Tracking an invasion front with environmental DNA.

Data from environmental DNA (eDNA) may revolutionize environmental monitoring and management, providing increased detection sensitivity at reduced cost and survey effort. However, eDNA data are rarely used in decision-making contexts, mainly due to uncertainty around (1) data interpretation and (2) whether and how molecular tools dovetail with existing management efforts. We address these challenges by jointly modeling eDNA detection via qPCR and traditional trap data to estimate the density of invasive European green crab (Carcinus maenas), a species for which, historically, baited traps have been used for both detection and control. Our analytical framework simultaneously quantifies uncertainty in both detection methods and provides a robust way of integrating different data streams into management processes. Moreover, the joint model makes clear the marginal information benefit of adding eDNA (or any other) additional data type to an existing monitoring program, offering a path to optimizing sampling efforts for species of management interest. Here, we document green crab eDNA beyond the previously known invasion front and find that the value of eDNA data dramatically increases with low population densities and low traditional sampling effort, as is often the case at leading-edge locations. We also highlight the detection limits of the molecular assay used in this study, as well as scenarios under which eDNA sampling is unlikely to improve existing management efforts.

Rapid assessment of management options for promoting stock rebuilding in data-poor species under climate change.

The development of species recovery plans requires considering likely outcomes of different management interventions, but the complicating effects of climate change are rarely evaluated. We examined how qualitative network models (QNMs) can be deployed to support decision making when data, time, and funding limitations restrict use of more demanding quantitative methods. We used QNMs to evaluate management interventions intended to promote the rebuilding of a collapsed stock of blue king crab (Paralithodes platypus) (BKC) around the Pribilof Islands (eastern Bering Sea) to determine how their potential efficacy may change under climate change. Based on stakeholder input and a literature review, we constructed a QNM that described the life cycle of BKC, key ecological interactions, potential climate-change impacts, relative interaction strengths, and uncertainty in terms of interaction strengths and link presence. We performed sensitivity analyses to identify key sources of prediction uncertainty. Under a scenario of no climate change, predicted increases in BKC were reliable only when stock enhancement was implemented in a BKC hatchery-program scenario. However, when climate change was accounted for, the intervention could not counteract its adverse impacts, which had an overall negative effect on BKC. The remaining management scenarios related to changes in fishing effort on BKC predators. For those scenarios, BKC outcomes were unreliable, but climate change further decreased the probability of observing recovery. Including information on relative interaction strengths increased the likelihood of predicting positive outcomes for BKC approximately 5-50% under the management scenarios. The largest gains in prediction precision will be made by reducing uncertainty associated with ecological interactions between adult BKC and red king crab (Paralithodes camtschaticus). Qualitative network models are useful options when data are limited, but they remain underutilized in conservation.

Evaluación Rápida de las Opciones de Manejo para la Promoción de la Recuperación de Especies con Deficiencia de Datos bajo el Cambio Climático Resumen El desarrollo de los planes de recuperación de especies requiere de la consideración de los resultados probables de las diferentes intervenciones de manejo, pero los efectos agravantes del cambio climático rara vez están incluidos en esta evaluación. Examinamos cómo los modelos cualitativos de redes (QNMs) pueden implementarse para apoyar la toma de decisiones cuando los datos, el tiempo y el financiamiento sufren limitaciones que restringen el uso de métodos cuantitativos más demandantes. Usamos los QNMs para evaluar las intervenciones de manejo con la intención de promover el repoblamiento del colapsado cangrejo rey azul (Paralithodes platypus) (BKC) alrededor de las islas Pribilof (oriente del Mar de Bering) y así determinar cómo su eficiencia potencial puede modificarse bajo el cambio climático. Con base en aportaciones de los grupos de interés y una revisión bibliográfica construimos una QNM que describía el ciclo de vida del BKC, sus interacciones ecológicas importantes, impactos potenciales del cambio climático, fortalezas relativas de interacción, y la incertidumbre en relación con las fortalezas de interacción y la presencia de vínculos. Realizamos análisis de sensibilidad para identificar las fuentes clave de incertidumbre en la predicción. Bajo un escenario de ausencia de cambio climático, los incrementos pronosticados en la población de BKC fueron confiables solamente cuando el reforzamiento de la población se realizó en un escenario de programa de cultivo de BKC. Sin embargo, cuando se incluyó el cambio climático, la intervención de conservación no pudo contrarrestar los impactos adversos del cambio climático, lo cual tuvo un efecto negativo generalizado sobre los BKC. Los escenarios de manejo restantes estuvieron relacionados con los cambios en los esfuerzos de pesca sobre los depredadores del BKC. Para los estos últimos escenarios, los resultados de la población de BKC no fueron confiables, pero el cambio climático disminuyó todavía más la probabilidad de observar una recuperación. La inclusión de información sobre las fortalezas relativas de interacción incrementó la posibilidad de predecir los resultados de la población de BKC en ∼ 5 - 50% bajo los escenarios de manejo. Las mayores ganancias en la precisión de la predicción se lograrán reduciendo la incertidumbre asociada con las interacciones ecológicas entre los BKC adultos y el cangrejo rey rojo (Paralithodes camtschaticus). Los modelos cualitativos de redes son opciones útiles cuando los datos son limitados, pero permanecen subutilizados en la conservación.

Metrics of progress in the understanding and management of threats to Australian birds.

Although evidence-based approaches have become commonplace for determining the success of conservation measures for the management of threatened taxa, there are no standard metrics for assessing progress in research or management. We developed 5 metrics to meet this need for threatened taxa and to quantify the need for further action and effective alleviation of threats. These metrics (research need, research achievement, management need, management achievement, and percent threat reduction) can be aggregated to examine trends for an individual taxon or for threats across multiple taxa. We tested the utility of these metrics by applying them to Australian threatened birds, which appears to be the first time that progress in research and management of threats has been assessed for all threatened taxa in a faunal group at a continental scale. Some research has been conducted on nearly three-quarters of known threats to taxa, and there is a clear understanding of how to alleviate nearly half of the threats with the highest impact. Some management has been attempted on nearly half the threats. Management outcomes ranged from successful trials to complete mitigation of the threat, including for one-third of high-impact threats. Progress in both research and management tended to be greater for taxa that were monitored or occurred on oceanic islands. Predation by cats had the highest potential threat score. However, there has been some success reducing the impact of cat predation, so climate change (particularly drought), now poses the greatest threat to Australian threatened birds. Our results demonstrate the potential for the proposed metrics to encapsulate the major trends in research and management of both threats and threatened taxa and provide a basis for international comparisons of evidence-based conservation science.

Medidas de Progreso en el Entendimiento y el Manejo de las Amenazas que Enfrentan las Aves Australianas Resumen Aunque los métodos basados en evidencias se han vuelto muy comunes para la determinación del éxito de las medidas de conservación del manejo de los taxones amenazados, hoy en día no existen medidas estandarizadas para la evaluación del progreso de la investigación o el manejo. Desarrollamos cinco medidas para cumplir con esta necesidad que tienen los taxones amenazados y para cuantificar la necesidad de una mayor acción y un alivio efectivo de las amenazas. Estas medidas (falta de investigación, éxito de la investigación, falta de manejo, éxito del manejo y porcentaje de reducción de amenazas) pueden agregarse para examinar las tendencias de un taxón individual o las tendencias de las amenazas para múltiples taxones. Probamos la utilidad de estas medidas por medio de su aplicación en aves australianas amenazadas, que parece ser la primera vez que se evalúa el progreso en la investigación y en el manejo de amenazas para el caso de varios taxones amenazados dentro de un grupo faunístico a escala continental. Se ha realizado algún tipo de investigación sobre casi tres cuartas partes de las amenazas conocidas para los taxones, y hay un claro entendimiento de cómo aliviar casi la mitad de las amenazas con el impacto más alto. Se ha intentado algún tipo de manejo con casi la mitad de las amenazas. Los resultados del manejo variaron desde ensayos exitosos hasta la mitigación completa de la amenaza, incluso para un tercio de las amenazas de alto impacto. Tanto el progreso en la investigación como en el manejo tendió a ser mayor para los taxones que estaban siendo monitoreados, o que ocurrían en islas oceánicas. La depredación por gatos tuvo el puntaje más como amenaza potencial. Sin embargo, ha habido poco de éxito en la reducción del impacto de la depredación por gatos, así que ahora el cambio climático (particularmente la sequía) es la mayor amenaza para las aves amenazadas en Australia. Nuestros resultados demuestran el potencial que tienen las medidas propuestas de encapsular las tendencias más importantes en la investigación y en el manejo tanto de las amenazas como de los taxones amenazados y de proporcionar una base para comparaciones internacionales de la ciencia de la conservación basada en evidencias.

Invasive European green crab (Carcinus maenas) predation in a Washington State estuary revealed with DNA metabarcoding.

Predation by invasive species can threaten local ecosystems and economies. The European green crab (Carcinus maenas), one of the most widespread marine invasive species, is an effective predator associated with clam and crab population declines outside of its native range. In the U.S. Pacific Northwest, green crab has recently increased in abundance and expanded its distribution, generating concern for estuarine ecosystems and associated aquaculture production. However, regionally-specific information on the trophic impacts of invasive green crab is very limited. We compared the stomach contents of green crabs collected on clam aquaculture beds versus intertidal sloughs in Willapa Bay, Washington, to provide the first in-depth description of European green crab diet at a particularly crucial time for regional management. We first identified putative prey items using DNA metabarcoding of stomach content samples. We compared diet composition across sites using prey presence/absence and an index of species-specific relative abundance. For eight prey species, we also calibrated metabarcoding data to quantitatively compare DNA abundance between prey taxa, and to describe an 'average' green crab diet at an intertidal slough versus a clam aquaculture bed. From the stomach contents of 61 green crabs, we identified 54 unique taxa belonging to nine phyla. The stomach contents of crabs collected from clam aquaculture beds were significantly different from the stomach contents of crabs collected at intertidal sloughs. Across all sites, arthropods were the most frequently detected prey, with the native hairy shore crab (Hemigrapsus oregonensis) the single most common prey item. Of the eight species calibrated with a quantitative model, two ecologically-important native species-the sand shrimp (Crangon franciscorum) and the Pacific staghorn sculpin (Leptocottus armatus)-had the highest average DNA abundance when detected in a stomach content sample. In addition to providing timely information on green crab diet, our research demonstrates the novel application of a recently developed model for more quantitative DNA metabarcoding. This represents another step in the ongoing evolution of DNA-based diet analysis towards producing the quantitative data necessary for modeling invasive species impacts.

Reciprocal inhibition versus unloading response during stretch reflex in humans.

Rotation of an upper limb joint produces excitatory stretch reflex peaks M1 and M2 in the stretched muscles and simultaneous decrease in electromyographic (EMG) activity in the shortened muscles. The objective of this study was to examine whether the decreased activity in the antagonists (rINHIB) is purely from unloading of the spindles or receives active inhibition involving inhibitory interneurons. If rINHIB is due only to unloading, then the termination of rINHIB should vary with the duration of perturbation used to elicit stretch reflex, namely shorter stretches should result in shorter values of decreased periods of EMG. To examine this question, rectangular pulses, ranging in duration from 25 to 150 ms, were used to stretch wrist flexors or extensors with a torque motor. These rectangular pulses resulted in joint rotations which peaked at times (T(peak)) ranging from approximately 75-160 ms. As shown by previous authors, when the duration of rotation was shortened, the magnitude of M1 did not change, while the magnitude of M2 decreased. However, termination time of rINHIB in the shortened muscles did not change with change in T(peak), implying thereby that unloading of spindles of the antagonist muscles is not the only mechanism for the reduction in activity and that inhibitory reflex pathways most likely contribute. Possible sources of inhibition are discussed for the short- and long-latency inhibition.

Low faecal haemoglobin concentration potentially rules out significant colorectal disease.

AIM: The study aimed to determine whether faecal haemoglobin (Hb) concentration can assist in deciding who with lower abdominal symptoms will benefit from endoscopy. METHOD: Faecal Hb concentrations were measured on single samples from 280 patients referred for lower gastrointestinal tract endoscopy from primary care in NHS Tayside who completed a faecal immunochemical test (FIT) for Hb and underwent subsequent endoscopy. RESULTS: Among 739 invited patients, FIT and endoscopy were completed by 280 (median age 63 (18-84) years; 59.6% women), with a median time between FIT and endoscopy of 9 days. Six (2.1%) participants had cancer, 23 (8.2%) had high-risk adenoma (HRA) (more than three adenomas or any > 1 cm), 31 (11.1%) low-risk adenoma (LRA) and 26 (9.3%) inflammatory bowel disease (IBD) as the most serious diagnosis. Those with cancer had a median faecal Hb of > 1000 ng Hb/ml buffer. Those with cancer + HRA + IBD had a median faecal Hb concentration of 75 ng Hb/ml buffer (95% CI 18-204), which was significantly higher than that of all remaining participants without significant colorectal disease (P < 0.0001). Using a cut-off faecal Hb concentration of 50 ng Hb/ml buffer, negative predictive values of 100.0%, 94.4%, 93.4% and 93.9% were found for cancer, HRA, LRA and IBD. Patients with reasons for referral other than rectal bleeding and family history did not have high faecal Hb concentrations. CONCLUSION: Faecal Hb concentration measurements have considerable potential to contribute to reducing unnecessary endoscopy for the majority of symptomatic patients.

Gamma knife radiosurgery for large vestibular schwannomas: a Canadian experience.

OBJECT: To review our institutional experience with Gamma Knife (GK) stereotactic radiosurgery in treating large vestibular schwannomas (VS) of 3 to 4 cm diameter. METHODS: We conducted a retrospective cohort review of all patients treated with GK for VS at our institution between November 2003 and March 2012. Data on age, sex, VS volume, location and maximal diameter, House-Brackmann (HB) facial nerve scores pre and post-GK, Gardner-Robertson (GR) hearing score pre and post-GK, GK treatment parameters, VS response time, complications and clinical outcome was recorded RESULTS: A total of 28 patients during the defined time period were identified. Three patients were lost to follow-up. Mean follow-up was 34.5 months. Tumor control occurred in 92%, and was maintained in 85.7% at two years. Facial nerve or hearing preservation occurred in all treated compared to pre-GK status, as per HB and GR grading. Transient complications occurred in 80%. Temporary vestibular dysfunction occurred in seven patients (28%). One patient (4%) had the permanent complication of worsening pre-GK hemifacial spasm. Four patients (16%) developed hydrocephalus post-GK. CONCLUSION: GK stereotactic radiosurgery as a primary treatment modality for large VS can provide acceptable tumor control rates with good facial nerve and hearing preservation, and low complication rates.

Gamma knife in the treatment of pituitary adenomas: results of a single center.

INTRODUCTION: Gamma Knife (GK) radiosurgery for pituitary adenomas can offer a means of tumor and biologic control with acceptable risk and low complication rates. METHODS: Retrospective review of all the patients treated at our center with GK for pituitary adenomas from Nov 2003 to June 2011. RESULTS: We treated a total of 86 patients. Ten were lost to follow-up. Mean follow was 32.8 months. There were 21 (24.4%) growth hormone secreting adenomas (GH), 8 (9.3%) prolactinomas (PRL), 8 (9.3%) adrenocorticotropic hormone secreting (ACTH) adenomas, 2 (2.3%) follicle stimulating hormone/luteinizing hormone secreting (FSH/LH) adenomas, and 47 (54.7%) null cell pituitary adenomas that were treated. Average maximum tumor diameter and volume was 2.21cm and 5.41cm³, respectively. The average dose to the 50% isodose line was 14.2 Gy and 23.6 Gy for secreting and non-secreting adenomas respectively. Mean maximal optic nerve dose was 8.87 Gy. Local control rate was 75 of 76 (98.7%), for those with followup. Thirty-three (43.4%) patients experienced arrest of tumor growth, while 42 (55.2%) patients experienced tumor regression. Of the 39 patients with secreting pituitary tumors, 6 were lost to follow-up. Improved endocrine status occurred in 16 (50.0%), while 14 (43.8%) demonstrated stability of hormone status on continued pre-operative medical management. Permanent complications included: panhypopituitarism (4), hypothyroidism (4), hypocortisolemia (1), diabetes insipidus (1), apoplexy (1), visual field defect (2), and diplopia (1). CONCLUSIONS: Gamma Knife radiosurgery is a safe and effective means of achieving tumor growth control and endocrine remission/stability in pituitary adenomas.

Gamma knife radiosurgery for high grade glial neoplasms: a Canadian experience.

OBJECT: To review our institutional experience with Gamma Knife (GK) stereotactic radiosurgery in treating focally recurrent high grade glial neoplasms of World Health Organization (WHO) grade III or IV. METHODS: We conducted a retrospective cohort review of all patients treated with GK for focally recurrent high grade gliomas at our institution between November 2003 and April 2013. Data on age, sex, tumor volume, location and maximal diameter, presenting clinical status, complications and clinical outcome was recorded. RESULTS: A total of 33 patients were identified. Four were lost to follow-up. Average post-GK and overall survival was 20.4 months (range: 3­72) and 63.3 months (range: 10­214) respectively. For WHO grade IV gliomas, the average post-GK and overall survival was 15.8 months (range: 3­77) and 40.1 months (range: 13­148) respectively. Similarily, for WHO grade III gliomas, the average post-GK and overall survival was 34.9 months (range: 6­72) and 136.4 months (range: 22­214) respectively. Twenty-two patients (75.9%) had post-GK edema, with 14 requiring dexamethasone and eight being asymptomatic. Four patients (13.8%) had imaging defined radiation necrosis. CONCLUSIONS: Gamma Knife SRS affords an extension of local tumor control, acceptable morbidity, and potentially prolonged survival, for highly selected patients with focally recurrent high grade glial neoplasms.Radiochirurgie par scalpel gamma pour les néoplasies gliales de haut grade de malignité : une expérience canadienne.

Blended learning: strengths, challenges, and lessons learned in an interprofessional training program.

This field report outlines the goals of providing a blended learning model for an interdisciplinary training program for healthcare professionals who care for children with disabilities. The curriculum blended traditional face-to-face or on-site learning with integrated online interactive instruction. Credit earning and audited graduate level online coursework, community engagement experiences, and on-site training with maternal and child health community engagement opportunities were blended into a cohesive program. The training approach emphasized adult learning principles in different environmental contexts integrating multiple components of the Leadership Education in Neurodevelopmental and Related Disabilities Program. This paper describes the key principles adopted for this blended approach and the accomplishments, challenges, and lessons learned. The discussion offers examples from training content, material gathered through yearly program evaluation, as well as university course evaluations. The lessons learned consider the process and the implications for the role of blended learning in this type of training program with suggestions for future development and adoption by other programs.

Gamma Knife radiosurgery of cavernous sinus meningiomas: an institutional review.

INTRODUCTION: Stereotactic radiosurgery offers a unique and effective means of controlling cavernous sinus meningiomas with a low rate of complications. METHODS: We retrospectively reviewed all cavernous sinus meningiomas treated with Gamma Knife (GK) radiosurgery between November 2003 and April 2011 at our institution. RESULTS: Thirty patients were treated, four were lost to follow- up. Presenting symptoms included: headache (9), trigeminal nerve dysesthesias/paresthesias (13), abducens nerve palsy (11), oculomotor nerve palsy (8), Horner's syndrome (2), blurred vision (9), and relative afferent pupillary defect (1). One patient was asymptomatic with documented tumor growth. Treatment planning consisted of MRI and CT in 17 of 30 patients (56.7%), the remainder were planned with MRI alone (44.3%). There were 8 males (26.7%) and 22 females (73.3%). Twelve patients had previous surgical debulking prior to radiosurgery. Average diameter and volume at time of radiosurgery was 3.4 cm and 7.9 cm3 respectively. Average dose at the 50% isodose line was 13.5 Gy. Follow-up was available in 26 patients. Average follow-up was 36.1 months. Mean age 55.1 years. Tumor size post GK decreased in 9 patients (34.6%), remained stable in 15 patients (57.7%), and continued to grow in 2 (7.7%). Minor transient complications occurred in 12 patients, all resolving. Serious permanent complications occurred in 5 patients: new onset trigeminal neuropathic pain (2), frame related occipital neuralgia (1), worsening of pre-GK seizures (1), and panhypopituitarism (1). CONCLUSION: GK offers an effective treatment method for halting meningioma progression in the cavernous sinus, with an acceptable permanent complication rate.

GABAB Receptor Chemistry and Pharmacology: Agonists, Antagonists, and Allosteric Modulators.

The GABAB receptors are metabotropic G protein-coupled receptors (GPCRs) that mediate the actions of the primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA). In the CNS, GABA plays an important role in behavior, learning and memory, cognition, and stress. GABA is also located throughout the gastrointestinal (GI) tract and is involved in the autonomic control of the intestine and esophageal reflex. Consequently, dysregulated GABAB receptor signaling is associated with neurological, mental health, and gastrointestinal disorders; hence, these receptors have been identified as key therapeutic targets and are the focus of multiple drug discovery efforts for indications such as muscle spasticity disorders, schizophrenia, pain, addiction, and gastroesophageal reflex disease (GERD). Numerous agonists, antagonists, and allosteric modulators of the GABAB receptor have been described; however, Lioresal® (Baclofen; ß-(4-chlorophenyl)-γ-aminobutyric acid) is the only FDA-approved drug that selectively targets GABAB receptors in clinical use; undesirable side effects, such as sedation, muscle weakness, fatigue, cognitive deficits, seizures, tolerance and potential for abuse, limit their therapeutic use. Here, we review GABAB receptor chemistry and pharmacology, presenting orthosteric agonists, antagonists, and positive and negative allosteric modulators, and highlight the therapeutic potential of targeting GABAB receptor modulation for the treatment of various CNS and peripheral disorders.

Gamma knife for cerebral arteriovenous malformations at a single centre.

BACKGROUND: We report the results of a consecutive series of patients treated with Gamma Knife (GK) Surgery for cerebral arteriovenous malformations (AVMs). METHODS: We retrospectively reviewed 69 patients treated with GK for cerebral AVMs between November 2003 and April 2009, recording clinical data, treatment parameters, and AVM obliteration rates in order to assess our effectiveness with GK in treating these lesions. RESULTS: Ten patients were lost to follow-up. Presentations included: seizure (24), hemorrhage (18), persistent headache (12), progressing neurological signs (10), and incidental (9). In 24 patients (34.8%) treatment planning consisted of digital subtraction angiography (DSA), magnetic resonance imaging (MRI), and computed tomogram (CT) angiography (CTA). Currently we rely predominantly on CTA and/or MRI scanning only. Fourty-one patients have been followed for a minimum of 3 years; average age 40.9 yr., 58.5% males. Average dose at the 50% isodose line was 20.3 Gy (range 16 to 26.4 Gy). Obliteration was observed in 87.8% by MRI, CT, or DSA. Not all obliteration was confirmed by DSA. Complications occurred in 12 of 59 (20.3%) patients, and in 11 of 41 (26.8%) with 3 year follow-up. Major (temporary) complications for the 59 included symptomatic cerebral edema (7), seizure (2), and hemorrhage (1). Major permanent complications occurred in one patient suffering a cranial nerve V deafferentation, and in two patients suffering a hemorrhage. CONCLUSION: GKS for cerebral AVM's offers an effective and safe method of treatment, with low permanent complication rate.

Quantitative determination of neuronal size and density using flow cytometry.

BACKGROUND: Recent anthropomorphic disturbances are occurring at an increasing rate leading to organisms facing a variety of challenges. This change is testing the information processing capacity (IPC) of all animals. Brain function is widely accepted to be influenced by a variety of factors, including relative size, number of neurons and neuronal densities. Therefore, in order to understand what drives an animals IPC, a methodological approach to analyze these factors must be established. NEW METHOD: Here we created a protocol that allowed for high-throughput, non-biased quantification of neuronal density and size across six regions of the brain. We used the Isotropic Fractionator method in combination with flow cytometry to identify neuronal and non-neuronal cells in the brains of adult rats. COMPARISON WITH EXISTING METHODS: The results obtained were comparable to those identified using stereological counting methods. RESULTS: By employing this new method, the number of nuclei in a specific brain region can be compared between replicate animals within an experiment. By calibrating the forward scatter channel of the flow cytometer with size standard beads, neuronal and non-neuronal nuclear sizes can be estimated simultaneously with nuclei enumeration. These techniques for nuclear counting and size estimation are technically and biologically reproducible. CONCLUSION: Use of flow cytometry provides a methodological approach that allows for consistency in research, so that information on brain morphology, and subsequent function, will become comparable across taxa.

Granulocyte/macrophage colony-stimulating factor stimulates the expression of the 5-lipoxygenase-activating protein (FLAP) in human neutrophils.

The synthesis of leukotrienes in human blood neutrophils chiefly relies on the activity of two enzymes, phospholipase A2 and 5-lipoxygenase (5-LO). In turn, the activation of the 5-LO requires the participation of a recently characterized membrane-bound protein, the 5-LO-activating protein (FLAP). In this study, we have investigated conditions under which FLAP expression in neutrophils may be modulated. Of several cytokines tested, only granulocyte/macrophage colony-stimulating factor (GM-CSF) (and to a lesser extent tumor necrosis factor alpha) significantly increased expression of FLAP. GM-CSF increased FLAP mRNA steady-state levels in a time- and dose-dependent manner. The stimulatory effect of GM-CSF on FLAP mRNA was inhibited by prior treatment of the cells with the transcription inhibitor, actinomycin D, and pretreatment of the cells with the protein synthesis inhibitor, cycloheximide, failed to prevent the increase in FLAP mRNA induced by GM-CSF. The accumulation of newly synthesized FLAP, as determined by immunoprecipitation after incorporation of 35S-labeled amino acids, was also increased after incubation of neutrophils with GM-CSF. In addition, the total level of FLAP protein was increased in GM-CSF-treated neutrophils, as determined by two-dimensional gel electrophoresis, followed by Western blot. GM-CSF did not alter the stability of the FLAP protein, indicating that the effect of GM-CSF on FLAP accumulation was the consequence of increased de novo synthesis as opposed to decreased degradation of FLAP. Finally, incubation of neutrophils with the synthetic glucocorticoid dexamethasone directly stimulated the upregulation of FLAP mRNA and protein, and enhanced the effect of GM-CSF. Taken together, these data demonstrate that FLAP expression may be upmodulated after appropriate stimulation of neutrophils. The increase in FLAP expression induced by GM-CSF in inflammatory conditions could confer upon neutrophils a prolonged capacity to synthesize leukotrienes.

Restoration through eradication? Removal of an invasive bioengineer restores some habitat function for a native predator.

Invasive aquatic macrophytes increase structural complexity in recipient systems and alter trophic and physical resources; thus, eradication programs that remove plant structure have potential to restore some impaired ecological functions. In this study we evaluate how an invasive ecosystem engineer, Atlantic smooth cordgrass (Spartina alterniflora), interferes with the movement and foraging activity of a mobile predator, Dungeness crab (Cancer magister), and whether removal of aboveground cordgrass structure rapidly reestablishes access to foraging habitats. By 2004, smooth cordgrass had invaded >25% of crab foraging habitat in Willapa Bay, Washington (USA), and transformed it into a highly structured landscape. However, by 2007 successful eradication efforts had eliminated most meadows of the cordgrass. In order to investigate the effect of smooth cordgrass on the habitat function of littoral areas for foraging crabs, we integrated field, laboratory, and statistical modeling approaches. We conducted trapping surveys at multiple sites and used a hierarchical model framework to examine patterns in catches prior to and following cordgrass removal (i.e., before-after control-impact design, BACI). Prior to eradication, catches of Dungeness crabs in unstructured habitats were 4-19 times higher than catches in adjacent patches of live cordgrass. In contrast, the results of post-eradication trapping in 2007 indicated similar catch rates of crabs in unstructured habitats and areas formerly invaded by the cordgrass. Subsequent laboratory experiments and video observations demonstrated that the rigid physical structure of smooth cordgrass shoots reduces the ability of Dungeness crabs to access prey resources and increases the risk of stranding. Taken together, these findings suggest that eliminating the structural complexity of invasive macrophytes may rapidly restore some ecological function (i.e., foraging area) for migratory predators like Dungeness crab. However, restoration of affected areas to a preinvasion state will also depend on long-term patterns of succession in invaded areas and the degree of persistence of physical changes that continue to alter biotic characteristics of the habitat. Our work highlights: (1) the efficacy of employing multiple methods of inquiry to evaluate causal relationships through mechanisms of interaction, and (2) the importance of targeting particular ecological functions when identifying both short- and long-term goals of restoration efforts.

Predictive validity and measurement issues in documenting quit intentions in population surveillance studies.

INTRODUCTION: Discrete classification of smokers by intention to quit is desirable in many public health and clinical settings. METHODS: Two methodological studies examine measurement properties of measures of discrete-time intention to quit smoking used in population-based tobacco surveillance surveys: an ecological comparison of rates of positive intention in relation to the form of measure used and a prospective analysis examining predictive validity of self-reported quit intentions using multiple possible points of dichotomization of an ordinal measure of intention to quit. The prospective analysis used a repeated measures design and follow-up to 1 year for 2,047 smokers in the Ontario Tobacco Survey cohort. RESULTS: The estimated percent of smokers intending to quit was significantly higher using the Stages of Change intention measure, relative to another single question measure. Significant dose-response effects were found. The sooner one intended to quit the more likely one was to make an attempt or achieve at least 30 days abstinence in the next 6 months. Intending to quit in a month or later was not associated with cessation during follow-up among respondents without prior attempts. Examination of cutpoints revealed no value, which maximized both positive and negative prediction. Regardless of quit attempt history, greatest predictive validity was found where respondents stated that they had no intention at all. DISCUSSION: Measures of intentions quit smoking in specific time periods and expressed as dichotomies have limited psychometric properties but utility in applied research. Our findings suggest a possible measurement effect warranting caution in comparisons across studies.

An approach to the assessment of risk from chronic radiation to populations of European lobster, Homarus gammarus (L.).

The basic principles underlying a four-discrete age group, logistic, growth model for the European lobster Homarus gammarus are presented and discussed at proof-of-concept level. The model considers reproduction, removal by predation, natural death, fishing, radiation and migration. Non-stochastic effects of chronic low linear energy transfer (LET) radiation are modelled with emphasis on (99)Tc, using three endpoints: repairable radiation damage, impairment of reproductive ability and, at higher dose rates, mortality. An allometric approach for the calculation of LD(50/30) as a function of the mass of each life stage is used in model calibration. The model predicts that at a dose rate of 1 Gy day(-1), lobster population reproduction and survival become severely compromised, leading eventually to population extinction. At 0.01 Gy day(-1), the survival rate of an isolated population is reduced by 10%, mainly through loss of fecundity, comparable to natural migration losses. Fishing is the main ecological stress and only dose rates in the range 0.03-0.1 Gy day(-1) can achieve discernible effects above it. On the balance of radiation and other ecological stresses, a benchmark value of 0.01 Gy day(-1) is proposed for the protection of lobster populations. This value appears consistent with available information on radiation effects in wildlife.

An approach for the assessment of risk from chronic radiation to populations of phytoplankton and zooplankton.

A conceptual model of the effects of chronic radiation on a population of phytoplankton and zooplankton in an oceanic nutrient layer is presented. The model shows that there are distinct threshold dose rates at which the different plankton populations become unsustainable. These are 10,400 microGy h(-1) for phytoplankton and 125 microGy h(-1) for zooplankton. Both these values are considerably greater than the current screening values for protection of 10 microGy h(-1). The model highlights the effects of predator-prey dynamics in predicting that when the zooplankton is affected by the radiation dose, the phytoplankton population can increase. In addition, the model was altered to replicate the dose rates to the plankton of a previous ERICA Irish Sea assessment (24 microGy h(-1) for zooplankton and 430 microGy h(-1) to phytoplankton). The results showed only a 10% decrease in the zooplankton population and a 15% increase in the phytoplankton population. Therefore, at this level of dose, the model predicts that although the dose rate exceeds the guideline value, populations are not significantly affected. This result highlights the limitations of a single screening value for different groups of organisms.

Risk factors for cerebrospinal fluid shunt infections during an outbreak: a case-control study.

BACKGROUND: There are few published reports of cerebrospinal fluid (CSF) shunt infection outbreaks. In 2017-2018, British Columbia Children's Hospital (BCCH) experienced an increase in CSF shunt infections co-incident with a move to new operating rooms and a change in shunt catheters used. AIMS: To describe how an outbreak was detected, investigations were undertaken to determine the cause, risk factors associated with CSF shunt infection during the outbreak, and changes implemented to attempt to control the outbreak. METHODS: Retrospective case-control study. Population included patients who underwent new shunt insertion or revision. Univariate logistic regression models were fitted for each of the variables. Associations with P-values <0.2 were considered of potential interest for further investigation. FINDINGS: There were six cases of CSF shunt infection and 19 controls. The causative organism was different in each case. The only risk factors that met the criteria for further investigation were being a neonate at the time of surgery [odds ratio (OR) 9.0, 95% confidence interval (CI) 0.7-125.3, P=0.10] and the presence of gastrointestinal disease (OR 3.8, 95% CI 0.5-26.2, P=0.18). No association was found with the operating room used or the surgical staff. In response to the outbreak, human traffic through the operating rooms was limited, rigid adherence to the wearing of surgical masks was enforced, and return to the previous CSF shunt catheters used was implemented. CONCLUSION: No modifiable risk factors were associated with CSF shunt infection. After implementation of surgical protocol changes, no further cases of CSF shunt infection linked to the outbreak were identified.