Search

Why you should read this article: • To enhance your knowledge of the concept of just culture when measuring and assuring safety • To identify how to apply a just culture approach to your organisation • To count towards revalidation as part of your 35 hours of CPD, or you may wish to write a reflective account (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers) This article presents a simple conceptual road map for implementing a just culture in healthcare settings. The concept of just culture was developed as one of five fundamental elements of a safety culture by psychology professor James Reason in 1997. A just culture requires an unbiased method of judging human error and is designed to develop organisational trust so that adverse medical events (errors) are reported and corrected before they combine with other errors to cause injury or death. To implement a just culture properly so as to increase organisational safety, practitioners must understand its role in enabling the error reporting needed to develop a safety culture. This article reviews these foundational concepts and explores the human causes of errors that a just culture addresses, the psychological importance of a just culture in enabling error reporting and how to implement a just culture in organisations. [ABSTRACT FROM AUTHOR]

Reverse Cumulative Distribution Curves (RCDCs) have proven to be a useful tool in summarizing immune response profiles in vaccine studies since their introduction by Reed, Meade, and Steinhoff (RMS) (1995). They are able to display virtually all of the treatment data and characterize summary statistics such as means or even their confidence intervals (CIs) that might be obscure. RMS mentioned their similarity to survival curves often used to summarize time-to-event data which are usually not normally distributed. The RCDCs, while intuitively pleasing and useful, contain important properties which allow for more powerful statistical applications. In this paper, we will suggest several widely used rank-based tests to compare the curves in the context of vaccine studies. These rank-based tests allow for comparisons between treatments, for stratified analyses, weighted analyses, and other modifications that make them the alternative of parametric analyses without the normality assumptions. Clinical trial identification: NCT01712984 and NCT01230957. [ABSTRACT FROM AUTHOR]

As part of a long-term research program, Cook Inlet beluga (Delphinapterus leucas) presence was acoustically monitored with two types of acoustic sensors utilized in tandem in moorings deployed year-round: an ecological acoustic recorder (EAR) and a cetacean and porpoise detector (C-POD). The EAR was used primarily to record the calls, whistles, and buzzes produced by belugas and killer whales (Orcinus orca). The C-POD was used to log and classify echolocation clicks from belugas, killer whales, and porpoises. This paper describes mooring packages that maximized the chances of successful long-term data collection in the particularly challenging Cook Inlet environment, and presents an analytical comparison of odontocete detections obtained by the collocated EAR and C-POD instruments from two mooring locations in the upper inlet. Results from this study illustrate a significant improvement in detecting beluga and killer whale presence when the different acoustic signals detected by EARs and C-PODs are considered together. Further, results from concurrent porpoise detections indicating prey competition and feeding interference with beluga, and porpoise displacement due to ice formation are described. [ABSTRACT FROM AUTHOR]

We estimated sex- and age-specific apparent survival of harbor seals (Phoca vitulina richardii) born at Tugidak Island, Alaska, from 2000 to 2007 using mark-recapture models and photographs of ventral pelage markings to identify individuals. Estimates of annual apparent survival (1 - (mortality + emigration)) of females were from 0.05 to 0.10 higher than those of males and were 0.820 for weaning (~1 month) to 1 year, 0.865 for 1-3 years, and 0.929 at 3-7 years. Annual survival of males was 0.717, 0.782, and 0.879 for the same ages. Highest mortality occurred preweaning, with cumulative mortality to 4 weeks of age of 0.259, indicating this is the most vulnerable period for Tugidak harbor seals. Estimates of survival, not biased by misidentification, required that an individual had at least 2 good-quality, matching photographs in the photograph library. The number of photographs available for matching improved resighting probabilities from 0.43 for seals with 2 photographs to 0.69 for seals with 8 photographs, but this heterogeneity did not affect survival estimates. Survival estimates based on photograph-identification data were nearly identical to those based on resightings of flipper-tagged seals using mark-recapture models with a preliminary double-tag-loss estimate of 2.5% per year. Photograph identification of natural pelage markings provides a viable method for estimating vital rates of harbor seals even at large haul-outs (> 1,000 animals) and may be useful for populations of conservation concern that require low disturbance of animals or where capturing sufficient numbers of seals for artificial marking is not feasible. [ABSTRACT FROM AUTHOR]

Examines eight key practices intrinsic to effective, systematic and repeatable patch management and proposes performance measures for evaluating it. Defense against Internet-based attacks; Key practices derived from industry pilot projects for improving patch management.

From the notion that our ideas of space are defined by their margins, this paper explores some of the social, symbolic and cultural means commonly used in particular contexts to determine both the definition of these perimeters and the various competing social structures implicit in their maintenance and function, or otherwise. In addition to first-hand accounts and ethno-graphies, the work draws on sources ranging from literature and journalism to architecture and social anthropology, all presented in terms of the author's long established, and much published, approach to SCOS events and the broader discontinuities of life in general. So, for example, the title of his proposed piece contains an oblique yet knowing reference to theories of relativity in that no matter how light the text may be, or lacking in gravity, it cannot easily be described within the space of ten and a half minutes. [ABSTRACT FROM AUTHOR]

Estimates seasonal rates of ruffed grouse mortality due to predation and hunting. Heavily hunted public lands vs. lightly hunted private lands; Hunting mortality as additive or compensatory; Details of study.

Focuses on the state of reform happening in the education systems in the United States. Standards of education; Uniformity; Concept of Goals 2000 in America's education policy; Issue of class size; Attitude toward teachers; Rating of students; Impact of a failed education system in the United States.

Studies the habitat selection by spotted owls during natal dispersal in western Oregon. Forest fragmentation; Probability of mortality of juvenile spotted owls; Selection of closed-canopy forests; Open sampling stands; Correlation of clearcuts and successful natal dispersal.

Examines the hypothesis indicating that an inherent risk of dispersal is an increased probability of death. Use of ruffed grouse as experimental animal; Calculation of mortality estimates the transience and colonization periods; Juvenile versus adults; Male versus female.

In recent years, the relatively high levels of organochlorine contaminants and increasing levels of brominated flame retardants found in tissues of marine mammals have raised concerns that exposure to these marine pollutants may compromise individual health. In this pilot study, levels of 11 polychlorinated biphenyls, 3 polybrominated diphenyl ethers, and the DDT metabolitep,p'-diphenyldichloroethylene were analyzed in whole blood of 7 free-ranging spotted seals (Phoca largha) from Bristol Bay, Alaska, sampled during 2000 and 2001. Blood concentrations of analytes were generally low (<1 ppb wet weight). Open-ocean foraging and feeding on a lower trophic level may contribute to the relatively lower levels of organohalogens found in this species as compared to the closely related harbor seal, Phoca vitulina, occurring in Bristol Bay. [ABSTRACT FROM AUTHOR]

• We established cocaine self-administered mice. • We observed microglial activation the brain striatum. • Cocaine differentially modulates microglial functional status in vivo. • NLRP3/IL1β may play critical roles in cocaine-mediated microglial activation. The evidence showing the involvement of microglial activation in the development of drug addiction remain scarce as microglia have not been systematically investigated in self-administered mice, a gold standard rodent model for drug addiction. Here we established the stable cocaine self-administration mice to examine microglial activation levels in various brain regions related to reward circuitry. Immunostaining for Iba1 showed a significant upregulation of intensity in the striatum but not in the medial prefrontal cortex (mPFc), hippocampus or thalamus. Further validation experiments showed that cocaine self-administered mice had significantly increased mRNA expression of ccl2 and IL1β in the striatum but not the mPFc compared to saline controls. Consistently, we found elevated protein levels of Iba1, CCL2, TLR4 and mature IL1β in the striatum, not in the mPFc of cocaine-receiving mice. In addition, cocaine-stimulated microglia had modified morphology including a reduced number of intersections, a shortened length and number of processes in the NAc. In summary, our results demonstrated that cocaine mediated microglial activation in a region-specific manner in vivo. These findings indicate that microglia could be activated in the early stage of cocaine addiction directly supporting the rationale that dysregulation on neuroimmune signaling is inherently involved in the development of drug addiction. [ABSTRACT FROM AUTHOR]

The present study explored the Immigrant Paradox (IP), generational differences in problematic alcohol use (alcohol consumption and alcohol-related consequences), among immigrants and US born groups from a number of ethnic minority backgrounds. Our approach separates group differences in problematic alcohol consumption in a counterfactual manner for immigrants and the US born to answer the following counterfactual question: "What would problematic alcohol use levels be for the US born had they been exposed to the alcohol use generation (or protective) processes of immigrants and vice versa?" Multidimensional measures of enculturation (involvement with heritage culture), acculturation (involvement with US culture), acculturative stress, and demographic covariates were used to statistically explain these differences. The sample consisted of Asian American (n = 1,153), Black American (n = 833), and Latinx (n = 1,376) college students from 30 universities. Results indicated significant generational differences in mean levels of alcohol consumption but not alcohol-related consequences. Differences in measured characteristics (endowments) marginally explained differences between immigrants and the US born. On the other hand, endowments significantly explained generational differences and represented an increase in alcohol consumption among immigrants if they had the endowments of the U.S. born. Results are discussed in light of cultural and social factors that contribute to the IP. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a method of estimating pulsatile ocular blood volume (POBV) from measurements taken during an ophthalmic exam, including axial length and using a tonometer capable of measuring intraocular pressure (IOP) and ocular pulse amplitude (OPA). Unpublished OPA data from a previous invasive study was used in the derivation, along with central corneal thickness (CCT) and axial length (AL), as well as IOP from the PASCAL dynamic contour tonometer (DCT) and intracameral (ICM) measurements of IOP for 60 cataract patients. Intracameral mean pressure was set to 15, 20, and 35 mmHg (randomized sequence) in the supine position, using a fluid-filled manometer. IOP and OPA measurements were acquired at each manometric setpoint (DCT and ICM simultaneously). In the current study, ocular rigidity (OR) was estimated using a published significant relationship of OR to the natural log of AL in which OR was invasively measured through fluid injection. Friedenwald's original pressure volume relationship was then used to derive the estimated POBV, delivered to the choroid with each heartbeat as a function of OR, systolic IOP (IOPsys), diastolic IOP (IOPdia), and OPA, according to the derived equation POBV = log (IOPsys/IOPdia) / OR. Linear regression analyses were performed comparing OPA to OR and calculated POBV at each of the three manometric setpoints. POBV was also compared to OPA/IOPdia with all data points combined. Significance threshold was p < 0.05. OR estimated from AL showed a significant positive relationship to OPA for both DCT (p < 0.011) and ICM (p < 0.006) at all three manometric pressure setpoints, with a greater slope for lower IOP. Calculated POBV also showed a significant positive relationship to OPA (p < 0.001) at all three setpoints with greater slope at lower IOP, and a significant negative relationship with IOPdia. In the combined analysis, POBV showed a significant positive relationship to OPA/ IOPdia (p < 0.001) in both ICM and DCT measurements with R2 = 0.9685, and R2 = 0.9589, respectively. POBV provides a straight-forward, clinically applicable method to estimate ocular blood supply noninvasively. Higher IOP in combination with lower OPA results in the lowest values of POBV. The simplified ratio, OPA/ IOPdia, may also provide a useful clinical tool for evaluating changes in ocular blood supply in diseases with a vascular component, such as diabetic retinopathy and normal tension glaucoma. Future studies are warranted. [ABSTRACT FROM AUTHOR]

Bowhead whales (Balaena mysticetus) face threats from diminishing sea ice and increasing anthropogenic activities in the Arctic. Passive acoustic monitoring is the most effective means for monitoring their distribution and population trends, based on the detection of their calls. Passive acoustic monitoring, however, is influenced by the sound propagation environment and ambient noise levels, which impact call detection probability. Modeling and simulations were used to estimate detection probability for bowhead whale frequency-modulated calls in the 80–180 Hz frequency band with and without sea ice cover and under various noise conditions. Sound transmission loss for bowhead calls is substantially greater during ice-covered conditions than during open-water conditions, making call detection ~ 3 times more likely in open-water. Estimates of daily acoustic detection probability were used to compensate acoustic detections for sound propagation and noise effects in two recording datasets in the northeast Chukchi Sea, on the outer shelf and continental slope, collected between 2012 and 2013. The compensated acoustic density suggests a decrease in whale presence with the retreat of sea ice at these recording sites. These results highlight the importance of accounting for effects of the environment on ambient noise and acoustic propagation when interpreting results of passive acoustic monitoring. [ABSTRACT FROM AUTHOR]

Each spring, most bowhead whales of the Bering-Chukchi-Beaufort (BCB) population migrate to the southeast Beaufort Sea and summer in Canadian waters. In August and September, they form aggregations, which are known to occur mainly in the shallow, shelf waters when oceanographic conditions promote concentration of their zooplankton prey. The movements of individual bowheads while they occupy these late summer habitats are less well known; our knowledge is based on photographic evidence and limited tagging studies conducted from 1982 to 2000. In this study, 85% (17) of the 20 satellite-tagged whales that could have spent some time in the Canadian portion of the Beaufort Sea during late summer 2006 to 2012 spent all or part of August and September there. We analyzed location data for 16 whales, using a two-state switching correlated random walk (CRW) behavioural model, and classified locations in the Canadian waters as associated with lingering behaviour (inferred foraging) or directed travel. We found that these whales spent the greatest proportion of their time lingering (59%), followed by traveling (22%), and transitioning between lingering and traveling (19%). Using only lingering locations for these tagged whales in all study years pooled, we calculated kernel densities and defined five areas within the 75% density contour as aggregation areas. Together, the five aggregation areas we defined comprised 25 341 km2, 14.1% of the total area used by these tagged whales in Canadian waters during August and September of the deployment years. Three aggregation areas were located in shallow waters of the Beaufort Sea Shelf and were used almost exclusively by immature tagged whales in our sample. Two other aggregation areas were observed, one in Darnley Bay and one in Viscount Melville Sound in the Canadian Arctic Archipelago. Each of these was used by one mature whale. Tagged whales were observed to use one or two aggregation areas in a single season, and rarely more. The proportion of lingering time spent in each aggregation area was highly variable among individuals. The largest aggregation area (10 877 km2), located over the Beaufort Shelf north of the Tuktoyaktuk Peninsula (5 - 52 m depth), was used by 13 of the 16 tagged whales, almost exclusively by the immature whales, including three of four that were tracked in two consecutive summers. The Beaufort Shelf overall (and possibly the Tuktoyaktuk Shelf, including the Outer Shelf, in particular) was especially important for immature bowhead whales, while mature whales used habitats beyond the Beaufort Shelf during late summer. Findings may be important to inform both decisions on management and mitigative actions relating to bowhead whale use of the Beaufort Shelf and studies that aim to improve our understanding of the prey base of BCB bowhead whales in the Canadian Beaufort Sea region. [ABSTRACT FROM AUTHOR]

Climate change is having profound impacts on animal populations, and shifts in geographic range are predicted in response. Shifts that result in range overlap between previously allopatric congeneric species may have consequences for biodiversity through interspecific competition, hybridization, and genetic introgression. Harbor seals ( Phoca vitulina) and spotted seals ( Phoca largha) are parapatric sibling species and areas of co-occurrence at the edges of their range, such as Bristol Bay, Alaska, offer a unique opportunity to explore ecological separation and discuss potential consequences of increased range overlap resulting from retreating sea ice. Using telemetry and genetic data from 14 harbor seals and six spotted seals, we explored the ecological and genetic separation of the two species by comparing their utilization distributions, distance from haul-out, dive behavior (e.g., depth, duration, focus), and evidence of hybridization. Firstly, we show that harbor and spotted seals, which cannot be visually distinguished definitively in all cases, haul-out together side by side in Bristol Bay from late summer to early winter. Secondly, we observed subtle rather than pronounced differences in ranging patterns and dive behavior during this period. Thirdly, most spotted seals in this study remained close to shore in contrast to what is known of the species in more northern areas, and lastly, we did not find any evidence of hybridization. The lack of distinct ecological separation in this area of sympatry suggests that interspecific competition could play an important role in the persistence of these species, particularly if range overlap will increase as a result of climate-induced range shifts and loss of spotted seal pagophilic breeding habitat. Our results also highlight the added complexities in monitoring these species in areas of suspected overlap, as they cannot easily be distinguished without genetic analysis. Predicted climate-induced environmental change will likely influence the spatial and temporal extent of overlap in these two sibling species. Ultimately, this may alter the balance between current isolating mechanisms with consequences for species integrity and fitness. [ABSTRACT FROM AUTHOR]

Satellite telemetry devices collect valuable information concerning the sites visited by animals, including the location of central places like dens, nests, rookeries, or haul-outs. Existing methods for estimating the location of central places from telemetry data require user-specified thresholds and ignore common nuances like measurement error. We present a fully model-based approach for locating central places from telemetry data that accounts for multiple sources of uncertainty and uses all of the available locational data. Our general framework consists of an observation model to account for large telemetry measurement error and animal movement, and a highly flexible mixture model specified using a Dirichlet process to identify the location of central places. We also quantify temporal patterns in central place use by incorporating ancillary behavioral data into the model; however, our framework is also suitable when no such behavioral data exist. We apply the model to a simulated data set as proof of concept. We then illustrate our framework by analyzing an Argos satellite telemetry data set on harbor seals ( Phoca vitulina) in the Gulf of Alaska, a species that exhibits fidelity to terrestrial haul-out sites. [ABSTRACT FROM AUTHOR]

Background Functional magnetic resonance imaging ( fMRI) has been used to evaluate the long-term consequences of early exposure to neurotoxic agents. fMRI shows that different patterns of brain activation occur in ethanol-exposed subjects performing a go/no-go response inhibition task. Pharmacologically, ethanol and general anesthetics have similar receptor-level activity in the brain. This study utilizes fMRI to examine brain activation patterns in children exposed to general anesthesia and surgery during early brain development. Methods After obtaining Nationwide Children's Hospital IRB approval, a surgical database was utilized to identify children aged 10-17 years with a history of at least 1 h of exposure to general anesthetics and surgery when they were between 0 and 24 months of age. Age- and gender-matched children without anesthesia exposure were recruited as a control group. All subjects were scanned while being presented with a go/no-go response inhibition task. Reaction time and accuracy data were acquired, and the blood-oxygen-level-dependent ( BOLD) fMRI signal was measured as a biomarker for regional neuronal activity. Results There were no differences in terms of performance accuracy and response time. The analysis did not reveal any significant activation differences in the primary region of interest (prefrontal cortex and caudate nucleus); however, activation differences were seen in other structures, including the cerebellum, cingulate gyrus, and paracentral lobule. Conclusions Early anesthetic exposure and surgery did not affect accuracy, response time, or activation patterns in the primary region of interest during performance of the task. Intergroup differences in activation patterns in other areas of the brain were observed, and the significance of these findings is unknown. fMRI appears to be a useful tool in evaluating the long-term effects of early exposure to general anesthesia. [ABSTRACT FROM AUTHOR]

The endangered beluga whale (Delphinapterus leucas) population in Cook Inlet, AK faces threats from a variety of anthropogenic factors, including coastal development, oil and gas exploration, vessel traffic, and military activities. To address existing gaps in understanding about the occurrence of belugas in Cook Inlet, a project was developed to use passive acoustic monitoring to document the year-round distribution of belugas, as well as killer whales (Orcinus orca), which prey on belugas. Beginning in June 2009, ten moorings were deployed throughout the Inlet and refurbished every two to eight months. Despite challenging conditions consisting of strong tidal currents carrying debris and seasonal ice cover, 83% of mooring deployments were successfully recovered. Noise from water flow, vessel traffic, and/or industrial activities was present at several sites, potentially masking some signals. However, belugas were successfully detected at multiple locations. Detections were relatively common in the upper inlet and less common or absent at middle and lower inlet locations. Killer whale signals were also recorded. Some seasonal variability in the occurrence of both belugas and killer whales was evident. [ABSTRACT FROM AUTHOR]

Like every healthcare system today, the Cleveland Clinic health system is a combination of medical hospitals, institutes, and services in which the implementation of uniform care methodologies faces significant barriers. The guiding principle of the Cleveland Clinic, 'Patients First,' focuses on the principle of patient- and family-centered care (PFCC) but deliberately lacks details due to the wide scope of care delivered by the organization. The Stanley Shalom Zielony Institute of Nursing Excellence (the Nursing Institute) at the Cleveland Clinic was charged with standardizing nursing practice across a system with 11,000 registered nurses and 800 advanced practice nurses. The challenge involved providing firm direction on delivering PFCC that was appropriate for all clinical disciplines and could be implemented quickly across existing practices and technologies. Successful implementation required full engagement in the concept of PFCC by what the Institute for Healthcare Improvement has termed the 'hearts and minds' of nurses. To achieve these ends, development of a systemwide nursing practice model was initiated. In this article the authors identify the essence of PFCC, consider barriers to PFCC, review their process of developing PFCC, and describe how the Cleveland Clinic health system has implemented a PFCC nursing practice model. In doing so the authors explore how the concept of 'Passion for Nursing' was used to stimulate nurse engagement in PFCC. [ABSTRACT FROM AUTHOR]

Background: Continuous epidural infusion (CEI) is commonly used for labour analgesia, but concerns over potential motor block, second-stage labour complications, and ineffective analgesia in late labour have prompted examining intermittent epidural bolus (IEB) as an alternative. However, evidence comparing these modalities is conflicting. The meta-analysis evaluates the analgesic efficacy of CEI vs IEB.Methods: Databases were searched for trials comparing CEI to IEB for labour analgesia. The two co-primary outcomes were risk of breakthrough pain and difference in area under the curve (AUC) for pain scores during the first 4 h post-epidural initiation. Local anaesthetic consumption, maternal outcomes (i.e. delivery mode, labour duration, and maternal satisfaction), and side-effects of epidural analgesia were also evaluated. Results were pooled using random-effects modelling. Trial sequential analysis (TSA) was used to evaluate evidence reliability.Results: Twenty-seven studies (3133 patients) were analysed. Compared with CEI, IEB decreased risk of breakthrough pain by 38% (risk ratio [95% confidence interval {CI}] of 0.62 [0.48, 0.81]; P=0.0004; I2=47%; 1164 patients) and reduced AUC of pain during the 4 h interval by 32.9% (mean difference [95% CI] of -16.7 mm h-1 [-18.9, -14.4]; P<0.0001; 1638 patients). Intermittent epidural bolus enhanced maternal satisfaction, shortened labour duration, decreased motor block, and reduced local anaesthetic consumption. The difference between the two groups was not statistically significant for epidural side-effects or mode of delivery. The TSA indicated adequate power for reliable inferences.Conclusions: Intermittent epidural bolus provides improved labour pain control during the first 4 h after epidural initiation with less breakthrough pain. Moderate- to high-quality evidence of intermittent epidural bolus superiority support its use as a safe and effective continuous epidural infusion alternative for labour analgesia. [ABSTRACT FROM AUTHOR]

Monitoring the dynamics and status of populations of harbor seals (Phoca vitulina richardii) requires efficient methods for estimating population parameters from mark--resight data. We used a test set of photographs from 182 individuals identified by flipper tags, scars, or unique pelage markings to test whether individuals could be identified accurately by their ventral pelage markings; to document efficiency and misidentification error rate associated with a computer-assisted photograph-matching system; and to test for bias in mark-recapture survival estimates resulting from misidentification errors. Pelage patterns of seals that were not of dark-intermediate or intermediate color phase were unique and stable from birth until 6-8 years, and from year to year as adults. The computer-assisted system greatly improved efficiency of photograph matching: 93.3% of good photographs and 69.9% of all photographs ranked 1st, and 95.2% of good photographs ranked in the top 0.3% of the ordered list for visual checking. Additional visual matching error averaged <3.0% for good photographs, and overall misidentification error rate was low at 1.8%, due to the availability of multiple photographs for matching. Inclusion of poor-quality photographs reduced ranking success by ~20% and increased additional visual matching error up to 20%. Bias in survival estimates was -7.0% for a misidentification rate of 8.8%, but was ≤1.1% for misidentification rates of <2.7%, achieved by restricting data to only good photos. Our study suggests that estimation of misidentification error rate, inclusion of only high-quality photographs, or use of models that account for misidentification error, are required to prevent bias in mark-recapture survival estimates when using data from natural-marking studies. [ABSTRACT FROM AUTHOR]

Abstract: The nonlinear approximations based on trigonometric generating functions are studied. It is shown that, by properly choosing generating functions, such nonlinear approximations to the derivative of the Dirac delta function on [−1,1] are the corresponding Gaussian quadratures applied to its Stieltjes integral representations by the generating functions. Moreover, the approximations are proved to be convergent and the error terms are obtained. [Copyright &y& Elsevier]

We previously showed that Month 13 50% plaque reduction neutralization test (PRNT50) neutralizing antibody (nAb) titers against dengue virus (DENV) correlated with vaccine efficacy (VE) of CYD-TDV against symptomatic, virologically-confirmed dengue (VCD) in the CYD14 and CYD15 Phase 3 trials. While PRNT is the gold standard nAb assay, it is time-consuming and costly. We developed a next-generation high-throughput microneutralization (MN) assay and assessed its suitability for immune-correlates analyses and immuno-bridging applications. We analyzed MN and PRNT50 titers measured at baseline and Month 13 in a randomly sampled immunogenicity subset, and at Month 13 in nearly all VCD cases through Month 25. For each serotype, MN and PRNT50 titers showed high correlations, at both baseline and Month 13, with MN yielding a higher frequency of baseline-seronegatives. For both assays, Month 13 titer correlated inversely with VCD risk. Like PRNT50, high Month 13 MN titers were associated with high VE, and estimated VE increased with average Month 13 MN titer. We also studied each assay as a valid surrogate endpoint based on the Prentice criteria, which supported each assay as a valid surrogate for DENV-1 but only partially valid for DENV-2, -3, and -4. In addition, we applied Super-Learner to assess how well demographic, Month 13 MN, and/or Month 13 PRNT50 titers could predict Month 13–25 VCD outcome status; prediction was best when using demographic, MN, and PRNT50 information. We conclude that Month 13 MN titer performs comparably to Month 13 PRNT50 titer as a correlate of risk, correlate of vaccine efficacy, and surrogate endpoint. The MN assay could potentially be used to assess nAb titers in immunogenicity studies, immune-correlates studies, and immuno-bridging applications. Additional research would be needed for assessing the utility of MN titer in correlates analyses of other DENV endpoints and over longer follow-up periods. [ABSTRACT FROM AUTHOR]

Anthropogenic noise has been identified as a major threat for the recovery of the endangered Cook Inlet beluga, Delphinapterus leucas, population, but little is known about its occurrence in critical habitat. We analyzed 8,756 h of acoustic recordings from different locations and months in Cook Inlet, Alaska, to describe anthropogenic noise, evaluate the potential for acoustic impact to Cook Inlet belugas, and provide management recommendations. Nine total sources of noise were identified: commercial ship, dredging, helicopter, jet aircraft (commercial or military non-fighter), fighter jet, propeller aircraft, outboard motor, pile driving, sub-bottom profiler, as well as four repetitive unidentified noise sources. Several noise metrics were compared across noise sources, months, and locations. A total of 6,263 anthropogenic acoustic events were detected and classified, for a total duration of 1,025 h representing 11.7% of the sound recordings analyzed. Anthropogenic noise was present in every day sampled. The natural background noise (i.e., ambient noise without anthropogenic contribution), in areas where currents and vegetative debris did cause minimal selfnoise, was below 120 dBrms re. 1μPa for 94% to 100% of the time; much lower than previously reported and unsupportive of the current application of the elevated behavioral harassment threshold for nonimpulsive noise of 125 dBrms. Based on spectral received levels and spatial and temporal prevalence, several anthropogenic noise sources in Cook Inlet have the potential to chronically mask beluga communication and hearing in most of the locations and periods sampled for this study. Current activities (e.g., shipping, dredging) exceed behavioral harassment levels on a daily basis in a significant portion of the critical habitat. Ship noise was identified as the top priority focus for noise mitigation management actions. A high concentration of noise sources was identified in the lower region of Knik Arm. This area is recommended for further research to evaluate the potential for beluga displacement and the basis to start considering cumulative impact effects in the permitting process. The amount of detected unidentified machinery noise or unclassifiable noises highlights the need for further research in coordination with industry, in particular in areas of oil and gas production (i.e., Trading Bay) or intense shipping related activities (i.e., facilities). Finally, unpermitted activities were also detected suggesting the need for further enforcement and outreach to increase the awareness towards this endangered population of belugas and the negative consequences of underwater noise in their protected habitat. [ABSTRACT FROM AUTHOR]

Background: The manufacture of insulin analogs requires sophisticated production procedures which can lead to differences in the structure, purity, and/or other physiochemical properties of resultant products that can affect their biologic activity. Here, we sought to compare originator and non-originator copies of insulin glargine for innate immune activity and mechanisms leading to differences in these response profiles in an in vitro model of human immunity. Methods: An endothelial/dendritic cell-based innate immune model was used to study antigen-presenting cell activation, cytokine secretion, and insulin receptor signalling pathways induced by originator and non-originator insulin glargine products. Mechanistic studies included signalling pathway blockade with specific inhibitors, analysis of the products in a Toll-like receptor reporter cell line assay, and natural insulin removal from the products by immunopurification. Findings: All insulin glargine products elicited at least a minor innate immune response comparable to natural human insulin, but some lots of a non-originator copy product induced the elevated secretion of the cytokines, IL-8 and IL-6. In studies aimed at addressing the mechanisms leading to differential cytokine production by these products, we found (1) the inflammatory response was not mediated by bacterial contaminants, (2) the innate response was driven by the native insulin receptor through the MAPK pathway, and (3) the removal of insulin glargine significantly reduced their capacity to induce innate activity. No evidence of product aggregates was detected, though the presence of some high molecular weight proteins argues for the presence of insulin glargine dimers or others contaminants in these products. Conclusion: The data presented here suggests some non-originator insulin glargine product lots drive heightened in vitro human innate activity and provides preliminary evidence that changes in the biochemical composition of non-originator insulin glargine products (dimers, impurities) might be responsible for their greater immunostimulatory potential. [ABSTRACT FROM AUTHOR]

Abstract Each fall, bowhead whales in the Bering-Chukchi-Beaufort (BCB) population migrate westward from summering grounds in the Beaufort Sea through the Chukchi Sea to the northern coast of Chukotka, Russia. Routes whales use when crossing the Chukchi Sea vary by year; in some years, whales migrate directly to the northern coast of Chukotka while in other years, whales may pause migration and linger, presumably to feed, in the central Chukchi Sea. To investigate how whale movements may be related to oceanographic variables we examined bowhead whale habitat selection within the Chukchi Sea in autumn (September--November) at two spatial scales. First, at the landscape scale (i.e. the Chukchi Sea), we compare oceanographic variables (e.g. temperature, salinity, and current velocity) at locations within used and randomly available tracks (i.e. paths of travel) to determine how oceanographic features are associated with where whales cross the Chukchi Sea in autumn. Second, at a local scale, we examine how directed travel or lingering within a whale's track is associated with oceanographic variables (e.g. temperature, salinity, and current velocity). Whale location data for 24 bowhead whales were paired with oceanographic data from a pan-arctic coupled ice-ocean model for 2006–2009. At the landscape scale, we found that whales generally followed water of Pacific origin characterized by temperatures <0ºC and salinities between 31.5 and 34.25. Bowhead whales avoided Alaskan Coastal Water and Siberian Shelf Water, the latter of which defines the western limit of their range, likely due to lower intrinsic densities of zooplankton prey. At the local scale, within their tracks, whales were more likely to interrupt directed movements and linger in areas characterized by stronger gradients in bottom salinity. [ABSTRACT FROM AUTHOR]

Background: In the CYD14 and CYD15 Phase 3 trials of the CYD-TDV dengue vaccine, estimated vaccine efficacy (VE) against symptomatic, virologically confirmed dengue (VCD) occurring between months 13 and 25 was 56.5% and 60.8%, respectively.Methods: Neutralizing antibody titers to the 4 dengue serotypes in the CYD-TDV vaccine insert were measured at month 13 in a randomly sampled immunogenicity subcohort and in all VCD cases through month 25 (2848 vaccine, 1574 placebo) and studied for their association with VCD and with the level of VE to prevent VCD.Results: For each trial and serotype, vaccinees with higher month 13 titer to the serotype had significantly lower risk of VCD with that serotype (hazard ratios, 0.19-0.43 per 10-fold increase). Moreover, for each trial, vaccinees with higher month 13 average titer to the 4 serotypes had significantly higher VE against VCD of any serotype (P < .001).Conclusions: Neutralizing antibody titers postdose 3 correlate with CYD-TDV VE to prevent dengue. High titers associate with high VE for all serotypes, baseline serostatus groups, age groups, and both trials. However, lowest titers do not fully correspond to zero VE, indicating that other factors influence VE. [ABSTRACT FROM AUTHOR]

Pheochromocytomas and extra-adrenal paragangliomas are catecholamine-secreting tumors that rarely occur in pregnancy. The diagnosis of these tumors in pregnancy can be challenging given that many of the signs and symptoms are commonly attributed to preeclampsia or other more common diagnoses. Early diagnosis and appropriate management are essential in optimizing maternal and fetal outcomes. We report a rare case of a catecholamine-secreting tumor in which diagnosis occurring at the time labor was being induced for concomitant preeclampsia with severe features. Her initial presentation in hypertensive crisis with other symptoms led to diagnostic workup for secondary causes of hypertension and led to eventual diagnosis of paraganglioma. Obtaining this diagnosis prior to delivery was essential, as this led to prompt multidisciplinary care, changed the course of her clinical management, and ultimately enabled good maternal and fetal outcomes. This case highlights the importance of maintaining a high index of suspicion for secondary causes of hypertension and in obstetric patients and providing timely multidisciplinary care. [ABSTRACT FROM AUTHOR]