets. In this study, we made use of extreme evolutionary sequence conservation as a filter to identify putative gene regulatory elements, and characterized the in vivo enhancer activity of a large group of non-coding elements in the human genome that are conserved in human-pufferfish, Takifugu (Fugu) rubripes, or ultraconserved in human-mouse-rat. We tested 167 of these extremely conserved sequences in a transgenic mouse enhancer assay. Here we report that 45% of these sequences functioned reproducibly as tissue-specific enhancers of gene expression at embryonic day 11.5. While directing expression in a broad range of anatomical structures in the embryo, the majority of the 75 enhancers directed expression to various regions of the developing nervous system. We identified sequence signatures enriched in a subset of these elements that targeted forebrain expression, and used these features to rank all approximately 3,100 non-coding elements in the human genome that are conserved between human and Fugu. The testing of the top predictions in transgenic mice resulted in a threefold enrichment for sequences with forebrain enhancer activity. These data dramatically expand the catalogue of human gene enhancers that have been characterized in vivo, and illustrate the utility of such training sets for a variety of biological applications, including decoding the regulatory vocabulary of the human genome.

My Deep Sea, My Backyard: a pilot study to build capacity for global deep-ocean exploration and research.

The deep ocean is the largest ecosystem on the planet, constituting greater than 90% of all habitable space. Over three-quarters of countries globally have deep ocean within their Exclusive Economic Zones. While maintaining deep-ocean function is key to ensuring planetary health, deficiencies in knowledge and governance, as well as inequitable global capacity, challenge our ability to safeguard the resilience of this vast realm, leaving the fate of the deep ocean in the hands of a few. Historically, deep-ocean scientific exploration and research have been the purview of a limited number of nations, resulting in most of humankind not knowing the deep ocean within their national jurisdiction or beyond. In this article, we highlight the inequities and need for increased deep-ocean knowledge generation, and discuss experiences in piloting an innovative project 'My Deep Sea, My Backyard' toward this goal. Recognizing that many deep-ocean endeavours take place in countries without deep-ocean access, this project aimed to reduce dependency on external expertise and promote local efforts in two small island developing states, Trinidad and Tobago and Kiribati, to explore their deep-sea backyards using comparatively low-cost technology while building lasting in-country capacity. We share lessons learned so future efforts can bring us closer to achieving this goal. This article is part of the theme issue 'Nurturing resilient marine ecosystems'.

Natural antibodies against nerve growth factor inhibit in vitro prostate cancer cell metastasis.

Prostate cancer is a major cause of death in older men, and bone metastasis is the primary cause of morbidity and mortality in prostate cancer. Prostate is an abundant source of nerve growth factor (NGF) that is secreted by malignant epithelial cells and utilized as an important autocrine factor for growth and metastasis. We previously showed that intravenous gammaglobulin (IVIg) contains natural antibodies against NGF, which inhibit growth and differentiation of the NGF-dependent cell line PC-12. In the present study, we examined the effects of these natural antibodies on in vitro migration or metastasis of two prostate cancer cell lines namely DU-145 and PC-3. Cancer cell migration was assessed using these cell lines in the upper chambers of Matrigel invasion chambers. The effects of IVIg and affinity-purified anti-NGF antibodies on cell migration through membrane into the lower chamber were assessed in dose/response experiments by a colorimetric method. Affinity-purified natural IgG anti-NGF antibody inhibited DU-145 migration by 38% (p = 0.01) and PC-3 migration by 25% (p = 0.02); whereas, a monoclonal anti-NGF antibody inhibited DU-145 migration by 40% (p = 0.01) and PC-3 migration by 37% (p = 0.02), at the same concentration. When IVIg was depleted of NGF-specific IgG by affinity chromatography, there was no significant inhibition of migration of the DU-145 and PC-3 cells at a concentration of 1 mg/well. Removal of the NGF-specific antibody from the IVIg was also demonstrated by a lack of effect on PC-12 cell differentiation. Therefore, IVIg is able to inhibit the migration of prostate cancer cell lines, through Matrigel chambers in vitro, only when the natural NGF-specific antibodies actively are present in IVIg.

A Successful Organized Effort to Improve Operating Room First-Case Starts in a Tertiary Academic Medical Center.

BACKGROUND: Operating room (OR) inefficiency drives up cost, decreases revenue, and leads to surgeon, staff, and patient dissatisfaction. Given a low mean first-case start rate in our tertiary academic medical center, we developed a process to improve first-case start rates in an effort to increase OR efficiency. METHODS: A working group of the OR Executive Committee was constituted to develop and implement a multistep operational plan. This plan was predicated on a sensible staggered start framework, coordination of stakeholder responsibilities, a visual preoperative Stop/Go checklist tool, real-time measurement, and feedback. RESULTS: Within 11 days of implementation, 95% of first-start OR cases were tracked to start on time. Throughout the observation period (May 2015-July 2016), the goal of a daily mean 80% on-time start rate was either met or exceeded. CONCLUSIONS: Implementation of an organized collaborative effort led to dramatic improvements in first OR case on-time rates. Such improvement in OR utilization may lead to an increase in staff and patient satisfaction and cost reduction.

Divergent estimates of herd-wide caribou calf survival: Ecological factors and methodological biases.

Population monitoring is a critical part of effective wildlife management, but methods are prone to biases that can hinder our ability to accurately track changes in populations through time. Calf survival plays an important role in ungulate population dynamics and can be monitored using telemetry and herd composition surveys. These methods, however, are susceptible to unrepresentative sampling and violations of the assumption of equal detectability, respectively. Here, we capitalized on 55 herd-wide estimates of woodland caribou (Rangifer tarandus caribou) calf survival in Newfoundland, Canada, using telemetry (n = 1,175 calves) and 249 herd-wide estimates of calf:cow ratios (C:C) using herd composition surveys to investigate these potential biases. These data included 17 herd-wide estimates replicated from both methods concurrently (n = 448 calves and n = 17 surveys) which we used to understand which processes and sampling biases contributed to disagreement between estimates of herd-wide calf survival. We used Cox proportional hazards models to determine whether estimates of calf mortality risk were biased by the date a calf was collared. We also used linear mixed-effects models to determine whether estimates of C:C ratios were biased by survey date and herd size. We found that calves collared later in the calving season had a higher mortality risk and that C:C tended to be higher for surveys conducted later in the autumn. When we used these relationships to modify estimates of herd-wide calf survival derived from telemetry and herd composition surveys concurrently, we found that formerly disparate estimates of woodland caribou calf survival now overlapped (within a 95% confidence interval) in a majority of cases. Our case study highlights the potential of under-appreciated biases to impact our understanding of population dynamics and suggests ways that managers can limit the influence of these biases in the two widely applied methods for estimating herd-wide survival.

SimSurvey: An R package for comparing the design and analysis of surveys by simulating spatially-correlated populations.

Populations often show complex spatial and temporal dynamics, creating challenges in designing and implementing effective surveys. Inappropriate sampling designs can potentially lead to both under-sampling (reducing precision) and over-sampling (through the extensive and potentially expensive sampling of correlated metrics). These issues can be difficult to identify and avoid in sample surveys of fish populations as they tend to be costly and comprised of multiple levels of sampling. Population estimates are therefore affected by each level of sampling as well as the pathway taken to analyze such data. Though simulations are a useful tool for exploring the efficacy of specific sampling strategies and statistical methods, there are a limited number of tools that facilitate the simulation testing of a range of sampling and analytical pathways for multi-stage survey data. Here we introduce the R package SimSurvey, which has been designed to simplify the process of simulating surveys of age-structured and spatially-distributed populations. The package allows the user to simulate age-structured populations that vary in space and time and explore the efficacy of a range of built-in or user-defined sampling protocols to reproduce the population parameters of the known population. SimSurvey also includes a function for estimating the stratified mean and variance of the population from the simulated survey data. We demonstrate the use of this package using a case study and show that it can reveal unexpected sources of bias and be used to explore design-based solutions to such problems. In summary, SimSurvey can serve as a convenient, accessible and flexible platform for simulating a wide range of sampling strategies for fish stocks and other populations that show complex structuring. Various statistical approaches can then be applied to the results to test the efficacy of different analytical approaches.

Implementing a novel movement-based approach to inferring parturition and neonate caribou calf survival.

In ungulates, parturition is correlated with a reduction in movement rate. With advances in movement-based technologies comes an opportunity to develop new techniques to assess reproduction in wild ungulates that are less invasive and reduce biases. DeMars et al. (2013, Ecology and Evolution 3:4149-4160) proposed two promising new methods (individual- and population-based; the DeMars model) that use GPS inter-fix step length of adult female caribou (Rangifer tarandus caribou) to infer parturition and neonate survival. Our objective was to apply the DeMars model to caribou populations that may violate model assumptions for retrospective analysis of parturition and calf survival. We extended the use of the DeMars model after assigning parturition and calf mortality status by examining herd-wide distributions of parturition date, calf mortality date, and survival. We used the DeMars model to estimate parturition and calf mortality events and compared them with the known parturition and calf mortality events from collared adult females (n = 19). We also used the DeMars model to estimate parturition and calf mortality events for collared female caribou with unknown parturition and calf mortality events (n = 43) and instead derived herd-wide estimates of calf survival as well as distributions of parturition and calf mortality dates and compared them to herd-wide estimates generated from calves fitted with VHF collars (n = 134). For our data, the individual-based method was effective at predicting calf mortality, but was not effective at predicting parturition. The population-based method was more effective at predicting parturition but was not effective at predicting calf mortality. At the herd-level, the predicted distributions of parturition date from both methods differed from each other and from the distribution derived from the parturition dates of VHF-collared calves (log-ranked test: χ2 = 40.5, df = 2, p < 0.01). The predicted distributions of calf mortality dates from both methods were similar to the observed distribution derived from VHF-collared calves. Both methods underestimated herd-wide calf survival based on VHF-collared calves, however, a combination of the individual- and population-based methods produced herd-wide survival estimates similar to estimates generated from collared calves. The limitations we experienced when applying the DeMars model could result from the shortcomings in our data violating model assumptions. However despite the differences in our caribou systems, with proper validation techniques the framework in the DeMars model is sufficient to make inferences on parturition and calf mortality.

Controlling postoperative use of i.v. acetaminophen at an academic medical center.

PURPOSE: Results of an interprofessional formulary initiative to decrease postoperative prescribing of i.v. acetaminophen are reported. SUMMARY: After a medical center added i.v. acetaminophen to its formulary, increased prescribing of the i.v. formulation and a 3-fold price increase resulted in monthly spending of more than $40,000, prompting an organizationwide effort to curtail that cost while maintaining effective pain management. The surgery, anesthesia, and pharmacy departments applied the Institute for Healthcare Improvement's Model for Improvement to implement (1) pharmacist-led enforcement of prescribing restrictions, (2) retrospective evaluation of i.v. acetaminophen's impact on rates of opioid-related adverse effects, (3) restriction of prescribing of the drug to 1 postoperative dose on select patient care services, and (4) guideline-driven pain management according to an enhanced recovery after surgery (ERAS) protocol. Monitored metrics included the monthly i.v. acetaminophen prescribing rate, the proportion of i.v. acetaminophen orders requiring pharmacist intervention to enforce prescribing restrictions, and prescribing rates for select adjunctive analgesics. Within a year of project implementation, the mean monthly i.v. acetaminophen prescribing rate decreased by 83% from baseline to about 6 doses per 100 patient-days, with a decline in the monthly drug cost to about $4,000. Documented pharmacist interventions increased 2.7-fold, and use of oral acetaminophen, ketorolac, and gabapentin in ERAS areas increased by 18% overall. CONCLUSION: An interprofessional initiative at a large medical center reduced postoperative use of i.v. acetaminophen by more than 80% and yielded over $400,000 in annual cost savings.

Time series analysis of variables associated with daily mean emergency department length of stay.

STUDY OBJECTIVE: We measure the effect of various input, throughput, and output factors on daily emergency department (ED) mean length of stay per patient (daily mean length of stay). METHODS: The study was a retrospective review of 93,274 ED visits between April 15, 2002, and December 31, 2003. The association between the daily mean length of stay and the independent variables was assessed with autoregressive moving average time series analysis (ARIMA). The following independent variables were measured per 24-hour period: number of elective surgical admissions, ED volume, number of ED admissions, number of ED ICU admissions, number of ED clinical attending hours, hospital medical-surgical occupancy (hospital occupancy), and day of the week. RESULTS: Three factors were independently associated with daily mean length of stay in time series analysis: number of elective surgical admissions, number of ED admissions, and hospital occupancy. The daily mean length of stay increased by 0.21 minutes for every additional elective surgical admission, 2.2 minutes for every additional admission, and 4.1 minutes for every 5% increase in hospital occupancy. Elective surgical admissions were associated with a maximum of 35 hours of additional ED dwell time. The model accounted for 31.5% of the variability in daily mean length of stay. The final model parameters for the ARIMA analysis were autoregressive term (1) moving average (1). CONCLUSION: Hospital occupancy and the number of ED admissions are associated with daily mean length of stay. Every additional elective surgical admission prolonged the daily mean length of stay by 0.21 minutes per ED patient. Autocorrelation exists between the daily mean length of stay of the current day and the previous day.

Fluctuation of spuriously elevated troponin I: a case report.

Serum troponin is a useful laboratory study for the diagnosis of acute myocardial infarction. However, elevations can also be seen in a variety of other diseases processes. Falsely positive troponin values caused by interference with current troponin assays have been reported. We report a unique case that demonstrates the fluctuation of falsely elevated troponin correlating with hemoglobin, serving as a marker of heterophile antibody levels. A 74-year-old gentleman presented to our Emergency Department with a several-day history of increasing shortness of breath associated with a new-onset chest pain and a troponin I level of 77.28 ng/mL. Throughout his stay, fluctuations in measured troponin levels correlated strongly with fluctuations in hemoglobin levels. Several investigations confirmed false elevated troponin levels secondary to heterophile antibody interference. We conclude that hemoglobin trending in our patient represented a surrogate measure of his heterophile antibody titers with time and that fluctuations in these levels correlated with respective fluctuations in the falsely elevated troponin levels.