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Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care., Global changes in both diagnostic and therapeutic practices in colorectal cancer care were evident in this survey conducted to analyze the impact of COVID-19 outbreak. The importance of this finding is that changes were associated with differences in health care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical variations.

Many sequenced behaviors, including locomotion, reaching, and vocalization, are patterned differently in different contexts, enabling animals to adjust to their current environments. However, how contextual information shapes neural activity to flexibly alter the patterning of actions is not yet understood. Prior work indicates such flexibility could be achieved via parallel motor circuits, with differing sensitivities to sensory context [1, 2, 3]; instead we demonstrate here how a single neural pathway operates in two different regimes dependent on recent sensory history. We leverage the Drosophila song production system [4] to investigate the neural mechanisms that support male song sequence generation in two contexts: near versus far from the female. While previous studies identified several song production neurons[5, 6, 7, 8], how these neurons are organized to mediate song patterning was unknown. We find that male flies sing ‘simple’ trains of only one syllable or mode far from the female but complex song sequences consisting of alternations between modes when near to her. We characterize the male song circuit from the brain to the ventral nerve cord (VNC), and find that the VNC song pre-motor circuit is shaped by two key computations: mutual inhibition and rebound excitability [9] between nodes driving the two modes of song. Weak sensory input to a direct brain-to-VNC excitatory pathway (via pC2 brain and pIP10 descending neurons) drives simple song far from the female. Strong sensory input to the same pathway enables complex song production via simultaneous recruitment of P1a neuron-mediated disinhibition of the VNC song pre-motor circuit. Thus, proximity to the female effectively unlocks motor circuit dynamics in the correct sensory context. We construct a compact circuit model to demonstrate that these few computations are sufficient to replicate natural context-dependent song dynamics. These results have broad implications for neural population-level models of context-dependent behavior [10] and highlight that canonical circuit motifs [11, 12, 13] can be combined in novel ways to enable circuit flexibility required for dynamic communication.

Sustained changes in mood or action require persistent changes in neural activity, but it has been difficult to identify the neural circuit mechanisms that underlie persistent activity and contribute to long-lasting changes in behavior. Here, we show that a subset of Doublesex+ pC1 neurons in the Drosophila female brain, called pC1d/e, can drive minutes-long changes in female behavior in the presence of males. Using automated reconstruction of a volume electron microscopic (EM) image of the female brain, we map all inputs and outputs to both pC1d and pC1e. This reveals strong recurrent connectivity between, in particular, pC1d/e neurons and a specific subset of Fruitless+ neurons called aIPg. We additionally find that pC1d/e activation drives long-lasting persistent neural activity in brain areas and cells overlapping with the pC1d/e neural network, including both Doublesex+ and Fruitless+ neurons. Our work thus links minutes-long persistent changes in behavior with persistent neural activity and recurrent circuit architecture in the female brain.

The recent spread of Zika virus (ZIKV) and its association with congenital defects and neurological disorders has created an urgent need to understand the pathogenesis of ZIKV and identify therapeutic strategies that will prevent or eliminate them. The neurodevelopmental defects associated with ZikV infections early in pregnancy are well documented, however the potential defects associated with infections in late pregnancy and perinatal period are less well characterized. Further, the long-term sequelae of these infections are not fully understood. Immunocompetent C57BL/6 mice infected at one day old (P1), which neurodevelopmentally model late pregnancy in humans, develop a transient neurological syndrome including unsteady gait, kinetic tremors, severe ataxia and seizures 10-15 days post-infection (dpi) but symptoms subside after a week, and most animals survive. Despite apparent recovery, MRI of convalescent mice shows reduced cerebellar volume that correlates with altered coordination and motor function as well as hyperactivity and impulsivity. Persistent mRNA levels of pro-inflammatory genes including Cd80, Il-1α, and Ifn-γ together with Cd3, Cd8 and perforin (PrfA), suggested the persistence of a low-grade inflammatory process. Further, the brain parenchyma of convalescent mice harbor multiple small foci with viral antigen, active apoptotic processes in neurons, and cellular infiltrates, surrounded by activated astrocytes and microglia as late as 1-year post-infection. Detection of negative-sense strand viral RNA and replication of virus derived from these convalescent mice by blinded passage in Vero cells confirmed that low levels of live ZikV persist in CNS of convalescent mice life-long. Our studies establish that Zika can establish reservoirs in CNS and suggest that anti-viral treatment that clears virus from the CNS as well as long-term neurological and behavioral monitoring may be needed for patients known to be exposed to ZikV at an early age.Author’s summaryThe congenital brain malformations associated with ZikV infections early in pregnancy are well documented, however whether apparently asymptomatic perinatal exposure could lead to long term sequelae is not fully understood. Using a non-lethal neonatal mouse model, we examine host-pathogen interactions, anatomical changes and behavioral patterns by following survivors of the acute infection for over 1 year. We discover that infectious Zika virus has the potential to remain in the CNS for life, lodged within small foci surrounded by gliosis and infiltrating immune cells that may act to limit the viral spread, but also interfere with healing and contribute to life-long neuropathic and behavioral sequelae. These results suggest that anti-viral treatment and long-term neurological and behavioral monitoring may be indicated for patients known to have been exposed to Zika virus, regardless of neurodevelopmental disease severity.

Therapeutic proteins can induce immune responses that affect their safety and efficacy. Product aggregates and innate immune response modulating impurities (IIRMI) are risk factors of product immunogenicity. In this study, we use Intravenous Immunoglobulin (IVIG), Avastin, and Human Serum Albumin (HSA) to explore whether increased aggregates activate innate immune cells or modify the response to IIRMI. We show that increased aggregates (shaken or stirred) in IVIG and Avastin, but not HSA, induced activation of MAPKs (pp38, pERK and pJNK) and transcription of immune-related genes including IL8, IL6, IL1β, CSF1, CCL2, CCL7, CCL3, CCL24, CXCL2, IRAK1, EGR2, CEBPβ, PPARg and TNFSF15 in human PBMC. The immunomodulatory effect was primarily mediated by FcγR, but not by TLR. Interestingly, increased aggregates in IVIG or Avastin magnified innate immune responses to TLR2/4 agonists, but diminished responses to TLR3/9 agonists. This study shows that IIRMI and aggregates can modify the activity of immune cells potentially modifying the milieu where the products are delivered highlighting the complex interplay of different impurities on product immunogenicity risk. Further, we show that aggregates could modify the sensitivity of PBMC-based assays designed to detect IIRMI. Understanding and managing immunogenicity risk is a critical component of product development and regulation.

Sustained changes in mood or action require persistent changes in neural activity, but it has been difficult to identify and characterize the neural circuit mechanisms that underlie persistent activity and contribute to long-lasting changes in behavior. Here, we focus on changes in the behavioral state ofDrosophilafemales that persist for minutes following optogenetic activation of a single class of central brain neurons termed pC1. We find that female pC1 neurons drive a variety of persistent behaviors in the presence of males, including increased receptivity, shoving, and chasing. By reconstructing cells in a volume electron microscopic image of the female brain, we classify 7 different pC1 cell types and, using cell type specific driver lines, determine that one of these, pC1-Alpha, is responsible for driving persistent female shoving and chasing. Using calcium imaging, we locate sites of minutes-long persistent neural activity in the brain, which include pC1 neurons themselves. Finally, we exhaustively reconstruct all synaptic partners of a single pC1-Alpha neuron, and find recurrent connectivity that could support the persistent neural activity. Our work thus links minutes-long persistent changes in behavior with persistent neural activity and recurrent circuit architecture in the female brain.

Arboviruses including alphavirus are responsible for most emerging infectious diseases worldwide. Recent outbreaks of chikungunya virus serve as a stark reminder to their pathogenic potential. There are no vaccines or therapeutics currently available to contain alphavirus outbreaks. In this study we evaluated the effect of immunomodulatory CpG ODN on the clinical progression of neurotropic Sindbis virus infection. Neonatal C57Bl-6 mice challenged with Sindbis virus AR339 (25 PFU Subcutaneous) infect neurons in the CNS leading to the development of ataxia, seizures, paralysis, and death. We show that systemic administration of CpG ODN modulates the cytokine and chemokine gene expression levels in the CNS and ultimately protects neonatal mice from lethal neurotropic infection. The protection conferred by CpG ODN is controlled by innate immune response and T and B cells were dispensable. Further, protection required Type I, Type II interferons, and TNF as well as functional NK cells, but did not involve iNOS. This study confirms that administration of innate immune modulators can be used as a strategy to boost host innate immune responses and protect against neurotropic viruses reducing their pathogenic footprint.

This paper investigates the variation of per capita personal income among counties within each state from 1969-2013. Department of Commerce BEA data and Department of Labor BLS data for 1969 to 2013 are analyzed. This study follows up on previous analysis of U.S. regional income variation by adjusting time series estimates for serial correction and using random effects models for panel data analysis. In addition, potential short-run disruption of a longer run trend is investigated by including an unemployment rate variable into the model. Results suggest that a general pattern of per capita income divergence has transpired in recent decades, contrary to conventional expectations of convergence.

This study was conducted on the Kootenai River, Idaho to provide insight on sampling requirements to optimize future monitoring effort associated with the response of fish assemblages to habitat rehabilitation. Our objective was to define the electrofishing effort (m) needed to have a 95% probability of sampling 50, 75, and 100% of the observed species richness and to evaluate the relative influence of depth, velocity, and instream woody cover on sample size requirements. Sidechannel habitats required more sampling effort to achieve 75 and 100% of the total species richness than main-channel habitats. The sampling effort required to have a 95% probability of sampling 100% of the species richness was 1100 m for main-channel sites and 1400 m for side-channel sites. We hypothesized that the difference in sampling requirements between main- and side-channel habitats was largely due to differences in habitat characteristics and species richness between main- and side-channel habitats. In general, main...

The inability of infants to mount proper follicular helper T (TFH) cell response renders this age group susceptible to infectious diseases. Initial instruction of T cells by antigen presenting cells and subsequent differentiation into TFH cells are controlled by T cell receptor signal strength, co-stimulatory molecules and cytokines such as IL-6 and IL-21. In immunized adults, IL-6 promotes TFH development by increasing the expression of CXCR5 and the TFH master transcription factor, B cell lymphoma 6. Underscoring the importance of IL-6 in TFH generation, we found improved antibody responses accompanied by increased TFH cells and decreased follicular regulatory helper T (TFR) cells, a Foxp3 expressing inhibitory CD4+ T cell occupying the germinal center (GC), when a tetanus toxoid conjugated pneumococcal polysaccharide type 14 vaccine was injected in adult mice together with IL-6. Paradoxically, in neonates IL-6 containing PPS14-TT vaccine suppressed the already impaired TFH development and antibody responses in addition to increasing TFR cell population. Supporting the diminished TFH development, we detected lower frequency of phospho-STAT-3+ TFH in immunized neonatal T cells after IL-6 stimulation than adult cells. Moreover, IL-6 induced more phospho-STAT-3+ TFR in neonatal cells than adult cells. We also measured lower expression of IL-6R on TFH cells and higher expression on TFR cells in neonatal cells than adult cells, a possible explanation for the difference in IL-6 induced signaling in different age groups. Supporting the flow cytometry findings, microscopic examination revealed the localization of Treg cells in the splenic interfollicular niches of immunized adult mice compared to splenic follicles in neonatal mice. In addition to the limitations in the formation of IL-21 producing TFH cells, neonatal mice GC B cells also expressed lower levels of IL-21R in comparison to the adult mice cells. These findings point to diminished IL-6 activity on neonatal TFH cells as an underlying mechanism of the increased TFR: TFH ratio in immunized neonatal mice.

Purpose This pilot study describes the career development programs (i.e., NIH KL2 awards) across five Clinical and Translational Science Award (CTSA) institutions within the University of California (UC) system, and examines the feasibility of a set of common metrics for evaluating early outcomes. Methods A survey of program administrators provided data related to the institutional environment within which each KL2 program was implemented. Application and progress report data yielded a combined data set that characterized KL2 awardees, their initial productivity, and early career outcomes. Results The pilot project demonstrated the feasibility of aggregating common metrics data across multiple institutions. The data indicated that KL2 awardees were an accomplished set of investigators, both before and after the award period, representing a wide variety of disciplines. Awardees that had completed their trainee period overwhelmingly remained active in translational research conducted within an academic setting. Early indications also suggest high rates of success with obtaining research funding subsequent to the KL2 award. Conclusion This project offers a model for how to collect and analyze common metrics related to the education and training function of the CTSA Consortium. Next steps call for expanding participation to other CTSA sites outside of the University of California system.

The lower Kootenai River, Idaho, was sampled during the summers of 2012 and 2013 to evaluate its fish assemblage structure at seven sites within main- and side-channel habitats where large-scale habitat rehabilitation was undertaken. Understanding the current patterns of fish assemblage structure and their relationships with habitat is important for evaluating the effects of past and future rehabilitation projects on the river. Species-specific habitat associations were modeled, and the variables that best explained the occurrence and relative abundance of fish were identified in order to guide future habitat rehabilitation so that it benefits native species. The results indicated that the side-channel habitats supported higher species richness than the main-channel habitats and that nonnative fishes were closely associated with newly rehabilitated habitats. This research provides valuable insight on the current fish assemblages in the Kootenai River and the assemblage-level responses that may occ...

This paper investigates recent trends of per capita personal income in the state of Oklahoma to ascertain what if any long-run trends are exhibited. Standard theoretical analysis suggests that per capita incomes are expected to converge, especially across regions. However, recent research indicates that the national trend is one of the regional income divergences. The question posed by this paper is whether or not the per capita income in Oklahoma supports evidence of divergence. The data for 1969 to 2012 obtained from Department of Commerce, Bureau of Economic Analysis (BEA) are analyzed. These data are used to regionalize the state into five distinct county-based areas. Results suggest that Oklahoma exhibits a transitional pattern from convergence to divergence during the period of study. The three objectives of this study are: 1) a test of the growth pole cycle theory; 2) an extension of previous analysis of Oklahoma regional income variation; and 3) a preliminary test of the impact of the 2008 recession on regional income variation. After identification and analysis of the five substate regions, an overview of the growth pole cycle theory explaining the hypothesized pattern is provided, followed by an exposition of the analytical methodology. The analytical results are twofold, first, a baseline analysis regressing variation on per capita income and second, the inclusion of the unemployment rate.

We applied an in vitro selection approach using two different plant lectins that bind to α2,3- or α2,6-linked sialic acids to determine which genetic changes of the A/California/04/09 (H1N1) virus alter hemagglutinin (HA) receptor binding toward α2,3- or α2,6-linked glycans. Consecutive passages of the A/California/04/09 virus with or without lectins in human lung epithelial Calu-3 cells led to development of three HA1 amino acid substitutions, N129D, G155E, and S183P, and one mutation in the neuraminidase (NA), G201E. The S183P mutation significantly increased binding to several α2,6 SA-linked glycans, including YDS, 6′SL(N), and 6-Su-6′SLN, compared to the wild-type virus (↑3.6-fold, P < 0.05). Two other HA1 mutations, N129D and G155E, were sufficient to significantly increase binding to α2,6-linked glycans, 6′SLN and 6-Su-6′SLN, compared to S183P (↑4.1-fold, P < 0.05). These HA1 mutations also increased binding affinity for 3′SLN glycan compared to the wild-type virus as measured by Biacore surface plasmon resonance method. In addition, the HA1 N129D and HA1 G155E substitutions were identified as antigenic mutations. Furthermore, the G201E mutation in NA reduced the NA enzyme activity (↓2.3-fold). These findings demonstrate that the A/California/04/09 (H1N1) virus can acquire enhanced receptor affinity for both α2,3- and α2,6-linked sialic receptors under lectin-induced selective pressure. Such changes in binding affinity are conferred by selection of beneficial HA1 mutations that affect receptor specificity, antigenicity, and/or functional compatibility with the NA protein.

Zika-infected patients can have eye involvement ranging from mild conjunctivitis to severe chorioretinal lesions, however the possible long-term sequelae of infection and timeline to recovery remain unknown. Here we describe the partial recovery of chorioretinal lesions in an immunocompetent patient diagnosed with bilateral posterior uveitis associated with Zika infection and show that some lesions resolved with focal atrophy evident as pigmentary changes on funduscopy. To better understand the progression of the lesions and correlate the changes in fundus imaging with local viral load, immune responses, and retinal damage, we developed a symptomatic mouse model of ocular Zika virus infection. Imaging of the fundus revealed multiple hypopigmentary patches indicative of chorioretinal degeneration as well as thinning of the retina that mirror the lesions in patients. Microscopically, the virus primarily infected the optic nerve, retinal ganglion cells, and inner nuclear layer cells, showing thinning of the outer plexiform layer. During acute infection, the eyes showed retinal layer disorganization, retinitis, vitritis, and focal choroiditis, with mild cellular infiltration and increased expression of tumor necrosis factor, interferon-γ, granzyme B, and perforin. Focal areas of gliosis and retinal degeneration persisted 60 dpi. The model recapitulates features of ZIKA infections in patients and should help elucidate the mechanisms underlying the damage to the eyes and aid in the development of effective therapeutics.

Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase (the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorder of glycosylation type IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replication and cellular entry may explain a decreased susceptibility to infections.

On reading the title of an article the reader can sometimes wonder what the author is trying to say, as the title seems so far removed from the research covered in the article. Do such authors forget that many readers of health and medical journals browse the list of contents (in a paper or electronic format) and use titles to select the article that attracts attention? Academic authors are often not clear enough in the titles of their articles, and hence may not attract as large a readership as possible. Any author would want their article to be read and cited, and to stand out in a crowded Table of Contents or a list of papers found in a search on electronic databases.DOI: http://dx.doi.org/10.3126/nje.v4i1.10138 Nepal Journal of Epidemiology 2014;4 (1): 344-347

As part of recovery efforts for the Kootenay population of Burbot Lota lota, we monitored 109 sonic-tagged, hatchery-reared Burbot released at 1–3 years of age throughout Kootenay Lake and the Kootenay River over a 3-year period. Our objectives were to evaluate broodstock choice, assess differences in survival and dispersal by release site and age, and evaluate spawning movements. Overall, release survival was high (66%) and there was dispersal throughout the system (up to 235 km), involving both lacustrine and riverine habitat. Spawning movements were extensive (up to 59 km/d upstream) and suggest the use of known spawning locations. However, most age-1 releases had lower survival and remained in the release tributaries for 1 year postrelease, which was longer than expected and which warrants further investigation. Overall, this telemetry study provides a positive outlook on the current aquaculture rehabilitation efforts for Kootenay Burbot and provides direction for further work. Received Septe...

The effects of six stocking densities on the survival and yield of larval Burbot Lota lota in a semi-intensive culture setting were investigated over a 3-year period. A stocking initiation trial indicated that a stocking date of at least 45 d after the first exogenous feeding (DPEF) would yield surviving juveniles after a 108-d semi-intensive culture period. Following this, stocking density was investigated, and larval Burbot were stocked into in-ground outdoor tanks 45 DPEF at densities of 50, 100, 150, 200, 250, and 300 larvae/m2. Tanks were harvested after 65 d, and the trials were repeated over two consecutive years. At harvest, the mean TL of fish ranged from 41 to 68 mm and the mean weight from 0.5 to 2.1 g over both years. Survival ranged from 1.0% to 12.7%, with lower stocking densities exhibiting higher survival. An exponential decay model revealed a significant influence of stocking density on survival, with 50 larvae/m2 being predicted to provide the highest survival and the maximum yi...

A conservation program developed by regional stakeholders incorporates stock enhancement as one of several approaches to restore an imperiled Burbot Lota lota population native to Idaho and British Columbia. Tagging juvenile fish is pivotal to stock enhancement monitoring; however, limited information is currently available on marks or tags applied to Burbot. We identified six criteria to guide artificial marker selection that are specific to imperiled juvenile fish. A short-term experiment with age-0 Burbot (65–92 mm TL) tested fin clips, freeze brands, visible implant elastomer, passive integrated transponders, and an unmarked control group. At 4 weeks posttagging, no significant differences were found between marking treatments with respect to fish survival (100%), absolute growth rate (0.15 ± 0.06 mm/d), specific growth rate (0.55 ± 0.32 g·g−1·d−1), or condition factor (0.64 ± 0.05). Mean tag retention ranged from 88% to 100%, and no significant differences were detected between treatments. R...

Burbot Lota lota is an emerging aquaculture species, in which fungal infestations during early life stage development are common. In this study, the tolerance of Burbot to external hydrogen peroxide (H2O2) treatment regimes was examined during four early life stages to determine species and life stage-specific sensitivity. Yolk-sac larvae tolerated three 1-h treatments up to 250 μL/L H2O2 without significant reduction in survival. Preflexion larvae tolerated only 100 μL/L H2O2 before survival was affected. In both cases, decreased survival was only observed after administration of three consecutive treatments. Flexion larvae tolerated up to 250 μL/L H2O2, but by the juvenile stage sensitivity again increased to 100 μL/L H2O2 before survival was affected. In these latter stages, decreased survival was observed immediately following the first H2O2 treatment, suggesting a mechanism for toxicity that is different than that in previous life stages. As has previously been shown, H2O2 can be effective f...

article i nfo The objective of this study was to determine the effect of temperature on growth and survival of larval and juvenile burbot, Lota lota maculosa. Burbot aquaculture is developing primarily in response to declining wild stocks and a need to restore such populations. Beyond conservation efforts, there is also potential to culture this species commercially. However, many important aspects of burbot culture remain unaddressed. In this study larval and juvenile burbot were reared at three constant water temperatures (10, 15, and 20 °C) in an intensive culture setting. Two 30 day trials were conducted during the larval life stage and one 60 day trial during the juvenile life stage. In Trial 1, larval burbot (mean total length±SD, 6.9±1.0 mm, approximately 65 days post hatch) reared at 20 °C grew the fastest, while growth was lowest in the 10 °C treatment. Survival was inversely related to temperature, with the lowest average of 6.6% observed in larvae reared at 20 °C. The percentage cannibalized was quantified and found to be positively correlated with water temperature, and reached 58.0% in larvae reared at 20 °C. In Trial 2, as larvae approached metamorphosis (12.9±1.9 mm, approximately 100 days post hatch), growth was also highest in fish at 20 °C and lowest in those at 10 °C. At this stage survival was higher in fish at lower temperatures, but the percentage cannibalized appeared independent of temperature, averaging over 50% in fish at all temperatures. In Trial 3, growth of juveniles (59.9±12.4 mm, approximately 205 days post hatch) reared at 15 and 20 °C was not significantly different, yet both displayed significantly increased growth relative to juveniles reared at 10 °C. Juveniles were fully transitioned to a dry diet, and survival averaged >93% in all culture temperatures. The percentage cannibalized during this life stage averaged b5%, and was not affected by temperature. This study demonstrated the importance of water temperature, as it clearly affects culture performance of larval and juvenile burbot. Results from this study have implications for maximizing growth during larval and juvenile life stages of this species, and provide a comparative, empirical framework for establishing conservation, or commercial aquaculture programs for burbot.

Burbot Lota lota are an emerging aquaculture species. To aid in predicting the natural and hormonal-manipulated timing of ovulation and for ensuring maximum viability of eggs at spawning, this study describes oocyte maturation of hatchery-reared burbot from vitellogenesis through ovulation. At a temperature of 4°C, visual polarization of the oil globule occurred 7–13 d preovulation. The lack of uniformity in individual oocyte development was observed and persisted until approximately 2 d before ovulation, at which point complete polarization was observed in all oocytes and a condensed blastomere was observed along the inner chorion. These preliminary observations imply that implantation of gonatotropin-releasing hormone (GnRH) decreased the final maturation stage of oocyte development by 2–4 d and may aid in initiating the maturation process, the induction of which appeared to be a threshold for either a female's progression to ovulation or nonovulation and atresia. Although additional investigat...

As enterprise resource planning (ERP) becomes the dominant management software in manufacturing and distribution systems in various industries, some problems associated with its origin, material requirements planning (MRP), still need to be resolved. We examine the effect of forecasting errors, one of the common operational problems in any business operation, in the context of an ERP-controlled manufacturing system. We consider a mitigating remedy, the use of a lot-sizing rule, to cope with the consequences of forecasting inaccuracy without resorting to costly inventory-oriented buffers. An ERP-controlled manufacturing system is simulated to see how these lot-sizing rules mitigate the forecast errors and subsequently generate acceptable system performance. The simulation results should help ease ERP users’ fear of committing another fatal error in demand forecasts, instead encouraging them to consider proper lot-sizing rules to cope with forecast errors.

Summary In the Kootenay River, British Columbia, Canada, burbot (Lota lota maculosa) numbers have diminished to near extirpation due to factors including physical changes to habitat and overfishing. Habitat restoration is currently underway but short-term recovery measures include the release of hatchery-reared burbot. Moyie Lake has been identified as a suitable brood source for a conservation aquaculture program but uncertainties remain regarding current population size, the feasibility of capturing broodstock and the ability to collect eggs from wild spawners. Specific objectives of our study were to: (i) develop a length at age key to provide a non-destructive means of population age structure identification, (ii) determine the location and general habitat characteristics of burbot spawning locations on Moyie Lake, (iii) provide a marked sample for future population estimation, and (iv) investigate the feasibility of collecting gametes for use in a conservation aquaculture program. A total of 181, 554, and 370 burbot were captured in 2009, 2010 and 2011, respectively. No significant relationship was established between length and age for burbot on Moyie Lake. Spawning burbot were observed over a number of different habitats, but high use areas consisted of steep banks dominated by a mix of gravel/boulder/cobble substrates. Mature burbot were reliably collected each year, and eggs from females were fertilized and transported to the hatchery. Egg survival was highly variable (range 0–98%) and resulted in an estimated 353 429, 3 032 143, and 3 970 283 eggs for use in the aquaculture program in 2009, 2010 and 2011, respectively. Results of this study demonstrate that gametes can be collected from adult burbot during spawning and eggs can be successfully fertilized in the field. Further methodological refinement aimed at improving egg fertilization and subsequent survival to the hatchery will be important as recovery moves forward.

As there are few larval-diet rearing methods for burbot Lota lota, it is important to develop these methods for ongoing conservation and future commercial aquaculture efforts. The performance and macronutrient composition of age-0 burbot were compared after fish were fed four different diets for 8 weeks. Diets included three commercial larval-rearing diets and Daphnia magna. Performance metrics involved mean length and weight, survival, and cannibalism. The macronutrient composition (dry matter) of fish and diets was measured as the percentages of moisture, lipid, protein, and ash, along with energy content. Significant differences in mean length and weight occurred, although survival and cannibalism were not different among treatments at the end of the experiment. Mean weight and length were significantly higher with diets 1 and 2. Fish fed diet 2 had the greatest mean survival (32%), followed by those fed the D. magna diet (30%), diet 3 (27%), and diet 1 (25%). Fish fed diet 1 experienced the g...

Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents.

Summary: Zaire Ebola virus (ZEBOV) survivors experience visual and CNS sequelae that suggests the ZEBOV glycoprotein can mediate neurotropism. Replication-competent rVSVΔG-ZEBOV-GP vaccine candidate is generally well tolerated; however, its potential neurotropism requires careful study. Here, we show that a single inoculation of rVSVΔG-ZEBOV-GP virus in neonatal C57BL/6 mice results in transient viremia, neurological symptoms, high viral titers in eyes and brains, and death. rVSVΔG-ZEBOV-GP infects the inner layers of the retina, causing severe retinitis. In the cerebellum, rVSVΔG-ZEBOV-GP infects neurons in the granular and Purkinje layers, resulting in progressive foci of apoptosis and neurodegeneration. The susceptibility to infection is not due to impaired type I IFN responses, although MDA5−/−, IFNβ−/−, and IFNAR1−/− mice have accelerated mortality. However, boosting interferon levels by co-administering poly(I:C) reduces viral titers in CNS and improves survival. Although these data should not be directly extrapolated to humans, they challenge the hypothesis that VSV-based vaccines are non-neurotropic. : Survivors of Ebola infections can experience neurologic and ocular symptoms, raising some concern that replication-competent vaccines expressing Ebola components could infect neurons in susceptible subjects. McWilliams et al. show that the rVSVΔG-EBOV-GP pseudovirus infects neurons in the eyes and brains of neonatal mice, causing tissue damage and lethality. Keywords: Ebola virus, ebolavirus, filovirus, Ebola glycoprotein, VSV, pseudotyped virus, VSV vaccine, innate immunity, neurotropism, neurovirulence, Ebola vaccine

Prepositioned areal electrofishing devices (PAEDs) are used to evaluate microhabitat use by fishes because they minimize fright biases associated with traditional electrofishing techniques (e.g., boat electrofishing). Similarly, fixed underwater videography (FUV) is commonly used to minimize the effect of observers on fish behavior. The specific objectives of this research were to evaluate estimates of taxonomic occurrence and diversity between PAEDs and FUV and determine an appropriate time interval between positioning and electrifying of a PAED to reduce effects of PAED positioning on fish occurrence. Video cameras were positioned instream at 28 locations on the Kootenai River, Idaho, prior to PAED deployment such that the entire immobilization zone of the PAED was captured on camera. Following a 4-min acclimation period, cameras recorded fish behavior approximately 15 min prior to and 20 min following PAED deployment. Electrical current was applied to the PAEDs for 20 s immediately following the FUV procedure, and immobilized fishes were collected and processed. Video footage was subsampled in the laboratory, and fishes in the video were identified and enumerated in 5-s or 20-s intervals. Fixed underwater videography sampled more taxa than PAEDs at any given site. However, fishes sampled with FUV were difficult to identify, and most individuals were classified as “unidentifiable.” Consequently, direct comparisons between FUV and PAEDs are limited. Our results indicate that PAEDs should remain undisturbed for a minimum of 12 min before the equipment is electrified. Both PAEDs and FUV provide an estimate of taxonomic occurrence, but logistical and financial constraints along with project objectives must be considered when selecting between these 2 gear types. Results from this study provide information on the effectiveness of each gear type as it relates to the characterization of riverine fish assemblages at a small spatial scale.

In this study, susceptibility and potential carrier status of burbot, Lota lota, were assessed for five important fish pathogens. Burbot demonstrated susceptibility and elevated mortality following challenge with infectious haematopoietic necrosis virus (IHNV) by immersion and to Aeromonas salmonicida by intraperitoneal (i.p.) injection. IHNV persisted in fish for at least 28 days, whereas A. salmonicida was not re-isolated beyond 17 days post-challenge. In contrast, burbot appeared refractory to Flavobacterium psychrophilum following intramuscular (i.m.) injection and to infectious pancreatic necrosis virus (IPNV) by immersion. However, i.p injection of IPNV resulted in re-isolation of virus from fish for the duration of the 28 day challenge. Renibacterium salmoninarum appeared to induce an asymptomatic carrier state in burbot following i.p. injection, but overt manifestation of disease was not apparent. Viable bacteria persisted in fish for at least 41 days, and bacterial DNA isolated by diagnostic polymerase chain reaction was detected from burbot kidney tissue 90 days after initial exposure. This study is the first to investigate susceptibility of burbot to selected fish pathogens, and this information will aid in efforts to culture and manage this species.